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Archive for the ‘Gene Therapy Research’ Category

CANbridge Pharmaceuticals Enters into Duchenne Muscular Dystrophy Gene Therapy Research Agreement with University of Washington School of Medicine -…

BEIJING & CAMBRIDGE, Mass., November 01, 2021--(BUSINESS WIRE)--CANbridge Pharmaceuticals, Inc., a leading China-based global rare disease-focused biopharmaceutical company committed to the research, development and commercialization of transformative therapies, announced that it has entered into a two-year sponsored research agreement with the University of Washington School of Medicine, in Seattle, Washington, for gene therapy research in Duchenne muscular dystrophy (DMD), a rare neuromuscular disease. The program will be under the direction of Jeffrey Chamberlain, Ph.D., professor in the Departments of Neurology, Medicine and Biochemistry, the McCaw Endowed Chair in Muscular Dystrophy at the University of Washington School of Medicine, and Director of the Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center of Seattle. Guy Odom, Ph.D., Research Assistant Professor in the Department of Neurology at the University of Washington, will serve as the co-principal investigator.

Dr. Chamberlain is internationally renowned as a pioneer and one of the top researchers in the field of gene therapies for muscle diseases. His lab has been studying muscular dystrophy mechanisms, particularly dystrophin structure, and gene therapy approaches. They were the first to show that adeno-associated virus (AAV) vectors could be used for systemic gene delivery to muscle.

"We are thrilled to enter into this research agreement with Dr. Chamberlain, who has been leading the world in DMD research for decades, as we advance our gene therapy research program in neuromuscular disorders," said James Xue, Ph.D., Founder, Chairman and CEO, CANbridge Pharmaceuticals Inc. "Duchenne muscular dystrophy is the most common of the hereditary neuromuscular diseases and, despite recent approvals for exon-skipping therapies, remains severely underserved medically. We believe that the best gene therapy for this devastating disease has not yet been discovered, and we look forward to working with Dr. Chamberlain and his team on their innovative research, as well as the new treatments that may arise from it."

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About Dystrophinopathies

Duchenne muscular dystrophy (DMD) is a rare muscle disorder, but it is one of the most frequent genetic conditions that primarily affects males. DMD usually presents in early childhood and is characterized by rapidly progressive muscle degeneration and weakness, leading to loss of ambulation by about 12 years of age. Cardiomyopathy is a common cause of morbidity and death in DMD patients. The incidence of DMD is estimated to be 1/3,500 1/5,000 male births worldwide and 1/4,560 in China, according to the National Organization for Rare Disease and published peer review.

About the Chamberlain Laboratory, University of Washington Department of Neurology

The lab is focused on muscular dystrophy research with two major goals: to develop a better understanding of the molecular basis of the pathophysiology of the diseases, and to develop gene and cell therapies that will correct and treat the muscular dystrophies. Major targets for therapy include Duchenne muscular dystrophy and LGMD2I.

About the Odom Laboratory, University of Washington Department of Neurology

The lab is focused on developing a more thorough understanding of the inherent muscle biology occurring during muscular dystrophy disease progression. As such, the labs research generally involves developing or improving genetic-based therapies.

About CANbridge Pharmaceuticals Inc.

CANbridge Pharmaceuticals Inc. is a China-based global rare disease-focused biopharmaceutical company committed to the research, development and commercialization of transformative therapies.

CANbridge has a comprehensive and differentiated pipeline of 13 drug assets with significant market potential, targeting some of the most prevalent rare diseases and rare oncology.

These include Hunter syndrome (MPS II) and other lysosomal storage disorders (LSDs), complement mediated disorders, hemophilia A, metabolic disorders, rare cholestatic liver diseases and neuromuscular diseases, as well as glioblastoma multiforme (GBM).

CANbridge strategically combines global collaborations and internal research to build and diversify its drug portfolio and invest in next-generation gene therapy technologies for rare disease treatments. CANbridge global partners include, but are not limited to, Apogenix, GC Pharma, Mirum, Wuxi Biologics, Privus, the University of Massachusetts Medical School (UMass) and LogicBio.

For more on CANbridge Pharmaceuticals Inc., please go to: http://www.canbridgepharma.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20211101005332/en/

Contacts

CANbridge Pharmaceuticals Inc. ir@canbridgepharma.com

Media: Deanne Eagle Planet Communications deanne@planetcommunications.nyc 917.837.5866

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CANbridge Pharmaceuticals Enters into Duchenne Muscular Dystrophy Gene Therapy Research Agreement with University of Washington School of Medicine -...

Parkinson’s gene therapy restores responses to dopamine-boosting drug in mouse models – FierceBiotech

Levodopa, the commonly prescribed dopamine-restoring drug for Parkinson's disease, loses its effectiveness over time. Researchers at Northwestern University say they've found a potential method forreviving the drug's benefits: gene therapy.

The researchers restored the ability of neurons to convert levodopa into dopamine in mice with a gene therapy that targets the substantia nigra region of the brain. By effectively recreating a healthy environment in the brain, the therapy eliminated abnormal brain activity that causes movement difficulties in Parkinson's patients, the teamreported in Nature.

The new findings also provided insights into why dopamine-releasing neurons wither away in Parkinson's. By studying the genetic features of theneurons in Parkinson's models, the Northwestern researchers showed that damage to the mitochondria, the power suppliers inside of dopamine-producing neurons, triggers events that lead to Parkinson's.

"Whether mitochondrial damage was a cause or consequence of the disease has long been debated. Now that this issue is resolved, we can focus our attention on developing therapies to preserve their function and slow the loss of these neurons," said James Surmeier, Ph.D., chair of neuroscience at Northwestern's Feinberg School of Medicine, in a statement.

Theinsights could be usedto develop tests that identify Parkinson'sin people five to 10 years before it manifests, Surmeier suggested.

RELATED:Neurocrine exits $165M Parkinson's pact with Voyager after FDA hold

Efforts to develop gene and cell therapies for Parkinson's are underway, with mixed results so far.Bayer has started two early-stage trials: a gene therapy being developed byits subsidiary AskBio and a stem cell treatment from its unit BlueRock Therapeutics.

Voyager Therapeutics has suffered several setbacks in its efforts to develop a gene therapy for Parkinson's.Sanofi ended its deal with Voyager in October 2017, AbbVie nixed its pact in August 2020 and Neurocrine Biosciences axed its tie-up in February of this year after a clinical hold was placed on a phase 2 trial last December. Pfizer inkeda $630 million pact with Voyager last month to use its capsids in neurologic and cardiovascular gene therapies, though the specific disease targets were not disclosed.

Other researchers are also looking for innovative ways to spruce up dopamine-producing neurons. A team at the University of San Diego, California developeda gene therapy technique that turned astrocyte cells into dopamine-producing neurons, for example.

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Parkinson's gene therapy restores responses to dopamine-boosting drug in mouse models - FierceBiotech

ACGT Scientific Advisory Council Chair Michael T. Lotze, MD, honored with Lifetime Achievement Award from Society for Immunotherapy of Cancer -…

image:Alliance for Cancer Gene Therapy (ACGT) Scientific Advisory Council Chair Michael T. Lotze, MD, of the University of Pittsburgh, will be honored with the 2021 Society for Immunotherapy of Cancer (SITC) Lifetime Achievement Award at the SITC 36th Annual Meeting, Nov. 10-14, in Washington D.C. view more

Credit: University of Pittsburgh

Alliance for Cancer Gene Therapy (ACGT) Scientific Advisory Council Chair Michael T. Lotze, MD, of the University of Pittsburgh, will be honored with the 2021 Society for Immunotherapy of Cancer (SITC) Lifetime Achievement Award at the SITC 36th Annual Meeting, Nov. 10-14, in Washington D.C.

Dr. Lotze is currently Chief Cellular Therapy Officer of Nurix Therapeuticsand professor of surgery, immunology and bioengineering at the University of Pittsburgh School of Medicine. He is widely regarded as the leader in exploring cancer as a disorder of cell death and is devising novel strategies to approach the disease in this context. He initiated the first approved gene therapy protocols at the National Institutes of Health and has treated more than 100 patients on gene therapy protocols at the University of Pittsburgh. He is the co-inventor of 10 patents in dendritic cell vaccines and antigen discovery, and author of more than 500 scientific papers and chapters in basic and applied tumor immunology and cytokine biology.

Dr. Lotze leads the 14 members of the ACGT Scientific Advisory Council in rigorously reviewing and monitoring the research selected for funding by ACGT. The importance and value that the Council contributes to the ACGT funding process distinguishes ACGT from many other funding agencies. Council members are among the most accomplished thought-leaders in the field of cancer cell and gene therapy. They are experienced scientists whose decades of research and patient care have elevated them into important leadership positions at top institutions across the U.S. and in Canada.

Society for Immunotherapy of Cancer is a member-driven organization dedicated to improving cancer patient outcomes by advancing the science and application of cancer immunotherapy through educational programs that foster scientific exchange and collaboration. Learn more about SITC at http://www.sitcancer.org.

Alliance for Cancer Gene Therapy

For more than 20 years, Alliance for Cancer Gene Therapy (ACGT) has funded research that is bringing innovative treatment options to people living with deadly cancers treatments that save lives and offer new hope to all cancer patients. The organization funds researchers who are pioneering the potential of cancer cell and gene therapy talented visionaries whose scientific advancements are driving the development of groundbreaking treatments for ovarian, prostate, sarcoma, glioblastoma, melanoma and pancreatic cancers. 100% of all public funds raised directly support research and programs. For more information, visitacgtfoundation.org, call (203) 358-5055,or join the Alliance for Cancer Gene Therapy community onFacebook,Twitter,LinkedIn, Instagram andYouTube @acgtfoundation.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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ACGT Scientific Advisory Council Chair Michael T. Lotze, MD, honored with Lifetime Achievement Award from Society for Immunotherapy of Cancer -...

BridgeBio Pharma Announces Dosing of First Patient in Phase 1/2 Trial of Investigational Gene Therapy for Canavan Disease – PRNewswire

PALO ALTO, Calif., Nov. 3, 2021 /PRNewswire/ --BridgeBioPharma, Inc. (Nasdaq: BBIO),a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, today announced that the first patient has been dosed in CANaspire, its Phase 1/2 clinical trial of BBP-812, an investigational adeno-associated virus (AAV) 9 gene therapy for the treatment of Canavan disease. Canavan disease is an ultra-rare and fatal disease that affects approximately 1,000 children in the United States and European Union. There are currently no approved therapies for the condition.

"Dosing the first patient in our Canavan disease trial is a significant achievement for our gene therapy team and we would not be here without the support of our collaborative partners in the patient, medical and scientific communities," said Eric David, M.D., J.D., CEO at BridgeBio Gene Therapy. "We are committed to the Canavan community and will work to advance this trial and the other programs in our gene therapy portfolio because we believe deeply in the potential of gene therapy to improve and save lives."

"Based on the efficacy and safety data we've observed in our preclinical studies, we are hopeful that our investigational gene therapy can become a meaningful treatment option for children living with Canavan. Right now, these children only have access to supportive care because there are currently no approved therapies to treat this devastating disease," added Adam Shaywitz, M.D., Ph.D., chief medical officer at BridgeBio Gene Therapy.

The Phase 1/2 open-label study is designed to evaluate the safety, tolerability, and pharmacodynamic activity of the company's AAV9 gene therapy, BBP-812, in pediatric patients with Canavan disease. In the initial dose-finding phase of the study, each patient will receive a single intravenous (IV) infusion of BBP-812. The primary outcomes of the study are safety, as well as change from baseline of urine and central nervous system N-acetylaspartate (NAA) levels. Motor function and development will also be assessed. Preclinical proof-of-concept data have shown the approach restores survival and normal motor function.

"Gene therapy is designed to treat diseases at their source, which for Canavan disease would be an extremely beneficial treatment option. Through this trial, we hope to provide evidence that this investigational therapy could represent a promising treatment option for Canavan patients and their families. We are grateful to the first family for participating," said Florian Eichler, M.D., director of the Leukodystrophy Service and principal investigator at Massachusetts General Hospital, the first clinical site open in the CANaspire trial.

BridgeBio's gene therapy was originally developed by Guangping Gao, Ph.D., and Dominic J. Gessler, M.D., Ph.D., at the University of Massachusetts Medical School. Dr. Gao, a pioneer in AAV gene therapy, was also the first person to clone the ASPA gene, which in its mutated form causes Canavan disease. Dr. Gao has been working on developing a cure for Canavan disease for more than 25 years.

"Throughout my career, I've been passionate about connecting with families in the Canavan community to understand how to help them through their journey. After decades of research and work, I'm thrilled that we have dosed the first patient in this trial. I'm hopeful that this represents a meaningful turning point for the Canavan community," said Dr. Gao, co-director of the Li Weibo Institute for Rare Diseases Research, director of the Horae Gene Therapy Center and Viral Vector Core, and professor at University of Massachusetts Medical School.

BridgeBio's investigational AAV9 gene therapy for Canavan disease is one of the Company's 14 programs that are in the clinic or commercial setting for patients living with genetic diseases and genetically-driven cancers. An initial Phase 1/2 data readout for Canavan disease is expected in 2022. For more information about the CANaspire trial, visit TreatCanavan.com or ClinicalTrials.gov (NCT04998396).

About BBP-812BBP-812 is an investigational AAV9 gene therapy for Canavan disease. Using AAV gene therapy, BridgeBio seeks to deliver functional copies of the ASPA gene throughout the body and into the brain, potentially correcting the disease at its source. Preclinical proof-of-concept results in Canavan disease models have shown the approach restores survival and normal motor function. BBP-812 was granted Fast Track Designation, Rare Pediatric Drug Designation, and Orphan Drug Designation by the U.S. Food and Drug Administration. BBP-812 was also granted Orphan Drug Designation by the European Medicines Agency.

About Canavan DiseaseAffecting approximately 1,000 children in the United States and European Union, Canavan disease is an ultra-rare, disabling and fatal disease with no approved therapy. Most children are not able to meet developmental milestones, are unable to crawl, walk, sit or talk, and pass away at a young age. The disease is caused by an inherited mutation of the ASPA gene, which codes for aspartoacylase, a protein that breaks down a compound called N-acetyl-L-aspartic acid (NAA). Deficiency of aspartoacylase activity results in accumulation of NAA, and ultimately results in toxicity to myelin in ways that are not well understood. Myelin insulates the nerves, and without it, neurons are unable to send and receive messages as they should. The current standard of care is limited to supportive therapy.

About BridgeBio Pharma, Inc.BridgeBio Pharma, Inc. (BridgeBio) is a commercial-stage biopharmaceutical company founded to discover, create, test and deliver transformative medicines to treat patients who suffer from genetic diseases and cancers with clear genetic drivers. BridgeBio's pipeline of over 30 development programs ranges from early science to advanced clinical trials, and its commercial organization is focused on delivering the company's first two approved therapies. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers, and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.comand follow us onLinkedInandTwitter.

BridgeBio Pharma, Inc. Forward-Looking StatementsThis press release contains forward-looking statements. Statements we make in this press release may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended (the "Securities Act"), and Section 21E of the Securities Exchange Act of 1934, as amended (the "Exchange Act"), which are usually identified by the use of words such as "anticipates," "believes," "estimates," "expects," "intends," "may," "plans," "projects," "seeks," "should," "will," and variations of such words or similar expressions. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements, including statements relating to the timing and success of BridgeBio's Phase 1/2 clinical trial of BBP-812 for the treatment of Canavan disease, expectations, plans and prospects regarding BridgeBio's regulatory approval process for BBP-812, the ability of BBP-812 to treat Canavan disease in humans, and the timing and success of initial top-line Phase 1/2 date of BBP-812, reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a number of risks, uncertainties and assumptions, including, but not limited to, BridgeBio's ability to continue and complete its Phase 1/2 clinical trial of BBP-812 for the treatment of Canavan disease, past data from preclinical studies not being indicative of future data from clinical trials, BridgeBio's ability to advance BBP-812 in clinical development according to its plans, the ability of BBP-812 to treat Canavan disease, the ability of BBP-812 to retain Fast Track Designation, Rare Pediatric Drug Designation, and Orphan Drug Designation from the U.S. Food and Drug Administration and Orphan Drug Designation from the European Medicines Agency, and potential adverse impacts due to the global COVID-19 pandemic such as delays in regulatory review, manufacturing and clinical trials, supply chain interruptions, adverse effects on healthcare systems and disruption of the global economy; as well as those set forth in the Risk Factors section of BridgeBio's most recent Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission (SEC) and in subsequent SEC filings, which are available on the SEC's website atwww.sec.gov.Moreover, BridgeBio operates in a very competitive and rapidly changing environment in which new risks emerge from time to time. Except as required by applicable law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

BridgeBio Media Contact: Grace Rauh[emailprotected](917) 232-5478

BridgeBio Investor Contact: Katherine Yau[emailprotected](516) 554-5989

SOURCE BridgeBio

https://bridgebio.com/

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BridgeBio Pharma Announces Dosing of First Patient in Phase 1/2 Trial of Investigational Gene Therapy for Canavan Disease - PRNewswire

Orchard Therapeutics Reports Third Quarter 2021 Financial Results and Highlights Recent Business Updates – BioSpace

Updates from OTL-201 Clinical Proof-of-Concept Study in MPS-IIIA and OTL-204 Preclinical Study for GRN-FTD at ESGCT Showcase Potential for HSC Gene Therapy in Multiple Neurodegenerative Disorders

Launch Activities for Libmeldy Across Key European Countries, including Reimbursement Discussions, Progressing in Anticipation of Treating Commercial Patients

Frank Thomas, President and Chief Operating Officer, to Step Down Following Transition in 2022; Search for a Chief Financial Officer Initiated

Cash and Investments of Approximately $254M Provide Runway into First Half 2023

BOSTONandLONDON, Nov. 04, 2021 (GLOBE NEWSWIRE) --Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today reported financial results for the quarter ended September 30, 2021, as well as recent business updates and upcoming milestones.

