Genetherapy

AVROBIO and Magenta Therapeutics Announce Collaboration to Evaluate Targeted Antibody-Drug Conjugate as a Potential Conditioning Regimen for…

May 9th, 2020

CAMBRIDGE, Mass.--(BUSINESS WIRE)--AVROBIO, Inc. (Nasdaq: AVRO) and Magenta Therapeutics (Nasdaq: MGTA) today announced a research and clinical collaboration agreement to evaluate the potential utility of MGTA-117, Magentas novel targeted antibody-drug conjugate (ADC) for conditioning patients before they receive one of AVROBIOs investigational lentiviral gene therapies.

The collaboration will combine AVROBIOs leadership in lentiviral gene therapies with Magentas expertise in ADC-based conditioning and is expected to further the two companies shared mission to enable patients to live free from disease. Under the collaboration, AVROBIO and Magenta will jointly evaluate MGTA-117 in conjunction with one or more of AVROBIOs investigational gene therapies. Magenta will retain all commercial rights to MGTA-117. AVROBIO will retain all commercial rights to its gene therapies and will be responsible for the clinical trial costs related to the evaluation of MGTA-117 with AVROBIOs gene therapies.

This agreement with Magenta springs from our strategic focus on maintaining technology leadership in gene therapy, said Geoff MacKay, AVROBIOs president and CEO. AVROBIO has always led by investing early in technological innovations that further the field of lentiviral gene therapy, such as plato, our proprietary platform designed to optimize the safety, potency and durability of our investigational lentiviral gene therapies. Were continually assessing new technologies that could be complementary to our plato platform to sustain our cutting-edge advantage and continue to evolve platos capabilities.

We believe targeted ADCs represent the next generation of medicines to prepare patients for gene therapy or transplant in a targeted, precise way. AVROBIOs investigational gene therapies complement our platform as well as our focus and commitment to patients. This partnership will allow Magenta to validate our conditioning platform in lentiviral gene therapy applications, said Jason Gardner, D.Phil., president and chief executive officer, Magenta Therapeutics. Weve selected ADCs as the preferred modality for our conditioning programs, as we believe they offer the most promising option for more patients. We have optimized our ADCs for gene therapy and transplant settings and look forward to collaborating with AVROBIO to evaluate MGTA-117 in specific gene therapy settings. Magenta will continue to develop MGTA-117 in other diseases, including blood cancers and genetic diseases.

MGTA-117, Magentas most advanced conditioning program, is a CD117-targeted antibody engineered for the transplant setting and conjugated to amanitin, a toxin in-licensed from Heidelberg Pharma. It is designed to precisely deplete only hematopoietic stem and progenitor cells and has shown high selectivity, potent efficacy, wide safety margins and broad tolerability in non-human primate models, suggesting that it may be capable of clearing space in bone marrow to support long-term engraftment and rapid recovery in humans. Magenta plans to complete IND-enabling studies this year.

AVROBIO currently uses a personalized conditioning regimen with precision dosing of busulfan, an extensively validated conditioning agent generally considered to be the gold standard for ex vivo lentiviral gene therapy, based on decades of general use and administration to hundreds of patients treated with lentiviral gene therapy candidates. The treating clinician uses therapeutic drug monitoring (TDM) to evaluate how quickly the patient metabolizes busulfan and adjusts the dose regimen accordingly with the goal of achieving the optimum result. AVROBIO has reported early clinical data with this precision conditioning regimen with TDM in its own clinical trials, adding to a body of data that suggest busulfan can effectively clear space in the patients bone marrow, where stem cells engraft, produce generations of daughter cells carrying the therapeutic gene and make the functional protein the patient needs to maintain cellular health.

About AVROBIO

Our mission is to free people from a lifetime of genetic disease with a single dose of gene therapy. We aim to halt or reverse disease throughout the body by driving durable expression of functional protein, even in hard-to-reach tissues and organs including the brain, muscle and bone. Our clinical-stage programs include Fabry disease, Gaucher disease and cystinosis and we also are advancing a program in Pompe disease. AVROBIO is powered by the plato gene therapy platform, our foundation designed to scale gene therapy worldwide. We are headquartered in Cambridge, Mass., with an office in Toronto, Ontario. For additional information, visit avrobio.com, and follow us on Twitter and LinkedIn.

About Magenta Therapeutics

Magenta Therapeutics is a clinical-stage biotechnology company developing medicines to bring the curative power of immune system reset through stem cell transplant to more patients with autoimmune diseases, genetic diseases and blood cancers. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise, a unique business model and broad networks in the stem cell transplant world to revolutionize immune reset for more patients. Magenta is based in Cambridge, Mass. For more information, please visit http://www.magentatx.com. Follow Magenta on Twitter: @magentatx.

AVROBIO Forward-Looking Statements

This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and phrases such as aims, anticipates, believes, could, designed to, estimates, expects, forecasts, goal, intends, may, plans, possible, potential, seeks, will, and variations of these words and phrases or similar expressions that are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding our business strategy for and the potential therapeutic benefits of our prospective product candidates, the design, commencement, enrollment and timing of ongoing or planned clinical trials, clinical trial results, product approvals and regulatory pathways, anticipated benefits of our gene therapy platform including potential impact on our commercialization activities, timing and likelihood of success, the expected benefits and results of our implementation of the plato platform in our clinical trials and gene therapy programs, the expected safety profile of our investigational gene therapies, and the potential and expected benefits of MGTA-117, Magentas investigational antibody-drug conjugate, including the ability of MGTA-117 to deplete hematopoietic stem and progenitor cells in order to clear space in bone marrow to support long-term engraftment in humans, as well as MGTA-117s potential application to AVROBIOs investigational gene therapies. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Results in preclinical or early-stage clinical trials may not be indicative of results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented.

Any forward-looking statements in this press release are based on AVROBIOs current expectations, estimates and projections about our industry as well as managements current beliefs and expectations of future events only as of today and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that any one or more of AVROBIOs product candidates will not be successfully developed or commercialized, the risk of cessation or delay of any ongoing or planned clinical trials of AVROBIO or our collaborators, the risk that AVROBIO may not successfully recruit or enroll a sufficient number of patients for our clinical trials, the risk that AVROBIO may not realize the intended benefits of our gene therapy platform, including the features of our plato platform, the risk that AVROBIO may not realize the intended benefit of MGTA-117 with respect to AVROBIOs investigational gene therapies, the risk that our product candidates or procedures in connection with the administration thereof will not have the safety or efficacy profile that we anticipate, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or trials involving AVROBIOs product candidates, the risk that we will be unable to obtain and maintain regulatory approval for our product candidates, the risk that the size and growth potential of the market for our product candidates will not materialize as expected, risks associated with our dependence on third-party suppliers and manufacturers, risks regarding the accuracy of our estimates of expenses and future revenue, risks relating to our capital requirements and needs for additional financing, risks relating to clinical trial and business interruptions resulting from the COVID-19 outbreak or similar public health crises, including that such interruptions may materially delay our development timeline and/or increase our development costs or that data collection efforts may be impaired or otherwise impacted by such crises, and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause AVROBIOs actual results to differ materially and adversely from those contained in the forward-looking statements, see the section entitled Risk Factors in AVROBIOs most recent Annual or Quarterly Report, as well as discussions of potential risks, uncertainties and other important factors in AVROBIOs subsequent filings with the Securities and Exchange Commission. AVROBIO explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.

Magenta Therapeutics Forward Looking Statements

This press release may contain forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws, including, without limitation, statements regarding the research and clinical collaboration agreement between Magenta and AVROBIO, including the timing, progress and success of the collaboration contemplated under the agreement, the successful evaluation MGTA-117 in conjunction with one or more of AVROBIOs investigational gene therapies under the agreement, the anticipated cost allocation and other commercial terms under the agreement, Magentas strategy and business plan, as well as the future development, manufacture and commercialization between AVROBIO and Magenta. The use of words such as may, will, could, should, expects, intends, plans, anticipates, believes, estimates, predicts, projects, seeks, endeavor, potential, continue or the negative of such words or other similar expressions can be used to identify forward-looking statements. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation, risks set forth under the caption Risk Factors in Magentas most recent Annual Report on Form 10-K, as updated by Magentas most recent Quarterly Report on Form 10-Q and its other filings with the Securities and Exchange Commission, as well as risks, uncertainties and assumptions regarding the impact of the COVID-19 pandemic to Magentas business, operations, strategy, goals and anticipated timelines, including, without limitation, Magentas ongoing and planned preclinical activities, ability to initiate, enroll, conduct or complete ongoing and planned clinical trials, timelines for regulatory submissions and financial position. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although Magenta believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, except as required by law, neither Magenta nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

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AVROBIO and Magenta Therapeutics Announce Collaboration to Evaluate Targeted Antibody-Drug Conjugate as a Potential Conditioning Regimen for...

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Edited Transcript of RGNX earnings conference call or presentation 7-May-20 8:30pm GMT – Yahoo Finance

May 9th, 2020

Rockville May 9, 2020 (Thomson StreetEvents) -- Edited Transcript of Regenxbio Inc earnings conference call or presentation Thursday, May 7, 2020 at 8:30:00pm GMT

* Kenneth T. Mills

REGENXBIO Inc. - CEO, President & Director

* Patrick J. Christmas

REGENXBIO Inc. - Senior VP & Chief Legal Officer

REGENXBIO Inc. - Senior VP & Chief Medical Officer

* Vittal K. Vasista

REGENXBIO Inc. - Senior VP & CFO

Chardan Capital Markets, LLC, Research Division - Director of Research & Head of Healthcare Research

SVB Leerink LLC, Research Division - MD of Genetic Medicines & Senior Research Analyst

Good afternoon, and welcome to the REGENXBIO First Quarter 2020 Earnings Conference Call. (Operator Instructions) As a reminder, this conference call is being recorded. I would now like to turn the call over to Mr. Patrick Christmas, Senior Vice President and General Counsel for REGENXBIO. You may begin.

Patrick J. Christmas, REGENXBIO Inc. - Senior VP & Chief Legal Officer [2]

Good afternoon, and thank you for joining us today. With us are Ken Mills, REGENXBIO's President and Chief Executive Officer; Dr. Steve Pakola, our Chief Medical Officer; and Vit Vasista, our Chief Financial Officer.

Earlier this afternoon, REGENXBIO released financial and operating results for the first quarter ended March 31, 2020. The press release reporting our financial results is available on our website at http://www.regenxbio.com.

Today's conference call will include forward-looking statements regarding our financial outlook in addition to regulatory and product development plans. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted and can be identified by words such as expect, plan, will, may, anticipate, believe, should, intend and other words of similar meaning. Any such forward-looking statements are not guarantees of future performance and involve certain risks and uncertainties. These risks are described in the Risk Factors and the Management's Discussion and Analysis sections of REGENXBIO's annual report on Form 10-K for the full year ended December 31, 2019, and comparable sections of REGENXBIO's other filings, which are on file with the Securities and Exchange Commission and available on the SEC's website.

Any information we provide on this conference call is provided only as of the date of this call, May 7, 2020. And we undertake no obligation to update any forward-looking statements we may make on this call on account of new information, future events or otherwise. Please be advised that today's call is being recorded and webcast. In addition, any unaudited or pro forma financial information that may be provided is preliminary and does not purport to project financial positions or operating results of the company. Actual results may differ materially.

I would now like to turn the call over to Ken.

Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [3]

Thank you, Patrick. Good afternoon, everyone, and thanks for joining us. On today's conference call, we'll provide a recap of our recent progress, advancing and expanding the NAV Technology Platform as well as expected future milestones. Steve will provide an update on our clinical programs, and Vit will provide an update on the financial results for the first quarter of 2020. Then we'll open the call for questions.

First, I want to take a moment to say that I hope everyone is healthy, staying safe during the COVID-19 pandemic. At REGENXBIO, we've made some changes to our business operations in order to support the health and safety of our employees and the community, and we're fortunate that we've been able to successfully advance our business during this time. As always, and especially throughout the past few months, our overall focus remains on the important goal of improving lives through the curative potential of gene therapy, and I'm grateful that our team is dedicated to this pursuit even in these challenging times. Along these lines, we've made important progress in recent months at REGENXBIO as we continue to see the remarkably consistent and durable effects of gene therapy treatment, patients with severe wet AMD.

If you haven't done so already, I highly recommend referring back to our webcast that we hosted on April 22, in which several leading retina specialists joined us to provide their perspectives on our recently announced data. Our RGX-314 gene therapy is designed to enable sustained production of an anti-VEGF antibody fragment in the eye, and we've now demonstrated stable and consistent results out to 2 years in the third dose cohort. We believe this is the longest time line of continuous therapeutic effects demonstrated in wet AMD patients from a single administration of an anti-VEGF treatment.

We also provided additional data from the fifth cohort, which received a higher dose of RGX-314 and in which 73% of patients remain anti-VEGF injection-free 9 months after a onetime administration of RGX-314. In our program, we're thinking carefully of all aspects of clinical management, not just anti-VEGF injections, are cognizant of the variables that might impact patient care and vision. And Steve will provide more details on these results and next steps for the program in his remarks.

Beyond RGX-314, we've continued to drive our internal gene therapy pipeline forward. As we previously announced in February, we presented encouraging initial data at the WORLDSymposium from Cohort 1, the Phase I/II trial for MPS II, and we look forward to providing additional data from these patients in mid-2020. We've begun enrolling patients in Cohort 2, where they're receiving a higher dose of RGX-121 and look forward to providing interim data on Cohort 2 in the second half of 2020.

We anticipate several other important updates this year including from our Phase I/II trial of RGX-501 for the treatment of HoFH, our Phase I/II trial of RGX-111 for the treatment of MPS-I and our RGX-181 program for the treatment of CLN2 disease, as well as our research programs in hereditary angioedema, neurodegenerative and neuromuscular diseases.

Lastly, construction of our GMP production facility here in Rockville continues, and the facility is expected to be operational in 2021. We expect the facility to enable us to strategically scale production while continuing to ensure high quality for patients. So with that, I'll turn the call over to Steve for a clinical and regulatory update.

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Stephen Pakola, REGENXBIO Inc. - Senior VP & Chief Medical Officer [4]

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Thanks, Ken. As you've mentioned, last month, we announced updated data from our Phase I/IIA study of RGX-314 for the treatment of wet AMD. We reported that the gene therapy continued to be well tolerated at all dose levels. And there were no reports of ocular inflammation beyond what is expected following routine vitrectomy. The latest efficacy update was focused on the 2-year data from Cohort 3 of the study. Patients in this cohort received [6 C] 10 genome copies per eye. And now at 2 years after administration of RGX-314, they have demonstrated markedly improved visual acuity and stable retinal thickness as well as significantly reduced need for anti-VEGF intraocular injections and stable protein expression.

50% of patients within this cohort did not receive any anti-VEGF injections over the full 2 years of the study. And one additional subject did not receive injections starting 9 months after the administration of RGX-314. We saw an impressive improvement in visual acuity with an increase of 14 letters in both the full cohort as well as the 4 patients who did not receive anti-VEGF injections in the second year of the study. This improved vision and durability of anti-VEGF activity is particularly meaningful, as real-world evidence has shown us that patients commonly lose vision over time, even with current standard of care.

And finally, Cohort 3 showed consistent protein production over 2 years, giving us confidence that the transduced cells in the retina have been producing the RGX-314 protein at a steady rate throughout the study. We also provided an interim update from Cohort 5. 73% of patients were anti-VEGF injection free over 9 months. We are very pleased with these results and look forward to additional efficacy data at the 1-year time point. We will use this data to then finalize the design of the pivotal program for RGX-314, which we expect to initiate in the second half of 2020. We are also planning to start trials of RGX-314 using the in-office suprachoroidal delivery approach in 2020 and for both wet AMD and diabetic retinopathy. We look forward to providing additional information about these trials over the coming months.

Turning to our rare disease portfolio. Data thus far from our Phase I/II trial of RGX-121 has been encouraging as patients in the first cohort demonstrated consistent and sustained reduction in heparan sulfate in the CSF, and available data support early signs of neurocognitive stability. We look forward to providing additional data from these 3 patients in mid-2020. Meanwhile, enrollment in Cohort 2 at a higher dose level continues and is expected to be complete in the first half of 2020, with interim data expected in the second half of 2020.

Recruitment screening and additional site activations are ongoing in our Phase I/II clinical trial evaluating RGX-111 for the treatment of MPS I. Recruitment in this trial had been previously focused on an initial patient over the age of 18, but the protocol was recently amended to allow enrollment of patients as young as 4 months of age.

We expect to provide a program update in the second half of 2020. We also anticipate updates from our Phase I/II trial of RGX-501 for the treatment of HoFH in the first half of this year. We have several other study programs headed towards the clinic, including the HAE and neuromuscular programs, and I look forward to providing additional details in the coming months. With that, I turn the call back over to Ken. Ken?

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Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [5]

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Thanks for that summary, Steve. REGENX has an extensive footprint in the gene therapy space, and we're always purposeful in developing partnerships with key players in the space to continue to realize the potential of NAV Technology. Our NAV Technology is currently being applied in 1 marketed product and more than 20 additional partnered product candidates.

We continue to track the positive progress of Novartis' ZOLGENSMA, which uses the NAV AAV9 vector. Novartis has stated that they're treating about 100 patients per quarter in the U.S. based on their current launch. We're encouraged by the success that the Novartis team in reaching patients. I believe that this is among the most successful launches of gene therapy so far and believe that it demonstrates the transformational impact that NAV Technology can have on the treatment of genetic diseases with significant unmet needs.

We were also pleased to see the positive regulatory developments in Japan and Europe this quarter, which signal additional validation of the technology across the globe. And importantly, for the entire gene therapy field, Novartis recently published additional detailed data for the intrathecal delivery of ZOLGENSMA, which has shown improvement in motor function and achievement of motor skills following treatment. I'm excited for the additional progress to come from this program.

In addition, we recently announced another exclusive worldwide license agreement with Ultragenyx, extending our companies' existing gene therapy partnership. This agreement will enable the Ultragenyx team to apply our NAV technology, AAV8 and AAV9 vectors to the development of a new gene therapy for a rare metabolic disorder, and provides further validation of the breadth and depth of our intellectual property portfolio.

Throughout the remainder of this year, we also anticipate regulatory updates from our partners like Audentes Therapeutics, now part of Astellas, for their gene therapy candidate for x-linked myotubular myopathy, which uses our NAV AAV8 vector. The promising milestones and achievements from our partners, as well as the progress in our own internal pipeline, provide additional validation the proprietary NAV Technology platform and further demonstrate the transformational impact that can come from a onetime administration of gene therapy.

With that summary, I want to turn the call over to Vit for a review of our financials.

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Vittal K. Vasista, REGENXBIO Inc. - Senior VP & CFO [6]

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Thank you, Ken. REGENXBIO ended the quarter on March 31, 2020 with cash, cash equivalents and marketable securities totaling $356.6 million compared to $400 million as of December 31, 2019. The decrease was primarily attributable to net cash used in operating activities of $35.6 million and cash used to purchase property and equipment of $4.6 million.

Revenues were $17.6 million for the 3 months ended March 31, 2020, compared to $900,000 for the same period in 2019. The increase was primarily attributable to $10 million of royalty revenue recognized on net sales of ZOLGENSMA in the first quarter of 2020 (inaudible) $7.2 million of license revenue recognized from new licensing granted to Ultragenyx during the period. Commercial sales of ZOLGENSMA commenced in the second quarter of 2019. The REGENXBIO is eligible to receive a milestone payment of $80 million from AveXis upon the achievement of $1 billion in cumulative net sales of ZOLGENSMA. As of the end of the first quarter of 2020, they have reported over $530 million in net sales, so we are more than halfway to that milestone.

Research and development expenses were $37 million for the 3 months ended March 31, 2020, compared to $25.2 million for the same period in 2019. The increase was primarily attributable to personnel-related costs as a result of increased headcount, laboratory and facility costs, expenses associated with conducting clinical trials for our lead product candidates, and externally sourced services for preclinical, regulatory and manufacturing-related activities.

General and administrative expenses were $14.8 million for the 3 months ended March 31, 2020, compared to $11.6 million for the same period in 2019. The increase was primarily attributable to personnel-related costs as a result of increased headcount, and professional fees for advisory and other services.

Net loss was $40 million or $1.08 basic and diluted net loss per share for the 3 months of March 31, 2020, compared to a net loss of $32.2 million or $0.89 basic and diluted net loss per share for the same period in 2019. As of March 31, 2020, we had approximately 37.2 million common shares outstanding.

Based on our current operating plan, we expect the balance in cash, cash equivalents and marketable securities of $356.6 million to fund the completion of our internal manufacturing capabilities and clinical advancement of our product candidates into 2022. With that, I will turn the call back to Ken to provide final thoughts.

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Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [7]

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Thanks for that update, Vit. So next week is the American Society of Gene and Cell Therapy Conference. And we've announced a number of scientific posters and presentations that will be shared. Our research and development team continues to demonstrate a deep and impressive knowledge in AAV discovery, characterization, delivery and significant experience and expertise in process development, production at large scale. So we look forward to participating with our industry partners, friends and colleagues, highlighting some of the work next week as well as continuing to share new data from our ongoing research throughout 2020.

Finally, as I've worked with our team to continue to pursue our mission for patients, balance the challenges and dealing with the COVID-19 pandemic, I've also reflected more on how the potential gene therapy treatments to help ease the burden on the medical community while also protecting patients, families, caregivers, even larger communities from certain risks involved current treatment options during events like what we're experiencing with this pandemic. There are many patient populations that rely on traveling, regular access (inaudible) medical care facilities for injections or infusions that are important, aesthetically necessary, sight-saving or life-saving medicines. Single administration gene therapy treatments can deliver important alternatives in moments where travel and access is restricted. Health care resources are limited, and product supplies may be threatened. Against the background of a pandemic that's taxing the global health care resources at unprecedented levels, it's even more apparent to me that our single-administration treatments have the potential to also create safer and more robust system for care.

The medical community and the biotech financial community should be doing everything possible to support and expedite single administration treatments, especially for large and at-risk populations. We continue to make strong progress in advancing key programs, broadening our internal care pipeline. After more than a decade of steadfast effort and focus, we remain dedicated and committed to improving lives through the curative potential of gene therapy.

With that, we're happy to turn the call over for questions. Operator?

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Questions and Answers

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Operator [1]

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(Operator Instructions) And your first question comes from Gena Wang with Barclays.

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Huidong Wang, Barclays Bank PLC, Research Division - Research Analyst [2]

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First related to resolution on the latest update in data was really impressive, especially after the update from other competitors. So another thing I wanted to ask you is, regarding the suprachoroidal data and the initiation first half this year, and also the clinical data, first cohort data by the end of this year. Just wondering what kind of data should we expect will you be presenting at the end of this year? Regarding the patient numbers, if we understand correctly, it's 6 patients? And what other data will you be able to share with us?

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Stephen Pakola, REGENXBIO Inc. - Senior VP & Chief Medical Officer [3]

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Gena, Steve here. Thanks for the questions. Yes, as you mentioned, our guidance is we continue to target starting our suprachoroidal delivery development program, first with a wet AMD and to kick that study off by the end of the first half of this year. And we still are guiding towards having interim initial data at the end of the year. We haven't actually disclosed how many patients we have in the study and other details, and we look forward to providing that later. But certainly, we stand by our guidance of giving an update based on some of the data that we'll have as of the end of the year. One of the nice things of the wet AMD indication is we already have a good handle on wet AMD in terms of looking at the appropriate types of endpoints, both anatomic, functional and treatment burden endpoints that we've talked about in the past and very recently with our recent data update in our subretinal delivery program. So we have a good handle on those types of endpoints. So I think you can envision similar types of data readouts.

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Operator [4]

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Your next question comes from Gbola Amusa with Chardan.

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Gbolahan Amusa, Chardan Capital Markets, LLC, Research Division - Director of Research & Head of Healthcare Research [5]

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Congrats as well on the 2-year durability data for 314. I had a couple of questions on the potential for inflammation for your in-office suprachoroidal approach. Obviously, there's a lot of benefit in going in the office, but some would argue there's greater potential for inflammation with that approach. So 1 -- 2 questions is, do you agree with that assessment? And then second, given that we've seen very recent and very early results with intravitreal gene therapy using expanded courses of prophylactic steroids addressing issues, maybe addressing thoroughly issues of inflammation with the (inaudible) capsid and wet AMD and also RP. Do those results go early? Do they motivate you to use an extended course of prophylactic steroids for your SCS microinjector programs? So those 2 questions then very quickly. Novartis just said that there's a multibillion-dollar potential for ZOLGENSMA, again, and this has updated guidance, and you got obviously up to 10% of that. What -- could you cover what they said [invites public forms] on the timing of the ramp towards that guidance?

