Archive for the ‘Gene Therapy Research’ Category

Gene therapy has been used to treat a person with haemophilia for the first time in Ireland, a patient group has announced.

The Irish Haemophilia Society (IHS) confirmed on Thursday morning that the person received gene therapy as part of a clinical trial. IHS chief executive Brian OMahony said the treatment is a momentous occasion for the haemophilia community in Ireland.

The general term haemophilia describes a group of inherited blood disorders in which there is a life-long defect in the clotting mechanism of the blood.

Since the 1970s, haemophilia has been treated by the administration of intravenous infusions of the missing clotting factor. However, work done by companies and academic institutions has given new hope that an effective treatment could be based on gene therapy, the IHS said.

The clinical trial uses a viral vector to deliver gene therapy to the persons liver intravenously. In the past, viruses such as HIV and Hepatitis C decimated the haemophilia population in Ireland through contaminated blood. It is ironic that a virus could now be the delivery system which offers the best hope of a practical cure for severe haemophilia, Mr OMahony said.

It is hoped that the effect of the gene therapy infusion will last for many years and possibly for a lifetime.

The principal investigator on the trial in Ireland is Dr Niamh OConnell of the National Coagulation Centre in St. Jamess Hospital. She said the gene therapy was ground breaking.

The opportunity to participate in clinical trials is part of the commitment of the National Haemophilia Service to personalise treatment and to improve the quality of life and outcomes for people with haemophilia.

The study, which is being run by drug manufacturer UniQure, involves three Irish patients among a total of 60 around the world. There will be an intensive period of monitoring of effectiveness at first, followed by a longer term evaluation over five years. Only one treatment is administered to trial patients.

The particular gene therapy is focused on patients who are missing clotting factor IX, the second most-common type of haemophilia. Earlier results show that the level of clotting factor increased from 1 per cent - generally seen as severe haemophilia - to between 33 and 51 per cent in a small number of individuals treated, levels seen in mild cases or even amongst the non-haemophiliac population.

Professor Martina Hennessy of the Wellcome HRB Clinicial Research facility in St Jamess, where the gene therapy was infused, said that access to high quality research is an integral part of good healthcare because it raises standards and pushes the boundaries of what can be achieved.

Delivering gene therapy requires specialised training and equipment, we have been preparing with Dr OConnell and her team for over a year to undertake this exciting work, in partnership with the Irish Haemophilia Society. Other trials are planned, we hope this expertise leads other Irish patient groups also being able to access potentially life changing treatments in the future, she said.

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Gene therapy used in clinical trial for person with haemophilia - The Irish Times

An emergency room physician, initially unable to diagnose a disoriented patient, finds on the patient a wallet-sized card providing access to his genome, or all his DNA. The physician quickly searches the genome, diagnoses the problem and sends the patient off for a gene-therapy cure. Thats what a Pulitzer prize-winning journalist imagined 2020 would look like when she reported on the Human Genome Project back in 1996.

The Human Genome Project was an international scientific collaboration that successfully mapped, sequenced and made publicly available the genetic content of human chromosomes or all human DNA. Taking place between 1990 and 2003, the project caused many to speculate about the future of medicine.

In 1996, Walter Gilbert, a Nobel laureate, said, The results of the Human Genome Project will produce a tremendous shift in the way we can do medicine and attack problems of human disease. In 2000, Francis Collins, then head of the HGP at the National Institutes of Health, predicted, Perhaps in another 15 or 20 years, you will see a complete transformation in therapeutic medicine. The same year, President Bill Clinton stated the Human Genome Project would revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases.

It is now 2020 and no one carries a genome card. Physicians typically do not examine your DNA to diagnose or treat you. Why not? As I explain in a recent article in the Journal of Neurogenetics, the causes of common debilitating diseases are complex, so they typically are not amenable to simple genetic treatments, despite the hope and hype to the contrary.

The idea that a single gene can cause common diseases has been around for several decades. In the late 1980s and early 1990s, high-profile scientific journals, including Nature and JAMA, announced single-gene causation of bipolar disorder, schizophrenia and alcoholism, among other conditions and behaviors. These articles drew massive attention in the popular media, but were soon retracted or failed attempts at replication. These reevaluations completely undermined the initial conclusions, which often had relied on misguided statistical tests. Biologists were generally aware of these developments, though the follow-up studies received little attention in popular media.

There are indeed individual gene mutations that cause devastating disorders, such as Huntingtons disease. But most common debilitating diseases are not caused by a mutation of a single gene. This is because people who have a debilitating genetic disease, on average, do not survive long enough to have numerous healthy children. In other words, there is strong evolutionary pressure against such mutations. Huntingtons disease is an exception that endures because it typically does not produce symptoms until a patient is beyond their reproductive years. Although new mutations for many other disabling conditions occur by chance, they dont become frequent in the population.

Instead, most common debilitating diseases are caused by combinations of mutations in many genes, each having a very small effect. They interact with one another and with environmental factors, modifying the production of proteins from genes. The many kinds of microbes that live within the human body can play a role, too.

Since common serious diseases are rarely caused by single-gene mutations, they cannot be cured by replacing the mutated gene with a normal copy, the premise for gene therapy. Gene therapy has gradually progressed in research along a very bumpy path, which has included accidentally causing leukemia and at least one death, but doctors recently have been successful treating some rare diseases in which a single-gene mutation has had a large effect. Gene therapy for rare single-gene disorders is likely to succeed, but must be tailored to each individual condition. The enormous cost and the relatively small number of patients who can be helped by such a treatment may create insurmountable financial barriers in these cases. For many diseases, gene therapy may never be useful.

The Human Genome Project has had an enormous impact on almost every field of biological research, by spurring technical advances that facilitate fast, precise and relatively inexpensive sequencing and manipulation of DNA. But these advances in research methods have not led to dramatic improvements in treatment of common debilitating diseases.

Although you cannot bring your genome card to your next doctors appointment, perhaps you can bring a more nuanced understanding of the relationship between genes and disease. A more accurate understanding of disease causation may insulate patients against unrealistic stories and false promises.This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Why Sequencing the Human Genome Failed to Produce Big Breakthroughs in Disease - Discover Magazine

Lets take inventory on the therapies that are being developed for the coronavirus epidemic. Here is a very thorough listof at Biocentury, and I should note that (like Stat and several other organizations) theyre making all their Covid-19 content free to all readers during this crisis. Id like to zoom in today on the potential small-molecule therapies, since some of these have the most immediate prospects for use in the real world.

The ones at the front of the line are repurposed drugs that are already approved for human use, for a lot of obvious reasons. The Biocentury list doesnt cover these, but heres an article at Nature Biotechnology that goes into detail. Clinical trials are a huge time sink they sort of have to be, in most cases, if theyre going to be any good and if youve already done all that stuff its a huge leg up, even if the drug itself is not exactly a perfect fit for the disease. So what do we have? The compound that is most advanced is probably remdesivir from Gilead, at right. This has been in development for a few years as an RNA virus therapy it was originally developed for Ebola, and has been tried out against a whole list of single-strand RNA viruses. That includes the related coronaviruses SARS and MERS, so Covid-19 was an obvious fit.

The compound is a prodrug that phosphoramide gets cleaved off completely, leaving the active 5-OH compound GS-44-1524. It mechanism of action is to get incorporated into viral RNA, since its taken up by RNA polymerase and it largely seems to evade proofreading. This causes RNA termination trouble later on, since that alpha-nitrile C-nucleoside is not exactly what the virus is expecting in its genome at that point, and thus viral replication is inhibited.

There are five clinical trials underway (heres an overview at Biocentury). The NIH has an adaptive-design Phase II trial that has already started in Nebraska, with doses to be changed according to Bayesian readouts along the way. There are two Phase III trials underway at China-Japan Friendship Hospital in Hubei, double-blinded and placebo-controlled (since placebo is, as far as drug therapy goes, the current standard of care). And Gilead themselves are starting two open-label trials, one with no control arm and one with an (unblinded) standard-of-care comparison arm. Those might read out first, depending on when they get off the ground, but will be only rough readouts due to the fast-and-loose trial design. The two Hubei trials and the NIH one will add some rigor to the process, but Im not sure when theyre going to report. My personal opinion is that I like the chances of this drug more than anything else on this list, but its still unlikely to be a game-changer.

Theres an RNA polymerase inhibitor (favipiravir) from Toyama, at right, thats in a trial in China. Its a thought a broad-spectrum agent of this sort would be the sort of thing to try. But unfortunately, from what I can see, it has already turned up as ineffective in in vitro tests. The human trial thats underway is honestly the sort of thing that would only happen under circumstances like the present: a developing epidemic with a new pathogen and no real standard of care. I hold out little hope for this one, but given that theres nothing else at present, it probably should be tried. As youll see, this is far from the only situation like this.

One of the screens of known drugs in China that also flagged remdesivir noted that the old antimalarial drug chloroquine seemed to be effective in vitro. It had been reported some years back as a possible antiviral, working through more than one mechanism, probably both at viral entry and intracellularly thereafter. That part shouldnt be surprising chloroquines actual mode(s) of action against malaria parasites are still not completely worked out, either, and some of what people thought they knew about it has turned out to be wrong. There are several trials underway with it at Chinese facilities, some in combination with other agents like remdesivir. Chloroquine has of course been taken for many decades as an antimalarial, but it has a number of liabilities, including seizures, hearing damage, retinopathy and sudden effects on blood glucose. So its going to be important to establish just how effective it is and what doses will be needed. Just as with vaccine candidates, its possible to do more harm with a rushed treatment than the disease is doing itself

There are several other known antiviral drugs are being tried in China, but I dont have too much hope for those, either. The neuraminidase inhibitors such as oseltamivir (better known as Tamiflu) were tried against SARS and were ineffective; there is no reason to expect anything versus Covid-19 although these drugs are a component of some drug cocktail trials. The HIV protease therapies such as darunavir and the combination therapy Kaletra are in trials, but thats also a rather desperate long shot, since theres no particular reason to think that they will have any such protease inhibition against what this new virus has to offer (and indeed, such agents werent much help against SARS in the end, either). The classic interferon/ribavirin combination seems to have had some activity against SARS and MERS, and is in two trialsfrom what I can see. Thats not an awful idea by any means, but its not a great one, either: if your viral disease has interferon/ribavirin as a front line therapy, it generally means that theres nothing really good available. No, unless we get really lucky none of these ideas are going to slow the disease down much.

There are a few other repurposed-protease-inhibitors ideas out there, such as this one. (Edit: I had seen this paper but couldnt track it down, so thanks to those who sent it along). This paper suggests that the TMPRSS2 protease is important for viral entry on the human-cell-side of the process, a pathway that has been noted for other coronaviruses. And it points out that there is a an approved inhibitor (in Japan) for this enzyme (camostat), so that would definitely seem to be worth a trial, probably in combination with remdesivir.

Thats about it for the existing small molecules, from what I can see. What about new ones? Dont hold your breath, is all I can say. A drug discovery program from scratch against a new pathogen is, as many readers here well know, not a trivial exercise. As this Bloomberg article details, many such efforts in the past (small molecules and vaccines alike) have come to grief because by the time they had anything to deliver the epidemic itself had passed. Indeed, Gileads remdesivir had already been dropped as a potential Ebola therapy.

You will either need to have a target in mind up front or go phenotypic. For the former, what youd see are better characterizations of the viral protease and more extensive screens against it. Two other big target areas are viral entry (which involves the spike proteins on the virus surface and the ACE2 protein on human cells) and viral replication. To the former, its worth quickly noting that ACE2 is so much unlike the more familiar ACE protein that none of the cardiovascular ACE inhibitors do anything to it at all. And targeting the latter mechanisms is how remdesivir was developed as a possible Ebola agent, but as you can see, that took time, too. Phenotypic screens are perfectly reasonable against viral pathogens as well, but youll need to put time and effort into that assay up front, just as with any phenotypic effort, because as anyone who does that sort of work will tell you, a bad phenotypic screen is a complete waste of everyones time.

One of the key steps for either route is identifying an animal model. While animal models of infectious disease can be extremely well translated to human therapy, that doesnt happen by accident: you need to choose the right animal. Viruses in general (and coronaviruses are no exception) vary widely in their effects in different species, and not just across the gaps of bird/reptile/human and the like. No, youll run into things where even the usual set of small mammals are acting differently from each other, with some of them not even getting sick at all. This current virus may well have gone through a couple of other mammalian species before landing on us, but youll note that dogs (to pick one) dont seem to have any problem with it.

All this means that any new-target new-chemical-matter effort against Covid-19 (or any new pathogen) is going to take years, and there is just no way around that. This puts small molecules in a very bimodal distribution: you have the existing drugs that might be repurposed, and are presumably available right now. Nothing else is! At the other end, for completely new therapies you have the usual prospects of drug discovery: years from now, lots of money, low success rate, good luck to all of us. The gap between these two could in theory be filled by vaccines and antibody therapies (if everything goes really, really well) but those are very much their own area and will be dealt with in a separate post.

Either way, the odds are that we (and I mean we as a species here) are going to be fighting this epidemic without any particularly amazing pharmacological weapons. Eventually well have some, but I would advise people, pundits, and politicians not to get all excited about the prospects for some new therapies to come riding up over the hill to help us out. The odds of that happening in time to do anything about the current outbreak are very small. We will be going for months, years, with the therapeutic options we have right now. Look around you: what we have today is what we have to work with.

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Covid-19 Small Molecule Therapies Reviewed - Science Magazine

In the months since the novel coronavirus rose from a regional crisis to a global threat, drug makers large and small have scrambled to advance their best ideas for thwarting a pandemic.

Some are repurposing old antivirals. Some are mobilizing tried-and-true technologies, and others are pressing forward with futuristic approaches to human medicine.

Heres a guide to some of the most talked-about efforts to treat or prevent coronavirus infection, with details on the science, history, and timeline for each endeavor.

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Approach: TreatmentStage: Phase 3

Gileads remdesivir, an intravenous treatment, has already been used to treat one infected patient in the U.S. and will soon be deployed in a pair of large, late-stage studies in Asia. Later this month, Gilead will recruit about 1,000 patients diagnosed with the coronavirus to determine whether multiple doses of remdesivir can reverse the infection. The primary goals are reducing fever and helping patients get out of the hospital within two weeks. The drug, which previously failed in a study on Ebola virus, is also being studied in smaller trials in China and the U.S.

Approach: VaccineStage: Phase 1

Moderna set a drug industry record with mRNA-1273, a vaccine candidate identified just 42 days after the novel coronavirus was sequenced. The company is working with the National Institutes of Health on a healthy-volunteer study expected to begin next month. If mRNA-1273 proves itself to be safe, the two organizations will enroll hundreds more patients to determine whether the vaccine protects against infection. Modernas product is a synthetic strand of messenger RNA, or mRNA, designed to convince bodily cells to produce antibodies against the virus. The company, founded in 2010, is yet to win Food and Drug Administration approval for any of its mRNA medicines.

Approach: VaccineStage: Preclinical

Like Moderna, CureVac uses man-made mRNA to spur the production of proteins. And, like Moderna, it got a grant from the nonprofit Coalition for Epidemic Preparedness Innovations to apply its technology to coronavirus. CureVac has said it expects to have a candidate ready for human testing within a few months. The company is also working with CEPI on a mobile mRNA manufacturing technology, one that would theoretically allow health care workers to rapidly produce vaccines to respond at the site of an outbreak.

Approach: VaccineStage: Preclinical

GlaxoSmithKline, one of the worlds largest vaccine manufacturers, is lending its technology to a Chinese biotech firm at work on a coronavirus vaccine. Under an agreement signed last month, GSK is providing its proprietary adjuvants compounds that enhance the effectiveness of vaccines to Clover Biopharmaceuticals, a privately held company based in Chengdu. Clovers approach involves injecting proteins that spur an immune response, thereby priming the body to resist infection. The company has not said when it expects to advance into human testing.

Approach: VaccineStage: Preclinical

Inovio has spent the last four decades working to turn DNA into medicine, and the company believes its technology could quickly generate a vaccine for the novel coronavirus. Working with CEPI grant money, Inovio has come up with a DNA vaccine it believes can generate protective antibodies and keep patients from infection. The company has partnered with a Chinese manufacturer, Beijing Advaccine Biotechnology, and is working through preclinical development with a candidate called INO-4800. The company expects to progress into clinical trials later this year.

Approach: Vaccine and treatmentStage: Preclinical

Johnson & Johnson, which has in the past responded to outbreaks of the Ebola and Zika viruses, is taking a multipronged approach to the coronavirus. The company is in the early days of developing a vaccine that would introduce patients to a deactivated version of the virus, triggering an immune response without causing infection. At the same time, J&J is working with the federal Biomedical Advanced Research and Development Authority on potential treatments for patients who are already infected, a process that includes investigating whether any of its older medicines might work against the coronavirus.