This quarter, we are pleased by the progress demonstrated by our investigational neurometabolic HSC gene therapy programs with promising preclinical and clinical updates at ESGCT, said Bobby Gaspar, M.D., Ph.D., chief executive officer of Orchard. With follow-up in OTL-201 for MPS-IIIA patients now ranging between 6 and 12 months, biomarker data remain highly encouraging, showing supraphysiological enzyme activity and corresponding substrate reductions in the CSF and urine. The launch strategy for Libmeldy is also advancing in Europe with momentum building on reimbursement discussions and patient finding activities.

Recent Presentations and Business Updates

Data presentations at ESGCT

Clinical and pre-clinical data from across the companys investigational hematopoietic stem cell (HSC) gene therapy portfolio were featured in two oral and seven poster presentations at the European Society of Gene & Cell Therapy Congress (ESGCT) on October 19-22. Highlights from key presentations are summarized below:

R&D Investor Event Summary

In September, Orchard hosted an R&D investor event highlighting its discovery and research engine in HSC gene therapy, including an update on the OTL-104 program in development for NOD2 Crohns disease (NOD2-CD) and potential new applications in HSC-generated antigen-specific regulatory T-cells (Tregs) and HSC-vectorization of monoclonal antibodies (mAbs).

The discussion also covered the differentiated profile of Orchards HSC gene therapy approach, which has exhibited favorable safety, long-term durability and broad treatment applicability.

Libmeldy (atidarsagene autotemcel) launch in Europe

Orchard is providing an update on the following key launch activities for Libmeldy in Europe:

Executive organizational update

The company also announced that Frank Thomas will step down from his role as president and chief operating officer, following a transition in 2022. A search for a chief financial officer is underway. Mr. Thomas other responsibilities will be assumed by existing members of the leadership team in commercial and corporate affairs. Orchard recently strengthened the executive team with the appointments of Nicoletta Loggia as chief technical officer and Fulvio Mavilio as chief scientific officer and the promotion of Leslie Meltzer to chief medical officer.

I want to extend my gratitude to Frank Thomas for his immense contributions to Orchard, said Gaspar. During his tenure, Frank oversaw the transition of the organization to a publicly traded company and has managed operations with a focus on cross-company innovation, including his role as a key architect in creating and executing the focused business plan we rolled out in 2020. Along with the entire board of directors and leadership team, I appreciate Franks commitment to facilitate a smooth transition during this time.

Gaspar continued, Our search is focused on a CFO to lead the broad strategic planning efforts necessary to capitalize on the full potential of our hematopoietic stem cell gene therapy platform.We have a strong team in place to aid Orchards success in this next phase of growth and are well capitalized through the anticipated completion of several value-creating milestones.

Upcoming Milestones

In June 2021, Orchard announced several portfolio updates following recent regulatory interactions for the companys investigational programs in metachromatic leukodystrophy (MLD), Mucopolysaccharidosis type I Hurler syndrome (MPS-IH) and Wiskott-Aldrich syndrome (WAS).

Third Quarter 2021 Financial Results

Revenue from product sales of Strimvelis were $0.7 million for the third quarter of 2021 compared to $2.0 million in the same period in 2020, and cost of product sales were $0.2 million for the third quarter of 2021 compared to $0.7 million in the same period in 2020. Collaboration revenue was $0.5 million for the third quarter of 2021, resulting from the collaboration with Pharming Group N.V. entered into in July 2021. This revenue represents expected reimbursements for preclinical studies and a portion of the $17.5 million upfront consideration received by Orchard under the collaboration, which will be amortized over the expected duration of the agreement.

Research and development (R&D) expenses were $20.8 million for the third quarter of 2021, compared to $14.7 million in the same period in 2020. The increase was primarily due to higher manufacturing and process development costs for the companys neurometabolic programs and lower R&D tax credits as compared to the same period in 2020. 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 development milestone payments under the companys agreements with third parties, and personnel costs to support these activities.

Selling, general and administrative (SG&A) expenses were $13.0 million for the third quarter of 2021, compared to $13.0 million in the same period in 2020. SG&A expenses are expected to increase in future periods as the company builds out its commercial infrastructure globally to support additional product launches following regulatory approvals.

Net loss was $36.4 million for the third quarter of 2021, compared to $20.3 million in the same period in 2020. The increase in net loss as compared to the prior year was primarily due to higher R&D expenses as well as the impact of foreign currency transaction gains and losses. The company had approximately 125.5 million ordinary shares outstanding as of September 30, 2021.

Cash, cash equivalents and investments as of September 30, 2021, were $254.1 million compared to $191.9 million as of December 31, 2020. The increase was primarily driven by net proceeds of $143.6 million from the February 2021 private placement and $17.5 million in upfront payments from the July 2021 collaboration with Pharming Group N.V., offset by cash used for operating activities and capital expenditures. The company expects that its cash, cash equivalents and investments as of September 30, 2021 will support its currently anticipated operating expenses and capital expenditure requirements into the first half of 2023. This cash runway excludes an additional $67 million that could become available under the companys credit facility and any non-dilutive capital received from potential future partnerships or priority review vouchers granted by the FDA following future U.S. approvals.

About Libmeldy / OTL-200

Libmeldy (atidarsagene autotemcel), also known as OTL-200, has been approved by the European Commission for the treatment of MLD in eligible early-onset patients characterized by biallelic mutations in the ARSA gene leading to a reduction of the ARSA enzymatic activity in children with i) late infantile or early juvenile forms, without clinical manifestations of the disease, or ii) the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline. Libmeldy is the first therapy approved for eligible patients with early-onset MLD.

The most common adverse reaction attributed to treatment with Libmeldy was the occurrence of anti-ARSA antibodies. In addition to the risks associated with the gene therapy, treatment with Libmeldy is preceded by other medical interventions, namely bone marrow harvest or peripheral blood mobilization and apheresis, followed by myeloablative conditioning, which carry their own risks. During the clinical studies, the safety profiles of these interventions were consistent with their known safety and tolerability.

For more information about Libmeldy, please see the Summary of Product Characteristics (SmPC) available on the EMA website.

Libmeldy is approved in the European Union, UK, Iceland, Liechtenstein and Norway. OTL-200 is an investigational therapy in the US.

Libmeldy was developed in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy.

About Orchard

At Orchard Therapeutics, our vision is to end the devastation caused by genetic and other severe diseases. We aim to do this by discovering, developing and commercializing new treatments that tap into the curative potential of hematopoietic stem cell (HSC) gene therapy. In this approach, a patients own blood stem cells are genetically modified outside of the body and then reinserted, with the goal of correcting the underlying cause of disease in a single treatment.

In 2018, the company acquired GSKs rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy. Today, Orchard has a deep pipeline spanning pre-clinical, clinical and commercial stage HSC gene therapies designed to address serious diseases where the burden is immense for patients, families and society and current treatment options are limited or do not exist.

Orchard has its global headquarters inLondonandU.S. headquarters inBoston. For more information, please visitwww.orchard-tx.com, and follow us onTwitterandLinkedIn.

Availability of Other Information About Orchard

Investors 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 (TwitterandLinkedIn), including but not limited to investor presentations and investor fact sheets,U.S. Securities and Exchange Commissionfilings, 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. Forward-looking statements include express or implied statements relating to, among other things, Orchards business strategy and goals, including its plans and expectations for the commercialization of Libmeldy, the therapeutic potential of Libmeldy (OTL-200) and Orchards product candidates, including the product candidates referred to in this release, Orchards expectations regarding its ongoing preclinical and clinical trials, including the timing of enrollment for clinical trials and release of additional preclinical and clinical data, the likelihood that data from clinical trials will be positive and support further clinical development and regulatory approval of Orchard's product candidates, and Orchards financial condition and cash runway into the first half of 2023. 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, these risks and uncertainties include, without limitation: the risk that prior results, such as signals of safety, activity or durability of effect, observed from clinical trials of Libmeldy will not continue or be repeated in our ongoing or planned clinical trials of Libmeldy, will be insufficient to support regulatory submissions or marketing approval in the US or to maintain marketing approval in the EU, or that long-term adverse safety findings may be discovered; the risk that any one or more of Orchards product candidates, including the product 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 Orchard may not successfully recruit or enroll a sufficient number of patients for its 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 or the receipt of restricted marketing approvals; the inability or risk of delays in Orchards ability to commercialize its product candidates, if approved, or Libmeldy, including the risk that Orchard may not secure adequate pricing or reimbursement to support continued development or commercialization of Libmeldy; the risk that the market opportunity for Libmeldy, or any of Orchards product candidates, may be lower than estimated; and the severity of the impact of the COVID-19 pandemic on Orchards business, including on clinical development, its supply chain and commercial programs. 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 quarterly report on Form 10-Q for the quarter endedSeptember 30, 2021, as filed with theU.S. Securities and Exchange Commission(SEC), as well as subsequent filings and reports filed with theSEC. 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.

Contacts

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

MediaBenjamin NavonDirector, Corporate Communications+1 857-248-9454Benjamin.Navon@orchard-tx.com

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Orchard Therapeutics Reports Third Quarter 2021 Financial Results and Highlights Recent Business Updates - BioSpace

Aruvant Announces ARU-1801 Data to be Presented at the 63rd American Society of Hematology (ASH) Annual Meeting – PRNewswire

NEW YORK and BASEL, Switzerland, Nov. 4, 2021 /PRNewswire/ --Aruvant Sciences ("Aruvant"), a private company focused on developing gene therapies for rare diseases, announced that an abstract demonstrating the clinical benefit of the company's lead product candidate ARU-1801 has been published online and will be the subject of a poster presentation at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition. The meeting will take place in Atlanta, Georgia fromDecember 11 to 14, 2021.Punam Malik, M.D., Director of the Cincinnati Comprehensive Sickle Cell Center and Program Leader of the Hematology and Gene Therapy Program at the Cincinnati Children's Hospital Medical Center, will present the data at6:00 to 8:00 PM ESTonDecember 13, 2021.

"Clinical data from our ongoing MOMENTUM study has shown 100 percent resolution of vaso-oclusive events (VOE) in our recently treated SCD patients at 18 and 12 months of follow up," said Will Chou, MD, Aruvant chief executive officer. "In addition, we are excited to be sharing additional clinical data at ASH that demonstrates how the unique anti-sickling potency of ARU-1801 translates to these robust clinical outcomes."

Dr. Malik will present data from theongoing MOMENTUM study, an open label Phase 1/2 clinical trial examining ARU-1801 as a one-time potentially curative gene therapy for individuals with sickle cell disease (SCD). The MOMENTUM study examines ARU-1801, an autologous lentiviral cell therapy with a modified, highly potent gamma globin payload, in individuals with severe SCD. Unlike investigational gene therapies that require fully myeloablative conditioning, ARU-1801 is given with reduced intensity conditioning (RIC), which is a lower dose chemotherapy. ARU-1801 is designed to address the limitations of current curative allogeneic transplant options, such as low donor availability, the risk of graft-versus-host disease and toxicity from myeloablative chemotherapy. The data to be presented at ASH highlights clinically meaningfulreduction in participants' VOEs and the unique attributes that contribute to the potency of ARU-1801.

"The emerging clinical data shows that ARU-1801 holds promise for achieving durable responses in patients with severe SCD using only reduced intensity conditioninga key differentiator from other investigational gene therapy regimens," said Dr. Malik. "Given the advantage for patients, providers and payers a reduced conditioning regimen offers, ARU-1801 has the potential to be an important option for SCD patients seeking gene therapy, including those in low resource settings."

Abstract and Poster Presentation Information

Title: Safety and Efficacy of ARU-1801 in Patients with Sickle Cell Disease: Early Results from the Phase 1/2 MOMENTUM Study of a Modified Gamma Globin Gene Therapy and Reduced Intensity Conditioning

Publication Number: 3970Session Name: 801. Gene Therapies: Poster IIIDate:Monday, December 13, 2021Presentation Time:6:00 to 8:00 PM ESTLocation: Georgia World Congress Center, Hall B5 or online through the ASHwebsite.

About Aruvant SciencesAruvant Sciences, part of the Roivant family of companies, is a clinical-stage biopharmaceutical company focused on developing and commercializing gene therapies for the treatment of rare diseases. The company has a talentedteamwith extensive experience in the development, manufacturing and commercialization of gene therapy products. Aruvant has an activeresearchprogram with a lead product candidate, ARU-1801, in development for individuals suffering fromSCD. ARU-1801, an investigational lentiviral gene therapy, is being studied in aPhase 1/2 clinical trial,the MOMENTUM study, as a one-time potentially curative treatment for SCD. Preliminary clinical data demonstrate engraftment of ARU-1801 and amelioration of SCD is possible with one dose of reduced intensity chemotherapy. The company's second product candidate, ARU-2801, is in development to cure hypophosphatasia, a devastating, ultra-orphan disorder that affects multiple organ systems and leads to high morbidity and mortality when not treated. Data from pre-clinical studies with ARU-2801 shows durable improvement in disease biomarkers and increased survival. For more information on the ongoing ARU-1801 clinical study, please visit http://www.momentumtrials.com,and for more on the company, pleasevisitwww.aruvant.com. Follow Aruvant on Facebook, Twitter @AruvantSciencesand on Instagram @Aruvant_Sciences.

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Sangamo Therapeutics Reports Recent Business and Clinical Highlights and Third Quarter 2021 Financial Results – BioSpace

BRISBANE, Calif.--(BUSINESS WIRE)-- Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, today reported third quarter financial results and provided business and clinical highlights.

We are delighted to share clinical data and business updates across several programs demonstrating that Sangamo has three important assets progressing toward late-stage development. Our gene therapy portfolio is advancing with accumulating safety and efficacy data in our Fabry and hemophilia A programs, and preliminary proof-of-concept data demonstrate the clinical potential of our zinc finger genome engineering technology in sickle cell disease. These data readouts show the progression of our first-generation genomic medicine pipeline and potentially pave the way for new treatments. Our next generation programs focus on genome regulation and allogeneic CAR-Treg cell therapy, where we have a robust preclinical pipeline in neurological and autoimmune diseases. We are energized by this momentum and look forward to continued execution of our corporate strategy, said Sandy Macrae, Chief Executive Officer of Sangamo.

Recent Clinical and Business Highlights

Fabry Disease First four patients dosed exhibited above normal -Gal A activity; Phase 3 planning initiated

Sickle Cell Disease Preliminary-proof-of-concept data will be presented at ASH as clinical program advances

Hemophilia A Four patients at highest dose experienced mean FVIII activity of 30.9% at week 104

Renal Transplant First patient enrolled, expect two patients to be dosed by mid-2022

Research, Manufacturing, and Corporate Updates

Third Quarter 2021 Financial Results

Consolidated net loss attributable to Sangamo for the third quarter ended September 30, 2021 was $47.7 million, or $0.33 per share, compared to a net loss attributable to Sangamo of $1.6 million, or $0.01 per share, for the same period in 2020.

Revenues

Revenues for the third quarter ended September 30, 2021, were $28.6 million, compared to $57.8 million for the same period in 2020, a decrease of $29.2 million.

The reduction in revenue was primarily due to a $39.3 million decrease related to our giroctocogene fitelparvovec and C9ORF72 collaboration agreements with Pfizer, resulting from the completion of our activities in 2020, and a $2.3 million decrease related to our collaboration agreement with Sanofi. These decreases were partially offset by higher revenues of $11.5 million and $1.3 million related to our collaboration agreements with Novartis and Biogen, respectively.