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Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [6]

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Steve, maybe I'll let you start with the 314 questions.

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Stephen Pakola, REGENXBIO Inc. - Senior VP & Chief Medical Officer [7]

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Okay. That makes sense. Gbola, that's a great question. Suprachoroidal delivery is a different route of administration than subretinal. Subretinal is the gold standard. That's where we have the most efficacy and safety and clear demonstration that there isn't inflammation associated with subretinal gene therapy. And that's obviously very excited about for our lead program with subretinal delivery. Suprachoroidal, the in-office potential delivery there, where we still are anatomically delivering very close to the target issue of the RPE and the photoreceptors, but you raise a legitimate question. What do we know about immune privilege or lack thereof and the potential for inflammation? Historically, there's been inflammation seen, an immune response with suprachoroidal delivery of earlier generation AAV vectors such as AAV2 and AAV5. One of the things that got us very excited about suprachoroidal delivery with our proprietary NAV technology is actual preclinical data in both small and large animal models, where we've seen no inflammation with suprachoroidal delivery of AAV8 vector including RGX-314 in multiple studies. So that gives us (inaudible) that perhaps there is less of a risk of inflammation with [suprachoroidal] delivery than exists with intravitreal, for example.

So with intravitreal, we know historically -- universally really, with preclinical and clinical experiments, that at the doses that you have to give with either AAV2 or other vectors, that you have to give a high enough dose to have fusion to get to the back of the eye, the target tissue and through the internal limiting membrane barrier, that invariably at doses where you get good transduction, you also see immune-mediated inflammation. And we continue to see that, frankly, validated in any preclinical experiments or clinical data that's come out with intravitreal administration.

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Kenneth T. Mills, REGENXBIO Inc. - CEO, President & Director [8]

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Gbola, just turning to the question about ZOLGENSMA. I think what we've seen most recently between Novartis' update at their last earnings call, and then they had an update around new data that was presented at MDA, is that for the IV route of administration, that's, of course, currently approved and being marketed, facilitating the sales numbers that we're seeing based on the U.S. approval, there's been some regulatory events in Japan and Europe. Specifically, they pointed to that indicate that reimbursement is coming in other jurisdictions as early as the end of the first half of this year. In addition, with respect to the new intrathecal data that we mentioned earlier in the call, that there was an update on the strong study showing improved outcomes as described, and there's been guidance from Novartis that a BLA could be filed or equivalents, I guess, worldwide, as early as the second half of 2020 or into 2021. So we continue to be really encouraged by the data, by what we're seeing in terms of the uptake of the use of gene therapy. Again, I think we're looking at what must mean among, if not the, most successful launch for gene therapy to date and are liking to see the regulatory and commercial milestones that are emerging.

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Operator [9]

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Your next question comes from Mani Foroohar with SVB Leerink.

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Mani Foroohar, SVB Leerink LLC, Research Division - MD of Genetic Medicines & Senior Research Analyst [10]

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Edited Transcript of RGNX earnings conference call or presentation 7-May-20 8:30pm GMT - Yahoo Finance

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ReportsnReports always aims at offering their clients an in-depth analysis and the best research material of the various market. This report on the global Regenerative Medicine Market is committed fulfilling the requirements of the clients by giving them thorough insights into the market. An exclusive data offered in this report is collected by research and industry experts team. Regenerative Medicine Market market spread across 137 Pages, profiling 10 companies and supported with tables and figures.

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#Top Key Players in the Regenerative Medicine Market include are Organogenesis Inc. (U.S.), Osiris Therapeutics, Inc. (U.S.), Vericel Corporation (U.S.), Stryker Corporation (U.S.), and NuVasive, Inc. (U.S.). The key players in the acellular products segment are Medtronic (Ireland), Acelity (KCI Concepts) (U.S.), Integra Life Sciences (U.S.), Cook Biotech Inc. (U.S.), and C.R. Bard (U.S.).

On the basis of applications, the segments are orthopedic & musculoskeletal disorders, dermatology, cardiology, diabetes, central nervous system diseases, and other applications. Oncology is the fastest growing application market. Increasing cancer incidence, rich product pipeline and increasing demand for cancer treatments fuelling the growth of the market.

Geographically, the Regenerative medicine market is dominated by North America, followed by Europe, Asia-Pacific, and the Rest of the World (RoW). Growth in the North American segment is primarily driven by rapidly increasing aging population and increase in chronic diseases are the major drivers for developed economies like the U.S.

#Target Audience for Regenerative Medicine Market: Healthcare providers & clinical experts,Service providers,Therapeutic companies,Contract manufacturers,Academic research institutes.

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List of Tables:

Table 1 Few Important Clinical Studies in the Regenerative Medicine: Market

Table 2 Cancer Incidence and Mortality, By Region, 20122035

Table 3 Funding for Regenerative Medicine Research By the Nih Under the 21st Century Cures Act

Table 4 Nih Funding for Regenerative Medicine Research in the Us, 20142016 (USD Million)

Table 5 California Institute of Regenerative Medicine Funding for Regenerative Medicine Research

Table 6 Number of Companies Operating in the Regenerative Medicine: Market, By Region (20142018)

Table 7 Market, By Type, 20172024 (USD Billion)

Table 8 Few of the Commercialized Cell-Based Immunotherapy & Cell Therapy Products

Table 9 Cell-Based Immunotherapy & Cell Therapy Products Market, By Region, 20172024 (USD Billion)

Table 10 Cell-Based Immunotherapy & Cell Therapy Products Market, By Type, 20172024 (USD Billion)

Table 11 Cell-Based Allogeneic Regenerative Medicine

Table 12 Allogeneic Products Market, By Region, 20172024 (USD Billion)

Table 13 Cell-Based Autologous Regenerative Medicine

Table 14 Autologous Products Market, By Region, 20172024 (USD Billion)

Table 15 Few of the Commercialized Tissue-Engineered Products

.and more

The rest is here:
Regenerative Medicine Market by Type [Cell-Based Immunotherapy & Cell Therapy (Allogeneic & Autologous Products), Tissue Engineering, Gene...

Recommendation and review posted by Bethany Smith

How COVID-19 is endangering the lives of Thalassemia patients – National Herald

May 9th, 2020

As the number of thalassemia patients is increasing in India, need for a prevention and control program is felt. With preventive health checks not being the norm in India, people suffering from thalassemia are unknowingly passing on this genetic disorder to their children. The need of the hour is to have a national policy on thalassemia which will help in not just creating awareness about the disease but also ensure strategies to prevent its spread, diagnosis, and treatment for all. Even though we have the highest number of thalassemia patients in South Asia, the promising treatment modalities like bone marrow transplant (BMT) and gene therapy have their own share of risks and shortcomings due to a lack of incentives and support for the research studies.

To save valuable lives, setting up of small or micro blood donation camps or mobile vans can be done following the social distancing norms in the areas of green zones across the country with the help of various welfare organizations. Making appeals through social media platforms to healthy people to come out in numbers and donate blood is one way to create an informed society.

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How COVID-19 is endangering the lives of Thalassemia patients - National Herald

Recommendation and review posted by Bethany Smith

Advanced Therapy Medicinal Products Market: Key Challenges and Winning Imperatives – BioSpace

May 9th, 2020

Lately, there has been remarkable shift in the therapeutics method. People are inclining towards personalized medication rather than pharmaceutical treatment methods. This is result of advancements in biological therapies. As a result, advanced therapy medicinal products market (ATMP) is emerging. Such products provide solution for conditions with no therapeutic alternatives. This is a key factor driving growth of the advanced therapy medicinal products market across the globe.

At present, regulations for ATMPs is at its budding stage. Extensive research activities has been going on, which is resulting in Investigational New Drug (IND) applications.

The upcoming advanced therapy medicinal products market analysis report provides insight about the upcoming trends and restraining factors likely to shape growth of the market during forecast period (2019-2029). The report also provides a comprehensive analysis of the key companies of the market and offers details about the capacities and competencies of these companies. The market report also focusses on the markets competitive landscape and provides detail of the product portfolio of various companies.

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Advanced Therapy Medicinal Products Market: Competitive Analysis

At present, the advanced therapy medicinal products market is growing at a lucrative rate. This growth rate is attributed to recent approval of various advanced therapy medicinal products. Post success of approved products, stakeholders are investing at enormously in clinical trials of advanced therapy medicinal products.

On the other hand, companies operating in the market are adopting various strategies to accelerate the product manufacturing rate. While most of the companies are relying on in-house production of therapies, few players such as Contract Manufacturing Organizations (CMOs) are opting for third-party service providers.

Upsurge in demand for gene therapy has resulted in widening of drug development landscape and rise in the number of new entrants. However, there is lack of production capabilities.

Also, several companies are strengthening their foothold in the global market by strategic alliances and acquiring small CAR T-cell therapy developers.

Some of the key players operating in the advanced therapy medicinal products market are-

Advanced Therapy Medicinal Products Market: Key Trends

Despite high cost of the products, the market is expanding at lucrative rate. The growth rate is attributed to various health benefits provided by new classes of therapies.

Registering clinical benefits and efficiency of the products, stakeholders in the market are developing new strategies to overcome the challenged and boost application of advanced therapy medicinal products

Advanced Therapy Medicinal Products Market: Regional Outlook

Availability of significant number of FDA approved advanced therapy medicinal products in the U.S. has accounted for the prominent share of North America region, in terms of revenue. Recently, approval of products such as Yescarta, Zolgensma, and Kymriah has led to prominent investment in the U.S. advanced therapy medicinal products market.

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Europe hold second-largest pharmaceutical market space across the globe. In coming years, cell therapy developers are anticipated to hold prominent share in the Europes drug revenue. Moreover, several academic institutes in Europe are conducting extensive research in early-stage cell therapy. This factor is likely to fuel the regional revenue contribution.

Meanwhile, global manufacturing companies operating in the market are enhancing their reach across Europe. This, in turn, may drive growth in the regional market.

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Advanced Therapy Medicinal Products Market: Key Challenges and Winning Imperatives - BioSpace

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Flexion Therapeutics Reports First-Quarter 2020 Financial Results and Recent Business Highlights – GlobeNewswire

May 9th, 2020

BURLINGTON, Mass., May 07, 2020 (GLOBE NEWSWIRE) -- Flexion Therapeutics, Inc. (Nasdaq:FLXN) today reported financial results and recent business highlights for the quarter ended March 31, 2020.

We were very pleased with ZILRETTAs trajectory earlier in the first quarter of 2020; however, in March we began to experience impacts from the COVID-19 pandemic, said Michael Clayman, M.D., President and Chief Executive Officer of Flexion Therapeutics. The pandemic negatively affected our customers ability to treat patients as well as our first-quarter sales, and we believe that COVID-19 will adversely impact revenue for the remainder of the year. That said, our field teams have been utilizing various technologies to engage in conversations with prescribing physicians, and our confidence in ZILRETTAs long-term potential is undiminished. In fact, given the cancellations and postponements of total knee replacement surgeries, we believe ZILRETTA has the potential to play an increasingly prominent role in a post-pandemic environment. However, since that time horizon is uncertain, we have taken meaningful actions to reduce our operating expenses.

Dr. Clayman added, We recently made the strategic decision to discontinue our Phase 2 trial investigating ZILRETTA in shoulder OA and adhesive capsulitis. Given the small number of patients enrolled in that trial, the uncertainty around when we will be able to restart it, as well as the costs required to maintain the study in an inactive status, we believe terminating the trial is the most responsible action at this time. Moving forward, we will look to leverage our learnings from the study and potentially incorporate them into a new trial design to advance ZILRETTA in these indications. We continue to plan to reinitiate the FX201 single ascending dose trial as soon as feasible. Ultimately, we are committed to ensuring Flexion emerges from the crisis in a position of strength and that we are ready to quickly reaccelerate our commercial and R&D activities.

First-Quarter Results & Financial HighlightsThe Company reported a net loss of $36.8 million for the first quarter of 2020, compared to a net loss of $41.5 million for the same period of 2019. Net sales of ZILRETTA were $20.1 million and $10.6 million for the three months ended March 31, 2020 and 2019, respectively. Cost of sales was $2.3 million and $1.8 million for the three months ended March 31, 2020 and 2019, respectively.

Research and development expenses were $21.1 million and $15.4 million for the three months ended March 31, 2020 and 2019, respectively. The increase in research and development expenses of $5.7 million was primarily due to an increase of $2.2 million in salary and other employee-related costs for additional headcount and stock compensation expense, an increase in expenses related to FX201, including the payment of $2.5 million to GeneQuine for dosing the first human patient in the Phase I clinical trial, and an increase in other portfolio expenses, primarily related to the $0.5 million milestone to Xenon Pharmaceuticals, offset by a decrease of $0.5 million in development expenses for ZILRETTA due to lower clinical trial expenses during the period.

Selling, general and administrative expenses were $29.3 million and $32.2 million for the three months ended March 31, 2020 and 2019, respectively. Selling expenses were $20.5 million and $23.8 million for the three months ended March 31, 2020 and 2019, respectively. The year-over-year decrease in selling expenses of $3.3 million was primarily due to a reduction in physician and patient marketing activities. General and administrative expenses were $8.8 million and $8.4 million for the three months ended March 31, 2020 and 2019, respectively, which represents an increase of $0.4 million.

Interest income was $0.4 million and $1.0 million for the three months ended March 31, 2020 and 2019, respectively. Interest expense was $4.7 and $3.9 million for the three months ended March 31, 2020 and 2019, respectively.

As of March 31, 2020, the Company had approximately $125.2 million in cash, cash equivalents and marketable securities compared with $136.7 million as of December 31, 2019.

ZILRETTA Commercial MetricsSince the launch of ZILRETTA in November 2017 through March 31, 2020:

Reductions in Operating ExpensesIn response to the economic and business disruption caused by COVID-19, Flexion undertook prudent and disciplined steps to reduce expenses across the organization. The Company believes these steps will enhance financial flexibility and liquidity and estimates they will deliver between $43 million and $53 million in savings this year.As a result, Flexion expects full-year 2020 operating expenses (including cost of sales, research and development, and selling, general and administrative) will be in the range of $167 million to $177 million.The Company expects to achieve these cost savings through:

ZILRETTA Supply ChainThe Company remains confident in its ability to maintain adequate commercial supply of ZILRETTA and expects its current finished goods inventory will be sufficient to meet demand for at least the remainder of 2020. To avoid excess levels of inventory, Flexion is temporarily suspending manufacturing activities for ZILRETTA. Since Flexion employs a condominium model at Patheons manufacturing site, the Company has the ability to reinitiate manufacturing following three months notice to Patheon once additional supply is needed.

Fortress Biotech Announces Exclusive Worldwide License Agreement With Columbia University to Develop Novel Oligonucleotide Platform for the Treatment…

May 9th, 2020

Oncogenuity, Inc., a Fortress partner company, enters into an agreement with Columbia University to develop a broad platform technology using oligonucleotides

Initial target is KRAS-driven cancers, often considered un-druggable

Platform being explored as a treatment for coronaviruses, including COVID-19

NEW YORK, May 08, 2020 (GLOBE NEWSWIRE) -- Fortress Biotech, Inc. (Nasdaq: FBIO) (Fortress), an innovative biopharmaceutical company, today announced that Oncogenuity, Inc. (Oncogenuity), a new Fortress partner company, has entered into an exclusive worldwide licensing agreement with Columbia University to develop novel oligonucleotides for the treatment of genetically driven cancers. The proprietary platform produces oligomers, now known as ONCOlogues, that are capable of binding gene sequences 1,000 times more effectively than complementary native DNA. The technology comes from the labs of Gary Schwartz, M.D., Division Chief, Hematology/Oncology, and Jeffrey Rothman, M.D., Ph.D., Assistant Professor of Medicine.

ONCOlogues are sensitive to a single base pair mismatch, resistant to degradation and use a proprietary delivery sequence to enter cells. ONCOlogues selectivity enables Oncogenuity to target genetically driven cancers caused by mutations without impacting wild-type (WT) DNA sequences, potentially limiting off-target toxicity. In addition, this allows ONCOlogues to target mutations that have historically been considered un-druggable.

Oncogenuity has established proof-of-concept in a pre-clinical setting for various cancer types. The companys most advanced program is targeting the KRAS mutation G12D, which was previously considered un-druggable and plays a significant role in various cancer types with substantial unmet need, including pancreatic and colorectal. Given the platforms ability to target any mutation, Oncogenuity will continue to evaluate other mutations simultaneously. The company anticipates additional data publications in the coming 12 months.

Additionally, Oncogenuity is exploring the platforms potential to treat coronaviruses. Coronaviruses have single-stranded RNA genomes, making them strong targets for ONCOlogues. The company is studying replacement sequences, which could help combat COVID-19 and provide proof-of-concept as a treatment for coronaviruses. These ongoing experiments would validate ONCOlogues as a possible treatment for COVID-19, as well as potentially expedite the discovery of treatments for future coronavirus outbreaks.

Lindsay A. Rosenwald, M.D., Fortress Chairman, President and Chief Executive Officer, said, We are excited to work with the excellent scientists and physicians at Columbia University again. Our last joint effort with Columbia University led to the formation of our partner company, Caelum Biosciences, Inc. (Caelum). Since formation, Caelum has raised approximately $60 million in development funding from a number of sources, with additional amounts available upon the satisfaction of certain milestones and will be initiating two registration clinical trials in the next several weeks. Building upon our success with Caelum, we are grateful to Columbia University for entrusting us to develop this highly innovative technology using oligonucleotides to target genetically driven cancers and coronaviruses. Using a targeted genetic approach to treat cancer has become essential to limiting toxicity and treating patients effectively. This technology has the potential to target mutations that have previously been considered un-druggable. Oncogenuity will aggressively pursue the development of ONCOlogues to ultimately provide patients with new, safe and effective treatment options.

Scientific Co-Founder Jeffrey Rothman, M.D., Ph.D., said, Through rigorous statistical, mechanical and molecular modeling, combined with gene sequence data, we are able to create sequence-specific, targeted therapeutics against oncogenes, which are the cause of and specific to tumor cells. Until now, achieving this goal had been considered nearly impossible. However, with these novel design features, we now have the ability to target cancer while potentially avoiding side effects, which are the main cause of dose-limitation, by design. There is much potential because we are able to target multiple genes and therefore, multiple cancers. Moreover, due to their single-strand format, application toward viral targets such as in COVID are even more facile given their easier accessibility. We are excited and determined to pursue this endeavor with Fortress Biotech and very much welcome their continued support.

About Oncogenuity, Inc.Oncogenuity, Inc. is a biopharmaceutical company focused on the development and commercialization of ONCOlogues for the treatment of genetically driven cancers and coronaviruses. Oncogenuitys lead asset targets a KRAS mutation, G12D. Oncogenuity is located in New York City and was founded by Fortress Biotech, Inc. (Nasdaq: FBIO).

About Fortress Biotech Fortress Biotech, Inc. (Fortress) is an innovative biopharmaceutical company that was recently ranked number 10 in Deloittes 2019 Technology Fast 500, an annual ranking of the fastest-growing North American companies in the technology, media, telecommunications, life sciences and energy tech sectors, based on percentage of fiscal year revenue growth over a three-year period. Fortress is focused on acquiring, developing and commercializing high-potential marketed pharmaceutical products and development-stage pharmaceutical product candidates. The company has five marketed prescription pharmaceutical products and over 25 programs in development at Fortress, at its majority-owned and majority-controlled partners and at partners it founded and in which it holds significant minority ownership positions. Such product candidates span six large-market areas, including oncology, rare diseases and gene therapy, which allow it to create value while mitigating risk for shareholders. Fortress advances its diversified pipeline through a streamlined operating structure that fosters efficient drug development. The Fortress model is driven by a world-class business development team that is focused on leveraging its significant biopharmaceutical industry expertise to further expand the companys portfolio of product opportunities. Fortress has established partnerships with some of the worlds leading academic research institutions and biopharmaceutical companies to maximize each opportunity to its full potential, including Alexion Pharmaceuticals, Inc., AstraZeneca, City of Hope, Fred Hutchinson Cancer Research Center, InvaGen Pharmaceuticals Inc. (a subsidiary of Cipla Limited), St. Jude Childrens Research Hospital and Nationwide Childrens Hospital. For more information, visit http://www.fortressbiotech.com.

Forward-Looking StatementsThis press release may contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, as amended. As used below and throughout this press release, the words we, us and our may refer to Fortress individually or together with one or more partner companies, as dictated by context. Such statements include, but are not limited to, any statements relating to our growth strategy and product development programs and any other statements that are not historical facts. Forward-looking statements are based on managements current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock price. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to our growth strategy; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; risks relating to the results of research and development activities; uncertainties relating to preclinical and clinical testing; risks relating to the timing of starting and completing clinical trials; our dependence on third-party suppliers; risks relating to the COVID-19 outbreak and its potential impact on our employees and consultants ability to complete work in a timely manner and on our ability to obtain additional financing on favorable terms or at all; our ability to attract, integrate and retain key personnel; the early stage of products under development; our need for substantial additional funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in our SEC filings. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as may be required by law. The information contained herein is intended to be reviewed in its totality, and any stipulations, conditions or provisos that apply to a given piece of information in one part of this press release should be read as applying mutatis mutandis to every other instance of such information appearing herein.

Company Contacts:Jaclyn Jaffe and William BegienFortress Biotech, Inc.(781) 652-4500ir@fortressbiotech.com

Investor Relations Contact:Daniel FerryLifeSci Advisors, LLC(617) 430-7576daniel@lifesciadvisors.com

Media Relations Contact:Tony Plohoros6 Degrees(908) 591-2839tplohoros@6degreespr.com

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Fortress Biotech Announces Exclusive Worldwide License Agreement With Columbia University to Develop Novel Oligonucleotide Platform for the Treatment...

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Orchard Therapeutics’ (ORTX) CEO Bobby Gaspar on Q1 2020 Results – Earnings Call Transcript – Seeking Alpha

May 9th, 2020

Orchard Therapeutics plc (NASDAQ:ORTX) Q1 2020 Earnings Conference Call May 7, 2020 8:00 AM ET

Company Participants

Renee Leck Director-Investor Relations

Bobby Gaspar Chief Executive Officer

Frank Thomas Chief Operating Officer

Conference Call Participants

Whitney Ijem Guggenheim

Esther Rajavelu Oppenheimer

Yaron Werber Cowen

Peter Kim Barclays

Operator

Ladies and gentlemen, thank you for standing by, and welcome to the Orchard Therapeutics First Quarter 2020 Investor Conference Call. [Operator Instructions] I would now like to hand off the conference over to your speaker today, Renee Leck, Director of Investor Relations. Please go ahead, maam.

Renee Leck

Thanks, Sonia. Good morning, everyone, and welcome to Orchards first quarter 2020 investor call. You can access the slides for todays call by going to the Investors section of our website, orchardtx.com.

Before we get started, Id like to remind everyone that statements we make on this call will include forward-looking statements. Actual events and results could differ materially from those expressed or implied by any forward-looking statements as a result of various risk factors and uncertainties, and including those set forth in our annual 10-K filed with the SEC and any other filings we may make. In addition, any forward-looking statements made on this call represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statements.

And with that, Ill turn the call over to our CEO, Bobby Gaspar.

Bobby Gaspar

Thanks, Renee. Hello, everyone, and welcome. Id like to start by first acknowledging the tremendous efforts of our organization and our partners in the health care field to ensure patients in need continue to receive care during this difficult time. Thank you, everyone.

The last few weeks have been an important period for Orchard. Since taking on the leadership, Frank and I, together with the executive team, have thought very carefully about what the new Orchard can become, how we can ensure that Orchard can fulfill its true potential and what we need to do to make that happen. When we think about our strategic vision as a company, its really all based on the potential of the hematopoietic stem cell gene therapy platform, where it can take us and the benefit it can provide for many patient populations even beyond our current portfolio of ultra-rare diseases. We have taken some bold and decisive actions that we believe will allow Orchard to achieve long-term growth and focus the company on sustainable value creation. This vision is supported by a new strategic plan that we have developed and which is built around four pillars. Each of these forms a chapter in our remarks this morning.

First, operating efficiencies. We have made a series of important changes to our operations that will enable us to sharpen our focus and more efficiently execute our strategy, which I will detail in a moment. Second is our commercial build. We are focused on establishing the right model for the diagnosis and treatment of patients undergoing HSC gene therapy, and see the true value of this approach over a series of ultra-rare products.

Third, one of the most exciting areas in gene therapy right now is the innovation taking place in manufacturing technologies that have the potential to deliver economies of scale. We want to be leaders and invest in this space, knowing that our near-term capacity needs are covered by our experienced CDMO network.