Approach: TreatmentStage: Preclinical

Regeneron has grown into a $50 billion business based on its ability to craft human antibodies out of genetically engineered mice. Now its tapping that technology in hopes of treating coronavirus. The company is immunizing its antibody-generating mice with a harmless analog of the novel coronavirus, generating potential treatments for the infection. The most potent antibody results will go into animal testing, and if everything goes according to plan, Regeneron will be ready for human testing by late summer. The last time Regeneron embarked on this process, during the Ebola outbreak of 2015, it came up with an antibody cocktail that roughly doubled survival rates for treated patients.

Approach: VaccineStage: Preclinical

Sanofi, which has successfully developed vaccines for yellow fever and diphtheria, is working with BARDA on an answer to the coronavirus. Sanofis approach involves taking some of the coronaviruss DNA and mixing it with genetic material from a harmless virus, creating a chimera that can prime the immune system without making patients sick. Sanofi expects to have a vaccine candidate to test in the lab within six months and could be ready to test a vaccine in people within a year to 18 months. Approval would likely be at least three years away, the company said. Sanofi previously put its technology to work against SARS, a close relative of the novel virus.

Approach: TreatmentStage: Preclinical

Vir Biotechnology, a company focused on infectious disease, has isolated antibodies from people who survived SARS, a viral relative of the novel coronavirus, and is working to determine whether they might treat the infection. Teaming up with Chinese pharma contractor WuXi Biologics, the San Francisco-based Vir is in the early stages of development and hasnt specified when it expects to have products ready for human testing. Virs CEO, Biogen veteran George Scangos, is also coordinating the trade group BIOs response to the coronavirus outbreak.

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A detailed guide to the coronavirus drugs and vaccines in development - STAT

Sunnybrook Hospital is shown in Toronto on Sunday Jan. 26, 2020. (The Canadian Press/Doug Ives)

A $16.7 million grant from the W. Garfield Weston Foundation will fund research for a new innovative way to treat brain diseases and disorders such as cancer and Alzheimers according to a press release from the Sunnybrook Health Sciences Centre from earlier this week.

Through the Weston Brain Institute, the W. Garfield Weston Foundation has established the Weston Family Focused Ultrasound Initiative at Sunnybrook, which is a health sciences centre researching and inventing the future of health care.

According to the press release the funding will go towards an initiative to create an one size fits all ultrasound device that promises to deliver a personalised way to treat brain diseases.

We are delighted to make this contribution to improve the treatment of brain diseases, Galen G. Weston, the president of The W. Garfield Weston Foundation said in a press release. This initiative is a unique opportunity to accelerate the development of this breakthrough technology while encouraging leadership and innovation in the Canadian medical technology sector.

The prospect of readying this device to benefit so many people in Canada and around the world is very exciting, he added.

The device will use focused ultrasound to open the blood brain barrier, which is the packed network of vessels that protects the brain from toxins, but also prevents the brain from getting help from treatments, such as chemotherapy, stem cells, or gene therapy.

Dr. Kullervo Hynynen, a physicist, the vice president of research innovation at Sunnybrook, and leads the team working on the prototype device, said that the vessels in the brain are special because they protect the brain from foreign agents.

They do not allow most of the medication to enter into brain cells, he said. This device will allow us to modulate that barrier and blood brain barrier and allow medications to get into that brain in the specified locations.

A prototype of a new device which will be custom-built for each patient and will deliver focused ultrasound without the need for real-time MRI is shown in a handout photo from Sunnybrook Hospital. Sunnybrook Hospital says a landmark $16.7-million grant could revolutionize the treatment of brain disorders including Alzheimers, brain cancer and ALS. (The Canadian Press/HO-Sunnybrook Hospital/Jason Mortlock)

Once the device is developed, Sunnybrook will launch three clinical trials to test the device and showcase the technology.

This technology holds tremendous promise for patients with difficult-to-treat brain disorders like Alzheimers disease, brain cancer and ALS, where the blood-brain barrier is a major obstacle, said Dr. Nir Lipsman, a neurosurgeon thats leading Sunnybrooks clinical team.

These are some of the most complex disorders that have no effective treatments, so were excited to move closer to testing the device in clinical trials. The impact of this technology on patient care will be felt across Canada and around the world.

The whole initiative is going to cost about $33 million, therefore Sunnybrook is looking towards the community to secure the rest of the funding it needs to complete its research.

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Philanthropic grant funds research for innovative way to treat brain disorders - Radio Canada International (en)

Voyager Therapeutics (NASDAQ:VYGR) had its price target trimmed by Wedbush from $34.00 to $27.00 in a research note published on Wednesday morning, The Fly reports. The brokerage currently has an outperform rating on the stock. Wedbush also issued estimates for Voyager Therapeutics Q2 2020 earnings at ($0.83) EPS, FY2020 earnings at ($3.18) EPS, Q1 2021 earnings at ($0.81) EPS, Q2 2021 earnings at ($0.79) EPS, Q3 2021 earnings at ($0.71) EPS, Q4 2021 earnings at ($0.69) EPS, FY2021 earnings at ($2.99) EPS, FY2022 earnings at ($2.76) EPS, FY2023 earnings at ($2.24) EPS and FY2024 earnings at $0.29 EPS.

Several other brokerages have also issued reports on VYGR. ValuEngine raised shares of Voyager Therapeutics from a sell rating to a hold rating in a research note on Tuesday, February 25th. Zacks Investment Research lowered shares of Voyager Therapeutics from a hold rating to a sell rating in a research note on Saturday, January 25th. Oppenheimer began coverage on shares of Voyager Therapeutics in a research note on Wednesday, February 5th. They set an outperform rating and a $26.00 target price on the stock. BidaskClub raised shares of Voyager Therapeutics from a strong sell rating to a sell rating in a research note on Wednesday, February 5th. Finally, Evercore ISI reissued a hold rating and set a $18.00 target price on shares of Voyager Therapeutics in a research note on Sunday, November 24th. Two equities research analysts have rated the stock with a sell rating, four have issued a hold rating and five have given a buy rating to the company. Voyager Therapeutics has a consensus rating of Hold and a consensus price target of $22.38.

NASDAQ:VYGR opened at $10.97 on Wednesday. The firms fifty day moving average is $12.34 and its 200-day moving average is $14.70. Voyager Therapeutics has a 52 week low of $10.13 and a 52 week high of $28.79.

In other Voyager Therapeutics news, COO Matthew P. Ottmer sold 3,724 shares of the companys stock in a transaction on Tuesday, January 21st. The shares were sold at an average price of $13.36, for a total transaction of $49,752.64. Following the transaction, the chief operating officer now owns 26,276 shares in the company, valued at $351,047.36. The transaction was disclosed in a filing with the SEC, which is accessible through this link. Also, CEO Andre Turenne sold 10,705 shares of the companys stock in a transaction on Tuesday, January 21st. The stock was sold at an average price of $13.36, for a total transaction of $143,018.80. Following the transaction, the chief executive officer now owns 85,545 shares in the company, valued at approximately $1,142,881.20. The disclosure for this sale can be found here. Over the last three months, insiders have sold 17,557 shares of company stock worth $234,562. 33.60% of the stock is owned by insiders.

Institutional investors and hedge funds have recently added to or reduced their stakes in the business. Steward Partners Investment Advisory LLC raised its holdings in Voyager Therapeutics by 335.0% during the fourth quarter. Steward Partners Investment Advisory LLC now owns 4,350 shares of the companys stock worth $60,000 after buying an additional 3,350 shares during the last quarter. Victory Capital Management Inc. raised its holdings in Voyager Therapeutics by 46.0% during the fourth quarter. Victory Capital Management Inc. now owns 6,199 shares of the companys stock worth $86,000 after buying an additional 1,954 shares during the last quarter. Russell Investments Group Ltd. acquired a new position in Voyager Therapeutics during the third quarter worth $139,000. AJO LP acquired a new position in Voyager Therapeutics during the fourth quarter worth $118,000. Finally, Jackson Wealth Management LLC acquired a new position in Voyager Therapeutics during the fourth quarter worth $120,000. Hedge funds and other institutional investors own 85.69% of the companys stock.

About Voyager Therapeutics

Voyager Therapeutics, Inc, a clinical-stage gene therapy company, focuses on the development of treatments for patients suffering from severe neurological diseases. The company's lead clinical candidate is the VY-AADC, which is in open-label Phase 1b clinical trial for the treatment of Parkinson's disease.

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Wedbush Cuts Voyager Therapeutics (NASDAQ:VYGR) Price Target to $27.00 - Redmond Register

Ben Osborn, UK Managing Director of Pfizer, talks about his role and whats on the horizon for Pfizer and the life sciences sector.

An introduction on who you are/your role and organisation

Throughout my 20 years at Pfizer, and as a parent to a son with a chronic health condition (a rare form of epilepsy), Ive experienced how remarkable the NHS can be in more ways than most firstly, as a father of a child with ongoing and complex medical needs, and secondly as a leader at Pfizer. This gives me a unique perspective on the NHS and wider healthcare and pharmaceutical industry. I have hands-on understanding and experience of the success of the NHS and where there are challenges.

In my role as Country Manager and Managing Director, I lead Pfizer in the UK to deliver against our purpose: breakthroughs that change patients lives. We are at an exciting point in time as an organisation and as a sector, and I am passionate about what we can all do to transform patients lives and support a thriving life sciences sector. Pfizers innovation spans the rarest to the most common of diseases, and our footprint across the UK is significant with 2,500 colleagues.

What does the landscape look like for 2020 and beyond in the life sciences/health tech sector?

As we head into a new decade, we face the greatest opportunity yet to better protect and invest in our nations health. We are living through an age of unprecedented innovation as we stand at the cusp of a new era of breakthroughs which have the potential to change patients lives.

Advances in science, data and technology, in particular digital, are driving change in the health system faster than ever before, and with the new Government refocusing its efforts on our health service, we are at a pivotal moment where the latest scientific research, renewed investment and collective ambition, can come together to create the impetus for change that we need to drive better outcomes and experience for patients.

Why is collaboration so important?

Simply put, the healthcare challenges of today are simply too complex for any one organisation to solve alone, given the diversity of expertise, resources, and skills required.

The approach to innovation has changed over recent years and requires everyone to take a much more collaborative approach and form greater, deeper and stronger collaborations.

We must work together as a sector (NHS, academia, industry, and patients) and use this unparalleled opportunity to reshape UK life sciences for the better, and to support the NHS to deliver world-leading healthcare that makes a real difference to patients. No single organisation has the answer. It is only through collective action and partnership that we can deliver our shared ambition.

Whats on the horizon for Pfizer?

As a global biopharmaceutical company we are going through an exciting period of change. We have shifted to become laser-focused on a single purpose: breakthroughs that change patients lives; and at the core of our culture, of everything we do, is how we can deliver against this to make a positive contribution to patients and the society in which we live and work.

Our pipeline has the potential to transform patient outcomes and NHS service delivery across key areas, including cardiomyopathy, vaccination, osteoarthritis pain and oncology, and we also have one of the industrys deepest gene therapy pipelines. It is through our partnerships with the NHS, academia and others, in Wales and across the UK, that we will bring these therapies to patients.

We recognise the challenges faced across healthcare systems, and we want to partner to shift the historic volume-based model to one centred on outcomes and value.

Tell us what TH2020 means to you and what you are hoping to achieve and talk about.

I am excited to be talking at TH2020 and to be a part of the stimulating debate around the progressive approach to health and care that is taking place in Wales. We recognise that Wales is a leader amongst the UK nations in the way it has embraced the innovation agenda, and is blazing a trail for approaches to value-based healthcare. I want to share our vision for life sciences, and how we can work with others to transform health and care in Wales and beyond.

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Exclusive Interview with Ben Osborn, UK Managing Director of Pfizer - Business News Wales

MONTREAL--(BUSINESS WIRE)--The venture capital fund AmorChem II is very proud to announce the financing of a new university project focusing on preclinical development of retinal gene augmentation to treat Peroxisome Biogenesis Disorders in the Zellweger spectrum (PBD-ZSD). The funds financing will bring together three major research groups from the Research Institute of the McGill University Hospital Centre (RI-MUHC), the University of Pennsylvania, and the University of Southern California.

This program is focused on developing and testing a gene therapy construct that may ultimately improve the well-being of patients with a disabling disorder by treating retinal degeneration. Retinal degeneration leading to blindness is a major, untreatable feature of PBD-ZSD. In fact, visual improvement is a critical symptomatic target that can substantially improve quality of life of patients. The collaborators propose to test the gene therapy targeting retinal photoreceptor cells in PEX1 animal models to study recovery of peroxisomal function, says Ins Holzbaur, Managing Partner at AmorChem.

It is particularly rewarding for us to finance such a promising and impactful program in an indication where the current standard of care is strictly supportive. This project allows AmorChem to address a major need in this multisystem disorder and enable the improvement of communication, learning, mobility and autonomy of patients with PBD-ZSD. In addition, the strategy of using retinal gene therapy could eventually open the door to using gene augmentation in other organ systems affected in this disorder, adds Elizabeth Douville, Managing Partner at AmorChem.

Three seasoned researchers are contributing a wide breadth of experience and knowledge to this project. The collaboration is led by Dr. Nancy Braverman from the RI-MUHC, internationally recognized for her work in peroxisomal diseases. In addition, the collaboration will benefit from the materials generated by Dr. Jean Bennett at the Center of Advanced Retinal and Ophthalmic Therapeutics at the University of Pennsylvania and the mammalian cell technology expertise of Dr. Joseph G Hacia from the University of Southern California.

"The innovative work by Dr. Braverman has tremendous potential to make a difference in the lives of patients with peroxisomal disorders. The partnership between the RI-MUHC, University of Pennsylvania, University of Southern California and Amorchem is an exemplary demonstration of the synergies required for translating this scientific discovery to tangible benefits for patients," adds Bruce Mazer, MD Executive Director and CSO (Interim), Research Institute of the McGill University Health Centre.

If the initial proof of concept studies are viable, AmorChem will exercise its Option to negotiate an exclusive license to the underlying technology.

About AmorChem

AmorChem (www.amorchem.com) is a leading early stage venture capital fund launched in 2011 in Montreal. The AmorChem team utilizes its deep understanding of fundamental science to uncover its therapeutic potential and focuses its core expertise in translational research to accelerate therapeutic drug discovery and development across a broad spectrum of disease areas. The fund capitalises on both its venture capital expertise and its entrepreneurial experience to spark the creation of start-up companies and help shape them into the next generation of biotech companies. With over $85M under management, AmorChem has financed over 30 university projects and started up several biotechnology companies from the fruits of this innovative research.

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AmorChem invests in a new gene therapy approach to help patients with a devastating orphan disease - Business Wire

The IPO market is feeling the effects of the coronavirus outbreak with a surge in the VIX volatility index weighing on IPO activity. Since 2015, a week in which VIX volatility has surpassed 35 has been followed by a week averaging two US IPO pricings. Our observational trend continues through 2020, as one biotech entered the public market this past week.  Six IPOs and three SPACs submitted initial filings with the SEC.

Passage Bio (PASG), a preclinical biotech developing gene therapies, priced at the high end of the range to raise $216 million at an $840 million market cap. The deal raised 72% more in proceeds than Passage Bio originally filed for. The company is furthering the research from UPenn’s Gene Therapy Program, which is headed by co-founder James Wilson. Bolstered by the recent performances of other large early stage biotech IPOs, Passage Bio finished up 23%, another sign that biotechs are pushing back against the effects of the coronavirus. Chinese medical information platform Zhongchao (ZCMD) began trading on Monday after raising $12 million in an IPO on Friday 2/21. The company was flat after its first day on the Nasdaq and is currently down 2%.

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IPO Weekly Recap: Yes, the IPO Market has caught the coronavirus

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IPO Weekly Recap: Yes, the IPO Market has caught the coronavirus - Nasdaq

From a cancer vaccine to gene insertion for those with Parkinson's, local researchers are breaking through.

Research is big business at Ohio State University, with medical funding currently exceeding a quarter of a billion dollars, according to Peter Mohler, vice dean for research at OSUs College of Medicine. Ohio State gets grants from the National Institutes of Health and other sources such as other government agencies, nonprofit foundations and industry contracts.

Funding for OSUs College of Medicine, alone, now includes some $268.5 million. What follows are some of the latest breakthroughs.

An Anticancer Vaccine

A new anticancer vaccine, called B-Vaxx, is still in the early stages of being tested but initial studies are promising. The first-ever human trial at Ohio State led by researcher Pravin Kaumaya, a professor in the college of medicines department of obstetrics and gynecology, showed that patients with metastatic or recurrent solid tumors that overexpress the HER-2 protein had a stronger immune response than they did to current treatments.

This means that B-Vaxx may be more effective in killing tumor cells in many types of aggressive breast, gastroesophageal, endometrial, ovarian, colorectal and lung cancers. Although more research and clinical trials are needed, the bottom line on this first report is that scientists have concluded that the vaccine induced patient antibodies that showed potent antitumor activity.

Hope for Parkinsons

Dr. Krystof Bankiewicz, a researcher specializing in neurodegenerative disorders, and Dr. Russell Lonser, chair of OSUs department of neurological surgery, have been working with transformational gene therapy to develop cures for Parkinsons and other neurodegenerative diseases.