GAAP and Non-GAAP operating expenses

2021

2020

2021

2020

$

62.5

$

45.3

$

179.0

$

128.3

14.5

16.2

47.1

50.2

77.0

61.5

226.1

178.5

(7.9

)

(6.7

)

(24.9

)

(19.1

)

$

69.1

$

54.8

$

201.2

$

159.4

Total operating expenses on a GAAP basis for the third quarter ended September 30, 2021 were $77.0 million compared to $61.5 million for the same period in 2020. Non-GAAP operating expenses, which exclude stock-based compensation expense, for the third quarter ended September 30, 2021 were $69.1 million compared to $54.8 million for the same period in 2020.

The increase in total operating expenses on a GAAP basis was primarily driven by our higher clinical and manufacturing supply expenses along with our increased headcount to support the advancement of our clinical trials and our ongoing collaborations.

Cash, cash equivalents and marketable securities

Cash, cash equivalents and marketable securities as of September 30, 2021 were $519.0 million compared to $692.0 million as of December 31, 2020.

Revised Financial Guidance for 2021

We are revising our full-year operating expense guidance initially provided on February 24, 2021 and reiterated most recently on August 5, 2021 as follows:

$285 to $305

$300 to $310

$255 to $275*

$265 to $275**

Conference Call

Sangamo will host a conference call today, November 4, 2021, at 9:15 a.m. Eastern Time, which will be open to the public. The call and live Q&A will be webcast.

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 5178059. Participants may access the live webcast via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations. Call replay will be available for one week following the conference call. 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 5178059.

About Sangamo Therapeutics

Sangamo Therapeutics is a clinical-stage biopharmaceutical company with a robust genomic medicines pipeline. Using ground-breaking science, including our proprietary zinc finger genome engineering technology and manufacturing expertise, Sangamo aims to create new genomic medicines for patients suffering from diseases for which existing treatment options are inadequate or currently dont exist. For more information about Sangamo, visit http://www.sangamo.com.

Forward-Looking Statements

This press release contains forward-looking statements regarding our current expectations. These forward-looking statements include, without limitation, statements relating to the therapeutic and commercial potential of our product candidates, the anticipated plans and timelines of Sangamo and our collaborators for screening, enrolling and dosing patients in and conducting our ongoing and potential future clinical trials and presenting clinical data from our clinical trials, the anticipated advancement of our product candidates to late-stage development including potential future Phase 3 trials, anticipated implementation of a protocol amendment for the Phase 3 AFFINE clinical trial of giroctocogene fitelparvovec and the resumption of the dosing of additional patients in the trial; our revised 2021 financial guidance related to GAAP and non-GAAP total operating expenses and stock-based compensation; our continued execution of our corporate strategy; the anticipated completion of our in-house cell therapy manufacturing facility in Valbonne, France; and other statements that are not historical fact. These statements are not guarantees of future performance and are subject to certain risks and uncertainties 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 effects of the evolving COVID-19 pandemic and the impacts of the pandemic on the global business environment, healthcare systems and business and operations of Sangamo and our collaborators, including the initiation and operation of clinical trials; the research and development process, including the enrollment, operation and results of clinical trials and the presentation of clinical data; the uncertain timing and unpredictable nature of clinical trials and clinical trial results, including the risk that any protocol amendment for the Phase 3 AFFINE trial of giroctocogene fitelparvovec may not be accepted by the relevant review bodies in a timely manner, or at all, or that the FDA may not lift its clinical hold on the Phase 3 AFFINE trial in a timely manner, or at all, each of which could further delay or preclude further patient dosing in the trial as well as the risks that therapeutic effects observed in clinical trial results will not be durable in patients and that final clinical trial data will not validate the safety and efficacy of our product candidates; reliance on results of early clinical trials, which results are not necessarily predictive of future clinical trial results; our limited experience manufacturing biopharmaceutical products, including the risks that we may be unable to maintain compliant manufacturing facilities, build additional facilities and manufacture our product candidates as intended; and our ability to achieve expected future financial performance.

There can be no assurance that we and our collaborators will be able to develop commercially viable products. Actual results may differ materially from those projected in these forward-looking statements due to the risks and uncertainties described above and other risks and uncertainties that exist in the operations and business environments of Sangamo and our collaborators. These risks and uncertainties are described more fully in our Securities and Exchange Commission filings and reports, including in our Annual Report on Form 10-K for the year ended December 31, 2020 as supplemented by our Quarterly Report on Form 10-Q for the quarter ended September 30, 2021. Forward-looking statements contained in this announcement are made as of this date, and we undertake no duty to update such information except as required under applicable law.

Non-GAAP Financial Measure

To supplement our financial results and guidance presented in accordance with GAAP, we present non-GAAP total operating expenses, which exclude stock-based compensation expense from GAAP total operating expenses. We believe that this non-GAAP financial measure, when considered together with our financial information prepared in accordance with GAAP, can enhance investors and analysts ability to meaningfully compare our results from period to period and to our forward-looking guidance, and to identify operating trends in our business. We have excluded stock-based compensation expense because it is a non-cash expense that may vary significantly from period to period as a result of changes not directly or immediately related to the operational performance for the periods presented. This non-GAAP financial measure is in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. We encourage investors to carefully consider our results under GAAP, as well as our supplemental non-GAAP financial information, to more fully understand our business.

2021

2020

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Oncternal Therapeutics Announces Formation of Cell Therapy – GlobeNewswire

SAN DIEGO, Nov. 02, 2021 (GLOBE NEWSWIRE) -- Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, today announced the establishment of its Cell Therapy Scientific Advisory Board (SAB). The Cell Therapy SAB is comprised of industry and academic leaders in the cell therapy field, covering important areas of expertise including cutting edge research, preclinical development, manufacturing, and clinical development.

The Cell Therapy SAB will play an important role in advising and guiding the companys efforts to develop safe and effective cell therapies targeting receptor-tyrosine kinase-like Orphan Receptor 1 (ROR1), leveraging our deep expertise on ROR1 and the single chain variable fragment (scFv) of our ROR1 antibodies, including cirmtuzumab. ROR1 is highly expressed by many solid tumors as well as hematological malignancies and confers both an aggressive phenotype and survival advantage to the tumor cells. Cirmtuzumab binding to ROR1 on leukemia and lymphoma cells decreases tumor cell proliferation and survival by blocking Wnt5a-induced activation, while it does not bind to normal adult tissues. Cirmtuzumab has also demonstrated encouraging safety and efficacy results in its ongoing Phase 1/2 study in combination with ibrutinib for the treatment of patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) as well as in a Phase 1b study in combination with paclitaxel for the treatment of patients with Her2-negative breast cancer.

We are pleased to welcome our newly appointed scientific advisors, whose deep expertise in cell therapy research and development will help us bring safe and effective ROR1 targeted cell therapies to patients faster, said James Breitmeyer, M.D., Ph.D., Oncternals President and CEO. We believe that ROR1 is an ideal target for next generation cell therapies due to its proven role in tumor progression and its wide expression in many cancer types with significant unmet needs.

The members of the Oncternal Cell Therapy SAB include:

Michael Wang, MD, Endowed Professor in the department of Lymphoma & Myeloma at MD AndersonDr. Wang has published more than 200 peer-reviewed papers and has presented his work at meetings nationally and internationally. He is the Director of the Mantle Cell Lymphoma (MCL) Program of Excellence and Co-Director of the B-Cell Lymphoma Moon Shot Program at the University of Texas MD Anderson Cancer Center. The Wang Laboratory at MD Anderson research program aims to elucidate the mechanisms underlying therapeutic resistance in B-cell lymphoma and to translate these findings to the clinic to improve patient outcomes. Dr. Wang obtained his M.D. from Shandong Medical University and M.S. from Beijing University Medical School, and completed his clinical training as a resident at Norwalk Hospital,Norwalk, Conn., and as a Fellow in Oncology and in Hematology at MD Anderson.

Angela Shen, MD, MBA, Clinical and Translational Market Sector Leader Mass General BrighamDr. Shen has unique, deep knowledge of the cell and gene therapy landscape having provided clinical, regulatory, and strategic leadership for autologous and allogeneic CAR-T cell therapies, NK cell therapies, and other novel cell therapy programs across industry. Dr. Shen currently hold a position at Mass General Brigham (formerly known as Partners HealthCare), an affiliate of Harvard Medical School and serves a part-time CMO at Walking Fish Therapeutics, Inc. Previously, she held Chief Medical Officer (CMO) positions at multiple biotech companies, including Arcellx, NKarta, Arvinas, and acting CMO of Tizona. Dr. Shen led the clinical team at Novartis responsible for designing and launching the industrys first multi-site, registration CAR-T cell therapy trial supporting the approval of Kymriah (CTL019, CART-19). She received a BS through Rensselaers accelerated biomedical program, and holds an MD from Albany Medical College in New York and MBA from New York University Stern School of Business.

Marcela V. Maus, MD, PhD, Associate Professor, Medicine, Harvard Medical School, Director of Cellular Immunotherapy, Cancer Center, Massachusetts General HospitalDr. Maus is a translational physician-scientist in the field of cancer immunology. Her laboratory focuses on the design, generation, and use of innovative forms of immune cell engineering, including chimeric antigen receptors and investigates basic mechanisms of human immunology to design and test novel immune-based therapeutic interventions in vitro, in mouse models, and in patients. Dr. Maus received her S.B. from the Massachusetts Institute of Technology, and her M.D. and Ph.D. degrees from the University of Pennsylvania. Dr. Maus trained in internal medicine at University of Pennsylvania and in hematology and medical oncology at Memorial Sloan Kettering, and is board-certified in these three disciplines. Her laboratory research training was focused on gene and cell therapies, and occurred in the laboratories of Dr. Katherine High, Dr. Michel Sadelain, and Dr. Carl June.

Sadik Kassim, PhD, Chief Technology Officer at Vor BiopharmaDr. Kassim is a cell and gene therapy bioprocessing and translational research expert. Dr. Kassim served as Executive Director at Kite Pharma where he led the development of manufacturing processes for autologous CAR-T and TCR-based cell therapies. He and his team at Kite led the BLA and MAA filing efforts for Kites X-19 product, which is a CD19 CAR-T therapy for Mantle Cell Lymphoma. Before Kite, Dr. Kassim served as Chief Scientific Officer at Mustang Bio, where he was the first employee and oversaw the foundational build-out of the companys preclinical and manufacturing activities. Earlier in his career, Dr. Kassim was Head of Early Analytical Development for Novartis Cell and Gene Therapies Unit, where he and his team contributed to the BLA and MAA filings for Kymriah. Dr. Kassim earned his BS in cell and molecular biology from Tulane University and received his PhD in microbiology and immunology from Louisiana State University. After receiving his PhD, he was a research fellow in the lab of Dr. James Wilson at the University of Pennsylvanias Gene Therapy Program.

About Oncternal Therapeutics

Oncternal Therapeutics is a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies for the treatment of cancers with critical unmet medical need. Oncternal focuses drug development on promising yet untapped biological pathways implicated in cancer generation or progression. The clinical pipeline includes cirmtuzumab, an investigational monoclonal antibody designed to inhibit the ROR1 pathway, a type I tyrosine kinase-like orphan receptor, that is being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) and in an investigator-sponsored, Phase 1b clinical trial in combination with paclitaxel for the treatment of women with HER2-negative metastatic or locally advanced, unresectable breast cancer, as well as a Phase 2 clinical trial of cirmtuzumab in combination with venetoclax, a Bcl-2 inhibitor, in patients with relapsed/refractory CLL. Oncternal is also developing a chimeric antigen receptor T cell (CAR-T) therapy that targets ROR1, which is currently in preclinical development as a potential treatment for hematologic cancers and solid tumors. The clinical pipeline also includes TK216, an investigational targeted small-molecule inhibitor of the ETS family of oncoproteins, that is being evaluated in a Phase 1/2 clinical trial for patients with Ewing sarcoma alone and in combination with vincristine chemotherapy. More information is available at https://oncternal.com.

Contact Information:

InvestorsRichard VincentChief Financial Officer858-434-1113rvincent@oncternal.com

MediaCorey DavisLifeSci Advisors212-915-2577cdavis@lifesciadvisors.com

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Oncternal Therapeutics Announces Formation of Cell Therapy - GlobeNewswire

Study links gene to cognitive resilience in the elderly – MIT News

Many people develop Alzheimers or other forms of dementia as they get older. However, others remain sharp well into old age, even if their brains show underlying signs of neurodegeneration.

Among these cognitively resilient people, researchers have identified education level and amount of time spent on intellectually stimulating activities as factors that help prevent dementia. A new study by MIT researchers shows that this kind of enrichment appears to activate a gene family called MEF2, which controls a genetic program in the brain that promotes resistance to cognitive decline.

The researchers observed this link between MEF2 and cognitive resilience in both humans and mice. The findings suggest that enhancing the activity of MEF2 or its targets might protect against age-related dementia.

Its increasingly understood that there are resilience factors that can protect the function of the brain, says Li-Huei Tsai, director of MITs Picower Institute for Learning and Memory. Understanding this resilience mechanism could be helpful when we think about therapeutic interventions or prevention of cognitive decline and neurodegeneration-associated dementia.

Tsai is the senior author of the study, which appears today in Science Translational Medicine. The lead authors are recent MIT PhD recipient Scarlett Barker and MIT postdoctoral fellow and Boston Childrens Hospital physician Ravikiran (Ravi) Raju.

Protective effects

A large body of research suggests that environmental stimulation offers some protection against the effects of neurodegeneration. Studies have linked education level, type of job, number of languages spoken, and amount of time spent on activities such as reading and doing crossword puzzles to higher degrees of cognitive resilience.

The MIT team set out to try to figure how these environmental factors affect the brain at the neuronal level. They looked at human datasets and mouse models in parallel, and both tracks converged on MEF2 as a critical player.

MEF2 is a transcription factor that was originally identified as a factor important for cardiac muscle development, but later was discovered to play a role in neuron function and neurodevelopment. In two human datasets comprising slightly more than 1,000 people all together, the MIT team found that cognitive resilience was highly correlated with expression of MEF2 and many of the genes that it regulates.

Many of those genes encode ion channels, which control a neurons excitability, or how easily it fires an electrical impulse. The researchers also found, from a single-cell RNA-sequencing study of human brain cells, that MEF2 appears to be most active in a subpopulation of excitatory neurons in the prefrontal cortex of resilient individuals.

To study cognitive resilience in mice, the researchers compared mice who were raised in cages with no toys, and mice placed in a more stimulating environment with a running wheel and toys that were swapped out every few days. As they found in the human study, MEF2 was more active in the brains of the mice exposed to the enriched environment. These mice also performed better in learning and memory tasks.

When the researchers knocked out the gene for MEF2 in the frontal cortex, this blocked the mices ability to benefit from being raised in the enriched environment, and their neurons became abnormally excitable.

This was particularly exciting as it suggested that MEF2 plays a role in determining overall cognitive potential in response to variables in the environment, Raju says.

The researchers then explored whether MEF2 could reverse some of the symptoms of cognitive impairment in a mouse model that expresses a version of the tau protein that can form tangles in the brain and is linked with dementia. If these mice were engineered to overexpress MEF2 at a young age, they did not show the usual cognitive impairments produced by the tau protein later in life. In these mice, neurons overexpressing MEF2 were less excitable.

A lot of human studies and mouse model studies of neurodegeneration have shown that the neurons become hyperexcitable in early stages of disease progression, Raju says. When we overexpressed MEF2 in a mouse model of neurodegeneration, we saw that it was able to prevent this hyperexcitability, which might explain why they performed cognitively better than control mice.

Enhancing resilience

The findings suggest that enhancing MEF2 activity could help to protect against dementia; however, because MEF2 also affects other types of cells and cellular processes, more study is needed to make sure that activating it wouldnt have adverse side effects, the researchers say.

The MIT team now hopes to further investigate how MEF2 becomes activated by exposure to an enriching environment. They also plan to examine some of the effects of the other genes that MEF2 controls, beyond the ion channels they explored in this study. Such studies could help to reveal additional targets for drug treatments.

You could potentially imagine a more targeted therapy by identifying a subset or a class of effectors that is critically important for inducing resilience and neuroprotection, Raju says.

The research was funded by the Glenn Center for Biology of Aging Research, the National Institute of Aging, the Cure Alzheimers Fund, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

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Vitamin D and mortality risk: Is there a causal link? – Medical News Today

Vitamin D is an essential nutrient thought to reduce the risk of chronic diseases, including cancer and cardiovascular disease. Observational studies have consistently found that vitamin D deficiency increases the risk of developing these conditions and of death from any cause.