Finally, central to this strategy is prioritizing our portfolio to enable the expansion of Orchards pipeline beyond ultra-rare to less-rare indications. We are disclosing two new research programs for the first time today, and these are a genetic subset of frontotemporal dementia or FTD, and a genetic subset of Crohns disease. We believe that the biological and clinical validation that has already been shown in our ultra-rare indications allow us to expand with confidence to these larger indications.

Turning to the first chapter in our new strategic plan. We are focused on improving the operational efficiency throughout the organization. This started with an extensive evaluation over the past six weeks of each program in our portfolio using several criteria that are shown here on the left-hand side of Slide 5. We undertook an objective analysis that involved both financial metrics and strategic considerations in identifying those programs where there was high need for patients and high-value creation for shareholders. As you can imagine, these were difficult decisions given the potentially transformative nature of many of these programs. Each has value, and we intend to realize that in different ways and over different time horizons.

Today, however, we believe our resources are best focused on Metachromatic Leukodystrophy, Wiskott-Aldrich syndrome, the MPS programs and our research programs. This also means that we have a balanced portfolio with late, mid and early stage programs. The programs I havent mentioned such as OTL-101 and ADA-SCID and the transfusion-dependent, beta-thalassemia program, OTL-300, will have a reduced investment moving forward. We will look for alternative ways to realize value with those programs, including through partnerships.

So Slide 6 brings together a summary of the operational changes that weve announced today. We believe these changes were important and necessary to enable Orchard to execute its mission and objectives at the highest level by matching our attention and resources to a set of core imperatives for the business. As summarized here, we expect to realize cash savings of approximately $15 million from the prioritization of our portfolio. Another $60 million in savings results from the decision to consolidate our R&D teams to one site and defer the investment in the manufacturing facility.

Finally, the more staged approach to the commercial build-out and 25% reduction to our existing workforce and future headcount planning will each yield another $25 million in savings. All of these cash savings are expected to be realized over 2020 and 2021, and result in total expected savings of $125 million over that period. With the revised plan, we now have cash runway into 2022 and no near term need to finance.

Its worth briefly mentioning that this $125 million savings is after making investments in the following key areas to support our new strategy, shown on Slide 7. In commercial, diagnostic and screening initiatives, including no-charge testing programs to help identify patients with MLD and other neurodegenerative conditions in time for treatment. In manufacturing, the technology, process innovations and efficiencies to drive scalability.

In R&D, initiatives in less-rare diseases that have the potential to fuel the companys future growth in a substantial way. This wasnt just an exercise to reduce expenses, but important decision-making to ensure our capital is deployed in a disciplined manner, while building a pipeline that can leverage our success across all phases of our business.

Now let me turn the call over to Frank to discuss additional key elements of the new plan.

Frank Thomas

Thanks, Bobby, and good morning, everyone. As you can tell from this mornings press release, we have carefully examined each aspect of our business. You heard that a moment ago from Bobby, with the way we are creating operational efficiencies, and I think you will see additional evidence in the next two sections as we summarize our latest thinking around commercial deployment and manufacturing.

Starting with commercial. We understand the importance of developing a commercial model that will demonstrate our ability to execute and bring these therapies to the market successfully. This model and the infrastructure that we build will also be leveraged for any future product launches.

As youll note from the bottom of Slide 9, each rare disease has certain dynamics that will impact the launch trajectory and speed with which we can penetrate the market. In fact, we anticipate our first two potential launches in WAS and MLD having distinct but complementary launch curves, as you can see from the illustrative diagrams.

Let me start with MLD on the left, where we expect to launch first in the EU, followed by the U.S. and then other countries around the world. We think an important inflection point on the revenue curve with MLD will come later when newborn screening is established, providing an opportunity for an acceleration in growth rate. Disease progression is a second important dynamic that will affect market penetration. Because MLD advances so rapidly, it will be important to diagnose patients early and get them treated.

For Wiskott-Aldrich syndrome, the dynamics are very different, and its reflected in the shape of the curve on the right. Unlike MLD, this disease is slower progressing and more readily diagnosed. We believe that WAS will provide an opportunity to treat a number of prevalent patients from the outset and also give us additional long-term revenue stream. This program, the BLA and MAA filings are on track for 2021.

Turning back to MLD for an update on the regulatory time line. We are on track to get a decision from the European Medicines Agency later this year, and if approved, launch in the EU in the first half of 2021. In the U.S., we recently engaged with the FDA on our planned BLA submission of OTL-200 for the treatment of MLD. The FDA has provided written feedback on the sufficiency of the companys data package, including the clinical endpoint, the natural history comparator and the CMC data package.

As a result of this feedback, we intend to file an IND later this year and also seek RMAT designation, both of which we believe will facilitate a more comprehensive dialogue to discuss the data more fully and resolve the open matters before submitting a BLA. We are committed to working closely with the agency, and well provide updated guidance on the new filing time lines for the BLA after further regulatory interaction.

On Slide 10, you can see that were tracking nicely for the launch of OTL-200 in the EU in the first half of 2021, if approved, with Germany being the first country where we expect to treat commercial patients. Many of the prelaunch activities are underway, and the team has been able to keep up momentum during the pandemic to work with key centers and progress with site qualifications. We intend to set up a network of treatment centers where MLD patients are often referred and who also have transplant expertise. These same centers can be leveraged in future launches, especially for programs in the neurometabolic franchise.

I previously mentioned the importance of diagnosis in MLD to identify patients at early stages of disease, and we are taking the necessary steps to achieve long-term success. Beyond typical disease awareness efforts, we are also looking at initiatives such as no-charge diagnostic testing with partners such as Invitae, and we are looking to facilitate newborn screening for MLD with funding of upcoming pilots in New York State and Italy that are designed to validate the assay and provide the data for wider implementation. Success in these key initiatives will support early MLD patient identification.

Coming up quickly behind MLD and the neurometabolic franchise, our two proof-of-concept programs in MPS disorders, where we have made recent progress even during this challenging period with COVID-19. For MPS-I, over the past year, weve shown promising preliminary proof-of-concept data with positive engraftment, biomarker correction and encouraging early clinical outcomes, and we are excited to announce our plan to begin a registrational trial next year, bringing this program one step closer to commercialization.

For MPS-IIIA, we announced late last month that the first patient was treated in a proof-of-concept trial at Royal Manchester Childrens Hospital, with enrollment planned to continue this year and interim data to be released in 2021.

You can see graphically on Slide 12 how the aggregation of these commercial markets lead to sustainable revenue growth. In addition, the infrastructure build is designed to provide the necessary commercial capabilities to realize the potential of the portfolio. On this slide, weve included the incidence figures for MLD and the incidence and prevalence figures for WAS to help you understand each opportunity as we see it today.

Given the dynamics at play for MLD that I described on Slide 9, we believe this opportunity should largely be tied to the incident patient population, which we believe ranges from 200 to 600 patients per year in countries where rare diseases are often reimbursed. Weve taken a more conservative view than previously on the addressable patient and market opportunity in countries such as those in the Middle East and Turkey, where the literature has a wide range of differing incident figures. Also, over time, with improved disease awareness, there may be prevalent patients identified who also could benefit from therapy. Our commercial strategy has always been and continues to be based not only on 1 product, but rather the aggregation of multiple potential products launching off one HSC gene therapy platform and infrastructure.

Turning to manufacturing. Weve also made some key changes to our approach in manufacturing and how we allocate capital in the short and mid-term. On Slide 14, youll see the main tenets of our new manufacturing strategy. First, in the near term, we plan to focus on innovative technologies to enable commercial scalability.

Second, to ensure the appropriate focus on those technologies, weve made a decision to consolidate R&D to a single site in London, which brings together our organization in a more efficient way. This will allow efforts made to improve our manufacturing processes to be quickly and easily shared and then scaled commercially to transfer to our third party manufacturers, all of whom are currently located in Europe. As part of this consolidation, we will close our California site, including the termination of the Fremont project and associated capital spend.

Third, we have strong relationships with CDMOs that will ensure supply of clinical and commercial product to satisfy near-term requirements. And longer term, we intend to identify a new site in the U.S. to eventually bring manufacturing capabilities in-house with a facility that is appropriately sized and fitted for future techniques and operations.

Slide 15 shows the three phases of our approach in manufacturing: invest, partner and build. Today, we are investing, and well continue to invest in technologies such as transduction enhancers, stable producer cell line and closed automated processing of the drug product. This will potentially reduce the amount of vector needed, drive down COGS and potentially change the way products are manufactured, making it less labor-intensive, less expensive and more consistent. In the near and mid-term, we will continue to rely on our manufacturing partners for the early planned launches in MLD and WAS. For example, MolMed has been with these programs since the beginning, and theyve been a reliable commercial partner with Strimvelis.

In addition to our existing CDMO network, we have begun to search for a drug product partner in the U.S. to complete a tech transfer and serve the U.S. market, thereby reducing scheduling challenges and creating some redundancy. And finally, over time, we plan to build in-house manufacturing capabilities closer to when there is a need for additional capacity. This enables us to explore options that are more aligned with our business in terms of scale and timing.

And with that, Ill turn the call back over to Bobby.

Bobby Gaspar

Thanks, Frank. In this section, Im going to briefly highlight the potential of HSC gene therapy to correct not only blood lineage cells, but also how through natural mechanisms, specific cell types may allow correction of disease in specific organ systems and enable expansion of our portfolio into new research indications.

As many of you know, and as shown on Slide 17, through HSC gene therapy, we are able to insert a working copy of the gene permanently into the genome of HSCs, and these genetically modified cells can lead to multiple corrected cell types in the bloodstream, including immune cells, red blood cells and platelets. In addition, HSCs can differentiate into cells of the monocyte macrophage lineage that naturally migrate into various organ systems, and thus gives us an opportunity to deliver genes and proteins directly to those organs, including the brain and the GI tract.

Within the neurometabolic space, in particular, we have understood through our preclinical and clinical programs in MLD, MPS-I and MPS-IIIA how HSC gene therapy can deliver genes and proteins to the CNS to correct neurodegeneration. Here is an example of this natural mechanism at work in Slide 18.

Data shows that there are a population of gene-modified HSCs that can naturally cross the blood-brain barrier, distribute throughout the brain, engraft as microglia and express enzyme that is taken up by neurons. We have seen this approach results in clinical benefits for patients with MLD, and we are also using the same approach for MPS-I and MPS-IIIA. Beyond this, we see that the HSC gene therapy approach could be used to deliver specific genes and proteins for other larger neurodegenerative conditions which have high unmet need.

One of the conditions we are disclosing today, and shown on Slide 19, is a specific genetic subset of frontotemporal dementia, where the underlying pathogenesis has a number of parallels with the neurometabolic conditions that we are already addressing. This program involves a broad strategic alliance with Dr. Alessandra Biffi, Boston Childrens Hospital and Padua University in Italy, to further explore the potential of ex vivo HSC gene therapy in neurometabolic and neurodegenerative conditions.

In other organ systems, such as the GI tract, there are similar mechanisms at work which are illustrated on Slide 20. Tissue resident macrophages in the gut wall are required to respond to bacterial invasion from the gut lumen and prevent infection. In certain disorders, such as X-linked chronic granulomatous disease or XCGD, defects in macrophage function results in an abnormal immune response and severe colitis.

Moving on to Slide 21. We have already seen in our XCGD program the modification of HSCs and migration of gene-modified cells into the gut can lead to resolution of colitis through presumed reconstitution of the immune response. Certain subsets of Crohns disease are also associated with mutations in genes that affect the response of macrophages to infection, and so our clinical observations that HSC gene therapy for XCGD suggest that the same approach may be applicable to this genetic subset of Crohns disease. This preclinical work is ongoing in our Orchard research laboratories.

As we advance our work in FTD and Crohns disease, and assuming we show preclinical proof-of-concept, these will become exciting opportunities for us to expand and address larger patient populations, either alone or in partnership. We believe we have truly just begun to explore the potential for HSC gene therapy in diseases such as these and others, and are excited to share more about the preclinical development of these programs later this year.

So to summarize our path forward on Slide 22, the next 12 to 18 months offers many important milestones as we continue our evolution to a commercial stage company and advance our next wave of clinical stage therapies. We anticipate approval and launch of OTL-200 for MLD in the EU, additional regulatory filings in Wiskott-Aldrich syndrome and MLD, a new registrational study next year in MPS-I, multiple clinical data readouts from our neurometabolic franchise and further detail and progress on our research programs in FTD and Crohns disease.

To wrap up our prepared remarks, we are confident that our new strategic plan and operational decisions announced today will set us on the right path to achieve long-term growth, build sustainable value and serve an even larger number of patients who could benefit from hematopoietic stem cell gene therapy.

Thank you very much. And now well use the rest of the time to answer your questions. So lets have the operator open up the line.

Question-and-Answer Session

Operator

Thank you. [Operator Instructions] And our first question comes from Whitney Ijem from Guggenheim. Your line is now open. Please go ahead.

Whitney Ijem

Hi, guys. Thanks for the question. So first, just wondering, can you give us some more color maybe on the discussions youre having with the FDA in MLD? Kind of what are they looking for? And I guess is the IND just sort of a tool to get RMAT? Or is there additional kind of clinical work you plan you think youll need to do?

Bobby Gaspar

Whitney, Bobby here. Thanks for that. In general, we cant go into all of the details, obviously, of the discussions with the FDA. But I think in the release and in the script, weve talked about the fact that theyve commented on certain endpoints, the natural history, the CMC package, et cetera. Now I think Id just like to say this is a and obviously, a very complex disease, a very ultra-rare population, we have extensive data set, and we have already filed with the EMA. Now for historical reasons, there hasnt been an IND in the U.S., and so we havent had the opportunity to discuss that data in full with the FDA.

What I can say is that we do have an extensive body of data. We want to be able to talk to the FDA and have a comprehensive dialogue to be able to explain that full data set. We feel confident that we have the endpoints that they are looking for and the data that they are asking for. But we need to have that conversation with them in order to be explain to be able to do that fully. So thats why were filing an IND filing, filing the RMAT, so we can have that dialogue. And once we can clarify those issues, then we can go ahead with submission of the BLA.

Whitney Ijem

Okay. Got it. And then just one quick follow-up on MLD. Can you remind us where you are with newborn screening, I guess, both in Europe and then in the U.S.?

Bobby Gaspar

Yes, sure. So newborn screening for MLD, I think, is an important, a very important issue, because, obviously, that means that well be able to get earlier diagnosis and have more patients be able to access therapy. So its a very important part of our kind of diagnostic initiatives in this disease.

What we have so far is that we have worked with a key scientist, where an assay has been developed, thats been published to show that there is an assay that weve done on a dry blood spot to understand the decrease in the enzyme activity and also the increase in the sulfur-type levels. And that assay is now going to be put into pilots, and we are funding a pilot in New York State, and that will start later this year. And were also looking at pilots in other states as well. Were also transferring that assay to Italy and that and were funding a program in Tuscany and in Italy where that will be rolled out. And were also looking for opportunities in other EU states as well. So Id say, there are already two that are going to start, we are looking to fund other pilots as well.

And together, that data will allow us to validate the assay but also allow wider implementation of newborn screening, and also for nomination, for example, onto the WAS panel for implementation in states in the U.S. So I say theres a lot of work going on in order to make sure that happens.

Whitney Ijem

Great. Thanks.

Operator

Thank you. And your next question comes from Esther Rajavelu from Oppenheimer. Your line is now open. Please go ahead.

Esther Rajavelu

Hey, guys. Congrats on all the changes. I guess, my first question again on MLD is Im trying to understand the duration between EU approval and NBS. I dont know if that math or if that graph was drawn to scale, but it looks like its almost a four-year lag from first approval to newborn screening. Can you help us understand the time line there?

Frank Thomas

You mean between EU and U.S. or around newborn screening or both?

Esther Rajavelu

Around newborn screening, generally, between EU approval and newborn screening.

Frank Thomas

Yes, sure. As Bobby mentioned, theres a pretty active program planned around newborn screening that I think we will expect will come over time in order to even apply for the Ross Panel, there are certain requirements that need to be met in terms of the number of patients or a number of children that have to be screened, identifying the positive patients and then you can apply on the Ross Panel.

And then from there, theres a process that you go through in the U.S., at least, on a state-by-state basis to get it added. So I think there are a number of steps along the way. We havent guided specifically on the time line, but I think there are other precedents out there that suggest that this could take years. Once we screen the once we apply for the Ross Panel to get sort of full reimbursement, but obviously, well focus on states initially after that approval that have the largest populations.

Esther Rajavelu

And my Yes, go ahead.

Bobby Gaspar

Esther for I was just going to say for the EU, obviously, were looking for approval for MLD later this year. As far as people screening in the EU is concerned, thats on a country-by-country basis, and sometimes its even certain states. But Ive worked on newborn screening for SCID, for example, in the EU. And now there are numerous countries in the EU that are screening for SCID with a number of pilots also in the pipeline as well. And so with that kind of experience, and we would be looking to kind of really facilitate that uptake in the EU and as in and in the U.S., as Frank has already mentioned.

Esther Rajavelu

Understood. And then the decision to defer CapEx, is that related to some of the time lines for U.S. versus EU approvals and the newborn screening? Or what really kind of went into that delay, given you already have some cost into that facility?

Frank Thomas

Yes. I can start, and Bobby can add on that again. I think, obviously, we continue to believe in-house manufacturing is an important capability that were going to want to have over some period of time. It really comes down to sort of when is the need for that capacity and capability relative to the various programs we have. Working with the CDMOs that we have today, we know that we have capacity for the MLD and WAS launches and for a period beyond the launch. So theres not an imminent need to secure the capacity today, and we think that deferring it makes the most sense. Well continue to work with CDMOs on those launches. We will look at bringing on a U.S. supplier for drug product to be able to more easily service the U.S. market.

And then longer term, look at, potentially, in-house manufacturing at a site and location that we think is more fitted to what the capacity needs will be. So I wouldnt say its tied to any sort of launch time lines because the plan always was to utilize CDMOs for WAS and MLD. But certainly, as those launches roll out and demand grows, our capacity needs will grow and that will be the appropriate time, we think, to make the investment.

Esther Rajavelu

Understood. Thank you very much.

Operator

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Orchard Therapeutics' (ORTX) CEO Bobby Gaspar on Q1 2020 Results - Earnings Call Transcript - Seeking Alpha

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Gene Editing Technologies Market What Factors will drive the Gene Editing Technologies Market in Upcoming Years and How it is Going to Impact on…

May 9th, 2020

Market Expertz has recently published a study titled Global Gene Editing Technologies Market Research Report. In this report, analysts have provided a detailed evaluation of the global Gene Editing Technologies market. It includes a comprehensive study of the Gene Editing Technologies Market alongside all the important factors that are likely to have an impact on the commercialization matrix of the market.

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A highly methodical quantitative as well as qualitative analysis of the global Gene Editing Technologies market has been covered in the report. The study evaluates the numerous aspects of this industry by studying its historical and forecast data. The research report also provides Porters five force model, in tandem with the SWOT analysis and PESTEL analysis of the Gene Editing Technologies market.

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Thermo Fisher ScientificMerckSangamo TherapeuticsLonzaTransposagen BiopharmaceuticalsEditas MedicineCRISPR TherapeuticsAgilent Technologies

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Double Strand Break RepairEngineered Nucleases

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Gene TherapyEradicating Diseases

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To summarize, the global Gene Editing Technologies market report studies the contemporary market to forecast the growth prospects, challenges, opportunities, risks, threats, and the trends observed in the market that can either propel or curtail the growth rate of the industry. The market factors impacting the global sector also include provincial trade policies, international trade disputes, entry barriers, and other regulatory restrictions.

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Gene Editing Technologies Market What Factors will drive the Gene Editing Technologies Market in Upcoming Years and How it is Going to Impact on...

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‘Transcient’ Damage to CNS Seen with Chemotherapy Used in Stem… – Multiple Sclerosis News Today

May 9th, 2020

A high-dose chemotherapy combination given to wipe out the immune system before its rescue withautologous hematopoietic stem cell transplant (aHSCT)can cause transient damage to neurons and supporting cells of the central nervous system in people with aggressive multiple sclerosis (MS), a Canadian study reports.

Nonetheless, its researchers believe that the risk of such neuronal toxicity is offset by the benefits of the aHSCT procedure in aggressive MS cases.

The study, Neurotoxicity after hematopoietic stem cell transplant in multiple sclerosis, was published in the journal Annals of Clinical and Translational Neurology.

aHSCT is an intensive yet effective treatment, particularly used to rebuild the immune system of people with aggressive MS.

The procedure begins with collecting a patients own (meaning autologous) healthy hematopoieticstem cellsfrom the bone marrow, followed by immunoablation the wiping out of the immune system with a high-dose chemotherapy combination that kills the patients immune cells. The hematopoieticstem cellsare then infused back to the person to generate a new and healthy immune system.

Intensity and duration of the chemotherapy given varies among centers.

In Canada, the chemotherapy regimen used in clinical practice is particularly intense and involves high doses of two agents, cyclophosphamide and busulfan. This combination is known to penetrate the central nervous system (CNS, brain and spinal cord), and to kill the CNS immune cells (called microglia) that go awry in MS.

Previously, researchers in Canada noted faster brain volume loss in MS patients over the six months following aHSCT. This was interpreted as a false (pseudo) shrinkage of brain volume due to lesser inflammation.They also thought that the toxicity related to the chemotherapy regimen itself could be a contributing factor, as chemotherapy can affect cognitive and memory abilities what patients refer to as chemo brain and chemo fog.

To test these interpretations, a team led by researchers at the University of Ottawameasured the levels of two markers serum neurofilament light chain (sNfL)and serum glial fibrillary acidic protein (sGFAP) in the blood (serum) of MS patients before and after the chemotherapy regimen in aHSCT.

sNfL has been proposed as a marker of neuron degeneration and damage, and sGFAP is a marker of astrocytes, cells involved in the provision of nutrients to neurons, the repair of nervous tissue following injury, and in facilitating neurotransmission (essential in nerve cell communication).

Researchers measured the levels of these two markers in blood samples from 22 MS patients with aggressive disease, all enrolled in the Phase 2 BMT trial (NCT01099930) in Canada. Blood samples were collected at specific times (three, six, nine, and 12 months) before and after aHSCT. Aggressive disease for this study was defined as having a poor predicted 10-year prognosis [likely course].

Blood samples from another 28 people of similar ages and with non-inflammatory diseases (including migraine, fibromyalgia, anxiety, Bells palsy, labyrinthitis, and depression) were used as controls.

sNfL levels prior to aHSCT were seen to be significantly elevated in the blood of MS patients (mean of 21.8 pg/mL) compared with controls (6.4 pg/mL). So too were blood levels of sGFAP: 107.4 pg/mL in MS patients versus 50.7 pg/mL in controls.

Three months after aHSCT, levels of sNfL significantly increased by 32.1% (from 21.8 to 28.8 pg/mL), and sGFAP levels by 74.8% (from 107.4 to 187.7 pg/mL) in 15 patients with available three-month data, compared to their pre-treatment levels. In two of these 15 people, both sNfL and sGFAP levels were lower three months after treatment.

Further analysis looked at changes from baseline (study start) and three-month post-aHSCT measures of sNfL levels and grey matter volume loss. This was done to look for correlations between early serum biomarker changes with clinical and MRI markers of possible neurotoxicity, the researchers wrote.

Their analysis found correlations at all early time points months one, two, four and six but not at nine or 12months post-treatment, highlighting that associated increases in both sNfL and MRI grey matter volume loss are temporary phenomena in the first year following IHASCT, they wrote.

Patients given the highest dose of busulfan (more than 700 mg) had the highest levels of sNfL and a greater extend of grey matter loss, shown by MRI, at three months post-treatment.

The chemotherapy regimen used increases sNfL and sGFAP levels in the first few months after treatment, the study noted, with sNfL increases correlated with the total busulfan dose given. The result is a transient worsening of posttreatment EDSS score as well as MRI volume loss, especially in the grey matter, the researchers wrote.

This study is the first to correlate these increases [rises in brain atrophy and serum markers of neurotoxicity] with doses of chemotherapy administered in aHSCT, they added.

Although we see transient neurotoxicity likely related to busulfan in this study, this has to put in the context of their highly active refractory disease, the team concluded. While the long-term effects of chemotherapeutic neurotoxicity are not known, in cases of aggressive MS, short-term chemotherapy-related neuronal toxicity may be a risk that is greatly offset by the benefit of long-term freedom from disease-related inflammation.

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.