A one-step solution for Parkinsons could be the insertion of a non-pathogenic virus thats been modified to do only one thing: deliver the missing gene to a specific region of the brain.

The missing gene, if implemented, stops the progression of Parkinsons. Administering it, however, is a complex procedure. An MRI scanner is used to directly implant it in the brain.

Six clinical trials regarding the gene therapy and its effects on neurodegenerative diseasesincluding Parkinsons, Alzheimers, Huntingtons and moreare underway at Ohio State. In fact, the clinical trials for pediatric patients have been so successful that registration of the therapy has been fast-tracked with the U.S. Food and Drug Administration. There is hope that the drug will be approved this year for use in children.

Brain Stimulation

A small 2018 study at Ohio State implanted electrodes into the frontal cortex of Alzheimers patients and programmed a pacemaker to deliver deep brain stimulation. DBS has already proven to be helpful for patients with Parkinsons, epilepsy and obsessive-compulsive disorder. And, it is currently being studied for addiction, chronic pain, multiple sclerosis, traumatic brain injury and more.

Two of three people showed statistical improvement, says Dr. Douglas Scharre, professor of neurology and clinical psychology at OSUs Center for Cognitive and Memory Disorders and its Center for Neuromodulation. One patient was able to plan an outing and handle money, make plans for an event and cook a simple meal. These may seem like minor improvements, but if the patient cant do it, the caregiver has to.

Atrial Fib: The Watchman

Among the 3,000 clinical trials at various stages at Ohio State in recent years has been apilot studylead by Dr. Ahmet Kilic, former OSU associate professor of cardiac surgery, on the efficacy of the Watchman, a tiny parachute-like device which is implanted into the heart to regulate the heartbeat of those who suffer from atrial fibrillation. (Kilic is now director of heart transplantation and mechanical circulatory support at Johns Hopkins Medicine.)

Along with reducing stroke risk, the Watchman allows for remote monitoring of heart function. Watchman patients also forgo the risk of excessive bleeding caused by long-term use of warfarin, such as Coumadin and other blood thinners. The implantnow in more than 100,000 peoplecan eliminate regular blood tests and food-and-drink restrictions that come with warfarin.

Expecting a Daughter?

Researchers at the Wexner Medical Center have found thatthat immune cell samples of women carrying girls produced more proteins called pro-inflammatory cytokines than those carrying boys, resulting in exacerbation of conditions such as asthma, and contributing to fatigue and achiness.

Too many of these cytokinescan really be unhelpful for our bodies functioning, explains Amanda Mitchell, lead author of the study while she was a postdoctoral researcher in the universitys Institute for Behavioral Medicine Research. Women carrying girls exhibited greater inflammatory responses when faced with some sort of immune challenge compared to women carrying boys.

Exercising and doing relaxing activities, such as meditation, are recommended. Also, eating healthy foods, including leafy greens, will better support healthy immune responses. Mitchell is now an assistant professor at the University of Louisvilles department of counseling and human development.

More Sleep EqualsHappier Marriages

According to the Centers for Disease Control and Prevention, 35 percent of Americans get less than seven hours of sleep per night, resulting in increased risk of stress-related inflammation and ensuing chronic illnesses such as cardiovascular disease, diabetes, arthritis and others.

In arecent studyat Ohio States Institute for Behavioral Medicine, married couples were asked to supply blood samples and information regarding hours they slept the previous two nights. They were then asked to resolve a conflict, with blood samples taken after the discussion. Although people who had slept less initially had no more inflammation than usual, there was a greater inflammatory response after the conflict. Furthermore, if both partners got less than seven hours of sleep the previous two nights, they were more likely to become hostile.

Couples using unhealthy resolution tactics had an even greater inflammatory response. In a marriage, sleep patterns often track together, explains Janice Kiecolt-Glaser, the senior author of the study and director of OSUs Institute for Behavioral Medicine Research. If one person is restless, or has chronic problems, that can impact the others sleep. If these problems persist over time, you can get this nasty reverberation within the couple.

Less Stress, Better Health

Dining on a Greek salad may be great, but if youre stressed, it may be no better for you than fish and chips, according to an Ohio State study published inMolecular Psychiatry. In the study, 58 women were given two different types of meals, one high in saturated fat, which has been linked to cardiovascular disease, and another with more heart-healthy, plant-based oil. The meals were similar in terms of calories and grams of fat. While inflammatory responses were predictably lower if the women were not stressed after the healthier meal, if a woman was stressed, it looked like she was eating the saturated fat meal in terms of her [inflammatory] responses, study author Kiecolt-Glaser told National Public Radio.

Even though the stressors were for everyday issues, such as dealing with a sick parent, the stress seemed to boost inflammation, increasing chances for disease and slowing the healing process. Still, more research needs to be done and there are plenty of ways to combat stress, includingdeep-breathing.

Immune Cells and Sex

An Ohio State study done on rats and reported in theJournal of Neurosciencefound that immune mast cells,usually ignored by neuroscientists, appear to play an important role in determining the gender of an animals sexual behavior.

When researchers, led by Kathryn Lenz, assistant professor of behavioral neuroscience, silenced the mast cells in male fetal rats, they found that the adult males were far less interested in having sex with females. In fact, they acted almost like females, according the study.

Newborn female rats whose mast cells were activated with a stimulating chemical did the opposite, showing more traditionally males behaviors. Lenz theorizes that if human development mirrors what was seen in this study, even relatively minor influencessuch as an allergic reaction, injury or inflammation during pregnancycould possibly steer sexual behavior and development.

On the Move: Its All Good

According to Bernadette Melnyk, chief wellness officer and dean of OSUs College of Nursing, researchers at the American College of Sports Medicine have confirmed that physical activity completed in any duration is associated with health benefits and count towards your recommended 150 minutes of weekly activity.

Traditionally, physical activity recommendations have focused on accumulating moderate-to-vigorous physical activity either in a continuous manner, such as going for a 30-minute run, or in short bouts performed throughout the day, according to theACSM. However, in 2018, thanks to the advent of digital and other activity trackers, the ACSM also recognized that most daily activity is sporadic and is typically performed in bouts that are less than 10 minutes in duration. Any such activity is now associated with favorable health-related outcomes.

Take time each day to get moving, even if only for five minutes, adds Melnyk.

Reprinted fromColumbus Monthly Health 2020.

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Medical Research and Innovation at Ohio State - Columbus Monthly

One in 14 Ontarians can expect to be diagnosed with colorectal cancer in their lifetime. COURTESY OF ED UTHMAN/FLICKR

University of Toronto scientists have identified a key protein as a common factor in the growth of many different types of colorectal cancer tumours, according to research published in the Journal of Cell Biology. Colorectal cancer develops in the colon or rectum. In Ontario, it is also the second most fatal cancer, and one in 14 Ontarians can expect to be diagnosed with this form of cancer in their lifetime.

In past research, scientists have linked the excessive accumulation of beta-catenin, a protein with crucial functions in cell development, to the expression of genes that drive tumour proliferation. Research has associated 80 per cent of colorectal cancers with gene mutations that greatly increase the production of beta-catenin.

The co-authors of the study have identified another protein, Importin-11, as the compound that enables beta-catenin transportation to the nucleus of the human cell. Cancer therapies that inhibit this transport could be a promising way to treat colorectal cancer.

Fundamental research provides new knowledge for cancer therapies

The Varsity spoke to Dr. Stephane Angers, a co-author of the study and an associate professor at U of Ts Department of Biochemistry. Angers lab has spent a considerable amount of time studying biological pathways the series of chemical changes during cellular development that give cells their final functions.

Angers noted that Monika Mis, the lead author of the study and a PhD student, uncovered the role of Importin-11 in colorectal cancer in Angers lab. Mis used the gene-editing CRISPR-Cas9 technology to screen genes in colorectal cancer calls to identify a novel gene, IPO11, which encodes for the protein Importin-11.

Current treatment options for colorectal cancer include surgery, chemotherapy, and other radiation therapy. Although this discovery is still in its fundamental stages, blocking the transport of beta-catenin holds great promise for developing new therapies.

As Angers put it, It provides new ammunition, new possibilities, and new knowledge that could lead in the future to new therapies, but it is very much at the discovery level at this point.

More research required to develop therapies

Further research could involve drug discovery and widen the scope of Importin-11 function in various cells. Researchers may also find it valuable to analyze existing data about colorectal cancer. The goal is to understand how the mutations affect tumour formation and develop therapies that harness this knowledge.

Angers lab is also investigating other potential applications of the Wnt pathway, a specific biological pathway associated with beta-catenin. A particularly interesting aspect is its role in regenerative medicine, which is the study of restoring human cells, tissues, and organs.

We think that with new molecules that we have developed we can now activate the pathway in order to promote the regenerative abilities of tissues, noted Angers.

Tags: biology, cancer, medicine, oncology

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New ammunition uncovered by U of T researchers to develop colorectal cancer treatment - Varsity

CAMBRIDGE, Mass. & BRISBANE, Calif.--(BUSINESS WIRE)--Biogen Inc. (Nasdaq: BIIB) and Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, today announced that they have executed a global licensing collaboration agreement to develop and commercialize ST-501 for tauopathies including Alzheimers disease, ST-502 for synucleinopathies including Parkinsons disease, a third undisclosed neuromuscular disease target, and up to nine additional undisclosed neurological disease targets. The companies will leverage Sangamos proprietary zinc finger protein (ZFP) technology delivered via adeno-associated virus (AAV) to modulate the expression of key genes involved in neurological diseases.

As a pioneer in neuroscience, Biogen will collaborate with Sangamo on a new gene regulation therapy approach, working at the DNA level, with the potential to treat challenging neurological diseases of global significance. We aim to develop and advance these programs forward to investigational new drug applications, said Alfred Sandrock Jr., M.D., Ph.D., Executive Vice President, Research and Development at Biogen.

There are currently no approved disease modifying treatments for patients with many devastating neurodegenerative diseases such as Alzheimers and Parkinsons, creating an urgency for the development of medicines that will not just address symptoms like the current standards of care, but slow or stop the progression of disease, said Sandy Macrae, CEO of Sangamo. We believe that the promise of genomic medicine in neuroscience is to provide a one-time treatment for patients to alter their disease natural history by addressing the underlying cause at the genomic level.

Sangamos genome regulation technology, zinc finger protein transcription factors (ZFP-TFs), is currently delivered with AAVs and functions at the DNA level to selectively repress or activate the expression of specific genes to achieve a desired therapeutic effect. Highly specific, potent, and tunable repression of tau and alpha synuclein has been demonstrated in preclinical studies using AAV vectors to deliver tau-targeted (ST-501) and alpha synuclein-targeted (ST-502) ZFP-TFs.

The combination of Sangamos proprietary zinc finger technology, Biogens unmatched neuroscience research, drug development, and commercialization experience and capabilities, and our shared commitment to bring innovative medicines to patients with neurological diseases establishes the foundation for a robust and compelling collaboration, said Stephane Boissel, Head of Corporate Strategy at Sangamo. This collaboration exemplifies Sangamos commitment to our ongoing strategy to partner programs that address substantial and diverse patient populations in disease areas requiring complex clinical trial designs and commercial pathways, therefore bringing treatments to patients faster and more efficiently, while deriving maximum value from our platform.

Under the terms of the collaboration, Biogen has exclusive global rights to ST-501 for tauopathies including Alzheimers disease, ST-502 for synucleinopathies including Parkinsons disease, and a third undisclosed neuromuscular disease target. In addition, Biogen has exclusive rights to nominate up to nine additional undisclosed targets over a target selection period of five years. Sangamo will perform early research activities, costs for which will be shared by the companies, aimed at the development of the combination of proprietary CNS delivery vectors and ZFP-TFs targeting therapeutically relevant genes. Biogen will then assume responsibility and costs for the investigational new drug-enabling studies, clinical development, related regulatory interactions, and global commercialization.

Sangamo will be responsible for GMP manufacturing activities for the initial clinical trials for the first three products of the collaboration and plans to leverage its in-house manufacturing capacity. Biogen will assume responsibility for GMP manufacturing activities beyond the first clinical trial for each of the first three products.

Upon closing of this transaction, Sangamo will receive $350 million comprised of $125 million in a license fee payment and $225 million from the sale of new Sangamo stock, or approximately 24 million shares at $9.21 per share. In addition, Sangamo may receive up to $2.37 billion in other development, regulatory, and commercial milestone payments, including up to $925 million in pre-approval milestone payments and up to $1,445 million in first commercial sale and other sales-based milestone payments. Sangamo will also be eligible to receive from Biogen tiered high single-digit to sub-teen double-digit royalties on potential net commercial sales of products arising from the collaboration. Closing of the transaction is contingent on completion of review under antitrust laws, including the Hart-Scott-Rodino (HSR) Antitrust Improvements Act of 1976 in the U.S.

Conference call

Sangamo will host a conference call at 8:00 a.m. ET tomorrow, Friday, February 28, which will be open to the public via telephone and webcast. During the conference call, Sangamo will discuss the collaboration, review financial results for the fourth quarter and full year 2019, and provide a business update. The conference call dial-in numbers are (877) 377-7553 for domestic callers and (678) 894-3968 for international callers. The conference ID number for the call is 4609858. Participants may access the live webcast via a link on the Sangamo website in the Investors and Media section under Events and Presentations. A conference call replay will be available for one week following the conference call on Sangamos website. The conference call replay numbers for domestic and international callers are (855) 859-2056 and (404) 537-3406, respectively. The conference ID number for the replay is 4609858.

About Biogen

At Biogen, our mission is clear: we are pioneers in neuroscience. Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological and neurodegenerative diseases as well as related therapeutic adjacencies. One of the worlds first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today Biogen has the leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, commercializes biosimilars of advanced biologics, and is focused on advancing research programs in multiple sclerosis and neuroimmunology, Alzheimers disease and dementia, neuromuscular disorders, movement disorders, ophthalmology, immunology, neurocognitive disorders, acute neurology, and pain.

Biogen routinely posts information that may be important to investors on its website at http://www.biogen.com. To learn more, please visit http://www.biogen.com and follow Biogen on social media Twitter, LinkedIn, Facebook, YouTube.

About Sangamo Therapeutics

Sangamo Therapeutics is committed to translating ground-breaking science into genomic medicines with the potential to transform patients lives using gene therapy, ex vivo gene-edited cell therapy, and in vivo genome editing and gene regulation. For more information about Sangamo, visit http://www.sangamo.com.

Biogen Safe Harbor

This press release contains forward-looking statements, made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including statements relating to the potential benefits and results that may be achieved through Biogens proposed collaboration with Sangamo; the anticipated completion and timing of the proposed transaction; the potential benefits, safety and efficacy of ST-501 and ST-502; the potential of Biogens commercial business and pipeline programs; Biogens strategy and plans; the potential treatment of neurological diseases; and risks and uncertainties associated with drug development and commercialization. These forward-looking statements may be accompanied by words such as aim, anticipate, believe, could, estimate, expect, forecast, goal, intend, may, plan, potential, possible, will, would, and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early stage clinical trials may not be indicative of full results or 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.

These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including, without limitation: risks that the proposed transaction will be completed in a timely manner or at all; the possibility that certain closing conditions to the proposed transaction will not be satisfied; uncertainty as to whether the anticipated benefits of the proposed collaboration can be achieved; risks of unexpected hurdles, costs or delays; uncertainty of success in the development and potential commercialization of ST-501 and ST-502 and other undisclosed neurological targets, which may be impacted by, among other things, unexpected concerns that may arise from additional data or analysis, the occurrence of adverse safety events, failure to obtain regulatory approvals in certain jurisdictions, failure to protect and enforce Biogens data, intellectual property, and other proprietary rights and uncertainties relating to intellectual property claims and challenges; product liability claims; and third party collaboration risks. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from Biogens expectations in any forward-looking statement. Investors should consider this cautionary statement, as well as the risks factors identified in Biogens most recent annual or quarterly report and in other reports Biogen has filed with the U.S. Securities and Exchange Commission. These statements are based on Biogens current beliefs and expectations and speak only as of the date of this press release. Biogen does not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

Sangamo Forward Looking Statements

This press release contains forward-looking statements regarding Sangamo's current expectations. These forward-looking statements include, without limitation, statements relating to the potential to use ZFP technology delivered via AAV to repress specific genes involved in neurological diseases, the ability of genomic medicine to provide one-time treatments, other statements regarding investigational therapies and their therapeutic benefits, statements related the anticipated effectiveness of the collaboration and the timing and benefits thereof, Sangamo's sale of shares of its common stock, receipt of an upfront payment and potential receipt of development- and sales-based milestones, as well as royalties on potential future sales, and other statements that are not historical fact. These statements are not guarantees of future performance and are subject to risks and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties related to: the research and development process; the ability to cause the agreements to become effective on the proposed terms and schedule, the ability to obtain clearance under the HSR and to satisfy the other closing conditions, and the potential for technological developments by Sangamo's competitors that will obviate Sangamo's technologies, the new, uncertain and time consuming gene regulation therapy development and regulatory process, including the risks that Sangamo and Biogen may not be successful in their research efforts under the collaboration and that, even if successful, Biogen may be unable to successfully develop and commercialize licensed products resulting from the collaboration; Sangamo's dependence on collaborative partners, including the risks that if Biogen were to breach or terminate the agreement or otherwise fail to successfully develop and commercialize licensed products resulting from the collaboration and in a timely manner, Sangamo would not obtain the anticipated financial and other benefits of the collaboration and the development and/or commercialization of Sangamo's gene editing technology could be delayed, perhaps substantially. There can be no assurance that the necessary milestones or approvals will be obtained for any of the product candidates in this collaboration. Actual results may differ from those projected in forward-looking statements due to risks and uncertainties that exist in Sangamo's operations and business environments. These risks and uncertainties are described more fully in Sangamo's filings with the U.S. Securities and Exchange Commission, including its most recent Annual Report on Form 10-K and most recent Quarterly Report on Form 10-Q. Forward-looking statements contained in this announcement are made as of this date, and Sangamo undertakes no duty to update such information except as required under applicable law.