Scientists do not know how exactly vitamin D levels might influence multiple health conditions. Some have suggested it may protect against cancer by regulating cadherins, which are proteins involved in cell-cell adhesion responsible for maintaining tissue architecture and regulation of cell growth and differentiation.

Despite this, several large randomized trials have not been able to find evidence that vitamin D supplementation for vitamin D deficiency has any benefit for cancer or cardiovascular disease.

This has made researchers question whether vitamin D levels really play a part in reducing the risk of these diseases or whether healthier people have naturally higher levels of the vitamin for other reasons.

Researchers led by the University of Cambridge in the United Kingdom conducted a study to see whether inherited genetic variants predisposing people to have higher vitamin D levels play a role in overall health.

Our investigation provides intriguing new evidence that suggests raising vitamin D levels may reduce the risk of major disease and mortality, but only for people who have low vitamin D levels, says Dr. Stephen Burgess, lead author of the study.

Maintaining adequate levels of vitamin D is important, but there appears to be no benefit in supplementation beyond a threshold level, he adds.

The study appears inThe Lancet Diabetes & Endocrinology.

The researchers initially gathered data from the UK Biobank, the European Prospective Investigation into Cancer and Nutrition Cardiovascular Disease study, and 31 studies from the Vitamin D Studies Collaboration.

Altogether, they analyzed health data from 386,406 middle-aged individuals with European ancestry. Each was followed for an average of 9.5 years, underwent 25-hydroxyvitamin D (25(OH)D) measurements, and did not have cardiovascular disease at baseline.

25(OH)D is the major circulating form of vitamin D in the body. It is measured via blood test to indicate vitamin D supply in the body from sunlight and nutrition.

Over the study period, 33,546 people developed coronary heart disease, 18,166 people had a stroke, and 27, 885 people died.

To understand the role of vitamin D levels in these health outcomes, the researchers investigated the participants inherited genetic variants predisposing them to higher vitamin D levels and analyzed their 25(OH)D measurements.

Similarly to authors of other studies, they found no link between genetic predisposition to higher vitamin D levels and coronary heart disease, stroke, or death.

However, among those with vitamin D deficiency, defined as lower than 25 nanomoles per liter (nmol/l), the researchers identified a strong link between genetic predisposition to higher vitamin D levels and a lower mortality risk.

They also found a link between a genetic predisposition to 10 nmol/l higher levels of 25(OH)D and a 30% lower all-cause mortality risk. Their analyses suggested similar effects on cardiovascular and cancer mortality.

These effects, however, were only evident in individuals with extremely low vitamin D levels, or those below 40 nmol/l.

Previous [] studies assumed a linear association between genetically predicted 25(OH)D, the main marker of vitamin D status, and cardiovascular disease, despite the evidence from cohort studies of observed 25(OH)D having a nonlinear association with cardiovascular disease, Prof. Robert Scragg, head of the School of Population Health at the University of Auckland in New Zealand, who was not involved in the study, told Medical News Today.

However, the current study [] shows a nonlinear association for genetically predicted 25(OH)D [and cardiovascular disease]. [] To my knowledge, this is the first study to do this type of analysis to see if the association is nonlinear. Interestingly, the study also shows no association when you combine all participants, which is what previous [] studies reported. The key difference is the stratification by baseline 25(OH)D level.

The fact that the beneficial effect is mainly in people with 25(OH)D levels below 25 nmol/l explains why the recent clinical trials observed null results as they did not have enough participants with very low 25(OH)D levels. In the ViDA study, we only had 91, while the VITAL study has been estimated to have had only about 500 not enough to show any effect.

The researchers highlight several potential mechanisms underlying the effects of vitamin D.

For example, animal studies have shown that vitamin D could regulate cardiac function due to its action on cardiac metalloproteinases, a group of enzymes that break down proteins, and fibroblasts, which are the most common type of cell in connective tissue.

Vitamin D also plays a role in endothelial cell function. These cells form the lining of blood vessels and regulate exchanges between blood and surrounding tissues. Via its effects on endothelial cells, vitamin D modulates:

The researchers add that vitamin D status also affects gene expression related to cell division and programed cell death, which could affect the growth of neoplasms that is, excessive growth and division of cells as well as DNA repair and immunomodulation in cancer.

The authors of the study conclude that genetic evidence suggests a causal relationship between 25(OH)D concentrations and mortality in people with low vitamin D levels.

However, they note some limitations to their results. For instance, they highlight that their analysis only included middle-aged individuals with European ancestry, meaning their results may not apply to people with different skin tones. Further analysis is needed, as people with dark skin often have lower vitamin D levels.

This study has addressed an important question of whether taking vitamin D will have an impact on reducing the risk of chronic diseases, such as cardiovascular diseases and cancer, Prof. Vimal Karani, professor in nutrigenetics and nutrigenomics at the University of Reading in the U.K., who was not involved in the study, told MNT. However, the findings can be generalized only to the European populations, given that the study has focused on participants of European ancestries.

Moreover, the effect has been observed only in those who have low vitamin D concentrations, which could be partly attributed to the choice of genetic instrument. [] The genetic risk score was generated using 21 genetic variants from four different gene regions, of which two genes are involved in the synthesis of [25(OH)D], and the other two are involved in the metabolism of vitamin D, he added.

Previous studies have shown that the variation in [25(OH)D] concentrations explained by synthesis genes is lesser than the variation explained by the metabolism genes. Even though the authors had performed a sensitivity analysis to see if the results were driven by a single gene region, the study did not look at the individual impact of synthesis and metabolism genetic risk scores, respectively, on the risk of major disease and mortality, and this might partly explain the effects seen only in those who have low vitamin D levels, he explained.

However, given that nearly 40% of Europeans are vitamin D deficient, and 13% are severely deficient, this study has significant public health implications in suggesting the need for taking vitamin D supplementation to overcome the risk of chronic diseases.

Prof. Vimal Karani

This study will rekindle the debate about vitamin D and cardiovascular disease, said Prof. Scragg. I think most researchers thought the matter was resolved after the findings of null results from two clinical trials of vitamin D supplementation the VITAL study from the [United States] and the ViDA study from New Zealand particularly in the light of previous [] studies, which showed no association between genetic markers of vitamin D status and cardiovascular disease.

Given that there is only a moderate beneficial effect in a small proportion of participants in the current study, it would take a huge clinical trial to [make similar observations for] vitamin D supplementation. I dont think a further clinical trial now will ever be done, particularly since participants in a trial can always purchase their own vitamin D if they believe they have been allocated to the placebo group, and thus weaken any effect from vitamin D, he explained.

Consequently, this study is likely to provide the strongest and most definitive evidence on whether vitamin D protects against cardiovascular disease and all-cause mortality, he concluded.

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Vitamin D and mortality risk: Is there a causal link? - Medical News Today

MIT Researchers Discover Gene Linked to Cognitive Resilience in the Elderly – SciTechDaily

MIT researchers have discovered a gene linked to cognitive resilience in the elderly. Environmental enrichment, they find, appears to activate the MEF2 protein, which controls a genetic program in the brain that promotes resilience to declines related to Alzheimers and age-related dementia. Credit: MIT News, iStockphoto

The findings may help explain why some people who lead enriching lives are less prone to Alzheimers and age-related dementia.

Many people develop Alzheimers or other forms of dementia as they get older. However, others remain sharp well into old age, even if their brains show underlying signs of neurodegeneration.

Among these cognitively resilient people, researchers have identified education level and amount of time spent on intellectually stimulating activities as factors that help prevent dementia. A new study by MIT researchers shows that this kind of enrichment appears to activate a gene family called MEF2, which controls a genetic program in the brain that promotes resistance to cognitive decline.

The researchers observed this link between MEF2 and cognitive resilience in both humans and mice. The findings suggest that enhancing the activity of MEF2 or its targets might protect against age-related dementia.

Its increasingly understood that there are resilience factors that can protect the function of the brain, says Li-Huei Tsai, director of MITs Picower Institute for Learning and Memory. Understanding this resilience mechanism could be helpful when we think about therapeutic interventions or prevention of cognitive decline and neurodegeneration-associated dementia.

Tsai is the senior author of the study, which was published on November 3, 2021, in Science Translational Medicine. The lead authors are recent MIT PhD recipient Scarlett Barker and MIT postdoctoral fellow and Boston Childrens Hospital physician Ravikiran (Ravi) Raju.

A large body of research suggests that environmental stimulation offers some protection against the effects of neurodegeneration. Studies have linked education level, type of job, number of languages spoken, and amount of time spent on activities such as reading and doing crossword puzzles to higher degrees of cognitive resilience.

The MIT team set out to try to figure how these environmental factors affect the brain at the neuronal level. They looked at human datasets and mouse models in parallel, and both tracks converged on MEF2 as a critical player.

MEF2 is a transcription factor that was originally identified as a factor important for cardiac muscle development, but later was discovered to play a role in neuron function and neurodevelopment. In two human datasets comprising slightly more than 1,000 people all together, the MIT team found that cognitive resilience was highly correlated with expression of MEF2 and many of the genes that it regulates.

Many of those genes encode ion channels, which control a neurons excitability, or how easily it fires an electrical impulse. The researchers also found, from a single-cell RNA-sequencing study of human brain cells, that MEF2 appears to be most active in a subpopulation of excitatory neurons in the prefrontal cortex of resilient individuals.

To study cognitive resilience in mice, the researchers compared mice who were raised in cages with no toys, and mice placed in a more stimulating environment with a running wheel and toys that were swapped out every few days. As they found in the human study, MEF2 was more active in the brains of the mice exposed to the enriched environment. These mice also performed better in learning and memory tasks.

When the researchers knocked out the gene for MEF2 in the frontal cortex, this blocked the mices ability to benefit from being raised in the enriched environment, and their neurons became abnormally excitable.

This was particularly exciting as it suggested that MEF2 plays a role in determining overall cognitive potential in response to variables in the environment, Raju says.

The researchers then explored whether MEF2 could reverse some of the symptoms of cognitive impairment in a mouse model that expresses a version of the tau protein that can form tangles in the brain and is linked with dementia. If these mice were engineered to overexpress MEF2 at a young age, they did not show the usual cognitive impairments produced by the tau protein later in life. In these mice, neurons overexpressing MEF2 were less excitable.

A lot of human studies and mouse model studies of neurodegeneration have shown that the neurons become hyperexcitable in early stages of disease progression, Raju says. When we overexpressed MEF2 in a mouse model of neurodegeneration, we saw that it was able to prevent this hyperexcitability, which might explain why they performed cognitively better than control mice.

The findings suggest that enhancing MEF2 activity could help to protect against dementia; however, because MEF2 also affects other types of cells and cellular processes, more study is needed to make sure that activating it wouldnt have adverse side effects, the researchers say.

The MIT team now hopes to further investigate how MEF2 becomes activated by exposure to an enriching environment. They also plan to examine some of the effects of the other genes that MEF2 controls, beyond the ion channels they explored in this study. Such studies could help to reveal additional targets for drug treatments.

You could potentially imagine a more targeted therapy by identifying a subset or a class of effectors that is critically important for inducing resilience and neuroprotection, Raju says.

Reference: MEF2 is a key regulator of cognitive potential and confers resilience to neurodegeneration by Scarlett J. Barker, Ravikiran M. Raju, Noah E.P. Milman, Jun Wang, Jose Davila-Velderrain, Fatima Gunter-Rahman, Cameron C. Parro, P. Lorenzo Bozzelli, Fatema Abdurrob, Karim Abdelaal, David A. Bennett, Manolis Kellis and Li-Huei Tsai, 3 November 2021, Science Translational Medicine.DOI: 10.1126/scitranslmed.abd7695

The research was funded by the Glenn Center for Biology of Aging Research, the National Institute of Aging, the Cure Alzheimers Fund, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

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MIT Researchers Discover Gene Linked to Cognitive Resilience in the Elderly - SciTechDaily

Elizabeth M. McNally, M.D., Ph.D., FAHA, named the American Heart Association’s 2021 Distinguished Scientist in Basic Cardiovascular Sciences -…

Embargoed until 7 a.m. CT / 8 a.m. ET Wednesday, Nov. 3, 2021

DALLAS, Nov. 3, 2021 The American Heart Association will present its 2021 Distinguished Scientist in Basic Cardiovascular Sciences to Northwestern Universitys Elizabeth M. McNally, M.D., Ph.D., FAHA. The Association designates Distinguished Scientist awards in several categories to members who have significantly advanced the understanding of cardiovascular, stroke or brain health. The six 2021 Distinguished Scientist awardees will be honored during the AssociationsScientific Sessions 2021, which will be fully virtual, Saturday, Nov. 13 through Monday, Nov. 15, 2021.

Dr. McNally was selected for this honor because of her multiple discoveries around the heredity of musculoskeletal and cardiovascular disorders. Her work impacts both scientific research and patient care. Additionally, Dr. McNally discovered new techniques for identifying and mapping genetic modifiers for inherited cardiovascular and myopathic disorders.

Thank you and congratulations to Dr. Elizabeth McNally, said Association President Donald M. Lloyd-Jones, M.D., Sc.M., FAHA. Her work continues to help us develop a deeper understanding of how genetic mutations exert their effects on cardiovascular disease. She leads an incredible team that is using these genetic signals to take the critically important step of developing of new therapies, particularly for inherited cardiac conditions such as cardiomyopathies.

Dr. McNally directs the Center for Genetic Medicine at Northwestern Universitys Feinberg School of Medicine in Chicago and is the Elizabeth J. Ward Professor of Genetic Medicine - a cardiologist with expertise in cardiovascular genetics. As a clinician, she developed one of the first cardiovascular genetics clinics in the nation, integrating genetic testing into cardiovascular care for patients and families.

Her research team at Northwestern discovers genetic causes of cardiac disorders and then works to define the mechanisms of how these genetic variants cause disease. By developing a deeper understanding as to how these genetic mutations exert their effects, she is using these genetic signals to drive the development of new treatments for cardiovascular disease. She has a special interest in neuromuscular genetic diseases like muscular dystrophy since these disorders often have accompanying cardiovascular complications.

Genetic treatments are becoming a reality, said Dr. McNally. As a physician scientist, its amazing to see some of these treatments beginning to make it to patients. In Duchenne Muscular Dystrophy, there are now multiple ongoing trials of gene therapy, and this will also be gene therapy that treats the heart. We also know about all the newly developing gene editing tools, and how these can be adapted to treat patients with genetic cardiovascular diseases and one day to also change genes to treat even more common forms of heart disease.

Dr. McNallys translational accomplishments have been recognized through an award from the Burroughs Wellcome Foundation and as a recipient a Distinguished Clinical Scientist Award from the Doris Duke Charitable Foundation. She serves on the Board of Directors for the Muscular Dystrophy Association and is currently the chair of the Associations Council on Basic Cardiovascular Sciences. She is a past president of the American Society for Clinical Investigation and currently president of the Association of American Physicians. Earlier this year, she was elected to the American Academy of Arts and Sciences.

Additional Resources:

The Association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific Association programs and events. The Association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers and health insurance providers and the Associations overall financial information are availablehere.

The American Heart AssociationsScientific Sessions 2021is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science for health care professionals worldwide. The three-day meeting will feature more than 500 sessions focused on breakthrough cardiovascular basic, clinical and population science updates in a fully virtual experience Saturday, Nov. 13 through Monday, Nov. 15, 2021. Thousands of leading physicians, scientists, cardiologists, advanced practice nurses and allied health care professionals from around the world will convene virtually to participate in basic, clinical and population science presentations, discussions and curricula that can shape the future of cardiovascular science and medicine, including prevention and quality improvement. During the three-day meeting, attendees receive exclusive access to more than 4,000 original research presentations and can earn Continuing Medical Education (CME), Continuing Education (CE) or Maintenance of Certification (MOC) credits for educational sessions. Engage in Scientific Sessions 2021 on social media via#AHA21.

About the American Heart Association

The American Heart Association is a leading force for a world of longer, healthier lives. With nearly a century of lifesaving work, the Dallas-based association is dedicated to ensuring equitable health for all. We are a trustworthy source empowering people to improve their heart health, brain health and well-being. We collaborate with numerous organizations and millions of volunteers to fund innovative research, advocate for stronger public health policies, and share lifesaving resources and information. Connect with us onheart.org,Facebook,Twitteror by calling 1-800-AHA-USA1.

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Elizabeth M. McNally, M.D., Ph.D., FAHA, named the American Heart Association's 2021 Distinguished Scientist in Basic Cardiovascular Sciences -...