Total Posts: 1,053

Patrcia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

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'Transcient' Damage to CNS Seen with Chemotherapy Used in Stem... - Multiple Sclerosis News Today

Recommendation and review posted by Bethany Smith

Stem Cell Therapy Market To Boom In Near Future By 2027 Scrutinized In New Research – Cole of Duty

May 9th, 2020

The Covid-19 (coronavirus) pandemic is impacting society and the overall economy across the world. The impact of this pandemic is growing day by day as well as affecting the supply chain. The COVID-19 crisis is creating uncertainty in the stock market, massive slowing of supply chain, falling business confidence, and increasing panic among the customer segments. The overall effect of the pandemic is impacting the production process of several industries including medical devices, pharmaceuticals, healthcare, biotechnology, and many more. Trade barriers are further restraining the demand- supply outlook. As government of different regions have already announced total lockdown and temporarily shutdown of industries, the overall production process being adversely affected; thus, hinder the overall Stem Cell Therapy Market globally. This report on Stem Cell Therapy Market provides the analysis on impact on Covid-19 on various business segments and country markets. The report also showcases market trends and forecast to 2027, factoring the impact of Covid -19 Situation.

The stem cell therapy marketwas valued at US$ 1,534.55 million in 2019 and is expected to grow at a CAGR of 16.7% from 2020to 2027 to reach US$ 5,129.66 million by 2027.

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What is Stem Cell Therapy Market?

Stem cells are preliminary body cells from which all other cells with specialized functions are generated. Under controlled environment in the body or a clinical laboratory, these cells divide to form more cells called daughter cells. Due to the advent of modern health science, these cells play a major role in understanding the occurrence of diseases, generation of advanced regenerative medicines, and drug discovery. There are certain sources such as embryo, bone marrow, body fats, and umbilical cord blood amongst others, where stem cells are generated. The global stem cell therapy market is driven by factors such asincreasing awareness related to the stem cells therapy in effective disease management and growing demand for regenerative medicines. However, high cost related with stem cell therapy is likely to obstruct the growth of the stem cell therapymarket during the forecast period. The growing research and development activities in Asia Pacific region is expected to offer huge growth opportunity for stem cell therapy market.

Researchers are further investigating stem cell therapy in autoimmune disorder. Other adult stem cells based treatments are under clinical trials. Hematopoietic stem cells are currently used for treating more than 80 medical diseases, which include diseases of the immune system, blood disorders, neurological disorders, metabolic disorders, genetic disorders, and several types of cancers like leukemia, lymphoma, etc.Emerging Players in the Stem Cell Therapy Market Research include:

A factor which can be a restraint for Stem Cell Therapy Market can be some companies do not collaborate with service providers or they dont take advantage of digitization as they dont have awareness for the same. Nevertheless, digitization in services is opting by an online company to know more exactly about consumer behavior plus it makes business policies flexible to adopt changes as per the market condition on which success and growth of an organization depend which will give more growth opportunities in coming years.

This report will help you determine and analyze your portfolio of key market players with information such as company profile, components and services offered, financial information from the past three years, and key developments it helps you to develop a strategy to gain a competitive edge in the past 5 years. The market payers from Stem Cell Therapy Market are anticipated to lucrative growth opportunities in the future with the rising demand for Stem Cell Therapy Market in the global market.

Key questions answered by this report:

Global Stem Cell Therapy Market By Type

Global Stem Cell Therapy Market By Treatment

Global Stem Cell Therapy Market ByApplication

Global Stem Cell Therapy Market By End User

Global Stem Cell TherapyMarket By Geography

Stem Cell Therapy Market Table of Contents:

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Stem Cell Therapy Market To Boom In Near Future By 2027 Scrutinized In New Research - Cole of Duty

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Avalon GloboCare advancing immune cell therapy to treat blood cancers using FLASH-CAR technology – Proactive Investors USA & Canada

May 9th, 2020

The adaptable FLASH-CAR platform can be used to create personalized cell therapy from a patients own cells, as well as off-the-shelf cell therapy from a universal donor

(NASDAQ: AVCO) announced Friday that it is advancing its next-generation immune cell therapy to treat blood cancers using FLASH-CAR technology co-developed with strategic partner Arbele Limited.

The adaptable FLASH-CAR platform can be used to create personalized cell therapy from a patients own cells, as well as off-the-shelf cell therapy from a universal donor.

Currently, the Chimeric Antigen Receptor T (CAR-T) cellular immunotherapy platform is available. It involves a patients own T-cells a type of white blood cell that protects against infections and other diseases including cancer that are turned into personalized cancer-fighting cells.

The T-cells are removed from the patient, reprogrammed in the lab using a viral vector to target cancer cells, and infused back into the patient as a cancer immunotherapy.

But in contrast to these existing therapies, Avalon said its FLASH-CAR platform uses next-generation CAR technology to modify patients T-cells and natural killer (NK) cells using a ribonucleic acid (RNA)-based platform rather than a viral vector.

Similar to T-cells, NK cells are a type of white blood cell, also able to attack cancer cells, but utilize different mechanisms. By using RNA molecules rather than a viral vector, Avalons RNA-based CAR technology is designed to rapidly create personalized CAR therapies in 1 to 2 days compared to the 10- to 14-day bio-manufacturing time necessary to generate currently available CAR-T cellular immunotherapy.

Avalon said its FLASH-CAR technology is also designed to reprogram the immune cells to hone in on multiple crucial cancer cell targets, called tumor antigens, to potentially achieve superior therapeutic effect. Avoiding the use of viral vectors and complicated bio-processing procedures significantly reduces manufacturing costs, resulting in a more affordable and potentially breakthrough therapy for cancer patients.

The FLASH-CAR technology can also be used to generate off-the-shelf,universal cell therapy that has the potential to reach even more patients.

Avalons first FLASH-CAR platform candidate, AVA-011, targets both CD19 and CD22 tumor antigens on cancer cells.

Pre-clinical research on AVA-011, including tumor cytotoxicity studies, has been successfully completed and Avalon said it is immediately entering the process development stage to generate clinical-grade CAR-T and CAR-NK cells for use in human clinical trials.

Avalon and Arbele have jointly filed for US patents for this RNA-based CAR platform cellular therapy and for other applications.

Avalon expects to begin a first-in-human clinical trial with AVA-011 for the treatment of relapsed or refractory B-cell lymphoblastic leukemia (B-ALL) and non-Hodgkin lymphoma in the first quarter of 2021. The goal is to use AVA-011 as a bridge to bone marrow stem cell transplant therapy, currently the only curative approach for patients with these blood cancers.

Avalon GloboCare is committed to decreasing the time it takes to deliver cellular immunotherapies to cancer patients, as well as lowering the cost of manufacturing by building on our unique RNA-based CAR platform that does not require using a viral vector, said CEO Dr David Jin.

We are accelerating our innovative discovery and development plan, as well as delivering precise clinical execution and leadership in cellular immunotherapy. Our pre-clinical studies are encouraging and we are excited for AVA-011 to enter the clinical development stage, including multi-center clinical trials following completion of process development to generate the cell therapy.

Arbele CEO John Luk added: Through this strategic partnership with Avalon GloboCare, we envision an accelerated scientific and clinical development of the RNA-based FLASH-CAR technology platform with great potential to generate 'off-the-shelf'immune effector cell therapies to treat both hematologic and solid malignancies.

Avalon, based in Freehold, New Jersey, specializes in developing cell-based technologies and is involved in the management of stem-cell banks and clinical laboratories.

The companys stock recently traded up 10% to $1.99a share in New York.

--UPDATES stock price--

Contact the author: [emailprotected]

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Avalon GloboCare advancing immune cell therapy to treat blood cancers using FLASH-CAR technology - Proactive Investors USA & Canada

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World Thalassemia Day: All you need to know from the expert – India Today

May 9th, 2020

Thalassemia is a type of inherited blood disorder. It is passed from parents to children through genes. This disorder involves lack of oxygen-carrying protein called hemoglobin (an important part of red blood cells). When there is insufficiency of hemoglobin in the body, the red blood cells dont function properly. It also reduces the life of RBC, which means fewer healthy RBC travel in the blood.

RBC carries oxygen to all the cells of the body. Oxygen acts as food, which is used by cells to function. Shortage of healthy RBC means shortage in supply of oxygen to all other cells of the body. This may lead to lethargy in a person. The person may feel tired, weak or short of breath. This condition is termed as Anaemia.

People with thalassemia may suffer from mild or acute Anaemia. Acute Anaemia can be very severe and can lead to damage of major organs. It can even cause death.

Thalassemia major babies are born to parents who are carriers of thalassemia gene. According to rough estimates, each year some 10000 babies are born in India with thalassemia. Best way to prevent or eliminate thalassemia is screening of all pregnant women between 9 to 12 weeks.

Thalassemia is diagnosed through blood tests which include doing a complete blood count (CBC) and special hemoglobin tests. Through a sample of blood, CBC measures the amount of hemoglobin and the different kind of blood cells, such as red blood cells. Hemoglobin tests measure the types of hemoglobin in blood.

Moderate and acute thalassemia is usually diagnosed in childhood. This is because signs and symptoms, such as acute Anemia usually occur at an early age of 2 years. People who have mild form of thalassemia may get diagnosed after a routine blood test, as it will detect if they have anemia.

Here's Dr. Rahul Bhargava, Director and Head, Hematology, Haemato- Oncology and Bone Marrow Transplant, Fortis Memorial Research Institute, Gurugram has to say about the treatments:

Blood Transfusion

Treatment of thalassemia major relies on regular blood transfusion at regular intervals, to keep Hb above 9 gm. percent. It will help prevent form short stature and other skeletal and facial deformities. Recurrent lifelong blood transfusion since 6 months of birth is necessary.

Iron Chelation Therapy

With transfusion comes the problem of iron deposition, as each blood transfusion lead to incremental iron deposition in various tissues like pituitary gland liver and heart leading to early death. So along with transfusion patient also needs iron chelation therapy. It can be either oral (defriprone and defreseirox) or IV desferoxmine. Serum ferritin is one of the surrogate markers of iron overload in thalassemia patients. It needs to be done every 3 months. Gov.s efforts of providing free blood products and iron chelators is bearing fruits as life expectancy has shown an upward trend.

Bone Marrow or Stem Cell Transplant

As it is commonly known, bone marrow or stem cell transplant is the only curative modality for thalassemia. If done at an early age, 80 percent patients can be cured. Source of stem cell could be either brother or sister whose HLA is a complete match. Otherwise fully matched HLA donor can be tried in various international registries. This process is called as match unrelated donor transplant.

Gene Therapy

Gene therapy is gaining lot of traction in field of hemoglobinopathies. It has shown remarkable result with minimum toxicities and sustained haemoglobin production in various trials. There has been no major risk of cancer or other late effects.

We have come a long way and probably this decade will bring the much awaited cheers to thalassaemics. Till then in India, prevention is the only strategy to reduce the burden on already stretched health care system.

Better rate of blood transfusion

Regular Blood screening has significantly impacted reduction of infections due to blood transfusion

Significant improvement in treatment

Bone Marrow Transplant and Stem cell transplantation has led to patients having a good quality of life

Read more| 10 things to keep in mind while travelling with Asthma

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World Thalassemia Day: All you need to know from the expert - India Today

Recommendation and review posted by Bethany Smith

CCR5 Receptor Appears Effective in Modulating Inflammation – Precision Vaccinations

May 9th, 2020

A Washington based biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announcedthe availability of thepre-print version of the manuscriptdescribing the immunological mechanism by whichleronlimabrestores immune function and impacts disease in COVID-19 patients.

This manuscript,Disruption of the CCL5/RANTES-CCR5 Pathway Restores Immune Homeostasis and Reduces Plasma Viral Load in Critical COVID-19, has been shared with the World Health Organization and is currently under peer review, said CytoDyn, Inc., as of May 6, 2020.

As described in thepre-print, in a cohort of 10critically ill patients, after treatment with leronlimab, these critically ill patients experienced reversed hyperimmune activation and inflammation, as well as reversed immunosuppression, therebyfacilitating a more effective immune responsecorrelated with decreases in SARS-CoV-2 level in blood.

These results demonstrate a novel approach to resolving unchecked inflammation whilerestoring immunologic deficiencies.

This is an important finding since according to various studies, a major driver of severe COVID-19 disease is excessive inflammation.

Nader Pourhassan, Ph.D., President and Chief Executive Officer of CytoDyn said in a press statement, We are now most hopeful the entire medical community will understand the potential benefit leronlimab can provide critically ill COVID-19 patients."

"Moreover, this discovery by Dr. Bruce Patterson that leronlimab decreases plasma viral load may have tremendous long-term positive ramifications to bring this pandemic under control. We are grateful that we are able to release this research at such a critical time for patients throughout the world.

Leronlimab (PRO 140) is being used as a treatment for severe COVID-19 under the emergency Investigational New Drug (IND) recently granted by the U.S. Food and Drug Administration (FDA).

Leronlimab is a drug candidate that is aCCR5 antagonist with the potential for multiple therapeutic indications.Leronlimab belongs to a group of HIV drugs calledCCR5antagonists.

The CCR5 receptor appears to play a central role in modulating immune cell trafficking to sites of inflammation. It may be crucial in the development of acute graft-versus-host disease (GvHD) and other inflammatory conditions.

Clinical studies by others further support the concept that blocking CCR5 using a chemical inhibitor can reduce the clinical impact of acute GvHD without significantly affecting the engraftment of transplanted bone marrow stem cells.

Previously, CytoDyn announced it is seeking a compassionate use designation for leronlimabfor the treatment of COVID-19 patients who are ineligible for participation in its two existing clinical trials. If this request is granted by the FDA, it will significantly expand the pool of patients who would be eligible to receive leronlimabtherapy.

CytoDyn is a late-stage biotechnology company developing innovative treatments for multiple therapeutic indications based on leronlimab, a novel humanized monoclonal antibody targeting the CCR5 receptor.

Precision Vaccinations publishes developing COVID-19 therapeutic drug news.

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CCR5 Receptor Appears Effective in Modulating Inflammation - Precision Vaccinations

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Sapelo Skin Care Combines High-Tech Ingredients and Southern Charm – Sarasota

May 9th, 2020

Sapelo Skin Care is one of those brands you'll love for a lifetime. Not only is it luxe, the products are also wrapped in the loveliest packaging, with designs that make me think of a beautifulobjetfound in a well-appointed Southern mansion. So it should be no surprise to learn that the brand is handmade in Savannah. Founders Stephanie Duttenhaver and Cindy Edward took note of the city's natural beauty, especially the rivers and creeks that swell with high tides twice each day, and followed those cues to craft a small-batch, non-toxic product. The twice-daily tinctures soothe and replenish the skin, boosting collagen, elastin and skin-cell restoration to give us the healthy glow we all want (especially as we spend more time indoors).

I gave four Sapelo products a go: the Gentle Seaweed Cleanser ($40), Milk & Honey Hydrating Mask ($75), Restoring Eye Serum ($95) and Spring Tide Serum ($195). I loved them all, and I will be returning to Saks Fifth Avenue at the Mall at University Town Centerwhich reopens with limited hours on May 12for a moisturizer to complete my regimen.

The cleanser sets the foundation for the serums, leaving the skin feeling clean and oh-so velvety. And the serums are heavenly, with bottles dispense the perfect droplet of product. They're clearly designed by women who know we do not like to waste a good thing.

Then there's the Milk & Honey Hydrating Mask, another winner. After all the ups and downs of our Sarasota temperatures these last months, my skin needed a little love and felt re-textured and re-hydrated after using the mask.

Now, it may just be me, a woman from New York, who feels that Southern woman knowthings. Such as how to deliver the hard truth with a smile (and you may even thank them for it). Or how to set a proper table for tea. Or in this case, the secret to aging gracefully.

So I had to know why Sapelo is so wonderful. Well, first, it is created in a pristine lab under careful supervision. There, Duttenhaver and Edward marry bio-active, Southern-inspired ingredients with a scientific system that mimics our body's natural healing process. It's my favorite kind of skincare: nature and science combined with cruelty-free ingredients, formulated without fillers, silicone, parabens, sulfates, GMOs, triclosan or petrochemicals.

What's more, Sapelo's formulations are a botanical profusion of gardenia stem cells, magnolia oil, oyster shell calcium, seaweed, essential oils and Georgia honey. Sigh. Now I'm craving a cold glass of sweet tea and a front porch.

Let's turn to Duttenhaver and Cindy Edwards for a quick Q&A.

Cindy Edwards: Sapelo Skin Care is named after one of the beautiful, largely undisturbed, and under-developed barrier islands off of the coast of Savannah, Georgia. It is a nod to our inspiration of nature and heeding lessons from generations of southern women to be gentle with our skin.

Stephanie Duttenhaver: Cindy and I both were looking for an authentic anti-aging strategy for our skin. We were seeing the first signs of aging, partly due to the effects of decades of southern sun exposure and to our unavoidable hormonal milestones! We were frustrated by the mediocre results of potions and lotions sold in luxury stores but were also wary of the quick-fix, invasive solutions, like dermabrasion, acid peels, and laser and light therapies.

My husband, a radiation oncologist, challenged me once with this comment: "When a radiation oncologist creates a laser burn on a cancer patient's skin, it's called a complication. But when skin is burned in a medical spa, clients pay for it. Does that make sense?"

The penny droppedmost mainstream dermatological procedures create damage to the skin; likewise, so do prestigious skincare brands containing retinoids and other acids. We realized that these strategies had one thing in common: creating havoc in the skin through damage and injury, then relying on the injury to recruit the body's immune system response to initiate repair and renewal.

When your skin is injured, your body releases a cascade of healing peptides, proteins, vitamins, and minerals to rebuild the damaged cells. We began to look at that cascade and wondered if we could replicate the restorative cascade in a skin care regimen that topically infused the same cascade but without the damage. It was at that moment we started to formulate the philosophy behind Sapelo Skin Care.

After three years of research, counsel with physicians and chemists, and the unerring support of friends and family, we launched our Three-Step Skin Recovery System. It is a gentle, stand-alone regimen that mimics our body's natural immune system response to injury but without the injury.

CE: We spent almost three years developing a product that nurtures and rejuvenates the skin gently and naturally by using Southern-inspired ingredients including gardenia stem cells, magnolia oil, oyster shells, Atlantic seaweed, bio-active peptides and micro-nutrients. We committed ourselves to only using the highest-quality ingredients in the highest quantity in our products.

For example: In our Renewing Serum, we use more than 4 percent hylauronic acid (HA) and a combination of three separate HAs at different molecular weights in order to flood the skin and really get down to all of the layers of the dermis, where new cells are produced.

SD: Relying on skin-damaging procedures and retinols as your anti-aging strategy. Our skin has an amazing capacity to heal, but that capacity is not unlimited. With repeated injury to your skin, year after year, your skin will thin we believe it leads to accelerated aging.

SD: Don't use acids to exfoliate your skin; use enzymes. Acids burn the skin, whether they are dead surface cells or healthy ones. But enzymes "eat" dead skin and leave healthy skin alone. Once you have removed the dead skin, that encourages a healthy environment for your complexion. I also do not like face scrubs. Use a soft cotton washcloth (I love baby washcloths!) to gently cleanse and remove dead skin.

SD: I love breakfast smoothies. Most mornings I will blend my favorite fruits, yogurt, cranberry juice, chia seeds and a collagen powder, which is full of peptides and amino acids, to make my daily concoction. My favorite collagen supplement is Beauty Collagen by Vital Proteins. It was developed to support collagen and hyaluronic acid production in the skin and hair. And it is manufactured in the U.S.that means a lot to me- especially in today's environment.

SD: Never turn down an opportunity to introduce or present your company's philosophy to an individual or group. As women, we are multitaskers and always juggling work, home, family and social connections. Cindy and I are no exceptionwe wonder how can we squeeze one more engagement into our day. The extra preparation and time you spend presenting your business at a small gathering or a grand occasion can often feel unwelcome or inconsequential. However, we have learned over and over again that every time we put energy out into the world, something of value always comes back to us, and that keeps us motivated and moving forward.

Sapelo Skin Care is available at Saks Fifth Avenue, 120 University Town Center Drive, Sarasota. The store is offering curbside service for purchases, returns, exchanges and alterations between 12-4 p.m., and plans to reopen to the public with limited hours12-6 p.m.on May 12. Call (941) 364-5300 for more information.

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Sapelo Skin Care Combines High-Tech Ingredients and Southern Charm - Sarasota

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11 Skincare Products To Try Now Injectables Are Off The Cards – British Vogue

May 9th, 2020

Youve probably seen those before-and-after quarantine memes, the ones featuring faces or more specifically, lips that have undergone a drastic change in shape in the absence of access to an aesthetician. Exaggerated they might be, but it is true that lockdown has left an injectable-shaped hole in some of our lives, and whether youre into them or not, our newly facial-free (and less-than-active) lifestyles are wreaking a certain amount of havoc on our skin anyway. For those who have regular in-clinic treatments, lockdown can mean that lines start to show, full lips diminish, cheeks depress and sunken eye sockets and dark circles re-appear, says aesthetic doctor Dr Sophie Shotter, who has temporarily shuttered her clinic and returned to the NHS frontline to join the fight against Covid-19. And, while the issue might seem trivial in light of everything else going on in the world, it is possible to harness the power of intelligent skincare to help mimic the effects of filler and Botox in lieu of the real thing. Dr Shotter shares her tips here.

Filler is routinely administered to add volume to the skin, usually in the face, says Shotter, who explains that its made from hyaluronic acid, a molecule we should all be utilising in our skincare routines to help soften fine lines. One of the best serums for the job is SkinCeuticals HA Intensifier, which boosts hyaluronic acid levels in the skin, making it look and feel firm, plump and hydrated. Alternatively, try LOrals Revitalift Filler Hyaluronic Acid for a more affordable option.

To smooth skin, Shotter also recommends BioEffect EGF Serum, which boosts skin thickness and collagen levels in the skin, meaning fewer wrinkles and a healthy glow. And finally, look to SkinBetter Science AlphaRet Overnight Cream to reap the benefits of prescription strength vitamin A (otherwise known as retinol): Retinol is the ultimate age management molecule that increases collagen levels, she says.

If youve had Botox before, you will know that its a toxin injected where there are dynamic lines to relax them and remove creases within the skin, says Shotter. There are products that mimic its effects: Meder Skincare Myo-Fix Concentrate, is full of muscle-relaxing peptides that work to block the nerve communicating with the muscle. Although it might sound daunting, its totally safe to use, and Shotter recommends regular and sustained use for the best results. Another great product to use if you usually have Botox administered superficially to regulate oil production is Institut Esthederms Pure System Pore Refiner Concentrate it is silicone based so refines their appearance beautifully.

Used religiously, there are products that can help to lift and plump the lips, although, like all of the products listed here, they wont have effects on a par with the treatment itself. One of the best to try is Fillerinas Lip Volume Grade 3, which contains six different hyaluronic acid molecules of varying weights and sizes, to deeply hydrate lips and give a fuller effect with continual use. Shotter also recommends a brilliant lip balm. Medik8s Mutiny Squalane Lip Balm helps to nourish and heal the lips, drawing moisture to the area to give them a plumper, more hydrated look, she says, adding that its important to use SPF to protect them from collagen-depleting UV rays. Protecting the health of the lips will help them stay plump and full.

Filler is often strategically placed to fill the hollows under the eyes, to refresh and hydrate and to lift dark circles, says Shotter. A (plant-based) stem cell serum, like Dr Levy Intense Stem Cell Eye Booster Concentrate, will boost the thickness of the delicate under eye skin, plus it also contains retinol and antioxidants to smooth fine lines and brighten the area. MGC Dermas CBD Stem Cells and Peptides Eye Cream is a brilliant option too, thanks to firming peptides, hyaluronic acid and calming CBD.

Terminally-ill teen with agonizingly-sensitive skin defies doctors to live to 19 – Metro.co.uk

May 9th, 2020

Marky Jaquez, 19, has recessive dystrophic epidermolysis bullosa, a condition found in fewer than one in one million newborns. (Picture: Melissa Jaquez/Metro.co.uk)

A teenager whose rare skin disorder means that even the slightest touch leaves him in extreme pain has defied doctors predictions to live to adulthood. Marky Jaquez, from Wichita, Kansas, cannot hug his parents, wear clothes or even walk because any friction causes layers of skin to peel away from his body.

Wheelchair-bound, Marky, 19, has never been able to walk because the ground would shred his feet like a cheese grater and must be covered head-to-toe in bandages to protect his fragile skin from tearing. He has recessive dystrophic epidermolysis bullosa, a condition found in an estimated one in one million newborns that often leads to life-threatening skin infections and even cancer.