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Biogen and Sangamo Announce Global Collaboration to Develop Gene Regulation Therapies for Alzheimer's, Parkinson's, Neuromuscular, and Other...

Tumors often fuel their growth by forming new blood vessels to provide oxygen and nutrients. Widely used drugs directed against VEGF or VEGFR inhibit this process. Unfortunately, though, those drugs have failed to rein in the aggressive brain cancer glioblastoma.

Nowscientists at the University of Pennsylvania have demonstrated that targeting a mechanism in a subset of stromal cells known as endothelial cellswhich line the inside of blood vesselsmight help overcome drug resistance in glioblastoma. They believe the finding could point to a new therapeutic strategy to make these malignant cancer cells vulnerable to chemotherapy.

The team found that a mechanism within the well-known Wnt/beta-catenin signaling pathway causes endothelial cells to act morelike stem cells, leading to an abnormal growth of blood vessels that makes brain cancer cells resistant to treatment. Blocking Wnt/beta-catenin sensitized glioblastoma (GBM) to chemotherapy in mice, according to a new study published in Science Translational Medicine.

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GBM is difficult to treat partly because the tumors themselves often harbor different mutations, which makes treatments focused on one molecular target ineffective. So the UPenn team, led by Yi Fan, M.D., Ph.D., lookedbeyond particular genetic abnormalities in different groups of cancer cells and instead focused on overcoming resistance.

Fan's team searched GBM endothelial cells for the regulatory mechanisms that control chemoresistance, and found increased activation of multiple stem cell-associated transcriptional factors. The upregulation of these factors allowed the cells to propagate and also correlated with cell resistance to the widely used chemotherapy drug temozolomide (TMZ).

RELATED: Immuno-oncology combo targeting rogue enzyme in glioblastoma extends survival in mice

Further analysis revealed that the resistance is enabled by the Wnt/beta-catenin pathway, which regulates stem cell renewal. Its abnormal activation has perviously been linked to multiple cancer types.

In mice that had their endothelial cell-specific beta-catenin knocked out, treatment with TMZ cut tumor volume by 90%, whereas treating normal mice only slowed tumor growth. In a mouse model of GBM, the researchers combined Wnt inhibitor XAV939 with TMZ and significantly extended survival when compared to animals that got either drug alone.

Theres huge demand for better treatment options for GBM, as the diseases five-year survival rate remains low at around 5% to 10%. Researchers at the MD Anderson Cancer Center recently foundthat blocking the immune-suppressing enzyme CD73 could add benefits to inhibiting the immune checkpoints PD-1 and CTLA-4 in GBM. And ateam at Cedars-Sinai developed a polymer scaffold to deliver either one of these two types of checkpoint inhibitors cross the blood-brain barrier directly to brain tumor sites.

Ziopharm Oncology used its experimental drug veledimex to boost the immune response to IL-12 gene therapy. Investigators recently found signs of positive responses of the regimen among a small group of patients with recurrent glioblastoma.

Fan believes his teams approach of using Wnt inhibitors to block endothelial cells boasts several advantages over directly attacking cancer cells. For one thing, treating these stromal cells would get at the root cause of tumor survival. Secondly, because it doesnt aim for genetic markers, it should remain effective even after tumors mutate.

Because stromal cells have a more stable genome, they will not mutate the way cancer cells do, meaning secondary resistance is unlikely, Fan said in a statement. The team now hopes to test the method in a clinical trial.

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How targeting tumor blood vessels may help overcome treatment resistance in glioblastoma - FierceBiotech

]]> High costs, data management issues and recruitment problems are some of the main challenges for personalised medicine in clinical development. Credit: US Air Force/Kemberly Groue Genome sequencing costs are falling fast, opening the playing field for developing highly personalised drug candidates. Personalised medicine in the 21st century offers the promise of therapies customised based on the study of what truly makes us unique: our DNA.

The importance of the individual has been widely established in medicine since time immemorial. The well-worn adage that physicians should treat the patient, not the disease has been around since the 19th century, and the awareness of that message is far older than that. Even Hippocrates, the father of Western medicine who treated patients in the fifth century BC, stressed the importance of treating each patient as an individual.

For the sweet [medicines] do not benefit everyone, nor do the astringent ones, nor are all patients able to drink the same things, Hippocrates wrote.

Hippocrates might have tailored his rudimentary treatments based on the patients age, physique and other easily observable factors, but personalised medicine in the 21st century offers the promise of therapies customised based on the study of what truly makes us unique: our DNA.

Advancements in genomics, proteomics, data analysis and other fields both medical and technical are gradually facilitating the development of laser-focused drugs, as well as the ability to predict peoples personal risk factors for particular diseases and how individual responses to various treatments might differ.

After years of anticipation, there is now evidence that governments around the world have clocked the importance of personalised medicine and are driving efforts to the build the genetic data sets and biobanks that are required to push the science forward. Former US President Barack Obama launched the Precision Medicine Initiative to great fanfare in 2015; the scheme has since evolved into the All of Us research programme, which aims to gather health data from more than a million US volunteer-citizens to unlock new insights.

In the UK, the 100,000 Genomes Project reached its goal of sequencing 100,000 whole genomes from 85,000 NHS patients with cancer or rare diseases. Genomics England has noted that so far, analysis of this data has revealed actionable findings in around one in four rare disease patients, while about 50% of cancer cases suggest the potential for a therapy or clinical trial.

You can match a blood transfusion to a blood type that was an important discovery, said Obama at the launch of the Precision Medicines Initiative, summarising the broad appeal of personalised therapies and diagnostics. What if matching a cancer cure to our genetic code was just as easy, just as standard? What if figuring out the right dose of medicine was as simple as taking our temperature?

The stage might be set for personalised healthcare to dramatically transform public health, but few in the medical field would deny that the world is hardly ready yet. Transitioning from the traditional one-cure-fits-all treatment model to new processes that leverage patients genetics, lifestyles and environmental risk factors is an immense task that presents challenges in both the laboratory and the clinic.

Oncology is, by a landslide, the field that has been most impacted by developments in precision medicine; around 90% of the top-marketed precision treatments approved in 2018 were cancer therapies, while other therapeutic areas have lagged far behind. The majority of approved precision medicines in oncology achieve something of a halfway house between the old way and the new they fall short of being tailored to a specific individual, but they allow for more detailed stratification of patients by the oncogenic mutations of their tumours, which may be driving cancer cell survival and growth.

Common examples of these mutations are HER-2 in certain breast and stomach cancers, BRAF in melanoma and EGFR in lung cancer. High expression of these proteins at cancer sites can be targeted by precision treatments, such as Roches monoclonal antibody Herceptin (trastuzumab) for HER-2, Genentechs BRAF inhibitor Zelboraf (vemurafenib), and Roches EGFR inhibitor Tagrisso (osimertinib). Regulators such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are also increasingly approving tumour-agnostic treatments the first and most famous of which is Mercks immunotherapy Keytruda (pembrolizumab) which target specific biomarkers regardless of tumour location.

But despite the availability of a growing menu of personalised cancer treatments, actually matching patients up to the right therapy can be difficult. According to a survey of US acute care organisations conducted by Definitive Healthcare and published in December 2019, just over 20% had established precision medicine programmes. Investment in genomic testing is vital to quickly get patients on the best treatment course, but financial and operational barriers remain.

The foremost among these is the cost associated with genomic sequencing and the use of companion diagnostic devices, cited by 28% of Definitive Healthcares respondents as the biggest challenge for already-established precision medicine schemes. Lack of expertise is another obstacle, as many physicians may struggle to accurately interpret test results without specialist assistance another major cost driver for clinics and hospital departments trying to build pathology teams that are up-to-date with the newest tests. A 2018 survey of 160 oncologists by Cardinal Health found that 60% of physicians who dont use genomic tests avoid them because of the difficulty of interpreting the data.

In clinical research and development, too, there are growing pains associated with moving the pharmaceutical pipeline towards drugs targeting smaller patient sub-groups. Again, cost is a central issue companion diagnostics dont come cheap, finding and validating biomarkers to guide targeted therapies is a lengthy task, and analysing vast amounts of data often requires new teams with specialised knowledge.

The expense of incorporating a host of new processes into innovative trial designs not to mention the cost of manufacturing cell and gene therapies obviously has an impact on the list price of personalised drugs that win approval. This is most clearly seen in the eye-watering prices of some of the worlds first truly individualised cancer treatments, chimeric antigen receptor T-cell (CAR-T) therapies.

Treatments such as Novartiss Kymriah and Gileads Yescarta remove T-cells from the patients blood, modify them to target tumour cell antigens and then infuse them back into the blood stream. These therapies have achieved impressive results in rare and advanced cancers, but cost upwards of $400,000 per patient, limiting their reimbursement options among both private and public payers. Promising advances in CAR-T manufacturing and potential off-the-shelf T-cell production could help bring these costs down in the years to come, but for now the problem remains.

As for the broader clinical trial eco-system, these studies have been historically set up to assess a drug candidates safety and efficacy in an increasingly large segment of the patient population, building evidence towards the regulatory approval process. Bringing a personalised medicine through the clinical development process is a new paradigm in a number of ways; as well as the aforementioned cost drivers, there can be an extra enrolment burden to identify and recruit patients this is already a common cause of trial failure, but its all the more difficult when youre looking to access a small patient sub-group with the appropriate biological profile.

The difficulty of providing sufficient evidence of safety and efficacy can also present issues where current regulations struggle to accommodate new innovations in personalised medicine. Smaller trial designs present statistical problems in terms of understanding a drugs definitive risk-benefit profile, and while some personalised applications can be discovered as part of larger trials that fail to meet their endpoints outside of a select patient group with particular biomarkers, many current regulations dont accept post hoc analysis and would require an entirely new trial.

Personalised medicine developers desire better guidance on how best to design a successful clinical trial for a personalised therapy, because absent guidance, they risk presenting suboptimal evidence regarding stratification options, reads a 2017 study on personalised medicine barriers, published in the Journal of Law and Biosciences. Designing clinical trials for differently responding subgroups (for example, biomarker-positive and biomarker-negative groups) requires additional time and resources. Companies are reluctant to make this investment without a commensurate increase in the certainty of regulatory approval.

The increasing use of surrogate endpoints, conditional approvals and real-world data is helping to address these issues, but theyre not yet an ideal solution. Conditional approvals rely on very careful post-marketing observation and analysis, while the value of surrogate endpoints has been questioned, adding to the tension between accelerating approvals and ensuring patient safety.

The ultimate benefits of creating more personalised treatments are clear, and their advantages for human health could, in the long-term, be matched by their economic returns. After all, quickly treating patients with the right therapy for them or, even better, using knowledge of a patients genetic risk profile to prevent illness in the first place would be a huge financial gain for overburdened health systems.

Todays costs are gradually falling, as NIH data on DNA sequencing costs demonstrate. But there is still a long way to go before we can wave goodbye to the blanket drug development that has dominated modern pharma for decades, even in the advanced field of oncology, let alone other therapeutic areas. Only a sustained and holistic push from regulators, drug developers, clinicians, governments and others will be enough to bring us over the line.

Read more from the original source:
Precision medicine in 2020: what barriers remain for drug developers? - pharmaceutical-technology.com

Every week there are numerous scientific studies published. Heres a look at some of the more interesting ones.

Some Antibiotics Prescribed During Pregnancy Linked to Birth Defects

Researchers at the University College London found that children of mothers prescribed macrolide antibiotics in the first trimester of pregnancy were at increased risk of major birth defects. The research was published in The BMJ. The birth defects include major malformations such as heart and genital defects, and four neurodevelopment disorders, cerebral palsy, epilepsy, ADHD, and autism spectrum disorder.

Macrolide antibiotics are used to treat a wide variety of bacterial infections and are among the most frequently prescribed antibiotics during pregnancy in Western countries, said Heng Fan, PhD candidate at UCL Great Ormond Street Institute of Child Health, and lead author of the study. This work builds on previous evidence of rare but serious adverse outcomes of macrolide use, especially for unborn babies. These adverse outcomes were assumed to be associated with the arrhythmic effect of macrolides, and policy advice about their use in pregnancy varies.

The investigators analyzed data from 104,605 children born in the UK from 1990 to 2016 from the Clinical Practice Research Datalink (CPRD), with a median follow-up of 5.8 years after birth. An additional 82,314 children whose mothers were given macrolides or penicillins before pregnancy and 53,735 who were siblings of children in the study acted as control cohorts. Major malformations were seen in 186 children of 8,632 whose mothers received macrolides at any point during pregnancy and 1,666 of 95,973 children whose mothers were dosed with penicillins during pregnancy. The researchers concluded that macrolides during the first three months of pregnancy were associated with an increased risk of any major malformation compared to penicillin.

The Mediterranean Diets Key Ingredient for Extending Lifespan

The Mediterranean diet has been noted for being heart-healthy and potentially improving lifespanheavy on fish, fruits, vegetables, grains, olive oil and red wine. Much research suggested the resveratrol found in red wine was the major contributor, but new research suggests it is actually the fat found in olive oil that activated a pathway known to increase lifespan and prevent aging-related diseases. It appears that the fat gets stored in lipid droplets and when the fat is broken down during exercise or fasting, the signaling and health benefits occur.

What Facebook and Genomes Have in Common

Computational biologists at Carnegie Mellon University took an algorithm used to study social networks like Facebook and adapted it to identify how DNA and Proteins behave in communities inside the cell nucleus. Proximity is a factor, because genes controlled by the same regulatory proteins benefit from being close to each other, but others can be relatively far apart but drawn together via shared interests. The MOCHI algorithm analyzes the spatial arrangement of all the genes and transcription factor proteins in a nucleus based on genome-wide chromosome interactions and global gene regulatory networks.

A 3D Atomic Scale Map of the 2019 Coronavirus

Investigators at the University of Texas at Austin and the NIH created the first 3D atomic scale map of the 2019 novel coronavirus. They used AMETEK Gatans K3 camera to map part of the virus called the spike protein, which is how the virus penetrates the host cells. The breakthrough should allow for more rapid vaccine and therapy development.

How Lung Cancer Cells Suck Up Energy

Researchers working with human lung cancer cells discovered how they modulate their energy consumption based on their surroundings. In addition, they discovered how cancer cells override those factors to maximize their energy use. They identified a protein called TRIM21 that appears able to prevent the degradation of metabolic enzymes, resulting in cancer cells keeping their metabolism high. Being able to interrupt this pathway could lead to new approaches to cancer therapies.

New Hope for Muscular Dystrophy

Although there are now a couple therapies on the market for Duchenne muscular dystrophy (DND), it is still incurable. Researchers at the University of Pennsylvania School of Medicine recently identified a group of small molecules that might lead to new treatments. The compounds eased repression of a specific gene, utrophin, in mouse muscle cells. This allows the body to produce more utrophin protein, which can be substituted for dystrophin, the protein whose absence causes DMD.

Were trying to find therapies that will restore a patients muscle function without resorting to gene therapy, said Tejvir S. Khurana, the studys senior author and professor of Physiology. Increasing utrophin is a major focus of muscular dystrophy research. While, ideally, we would replace the missing dystrophin in patients, there are a number of technical and immunological problems associated with this approach.

One is simply that the dystrophin gene is the largest in the body, and cant be fit into the viruses used for gene therapy. Most approaches along those lines use truncated dystrophin genes or other means to introduce a partial dystrophin gene or gene product. The other problem is that because the human body of DMD patients doesnt have regular amounts or types of dystrophin, introducing dystrophin to the body often stimulates an immune response as the immune system reacts to it as an invader.

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Research Roundup: Antibiotics Linked to Birth Defects and More - BioSpace

A large biotech is partnering with a firm developing cell and gene therapies on treatments for neurological diseases like Alzheimers and Parkinsons.