Cellectis Provides Business Update and Reports Financial Results for Third Quarter and First Nine Months 2021 – GlobeNewswire

Sponsored programs at ASH 2021 - preliminary clinical data to be presented at ASH 2021 for product candidate UCART22 and preclinical data from Cellectis gene therapy product candidate TALGlobin01

Partnered programs at ASH 2021 ALPHA2 and UNIVERSAL abstracts selected for oral presentations, ALPHA abstract selected for poster presentation

Preclinical data forRAG1deficiencySevere Combined Immunodeficiency (SCID) andSTAT3 forHyperIgEsyndrome presented at ESGCT 2021

Preclinical data supporting anti-tumor activity of UCARTMESO to be presented at SITC 2021 on November 12, 2021

Qualification of facility equipment and systems completed for

Raleigh GMP manufacturing site; Paris GMP manufacturing site now operational, focusing on the production of starting and raw materials for Cellectis UCART product candidates

Donald A Bergstrom, M.D., Ph.D., appointed as a Board Observer on Cellectis Board of Directors

Cash position1 of $216 million as of September 30, 2021

NEW YORK, Nov. 04, 2021 (GLOBE NEWSWIRE) -- Cellectis S.A. (NASDAQ: CLLS EURONEXT GROWTH: ALCLS) (the Company), a gene-editing company with clinical-stage immuno-oncology programs using allogeneic chimeric antigen receptor (CAR)-T cells and gene therapy programs for genetic diseases, today announced results for the three-month and nine-month periods ending September 30, 2021.

Cellectis will hold a conference call for investors on Friday, November 5, 2021, at 8:00 AM ET / 2:00 PM CET. The call will include the Companys third quarter results, and an update on business activities.

________________________1Cash position includes cash, cash equivalents and current financial assets and restricted cash. Restricted cash was $6 million as of September 30, 2021.

The live dial-in information for the conference call is:

US & Canada only: +1 877-407-3104

International: +1 201-493-6792

In addition, a replay of the call will be available until November 19th, by calling +1 877-660-6853 (Toll Free US & Canada); +1 201-612-7415 (Toll Free International).

Conference ID: 13724432

2021 has been a productive year thus far for Cellectis. We have made great progress during Q3 with both our clinical trials and preclinical product candidate pipeline, and are eager to share additional preliminary data from our BALLI-01 clinical trial and disclose initial pre-clinical data from TALGlobin01, at ASH this year, said Dr. Andr Choulika, Chief Executive Officer of Cellectis. With regard to our preclinical UCART pipeline focusing on solid tumors, we have made notable progress with UCARTMESO, targeting mesothelin - expressing solid tumors, and are excited to share new pre-clinical data that support anti-tumor activity at the Society for Immunotherapy of Cancer (SITC) Annual Meeting later this month.

GMP production remains on track for Cellectis Manufacturing site in Raleigh, NC, where qualification of facility equipment and systems was completed during Q3. Cellectis also continues to expand its internal manufacturing capabilities with its Paris site, which is now operational. Cellectis continues to leverage its expertise in gene editing and clinical development to transform the lives of patients with cancer and rare genetic diseases, and we look forward to continuing this effort in Q4, into 2022, and beyond.

Allogeneic CAR-T Cell Development Programs

Sponsored Phase 1 Studies

Cellectis continues to make progress in its proprietary programs enrolling patients in its three sponsored Phase 1 dose escalation trials:

UCART22 is an allogeneic CAR-T cell product candidate targeting CD22 being evaluated in patients with relapsed or refractory B cell acute lymphoblastic leukemia (r/r B-ALL) in the BALLI-01 Phase 1, multi-center dose-escalation clinical study.

UCART123 is an allogeneic CAR T-cell product candidate targeting CD123 being evaluated in patients with relapsed or refractory acute myeloid leukemia (r/r AML) in the AMELI-01 Phase 1, multi-center dose-escalation clinical study.

UCARTCS1 is an allogeneic CAR T-cell product candidate targeting CS1 being evaluated in patients with relapsed or refractory multiple myeloma (r/r MM) in the MELANI-01 Phase 1, multi-center dose-escalation clinical study.

Cellectis to present updated clinical data on BALLI-01 investigating UCART22 product candidate in R/R B-ALL at the 2021 American Society of Hematology Annual meeting

Wholly-controlled UCART Preclinical Programs

UCART20x22, is in development as the first allogeneic dual CAR-T cell product candidate which is being developed for patients with B-cell Non-Hodgkin lymphoma.

UCARTMESO, is an allogeneic CAR-T cell product candidatetargeting mesothelin,which is being developedforpatients withmesothelin expressing solidtumors.

Gene Therapy Programs

.HEAL is a gene therapy platform for genetic diseases developed by Cellectis. The platform leverages the power of TALEN gene editing technology to perform genome surgery resulting in highly efficient and precise gene inactivation, insertion, and correction in hematopoietic stem cells (HSCs). Cellectis has announced programs in sickle cell disease, lysosomal storage disorders and primary immunodeficiencies.

Sickle Cell Disease

TALGlobin01, is an autologous ex vivo TALEN-edited CD34+ HSC therapy for the treatment of SCD

TALGlobin01 is developed using both TALEN technology to induce a double strand DNA break in the SCD-causing hemoglobin subunit beta (HBB) gene and adeno-associated virus (AAV) particles containing a DNA repair template designed to correct the faulty HBB gene via endogenous homology directed repair.

Cellectis to present preclinical data on TALGlobin01 for the treatment of Sickle Cell Disease at the 2021 American Society of Hematology Annual meeting

Primary Immunodeficiencies

In collaboration with professor ToniCathomen,Scientific Director at the Center for Chronic Immunodeficiency, Medical Center - University of Freiburg, Germany, Cellectis is developing two gene edited HSC product candidates to address primary immunodeficiencies.

The authors presented encouraging preclinical data for RAG1 for Severe Combined Immunodeficiency (SCID) and STAT3 for HyperIgEsyndrome, at the European Society of Gene and Cell Therapy (ESGCT) Congress held on October 19-22, 2021.

RAG1 Severe Combined Immunodeficiency (SCID)

HyperIgEsyndrome

Licensed Allogeneic CAR-T Cell Development Programs

ALLOGENE/SERVIER: ALLO-501 and ALLO-501A in patients with relapsed/refractory non-Hodgkin lymphoma (r/r NHL)

CD19 AlloCAR T program utilizes Cellectis technologies. ALLO-501 and ALLO-501A are being jointly developed under a collaboration agreement between Servier and Allogene based on an exclusive license granted by Cellectis to Servier. Servier grants to Allogene exclusive rights to ALLO-501 and ALLO-501A in the U.S., while Servier retains exclusive rights for all other countries.

ALLOGENE: ALLO-715 in patients with relapsed/refractory multiple myeloma (r/r MM)

The anti-BCMA AlloCAR T program, which utilize the Cellectis TALEN technologies, are licensed exclusively from Cellectis by Allogene and Allogene holds global development and commercial rights to these AlloCAR T programs.

Manufacturing Facility

Paris Starting Materials Manufacturing Facility

Raleigh GMP Manufacturing Facility

New appointment

Board appointment

Financial Results

The interim condensed consolidated financial statements of Cellectis, which consolidate the results of Calyxt, Inc. of which Cellectis is a 64.2% stockholder (as of September 30, 2021), have been prepared in accordance with International Financial Reporting Standards, as issued by the International Accounting Standards Board (IFRS).

We present certain financial metrics broken out between our two reportable segments Therapeutics and Plants in the appendices of this Q3 2021 and First Nine Months 2021 financial results press release. Third Quarter and First Nine Months 2021 Financial Result.

Cash: As of September 30, 2021, Cellectis, including Calyxt, had $216 million in consolidated cash, cash equivalents, current financial assets and restricted cash of which $201 million are attributable to Cellectis on a stand-alone basis. This compares to $274 million in consolidated cash, cash equivalents, current financial assets and restricted cash as of December 31, 2020, of which $244 million was attributable to Cellectis on a stand-alone basis. This net decrease of $58 million primarily reflects (i) $92 million of net cash flows used in operating, investing and lease financing activities of Cellectis, (ii) $15 million of net cash flows used in operating, capital expenditures and lease financing activities of Calyxt and (iii) $6 million of unfavorable FOREX impact which was partially offset by (iv) $45 million of net equity proceeds raised from sales under the Companys At-The-Market (ATM) program in April 2021 and (v) $10 million of proceeds from stock options exercises at Cellectis. Based on the current operating plan, Cellectis excluding Calyxt anticipates that the cash, cash equivalents, and restricted cash of $201 million as of September 30, 2021 will fund its operations into early 2023.

Revenues and Other Income: Consolidated revenues and other income were $11 million for the three months ended September 30, 2021 compared to $9 million for the three months ended September 30, 2020. Consolidated revenues and other income were $53 million for the nine months ended September 30, 2021 compared to $67 million for the nine months ended September 30, 2020. 50% of consolidated revenues and other income was attributable to Cellectis in the first nine months of 2021. This decrease between the nine months ended September 30, 2021 and 2020 was mainly attributable to a $28 million upfront payment received in March 2020 and the recognition of $19 million of other previously-received upfront and milestone payments on the five released targets based on the March 2020 amendment of the License, Development and Commercialization Agreement signed with Servier as well as a decrease in licenses revenue. That was partially offset by (i) the recognition of $15 million in Cytovia stock or an upfront non-cash payment of $15 million if certain conditions are not met by December 31, 2021, (ii) the recognition of a $5 million milestone payment from Allogene related to the Phase 1 clinical study for ALLO-316, in advanced or metastatic clear cell renal cell carcinoma, (iii) $15 million from higher high oleic soybean revenues and by (iv) $1.5 million from the PPP Loan forgiveness at Calyxt.

Cost of Revenues: Consolidated cost of revenues were $9 million for the three months ended September 30, 2021 compared to $8 million for the three months ended September 30, 2020. Consolidated cost of revenues was $29 million for the nine months ended September 30, 2021 compared to $18 million for the nine months ended September 30, 2020. This increase was primarily explained by the cost of products sold during the period by Calyxt.

R&D Expenses: Consolidated R&D expenses were $34 million for the three months ended September 30, 2021 compared to $20 million for the three months ended September 30, 2020. Consolidated R&D expenses were $97 million for the nine months ended September 30, 2021 compared to $64 million for the nine months ended September 30, 2020. 91% of consolidated R&D expenses was attributable to Cellectis in the first nine months of 2021. The $33 million increase between the first nine months of 2021 and 2020 was primarily attributable to (i) higher wages and salaries and social charges on stock option grants of $12 million, to (ii) higher purchases, external and other expenses of $19 million and to (iii) higher non-cash stock-based compensation expenses of $2 million.

SG&A Expenses: Consolidated SG&A expenses were $10 million for the three months ended September 30, 2021 and 2020. Consolidated SG&A expenses were $28 million for the nine months ended September 30, 2021 compared to $31 million for the nine months ended September 30, 2020. 59% of consolidated SG&A expenses was attributable to Cellectis in the first nine months of 2021. The $3 million decrease was attributable to lower non-cash stock-based compensation expenses of $5 million which was partially offset by higher wages and salaries and social charges on stock option grants of $1 million and higher other expenses of $1 million.

Net Income (loss) Attributable to Shareholders of Cellectis: The consolidated net loss attributable to shareholders of Cellectis was $37 million (or $0.82 per share) for the three months ended September 30, 2021, of which $33 million was attributed to Cellectis, compared to $30 million (or $0.71 per share) for the three months ended September 30, 2020, of which $25 million was attributed to Cellectis. The consolidated net loss attributable to Shareholders of Cellectis was $89 million (or $2.00 per share) for the nine months ended September 30, 2021, of which $75 million loss was attributed to Cellectis, compared to a loss of $42 million (or $0.98 per share) for the nine months ended September 30, 2020, of which $21 million was attributable to Cellectis. This $48 million increase in net loss between first nine months 2021 and 2020 was primarily driven by a decrease in revenues and other income of $13 million and by an increase in operating expenses of $39 million partially offset by $7 million increase in net financial gain.

Adjusted Net Income (Loss) Attributable to Shareholders of Cellectis: The consolidated adjusted net loss attributable to shareholders of Cellectis was $32 million (or $0.71 per share) for the three months ended September 30, 2021, of which $29 million is attributed to Cellectis, compared to a net loss of $27 million (or $0.63 per share) for the three months ended September 30, 2020, of which $22 million was attributed to Cellectis. The consolidated adjusted net loss attributable to Shareholders of Cellectis was $80 million (or $1.79 per share) for the nine months ended September 30, 2021, of which $66 million loss was attributable to Cellectis, compared to a loss of $30 million (or $0.72 loss per share) for the nine months ended September 30, 2020, of which $13 million was attributable to Cellectis. Please see "Note Regarding Use of Non-GAAP Financial Measures" for reconciliation of GAAP net income (loss) attributable to shareholders of Cellectis to adjusted net income (loss) attributable to shareholders of Cellectis.

We currently foresee focusing our cash spending at Cellectis for the Full Year of 2021 in the following areas:

CELLECTIS S.A.(unaudited)STATEMENT OF CONSOLIDATED FINANCIAL POSITION($ in thousands, except per share data)

CELLECTIS S.A.STATEMENT OF CONSOLIDATED OPERATIONS Third quarter(unaudited)($ in thousands, except per share data)

CELLECTIS S.A.STATEMENT OF CONSOLIDATED OPERATIONS First nine months(unaudited)($ in thousands, except per share data)

CELLECTIS S.A.DETAILS OF KEY PERFORMANCE INDICATORS BY REPORTABLE SEGMENTS Third Quarter(unaudited) - ($ in thousands)

CELLECTIS S.A.DETAILS OF KEY PERFORMANCE INDICATORS BY REPORTABLE SEGMENTS First nine-months(unaudited) - ($ in thousands)

Note Regarding Use of Non-GAAP Financial Measures

Cellectis S.A. presents adjusted net income (loss) attributable to shareholders of Cellectis in this press release. Adjusted net income (loss) attributable to shareholders of Cellectis is not a measure calculated in accordance with IFRS. We have included in this press release a reconciliation of this figure to net income (loss) attributable to shareholders of Cellectis, which is the most directly comparable financial measure calculated in accordance with IFRS. Because adjusted net income (loss) attributable to shareholders of Cellectis excludes Non-cash stock-based compensation expensea non-cash expense, we believe that this financial measure, when considered together with our IFRS financial statements, can enhance an overall understanding of Cellectis financial performance. Moreover, our management views the Companys operations, and manages its business, based, in part, on this financial measure. In particular, we believe that the elimination of Non-cash stock-based expenses from Net income (loss) attributable to shareholders of Cellectis can provide a useful measure for period-to-period comparisons of our core businesses. Our use of adjusted net income (loss) attributable to shareholders of Cellectis has limitations as an analytical tool, and you should not consider it in isolation or as a substitute for analysis of our financial results as reported under IFRS. Some of these limitations are: (a) other companies, including companies in our industry which use similar stock-based compensation, may address the impact of Non-cash stock- based compensation expense differently; and (b) other companies may report adjusted net income (loss) attributable to shareholders or similarly titled measures but calculate them differently, which reduces their usefulness as a comparative measure. Because of these and other limitations, you should consider adjusted net income (loss) attributable to shareholders of Cellectis alongside our IFRS financial results, including Net income (loss) attributable to shareholders of Cellectis.

RECONCILIATION OF GAAP TO NON-GAAP NET INCOME Third Quarter(unaudited)($ in thousands, except per share data)

(1)When we have adjusted net loss, in accordance with IFRS, we use the Weighted average number of outstanding shares, basic to compute the Diluted adjusted net income (loss) attributable to shareholders of Cellectis ($/share). When we have adjusted net income, in accordance with IFRS, we use the Weighted average number of outstanding shares, diluted tocompute the Diluted adjusted net income (loss) attributable to shareholders of Cellectis ($/share)

RECONCILIATION OF GAAP TO NON-GAAP NET INCOME First nine-months(unaudited)($ in thousands, except per share data)

(1)When we have adjusted net loss, in accordance with IFRS, we use the Weighted average number of outstanding shares, basic to compute the Diluted adjusted net income (loss) attributable to shareholders of Cellectis ($/share). When we have adjusted net income, in accordance with IFRS, we use the Weighted average number of outstanding shares, diluted tocompute the Diluted adjusted net income (loss) attributable to shareholders of Cellectis ($/share)

About CellectisCellectis is a gene editing company, developing first of its kind therapeutic products. Cellectis utilizes an allogeneic approach for CAR-T immunotherapies in oncology, pioneering the concept of off-the-shelf and ready-to-use gene-edited CAR T-cells to treat cancer patients, and a platform to make therapeutic gene editing in hemopoietic stem cells for various diseases. As a clinical-stage biopharmaceutical company with over 21 years of expertise in gene editing, Cellectis is developing life-changing product candidates utilizing TALEN, its gene editing technology, andPulseAgile, its pioneering electroporation system to harness the power of the immune systemin order totreat diseases with unmet medical needs.As part of its commitment to a cure, Cellectis remains dedicated to its goal of providing lifesaving UCART product candidates for multiple cancers including acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia (B-ALL) and multiple myeloma (MM)..HEALis a new platform focusing on hemopoietic stem cells to treat blood disorders, immunodeficiencies andlysosomialstorage diseases.Cellectis headquarters are in Paris, France, with locations in New York, New York and Raleigh, North Carolina. Cellectis is listed on the Nasdaq Global Market (ticker: CLLS) and on Euronext Growth (ticker: ALCLS).