The illness is caused by a faulty gene, passed onto children by parents. Tragically, Markys brother Carlos was born with it too, and died aged just 14. Doctors warned Markys parents he was unlikely to live beyond the age of 11, but he defied that grim prediction and will celebrate his 20th birthday later this year.

His mom, Melissa Jaquez, 40, said: Marky only has one layer of skin and because of his genetic makeup, the skin has no way of anchoring itself the body. Any form of touch or friction means his skins just tears away.

Its world shattering to think I will lose both of my boys to this and I dont want to think about what life will be like afterwards. I feel like my purpose in life is to give Mary the best life I can for the time that I have him.

I am not able to hug my son because any friction just causes his skin to come away and tear right off. It causes him excruciating pain and I feel so much guilt, but theres nothing I can do to help him.

But despite all of this he is a very happy and joyful boy and he amazes me every single day. Hes an inspiration and proves to everyone that you can keep going with whatever youre going through, no matter how bad it is.

Marky is the youngest of three brothers born to healthcare worker, Melissa. Eldest son Michael is 24, with Carlos dying of heart failure caused by the skin condition in 2015. Marky and Carlos, who would be 21 this year, were both born with the same condition after inheriting a faulty gene from their parents.

Melissa said doctors suspect both she and the boys father carry the faulty gene that causes the genetic mutation. Although both are unaffected themselves, they have an estimated 25% chance of having a child born with recessive dystrophic epidermolysis bullosa. Melissa has since split up with Marky and Carlos father neither of whom knew they carried the faulty gene until Carlos was born, she said.

Melissa said she became aware of the risks involved with having a child after Carlos was born, but claims she was told by a clinician that the chance of her having a second child with the same condition would be less than 1%.

Melissa said: I lost Carlos to the condition because his heart just gave up. His body was in a constant battle to repair his wounds and that took its toll eventually.

His condition was much more progressive than Markys. He got real bad, real quick and by the end could not even breathe on his own.

My pregnancy with Marky was unplanned, but when I got pregnant I was told the chance of me having another baby with the same condition is 1%. They said having two children with it is unheard of.

Marky was born with the most severe type of epidermolysis bullosa meaning he was delivered without skin on his hands, feet and chest because because of the friction of childbirth.

Ever since Marky was little, Melissa, who is now married to Marcos, 30, has had to spend up to three hours a day covering his skin in protective bandages and cleaning open wounds to prevent infection.

She has said every day of motherhood so far has felt like a battle and admits she has struggled to have a normal mother and son relationship with Marky, because of his condition.

Every day is such a massive challenge for us. I struggle with the grief of knowing that when I walk into my sons room in a morning, we cant have fun. I dont get to do the normal things that a mom and a son does.

Instead when I go into his room I know I have to cause him pain and spend two hours doing his bandages. That does give me a lot of anxiety and guilt.

Taking his bandages off does cause excruciating pain. We have to soak his skin every day to soothe his wounds and give him pain medication. Its incredibly upsetting for me.

Whilst there is no cure for epidermolysis bullosa and Marky is highly likely to sadly one day lose his life to the condition, Melissa is hopefully he will survive for several more years.

He has been selected to take part in experimental treatment to create genetically modified skin stem cells that can slow down the effects of the progressive disease. The family plan to travel to Stamford Hospital, Connecticut, later this year to undergo the treatment.

Melissa and Marcos work opposite shifts and have a carer who comes to help look after Marky for three hours each day. Melissa has paid tribute to her amazing son, who she believes can go on to live for many happy years, despite the predictions of doctors.

She said: The treatment at Stamford could add several years to his life. It will reduce the pain and make it easier for his body to cope.

We have tried for that treatment for years, so were thrilled.

Marky has always been an incredibly happy boy and he has just got on with it, without ever moaning or saying why me. Ive had messages from people all over the world to say Marky has inspired them.

Hes an amazing human being and he makes me so proud.

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Terminally-ill teen with agonizingly-sensitive skin defies doctors to live to 19 - Metro.co.uk

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Top 10 Best The Body Shop Anti Aging Body Creams 2020 – Best gaming pro

May 9th, 2020

This story was initially printed 2020/03/19 9:55am PDTon Mar 19, 2020 and final up to date 2020/05/08 11:34am PDTCould eight, 2020.

Again at F8 2019, Fb promised a redesign for its cellular apps and web site. The Android app began receiving the brand new interface nearly instantly, however the change was solely promised on the net in the following few months. Now, it is beginning to roll out and together with it comes a brand new darkish mode possibility.

For the previous few days, many users have reported that they received prompted by Fb to check out the brand new interface. After accepting, they get requested in the event that theyd like to make use of the white or darkish structure. The selection can also be out there underneath the fast settings accessible from the highest proper avatar.

Picture credit score: @teepusahab, @kimsantoshansen

After all, the brand new design isnt universally liked, and it even has issues with text readability in a few dark mode screens. However that is the worth of any early launch.

If you arent getting prompted by Fbs web site to attempt the brand new look, there does not appear to be any workaround to force-trigger it simply but.

Rolling out to more users

The new Facebook web UI with the dark theme seems to be rolling out widely. Thanks, Anurag Dalmia!

Facebook announcement

Based on the reports we received, it was clear that Facebooks new look was already being widely deployed, but today the company has put the final pin in this story by formally announcing the UI overhaul.

In a news post, Fb discusses its planning and analysis efforts that went in to designing the brand new interface. Not everybodys been a fan of those modifications, however at the very least we are able to hear Fb out on why it thinks this new look is superior.

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Top 10 Best The Body Shop Anti Aging Body Creams 2020 - Best gaming pro

Recommendation and review posted by Bethany Smith

ROCKET PHARMACEUTICALS : Management’s Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) – marketscreener.com

May 9th, 2020

You should read the following discussion and analysis of our financial conditionand results of operations together with the condensed consolidated financialstatements and related notes that are included elsewhere in this QuarterlyReport on Form 10-Q and our Annual Report on Form 10-K for the fiscal year endedDecember 31, 2019 filed with the U.S. Securities and Exchange Commission, or theSEC, on March 6, 2020, or our 2019 Form 10-K. This discussion containsforward-looking statements based upon current plans, expectations and beliefsthat involve risks and uncertainties. Our actual results may differ materiallyfrom those anticipated in these forward-looking statements as a result ofvarious factors, including, but not limited to, those discussed in the sectionentitled "Risk Factors" and elsewhere in this Quarterly Report on Form 10-Q. Inpreparing this MD&A, we presume that readers have access to and have read theMD&A in our 2019 Form 10-K, pursuant to Instruction 2 to paragraph (b) of Item303 of Regulation S-K. Unless stated otherwise, references in this QuarterlyReport on Form 10-Q to "us," "we," "our," or our "Company" and similar termsrefer to Rocket Pharmaceuticals, Inc.

We are a clinical-stage, multi-platform biotechnology company focused on thedevelopment of first, only and best-in-class gene therapies, with directon-target mechanism of action and clear clinical endpoints, for rare anddevastating diseases. We currently have three clinical-stage ex vivo lentiviralvector ("LVV") programs currently enrolling patients in the US and EU forFanconi Anemia ("FA"), a genetic defect in the bone marrow that reducesproduction of blood cells or promotes the production of faulty blood cells,Leukocyte Adhesion Deficiency-I ("LAD-I"), a genetic disorder that causes theimmune system to malfunction and Pyruvate Kinase Deficiency ("PKD"), a rare redblood cell autosomal recessive disorder that results in chronic non-spherocytichemolytic anemia. Of these, both the Phase 2 FA program and the Phase 1/2 LAD-Iprogram are in registration-enabling studies in the US and EU. In addition, inthe US we have a clinical stage in vivo adeno-associated virus ("AAV") programfor Danon disease, a multi-organ lysosomal-associated disorder leading to earlydeath due to heart failure. Finally, we have a pre-clinical stage LVV programfor Infantile Malignant Osteopetrosis ("IMO"), a genetic disorder characterizedby increased bone density and bone mass secondary to impaired bone resorption -this program is anticipated to enter the clinic in 2020. We have globalcommercialization and development rights to all of these product candidatesunder royalty-bearing license agreements. Additional work in the discovery stagefor an FA CRISPR/CAS9 program as well as a gene therapy program for the lesscommon FA subtypes C and G is ongoing.

Recent Developments

On February 20, 2020, we entered into separate, privately negotiated exchangeagreements (the "Exchange Agreements") with certain holders of our outstanding5.75% Convertible Senior Notes due 2021 (the "2021 Convertible Notes") to extendthe maturity date by one year. Pursuant to the Exchange Agreements, we exchangedapproximately $39.35 million aggregate principal amount of the 2021 ConvertibleNotes (which represents approximately 76% of the aggregate outstanding principalamount of the 2021 Convertible Notes) for (a) approximately $39.35 millionaggregate principal amount of 6.25% Convertible Senior Notes due August 2022(the "2022 Convertible Notes") (an exchange ratio equal to 1.00 2022 ConvertibleNote per exchanged 2021 Convertible Note) and (b) $119,416 in cash to pay theaccrued and unpaid interest on the exchanged 2021 Convertible Notes from, andincluding, February 1, 2020 to February 20, 2020. The 2022 Convertible Noteswere issued in private placements exempt from registration in reliance onSection 4(a) (2) of the Securities Act of 1933, as amended (the "SecuritiesAct"). Upon completion of the exchange transactions, approximately $12.65million aggregate principal amount of 2021 Convertible Notes remainedoutstanding.

Gene Therapy Overview

Genes are composed of sequences of deoxyribonucleic acid ("DNA"), which code forproteins that perform a broad range of physiologic functions in all livingorganisms. Although genes are passed on from generation to generation, geneticchanges, also known as mutations, can occur in this process. These changes canresult in the lack of production of proteins or the production of alteredproteins with reduced or abnormal function, which can in turn result in disease.

Gene therapy is a therapeutic approach in which an isolated gene sequence orsegment of DNA is administered to a patient, most commonly for the purpose oftreating a genetic disease that is caused by genetic mutations. Currentlyavailable therapies for many genetic diseases focus on administration of largeproteins or enzymes and typically address only the symptoms of the disease. Genetherapy aims to address the disease-causing effects of absent or dysfunctionalgenes by delivering functional copies of the gene sequence directly into thepatient's cells, offering the potential for curing the genetic disease, ratherthan simply addressing symptoms.

We are using modified non-pathogenic viruses for the development of our genetherapy treatments. Viruses are particularly well suited as delivery vehiclesbecause they are adept at penetrating cells and delivering genetic materialinside a cell. In creating our viral delivery vehicles, the viral (pathogenic)genes are removed and are replaced with a functional form of the missing ormutant gene that is the cause of the patient's genetic disease. The functionalform of a missing or mutant gene is called a therapeutic gene, or the"transgene." The process of inserting the transgene is called "transduction."Once a virus is modified by replacement of the viral genes with a transgene, themodified virus is called a "viral vector." The viral vector delivers thetransgene into the targeted tissue or organ (such as the cells inside apatient's bone marrow). We have two types of viral vectors in development, LVVand AAV. We believe that our LVV and AAV-based programs have the potential tooffer a long-lasting and significant therapeutic benefit to patients.

Gene therapies can be delivered either (1) ex vivo (outside the body), in whichcase the patient's cells are extracted and the vector is delivered to thesecells in a controlled, safe laboratory setting, with the modified cells thenbeing reinserted into the patient, or (2) in vivo (inside the body), in whichcase the vector is injected directly into the patient, either intravenously("IV") or directly into a specific tissue at a targeted site, with the aim ofthe vector delivering the transgene to the targeted cells.

We believe that scientific advances, clinical progress, and the greaterregulatory acceptance of gene therapy have created a promising environment toadvance gene therapy products as these products are being designed to restorecell function and improve clinical outcomes, which in many cases includeprevention of death at an early age.

--------------------------------------------------------------------------------

The chart below shows the current phases of development of Rocket's programs andproduct candidates:

LVV Programs. Rocket's LVV-based programs utilize third-generation,self-inactivating lentiviral vectors to target selected rare diseases.Currently, Rocket is developing LVV programs to treat FA, LAD-I, PKD, and IMO.

Fanconi Anemia Complementation Group A (FANCA):

FA, a rare and life-threatening DNA-repair disorder, generally arises from amutation in a single FA gene. An estimated 60 to 70% of cases arise frommutations in the Fanconi-A ("FANCA") gene, which is the focus of our program. FAresults in bone marrow failure, developmental abnormalities, myeloid leukemiaand other malignancies, often during the early years and decades of life. Bonemarrow aplasia, which is bone marrow that no longer produces any or very few redand white blood cells and platelets leading to infections and bleeding, is themost frequent cause of early morbidity and mortality in FA, with a median onsetbefore 10 years of age. Leukemia is the next most common cause of mortality,ultimately occurring in about 20% of patients later in life. Solid organmalignancies, such as head and neck cancers, can also occur, although at lowerrates during the first two to three decades of life.

Although improvements in allogeneic (donor-mediated) hematopoietic stem celltransplant ("HSCT"), currently the most frequently utilized therapy for FA, haveresulted in more frequent hematologic correction of the disorder, HSCT isassociated with both acute and long-term risks, including transplant-relatedmortality, graft versus host disease ("GVHD"), a sometimes fatal side effect ofallogeneic transplant characterized by painful ulcers in the GI tract, livertoxicity and skin rashes, as well as increased risk of subsequent cancers. Ourgene therapy program in FA is designed to enable a minimally toxic hematologiccorrection using a patient's own stem cells during the early years of life. Webelieve that the development of a broadly applicable autologous gene therapy canbe transformative for these patients.

Each of our LVV-based programs utilize third-generation, self-inactivatinglentiviral vectors to correct defects in patients' HSCs, which are the cellsfound in bone marrow that are capable of generating blood cells over a patient'slifetime. Defects in the genetic coding of HSCs can result in severe, andpotentially life-threatening anemia, which is when a patient's blood lacksenough properly functioning red blood cells to carry oxygen throughout the body.Stem cell defects can also result in severe and potentially life-threateningdecreases in white blood cells resulting in susceptibility to infections, and inplatelets responsible for blood clotting, which may result in severe andpotentially life-threatening bleeding episodes. Patients with FA have a geneticdefect that prevents the normal repair of genes and chromosomes within bloodcells in the bone marrow, which frequently results in the development of acutemyeloid leukemia ("AML"), a type of blood cancer, as well as bone marrow failureand congenital defects. The average lifespan of an FA patient is estimated to be30 to 40 years. The prevalence of FA in the US and EU is estimated to be about4,000, and given the efficacy seen in non-conditioned patients, the addressableannual market opportunity is now thought to be in the 400 to 500 range.

We currently have one LVV-based program targeting FA, RP-L102. RP-L102 is ourlead lentiviral vector based program that we in-licensed from Centro deInvestigaciones Energticas, Medioambientales y Tecnolgicas ("CIEMAT"), whichis a leading research institute in Madrid, Spain. RP-L102 is currently beingstudied in our sponsored Phase 2 registrational enabling clinical trialstreating FA patients initially at the Center for Definitive and CurativeMedicine at Stanford University School of Medicine ("Stanford") and HospitalInfantil de Nino Jesus ("HNJ") in Spain. The Phase 2 portion of the trial isexpected to enroll ten patients total from the U.S. and EU. Patients willreceive a single IV infusion of RP-L102 that utilizes fresh cells and "ProcessB" which incorporates a modified stem cell enrichment process, transductionenhancers, as well as commercial-grade vector and final drug product.

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Table of ContentsIn October 2019, at the European Society of Cell and Gene Therapy ("ESGCT") 2019Annual Congress, long-term Phase 1/2 clinical data of RP-L102, from the clinicaltrial sponsored by CIEMAT, for FA "Process A", without the use of myeloablativeconditioning was presented demonstrating evidence of increasing and durableengraftment leading to bone marrow restoration exceeding the 10% thresholdagreed to by the FDA and EMA for the ongoing registration-enabling Phase 2trial. In patient 02002, who received what we consider adequate drug product,hemoglobin levels are now similar to those in the first year after birth,suggesting hematologic correction over the long term.

During the third quarter of 2019, we received alignment from the FDA on thetrial design and the primary endpoint. This alignment was similar to thatpreviously received from the European Medicines Agency ("EMA"). Resistance tomitomycin-C, a DNA damaging agent, in bone marrow stem cells at a minimum timepoint of one year to serve as the primary endpoint for our Phase II study. InDecember 2019, we announced that the first patient of the global Phase 2 studyfor RP-L102 "Process B" for FA received investigational therapy. There will betotal of 10 patients enrolled in the global Phase 2 studies.

In December 2019, we also announced preliminary results from two pediatricpatients treated with "Process B" RP-L102 prior to development of severe bonemarrow failure in our Phase 1 trial of RP-L102 for FA. To evaluate transductionefficiency, an analysis of the proportion of the MMC-resistant colony formingcells was conducted and both patients have thus far exhibited early signs ofengraftment, including increases in blood cell lineages in one patient. Nodrug-related safety or tolerability issues have been reported.

Leukocyte Adhesion Deficiency-I (LAD-I):

LAD-I is a rare autosomal recessive disorder of white blood cell adhesion andmigration, resulting from mutations in the ITGB2 gene encoding for the Beta-2Integrin component, CD18. Deficiencies in CD18 result in an impaired ability forneutrophils (a subset of infection-fighting white blood cells) to leave bloodvessels and enter into tissues where these cells are needed to combatinfections. As is the case with many rare diseases, true estimates of incidenceare difficult; however, several hundred cases have been reported to date.

Most LAD-I patients are believed to have the severe form of the disease. SevereLAD-I is notable for recurrent, life-threatening infections and substantialinfant mortality in patients who do not receive an allogeneic HSCT. Mortalityfor severe LAD-I has been reported as 60 to 75% by age two in the absence ofallogeneic HCST.

We currently have one program targeting LAD-I, RP-L201. RP-L201 is a clinicalprogram that we in-licensed from CIEMAT. We have partnered with UCLA to leadU.S. clinical development efforts for the LAD-I program. UCLA and its Eli andEdythe Broad Center of Regenerative Medicine and Stem Cell Research is servingas the lead U.S. clinical research center for the registrational clinical trialfor LAD-I, and HNJ is serving as the lead clinical site in Spain.

The ongoing open-label, single-arm, Phase 1/2 registration enabling clinicaltrial of RP-L201 has dosed one severe LAD-I patient in the U.S. to assess thesafety and tolerability of RP-L201. The first patient was treated with RP-L201in third quarter 2019. This study has received $6.5 million CLIN2 grant awardfrom the California Institute for Regenerative Medicine ("CIRM") to support theclinical development of gene therapy for LAD-I.

In December 2019, we announced initial results from the first pediatric patienttreated with RP-L201, demonstrating early evidence of safety. Analyses ofperipheral vector copy number ("VCN"), and CD18-expressing neutrophils wereperformed through three months after infusion of RP-L201 to evaluate engraftmentand phenotypic correction. The patient exhibited early signs of engraftment withVCN myeloid levels at 1.5 at three months and CD-18 expression of 45%. No safetyor tolerability issues related to RP-L201 administration (or investigationalproduct) had been identified as of that date. The study is expected to enrollnine patients globally.

Pyruvate Kinase Deficiency (PKD):

Red blood cell PKD is a rare autosomal recessive disorder resulting frommutations in the pyruvate kinase L/R ("PKLR") gene encoding for a component ofthe red blood cell ("RBC") glycolytic pathway. PKD is characterized by chronicnon-spherocytic hemolytic anemia, a disorder in which RBCs do not assume anormal spherical shape and are broken down, leading to decreased ability tocarry oxygen to cells, with anemia severity that can range from mild(asymptomatic) to severe forms that may result in childhood mortality or arequirement for frequent, lifelong RBC transfusions. The pediatric population isthe most commonly and severely affected subgroup of patients with PKD, and PKDoften results in splenomegaly (abnormal enlargement of the spleen), jaundice andchronic iron overload which is likely the result of both chronic hemolysis andthe RBC transfusions used to treat the disease. The variability in anemiaseverity is believed to arise in part from the large number of diverse mutationsthat may affect the PKLR gene. Estimates of disease incidence have rangedbetween 3.2 and 51 cases per million in the white U.S. and EU population.Industry estimates suggest at least 2,500 cases in the U.S. and EU have alreadybeen diagnosed despite the lack of FDA-approved molecularly targeted therapies.Enrollment is currently ongoing and we anticipate treating the first patient inthe third quarter of 2020.

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Table of ContentsWe currently have one LVV-based program targeting PKD, RP-L301. RP-L301 is aclinical stage program that we in-licensed from CIEMAT. The IND for RP-L301 toinitiate a global Phase 1 study was cleared by the FDA in October 2019. Thisprogram has been granted EMA orphan drug disease designation and FDA orphan drugdisease designation ("ODD").

This global Phase 1 open-label, single-arm, clinical trial is expected to enrollsix adult and pediatric transfusion-dependent PKD patients in the U.S. andEurope. Lucile Packard Children's Hospital Stanford will serve as the lead sitein the U.S. for adult and pediatric patients, and Hospital InfantilUniversitario Nio Jess will serve as the lead site in Europe for pediatricsand Hospital Universitario Fundacin Jimnez Daz will serve as the lead site inEurope for adult patients.

Infantile Malignant Osteopetrosis (IMO):

IMO is a genetic disorder characterized by increased bone density and bone masssecondary to impaired bone resorption. Normally, small areas of bone areconstantly being broken down by special cells called osteoclasts, then madeagain by cells called osteoblasts. In IMO, the cells that break down bone(osteoclasts) do not work properly, which leads to the bones becoming thickerand not as healthy. Untreated IMO patients may suffer from a compression of thebone-marrow space, which results in bone marrow failure, anemia and increasedinfection risk due to the lack of production of white blood cells. Untreated IMOpatients may also suffer from a compression of cranial nerves, which transmitsignals between vital organs and the brain, resulting in blindness, hearing lossand other neurologic deficits.

We currently have one LVV-based program targeting IMO, RP-L401. RP-L401 is apreclinical program that we in-licensed from Lund University, Sweden. Thisprogram has been granted ODD and Rare Pediatric Disease designation from theFDA. The FDA defines a "rare pediatric disease" as a serious andlife-threatening disease that affects less than 200,000 people in the U.S. thatare aged between birth to 18 years. The Rare Pediatric Disease designationprogram allows for a sponsor who receives an approval for a product topotentially qualify for a voucher that can be redeemed to receive a priorityreview of a subsequent marketing application for a different product. We havepartnered with UCLA to lead U.S. clinical development efforts for the IMOprogram and anticipate that UCLA will serve as the lead U.S. clinical site forIMO. We intend to file an IND for IMO and commence our clinical trial in thefourth quarter of 2020.

Danon disease is a multi-organ lysosomal-associated disorder leading to earlydeath due to heart failure. Danon disease is caused by mutations in the geneencoding lysosome-associated membrane protein 2 ("LAMP-2"), a mediator ofautophagy. This mutation results in the accumulation of autophagic vacuoles,predominantly in cardiac and skeletal muscle. Male patients often require hearttransplantation and typically die in their teens or twenties from progressiveheart failure. Along with severe cardiomyopathy, other Danon disease symptomscan include skeletal muscle weakness, liver disease, and intellectualimpairment. There are no specific therapies available for the treatment of Danondisease. RP-A501 is in clinical trials as an in vivo therapy for Danon disease,which is estimated to have a prevalence of 15,000 to 30,000 patients in the U.S.and the EU, however new market research is being performed and the prevalence ofpatients may be updated in the future.

In January 2019, we announced the clearance of our IND application by the FDAfor RP-A501, and in February 2019, we were notified by the FDA that we weregranted Fast Track designation for RP-A501. University of California San DiegoHealth is the initial and lead center for our Phase 1 clinical trial.

On May 2, 2019, we presented additional preclinical data at the ASCGT annualmeeting, indicating that high VCN, in Danon disease-relevant organs in both miceand non-human primates ("NHN's"), with high concentrations in heart and livertissue (for NHP, cardiac VCN was approximately 10 times higher on average thanin skeletal muscle and central nervous system), which is consistent withreported results in several studies of heart tissue across different species.There were no treatment-related adverse events or safety issues up to thehighest dose. We have dosed three patients in the RP-A501 phase 1 clinicaltrial. We will continue further enrollment with clinical data read-outs in thefourth quarter of 2020.

As of March 2020, we have dosed three patients in the RP-A501 phase 1 clinicaltrial. This completes the first low dose cohort of the Phase 1 study. Based onthe preliminary safety and efficacy data review of this completed cohort, boththe FDA and IDMC has provided clearance to advance to a higher dose cohort inPhase 1 Trial of RP-A501 for Danon Disease. We will continue further enrollmentwith clinical data read-outs in the second half of 2020.