Cambridge, Massachusetts-based Biogen said Thursday afternoon after markets closed that it had partnered with Brisbane, California-based Sangamo Therapeutics in a deal that could be worth up to $2.7 billion. The partnership will initially focus on two preclinical Sangamo gene therapy candidates ST-501 for tauopathies such as Alzheimers and ST-502 for synucleinopathies like Parkinsons disease, plus an undisclosed neuromuscular target. It also includes exclusive rights for up to nine other undisclosed neurological targets.

Biogen will pay Sangamo $350 million upfront, which includes a license fee and equity investment, while Sangamo will be eligible for up to $2.37 billion in milestone payments, plus royalties.

Shares of Sangamo were up more than 28% on the Nasdaq after markets opened Friday. The company had also announced its fourth quarter and full year 2019 financial results. Biogens shares were down 2.6%.

Sangamo had reached out to multiple companies in a competitive process. While declining to say how many companies the biotech had spoken to, Sangamo head of corporate strategy Stephane Boissel said in a phone interview that it had put together multiple term sheets.

Its a combination of economics, but also the expertise of that partner in that particular field, Boissel said, referring to why the company had chosen Biogen. Biogen, in the pharma world, is probably the best franchise when it comes to neurology.

Adrian Woolfson, Sangamos executive vice president for research and development, said in the same call that it was also because of an appreciation for Biogens enthusiasm and energy.

I think its fair to say we had a very good chemistry with them at a personal level when we went to meet with them in Boston, and we seemed to get along very well, Woolfson said.

Sangamo has existing partnerships with a number of other firms, including Pfizer and Gilead Sciences.

Biogens moves into Alzheimers disease have not been without controversy. The company plans to file for Food and Drug Administration approval of aducanumab, a monoclonal antibody targeting the amyloid beta protein that has long dominated Alzheimers research. The company initially halted the Phase III development program for the drug when it was predicted to fail, but revived it when a post-hoc analysis indicated potential efficacy. Investors have remained skeptical.

Still, that did not come up in the minds of Sangamos executives, Boissel said. While emphasizing that he could not compare the two companies approaches, Woolfson added that gene therapies are potentially better ways to address neurological diseases like Alzheimers because they can switch off genes completely rather than being limited to taking out specific proteins, as monoclonal antibodies are.

ST-501 targets tau, another protein that has been researched as a potential therapeutic target in Alzheimers. ST-501 and ST-502 use adeno-associated viral vectors to deliver zinc finger protein transcription factors (ZFP-TFs), a form of gene therapy that Sangamo said in its quarterly earnings presentation is ideally suited to neurological disorders due to its ability to up- or down-regulate gene expression.

Boissel did not disclose specific timelines for ST-501 and ST-502, but noted that the next steps in their development will be preclinical studies to enable them to enter the clinic.

Photo: John Tlumacki, The Boston Globe, via Getty Images

Read more:
Biogen teams up with Sangamo in gene therapy deal worth up to $2.7B - MedCity News

Newswise CLEVELANDResearchers at Case Western Reserve University have used a unique method to safely deliver gene therapy to fight a rare, but irreversible, genetic eye disorder known as Stargardt disease.

By using chemically modified lipidsinstead of the viruses most commonly used as carriersStargardt disease did not return in animal models for up to eight months after treatment, said lead researcher Zheng-Rong Lu, the M. Frank Rudy and MargaretDomiter Rudy Professor ofBiomedical Engineering at the Case School of Engineering, with a dual appointment at the School of Medicine.

Lus research, recently published in the journal Molecular Therapy, was funded in part through a Gund-Harrington Scholar grant, a partnership between Harrington Discovery Institute at University Hospitals and the Foundation Fighting Blindness.

This grant provides innovative scientists like Dr. Lu both funding and drug development expertise to advance research that will defeat diseases that limit millions of people from experiencing the gift of sight, said Jonathan S. Stamler, MD, President, Harrington Discovery Institute and Robert S. and Sylvia K. Reitman Family Foundation Distinguished Chair of Cardiovascular Innovation at University Hospitals and Case Western Reserve University School of Medicine. It is very encouraging to see Dr. Lus work move closer to human trials.

A so-far incurable disorder

The research may give some hope to people with Stargardt disease, an inherited disorder of the retina also known as macular dystrophy or juvenile macular degeneration because it often surfaces during childhood or adolescence.

Although individuals with Stargardt disease rarely go completely blind, they progressively lose vision in both eyes, become very sensitive to light and, in some cases, develop color blindness.

Were really excited because there is a potential to help people with Stargardt, Lu said. But we believe this success could also apply to other disorders as a platform therapy for delivering other genes through the use of the lipids.

Lipids are simple organic compounds, or fatty acids, that are insoluble in water, including various natural oils, waxes and steroids.

Because they are basically unsaturated oil, the likelihood of damage to the eye is low, which isnt always true with the viral gene therapy, Lu said.

Gene therapy offers best hope

There are a lot of researchers trying to figure out how to treat this disease right now with little success, Lu said. The best hope is gene therapy.

Gene therapy is the technology in which genetic material is introduced into cells by an engineered carrier to compensate for abnormal genes or to make a beneficial protein.

The most successful gene therapy carriers so far have been certain viruses (the AAV, or adeno-associated virus, especially) because they can deliver the new gene by infecting the target cell.

But the Stargardt-associated gene, known as the ABCA4 gene, turns out to be too large to fit within that popular virus, Lu said.

Lu said other researchers have attempted to remedy that problem by splitting ABCA4 into pieces and then trying to reassemble it inside the eyewith limited success.

Other researchers have modified a larger virus to carry ABCA4 into the eyes, a technology tested in human trials as far back as 2011, but which still hasnt been fully commercialized.

He said he and his collaborators have also already met with investors to expedite the commercialization of the platform used for Stargardt.

Further, this gene therapy product could be classified as an orphan drug by the U.S. Food and Drug Administration (FDA) because Stargardt is a rare disease, increasing the likelihood of faster FDA approval after clinical trials, Lu said.

The non-viral gene therapy is also much more cost-effective for production than the virus-based therapy and has a potential to significantly reduce the high price of gene therapy in the eye, he said.

We think that within two to three years we could really be helping people after further demonstration of its safety and efficacy, Lu said.

MEDIA CONTACTS:

Michael Scott, Case Western Reserve University

216.368.1004, mike.scott@case.edu

Carly Belsterling, University Hospitals

412.889.8866, carly.belsterling@uhhospitals.org

###

Case Western Reserve University

Case Western Reserve University is one of the country's leading private research institutions. Located in Cleveland, we offer a unique combination of forward-thinking educational opportunities in an inspiring cultural setting. Our leading-edge faculty engage in teaching and research in a collaborative, hands-on environment. Our nationally recognized programs include arts and sciences, dental medicine, engineering, law, management, medicine, nursing and social work. About 5,100 undergraduate and 6,200 graduate students comprise our student body. Visit case.edu to see how Case Western Reserve thinks beyond the possible.

Harrington Discovery Institute

The Harrington Discovery Institute at University Hospitals in Cleveland, OHpart of The Harrington Project for Discovery & Developmentaims to advance medicine and society by enabling our nations most inventive scientists to turn their discoveries into medicines that improve human health.The institute was created in 2012 with a $50 million founding gift from the Harrington family and instantiates the commitment they share with University Hospitals to a Vision for a Better World.

The Harrington Project for Discovery & Development

The Harrington Project for Discovery & Development (The Harrington Project), founded in 2012 by the Harrington Family and University Hospitals of Cleveland, is a $300 million national initiative built to bridge the translational valley of death. It includes the Harrington Discovery Institute and BioMotiv, a for-profit, mission-aligned drug development company that accelerates early discovery into pharma pipelines. For more information, visit:HarringtonDiscovery.org.

Visit link:
Scientists successfully test new way to deliver gene therapy - Newswise

Rare Disease Day is celebrated across the globe to raise awareness amongst the general public and policymakers about rare diseases and how they impact patients lives. The first Rare Disease Day was celebrated in 2008 on February 29 because of its rare date and since then, occurs on the last day in February each year, a month with a rare number of days.

Although rare suggests not many people are affected with a condition, collectively, 300 million people around the world live with a rare disease and they face similar challenges. The barrier to an accurate diagnosis means patients may doctor hop and spend years getting a host of tests done because no one is familiar with the condition and can diagnose it. Theres often frustration due to this lack of understanding from health care professionals, and living in the unknown.

Even with a diagnosis, more than 90% of rare diseases are still without an FDA approved treatment, according to the National Organization for Rare Disorders.

Some rare diseases may cause a multitude of different health problems that keep children from going to school or being able to socialize with others in the same way their peers can. Similarly, rare diseases may affect physical appearance and make children self-conscious or have low self-esteem.

LISTEN UP: Add the newMichigan Medicine News Breakto your Alexa-enabled device, orsubscribe to our daily updates oniTunes,Google PlayandStitcher.

Michigan Medicine researchers are constantly working to better understand the mechanisms behind rare diseases. Education helps health care professionals make accurate diagnoses, create treatment methods and improve the quality of life for those that live with these conditions.

Heres a sampling of their research from the last year.

Systemic Scleroderma Treatments: Where Are We Now?A new and novel outcome measure is being used to determine effectiveness of new scleroderma treatments.

Gene Therapy Treatment Targets Rare Mutation Tied to BlindnessAdvances in gene therapy are yielding new options for treating inherited retinal degenerations, giving specialists new tools and new hope for patients and families.

A Mission to Improve Cystic Fibrosis Treatment Across the GlobeTo reach patients in need, one doctor has developed atraining program to improve testingand care available for those with thegenetic disease, starting intheMiddle East.

Accelerating Childrens Access to New Treatments for High Risk Brain TumorsMichigan Medicine joins an exclusive, global network that helps speed up the process of linking children with incurable brain cancer to promising clinical trials.

A New Clue in the Mystery of ALS, Frontotemporal DementiaMichigan Medicine researchers identify a potential therapeutic target for neurodegenerative conditions using animal models.

Drug Trial Seeking First Ever Treatment for Dangerous Side Effect of Prader-Willi SyndromeA worldwide research effort is underway for finding a treatment option for hyperphagia, the most common genetic cause of life threatening childhood obesity.

Arthritis Treatment Could Provide Relief for Lichen Planus Skin RashIts often difficult to manage patients with this skin inflammation, but new research identifies a target that existing medications may be able to address.

Approach Could Help in Treating Glioblastoma, Other Rare CancersMichigan led research presents a new way of uncovering predictive biomarkers when data from large randomized trials arent available.

Sickle Cell Disease Could Be Treated by Turning Back the ClockReactivating genes normally active before birth could prevent the harmful effects of this blood disorder with few treatment options.

Registry Helps Move Aortic Dissection Care Forward Diagnosis, treatments and outcomes for acute aortic dissection have evolved, with an international registry revealing trends and the power of using data.

MORE FROM MICHIGAN: Sign up for our weekly newsletter

To learn more about Rare Disease Day, visit the National Organization for Rare Disorders website.

Read more here:
10 Studies That Highlight the Importance of Rare Disease Research - Michigan Medicine

We made tremendous progress last year as we build a diversified portfolio in retinal diseases that includes both therapeutics and gene therapy, setting the stage for IVERIC bio to be a leader in developing transformative therapies to treat retinal diseases, stated Glenn P. Sblendorio, Chief Executive Officer and President of IVERIC bio. We achieved a major milestone with our positive Zimura pivotal clinical trial results in geographic atrophy secondary to dry AMD. Our goal is to continue to build on this momentum. Following the positive data, our team quickly started working on our second Zimura pivotal clinical trial in GA with plans to enroll the first patient next month. Our lead gene therapy programs in rhodopsin mediated adRP and BEST1 related retinal diseases continue to advance towards Phase 1/2 clinical trials and we expect to identify our lead minigene construct for LCA10 later in the year.

Therapeutics Programs

Zimura (avacincaptad pegol): Complement C5 Inhibitor

HtrA1 Inhibitor

Gene Therapy Programs in Orphan Inherited Retinal Diseases

Corporate Update

In December 2019, the Company completed an underwritten public offering in which it sold 7,750,000 shares of its common stock at a price of $4.00 per share, and it also sold to certain investors pre-funded warrants to purchase 3,750,000 shares of its common stock at a price of $3.999 per share underlying each warrant. The Company raised approximately $42.6 million in net proceeds from this offering.

During the fourth quarter of 2019, IVERIC bio appointed Guangping Gao, PhD as Chief Strategist, Gene Therapy, and Abraham Scaria, PhD as Chief Scientific Officer.

Fourth Quarter and Year End 2019 Financial Results and 2020 Cash Guidance

As of December 31, 2019, the Company had $125.7 million in cash and cash equivalents. The Company estimates that its year-end 2020 cash and cash equivalents will range between $60 million and $70 million. The Company also estimates that its cash and cash equivalents will be sufficient to fund its operations and capital expenditure requirements as currently planned into the beginning of 2022. These estimates are based on the Companys current business plan, including initiation of the Zimura ISEE2008 trial and the continuation of the Companys other on-going research and development programs. These estimates do not reflect any additional expenditures, including associated development costs, in the event the Company in-licenses or acquires any new product candidates or commences any new sponsored research programs.

2019 Financial Highlights

Conference Call/Web Cast Information

IVERIC bio will host a conference call/webcast to discuss the Companys financial and operating results and provide a business update. The call is scheduled for February 27, 2020 at 8:00 a.m. Eastern Time. To participate in this conference call, dial 800-458-4121 (USA) or 323-794-2598 (International), passcode 6010573. A live, listen-only audio webcast of the conference call can be accessed on the Investors section of the IVERIC bio website at http://www.ivericbio.com. A replay will be available approximately two hours following the live call for two weeks. The replay number is 888-203-1112 (USA Toll Free), passcode 6010573.

About IVERIC bio

IVERIC bio is a biopharmaceutical company focused on the discovery and development of novel treatment options for retinal diseases with significant unmet medical needs. Vision is Our Mission. For more information on the Company please visit http://www.ivericbio.com.

Forward-looking Statements

Any statements in this press release about the Companys future expectations, plans and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Forward-looking statements include any statements about the Companys strategy, future operations and future expectations and plans and prospects for the Company, and any other statements containing the words anticipate, believe, estimate, expect, intend, goal, may, might, plan, predict, project, seek, target, potential, will, would, could, should, continue, and similar expressions. In this press release, the Companys forward looking statements include statements about its expectations to use its previously announced clinical trial of Zimura for the treatment of geographic atrophy as a pivotal trial, its development strategy for Zimura, including its plans and expectations regarding a second, pivotal clinical trial evaluating Zimura for the treatment of geographic atrophy, the implementation of its business plan, the projected use of cash and cash balances, the timing, progress and results of clinical trials and other research and development activities, the potential utility of its product candidates, and the potential for its business development strategy. Such forward-looking statements involve substantial risks and uncertainties that could cause the Companys development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, those related to the initiation and the progress of research and development programs and clinical trials, availability of data from these programs, reliance on university collaborators and other third parties, establishment of manufacturing capabilities, expectations for regulatory matters, need for additional financing and negotiation and consummation of business development transactions and other factors discussed in the Risk Factors section contained in the quarterly and annual reports that the Company files with the Securities and Exchange Commission. Any forward-looking statements represent the Companys views only as of the date of this press release. The Company anticipates that subsequent events and developments will cause its views to change. While the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so except as required by law.

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2018

2019

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$

11,567

$

16,128

$

39,644

$

41,737

6,275

5,667

21,628

23,612

17,842

21,795

61,272

65,349

(17,842

)

(21,795

)

(61,272

)

(65,349

)

369

677

2,151

2,389

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125,000

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Go here to see the original:
IVERIC bio Reports Fourth Quarter and Year End 2019 Operational Highlights and Financial Results - BioSpace

BOSTON and LONDON, Feb. 27, 2020 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global leader in gene therapy, today reported business highlights and financial results for the year ended December 31, 2019, as well as 2020 strategic priorities and upcoming milestones.

We are inspired by the possibilities ahead for Orchard in 2020 and beyond to bring the benefits of our gene therapy approach to patients worldwide, said Mark Rothera, president and chief executive officer of Orchard. As we prepare for the anticipated EU approval of OTL-200 for MLD, we are strengthening the foundation of our global commercial infrastructure that could one day support multiple potentially transformative products. We are also continuing to propel the business forward by advancing our next wave of proof-of-concept trials evaluating the potential for gene-corrected stem cells in a broader range of neurometabolic disorders.With strong execution in 2019 and a solid balance sheet heading into 2020, we are well-positioned to deliver value to our shareholders.

Recent 2020 Achievements

2020 / 2021 Corporate Priorities and Expected Key Milestones

1Patient was treated by the Royal Manchester Childrens Hospital (RMCH) under a Specials license, granted by the UK government for the use of an unlicensed pharmaceutical product in situations of high unmet need when there is no other treatment option available. Orchard holds the license to the MPS-IIIA investigational gene therapy product (OTL-201) and is funding the proof-of-concept clinical trial being conducted at RMCH, which utilizes the same technology and procedures that were used to treat this first MPS-IIIA patient.