For more information, visitwww.cellectis.com Follow Cellectis on social media: @cellectis, LinkedIn and YouTube.

For further information, please contact:

Media contacts:Margaret Gandolfo, Senior Manager, Communications, +1 (646) 628 0300Pascalyne Wilson,Director,Communications,+33776991433, media@cellectis.com

Investor Relation contact:EricDutang, Chief Financial Officer,+1 (646) 630 1748,investor@cellectis.com

Forward-looking Statements

This presentation contains forward-looking statements within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by words such as at this time, anticipate, believe, expect, on track, plan, scheduled, and will, or the negative of these and similar expressions. These forward-looking statements, which are based on our managements current expectations and assumptions and on information currently available to management, include statements about our research and development projects and priorities, our pre-clinical project development efforts and the timing of our presentation of data. These forward-looking statements are made in light of information currently available to us and are subject to numerous risks and uncertainties, including with respect to the numerous risks associated with biopharmaceutical product candidate development as well as the duration and severity of the COVID-19 pandemic and governmental and regulatory measures implemented in response to the evolving situation. With respect to our cash runway, our operating plans, including product development plans, may change as a result of various factors, including factors currently unknown to us. Furthermore, many other important factors, including those described in our Annual Report on Form 20-F and the financial report (including the management report) for the year ended December 31, 2020 and subsequent filings Cellectis makes with the Securities Exchange Commission from time to time, as well as other known and unknown risks and uncertainties may adversely affect such forward-looking statements and cause our actual results, performance or achievements to be materially different from those expressed or implied by the forward-looking statements. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future.

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Cellectis Provides Business Update and Reports Financial Results for Third Quarter and First Nine Months 2021 - GlobeNewswire

Intellia Therapeutics Announces Third Quarter 2021 Financial Results and Highlights Recent Company Progress – BioSpace

CAMBRIDGE, Mass., Nov. 04, 2021 (GLOBE NEWSWIRE) --Intellia Therapeutics (NASDAQ:NTLA), a leading clinical-stage genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology bothin vivoandex vivo, today reported financial results for the third quarter ended September 30, 2021, and recent operational highlights.

Intellia continues to make important progress toward advancing its full-spectrum genome editing pipeline. Today, we are pleased to share that we remain highly encouraged by the safety profile, consistency of TTR reduction and ongoing effect of NTLA-2001 in the Phase 1 study. We believe we are closing in on identifying the recommended therapeutic dose for NTLA-2001 in patients with ATTR amyloidosis with polyneuropathy for further evaluation in Part 2, a single-dose expansion cohort. Additionally, while it has long been our plan to develop NTLA-2001 for all forms of ATTR amyloidosis, we have decided to accelerate the evaluation of NTLA-2001 in patients with ATTR amyloidosis whose primary clinical manifestation is cardiomyopathy. Based on the strength of our interim dataset, we are now seeking regulatory feedback for inclusion of the ATTR-CM patient population in our current Phase 1 study. We look forward to sharing updates from this program in Q1 2022, said Intellia President and Chief Executive Officer John Leonard, M.D. Beyond our lead program, we remain focused on advancing NTLA-2002 for HAE and NTLA-5001 for AML. We received regulatory clearance for both programs to initiate first-in-human studies and we expect those studies to begin later this year. Finally, we nominated two gene insertion development candidates NTLA-3001, our wholly owned AATD program, and a Factor 9 gene insertion candidate for Hem B in collaboration with Regeneron. Our rapidly expanding pipeline is yet one more example of the benefits of our modular platform in generating novel and potentially curative treatment options for the patients we aim to serve.

Third Quarter 2021 and Recent Operational Highlights

In Vivo Program Updates

Ex Vivo Program Updates

Research and Corporate Updates

Upcoming Events

The Company will participate in the following events during the fourth quarter of 2021:

Upcoming Milestones

The Company has set forth the following for pipeline progression:

Third Quarter 2021 Financial Results

Conference Call to Discuss Third Quarter Earnings

The Company will discuss these results on a conference call today, Thursday, November 4, at 8 a.m. ET.

To join the call:

A replay of the call will be available through the Events and Presentations page of the Investors & Media section on Intellias website at http://www.intelliatx.com, beginning on November 4 at 12 p.m. ET.

About Intellia TherapeuticsIntellia Therapeutics, a leading clinical-stage genome editing company, is developing novel, potentially curative therapeutics using CRISPR/Cas9 technology. To fully realize the transformative potential of CRISPR/Cas9, Intellia is pursuing two primary approaches. The companys in vivo programs use intravenously administered CRISPR as the therapy, in which proprietary delivery technology enables highly precise editing of disease-causing genes directly within specific target tissues. Intellias ex vivo programs use CRISPR to create the therapy by using engineered human cells to treat cancer and autoimmune diseases. Intellias deep scientific, technical and clinical development experience, along with its robust intellectual property portfolio, have enabled the company to take a leadership role in harnessing the full potential of CRISPR/Cas9 to create new classes of genetic medicine. Learn more at intelliatx.com. Follow us on Twitter @intelliatweets.

Forward-Looking Statements This press release contains forward-looking statements of Intellia Therapeutics, Inc. (Intellia or the Company) within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding Intellias beliefs and expectations regarding its: ability to complete clinical studies for NTLA-2001 for the treatment of transthyretin (ATTR) amyloidosis pursuant to its clinical trial applications (CTA), including submitting additional regulatory applications in other countries; clinical data from the ongoing single-ascending dose portion of the Phase 1 study evaluating NTLA-2001; expectations on regulatory approval to expand the Phase 1 trial population to include patients with ATTR with cardiomyopathy (ATTR-CM); expectations of being able to initiate clinical trials for NTLA-2002 for the treatment of hereditary angioedema (HAE) and NTLA-5001 for the treatment of acute myeloid leukemia (AML); ability to enroll patients in its Phase 1/2 study for NTLA-2002 for the treatment of hereditary angioedema (HAE) in New Zealand and the United Kingdom; its IND-enabling activities for NTLA-3001 for the treatment of alpha-1 antitrypsin deficiency; nomination and continued preclinical development of new development candidates; expectations for a new collaboration with Regeneron for a Factor 9 (F9) development candidate for its Hemophilia B program; expectations for a new collaboration with SparingVision for the treatment of ocular diseases; advancement and expansion of its CRISPR/Cas9 technology to develop human therapeutic products, as well as its ability to maintain and expand its related intellectual property portfolio; statements regarding the timing of regulatory filings regarding its development programs; plans to attend and present data at scientific conferences later this year; and our expectations regarding our use of capital and our ability to fund operations beyond the next 24 months.

Any forward-looking statements in this press release are based on managements current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: risks related to Intellias ability to protect and maintain its intellectual property position; risks related to Intellias relationship with third parties, including its licensors and licensees; risks related to the ability of its licensors to protect and maintain their intellectual property position; uncertainties related to the authorization, initiation and conduct of studies and other development requirements for its product candidates; the risk that any one or more of Intellias product candidates will not be successfully developed and commercialized; the risk that the results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies; the risk that regulatory approval to expand the Phase 1 patient population to include patients with ATTR-CM will be denied; risks related to the COVID-19 pandemic including the effects of the Delta variant; and the risk that Intellias collaborations with Regeneron, SparingVision or its other collaborations will not continue or will not be successful. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Intellias actual results to differ from those contained in the forward-looking statements, see the section entitled Risk Factors in Intellias most recent quarterly report on Form 10-Q as well as discussions of potential risks, uncertainties, and other important factors in Intellias other filings with the Securities and Exchange Commission (SEC). All information in this press release is as of the date of the release, and Intellia undertakes no duty to update this information unless required by law.

Intellia Contacts:

Investors:Ian KarpSenior Vice President, Investor Relations and Corporate Communications+1-857-449-4175ian.karp@intelliatx.com

Lina LiDirector, Investor Relations+1-857-706-1612lina.li@intelliatx.com

Media:Matt CrensonTen Bridge Communications+1-917-640-7930media@intelliatx.commcrenson@tenbridgecommunications.com

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Intellia Therapeutics Announces Third Quarter 2021 Financial Results and Highlights Recent Company Progress - BioSpace

Taysha Announces Exclusive Option from UTSW to License Worldwide Rights to Clinical-Stage AAV9 Gene Therapy Program for CLN7 Disease, a Research…

CLN7 program currently in Phase 1 clinical proof-of-concept trial with preliminary data anticipated by year-end 2021

Intrathecal dosing of the high dose first-generation construct resulted in nearly complete normalization of impaired open field and motor function and more than doubled median life expectancy in MSFSD8 knockout mice; data to be presented at upcoming 17th Annual International Congress on Neuronal Ceroid Lipofuscinosis

Taysha also enters into a research collaboration with UT Southwestern to develop next-generation construct for CLN7 disease, which is expected to improve potency, safety profile, packaging efficiency and manufacturability over first-generation construct

Initiation of a planned pivotal CLN7 clinical trial with next-generation construct anticipated in 2022, with reference to human proof-of-concept data generated from first-generation construct

Provides a grant to Batten Hope, the leading CLN7 patient advocacy group, to support patient awareness, disease education and newborn screening initiatives

Estimated prevalence of CLN7 disease is 4,000 patients worldwide

Taysha expected to have five clinical stage programs by year-end 2021

Webcast today at 8:00 AM Eastern Time

DALLAS, October 05, 2021--(BUSINESS WIRE)--Taysha Gene Therapies, Inc. (Nasdaq: TSHA), a patient-centric, pivotal-stage gene therapy company focused on developing and commercializing AAV-based gene therapies for the treatment of monogenic diseases of the central nervous system (CNS) in both rare and large patient populations, today announced that it has obtained an exclusive option from UT Southwestern (UTSW) to license worldwide rights to a clinical-stage AAV9 gene therapy replacement program for the treatment of CLN7 disease. The company has also entered into a research collaboration with UTSW to develop a next-generation construct for the treatment of CLN7 disease, which is expected to improve potency, safety profile, packaging efficiency and manufacturability over the first-generation construct. Completion of the next-generation construct design is anticipated by year-end 2021, with commercial-grade GMP material expected in 2022.

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The first-generation construct for the CLN7 program was developed in the laboratory of Steven Gray, Ph.D., Associate Professor at UT Southwestern Medical Center and Chief Scientific Advisor for Taysha, with financial support from Milas Miracle and Batten Hope, the leading CLN7 patient advocacy groups. The CLN7 program is currently in a Phase 1 clinical proof-of-concept trial run by UTSW, and Taysha expects the availability of preliminary human proof-of-concept clinical safety and efficacy data from the first-generation construct by year-end 2021. Taysha intends to initiate a planned pivotal trial using a next-generation construct in 2022, with reference to the human proof-of-concept clinical data being generated from the first-generation construct.

In addition, Taysha has provided a grant to Batten Hope to support patient awareness, disease education and newborn screening initiatives.

CLN7 disease is a rare, fatal and rapidly progressive neurodegenerative disease that is a form of Batten disease. CLN7 is caused by autosomal recessive mutations in the MFSD8 gene that results in lysosomal dysfunction. Disease onset occurs around two to five years of age, with death often ensuing in young adolescence. Patients experience gradual nerve cell loss in certain parts of the brain and typically present with seizures, vision loss, speech impairment and mental and motor regression. Currently, there are no approved therapies to treat CLN7 disease, which impacts an estimated 4,000 patients globally.

Preclinical data in rodents supported advancement of the first-generation construct into a Phase 1 clinical proof-of-concept study in patients with CLN7 disease. In an in vivo efficacy study, intrathecal (IT) administration of the first-generation construct to MFSD8 knockout mice with high or low doses resulted in clear age and dose effects with early intervention and high dose achieving the best therapeutic benefits. IT high dose of the first-generation construct in younger knockout mice resulted in: 1) widespread MFSD8 mRNA expression in all tissues assessed; 2) nearly complete normalization of impaired open field and rotarod performance at 6 and 9 months post injection; 3) more than doubled median life expectancy (16.82 months versus 7.77 months in untreated knockout mice); and 4) maintained healthy body weight for a prolonged period of time. Toxicology studies in wild type rodents demonstrated safety and tolerability of IT administration of the first-generation construct. These preclinical data will be presented by Xin Chen, Ph.D., Assistant Professor, Department of Pediatrics at UT Southwestern, in an oral presentation at the 17th Annual International Congress on Neuronal Ceroid Lipofuscinosis on October 8, 2021.

"The CLN7 program is a strategic addition to our gene therapy pipeline focused on monogenic CNS diseases. Encouraging preclinical data generated in relevant rodent models suggest that the first-generation construct has the potential to reduce overall disease pathology, preserve motor function and ultimately prolong survival," said RA Session II, President, Founder and Chief Executive Officer of Taysha. "The first-generation construct is currently in a Phase 1 clinical proof-of-concept trial with two patients dosed to date, and we look forward to the availability of preliminary data by year-end. With human proof-of-concept clinical data to reference, we expect to advance a next-generation construct into a planned pivotal trial in 2022, which we anticipate should improve potency, safety, packaging efficiency and manufacturability over the first-generation construct. Importantly, we are also pleased to announce our grant to Batten Hope, the leading CLN7 disease nonprofit patient advocacy organization, to support patient awareness, disease education and newborn screening initiatives. We believe a gene therapy approach has the potential to address a significant unmet need in an estimated 4,000 patients globally."

Gina Hann, Batten Hope Founder, President and Treasurer, added, "Our mission is to support families with children suffering from terminal and rapidly progressive neurodegenerative diseases like CLN7. We are honored to receive Tayshas support to raise awareness, increase newborn screening and help patients gain access to potentially transformative treatments that offer hope and therapeutic advancement for conditions with significant unmet needs."

UTSW is currently enrolling patients in an investigator-sponsored Phase 1 open-label, dose escalation clinical proof-of-concept trial at Dallas Childrens Hospital for an intrathecally dosed AAV9-based gene replacement therapy for the treatment of infantile CLN7 disease. The primary endpoint of the trial is safety and tolerability by incidence and severity of treatment related serious adverse events. Secondary efficacy endpoints include the Clinical Global Impression, neuropsychological, ataxia and motor function assessments and quality of life. The design rationale and a discussion of outcome measures for this clinical trial will be presented as a poster at the upcoming 17th Annual International Congress on Neuronal Ceroid Lipofuscinosis. To date, one patient has been dosed at 5x1014 total vg and a second patient was dosed at 1x1015 total vg as measured by the qPCR method. UTSW continues to enroll patients in this Phase 1 study at 1x1015 total vg and expects to dose additional patients in the near term. Preliminary safety and efficacy data are expected by the end of 2021.

With the addition of the CLN7 program, Taysha expects to have five clinical stage programs by year-end. As such, the TSHA-104 program for the treatment of SURF1-associated Leigh syndrome will transition to the companys collaborators at UTSW to complete IND-enabling studies, followed by a planned investigator-initiated clinical trial by the end of 2022. Taysha will continue to support the SURF1 natural history study in partnership with UTSW.

Financial terms of the agreements were not disclosed.

Webcast Information

Taysha management will host a webcast today at 8:00 am ET / 7:00 am CT to discuss todays news. To participate, please access the following link: http://lifesci.rampard.com/WebcastingAppv5/Events/eventsDispatcher.jsp?Y2lk=MTQ1MQ==. The live webcast and replay may also be accessed by visiting Tayshas website at https://ir.tayshagtx.com/news-events/events-presentations. An archived version of the webcast will be available on the website for 60 days.