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In addition to its LVV and AAV programs, we also have a program evaluatingCRISPR/Cas9-based gene editing for FA. This program is currently in thediscovery phase. CRISPR/Cas9-based gene editing is a different method ofcorrecting the defective genes in a patient, where the editing is very specificand targeted to a particular gene sequence. "CRISPR/Cas9" stands for Clustered,Regularly Interspaced Short Palindromic Repeats ("CRISPR") Associated protein-9.The CRISPR/Cas9 technology can be used to make "cuts" in DNA at specific sitesof targeted genes, making it potentially more precise in delivering genetherapies than traditional vector-based delivery approaches. CRISPR/Cas9 canalso be adapted to regulate the activity of an existing gene without modifyingthe actual DNA sequence, which is referred to as gene regulation.

Strategy

We seek to bring hope and relief to patients with devastating, undertreated,rare pediatric diseases through the development and commercialization ofpotentially curative first-in-class gene therapies. To achieve these objectives,we intend to develop into a fully-integrated biotechnology company. In the near-and medium-term, we intend to develop our first-in-class product candidates,which are targeting devastating diseases with substantial unmet need, developproprietary in-house analytics and manufacturing capabilities and continue tocommence registration trials for our currently planned programs. In the mediumand long-term, we expect to submit our first biologics license applications("BLAs"), and establish our gene therapy platform and expand our pipeline totarget additional indications that we believe to be potentially compatible withour gene therapy technologies. In addition, during that time, we believe thatour currently planned programs will become eligible for priority review vouchersfrom the FDA that provide for expedited review. We have assembled a leadershipand research team with expertise in cell and gene therapy, rare disease drugdevelopment and commercialization.

We believe that our competitive advantage lies in our disease-based selectionapproach, a rigorous process with defined criteria to identify target diseases.We believe that this approach to asset development differentiates us as a genetherapy company and potentially provides us with a first-mover advantage.

Financial Overview

Since our inception, we have devoted substantially all of our resources toorganizing and staffing the Company, business planning, raising capital,acquiring or discovering product candidates and securing related intellectualproperty rights, conducting discovery, research and development activities forthe programs and planning for potential commercialization. We do not have anyproducts approved for sale and have not generated revenue from product sales.From inception through March 31, 2020, we raised net cash proceeds ofapproximately $373.1 million from investors through both equity and convertibledebt financing to fund operating activities. As of March 31, 2020, we had cash,cash equivalents and investments of $275.9 million.

Since inception, we have incurred significant operating losses. Our ability togenerate product revenue sufficient to achieve profitability will depend heavilyon the successful development and eventual commercialization of one or more ofthe current or future product candidates and programs. We had net losses of$24.7 million for the three months ended March 31, 2020 and $77.3 million forthe year ended December 31, 2019. As of March 31, 2020, we had an accumulateddeficit of $207.8 million. We expect to continue to incur significant expensesand higher operating losses for the foreseeable future as we advance our currentproduct candidates from discovery through preclinical development and clinicaltrials and seek regulatory approval of our product candidates. In addition, ifwe obtain marketing approval for any of their product candidates, we expect toincur significant commercialization expenses related to product manufacturing,marketing, sales and distribution. Furthermore, we expect to incur additionalcosts as a public company. Accordingly, we will need additional financing tosupport continuing operations and potential acquisitions of licensing or otherrights for product candidates.

Until such a time as we can generate significant revenue from product sales, ifever, we will seek to fund our operations through public or private equity ordebt financings or other sources, which may include collaborations with thirdparties and government programs or grants. Adequate additional financing may notbe available to us on acceptable terms, or at all. We can make no assurancesthat we will be able to raise the cash needed to fund our operations and, if wefail to raise capital when needed, we may have to significantly delay, scaleback or discontinue the development and commercialization of one or more productcandidates or delay pursuit of potential in-licenses or acquisitions.

Because of the numerous risks and uncertainties associated with productdevelopment, we are unable to predict the timing or amount of increased expensesor when or if we will be able to achieve or maintain profitability. Even if weare able to generate product sales, we may not become profitable. If we fail tobecome profitable or are unable to sustain profitability on a continuing basis,then we may be unable to continue our operations at planned levels and be forcedto reduce or terminate our operations.

Revenue

To date, we have not generated any revenue from any sources, including fromproduct sales, and we do not expect to generate any revenue from the sale ofproducts in the near future. If our development efforts for product candidatesare successful and result in regulatory approval or license agreements withthird parties, we may generate revenue in the future from product sales.

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Research and Development Expenses

Our research and development program ("R&D") expenses consist primarily ofexternal costs incurred for the development of our product candidates. Theseexpenses include:

expenses incurred under agreements with research institutions that conduct

research and development activities including, process development,

preclinical, and clinical activities on Rocket's behalf;

costs related to process development, production of preclinical and clinical

materials, including fees paid to contract manufacturers and manufacturing

input costs for use in internal manufacturing processes;

consultants supporting process development and regulatory activities; and

costs related to in-licensing of rights to develop and commercialize our

product candidate portfolio.

We recognize external development costs based on contractual payment schedulesaligned with program activities, invoices for work incurred, and milestoneswhich correspond with costs incurred by the third parties. Nonrefundable advancepayments for goods or services to be received in the future for use in researchand development activities are recorded as prepaid expenses.

Our direct research and development expenses are tracked on a program-by-programbasis for product candidates and consist primarily of external costs, such asresearch collaborations and third party manufacturing agreements associated withour preclinical research, process development, manufacturing, and clinicaldevelopment activities. Our direct research and development expenses by programalso include fees incurred under license agreements. Our personnel, non-programand unallocated program expenses include costs associated with activitiesperformed by our internal research and development organization and generallybenefit multiple programs. These costs are not separately allocated by productcandidate and consist primarily of:

Our research and development activities are central to our business model.Product candidates in later stages of clinical development generally have higherdevelopment costs than those in earlier stages of clinical development. As aresult, we expect that research and development expenses will increasesubstantially over the next several years as we increase personnel costs,including stock-based compensation, support ongoing clinical studies, seek toachieve proof-of-concept in one or more product candidates, advance preclinicalprograms to clinical programs, and prepare regulatory filings for productcandidates.

We cannot determine with certainty the duration and costs to complete current orfuture clinical studies of product candidates or if, when, or to what extent wewill generate revenues from the commercialization and sale of any of our productcandidates that obtain regulatory approval. We may never succeed in achievingregulatory approval for any of our product candidates. The duration, costs, andtiming of clinical studies and development of product candidates will depend ona variety of factors, including:

the scope, rate of progress, and expense of ongoing as well as any future

clinical studies and other research and development activities that we

undertake;

future clinical trial results;

uncertainties in clinical trial enrollment rates;

changing standards for regulatory approval; and

the timing and receipt of any regulatory approvals.

We expect research and development expenses to increase for the foreseeablefuture as we continue to invest in research and development activities relatedto developing product candidates, including investments in manufacturing, as ourprograms advance into later stages of development and as we conduct additionalclinical trials. The process of conducting the necessary clinical research toobtain regulatory approval is costly and time-consuming, and the successfuldevelopment of product candidates is highly uncertain. As a result, we areunable to determine the duration and completion costs of research anddevelopment projects or when and to what extent we will generate revenue fromthe commercialization and sale of any of our product candidates.

Our future research and development expenses will depend on the clinical successof our product candidates, as well as ongoing assessments of the commercialpotential of such product candidates. In addition, we cannot forecast with anydegree of certainty which product candidates may be subject to futurecollaborations, when such arrangements will be secured, if at all, and to whatdegree such arrangements would affect our development plans and capitalrequirements. We expect our research and development expenses to increase infuture periods for the foreseeable future as we seek to complete development ofour product candidates.

The successful development and commercialization of our product candidates ishighly uncertain. This is due to the numerous risks and uncertainties associatedwith product development and commercialization, including the uncertainty of:

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Table of Contents

the scope, progress, outcome and costs of our clinical trials and other

research and development activities;

the efficacy and potential advantages of our product candidates compared to

alternative treatments, including any standard of care;

the market acceptance of our product candidates;

obtaining, maintaining, defending and enforcing patent claims and other

intellectual property rights;

significant and changing government regulation; and

the timing, receipt and terms of any marketing approvals.

A change in the outcome of any of these variables with respect to thedevelopment of our product candidates that we may develop could mean asignificant change in the costs and timing associated with the development ofour product candidates. For example, if the FDA or another regulatory authoritywere to require us to conduct clinical trials or other testing beyond those thatwe currently contemplate for the completion of clinical development of any ofour product candidates that we may develop or if we experience significantdelays in enrollment in any of our clinical trials, we could be required toexpend significant additional financial resources and time on the completion ofclinical development of that product candidate.

General and Administrative Expenses

General and administrative ("G&A") expenses consist primarily of salaries andrelated benefit costs for personnel, including stock-based compensation andtravel expenses for our employees in executive, operational, finance, legal,business development, and human resource functions. In addition, othersignificant general and administrative expenses include professional fees forlegal, patents, consulting, investor and public relations, auditing and taxservices as well as other expenses for rent and maintenance of facilities,insurance and other supplies used in general and administrative activities. Weexpect general and administrative expenses to increase for the foreseeablefuture due to anticipated increases in headcount to support the continuedadvancement of our product candidates. We also anticipate that we will incurincreased accounting, audit, legal, regulatory, compliance and director andofficer insurance costs as well as investor and public relations expenses.

Interest Expense

Interest expense is related to the 2021 Convertible Notes, which mature inAugust 2021, and the 2022 Convertible Notes, which mature in August 2022.

Interest Income

Interest income is related to interest earned from investments.

Critical Accounting Policies and Significant Judgments and Estimates

Our consolidated financial statements are prepared in accordance with generallyaccepted accounting principles in the U.S. The preparation of our financialstatements and related disclosures requires us to make estimates and judgmentsthat affect the reported amounts of assets, liabilities, costs and expenses, andthe disclosure of contingent assets and liabilities in our financial statements.We base our estimates on historical experience, known trends and events andvarious other factors that we believe are reasonable under the circumstances,the results of which form the basis for making judgments about the carryingvalues of assets and liabilities that are not readily apparent from othersources. We evaluate estimates and assumptions on an ongoing basis. Actualresults may differ from these estimates under different assumptions orconditions.

Our significant accounting policies are described in more detail in our 2019Form 10-K, except as otherwise described below.

Results of Operations

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Its In The Genes? Scientists Think Coronavirus Exploits Silent Hidden Mutations In The Body – International Business Times

May 9th, 2020

KEY POINTS

Health experts have been baffled as to why there are people infected with COVID-19 and yet barely feel the infection while others suffer life-threatening symptoms even if healthy and young. Scientists are looking for answers in the genes of patients, trying to discover mutations that affect the immune response, hoping that it could help in coming up with new treatments.

Profile Of A Severe Case

During the early days of the pandemic, a general profile of a severe case of coronavirus infection started to emerge. They are older adults with pre-existing medical conditions and are likely to be male. As the virus continued to infect more people, a small fraction started to deviate from the general profile.

Health experts are starting to see around 5% of those infected are under the age of 50 and do not have any underlying health conditions. These are the group of patients that interest Dr. Jean-Laurent Casanova, a geneticist and head of the St. Giles Laboratory of Human Genetics of Infectious Diseases.

Dr. Casanova told the AFP it is possible for someone who joined a marathon in October 2019 to find himself in intensive care, ventilated and intubated in April 2020. He revealed his desire to know if these types of patients have rare genetic mutations that have been triggered by the coronavirus infection. The assumption is that these patients have genetic variations that are silent until the virus is encountered, the doctor said. coronavirus silent mutation in human body may be the one exploited by the virus Photo: TPHeinz - Pixabay

A Huge Global Effort

The geneticist co-founded the COVID Human Genetics Effort, a collaborative work that seeks to know more about the genome of severely-ill young patients in several countries worldwide. These include patients in Europe, Japan, Iran, China, and the United States.

Dr. Casanovas group is also studying those who did not get infected despite being exposed many times. He said their main goal is to know why some are sicker than others, a knowledge that the geneticist said might help them in their quest to develop anti-viral therapies.

Gene Mutations Have A Long History

Scientists have long known that gene mutations can make people more susceptible to an array of infectious diseases, ranging from influenza to viral encephalitis. These gene mutations can also offer protection sometimes.

In the 1990s, a group of researchers found out that some rare mutations of a single gene successfully protected people against HIV infection. This discovery led to a betterunderstanding of how the virus worked and eventually paved the way for scientists to develop new treatments.

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Its In The Genes? Scientists Think Coronavirus Exploits Silent Hidden Mutations In The Body - International Business Times

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LYNPARZA (olaparib) Approved by FDA as First-Line Maintenance Treatment with Bevacizumab for HRD-Positive Advanced Ovarian Cancer – BioSpace

May 9th, 2020

The approval was based on a biomarker subgroup analysis of 387 patients with HRD-positive tumors from the Phase 3 PAOLA-1 trial, which showed that LYNPARZA in combination with bevacizumab reduced the risk of disease progression or death by 67% (HR 0.33 [95% CI, 0.25-0.45]). It improved progression-free survival (PFS) to a median of 37.2 months vs. 17.7 months with bevacizumab alone in patients with HRD-positive advanced ovarian cancer.

The most common adverse reactions (ARs) 10% in the overall trial population for PAOLA-1 when treated with LYNPARZA in combination with bevacizumab (N=535) and at a 5% frequency compared to bevacizumab alone (N=267) were fatigue (53% vs. 32%), nausea (53% vs. 22%), anemia (41% vs. 10%), lymphopenia (24% vs. 9%), vomiting (22% vs. 11%) and leukopenia (18% vs. 10%). Grade 3 or above ARs were anemia (17% vs. <1%), lymphopenia (7% vs. 1%), fatigue (5% vs. 2%), nausea (2% vs. 1%), leukopenia (2% vs. 2%) and vomiting (2% vs. 2%). Additional adverse reactions that occurred in 10% of patients receiving LYNPARZA in combination with bevacizumab irrespective of the frequency compared to bevacizumab alone were diarrhea (18%), neutropenia (18%), urinary tract infection (15%) and headache (14%). Fatal adverse reactions occurred in one patient due to concurrent pneumonia and aplastic anemia. Serious adverse reactions occurred in 31% of patients who received LYNPARZA in combination with bevacizumab. Serious adverse reactions in >5% of patients included hypertension (19%) and anemia (17%).

In addition, venous thromboembolic events occurred more commonly in patients receiving LYNPARZA in combination with bevacizumab (5%) than in those receiving bevacizumab alone (1.9%). ARs led to dose interruption in 54% of patients on LYNPARZA in combination with bevacizumab, while 41% of patients on LYNPARZA in combination with bevacizumab had a dose reduction. Discontinuation of treatment due to ARs occurred in 20% of patients on LYNPARZA in combination with bevacizumab.

Approximately one in two women with advanced ovarian cancer has an HRD-positive tumor. For patients with advanced ovarian cancer, the primary aim of first-line maintenance treatment is to delay disease progression for as long as possible.

Isabelle Ray-Coquard, principal investigator of the PAOLA-1 trial and medical oncologist, Centre Lon Brard and President of the GINECO group, said, Ovarian cancer is a devastating disease. The magnitude of benefit in HRD-positive patients in the PAOLA-1 trial is impactful. I look forward to seeing this translate into clinical practice.

Dave Frederickson, executive vice president, head of the oncology business unit, AstraZeneca, said, This approval represents another milestone for LYNPARZA in patients with ovarian cancer. The median progression-free survival of more than three years offers new hope for women to delay relapse in this difficult-to-treat disease. These results further establish that HRD-positive is a distinct subset of ovarian cancer and HRD testing is now a critical component of diagnosis and tailoring of treatment for women with advanced ovarian cancer.

Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said, Advances in understanding the role of biomarkers and PARP inhibition have fundamentally changed how physicians treat this aggressive type of cancer. Todays approval based on the PAOLA-1 trial highlights the importance of HRD testing at diagnosis to identify those who may benefit from LYNPARZA in combination with bevacizumab as a first-line maintenance treatment.

The full results from the Phase 3 PAOLA-1 trial were published inThe New England Journal of Medicine.

Regulatory reviews are currently underway in the European Union, Japan and other countries for LYNPARZA in combination with bevacizumab as a first-line maintenance treatment for patients with advanced ovarian cancer. As part of a broad development program, LYNPARZA is being assessed as a monotherapy and in combination across multiple tumor types.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in <1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The duration of therapy in patients who developed secondary MDS/AML varied from <6 months to >2 years. All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy, and some also had a history of more than one primary malignancy or of bone marrow dysplasia.

Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery.

If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

Pneumonitis: Occurred in <1% of patients exposed to LYNPARZA, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment.

Females

Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.

Males

Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.

ADVERSE REACTIONSFirst-Line Maintenance BRCAm Advanced Ovarian Cancer

Most common adverse reactions (Grades 1-4) in 10% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), UTI (13%), thrombocytopenia (11%), and stomatitis (11%).

Most common laboratory abnormalities (Grades 1-4) in 25% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for SOLO-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%).

ADVERSE REACTIONSFirst-Line Maintenance Advanced Ovarian Cancer in Combination with Bevacizumab

Most common adverse reactions (Grades 1-4) in 10% of patients treated with LYNPARZA/bevacizumab compared to a 5% frequency for placebo/bevacizumab in the first-line maintenance setting for PAOLA-1 were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%) and leukopenia (18%). In addition, the most common adverse reactions (10%) for patients receiving LYNPARZA/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%), and headache (14%).

In addition, venous thromboembolic events occurred more commonly in patients receiving LYNPARZA/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%).

Most common laboratory abnormalities (Grades 1-4) in 25% of patients for LYNPARZA in combination with bevacizumab in the first-line maintenance setting for PAOLA-1 were: decrease in hemoglobin (79%), decrease in lymphocytes (63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease in absolute neutrophil count (35%), and decrease in platelets (35%).

ADVERSE REACTIONSMaintenance Recurrent Ovarian Cancer

Most common adverse reactions (Grades 1-4) in 20% of patients in clinical trials of LYNPARZA in the maintenance setting for SOLO-2 were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).

Study 19: nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), decreased appetite (21%), and dyspepsia (20%).

Most common laboratory abnormalities (Grades 1-4) in 25% of patients in clinical trials of LYNPARZA in the maintenance setting (SOLO-2/Study 19) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%).

ADVERSE REACTIONSAdvanced gBRCAm Ovarian Cancer

Most common adverse reactions (Grades 1-4) in 20% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: fatigue/asthenia (66%), nausea (64%), vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%), and arthralgia/musculoskeletal pain (21%).

Most common laboratory abnormalities (Grades 1-4) in 25% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer (pooled from 6 studies) were: decrease in hemoglobin (90%), mean corpuscular volume elevation (57%), decrease in lymphocytes (56%), increase in serum creatinine (30%), decrease in platelets (30%), and decrease in absolute neutrophil count (25%).

ADVERSE REACTIONSgBRCAm, HER2-Negative Metastatic Breast Cancer

Most common adverse reactions (Grades 1-4) in 20% of patients in OlympiAD were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%).

Most common laboratory abnormalities (Grades 1-4) in 25% of patients in OlympiAD were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%).

ADVERSE REACTIONSFirst-Line Maintenance gBRCAm Metastatic Pancreatic Adenocarcinoma

Most common adverse reactions (Grades 1-4) in 10% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for POLO were: fatigue (60%), nausea (45%), abdominal pain (34%), diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%), and stomatitis (10%).

Most common laboratory abnormalities (Grades 1-4) in 25% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for POLO were: increase in serum creatinine (99%), decrease in hemoglobin (86%), increase in mean corpuscular volume (71%), decrease in lymphocytes (61%), decrease in platelets (56%), decrease in leukocytes (50%), and decrease in absolute neutrophil count (25%).

DRUG INTERACTIONS

Anticancer Agents: Clinical studies of LYNPARZA in combination with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

CYP3A Inhibitors: Avoid concomitant use of strong or moderate CYP3A inhibitors. If a strong or moderate CYP3A inhibitor must be co-administered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A inducers when using LYNPARZA. If a moderate inducer cannot be avoided, there is a potential for decreased efficacy of LYNPARZA.

USE IN SPECIFIC POPULATIONS

Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.

Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.

Hepatic Impairment: No adjustment to the starting dose is required in patients with mild or moderate hepatic impairment (Child-Pugh classification A and B). There are no data in patients with severe hepatic impairment (Child-Pugh classification C).

Renal Impairment: No dosage modification is recommended in patients with mild renal impairment (CLcr 51-80 mL/min estimated by Cockcroft-Gault). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose of LYNPARZA to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr 30 mL/min).

INDICATIONS

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

First-Line Maintenance BRCAm Advanced Ovarian Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance HRD Positive Advanced Ovarian Cancer in Combination with Bevacizumab

In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:

Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Maintenance Recurrent Ovarian Cancer

For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.

Advanced gBRCAm Ovarian Cancer

For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

gBRCAm HER2-Negative Metastatic Breast Cancer

For the treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance gBRCAm Metastatic Pancreatic Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Please click here for complete Prescribing Information, including Patient Information (Medication Guide).

About PAOLA-1

PAOLA-1 is a double-blind Phase 3 trial evaluating the efficacy and safety of LYNPARZA in combination with standard-of-care bevacizumab vs. bevacizumab alone, as a first-line maintenance treatment for advanced FIGO Stage III-IV high grade serous or endometroid ovarian, fallopian tube, or peritoneal cancer patients who had a complete or partial response to first-line treatment with platinum-based chemotherapy and bevacizumab.

PAOLA-1 is an ENGOT (European Network of Gynaecological Oncological Trial groups) trial, sponsored by ARCAGY Research (Association de Recherche sur les CAncers dont GYncologiques) on behalf of GINECO (Groupe dInvestigateurs National des Etudes des Cancers Ovariens et du sein). ARCAGY-GINECO is an academic group specializing in clinical and translational research in patients cancers and a member of the GCIG (Gynecologic Cancer InterGroup).

In the U.S., eligible advanced ovarian cancer patients will be selected for therapy based on the FDA-approved myChoice HRD Plus, an HRD test designed to detect when a tumor has lost the ability to repair double-stranded DNA breaks. Myriad Genetics, Inc. owns and commercializes myChoice HRD Plus.

About LYNPARZA (olaparib)

LYNPARZA is a first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. Inhibition of PARP with LYNPARZA leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. LYNPARZA is being tested in a range of tumor types with defects and dependencies in the DDR.

LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has a broad and advanced clinical trial development program, and AstraZeneca and Merck are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types.

About Ovarian Cancer

Ovarian cancer is the fifth most common cause of death from cancer in women in the United States. This year, it is estimated that more than 21,000 women will be diagnosed with ovarian cancer and nearly 14,000 women will die of this disease.

Women with ovarian cancer are often diagnosed with advanced disease, which has a five-year survival rate of about 48%. For newly diagnosed advanced ovarian cancer, the primary aim of treatment is to delay progression of the disease for as long as possible. BRCA1/2 mutations are found in approximately 22% of all ovarian cancers and approximately 50% of ovarian cancers are HRD-positive.

About Homologous Recombination Deficiency

HRD encompass a wide range of genetic abnormalities, including BRCA mutations, that can be detected using tests. As the BRCA gene drives DNA repair via homologous recombination, mutation of this gene leads to homologous recombination deficiency thereby interfering with normal cell DNA repair mechanisms. BRCA mutations are just one of many HRDs which confer sensitivity to PARP inhibitors including LYNPARZA.

About the AstraZeneca and Merck Strategic Oncology Collaboration

In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize certain oncology products, including LYNPARZA, the worlds first PARP inhibitor, for multiple cancer types. Working together, the companies will develop these products in combination with other potential new medicines and as monotherapies. Independently, the companies will develop these oncology products in combination with their respective PD-L1 and PD-1 medicines.

Mercks Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit http://www.merck.com/clinicaltrials.

About Merck

For more than 125 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the worlds most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit http://www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the company) includes forward-looking statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the companys management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the recent global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the companys ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the companys patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the companys 2019 Annual Report on Form 10-K and the companys other filings with the Securities and Exchange Commission (SEC) available at the SECs Internet site (www.sec.gov).

View source version on businesswire.com: https://www.businesswire.com/news/home/20200508005523/en/

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LYNPARZA (olaparib) Approved by FDA as First-Line Maintenance Treatment with Bevacizumab for HRD-Positive Advanced Ovarian Cancer - BioSpace

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From blood clots to ‘Covid toe’: Experts confounded by series of medical mysteries – The Straits Times

May 9th, 2020

LONDON When the first cases of a new coronavirus started to appear in China last December, the disease seemed to be a particularly aggressive respiratory infection. An "urgent notice" that month from the Wuhan health commission warned of "successive cases of unknown pneumonia".