Fourth Quarter 2019 Financial Results

Cash, cash equivalents and investments as of December 31, 2019, were $325.0 million compared to $335.8 million as of December 31, 2018. The decrease was primarily driven by the net cash used to fund operations in 2019, partially offset by proceeds from the companys public equity offering in June 2019 and the proceeds from the first drawdown under a credit facility entered in May 2019. During the three months ended December 31, 2019, the companys cash used to fund operations and capital expenditures totaled approximately $43.8 million. The quarterly burn rate is expected to increase in 2020 due to the growth in operating expenses to support the potential launch of OTL-200 in the second half of 2020 and the companys planned capital investment on its in-house manufacturing facility.

During the three months ended December 31, 2019, the company recognized $0.6 million in revenue related to European sales of Strimvelis, the first gene therapy approved by the EMA for ADA-SCID.

Research and development expenses were $30.9 million for the three months ended December 31, 2019, compared to $17.4 million in the same period in 2018. R&D expenses include the costs of clinical trials and preclinical work on the companys portfolio of investigational gene therapies, as well as costs related to regulatory, manufacturing, license fees and milestone payments under the companys agreements with third parties, and personnel costs to support these activities. The company expects R&D expenses to continue to increase as its programs advance through development.

Selling, general and administrative expenses were $18.5 million for the three months ended December 31, 2019, compared to $12.0 million in the same period in 2018. The increase was primarily due to increased investment to prepare for the potential commercialization of multiple late-stage programs, as well as higher costs to support public company operations and stock-based compensation.

Net loss attributable to ordinary shareholders was $45.4 million for the three months ended December 31, 2019, compared to $25.1 million in the same period in 2018. The increase in net loss as compared to the prior year was primarily due to higher costs related to pre-launch activities on the companys later-stage programs in development and expenses associated with being a public company. The company had 96.9 million ordinary shares outstanding as of December 31, 2019.

The company expects that its existing cash, cash equivalents and investments will enable funding of its anticipated operating and capital expenditure requirements into the second half of 2021.

Conference Call & Webcast Information

Orchard will host a conference call and live webcast with slides today at 8:00 a.m. ET to discuss its 2019 financial results and other business updates. To participate in the conference call, please dial 866-930-5155 (U.S. domestic) or +1-409-937-8974 (international) and refer to conference ID 8096875. A live webcast of the presentation will be available under "News & Events" in the Investors & Media section of the company's website at orchard-tx.com and a replay will be archived on the Orchard website following the presentation.

About OrchardOrchard Therapeutics is a global gene therapy leader dedicated to transforming the lives of people affected by rare diseases through innovative, potentially curative gene therapies. Our ex vivo autologous gene therapy approach harnesses the power of genetically-modified blood stem cells and seeks to permanently correct the underlying cause of disease in a single administration. The company has one of the deepest gene therapy pipelines in the industry and is advancing seven clinical-stage programs across multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist, including inherited neurometabolic disorders, primary immune deficiencies and blood disorders.

Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit http://www.orchard-tx.com, and follow us on Twitter and LinkedIn.

Availability of Other Information About OrchardInvestors and others should note that Orchard communicates with its investors and the public using the company website (www.orchard-tx.com), the investor relations website (ir.orchard-tx.com), and on social media (twitter.com/orchard_tx and http://www.linkedin.com/company/orchard-therapeutics), including but not limited to investor presentations and investor fact sheets, U.S. Securities and Exchange Commission filings, press releases, public conference calls and webcasts. The information that Orchard posts on these channels and websites could be deemed to be material information. As a result, Orchard encourages investors, the media, and others interested in Orchard to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Orchards investor relations website and may include additional social media channels. The contents of Orchards website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.

Forward-Looking Statements

This press release contains certain forward-looking statements about Orchards strategy, future plans and prospects, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements may be identified by words such as anticipates, believes, expects, plans, intends, projects, and future or similar expressions that are intended to identify forward-looking statements. Forward-looking statements include express or implied statements relating to, among other things, the companys business strategy and goals, the therapeutic potential of Orchards product candidates, including the product candidate or candidates referred to in this release, Orchards expectations regarding the timing of regulatory submissions for approval of its product candidates, including the product candidate or candidates referred to in this release, the timing of interactions with regulators and regulatory submissions related to ongoing and new clinical trials for its product candidates, the timing of announcement of clinical data for its product candidates and the likelihood that such data will be positive and support further clinical development and regulatory approval of these product candidates, the likelihood of approval of such product candidates by the applicable regulatory authorities, the likelihood the company will initiate construction of an in-house manufacturing facility in 2020, and the companys financial condition and cash runway into the second half of 2021. These statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond Orchards control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, the risks and uncertainties include, without limitation: the risk that any one or more of Orchards product candidates, including the product candidate or candidates referred to in this release, will not be approved, successfully developed or commercialized, the risk of cessation or delay of any of Orchards ongoing or planned clinical trials, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies or clinical trials will not be replicated or will not continue in ongoing or future studies or trials involving Orchards product candidates,the delay of any of Orchards regulatory submissions, the failure to obtain marketing approval from the applicable regulatory authorities for any of Orchards product candidates, the receipt of restricted marketing approvals, and the risk of delays in Orchards ability to commercialize its product candidates, if approved. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements.

Other risks and uncertainties faced by Orchard include those identified under the heading "Risk Factors" in Orchards annual report on Form 20-F for the year ended December 31, 2018, as filed with the U.S. Securities and Exchange Commission (SEC) on March 22, 2019, as well as subsequent filings and reports filed with the SEC. The forward-looking statements contained in this press release reflect Orchards views as of the date hereof, and Orchard does not assume and specifically disclaims any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

Consolidated Statements of Operations Data(in thousands, except share and per share data)(Unaudited)

Consolidated Balance Sheet Data(in thousands)(Unaudited)

Contacts

InvestorsRenee LeckDirector, Investor Relations+1 862-242-0764Renee.Leck@orchard-tx.com

MediaMolly CameronManager, Corporate Communications+1 978-339-3378media@orchard-tx.com

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Orchard Therapeutics Reports 2019 Financial Results and Reviews Key Strategic Priorities for 2020 - BioSpace

Gene therapy products approved between the years 2003 and 2017 include Gendicine, Oncorine, Rexin-G, Neovasculgen, Glybera, Imlygic, Strimvelis, Zalmoxis, Kymriah, Yescarta and Luxturna. Gendicine was approved for head and neck squamous cell carcinoma and has been in the Chinese market since 2003. Rexin-G was approved in the Philippines back in 2007 for the treatment of primary and metastatic cancer. Oncorine was approved in China in 2005 for nasopharyngeal carcinoma. The Russian market has Neovasculgen from 2011 for the treatment of peripheral arterial disease (PAD) and critical limb ischemia. The first gene therapy approved in E.U. was Glybera in 2012 for the treatment of familial lipoprotein lipase deficiency (LPL), however in October 2017 it was pulled from the market due to lack of patient demand. In 2015, Imlygic was approved in E.U. and also in the U.S. to treat melanoma, and Phase II results released in 2017 indicated its efficacy in combination with the checkpoint-inhibitor, Yervoy. In the E.U., Strimvelis was approved in 2016 for the treatment of adenosine deaminase severe combined immunodeficiency (ADA-SCID). In 2016, Zalmoxis was approved in E.U. for the treatment of leukemia. 2017 was a bumper year for gene therapy with Kymriah, Yescarta and Luxturna all gaining FDA approval.

Browse Complete Global Gene Therapy Market Analysis and Forecasts Report at https://www.reportsnreports.com/reports/1370259-global-gene-therapy-market-analysis-forecast-to-2022.html

Since the FDA approved Kymriah (tisagenlecleucel), Yescarta (Axicabtagene ciloleucel) and Luxturna (voretigene neparvovec-rzyl) in 2017, the US gene therapy space has expanded significantly, underlined by the fact that over 55% of completed and ongoing trials are located in this geographic. Growth in the gene therapy industry has resulted in new commercial initiatives and the emergence of new startups and spin-off biotechs. Furthermore, gene therapy specifically has raised well over $600 million of venture capital in the last five years. Early stage companies have raised seed, Series A and Series B investment steadily since the market took off, including Spark Therapeutics, Avalanche Biotech, uniQure, Voyager Therapeutics, Editas Medicine and GenSight.

In 2017, theGene Therapy Marketfor technologies, services and products was estimated to be worth $x million, with a potential to reach $363 million by 2022. The main market space is cancer which currently holds x% market share. This indication generated $x million in 2017 and will generate $x million in 2022. This is followed by rare diseases, cardiovascular, neurological and ocular indications. Looking at the market by technology, at present, gene product therapeutics generate the majority of revenue with over $x million in 2017, growing to $x million by 2022. Viral vectors are set to generate $x million in 2017, and will rise to $x million in 2022, and by then gene therapy services such as vector development and transfection will hit $x million. At present, the Americas have penetrated the market significantly with 65% geographic share, followed by Europe (x%) and the RoW (x%).

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Global gene therapy market is forecast to hit $363 million by 2022 from $x million in 2017. Strengthened by recent approvals of Kymriah, Yescarta and Luxturna in the US, and a committed European, Japanese and Chinese environment, gene therapy is set to become a significant player in the bio-pharmaceutical industry. The space covers many therapeutic areas specifically, oncology, rare diseases, Parkinsons, HIV, severe combined immuno-deficiencies (SCID) and hemophilia. Recently, in November 2017, the FDA indicated that gene therapies will now qualify for a fast approval process, which will bring more therapies to market faster. However, the space also has significant challenges, such as manufacturing logistics, reimbursement and its high cost. This 310 page market analysis cutting-edge report tackles this growing but challenging industry, it highlights its strengths, weaknesses and opportunities and provides a comprehensive account of major companies, clinical trials and technological advancement.

Renewed interest has encouraged start-up companies to affiliate with academic centers for tech know-how. As clinical trials advance towards licensure, more meticulous product characterization using improved analytical methods and progressively higher regulatory compliance will be required. Some of the ongoing clinical trials are closing on to produce promising results, including one for hemophilia B caused by the deficiency of Factor IX using a recombinant adeno-associated virus (AAV) as a vector. The product candidate if succeeds will be a relatively cheaper alternative to the expensive and lifelong factor replacement therapy.

A second example of a successful outcome in gene therapy are studies conducted by independent laboratories focusing on sub-retinal delivery of recombinant AAV expressing retinal pigment epithelial RPE65 for Leber Congenital Amaurosis Type 2. A third example is the clinical trial involving nine children with X-linked severe combined immunodeficiency (SCID-X1) treated with autologous bone marrow CD34+ cells transduced with a self-inactivating (SIN) -retroviral vector expressing the IL-2 receptor -chain. This novel strategy involves ex vivo gene transfer using recombinant retroviral or lentiviral vectors of chimeric antigen receptors consisting of antibody-binding domains fused to T-cell-signaling domains into patient T lymphocytes.

Access this Research Report athttps://www.reportsnreports.com/contacts/discount.aspx?name=1370259

As gene therapies are generally meant for one time or short duration treatments, they are customized to individuals confined to small patient populations. Therefore, manufacturing firms are expected to seek premium prices for these therapies. Because of this, these therapies will have to face valuation and reimbursement challenges. Stakeholders will show reservations about the hefty price tags and they will require significant data to be convinced. With the removal of Gylbera from the EU market in 2017, due to the fact that only one patient was treated with the drug, all eyes are focused on the number of end patients that will be treated, and their ability to pay. To that end, launching of new drugs may have to be delayed in order to collect more data for payers. Furthermore, annuity based reimbursement agreements and pay-for-performance scenarios will have to be tackled.

This report provides the reader with:Current Global Market Worth and Forecast with CAGR Through 2022Sub-Market Worth by Therapeutic Area (Cancer, Rare Diseases, Cardiovascular, Neurological, Ocular) and Forecast with CAGR Through 2022Sub-Market Worth by Geography (Americas, Europe, RoW) and Forecast with CAGR Through 2022Sub-Market Worth by Technology (Gene Product, Service, Viral Vectors) and Forecast with CAGR Through 2022Insight into gene therapy technologies, challenges associated with developing therapeutic genes and disadvantages of gene therapy.Full outline of the gene therapy industry from the formative years through to products discovered during 1990 and 2017.Detailed descriptions of commercialized products approved between 2003 and 2017 that include: Gendicine, Rexin-G, Oncorine, Neovasculgen, Glybera, Imlygic, Strimvelis, Zalmoxis, Kymriah, Yescarta and Luxturna.Description of seven of the Phase III product candidates that include: Generx, Collategene, LentiGlobin, Lenti-D, VM-202, Invosa and GS-010.Description of 21 Phase II product candidates that are set to have significant market share.Commercialization status of gene therapies in by geographic regionEvaluation of gene therapy pricingDescription of the firstever warranty offer by GSK for Strimvelis.A detailed analysis of various types of viruses used as vectors.Description of clinical applications of gene therapy and the various genetic and infectious diseases addressed by gene therapy.Description of 77 companies that are directly and indirectly associated with gene therapy industry.

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Key Questions Answered in this Report:

What is the size of gene therapy market?What is the CAGR and market size over the next five years?What are the different sub-markets and their worth/CAGR over the next five years?What is gene augmentation therapy?What is suicide gene therapy?How is ex vivo gene delivery different from in vivo gene delivery?What are the types of gene therapies classified on the basis of targeted cell types?What is the role of CRISPR technology in gene therapy?What are the approved gene therapy products?How many gene therapy product candidates have reached the Phase III stage?How many Phase II gene therapy product candidates are there?What is the commercialization status of gene therapies in E.U. member countries?What are the prices of gene therapy products?What are the reasons for this extortionate pricing of gene therapies?Which company is offering warranty for its gene- therapy product?What is the current strength of gene therapy industry?Is it true that the real strength of gene therapy industry is based on the number of clinical trials?What is the total number of ongoing clinical trials as of 2017?What is the distribution of clinical trials by geography?Which countries are associated with gene therapy clinical trials?What are the major indications addressed by the clinical trials?Which genes are transferred in these clinical trials?How many Big Pharma are associated with the gene therapy industry?What are non-viral and viral vectors?What are the various features of viral vectors?Which viral vectors are predominantly used in gene therapy clinical trials?What are the major diseases addressed by therapeutic genes?Where is the gene therapy market heading, and what opportunities and challenges will it face?

This content has been distributed via WiredRelease press release distribution service. For press release service enquiry, please reach us at contact@wiredrelease.com.

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Gene Therapy Market CAGR and Market Size over the next five years - PharmiWeb.com

Early proponents of genome sequencing made misleading predictions about its potential in medicine.

An emergency room physician, initially unable to diagnose a disoriented patient, finds on the patient a wallet-sized card providing access to his genome, or all his DNA. The physician quickly searches the genome, diagnoses the problem and sends the patient off for a gene-therapy cure. Thats what a Pulitzer prize-winning journalist imagined 2020 would look like when she reported on the Human Genome Project back in 1996.

The Human Genome Project was an international scientific collaboration that successfully mapped, sequenced and made publicly available the genetic content of human chromosomes or all human DNA. Taking place between 1990 and 2003, the project caused many to speculate about the future of medicine. In 1996, Walter Gilbert, a Nobel laureate, said, The results of the Human Genome Project will produce a tremendous shift in the way we can do medicine and attack problems of human disease. In 2000, Francis Collins, then head of the HGP at the National Institutes of Health, predicted, Perhaps in another 15 or 20 years, you will see a complete transformation in therapeutic medicine. The same year, President Bill Clinton stated the Human Genome Project would revolutionize the diagnosis, prevention, and treatment of most, if not all, human diseases.

It is now 2020 and no one carries a genome card. Physicians typically do not examine your DNA to diagnose or treat you. Why not? As I explain in a recent article in the Journal of Neurogenetics, the causes of common debilitating diseases are complex, so they typically are not amenable to simple genetic treatments, despite the hope and hype to the contrary.

The idea that a single gene can cause common diseases has been around for several decades. In the late 1980s and early 1990s, high-profile scientific journals, including Nature and JAMA, announced single-gene causation of bipolar disorder, schizophrenia, and alcoholism, among other conditions and behaviors. These articles drew massive attention in the popular media, but were soon retracted or failed attempts at replication. These reevaluations completely undermined the initial conclusions, which often had relied on misguided statistical tests. Biologists were generally aware of these developments, though the follow-up studies received little attention in popular media.

There are indeed individual gene mutations that cause devastating disorders, such as Huntingtons disease. But most common debilitating diseases are not caused by a mutation of a single gene. This is because people who have a debilitating genetic disease, on average, do not survive long enough to have numerous healthy children. In other words, there is strong evolutionary pressure against such mutations. Huntingtons disease is an exception that endures because it typically does not produce symptoms until a patient is beyond their reproductive years. Although new mutations for many other disabling conditions occur by chance, they dont become frequent in the population.