About Taysha Gene Therapies

Taysha Gene Therapies (Nasdaq: TSHA) is on a mission to eradicate monogenic CNS disease. With a singular focus on developing curative medicines, we aim to rapidly translate our treatments from bench to bedside. We have combined our teams proven experience in gene therapy drug development and commercialization with the world-class UT Southwestern Gene Therapy Program to build an extensive, AAV gene therapy pipeline focused on both rare and large-market indications. Together, we leverage our fully integrated platforman engine for potential new cureswith a goal of dramatically improving patients lives. More information is available at http://www.tayshagtx.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "anticipates," "believes," "expects," "intends," "projects," and "future" or similar expressions are intended to identify forward-looking statements. Forward-looking statements include statements concerning the potential of our product candidates, as well as the CLN7 program, to positively impact quality of life and alter the course of disease in the patients we seek to treat, our expectations regarding the benefits of a next-generation construct for CLN7, our research, development and regulatory plans for our product candidates, the potential for these product candidates to receive regulatory approval from the FDA or equivalent foreign regulatory agencies, and whether, if approved, these product candidates will be successfully distributed and marketed, and the potential market opportunity for these product candidates. Forward-looking statements are based on managements current expectations and are subject to various risks and uncertainties that could cause actual results to differ materially and adversely from those expressed or implied by such forward-looking statements. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. Risks regarding our business are described in detail in our Securities and Exchange Commission ("SEC") filings, including in our Annual Report on Form 10-K for the full-year ended December 31, 2020, and our Quarterly Report on Form 10-Q for the quarter ended June 30, 2021, both of which are available on the SECs website at http://www.sec.gov. Additional information will be made available in other filings that we make from time to time with the SEC. Such risks may be amplified by the impacts of the COVID-19 pandemic. These forward-looking statements speak only as of the date hereof, and we disclaim any obligation to update these statements except as may be required by law.

View source version on businesswire.com: https://www.businesswire.com/news/home/20211005005463/en/

Contacts

Company Contact: Kimberly Lee, D.O.SVP, Corporate Communications and Investor RelationsTaysha Gene Therapiesklee@tayshagtx.com

Media Contact: Carolyn HawleyCanale Communicationscarolyn.hawley@canalecomm.com

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Taysha Announces Exclusive Option from UTSW to License Worldwide Rights to Clinical-Stage AAV9 Gene Therapy Program for CLN7 Disease, a Research...

Amicus, looking for a boost, sells its gene therapy work to a SPAC – BioPharma Dive

Dive Brief:

When Amicus acquired a privately held biotech called Celenex in 2018, it appeared to signal a new direction for a company that had already been around for almost two decades. Amicus spent all that time developing chemical drugs known as "pharmacological chaperones," and after a series of ups and downs, had finally brought the first of them, Galafold, to market.

Acquiring Celenex, however, made Amicus a gene therapy developer too. Celenex had several research programs that originated within Nationwide Children's Hospital, one of the nation's top gene therapy hubs. Amicus has since bought several others from the University of Pennsylvania, further establishing gene therapy research as a top priority and quietly giving the New Jersey biotech one of the larger portfolios in the industry.

But Amicus has paid a price, as it still isn't profitable despite having an approved product. The company spent nearly $500 million on expenses last year, largely to fund its pipeline. Its shares also continue to hover around $11 apiece, almost exactly where they were when the biotech began its gene therapy work three years ago.

The value of those assets "has largely gone unrecognized to date," Crowley said on a conference call with analysts. Executives believe housing those assets in a separate company "is the best way to unlock that value for shareholders," he said.

To do this, Amicus has sold its gene therapy business into a special purpose acquisition company, or SPAC, a popular tool of late for biotech investors to take their startups public or acquire stakes in emerging biotechs. The business has been renamed Caritas and will trade on the Nasdaq stock exchange when the deal closes either later this year or early next.

Crowley, who has led Amicus from the start, will join Caritas, which will start with two gene therapies for Batten's disease in clinical testing, several others behind it, more than 115 employees and $400 million in cash. But Amicus will also be able to benefit from Caritas' progress. According to Bradley Campbell, Amicus' chief operating officer and soon-to-be replacement CEO, the company will still hold a 36% stake in its spinout, partial rights to preclinical gene therapies for Fabry and Pompe, and "rights of first negotiation" to others for certain muscular dystrophies.

The companies also believe splitting in two will help each move faster, with Caritas investing solely in gene therapy development and manufacturing and Amicus working to broaden use of Galafold and secure approvals of AT-GAA. Amicus is also getting a $200 million investment from Perceptive and other investors in the deal.

The transaction makes sense given it could "enhance investor interest" in Amicus's gene therapy work, wrote SVB Leerink analyst Joseph Schwartz. Even so, the deal may raise questions about Amicus's long-term growth prospects beyond its two top drugs, wrote Stifel analyst Dae Gon Ha.

"We think investors may question the timing, and its potential significance in the grand scheme of AT-GAA and [Amicus] shares," he wrote.

Amicus shares briefly jumped 10% pre-market before those gains were erased.

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Amicus, looking for a boost, sells its gene therapy work to a SPAC - BioPharma Dive

Aruvant to Participate in 2021 Cell & Gene Meeting on the Mesa to be Held Online and in Person October 12 to 14, 2021 – Yahoo Finance

Company to sponsor SCDAA 49th Annual National Convention to be held October 12 to 16, 2021

NEW YORK and BASEL, Switzerland, Oct. 5, 2021 /PRNewswire/ -- Aruvant Sciences, a private company focused on developing gene therapies for rare diseases, today announced that members of the Aruvant leadership team will participate in the annual Cell & Gene Meeting on the Mesa which is taking place in person in Carlsbad, CA and online from October 12 to October 14, 2021. In addition, Aruvant will be a corporate sponsor of the upcoming 49th Annual National Sickle Cell Disease Association of America (SCDAA) Convention to be held October 12 to October 16, 2021, online.

(PRNewsfoto/Aruvant Sciences)

At the Meeting on the Mesa conference, Dr. Palani Palaniappan, Aruvant's chief technology officer, will participate in the panel titled, "What's Next for Advanced Therapies", taking place live Tuesday, October 12 from 7:15 to 8:45 AM PST. In addition, Dr. Will Chou, chief executive officer, will give a company presentation and provide an update on the development of ARU-1801, an investigational lentiviral gene therapy for sickle cell disease (SCD), and ARU-2801, a one-time, adeno-associated virus gene therapy designed to deliver potentially curative efficacy to patients with hypophosphatasia without the limitations of chronic administration. The presentation will include ARU-2801 preclinical data and clinical data from the ongoing Phase 1/2 MOMENTUM study of ARU-1801 in patients with severe SCD.

In addition, Aruvant is a sponsor of the SCDAA annual meeting. SCDAA's Annual National Convention is a four-day conference designed to address the multifactorial aspects of SCD and sickle cell trait. This year's theme is "Unstoppable: Working Together for Sickle Cell". Click here to view the full program. The Aruvant Meeting on the Mesa presentation and panel discussion will be available for registered participants at http://www.meetingonthemesa.com on October 12, 2021.

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About Aruvant SciencesAruvant Sciences, part of the Roivant family of companies, is a clinical-stage biopharmaceutical company focused on developing and commercializing gene therapies for the treatment of rare diseases. The company has a talented team with extensive experience in the development, manufacturing and commercialization of gene therapy products. Aruvant has an active research program with a lead product candidate, ARU-1801, in development for individuals suffering from sickle cell disease (SCD). ARU-1801, an investigational lentiviral gene therapy, is being studied in a Phase 1/2 clinical trial, the MOMENTUM study, as a one-time potentially curative treatment for SCD. Preliminary clinical data demonstrate engraftment of ARU-1801 and amelioration of SCD is possible with one dose of reduced intensity chemotherapy. The company's second product candidate, ARU-2801, is in development to cure hypophosphatasia, a devastating, ultra-orphan disorder that affects multiple organ systems and leads to high mortality when not treated. Data from pre-clinical studies with ARU-2801 shows durable improvement in disease biomarkers and increased survival. For more information on the ongoing ARU-1801 clinical study, please visit http://www.momentumtrials.com and for more on the company, please visit http://www.aruvant.com. Follow Aruvant on Facebook, Twitter @AruvantSciences and on Instagram @Aruvant_Sciences.

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Aruvant to Participate in 2021 Cell & Gene Meeting on the Mesa to be Held Online and in Person October 12 to 14, 2021 - Yahoo Finance

New Culture Medium Supports Expansion of Natural Killer Cells for Cell and Gene Therapies – PRNewswire

CARLSBAD, Calif., Oct. 5, 2021 /PRNewswire/ -- Thermo Fisher Scientific today announced the launch of Gibco Cell Therapy Systems (CTS) NK-Xpander Medium, a GMP-manufactured cell culture medium that supports large-scale growth and culture of functional natural killer (NK) cells with or without the use of feeder cells. This is the first medium from Thermo Fisher specifically designed to support expansion of NK cells for cell therapy applications and is supported by raw material traceability and regulatory documentation.

"Cell therapy developers are increasingly turning to NK cells because they do not elicit the kinds of active immune responses that trigger conditions such as graft versus host disease," said Mark Powers, vice president, research and development at Thermo Fisher Scientific. "With NK-Xpander Medium, manufacturers can reach the necessary scale they need for NK cell therapies while minimizing regulatory burden and risk."

NK cells grown in NK-Xpander Medium exhibit a greater rate of expansion when compared to NK cells grown in other media and demonstrate cell killing in in vitro and in vivo models. In addition to their low immunogenicity, the ease of availability and sourcing of NK cells, coupled with efficient in vitro expansion, make them ideally suited for the development of allogeneic cell therapies. Unlike autologous therapies, which are produced using a patient's own cells, allogeneic cell therapies are derived from healthy donor tissue, and are more conducive to cost-effective scale-up of cell therapy manufacturing.

"NK cell therapies hold promising applications in treating solid tumors, which haven't been well served by therapies derived from other cell types," said Richard Eckert, professor and chairman at University of Maryland School of Medicine. "To capitalize on the promise of these therapies, our lab used human NK cells grown in Gibco CTS NK-Xpander Medium to study their impact on solid tumor-derived cancer cells. The NK cells cultured in NK-Xpander Medium displayed robust and potent cancer cell killing activity."

NK-Xpander Medium is part of Thermo Fisher's CTS product line, a comprehensive portfolio of GMP-manufactured products backed by regulatory documentation and designed to work synergistically, from cell isolation/activation to gene transfer and cell expansion, to address cell therapy developers' manufacturing workflow needs.

To learn more about Thermo Fisher's cell and gene therapy solutions, please visit http://www.thermofisher.com/CGT. To learn more about Gibco CTS NK-Xpander Medium, please visit http://www.thermofisher.com/nkcelltherapy.

* For Research Use or Manufacturing of Cell, Gene, or Tissue-Based Products. This product is not intended for direct administration into humans or animals.

About Thermo Fisher Scientific Thermo Fisher Scientific Inc. is the world leader in serving science, with annual revenue of approximately $35 billion. Our Mission is to enable our customers to make the world healthier, cleaner and safer. Whether our customers are accelerating life sciences research, solving complex analytical challenges, improving patient diagnostics and therapies or increasing productivity in their laboratories, we are here to support them. Our global team of more than 90,000 colleagues delivers an unrivaled combination of innovative technologies, purchasing convenience and pharmaceutical services through our industry-leading brands, including Thermo Scientific, Applied Biosystems, Invitrogen, Fisher Scientific, Unity Lab Services and Patheon. For more information, please visitwww.thermofisher.com.

# # #

Media Contact Information:

Mauricio Minotta Phone: 760-805-5266 Email: [emailprotected]

Jessika Parry Phone: 419-266-4016Email: [emailprotected]

SOURCE Thermo Fisher Scientific

http://www.thermofisher.com

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New Culture Medium Supports Expansion of Natural Killer Cells for Cell and Gene Therapies - PRNewswire

Sarepta Therapeutics Opens Genetic Therapies Center of Excellence in Columbus, Ohio – Stockhouse

CAMBRIDGE, Mass., Oct. 04, 2021 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today celebrated the grand opening of the Genetic Therapies Center of Excellence (GTCOE), its new research facility in Columbus, Ohio.

The 85,000 square foot state-of-the-art facility expands Sarepta’s research and development capabilities and footprint, which includes sites in Cambridge, Andover and Burlington, Mass. With more than 70 employees today and plans to double the number of employees by the end of 2022, the Center is focused on discovery, pre-clinical and clinical development supporting Sarepta’s pipeline of genetic medicines which includes RNA, gene therapy and gene editing programs. The Center also supports process development and optimization work that enables the transition from clinical-scale to commercial-scale manufacturing, a critical task facing companies developing gene therapies.

Advances in the science of genetic medicine are creating incredible opportunities to develop medicines with the potential to transform the lives of people with rare diseases. Sarepta’s Genetic Therapies Center of Excellence complements and enhances our existing research and development expertise and will play a central and strategic role in our future as the leader in precision genetic medicine,” said Doug Ingram, president and chief executive officer, Sarepta.

Among the guests joining the Sarepta team today for a dedication, ribbon-cutting ceremony and facility tours: The Honorable Jon Husted, Ohio’s Lieutenant Governor; Pat Furlong, president and chief executive officer, Parent Project Muscular Dystrophy (PPMD); Jessica Evans, assistant director, The Speak Foundation; local officials; and luminaries from Columbus’ growing biotechnology sector. At the event, Sarepta also announced a $20,000 donation to the Ronald McDonald House Charities of Central Ohio, with Dee Anders, chief executive officer and executive director, Ronald McDonald House Charities of Central Ohio, present to accept.

Sarepta has operated in Columbus since 2018 and we’re proud to be at the forefront of Columbus’ emergence as a leading hub for biotechnology committed to the local community and the patients and families we serve,” said Louise Rodino-Klapac, Ph.D., Sarepta’s Columbus-based executive vice president and chief scientific officer. Our growing presence in Ohio will help us strengthen our close working relationships with long-standing local partners such as Nationwide Children’s Hospital, while we work with the greatest urgency to advance our pipeline, further the science of genetic medicine and create an environment where future generations of scientific talent will thrive.”

Sarepta Therapeutics’ decision to expand in Ohio is the latest example that Ohio is a great state to grow a business,” said Lt. Governor Jon Husted. When we created the Columbus Innovation District last year, we were focused on cultivating the right environment in central Ohio to attract new investments and jobs in gene and cell therapy. This new facility is a victory, as it builds on our strategy, creating jobs and producing some of the most advanced research and development of precision genetic medicine, further solidifying Ohio as a leader in gene therapy.”

About Sarepta Therapeutics Sarepta is on an urgent mission: engineer precision genetic medicine for rare diseases that devastate lives and cut futures short. We hold leadership positions in Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophies (LGMDs), and we currently have more than 40 programs in various stages of development. Our vast pipeline is driven by our multi-platform Precision Genetic Medicine Engine in gene therapy, RNA and gene editing. For more information, please visit http://www.sarepta.com or follow us on Twitter, LinkedIn, Instagram and Facebook.

Internet Posting of Information We routinely post information that may be important to investors in the 'For Investors' section of our website at http://www.sarepta.com. We encourage investors and potential investors to consult our website regularly for important information about us.

Forward-Looking Statements This press release contains "forward-looking statements." Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "will," "intends," "potential," "possible" and similar expressions are intended to identify forward-looking statements. These forward-looking statements include statements regarding potential opportunities in the rare disease space; the potential transformative benefits of medicines in the rare disease space; our plans to double the number of employees in Columbus, Ohio by the end of 2022; and the potential for our growing presence in Ohio to help strengthen our close working relationships with long-standing local partners while we work with the greatest urgency to advance our pipeline, further the science of genetic medicine and create an environment where future generations of scientific talent will thrive.

These forward-looking statements involve risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Many of these risks and uncertainties are beyond our control. Known risk factors include, among others: we may not be able to execute on our business plans and goals, including meeting our expected or planned regulatory milestones and timelines, clinical development plans, and bringing our product candidates to market, due to a variety of reasons, many of which are outside of our control, including possible limitations on company financial and other resources, manufacturing limitations that may not be anticipated or resolved for in a timely manner, regulatory, court or agency decisions, such as decisions by the United States Patent and Trademark Office with respect to patents that cover our product candidates; the impact of the COVID-19 pandemic; and those risks identified under the heading Risk Factors” in our most recent Annual Report on Form 10-K for the year ended December 31, 2020, and most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) as well as other SEC filings we make, which you are encouraged to review.

Any of the foregoing risks could materially and adversely affect the Company’s business, results of operations and the trading price of Sarepta’s common stock. For a detailed description of risks and uncertainties we face, we encourage you to review our SEC filings. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release. We undertake no obligation to update forward-looking statements based on events or circumstances after the date of this press release, except as required by law.