Respiratory symptoms are still the first signs that doctors look for in suspected Covid-19 cases: cough, shortness of breath and fever.

But, less than five months after it was first identified, this new coronavirus is managing to throw up a series of medical mysteries - from blood clots and strokes to digestive problems - that are confounding the scientific community.

From head to foot, Covid-19 causes a fiendish variety of symptoms. Some are relatively mild, such as loss of smell and taste or chilblain-like sores on toes. But others may be fatal, such as when what doctors call an immune storm destroys vital organs. The more this virus is studied, the more complex it appears to be. "Every day we're learning of new tricks that the virus plays," Imperial College London's professor of experimental medicine Peter Openshaw says. "It is remarkable to see a disease unfolding in front of our eyes with so many twists and turns."

The proliferation of complex symptoms is not just a challenge for doctors treating the disease, but also for health systems trying to adapt to the pandemic. In the early months, the focus was on getting hold of ventilators that could help patients with severe respiratory problems. But now hospitals are also scrambling for more kidney dialysis machines and anticoagulant drugs.

A single individual can suffer the disease in more than one form, Prof Openshaw adds. "There are accounts of people experiencing one symptom, for example coughing, appearing to recover or go into remission and then returning with a more serious systemic disease."

With the worldwide death toll from Covid-19 already nearing 260,000 and confirmed cases close to exceeding 3.7 million, according to Johns Hopkins University, scientists have mobilised at a speed and on a scale unprecedented in the history of medicine, in an effort to understand the myriad ways in which the virus affects the human body. They hope that their research will not only improve clinical care of patients but also help the development of drugs and vaccines.

The initial diagnosis was that it was a respiratory infection, like its sister diseases Sars and Mers which are also caused by coronaviruses.

Respiratory symptoms remain the most common manifestations of Covid-19 in patients who go to hospital, according to a study of almost 17,000 people admitted to 166 UK hospitals carried out by a research consortium from Imperial College and Liverpool and Edinburgh universities. About two-thirds of patients in the study - the largest of Covid-19 hospital patients outside China - were admitted suffering from respiratory symptoms, says Dr Annemarie Docherty of Edinburgh, the lead author of the paper. But that proportion may have been raised by the fact that they reflect the official case definition of Covid-19.

But two other clusters of symptoms also dominate hospital admissions: systemic musculoskeletal symptoms (muscle and joint pain and fatigue) and enteric symptoms (abdominal pain, vomiting and diarrhoea). Many patients suffer from several symptoms simultaneously.

How the immune system reacts to Covid-19 is key to the course of the disease in adults. People who have been suffering with mild to moderate symptoms for a week or so often seem to hit a critical point: usually their immune system gets the virus under full control and sets them on a path to full recovery - but sometimes it goes into overdrive, triggering systemic inflammation and in severe cases a "cytokine storm" that destroys tissues and whole organs.

Inflammation also helps to explain why obesity makes people more susceptible to severe Covid-19. Seventy-three per cent of coronavirus patients in UK intensive care units are overweight or obese, with a body mass index above 25. "Fat cells secrete chemicals that increase the body's inflammatory response," says Liverpool University's professor of child health Calum Semple.

Kidney damage has emerged as another of the most frequent serious consequences of Covid-19, with 23 per cent of patients in intensive care requiring renal support. As with other organs, it is uncertain to what extent the virus is directly attacking the kidneys or whether the harm results more from generalised overactivity of the immune system and consequent changes in the patient's blood circulation.

Cardiovascular disease is the most common pre-existing health condition in people who die of Covid-19, ahead of lung and respiratory disorders such as asthma and chronic obstructive pulmonary disease. And many patients without a previous history of heart trouble develop severe cardiac symptoms while they are in hospital.

"When we first heard about the coronavirus we expected people with lung and breathing problems to be most at risk but that has not been the case," says the British Heart Foundation's medical director Nilesh Samani. "We need to understand why the virus is causing so many problems outside the lungs - and cardiovascular complications in particular."

The exaggerated immune response to the virus sometimes causes abnormal blood clotting. If this thrombosis happens in the brain, it may trigger a stroke. Neurologists at University College London (UCL) studied six Covid-19 patients who suffered acute stroke as a result of a large arterial blockage - in five of the cases more than a week after suffering headache, cough and fever and in one patient before other symptoms appeared.

The UCL researchers found all six patients had markedly raised blood levels of a protein fragment called D-dimer associated with abnormal clotting. The findings suggest that early testing for D-dimer could enable doctors to prescribe blood-thinning drugs to people at risk, reducing the chance of stroke or harmful clotting elsewhere in the body. "Early use of anticoagulant drugs might be helpful but this needs to be balanced against their brain bleeding risk," says study leader David Werring.

STRAITS TIMES GRAPHICS

"This study is consistent with the growing evidence that people hospitalised with Covid-19 are at risk from blood clots in multiple locations: the lungs (causing pulmonary embolus), the brain (causing stroke) and the veins (causing DVT)," says professor of cardiovascular medicine Tim Chico at Sheffield University. "The risk of blood clots with Covid-19 appears to be even greater than the increased risk of blood clots seen in other severe illnesses."

The coronavirus also seems capable of attacking the brain and nervous system directly, as well as indirectly through abnormal blood clotting, though the evidence for acute symptoms of neural infection is limited. The effects may show up in the longer term as post-viral fatigue.

Neurons in the olfactory bulb, which transmits information from the nose to the brain, are apparently infected by the virus. Indeed, anosmia - loss of the sense of smell - is one of the most frequently reported symptoms of mild infection, affecting about half of patients and lasting for several weeks in some cases.

The good news for those who develop anosmia is that they are much less likely to become seriously ill with Covid-19. Dr Carol Yan and colleagues at the University of California San Diego (UCSD) reported last week that patients reporting loss of smell were 10 times less likely to be admitted to hospital for Covid-19 than those without loss of smell.

The UCSD researchers suggest that a relatively small dose of virus delivered to the upper airway, where it causes anosmia, may be less likely to overwhelm the host immune response. "This hypothesis is in essence the concept underlying live vaccinations, where low dosage and a distant site of inoculation generates an immune response without provoking a severe infection," they say.

The declining strength of the immune system with age is a partial explanation for the increasing incidence of Covid-19 in older people. PHOTO: AFP

Besides anosmia, the most frequently seen minor symptoms are rashes, pustules and blisters on the skin - including lesions like chilblains that dermatologists are calling "Covid toe".

The results from the study led by Imperial College, Liverpool and Edinburgh universities echo other findings that the disease is much more common in men - who make up 60 per cent of UK Covid-19 hospital admissions - and its severity rises markedly with advancing years (the median age of patients is 72). The strong associations with the male sex and old age are a particular feature of Covid-19 compared with other infectious illnesses.

Data from the UK Intensive Care National Audit & Research Centre shows that men make up 71.5 per cent of patients whose disease becomes severe enough to require intensive care treatment. A comparable control group of patients critically ill with non-Covid viral pneumonia was just 54.3 per cent male.

"The reason behind this difference in Covid risk is unknown," says Dr James Gill, honorary clinical lecturer at Warwick Medical School. "There are several schools of thought on the matter, from the assumption that simply men don't look after their bodies as well, with higher levels of smoking, alcohol use, obesity and other deleterious health behaviours, through to immunological variations in genders. Women may have a more aggressive immune system, meaning a greater resilience to infections."

University of Oxford's professor of immunology Philip Goulder points out that several critical immune genes are located on the X chromosome - of which women have two copies and men one. "The immune response to coronavirus is therefore amplified in females," he says.

The declining strength of the immune system with age is also a partial explanation for the increasing incidence of the disease in older people, though it is not clear why this trend is more pronounced in Covid-19 than in many other viral infections.

Children are remarkably - but not completely - resistant to the disease. Just 3 per cent of UK hospital patients are under 18. Again no one knows quite why. But one answer may lie in the "keyhole" through which coronavirus enters human cells, known as the ACE2 receptor. In children these receptors have not developed to their full adult stage and therefore may not fit the "spike protein" that the virus uses to enter cells.

It is also possible that ACE2 develops more quickly in children's upper airways than their lower respiratory tract, allowing them to become infected - and thus able to transmit Covid-19 - without showing the same progression to severe symptoms.

The National Health System in London and the UK Paediatric Intensive Care Society recently alerted doctors to a rise in the number of children suffering from "a multi-system inflammatory state" similar to toxic shock, which might result from the immune system overreacting to viral infection. Italian and US paediatricians have noticed a similar body-wide inflammatory syndrome in children.

This paediatric condition is rare but researchers are investigating, says Prof Semple. "Some respiratory viruses are associated with a systemic inflammatory response, typically two weeks after infection. But this could be a phenomenon of heightened awareness."

Research also shows that children are remarkably - but not completely - resistant to the disease. PHOTO: AFP

For Prof Openshaw, the mysteries of Covid-19 recall the early days of the HIV/Aids outbreak in the 1980s - except that this time, they are unfolding much more quickly. "We need the answers also to appear far faster than they did with HIV," he says.

A global research effort is on to discover human genetic factors that would help to explain why Covid-19 infection varies so much in its symptoms.

Although much of the variation results from environmental and lifestyle factors, scientists are convinced that genetics play a significant role too.

"Experience with other viruses shows that genetics can explain some of the different responses to infection," says Dr Mark Daly, director of the Institute for Molecular Medicine Finland in Helsinki, who is coordinating the global response through the Covid-19 Host Genetics Initiative.

For example, genetic mutations on the CCR5 protein, which HIV uses to enter human cells, make rare individuals resistant to Aids. Researchers may find comparable variations in the human ACE2 protein, entry point of the coronavirus, designated as Sars-Cov-2, that causes Covid-19.

The Covid programme has two overlapping components. One uses human genomes already obtained for other research purposes from volunteers through bodies such as UK Biobank and Genomics England - and looks for differences in DNA between participants who become ill with Covid-19 and those who do not.

The other part obtains the fresh genomes from Covid-19 patients, looking for variations that might explain why some experience only mild symptoms while others become severely ill.

Genomics England, a public body owned by the UK Department of Health and Social Care, is involved in both approaches. Dr Mark Caulfield, its chief scientist, says it is too early to have obtained any results. "But I am confident that reading whole genomes will help to identify variation that affects response to Covid-19 and to discover new therapies."

Prof Daly hopes the initiative will have tens of thousands of human genomes to analyse. "We particularly want to identify a subset of younger individuals with no comorbidities who have a severe response to Sars-Cov-2 infection," he says.

FINANCIAL TIMES

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From blood clots to 'Covid toe': Experts confounded by series of medical mysteries - The Straits Times

Recommendation and review posted by Bethany Smith

HGH Replacement Clinics of Florida: Choose Only the Best – South Florida Reporter

May 9th, 2020

If youre looking for a natural way to increase your energy and feel younger, you may be curious about Human Growth Hormone. While its sometimes painted in a negative light, due to its abuse by athletes and bodybuilders, when used properly, growth hormone replacement therapy is a safe and scientific way to regain energy and improve your overall quality of life.

What is Human Growth Hormone?

Human Growth Hormone (or HGH) is a protein that is secreted in spurts by thepituitary gland. HGH is secreted after exercise, trauma and right before falling asleep. Under normal conditions, levels alternate throughout the day, with the highest amount appearing at night. Human Growth Hormone secretion rises during childhood, peaks at puberty and starts to decline in middle age.

What Does Human Growth Hormone Do?

HGH is responsible for promoting vertical growth in kids and teens, as well as a few key metabolic responsibilities throughout adulthood.

Functions include: stimulating the growth of bone and cartilage raising the production of protein in the body utilizing fat and regulating blood sugar

Our bodies natural production of this vital hormone starts to declines in our thirties.The results can lead to:

But isnt this just a normal part of aging? Dont we simply have to embrace that, as we get older, we are going to put on a few pounds and need to double our espresso order? Not necessarily.

Replacement Therapy is a safe, medically supervised treatment for growth hormone deficiency in adults. Studies have proven that the replacement of growth hormone can lead to: increased lean muscle mass decreased fat mass

Where Can I Access Hormone Replacement Therapy?

The following clinics in Florida are certified in the administration of hormone replacement therapy:

With locations in Jacksonville, Miami, Orlando, Tampa and West Palm Beach, Ehormones MD offers a convenient way to explore hormone replacement therapy. They have a team of medical doctors who will design a unique protocol for you based on your lab work. Medications and supplies are shipped directly to your home. You can administer the hormones by yourself via a small needle into your lower belly every night, before bed. Follow-up lab work is scheduled five to eight weeks following the start of treatment, with additional labs every six months thereafter. Additional services include fitness programs, nutrition plans, stress reduction plans and ongoing evaluations.

Health Gains clinics are located in Aventura and Madeira Beach, Florida. The clinics offer white-glove concierge service with no waiting. Their highly trained medical team includes doctors, nurse practitioners and bi-lingual medical assistants. The latest technology is combined with a spa-like environment to help patients overcome the symptoms of aging and improve their quality of life. Services also include Peptide Therapy, Thyroid Hormone Therapy and Testosterone Therapy for men.

Located in Miami,HGH Therapy Clinicwas founded in 2009 as a free information center for endocrine problems. Since then, it has evolved into state-of-the-art facility featuring the best and newest technologies of hormone treatment. Their team of doctors includes specialists in endocrinology, diabetes, metabolism and internal medicine. They specialize in Growth Hormone Deficiency Treatment for both men and women.

The goal of the Rejuvenation Clinic is to promote vitality through the early detection of hormonal imbalances. Their patient advocate support team will empower you to understand your treatment from start to finish. The process starts by filling out a confidential medical history form online. Within minutes, you will be assigned to a wellness advisor who will help you to set up a physical exam and a lab test. Additional treatments include Testosterone Therapy, Intracavernous Injection Therapy (ICI), supplements and amino acids.

AtTampa Rejuvenation, a team of doctors and nurse practitioners are there to help you achieve optimal health through weight loss and bioidentical hormone replacement therapy. With three convenient locations in Tampa and one in Brandon, FL, accessing the treatment you need is easy. Services include hormone therapy for both men and women, as well as treatments for adrenal fatigue, thyroid issues and hair restoration.

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HGH Replacement Clinics of Florida: Choose Only the Best - South Florida Reporter

Recommendation and review posted by Bethany Smith

What Causes Chin Acne And How Should You Treat It? – Grazia

May 9th, 2020

According to The International Dermal Institute, 55% of women over 25 have adult acne. And chin acne lets call it ch-acne is the second most common kind of adult acne (67%) falling shortly behind cheek acne (81%). But why do spots congregate in this relatively small area of the face? Weve spoken to Dr Nick Lowe, Consultant Dermatologist at The Cranley Clinic and co-author of Perfectly Clear, to find out why the chin has become a sebum battleground.

Acne tends to occur more in areas with a lot of oil-producing glands, AKA sebaceous glands, explains Lowe. Pores can become blocked by excess oil from the glands, and acne bacteria builds up below the skin, producing inflamed spots. One of the highest concentrations of these glands is, you guessed it, around your chin area.

But theres more to it. For starters, particular irritants specific to the chin can cause breakouts that look just like, but actually arent, acne (more on this later). Also, as much as we all hate to admit this, it looks like those old wives tales were right factors like touching your face, as well as eating sugary food, play a big part too.

Read on to discover the main causes of chin acne, or ch-acne, and how to tackle it.

Acne is caused when a pesky group of hormones caused androgens are released often as a response to your contraception. This type of acne is characterised by smaller inflamed spots around the mouth and chin although you can also get larger, cystic acne spots on the chin too.

Sound familiar? 'It tends to be contraceptives with high progesterone compared to oestrogen that aggravates acne,' says Nick. So if youre on something like the progesterone mini-pill or the hormonal implant (which releases progestogen, a hormone similar to progesterone) and youre getting acne flare-ups around your chin and mouth then, well, it adds up. Instead, you could switch to a low progesterone contraceptive pill that actually helps your skin, like Yasmin.

Your chin also acts as a landing pad for your toothpaste, which, it turns out, is chock-a-block with irritants especially one ubiquitous ingredient: fluoride. This condition, where acne-like symptoms occur around the mouth and chin area, looks like acne, but its actually peri-oral dermatitis, explains Nick.

A secondary culprit is sodium lauryl sulphate (SLS), which is present in toothpaste brands as well as many other cosmetics such as shampoo. However, this will only irritate skin, rather than single-handedly cause something which resembles acne, explains Nick.

While we're not suggesting for a minute you ditch toothpaste in the name of good skin, there are some great irritant-free toothpastes that do the job just as well as your go-to brand. Try JASONs brilliant range of SLS-free, fluoride-free toothpastes.

Sadly, when tackling acne, your diet could be the cause. There are two main food culprits to avoid if you get chin acne, according to Nick. First off, its high GI foods like chocolate, white bread and sugary breakfast cereals (check the sugar content of your granola). The body produces insulin-like hormones to deal with the high amount of carbohydrate youre absorbing in the bowel, and for some those hormones cause acne.

Milk can also be a trigger. In people susceptible to acne, drinking milk including skimmed can make the condition worse, because it contains androgenic hormones. Nick recommends swapping to soy or almond milk over a six to eight-week trial. It takes that long to see an improvement. The good news is, yoghurt doesnt seem to have the same effect, thanks to the fermenting process removing some of the hormones; so your mid-morning Fage habit is safe.

Yes, you're mobile phone can cause spots...and anything else coming into contact with your chinny chin chin, basically. If you rest your chin on your hands or phone, the friction can block the pores, causing acne bacteria to build up, says Nick. Same story if you wear a cycling helmet with a chin strap. If you have existing acne, friction aggravates the inflamed spots so snogging your stubbly boyfriend wont help either.

As for me, my acne struggle had a happy ending. A course of antibiotics (to kill the acne bacteria) and a new contraception pill (Yasmin, my old friend) got rid of most of it. Then, just three months ago, the last nail in the coffin was changing my toothpaste who knew fluoride was the cause of my remaining acne-that-isnt-actually-acne?

For those still battling acne, on the chin or otherwise and believe me, I know how crap it is Nicks advice is to stick with finding a solution: If you have acne that is continuing, look at all your habits: your toothpaste, your diet and your contraception. Start off with topical medicine, then look into these other factors and find what works for you.

Shop the best products for acne-prone skin:

Apply a thin layer of this serum meets moisturiser all over the affected area and let the five acids (including Salicylic and Glycolic acid) get to work to minimise the appearance of spots.

Keep this handy stick in your handbag and apply it at the first sign of a spot - so, whenever that sore, swollen bump appears. Formulated with 2% salicylic acid to exfoliate the skin and tea-tree oil to calm the area - you'll notice the benefits in no time.

It might sound counter intuitive to add more oil to oily skin but it can in fact help to balance the skin's mantle. This blemish oil calms irritated skin, helps to heal spots and will also treat scars.

La Roche-Posay's anti-blemish cream is formulated to target oily, blemish-prone skin. It has become a cult product for beauty buffs who have raved about its magical ability to unclog pores, minimise imperfections and give the surface of the skin a smooth velvety finish.

The Body Shop's Tea Tree Oil range is proven to contain healing and antibacterial properties for every type of skin. The Body Shop claim that the range can create clearer skin in 3-days without over-stripping the skin. We love the Tea Tree Squeaky Clean Scrub (with biodegradable micro-beads) and Tea Tree Night Lotion to combat shine and impurities day and night.

This highly coveted skin elixir is not only surprisingly affordable but also promises to refresh and repair your complexion by clearing up and soothing whiteheads overnight. All Mario Badescu asks is that you dip a cotton swab into the pink sediment, dab on a pimple and wash off in the morning. Do not shake the bottle.

Enriched with cocoa butter, rosemary, eucalyptus and chamomile this indulgent cream cleanses, soothes and moisturises. Used alongside Liz Earle's pure cotton cloth, dead skin cells and daily grime are lifted away to reveal brighter looking skin.

Aesop is fast becoming the favorite beauty brand of the year because of the visible results. The parsley seed extract cleanses deep within the pores - exactly what you need for troublesome skin. Frequent use of this product will prevent future breakouts, and using this overnight won't leave you feeling oily or clogged up the next morning.

Dermalogica's Clay Cleanser treats spots when used as a wash and as a face mask. It concentrates on the affected area and uses refreshing cucumber to leave you feeling rejuvenated.

The most common places for acne and spots, particularly in the winter months, are your cheeks and jawline. To prevent this your skin must be well moisturized, and this Origins product is enriched with boosting ingredients to brighten your complexion. And it's completely oil-free.

Apply this serum onto your acne scars or discolouration after you've washed your face and before you moisturise, and overtime it will even your complexion.

READ MORE: Breakout Breakdown: What Is Actually Causing Your Spots?

READ MORE: Everything You Need To Know About Pimple Patches Do They Really Keep Spots At Bay?

View post:
What Causes Chin Acne And How Should You Treat It? - Grazia

Recommendation and review posted by Bethany Smith

Edited Transcript of PTGX earnings conference call or presentation 7-May-20 9:00pm GMT – Yahoo Finance

May 9th, 2020

MILPITAS May 9, 2020 (Thomson StreetEvents) -- Edited Transcript of Protagonist Therapeutics Inc earnings conference call or presentation Thursday, May 7, 2020 at 9:00:00pm GMT

* Dinesh V. Patel

Protagonist Therapeutics, Inc. - CEO, President, Interim PAO, Secretary & Director

* Donald A. Kalkofen

Protagonist Therapeutics, Inc. - CFO

* Samuel R. Saks

Protagonist Therapeutics, Inc. - Chief Medical Officer

* Christopher N. Marai

Nomura Securities Co. Ltd., Research Division - MD & Senior Analyst of Biotechnology

SVB Leerink LLC, Research Division - MD of Rare Diseases & Senior Research Analyst

Good day, and welcome to the Protagonist Therapeutics PTG-300 Development Update Call. Please note that today's conference is being recorded. At this time, I would like to introduce Don Kalkofen, Protagonist's Chief Financial Officer. Please go ahead.

Donald A. Kalkofen, Protagonist Therapeutics, Inc. - CFO [2]

Thank you, operator. Good afternoon, everyone. Please note that a replay of today's call will be available at the Investors section of our website at protagonist-inc.com.

Before we begin, I'd like to remind you that today's discussion will include statements about the company's future expectations, plans and prospects that constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our quarterly and annual reports on forms 10-Q and 10-K, which are on file with the SEC. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our view should change.

With that, I will now turn the call over to Dinesh Patel, President and CEO, to provide you an update on the company's progress to date.

Dinesh V. Patel, Protagonist Therapeutics, Inc. - CEO, President, Interim PAO, Secretary & Director [3]

Thanks, Don. Good afternoon, everyone, and thank you all for joining us today. On today's call, we'll also hear from Samuel Saks, our Chief Medical Officer; and Dr. Ronald Hoffman, Professor of Medicine in Hematology and Medical Oncology at the Mount Sinai Hospital in New York City. Dr. Hoffman has been involved in the Phase II clinical study of PTG-300 in polycythemia vera, and he will provide a brief overview of the disease and his perspectives on PTG-300 and its potential benefits as the novel treatment for polycythemia vera or PV.

Also present for the call today are David Liu, our Chief Scientific Officer and Head of R&D; and Suneel Gupta, our Chief Development Officer. We are pleased to have all these individuals available to address questions during the Q&A session of today's call.

So let's start with Slide #3. As you are well aware, Protagonist started the year 2020 with 3 clinical assets, all of which have been discovered through the use of our peptide technology platform in 6 different clinical proof-of-concept studies. The 3 assets fall in 2 broad categories: PTG-300 for various blood disorders, most of which are rare disease; and oral GI-restricted targeted peptide PTG-200 and PN-943 for inflammatory bowel disease, or IBD. All of these assets have a multibillion-dollar potential in multiple indications.

PTG-300 peptide mimetic of the natural hormone hepcidin that serves as a master regulator of iron homeostasis storage and distribution in the body was being pursued in Phase II open-label proof-of-concept studies in beta-thalassemia, or beta-thal; polycythemia vera, or PV; hereditary hemochromatosis, or HH; and an investigator-sponsored study in myelodysplastic syndrome, or MDS. As you may recall, a major objective for 2020 was to pick our first clinical indication for PTG-300 that we can progress towards a pivotal study in 2021.

Today, we are pleased to announce initial but yet very robust clinical data from our polycythemia vera program. And the selection and prioritization of polycythemia vera as the first indication for a pivotal study with 300. This decision is based on 3 criteria: strength and consistency of the clinical data, favorable regulatory path forward and the commercial opportunity. This is our major announcement today. And while most of our discussion will be around 300 and polycythemia vera, let me also take this opportunity to talk briefly about our oral gut-restricted IBD assets, largely in the context of corporate update and cash runway.