Instead, most common debilitating diseases are caused by combinations of mutations in many genes, each having a very small effect. They interact with one another and with environmental factors, modifying the production of proteins from genes. The many kinds of microbes that live within the human body can play a role, too.

A silver bullet genetic fix is still elusive for most diseases.

Since common serious diseases are rarely caused by single-gene mutations, they cannot be cured by replacing the mutated gene with a normal copy, the premise for gene therapy. Gene therapy has gradually progressed in research along a very bumpy path, which has included accidentally causing leukemia and at least one death, but doctors recently have been successful treating some rare diseases in which a single-gene mutation has had a large effect. Gene therapy for rare single-gene disorders is likely to succeed, but must be tailored to each individual condition. The enormous cost and the relatively small number of patients who can be helped by such a treatment may create insurmountable financial barriers in these cases. For many diseases, gene therapy may never be useful.

The Human Genome Project has had an enormous impact on almost every field of biological research, by spurring technical advances that facilitate fast, precise and relatively inexpensive sequencing and manipulation of DNA. But these advances in research methods have not led to dramatic improvements in treatment of common debilitating diseases.

Although you cannot bring your genome card to your next doctors appointment, perhaps you can bring a more nuanced understanding of the relationship between genes and disease. A more accurate understanding of disease causation may insulate patients against unrealistic stories and false promises.

Written by Ari Berkowitz, Presidential Professor of Biology; Director, Cellular & Behavioral Neurobiology Graduate Program, at the University of Oklahoma.

Originally published on The Conversation.

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Sequencing the Human Genome Was Supposed to Revolutionize Treatment of Disease Heres Why It Failed - SciTechDaily

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Orchard Therapeutics(NASDAQ:ORTX)Q42019 Earnings CallFeb 27, 2020, 8:00 a.m. ET

Operator

Ladies and gentlemen thank you for standing by and welcome to the Orchard Therapeutics Fourth Quarter 2019 Earnings Conference Call.

[Operator Instructions] I would now like to hand the conference over to your host for today Ms. Renee Leck.

Renee Leck -- Director of Investor Relations

Thanks operator. Good morning everyone and welcome to Orchard's Fourth Quarter 2019 Investor Update. You can access slides for today's call by going to the Investors section of our website orchard-tx.com. Before we get started I would 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 including those set forth in the most recent Form 20-F filed with the SEC and any other filings that we 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 I'll turn the call over to our President and CEO Mark Rothera.

Mark Rothera -- President and Chief Executive Officer

Good morning. Thank you for joining us and happy Rare Disease Week. One of the themes of this year's campaign is to reframe what it means to have a rare disease. This fits really well with our view that the term patient should be considered a temporary label given the potentially transformative and even curative effect that our one-time investigational gene therapies can provide. At Orchard we are harnessing the power of genetically modified blood stem cells as we seek to correct the underlying cause of severe rare diseases. We have now treated over 170 patients across seven different diseases and demonstrated durable outcomes going out to 18 years or more. If you break this down into cumulative patient years of exposure that's about 750 patient years of data supporting the clinical profile of our gene therapies. This is all to say that our clinical data is really on another level in terms of durability of response and safety. Our business strategy is to create value by commercializing multiple valuable gene therapy programs for rare diseases via highly efficient global commercial platform and benefiting from increasing manufacturing and regulatory efficiencies over time. The key steps to executing on our strategy can be broken down into a number of components.

Firstly we have built a fully integrated company with industry-leading capabilities in research in medical corporate strategy manufacturing regulatory affairs and commercial across an organization that is approximately 300 people strong. Secondly we've established an extensive pipeline of seven clinical stage hematopoietic stem cell gene therapy programs. Thirdly we're establishing an efficient global manufacturing and supply chain leveraging our existing CMO relationships but also our emerging in-house capabilities. Fourthly we're establishing a global commercial footprint on a phased basis. And finally we are keeping in mind the potential to use business development as a tool to create additional value. Now turning to our three lead programs in MLD ADA-SCID and WAS. There are a number of exciting near-term milestones as these programs progress toward potential regulatory filings approvals and launch. For MLD our key priority is to obtain approval for and launch OTL-200 in Europe in the second half of 2020. A BLA filing for OTL-200 in the United States is planned for late 2020 or early 2021. Regulatory filings for OTL-101 for ADA-SCID and OTL-103 for WAS are not that far behind. We plan to initiate a rolling BLA filing in the United States for OTL-101 in the first half of the year with completion of the file anticipated within 12 months. BLA and MAA regulatory filings for OTL-103 in the U.S. and Europe are planned for 2021.

The clinical work supporting efficacy and safety for ADA-SCID and WAS is complete. For ADA-SCID as per FDA guidance work on process validation runs and release criteria is ongoing using the commercial drug manufacturing process with patient cells. For WAS we've enrolled six patients in the ongoing cryopreserve study and expect to report preliminary data sometime this year. It's our plan that the focused commercial infrastructure we are establishing for MLD will serve as the backbone for the future planned launches of ADA-SCID and WAS with only modest additions needed to accommodate the additional launches. All together we believe there is at least a $1.5 billion incidence-based annual opportunity for our lead three programs in the geographies that we intend to cover that reimburse orphan drugs. Now let's focus on the MLD commercialization strategy. We're focused on four strategic imperatives that are key to the commercial launch preparations: patient identification a phased global infrastructure build supply readiness and market access. Starting with patient identification this is an area of high importance as the earlier patients are treated the better their long-term clinical outcomes. So far we've studied MLD patients with the infantile and juvenile forms of the disease and so we'll be targeting a pediatric label at launch. In MLD we estimate that approximately 500 to 800 patients are born each year in the approximately 50 countries that typically reimburse rare disease therapies. Of these we estimate 80% of the incident population will be eligible for OTL-200 at launch.

In terms of prevalence we believe that up to 30% of MLD patients living with a slower progressing juvenile form of the disease could be eligible at launch assuming we secure our target pediatric MLD label. This figure could grow to approximately 80% if we take into account adult MLD patients and assuming we can successfully expand our label. In order to identify these patients we have near and longer term initiatives ongoing. Disease awareness is the first key area. Now that a first-ever treatment for MLD is approaching a potential regulatory approval there is a strong incentive to improve patient diagnosis. Together with patient advocacy groups we are using targeted tools and resources to educate pediatricians and other specialists on the early symptoms of MLD so physicians suspect and test for an MLD diagnosis sooner. Improving access to the appropriate diagnostic tests is another important area. We have a sponsor diagnostic testing program to help identify patients prior to newborn screening coming online. Our goal is that within 14 days of early suspicion a confirmatory test can be done. Our ultimate goal is universal newborn screening using blood spots. An assay has been developed and we're now initiating with collaborators pilot studies in both Europe and the United States starting with New York State and Italy to validate these assays find patients and ultimately support the adoption of national screening programs. When launching a product for a rare disease it's important to have a focused and dedicated commercial team that enables you to bring these medicines to patients around the world as soon as possible. Building a global commercial footprint is our second imperative. We're doing this on a phased approach through a combination of direct Orchard team presence but also coverage via highly experienced partners in some geographies for example in the Middle East and Turkey where we expect a higher incidence of patients also.

Phase one is the EMEA regional buildout which is mostly complete and includes a team of 25 commercial FTEs. We are working on qualifying approximately six treatment centers in the EMEA region at launch with specialized expertise in transplant and neurometabolic disease area knowledge. Phase two is our U.S. buildout which is under way and will grow over the next 18 months in anticipation of the OTL-200 filing at the end of this year or early next and a potential subsequent approval. Phase three will extend Orchard coverage to the countries in other parts of the world that typically reimburse orphan drugs particularly key countries in Latin America and Asia. This will start in 2021. Our third imperative covers the commercial launch supply. We have a great partner in MolMed based in Milan Italy. They have been working on the MLD program for eight years now and also have commercial manufacturing experience supporting Strimvelis. Our goal is to have vector inventory at launch in line with anticipated demand and a robust supply chain between MolMed and the qualified treatment centers. I'll touch on the fourth strategic imperative around pricing and market access at the close of the call. We believe there is a tremendous potential to treat a broad range of diseases with high unmet need using hematopoietic stem cell gene therapy approach including other neurometabolic and neurodegenerative disorders.

Let me now hand it over to Bobby to develop this topic along with providing updates from the MPS-I and MPS-IIIA programs. Bobby?

Bobby Gaspar, M.D., Ph.D. -- President of Research and Chief Scientific Officer

Thanks Mark. Data in both MPS-I and MPS-IIIA were featured at WORLD and I'll start by briefly highlighting those presentations. I'll also be providing an overview of our proof-of-concept study in MPS-IIIA which was recently initiated. Our approach for both diseases use the same ex vivo HSC gene therapy approach that has delivered such promising results in MLD that is the overexpression of enzyme in HSCs that have the ability to migrate across the blood-brain barrier and deliver enzyme to the CNS. Let's start with MPS-I. And I want to spend some time discussing the proof-of-concept cohort as a whole now that median follow-up is out to six months in seven evaluable patients. As a reminder MPS-I is a lysosomal storage disease characterized by neurodevelopmental deterioration severe skeletal manifestations and cardiopulmonary complications leading to death in early childhood. Allogeneic hematopoietic stem cell transplant remains the standard of care; however significant residual manifestations of the disease remain after treatment. As of the later stage cut all patients undergoing HSC gene therapy have engrafted and all evaluable patients showed sustained supranormal IDUA activity in the bloodstream and the cerebrospinal fluid or CSF. This was accompanied by a concurrent drop in heparan and dermatan sulfate both in the urine and CSF that normalize rapidly within three to six months post-treatments.

The most important aspect of this data is that murine studies and analysis of patients undergoing allogeneic HSCT suggest that clinical outcomes correlate strongly with the level of IDUA enzyme expression. For example in a murine model of MPS-I a transplant with wild type cells did not fully correct the CNS and skeletal defects whereas overexpression of IDUA through lentiviral vector-mediated HSC gene therapy was able to do so. Similarly in a large published study of allo HSCT patients the level of IDUA expression achieved in the periphery was a highly significant predictor of long-term clinical outcomes. At 12 months post-gene therapy the patient with the longest follow-up is showing signs of resumed growth and bone remodeling improved motor skills and a stable cognitive score in line with evidence of metabolic correction. The trial has currently treated eight patients and we expect additional interim data to be presented this year before full proof-of-concept results are available in 2021. Let's now turn our attention to MPS-IIIA. This is one of the most frequent forms of mucopolysaccharidosis and has no approved treatments. At WORLD we were encouraged to see the University of Manchester present data on the first MPS-IIIA patient treated with ex vivo HSC gene therapy on a compassionate use basis who is doing very well. Engraftment of gene-corrected cells appears stable and enzyme levels well above the upper limits of normal at nine months post-treatment.

The vector and cell transduction protocols used to treat those compassionate use patients are the same as those used in our recently initiated proof-of-concept study. I'll briefly review the study's outcome measures and target patient population in order to provide a sense of scope and objectives. Patients between the ages of three months and two years with normal cognitive function are eligible for the trial. We're enrolling young patients in this initial study because as we've seen in MLD patients treated at a very early stage of the disease or who are asymptomatic have the best response presumably because the extent of irreversible CNS damage is limited. As a first-in-human study the primary objective is to evaluate the safety and tolerability of OTL-201 in addition to engraftment and biological efficacy measured by SGSH expression in leukocytes at 12 months post-treatment. Key secondary endpoints include cognitive and behavioral measures as well as quality of life and activities daily living at three years post-gene therapy which is typically when we begin to see decline in these functions in untreated individuals. The first patient in this trial has been enrolled and we expect to report preliminary data later this year. As patients are enrolled and the study progresses interim data cuts will be presented.

I want to look ahead now to some exciting new initiatives. Using the natural ability of HSCs to deliver therapeutic genes to the CNS and other tissues we believe there is a tremendous potential to treat more neurodegenerative diseases and new therapeutic areas. We will do this by external collaborations and also through in-house discovery and preclinical efforts in our established research laboratories in London. In January we were excited to announce in a new agreement with Dr. Alessandra Biffi a leading expert in gene therapy to help support the expansion of our portfolio into additional areas of critical need for patients including new programs for rare and non-rare neurodegenerative diseases. As the expert that first established our MLD and MPS-I programs her experience and partnership will be invaluable.

It's an exciting time at Orchard and we look forward to keeping you updated on these programs as the data matures. On that I'll turn the call over to Frank.

Frank Thomas -- Chief Operating Officer and Chief Financial Officer

Thanks Bobby. I'm going to start by reviewing our fourth quarter results which are summarized in this morning's press release. Then I'll touch a bit on our outlook for the rest of the year and the upcoming launches for our lead programs. Starting with the financial results we ended the fourth quarter with $325 million in cash and investments compared to $336 million at the end of 2018. Consistent with our previous guidance we expect that our existing cash and investments will fund our anticipated operating and capital expenditures into the second half of 2021. During the fourth quarter we recognized $0.6 million in revenue related to Strimvelis. Research and development expenses were approximately $31 million in the fourth quarter of 2019 compared to $17 million in 2018. The increase was primarily driven by higher cost to advance our programs through later stages of development including the addition of our clinical stage MPS-I program in 2019. SG&A expenses were $19 million for the fourth quarter of 2019 compared to $12.0 million in 2018. The increase was primarily due to investments to prepare for the potential commercialization of our late-stage programs as well as G&A costs to support public company operations in 2019.

We used about $44 million of cash to fund operations in the fourth quarter of 2019. We expect the quarterly burn rate to increase in 2020 due to the capital investment for the manufacturing facility as well as sequential quarterly growth in operating expenses to support the potential launch of OTL-200 in the second half of 2020. I wanted to also use today's call to touch on our outlook for our lead programs. We are building a global commercial infrastructure and a manufacturing platform that we can leverage with each subsequent product launch. Notably each rare disease in our portfolio has its own set of unique factors that will influence the uptake curves as we enter the launch phase. A few of these factors include first is there a pool of prevalent patients and how easy will it be to identify and treat these patients? Second does the disease currently have a high level of awareness and diagnostic tools in place to aid patient identification? And third where will we launch first? To illustrate this with an example for a disease like ADA-SCID newborn screening is already established in all 50 states in the U.S. and some countries in Europe. So this gives us confidence that we should be able to quickly identify the incident population eligible for gene therapy driving faster uptake. Another example for a disease like WAS patients typically live longer due to the slower progressing nature of the disease and many have already been diagnosed. This will likely make the treatment of prevalent patients a key driver in early uptake. We are also planning to launch these two therapies first in this U.S. where adoption can often happen quicker.

Turning to MLD OTL-200 is an investigational treatment for a condition that is characterized by rapid progression. This means that our work to raise the awareness for physicians and implement diagnostic initiatives will be crucial in driving adoption before newborn screening is in place. Also we are planning to launch MLD first in Europe assuming approval and there will be country-by-country negotiations with payers which will mean a phased rollout across the continent. With the potential second half European MLD approval we expect meaningful revenues starting in 2021. We anticipate all three lead programs to be generating U.S. revenue by 2022. So in conclusion we believe that we're taking the necessary steps to position these programs for long-term success and demonstrating the scalability of our platform approach. As I said earlier in my remarks the investments we made in 2019 and the continued buildout of commercial and manufacturing in 2020 will take us a long way toward achieving our vision of building a fully integrated company with industry-leading capabilities.

And now Mark back to you.

Mark Rothera -- President and Chief Executive Officer

Thank you Frank. In closing as we get closer to our anticipated OTL-200 launch I'd like to address the four strategic imperatives for OTL-200 namely market access. We are seeking to bring a new type of medicine to the world. A one-off administration with the potential to deliver lifelong transformative benefit including the potential to cure. As a company we have committed to four key principles that will guide our approach to value and pricing which we've been proactively discussing and sharing with stakeholders. Firstly we are committed to share value. I think our investigational gene therapies are intrinsically very valuable medicines to the patient but also to the family whom according to recent research spends an average of 17 hours a day on caregiving responsibilities for an MLD child. We also expect the healthcare system and society more broadly to benefit from the potential value of these medicines. And certainly we want to reinvest some of this value in future innovation for other rare disease patients who are in need. Secondly we're committed to risk sharing. We recognize that gene therapies are still new to the system and questions exist about the durability of response over the long term. Having treated more than 170 patients and seeing follow-up now in our own portfolio spanning upwards of 18 years we are confident in the durability of response and are willing to engage in payment models that share risk if that is so required.

Thirdly we are committed to informed pricing applying well-developed robust and recognized tools to the best available evidence we have to measure value and in turn determine pricing. For instance we recently conducted an MLD caregiver research exercise in close partnership and consultation with leading KOLs and advocacy groups using standard well-accepted instruments like PedsQL. Early findings from this project presented two weeks ago at WORLD indicate that children with MLD experience roughly 20 outpatient visits and three inpatient visits in the last year. On average six days are spent in hospital per inpatient visit. That's an incredible amount of time for these parents to be away from work away from the rest of their family and community and knowing that the care for their child is only palliative. Unsurprisingly then our findings suggest 83% of parents were forced to miss work caring for their child with 68% of this being unpaid leave. Finally we will engage with stakeholders across the continuum to help evolve the way our healthcare system thinks about delivers and pays for gene therapy medicines. For years it's mostly been about managing chronic conditions and treating symptoms of disease. It's in everyone's interest that there is a successful path forward for one-off potentially curative medicines to be made available to patients.

Thank you for your time and attention. Operator you may now open the line for questions.

Operator

[Operator Instructions] Our first question or comment comes from the line of Anupam Rama from JP Morgan. Your line is open.

Anupam Rama -- JP Morgan -- Analyst

Hey, guys, thanks so much for taking the question. And how are you thinking about the initial size and scope of the sales infrastructure buildout in the EU for OTL-200 particularly as we think about layering on indications over the next several years? And maybe you can touch on the U.S. market as well. And then a quick second one on OTL-101. The rolling BLA's supposed to be starting here in the first half but what are the gating factors to completing it given the known preclinical data and clinical data? Is it really CMC related? I guess the guidance is that the OTL-101 filing would complete within 12 months but I guess why wouldn't it be quicker given everything that we know so far? Thanks so much.

Mark Rothera -- President and Chief Executive Officer

And the first one was about the size and scope of the team in Europe and then the overlay for the additional launches. And so as we mentioned for rare disease programs you really need a highly focused team. It doesn't have to be a large team but focused and dedicated as we have. We've guided to the fact that we have 25 FTEs out in markets in Europe with the major focus on the biggest markets such as Germany France UK and Italy. But I think one of the advantages of having our team in those countries is they are also sort of regional hubs for clusters of countries. So with the teams that we're building we expect patients to be referred not only from within those countries but from adjoining countries into those referential qualified centers for treatment. You asked a bit about how do we scale up. Well the good thing is that once you've established sort of a core group with some of the key capabilities like for example a general manager for Germany medical marketing and sales you really are looking at sort of adding just incrementally. You don't need another general manager you don't need another medic you don't need another head of marketing but what you might need is some additional people on the ground to meet additional customers to support patients getting to those treatment centers. So it is kind of incremental.

And the same is true in the U.S. where we'll begin well we are already preparing the buildout this year and into next with the MLD timeline in mind. And the other thing that I think is very efficient is for the most part you're talking about the same treatment centers the same qualified centers that can treat MLD patients or ADA-SCID patients or WAS patients. And again you might add a few incrementally to what you start with over time but again it's not a copy/paste. So the second question you asked was about the ADA-SCID program. So you're quite right that essentially we've done the clinical work on efficacy and safety. We've last year we talked about the cryo data that showed that cryo is performing like fresh. And really our key focus as per FDA guidance is the process validation work where we're using the commercial vector with a commercial drug manufacturing process using patient material which is something that they've specifically asked for. So we're guiding to initiating the rolling BLA in the first half of this year. That work that I just alluded to is ongoing and I think we'll feature in the final module that we will then present to close the filing. And as you mentioned we have up to 12 months to do that. And that for the moment is the guidance we're giving.

Anupam Rama -- JP Morgan -- Analyst

Great. Thanks for taking our questions.

Mark Rothera -- President and Chief Executive Officer

Thank you.

Operator

Thank you. Our next question or comment comes from the line of Whitney Ijem from Guggenheim. Your line is open.

Whitney Ijem -- Guggenheim -- Analyst

Hey, good morning. Thanks for taking the question. This one is to follow up on some of the comments around market access. Kind of sounds like you're doing a lot of work on sort of the establishing value side. But from a logistical perspective on the reimbursement side I guess what work is ongoing around coding or kind of any other like logistical reimbursement type considerations that we should be thinking about?

Mark Rothera -- President and Chief Executive Officer

I think the first focus from a market access point of view is the potential launch of OTL-200 in Europe in the second half of this year. So for that there are many aspects that have been ongoing. Engagement with payers and making sure that the payers appreciate the background to the product the data and the benefit that we're able to convey to patients and the durability of that response. So a lot of this is an educational exercise. One thing we're very delighted with is a clear signal of willingness to pay given the fact that this is a product for a very high unmet need very severe condition that affects children and for which there are no treatments today and where the dataset that you've seen is very compelling. As you know in Europe there are I think this was alluded to in Frank's comment it's a sort of phased launch and so we also are engaging in the variety of different processes in different countries in order to be able to be well prepared on approval to move those forward as quickly as possible. And to remind you the lead country in Europe is typically Germany where you can launch relatively fast after an approval and have about a one-year time frame to complete the negotiations. So I hope that answers your question. If there's anything else you need to know please let me know.

Whitney Ijem -- Guggenheim -- Analyst

Maybe just one quick follow-up. Sort of in that same vein as we think about uptake or kind of penetration into the European markets versus the U.S. markets again with sort of reimbursement and the difference in the reimbursement frameworks in those geographies any color you can give or kind of how you guys thinking about that at this point?

Mark Rothera -- President and Chief Executive Officer

So it is a cascade of launches in Europe. So it's a very large market collectively as you know with 450 million inhabitants 28 countries. And it is a cascade of different launches with each country having a specific process for approval. I would say that one of the things that we have I think in the favor of launching a product like MLD in terms of the impetus to get this to market quickly is that really there's no treatment for these children and it is very severe. And so and the data is compelling. And so I think that there is a willingness to work with us now prospectively but also rapidly through these processes because time really matters for these children.

Operator

Thank you. Our next question or comment comes from the line of Esther Rajavelu from Oppenheimer. [Operator Instructions] Okay we'll move on. Our next question or comment comes from Gena Wang from Barclays. Your line is open.

Gena Wang -- Barclays -- Analyst

Thank you for taking my questions. I have two. One is regarding the MLD launch and the other is regarding the pipeline. So for the MLD launch just wondering Mark you mentioned that MolMed had a will have sufficient inventory being produced to meet expected launch demand. Just wondering those inventory are you referring to vectors and the plasmid? And what is the expected launch demand in terms of the number of patients? And also the capacity of the MolMed how many patient product can they process at the same time?

Mark Rothera -- President and Chief Executive Officer

Yes we're obviously delighted to have a partner like MolMed who have been working on the MLD program now for eight years and they have commercial manufacturing experience doing that already for the Strimvelis program. So it's a great partner to have on this program. So we work with MolMed actually on a whole range of programs. And we have capacity that is if you like fungible flexible depending on the various programs and their different stages of importance in demand. So we have the ability with MolMed to titrate very rapidly according to demand which is helpful. But the key thing that I was alluding to was the vector inventory as being one of the things that we wanted to make sure we had in place to allow us to meet the demand. Drug product manufacturing suites are also available at MolMed. And again there is certain flexibility there because we can manage across our portfolio of programs with them. At this time we're not guiding to patient numbers specifically. If that changes in the future we'll let you know. But our intention is to make sure we're matching supply with anticipated demand.

Gena Wang -- Barclays -- Analyst

And then my next question is regarding the pipeline. For MPS-IIIA and the MPS-I just wondering what based on your discussion with FDA and the other drug approval in the past what could be the latest thoughts for approvable endpoints and will you start to share the data of those the endpoints with us in the future?

Mark Rothera -- President and Chief Executive Officer

I'm going to turn that over to Bobby.

Bobby Gaspar, M.D., Ph.D. -- President of Research and Chief Scientific Officer

So as far as let me start with MPS-I first of all. So this is a proof-of-concept study where the primary endpoints currently are as far as efficacy endpoints are concerned are around biological parameters; the enzyme activity reduction in substrate levels. The clinical endpoints are exploratory at the moment in this proof-of-concept study. And so we will move from this to a registrational study and the data from the proof-of-concept study will inform the endpoints for the registrational study. And so obviously we are having thoughts about what those endpoints would be in the registrational study and they need to be clinically meaningful endpoints. And we'll I'd say we can't give you details about that at the moment but obviously the major issues in MPS-I are around cognitive defects skeletal defects etc. And so we'll look at how we can capture those in the registrational study. And once we've got to more detail and agreement around that we'll share that data with you. As far as MPS-IIIA is concerned again we're in a proof-of-concept study at the moment at the University of Manchester. And again within that there are cognitive endpoints that are and behavioral endpoints that are being measured. And so that study has just started with the first patient having been enrolled.

Gena Wang -- Barclays -- Analyst

Bobby just follow-up question regarding MPS-I. So that has been a while ago. IDUA then got approval based on the SVC and the 6-minutes walk test. Do you think this will still be the case or you think that going forward the endpoint that could change also diverge from this?

Bobby Gaspar, M.D., Ph.D. -- President of Research and Chief Scientific Officer

I mean I think at the moment I'd say we are looking at a number of exploratory endpoints within the proof-of-concept study and that includes we're looking at IQ we're looking at skeletal abnormalities growth etc. So we're looking at a number of things. And so I'd say we'll need to take that on board first before we decide what the endpoints will be for the registrational study. And I know you've talked about ERT being approved on the basis of 6-minute walk test etc. but things have moved on since that time. And also remember ERT doesn't have the ability to correct the CNS which is one of the major abnormalities one of the severe problems associated with MPS-I. So we would want to capture that within our endpoints for the registrational study.

Gena Wang -- Barclays -- Analyst

Okay great. Thank you very much.

Bobby Gaspar, M.D., Ph.D. -- President of Research and Chief Scientific Officer

Okay. Thank you.

Operator

Thank you. Our next question or comment comes from the line of Graig Suvannavejh from Goldman Sachs. Your line is open.

Graig Suvannavejh -- Goldman Sachs -- Analyst

Hi, good morning, or good afternoon, folks. Thanks for taking my questions. I've actually got a few but I'll try to keep them to maybe two or 3. First just on your opening comments around seeing the commercial revenue opportunity for your three lead programs at $1.5 billion is there any other color you can provide in terms of perhaps sizing magnitude if they're all equally say $500 million apiece or how should we be thinking about that? My second question just has to is focused more around OTL-200 and given that you're launching into Europe first how should we think about subsequent U.S. pricing? Should we be expecting that the price will be similar between the two geographies or we commonly think about pricing in Europe being less than what we see in the U.S. And then my final question is for Frank and the model. Thanks for the color around quarterly cash burn and how it will increase versus your exit rate in fourth quarter. But first half or second half should we just continue to steadily assume quarterly increase in cash burn as we evolve from the beginning of the year toward the second half of the year? Thanks.

Mark Rothera -- President and Chief Executive Officer

So I'll start with the first two and then hand over to Frank. You ask about any more color on the $1.5 billion annual incidence opportunity-driven revenue opportunity for the lead three programs. So reminding ourselves it's MLD ADA-SCID and WAS. And when we look at the global incidence in those key markets around the world when you you asked about more color the largest indication is MLD and then WAS and then ADA-SCID on an incidence basis. And we're expecting approximately 80% of the incident patients in those three indications to be eligible for our gene therapies at a minimum. It could actually be higher for a number of reasons I could go into as well. And when you look at that collectively using current gene therapy pricing analogs as a guide you can see it's at least a $1.5 billion annual opportunity. But I think very important color here is that that does not account for a really important upside which is prevalence. And we've also given an indication about the prevalent pool in each of the indications. I think Frank alluded to that in the prepared remarks. So Wiskott-Aldrich syndrome for example which is a slower progressing disease has a very significant prevalent pool. We estimate 3000 to 5000 patients worldwide living with that condition living with a sort of that need treatment. And we expect that about 55% of those could be eligible for gene therapy. So I think as Frank alluded to we see that as an especially prevalent play as far as the revenue build is concerned in that incident.

With regard to MLD we see it roughly as a balanced approach with both incidence but a 30% prevalent pool in the juvenile population that would be eligible for treatment we think at launch. But ultimately this would be an incident-based treatment. So on the second point you talked about which is OTL-200 pricing I think there are many reasons to consider the fact that MLD pricing could be actually with a relatively tight corridor between U.S. and Europe because this is a very high unmet need very severe disease. There are no treatment options. And I think given the data that we've generated as well as the durability of response I think we have a compelling case to make to payers both sides of the Atlantic. But that said I think we are of course launching in Europe first and the pricing will be set for Europe to start with. And then there's another year or so before we get to the U.S. launch. So in that time we will be watching carefully listening learning and we'll take a view on the U.S. price ultimately closer to the U.S. launch. So the third question was over to you Frank if I can hand it over to you.

Frank Thomas -- Chief Operating Officer and Chief Financial Officer

Yes sure. No problem. So Graig on the modeling question I think for 2020 think about the growth in opex to be sort of incremental sequential growth on top of Q4. And I wouldn't say I mean if there's an inflection within there it would likely come in the second half of the year as we start to ramp up some of the commercial spend on the U.S. in preparation for a potential launch in the U.S. for MLD. But I would say generally just incremental growth quarter on quarter. In terms of the other piece which is the capex because we'll start construction on the manufacturing facility in 2020 I think we've previously earmarked about $70 million to $80 million total capex which will be spread over 2020 and 2021. So the construction activities will ramp up I would say second half of 2020 and first half 2021 largely. So that's how I would model the capex and the burn associated with the manufacturing facility.

Graig Suvannavejh -- Goldman Sachs -- Analyst

Great. Thank you very much for my questions.

Frank Thomas -- Chief Operating Officer and Chief Financial Officer

Thank you.

Operator

Thank you. Our next question or comment comes from the line of Yaron Werber from Cowen. Your line is open.

Yaron Werber -- Cowen -- Analyst

Ron, thanks very much for taking the question. Actually two if I might actually. So just really briefly I wanted to touch first on Strimvelis how we should kind of think about the slight up and down quarter-over-quarter sales. And more importantly I think how you're thinking about the drug moving forward particularly as the other ADA-SCID therapy approaches commercialization. And then just a question on the X-CGD and thalassemia programs mostly just kind of regarding on excuse me regarding timelines there when you think we might have next data and whether you're also considering a staggered filing and launch between Europe and the U.S. for X-CGD as well. Thanks.

Mark Rothera -- President and Chief Executive Officer

So Strimvelis has been a tremendously helpful learning tool for us about ex vivo gene therapy. It is a great product. It's available only in one center in the world in Milan Italy. And so we've learned a lot about helping patients move to treatment center in fact in many cases from one country to another what it takes to help those patients be well-managed and go through the treatment process. And yes it is a little bit bumpy and that to some extent depends on the identification of patients. And then the various stages of patient going through the decision making process between staying locally let's say for bone marrow transplant what the risks of that entails or going over to a center in Milan Italy for treatment. And I think one of the important distinctions to make going forward is that with our programs as you know we've gone from cryopreserved gene modified stem cells so where Strimvelis is only available as a fresh formulation which means patients have to do the traveling. As we look forward with our cryopreserved gene modified stem cells it's really those cells that are going to do the travel for the most part which is going to make it a lot easier for patients along this journey. So again I think the overall message is we've used this as a learning tool to prepare ourselves for launch for our OTL-200 and beyond. So for Bobby maybe you could answer the next question?

Bobby Gaspar, M.D., Ph.D. -- President of Research and Chief Scientific Officer

Yes. So Yaron as far as X-CGD and beta-thal is concerned there are some similarities as far as the work we're doing in those two programs. So for X-CGD as you know the proof of concept is complete. And our initial thoughts on the pivotal study was that it would focus on late adolescence and adults where the best results were seen. But really in order to treat as many patients as possible we want to be able to treat pediatric patients as well. And so we need to see this year outcomes in pediatric patients. So that's part of the work for this year. But the other thing is this is a large prevalent population that we've talked about and so we need to get a manufacturing process that is appropriate to treat that number of patients. So we are spending again time this year on ensuring a manufacturing process that is fit for the commercial opportunity and that involves the use of transduction enhances for example to optimize the use of vectors. So that CMC work is ongoing as well. And third that latter part is really again what is what we're doing as far as beta-thalassemia is concerned. Proof of concept again established in that condition large patient population and opportunity and trying to get the manufacturing process correct in order to be able to serve that opportunity. And as I say that's predominantly looking at both the drug product process use of transduction enhances and also looking at vector as well. So I hope that addresses your question.

Yaron Werber -- Cowen -- Analyst

Sure. Thanks very much guys.

Bobby Gaspar, M.D., Ph.D. -- President of Research and Chief Scientific Officer

Thanks.

Operator

Thank you. Our next question or comment comes from the line of David Nierengarten from Wedbush Securities. Your line is open.

David Nierengarten -- Wedbush Securities -- Analyst

Hey, thanks for taking the question. I had one on the MLD patient numbers and incidence versus prevalence. And I know there's a little bit of a probably a blurry line but the incidence numbers that you provided are strictly births or new diagnoses? And I'm asking about new diagnoses because of course those might be a delayed diagnosis and so might actually be counted by some as a prevalent patient. So I was just wondering if you could provide a little bit more detail on those patient estimates for MLD. Thanks.

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Orchard Therapeutics (ORTX) Q4 2019 Earnings Call Transcript - Motley Fool

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UPDATED: A name emerges out of the Gilead M&A rumor mill, and it's a cancer biotech - Endpoints News