The enrollment rate of Phase II studies of these agents, namely the oral alpha-4-beta-7 integrin antagonist PN-943 for ulcerative colitis and the oral interleukin-23 receptor antagonist PTG-200 for Crohn's disease are understandably going to be influenced by the current COVID-19 situation. Therefore, while these studies are continuing, we believe it is appropriate to remove future guidance on the timelines for top line data from these studies.

In addition to the decision to focus our efforts towards rapidly advancing 300 in polycythemia vera indication, we are continuing the ongoing proof-of-concept study of 300 in hereditary hemochromatosis as a potential second indication and are also deciding to now discontinue further development of 300 for beta-thalassemia as well as for myelodysplastic syndrome.

On the financial side, we ended the first quarter of this year with about $117 million in cash and investments. By factoring in the delay in enrollment and the associated clinical development costs, coupled with a reduction in operational needs and expenditures, we are now extending our cash runway by an additional 6 months through the middle of 2022.

Now let's go to Slide #4, and let me turn to PTG-300, a major highlight of today's call and to provide rationale for why we are pursuing polycythemia vera as our first indication. First and foremost, it's the robust and consistent clinical responses we have seen in our ongoing Phase II PV trial. Although small, the data set is very compelling and consistent. On 6 out of 6, dose compliant patients treated for up to 28 weeks with 300 are phlebotomy free as of today. These are very noteworthy results. Keeping in mind that prior to entering our study, these subjects were receiving frequent phlebotomies in the weeks leading up to enrollment. We are obviously very encouraged by these results, and the enrollment in the study continues with 8 patients enrolled to date. And we have also decided to now expand the current study from 30 patients to 50 patients.

The second factor is the regulatory path forward for the development of 300 in polycythemia vera indication. As you know, approved drugs for polycythemia vera fall into the orphan drug designation category by virtue of it being a rare disease in the U.S. and Europe. And orphan status provide certain benefits to the drug developer, including 7 years of market exclusivity upon FDA approval, prescription drug use of fee waivers and tax credits for qualified clinical trial.

The third factor besides the data and the regulatory path is the very significant commercial opportunity that lies ahead of us based on the significant unmet need that exists today for these patients. And specifically, by virtue of PTG-300 being a novel mechanism-based, first-in-class non-cytoreductive natural hormone mimetic agent. While PV is a rare disease, there are approximately 100,000 people in the U.S. living with this disease, and this number is unfortunately expected to grow as the population ages. The majority of PV patients are treated with phlebotomies, cytoreductive therapies or a combination of those treatments.

Jakafi is the only FDA-approved cytoreductive therapy in PV and despite having a limited indication in patients who have had an inadequate response to current treatment, Jakafi is expected to reach almost $2 billion in sales in 2020, and the largest percentage growth is in the PV population, 19% year-over-year based on their most recently quarterly update. PTG-300 has the potential to address a significant unmet need in this category where there is a lack of new cytoreductive agents in development. 300 offers the potential of keeping patients phlebotomy-free without causing iron deficiency.

So to summarize, we are incredibly encouraged by our preliminary but strong and consistent data and, therefore, are electing to focus our resources on expedited development of 300 for polycythemia vera.

To speak more about this, I would now like to introduce our Chief Medical Officer, Dr. Samuel Saks. Sam?

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Samuel R. Saks, Protagonist Therapeutics, Inc. - Chief Medical Officer [4]

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Thanks, Dinesh. As Dinesh mentioned, we are really encouraged by the results we have seen in the ongoing Phase II study of PTG-300 in patients with polycythemia vera. Dr. Hoffman is going to walk you through the study results in detail, but I wanted to highlight why I believe this data has prompted us to focus on PV as the first indication for 300.

The majority of PV patients today are treated with phlebotomy, or phlebotomy in combination with cytoreductive therapies to control erythrocytosis and keep the hematocrit levels below 45%, as indicated in many treatment guidelines. There is a large body of evidence that shows that managing hematocrit is challenging and regardless of best available therapy, they're a substantial portion of patient segments that have poorly controlled hematocrit and therefore, a higher mortality rate compared to age match controls. The treatment paradigm of PV allows patients to enter what I call the danger zone before they get the next treatment. So even those people who are considered well-controlled have increased hematocrit leading up to their phlebotomy. Self-administered 300 may reduce doctor visits and the anxiety associated with the uncertainty of phlebotomy at that time. Phlebotomy is those of donated blood know, is associated with acute symptoms and difficulties. But the real problem in these patients is the potential for chronic symptoms related to iron deficiency in phlebotomized patients.

PTG-300 offers the possibility of putting the control of the hematocrit in the patient's hands with a weekly self-injected mimetic of an endogenous hormone mimetic. With a clear decision to focus PTG-300 development in PV, we are expanding the current study to include additional patients, and we'll be also hosting a scientific planning meeting with leaders in the field of myeloproliferative neoplasms. We will also be working with patient advocates to discuss pivotal and future studies in polycythemia vera.

I will close by saying that while further follow-up and data from additional patients will be needed to confirm the continuity of the robust clinical responses observed to date, we believe this study provides a compelling rationale to initiate planning for a pivotal program in PV. In the near term, we are expanding the current study to include additional patients as we focus on these encouraging results.

Finally, I want to express how proud I am of the entire clinical development team of Protagonist and all the Protagonist employees that helped us to get where we are today with this program.

With that, I would like to turn it over to Dr. Hoffman, who needs no introduction. He's a recognized expert in the field of myeloproliferative disorders and is Director of the Myeloproliferative Disease Program at The Icahn School of Medicine at Mount Sinai and an investigator in the 300 study. Dr. Hoffman?

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Ronald Hoffman, [5]

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Yes. Thank you very much, Sam. Thanks for the opportunity to present this really exciting data. So if we can go to Slide 7, I can educate the audience on what polycythemia vera is so they can have a better understanding of the potential for 300 and put this in context.

So as you can see here, this slide is entitled "What is Polycythemia Vera?" Well, polycythemia vera is a member of a group of chronic hematologic malignancies termed myeloproliferative neoplasms. And these neoplasms are unusual in that patients frequently live several decades. And these neoplasms occur at the level of the hematopoietic stem cell. And unlike leukemia, they are characterized by increased production of mature blood cells. In polycythemia vera, the cell that's most destructive to the patients are really the increased production of red blood cells. And that's the term erythrocytosis that you've heard previously and we'll hear subsequently.

Now the interesting thing about this disease is that there are 100,000 cases of polycythemia vera in the United States. This disease occurs across races and age groups. And the critical diagnostic warning sign is that of an elevated hematocrit, which is the hallmark of the disease. I think the importance of this drug is that although there's 100,000 cases of these patients, these patients, as I mentioned, live for several decades, so the usage of this drug would be quite prolonged over that period of time.

The disease occurs primarily in individuals who are 50 to 70 years of age. There is, however, a higher incidence in young females who present with life-threatening thrombotic events. The thrombotic events that occur in patients with polycythemia vera include strokes, as well as life-threatening thrombosis of arteries or veins within the venus -- within the abdominal cavity. There's a very high incidence of acute myocardial infarction, cerebral vascular incidents and strokes. The women that we've talked about, the young women, they are particularly prone to develop thrombosis within the abdominal cavity, especially the hepatic vein, and that leads to a life-threatening condition called Budd-Chiari syndrome. In its most severe forms, it requires liver transplantation.

Over the last 15 years, there's been tremendous understanding -- new understanding of this group of myeloproliferative neoplasms. And they've been shown to be characterized by mutations in genes that are associated with myeloid blood cell production. So the myeloproliferative neoplasms are associated with 3 driver mutations: one involving JAK2, the other gene called calreticulin and the other MPL, which is a receptor for the hormone thrombopoietin. Virtually 99% of patients with polycythemia vera have a mutation in JAK2. Most commonly, it is a mutation that occurs at exon 14, which is the JAK2V617F mutation. A smaller group of patients have a mutation in exon 12, and those are referred to as exon 12 patients, and they have a similar phenotype, again, elevated hematocrits, increased thrombosis and shorter lifespan due to these thrombotic events and severe erythrocytosis.

Next slide, please. We're going to talk now about the diagnosis, symptoms and treatment of polycythemia vera, so that you can get an understanding of the role of -- the potential role of PTG-300. The diagnosis of polycythemia vera is triggered by finding an elevated hematocrit serendipitously or by a thrombotic event, and that initiates the physician looking for the diagnosis. So for instance, a patient could present within an acute myocardial infarction and be found to have hematocrit. These warning signs, then prompt, the blood tests to be performed that look for the presence of the JAK2V617F mutation or the exon 12 mutation of JAK2V617F is not present. And sometimes, a bone marrow examination is required to perform histopathologic confirmation of the diagnosis.

This disease is not only complicated by thrombotic episodes, but it's also complicated by burdensome systemic symptoms, including fatigue, headache, visual symptoms, night sweats and itchiness. And this itchiness characteristically occurs on exposure to water and has termed aquagenic pruritus. This might seem like a trivial symptom but aquagenic pruritus can be so severe that patients are unable to shower for months or can lead to such stress that occasionally, we've unfortunately had patients who have succumbed to suicide. Thrombotic events is the greatest risk to patients with polycythemia vera. These thrombotic events, as I mentioned, include heart attacks, strokes, deep vein thrombosis or pulmonary embolism or the Budd-Chiari syndrome. The cardinal feature of treatment and reduction of this thrombotic risk is to reduce the hematocrit below 45%. Again, the hematocrit is just the measure that we use of the number of red blood cells and the degree of erythrocytosis. And that assures that essentially the viscosity of the blood or the stickiness of the book is reduced, thereby reducing the incidence of thrombosis.

So normalization of the hematocrit using therapeutic phlebotomy is very common, and it is really the first treatment in newly diagnosed patients with polycythemia vera. Unfortunately, therapeutic phlebotomy leads to the removal of red blood cells, which contain iron and it leads to more severe iron deficiency contributing to many of the exacerbation, of many of the systemic symptoms that I referred to previously. And those patients that require frequent phlebotomies or at their advanced stage that is over 60 years of age or have thrombosis, a prior thrombosis, it is the recommendation of the standard of care that those patients all be treated with hydroxyurea, interferon or Jakafi. It is in this situation that 300 is especially attractive drug because it can be used to treat patients who are not requiring myelosuppressive agents or it could be a replacement for those myelosuppressive agents. Again, the site of the reductive agents are hydroxy and interferon, which are used in combination with phlebotomy, with supplemental phlebotomy, or an alternative drug is Jakafi or ruxolitinib, which is the only U.S. FDA-approved product for phlebotomy. Each of these drugs, and I can go into that in detail during the question-and-answer period are associated with significant adverse effects and have a question -- and have a questionable surrounding their tolerability. Significant evidence, as I've mentioned, shows that controlling the hematocrit below 45% is the most important factor in minimizing thrombosis, cardiovascular events and death due to thrombosis.

Please let's go to the next slide. So we're going to talk a little bit about phlebotomy, which many of you have probably experienced when you donate blood. So most patients receive phlebotomy initially. Phlebotomy is basically the removal of a unit of blood to reduce the hematocrit below 45%. So our target is to keep those patients always below 45% because it's been well demonstrated in the literature that, that reduces significantly the incidence of thrombosis. And the incidence of thrombosis has been shown to be reduced when the degree of time with an adequate of 45% is maximized. In addition, these would patients receive low-dose aspirin to paralyze their platelets and their -- or further augment this antithrombogenesis in patients with polycythemia vera. Patients who undergo phlebotomies will often report feeling tired or dizzy after the phlebotomy. And especially in the elderly, this is a major factor. Many of these patients become hypertensive, require long stays in our outpatient facility or require fluid infusions because -- or going to congestive heart failure because of their poor fluid balance. Furthermore, regular phlebotomy results in iron deficiency that makes -- the augmentation of iron deficiency that may have a debilitating -- that may have debilitating symptoms. As I mentioned, particularly severe fatigue, weakness and cognitive impairments. This cognitive impairment is a really big deal because many of the patients complain of having a fuzzy brain syndrome, and they cannot concentrate and do their jobs. In addition, some of the patients have craving for unusual substances such as ice or clay, which is termed pica. And then, unfortunately, some of the patients have a restless leg syndrome, which prevents them from going to sleep. Three or more phlebotomies in a year in those patients receiving hydroxyurea is associated with an inferior prognosis and a higher incidence of thrombotic events. So you can also think that in those -- in that situation, even in a patient who is receiving hydroxyurea, their combination therapy with 300 could eliminate those frequent phlebotomies and further improve the treatment regimen for these patients.

I think the most important part that you'll see about this drug are the real high-quality aspect of it is that we see these patients, let's say, a 3- or 4-month intervals. At that 3- or 4-month interval, we see that they have an elevated amount of hematocrit and that triggers us to do a phlebotomy. But in reality, we have no way to monitor them during the interval between their visits, and it's likely that for significant periods of time, they have an elevated hematocrit that's only detected at the time of their visit to our clinic. So as you'll see, the really cool part about PTG-300 is that there's a sustained hematocrit control, which we've really never been able to achieve with any of the other agents or but -- or with phlebotomy alone.

Let's go now on to Slide #10, which is PTG-300 and non-cytoreductive hepcidin hormone mimetic, its mechanism of action. So how does this drug really work? Well, hepcidin hormone, has been established recently in the last couple of decades, is playing a primary role in promoting the sequestration of iron and macrophages and decreasing iron availability for the production of red blood cells. So macrophages are a type of white blood cell, and they are present not only in the bone marrow, but they're also present in all other body tissues. But the macrophages in the marrow are termed nursing cells because their activity is essentially to feed iron to red blood cells in the marrow and to alter -- to allow them to produce additional red cells. This process is disregulated by the JAK2 mutation leading to erythrocytosis. So PTG-300 is believed to limit the excess production red cells in polycythemia vera by essentially allowing that iron to remain in the macrophages. Therefore, preventing its transfer into the erythroid precursors. In addition, it blocks the iron that's present in the macrophages in the tissues outside of the marrow. And therefore, we believe alleviates many of the systemic symptoms that are associated with polycythemia vera.

Let's now go on to Slide 11, which is the Phase II study design. This is a really interesting manner in which this study has been constructed. You can see there are 3 phases. Part one is the dose-finding period, which is over 28 days. And there are 2 components to that. I believe a dose -- effective dose-finding phase, where we essentially dose-escalate patients to meet the inadequate requirements. Then a 12- to 14-week period where we essentially have efficacy evaluation that is to maintain the patient's hematocrit below 45%. And then there's part 2 as a blinded withdrawal where the patients are randomized to receive either the fixed active dose or placebo dose for up to 12 weeks. And then I'm sure the patients will be happy about that, those that go on placebo, they will then allow them -- we will be allowed to put them on to an open-label extension phase up to 52 weeks where they will again be able to receive 300. If the patient's hematocrits exceed 45%, they get supplemental phlebotomies.

Let's go on to Slide #12. This is essentially the responses that we've seen in the 7 patients that have been described, that have been evaluated. The red triangles indicate the phlebotomies, and you can see a lot of them to the left of the solid line. And that's the 32 weeks prior to treatment. And you can see that each of these patients, and these were entry criteria, had at least 3 phlebotomies during that period. And then you can see this dotted line, and that's the time at which the doses -- the drug was started. And the first thing that strikes you is that there are a lot of red triangles to the left and only one red triangle to the right, and that's one of our patients who missed one dose due to the -- unfortunately, due to the pandemic. And the numbers indicate the doses that were administered over that period of time. So for instance, you can see in patient 150201, there was a dose escalation and then de-escalation, which I'll discuss on the subsequent slide. So this really -- this slide really summarizes and probably is our most important slide. And it basically shows that with the administration of this drug and careful titration that phlebotomy is almost virtually eliminated.

Next slide. Let's focus on 2 patients. One is the top patient, which is the blue line. And you can see that this patient -- this is the individual who missed the dose because of the COVID infection. And you can see that he was started at 10 milligrams, then went up to 20 milligrams. And on 20 milligrams, he had a hematocrit 47.5, he was unable to come in at that time because of the COVID infection. So we increased his dose to 40 milligrams, his hematocrit dropped, but it was still above 45. He came in, we phlebotomized him, and we've kept him now on 40 milligrams, and you would have seen on Wednesday, and he did not require a phlebotomy and his hematocrit was below 45.

If you look at the bottom patient who is in bright red, you can see that, that patient started at time 0 on 10, then was increased to 20 and then on week 7 was -- got 40 milligrams and then on week 12 got 80 milligrams. And you can see that, that led to a hematocrit dropping to 37.5. We cut our dose to 40 milligrams, and you can see that over that period of time, she has remained phlebotomy-free. We saw her on Wednesday, and she again remains below hematocrit of 45. So there's a dose adjustment that you can easily do. The drugs are being administered at home by the patients, giving them a lot of freedom and also empowering them to control their own disease.

If we go to Slide 14. This addresses how do we know that PTG-300 is really hitting its target. And what we're measuring here is serum ferritin. And if you can recall, ferritin is a molecule that reflects storage iron. And you can see these numbers in the vertical column, and if you're below 25, that indicates that one is iron-deficient. And you can see it with the administration of the drug at subsequent doses over time, the ferritin doses, the ferritin levels increased in each of these patients except the bottom line where a patient received an extremely hematocrit control with an extremely low dose of 300. So these data indicate that the drug is acting on target.

What about the adverse defense? Because this is a chronic disease, one must anticipate that patients will be treated over decades. This is a small sample set but you can see that we had no serious adverse events and the adverse events that were recorded were essentially just irritations, essentially at the injection site that slowly resolved and one of the patients had a bruise at a 10-milligram dose.

Let's go on now to Page 16, which is our summary. So just to start this off. I think phlebotomy is used -- has probably been used for almost 100 years. And for at least, since I've been in this field, which is from the 70s, there's been great debate about what is the optimal myelosuppressive agent. There's great concern about chemotherapy being used in these patients, perhaps increasing the incidence of evolution to acute myeloid leukemia. We never really anticipated that a hormone therapy might be used for this type of disease. So I think this really represents -- this trial really represents a paradigm shift and it has great importance for patients with polycythemia vera. So I think we can easily conclude that the additional data demonstrates the potential of this drug to almost entirely avoid the need for bottoming the treatment of polycythemia vera. All dose compliant patients were phlebotomy-free. Persistent control of hematocrit levels, I think that's really one of the most important issues is that the patients are -- have a sustained control of their hematocrit, which we anticipate will lead to sustained alleviation of their systemic symptoms and elimination of thrombotic episodes. And again, as I tried to indicate to you these elevated hematocrit levels are associated with significant cardiovascular events such as heart attack and stroke. This drug also offers the possibility of weekly administration without the up and down excursions inherent in phlebotomy therapy or any of the toxicities associated with phlebotomy therapy that I discussed with you.

Also, this reduction in phlebotomy may allow sufficient iron to be available systemically to avoid symptoms that we know that are related to iron deficiency. So PTG-300 has the potential as the first non-cytoreductive therapy for PV. This drug is well tolerated and has a safety profile similar with results in prior studies. So as you can see from my presentation, I'm extremely enthusiastic about this drug and its future. Thank you for your time.

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Dinesh V. Patel, Protagonist Therapeutics, Inc. - CEO, President, Interim PAO, Secretary & Director [6]

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Thank you, Dr. Hoffman. I would like to note that the results we have discussed today address the study data as of May 1, and the study continues to enroll. And our plan will be to submit to present additional data at upcoming medical meetings. So at Protagonist, we are now working on 4 clinical programs with our 3 candidates, all discovered through our technology platform.

Our priorities are: one, advancing PTG-300 in polycythemia vera as well as in hereditary hemochromatosis; two, advancing PN-943 to a Phase II study in ulcerative colitis; and three, working closely with our partner, Janssen, to continue Phase II development of PTG-200 in Crohn's disease. As a result of our ability to limit our focus with 300 to PV and HH, we have organized our efforts to extend our cash runway for an additional 6 months. We have taken steps to manage and lower our operating costs and align our resources around our current studies. As a consequence, we now have adequate financial resources to fund planned operating and capital expenditures through the middle of 2022.

Finally, we are mindful of the impact that the current coronavirus outbreak may have on our local operations and global activities. As we disclosed in our financial results released today, we are suspending guidance for PN-943 Phase II initiation and PTG-200 Phase II data, and we are actively working to minimize impact on timelines and move as quickly as conditions would permit. Our priority is maintaining the health and safety of our employees and those who are participating in our studies. We will continue to monitor changing conditions carefully and provide updates as appropriate.

With that, we would like to now open up the call for questions. Operator?

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Questions and Answers

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Operator [1]

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(Operator Instructions) Our first question comes from the line of Chris from Nomura.

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Christopher N. Marai, Nomura Securities Co. Ltd., Research Division - MD & Senior Analyst of Biotechnology [2]

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This is Chris Marai from Nomura Instinet. Maybe the first one is for the physician on the line. Thank you so much for the overview of PV. I was curious how you look at a therapeutic like PTG-300 in terms of clinical practice on sort of an everyday basis as you see PV patients? And how do you think it may fit, assuming this profile remains consistent in sort of the treatment lines of PV, how you may see its usage, in particular relative to drugs like Jakafi?

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Ronald Hoffman, [3]

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Okay. I think that's a really terrific question. I think its use would be quite wise -- wide. I think virtually all patients with PV would be candidates for this drug. We've -- as you can see, we have treated young patients and also older patients with this drug. So it's been well tolerated. I think the advantage, again, is that, especially with young patients, those individuals, we do not want to give life-long myelosuppressive therapy or interferon or Jakafi because of unanticipated -- potential for unanticipated adverse effects. So if they have an increased phlebotomy requirement, this would be an ideal treatment for those folks because basically, it would free them up from returning to the clinic as frequently as they do and requiring repeated phlebotomies. When we risk-stratify these patients, those patients that go on the 3 treatments that I've discussed before, frequently, they still require phlebotomies, and it's been shown by European investigators, if you have additional phlebotomies during your administration of these drugs, that you are an increased risk of thrombosis. So in that setting, this drug could be an adjunctive agent that would eliminate the needs for phlebotomy.

Alternatively, and I could see this developing quite quickly, patients are frequently unwilling to take any of these agents, especially hydroxyurea and interferon because of the potential of hydroxyurea and the concern about interferon essentially having systemic symptoms, problems with individuals about immune disease and also its effect to exacerbate depression in patients. So in those individuals, I could see and even in those high-risk patients, if we can control their hematocrits with this drug, which I think we can easily do, and we've demonstrated that. That this drug would be a real competitor for any of those agents. So I think it could be essentially utilized potentially for the broad swath of patients with polycythemia vera. So I think -- and for long periods of time, that's the issue that I'd like to really emphasize to you. For instance, like young females who have Budd-Chiari syndrome, and we usually put those young females on myelosuppressive therapy and interferon for life-long periods of time, and they can live several decades. They would far prefer being on a non-chemotherapy, non-biologic agent like interferon, it would really liberate them, especially from the adverse effects.

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Christopher N. Marai, Nomura Securities Co. Ltd., Research Division - MD & Senior Analyst of Biotechnology [4]

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Okay. That's very helpful. And then I was wondering if we could touch upon the data for a minute. Dr. Hoffman, could you elaborate on some of the effects of spleen size that you may have observed in the trial, if any? What you would hope to see there on an endpoint like that in a patient population like this?

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Ronald Hoffman, [5]

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Yes. So in this situation, what you have to understand is this is not myelofibrosis. So in reality, most patients with -- or virtually all patients -- I'll say most, the overwhelming majority of patients with patients with polycythemia that don't have symptomatic splenomegaly. So the endpoints that have been used in the past, let's say, for Jakafi for reduction of spleen size are of minimal importance. So these patients, even though some of them have high-risk disease, really didn't have -- they had minimal splenomegaly at all, only 40% of patients with polycythemia vera have splenomegaly and only for our advanced disease it's symptomatic. So the sample size is too small. In animal models, when hepcidin mimetics were given, those are polycythemia vera animal models, the administration of a different hepcidin mimetic did lead to reduction in splenomegaly but we really were not able to assess this because none of these patients really had significant splenomegaly. So we await treating patients like that to see if the data in the mice is recapitulated in humans as it relates to spleen size.

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Christopher N. Marai, Nomura Securities Co. Ltd., Research Division - MD & Senior Analyst of Biotechnology [6]

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Very helpful.

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Operator [7]

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Our next question comes from the line of George Farmer of BMO.

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Read more:
Edited Transcript of PTGX earnings conference call or presentation 7-May-20 9:00pm GMT - Yahoo Finance

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