Source: Sarepta Therapeutics, Inc.

Investor Contact: Ian Estepan, 617-274-4052 iestepan@sarepta.com

Media Contact: Tracy Sorrentino, 617-301-8566 tsorrentino@sarepta.com

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Sarepta Therapeutics Opens Genetic Therapies Center of Excellence in Columbus, Ohio - Stockhouse

Castle Creek Biosciences Expands its Innovative Gene Therapy Platform for Rare Genetic Connective Tissue Disorders through Research Collaboration with…

EXTON, Pa., Sept. 29, 2021 /PRNewswire/ --Castle Creek Biosciences, Inc., a clinical-stage cell and gene therapy company focused on developing and commercializing disease-modifying therapies for patients suffering from rare diseases for which there is a lack of available treatment options, today announced a research collaboration with Mayo Clinic to advance discovery and pre-clinical development of investigational gene therapy candidates for the treatment of osteogenesis imperfecta (OI) and classical Ehlers-Danlos syndrome (EDS), which are rare genetic connective tissue disorders that currently have no treatments approved by the U.S. Food & Drug Administration (FDA). The research will be led by principal investigator David R. Deyle, M.D., a board-certified medical geneticist with the department of medical genetics at Mayo Clinic and a leader in the field of connective tissue disorders.

"We are honored to be working with Dr. Deyle and his highly regarded research team at Mayo Clinic to identify and evaluate gene therapy candidates that hold promise for treating debilitating, rare connective tissue disorders with high unmet medical needs," said Matthew Gantz, president and chief executive officer of Castle Creek Biosciences. "We expect this initiative will be the first of multiple Castle Creek strategic collaborations with leading medical research institutions that have the potential to expand our innovative gene therapy discoveries for rare diseases and offer hope to underserved patient communities impacted by these devastating conditions."

Osteogenesis imperfecta, also known as brittle bone disease, is caused by genetic mutations that affect the synthesis of Type I collagen and can lead to fragile bones, scoliosis, short stature, dental disorders, and laxity of skin ligaments. OI is estimated to affect one in 6,600 people in the U.S. and may be diagnosed at any age. Classical EDS results from genetic mutations affecting synthesis of Type V collagen and is associated with skin hyperextensibility and fragility, hypotonia, joint instability, chronic pain, and fragile blood vessels. Vascular and pulmonary complications have also been reported. EDS is estimated to affect one in 20,000 people in the U.S.

"Castle Creek is leveraging its proven expertise and experience in rare diseases and late-stage clinical development of cell and gene therapies to establish strategic collaborations with world-class research organizations for studying early-stage novel treatments to address critical, unmet medical challenges of patients suffering from rare genetic conditions," said Jeff Aronin, founder and chairman of Castle Creek Biosciences, and founder, chairman and chief executive officer of Paragon Biosciences, LLC. "We commend Matthew and his leadership team for their strategic insight and guidance that have long-term potential to fuel discovery and advancement of innovative gene therapy candidates and enhance the depth of Castle Creek's pipeline."

For this research collaboration, Castle Creek will contribute its proficiency in rare diseases and gene therapy development and has licensed intellectual property related to OI and classical EDS from Mayo Clinic. Following completion of the discovery through pre-clinical development phases at Mayo Clinic, Castle Creek anticipates moving into clinical development of selected gene therapy candidates at its in-house, commercial-scale current good manufacturing practices (cGMP) manufacturing facility located in Exton, Pa.

About Castle Creek Biosciences, Inc.

Castle Creek Biosciences, Inc. is a clinical-stage cell and gene therapy company focused on developing and commercializing disease-modifying therapies for patients suffering from rare diseases for which there is a lack of available treatment options. The company's proprietary autologous fibroblast platform potentially allows for the development ofpersonalized, targeted and redosable cell-based gene therapy product candidates formonogenic and chronic disorders. The company's most advanced product candidate, dabocemagene autoficel (D-Fi), is currently being evaluated in a Phase 3 clinical trial for the localized treatment of chronic wounds due to recessive dystrophic epidermolysis bullosa (RDEB). The company is also currently evaluating FCX-013 in a Phase 1/2 clinical trial for the treatment of moderate to severe localized scleroderma. In addition, Castle Creek Biosciences is pursuing discovery and potential development of early-stage novel product candidates with the goal of expanding its robust pipeline into other rare diseases and broader indications where there are significant unmet needs. The company operates an in-house, commercial-scale manufacturing facility in Exton, Pennsylvania that benefits from the validated systems and processes previously implemented at the site for manufacture of an FDA-approved cell therapy product.Castle Creek Biosciences, Inc. is a portfolio company of Paragon Biosciences, LLC. For more information, visit https://castlecreekbio.com/or follow Castle Creek on Twitter @CastleCreekBio.

About Paragon Biosciences, LLC

Paragon is a global life science leader that creates, builds and funds innovative biology-based companies in three key areas: cell and gene therapy, adaptive biology and advanced biotechnology. The company's current portfolio includesCastle Creek Biosciences,CiRC Biosciences,Emalex Biosciences,Evozyne,Harmony Biosciences,Qlarity Imaging,Skyline Biosciences, and a consistent flow of incubating companies created and supported by the Paragon Innovation Capital model. Paragon stands at the intersection of human need, life science, and company creation. For more information, please visithttps://paragonbiosci.com/.

Media Contacts

Jenna Urban Berry & Company Public Relations 212.253.8881 [emailprotected]

Karen CaseyCastle Creek Biosciences302.750.4675 [emailprotected]

SOURCE Castle Creek Biosciences, Inc.

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Castle Creek Biosciences Expands its Innovative Gene Therapy Platform for Rare Genetic Connective Tissue Disorders through Research Collaboration with...

Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing Market to Witness Huge Growth by 2028 | BioReliance, Cobra Biologics, Oxford BioMedica…

Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing Market report focused on the comprehensive analysis of current and future prospects of the Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing industry. It describes the optimal or favourable fit for the vendors to adopt successive merger and acquisition strategies, geography expansion, research & development, and new product introduction strategies to execute further business expansion and growth during a forecast period. An in-depth analysis of past trends, future trends, demographics, technological advancements, and regulatory requirements for the Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing market has been done in order to calculate the growth rates for each segment and sub-segments.

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Note In order to provide more accurate market forecast, all our reports will be updated before delivery by considering the impact of COVID-19.

Top Key Vendors of this Market are:

BioReliance, Cobra Biologics, Oxford BioMedica, UniQure, FinVector, MolMed, MassBiologics, Richter-Helm, FUJIFILM Diosynth Biotechnologies, Lonza, Aldevron, Eurogentec, Cell and Gene Therapy Catapult, Biovian, Thermo Fisher Scientific (Brammer Bio), VGXI, PlasmidFactory, bluebird bio, Novasep, Spark Therapeutics, Vigene Biosciences.

Global Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing Market Segmentation:

Product Type Segmentation:

CancersInherited DisordersViral InfectionsOthers

Industry Segmentation:

CancersInherited DisordersViral InfectionsOthers

Various factors are responsible for the markets growth trajectory, which are studied at length in the report. In addition, the report lists down the restraints that are posing threat to the global Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing market. This report is a consolidation of primary and secondary research, which provides market size, share, dynamics, and forecast for various segments and sub-segments considering the macro and micro environmental factors. It also gauges the bargaining power of suppliers and buyers, threat from new entrants and product substitute, and the degree of competition prevailing in the market.

The influence of the latest government guidelines is also analysed in detail in the report. It studies the Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing markets trajectory between forecast periods. The cost analysis of the Global Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing Market has been performed while keeping in view manufacturing expenses, labour cost, and raw materials and their market concentration rate, suppliers, and price trend.

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The report provides insights on the following pointers:

Market Penetration: Comprehensive information on the product portfolios of the top players in the Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing market.

Competitive Assessment: In-depth assessment of the market strategies, geographic and business segments of the leading players in the market.

Product Development/Innovation: Detailed insights on the upcoming technologies, R&D activities, and product launches in the market.

Market Development: Comprehensive information about emerging markets. This report analyzes the market for various segments across geographies.

Market Diversification: Exhaustive information about new products, untapped geographies, recent developments, and investments in the Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing market.

Regions Covered in the Global Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing Market Report 2021: The Middle East and Africa (GCC Countries and Egypt) North America (the United States, Mexico, and Canada) South America (Brazil etc.) Europe (Turkey, Germany, Russia UK, Italy, France, etc.) Asia-Pacific (Vietnam, China, Malaysia, Japan, Philippines, Korea, Thailand, India, Indonesia, and Australia)

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Table of Contents

Global Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing Market Research Report 2021 2027

Chapter 1 Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing Market Overview

Chapter 2 Global Economic Impact on Industry

Chapter 3 Global Market Competition by Manufacturers

Chapter 4 Global Production, Revenue (Value) by Region

Chapter 5 Global Supply (Production), Consumption, Export, Import by Regions

Chapter 6 Global Production, Revenue (Value), Price Trend by Type

Chapter 7 Global Market Analysis by Application

Chapter 8 Manufacturing Cost Analysis

Chapter 9 Industrial Chain, Sourcing Strategy and Downstream Buyers

Chapter 10 Marketing Strategy Analysis, Distributors/Traders

Chapter 11 Market Effect Factors Analysis

Chapter 12 Global Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing Market Forecast

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Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing Market to Witness Huge Growth by 2028 | BioReliance, Cobra Biologics, Oxford BioMedica...

Transforming Growth Factor Sales Gaining Traction & to reach US$ 709.9 Mn with Significant Development in Cell Therapy Research – PRNewswire

Cell therapy plays an important role in vascular and hematopoietic, neural, skeletal, pancreatic, periodontal, and mucosal tissue regeneration. Platelet-derived growth factors and bone morphogenetic factors are gaining high demand for diabetic neuropathic ulcers and periodontal defects, and tissue regeneration at sites of tibia fractures. Increasing demand for transforming growth factors in regenerative medicine is expected to propel market growth substantially over the coming years.

Stem cell research continues to expand due to high adoption of stem cell treatment. Therefore, bone morphogenetic proteins (BMPs) and TGF-beta proteins are gaining demand and supporting the clinical development of cellular therapies. Cell culture has helped the most in oncology research as cancer cells are more responsive to culture in vitro, which, in turn, is drive demand in research areas.

Increasing healthcare R&D expenditure further improves the chances of breakthrough treatment options. Rapidly growing healthcare expenditure is resulting in new molecule discovery, evaluation of various molecules for possible disease treatment, and adoption of innovative approaches in these studies.

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Key manufacturers of transforming growth factor are focusing on the development of technology to cater to specific research requirements.

The COVID-19 pandemic affected health services for other diseases such as hypertension, cancer, diabetes, and cardiovascular diseases. Selective procedures such as orthopedic joint replacement were impacted. Shifted focus of healthcare professionals from these diseases to address the COVID-19 crisis negatively impacted the overall healthcare industry.

However, the transforming growth factor space did not see any long-term adverse effect on its business. A short-term impact of COVID-19 has been seen on the market due to disruptions in the supply chain and research activities during lockdowns. The market is projected to experience smooth growth over the coming years.

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Key Takeaways from Market Stud

By grade, the GMP segment is fast-growing at CAGR of 9.3%, on the back of rise is demand for supreme quality growth factors across regions.

Based on product, bone morphogenetic proteins (BMPs) is leading with over 43% market share.

Oncology research is estimated to lead the market by application. This segment accounted for approximately 22% share of the market.

Pharmaceutical and biotechnology companies lead demand for transforming growth factors with a market share of 48%.

By region, North America is set dominate the global market with a value share of around 41%. Europe is slated to be the second-largest leading region with a value share of 32%.

"Increasing drug discovery and stem cell research is expected to drive market expansion of transforming growth factors over the next ten years," says an analyst of Persistence Market Research.

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Market Competition

Agreements, collaborations, and partnerships have emerged as the key growth strategy adopted by industry players. By focusing on these strategies, key stakeholders are expanding their geographic footprints and strengthening their existing product portfolios.

In February, 2019, Roche entered into a definitive merger agreement to acquire Spark Therapeutics.

In 2021, Bio-Techne Corporation) and Catamaran Bio expanded their collaboration for the development of cell engineering and cell process technologies for use by Catamaran in the manufacturing of CAR-NK cell therapy products.

What Does the Report Cover?

Persistence Market Research offers a unique perspective and actionable insights on the transforming growth factor market in its latest study, presenting historical demand assessment of 2016 2020 and projections for 2021 2031.

The research study is based on the product (activin, bone morphogenetic proteins (BMPs), TGF-beta proteins), grade (GMP grade, NON-GMP grade), application (oncology research, haematology research, wound healing research, dermatology research, cardiovascular disease & diabetes, cell therapy and ex vivo manufacturing, others), end user (pharmaceutical and biotechnology companies, research centres & academic institutes, CMOs and CDMOs), across seven key regions of the world.

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Transforming Growth Factor Sales Gaining Traction & to reach US$ 709.9 Mn with Significant Development in Cell Therapy Research - PRNewswire

Longeveron Successfully Advancing its Cell-Based Therapy Studies in a Growing Industry Segment – Yahoo Finance

Research and development of stem cell-based therapies, where a patients own cells, or those from a donor, are used to fight injury and disease, is one of the fastest growing areas in the biotech space. Longeveron Inc. (NASDAQ: LGVN), a clinical-stage biotechnology company in the thick of clinical development, continues to advance its investigational therapeutic, Lomecel-B, for chronic, aging-related and life-threatening conditions.

The company recently announced the results of its randomized, blinded and placebo-controlled Phase 2 trial to evaluate the safety and efficacy of its proprietary Lomecel-B infusion in frail, older patients between 70 and 85 years old. The trial, which was partially funded by the National Institute on Aging, evaluated a single intravenous infusion of 4 different doses of Lomecel-B cell therapy compared to placebo on the change in the distance a person could walk in 6 minutes (a test known as the 6-minute walk test). Results showed that a single infusion of Lomecel-B resulted in an increase in walk distance of approximately 50 meters (164 feet) at 6 and 9 months after infusion, while the placebo-treated subjects showed minimal improvement at 6 months and a deterioration by 9 months.

Lomecel-B is a proprietary allogeneic product comprised of medicinal signaling cells (MSCs) from the bone marrow of adult donors, which are culture-expanded in Longeverons current good manufacturing practice cell-processing facility. According to trial results so far, Lomecel-B, and MSCs in general, may be injected or infused into an unrelated recipient without triggering a harmful reaction (rejection) due to the biochemical properties of these specialized cells. This is in part what makes this class of biologic so intriguing for use as a regenerative therapeutic.

A growing global trend is for biotech companies to direct their services to the cell and gene therapy industry and moving to expand into a new branch of the pharmaceutical contract development and manufacturing organization world.

Story continues

The U.S. Food and Drug Administration (FDA) has approved a small number of cell and gene therapy drugs. Still, a new product pipeline is fighting for the agencys attention with approximately 1,200 experimental therapies more than half in Phase 2 clinical trials. The annual sales growth estimates for cell therapies are projected to reach 15%.

Longeveron has also initiated a Phase 2 trial evaluating the safety and efficacy of Lomecel-B injection into the heart of children born with hypoplastic left heart syndrome (HLHS), a rare and often fatal congenital heart defect.

Longeveron believes that using the same cells that promote tissue repair, organ maintenance and immune system function can develop safe and effective therapies for some of the most challenging diseases and conditions associated with aging.

We continue to make steady progress advancing our Lomecel-B clinical research programs forward, Longeveron CEO Geoff Green said. We have encouraging top-line results from our Aging Frailty program, and anticipate initiating a Phase 2 trial in Alzheimers disease later this year.

Longeveron shared their review of the Aging Frailty trial data with independent frailty experts, with the objective of planning the next steps for the program. The company presented clinical data at the 2021 International Conference on Frailty & Sarcopenia Research on Sept. 29 during a round-table presentation.

Learn more about Longeveron at http://www.longeveron.com.

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2021 Benzinga.com. Benzinga does not provide investment advice. All rights reserved.

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Longeveron Successfully Advancing its Cell-Based Therapy Studies in a Growing Industry Segment - Yahoo Finance

Global Hemoglobinopathies Markets, 2021-2028 – High Unmet Needs / Increasing R&D Investment / Initiatives to Improve Disease Awareness -…

DUBLIN--(BUSINESS WIRE)--The "Global Hemoglobinopathies Market Size, Share & Trends Analysis Report by Type (Thalassemia, Sickle Cell Disease, Other Hemoglobin (Hb) Variants), by Diagnosis, by Therapy, by Region, and Segment Forecasts, 2021-2028" report has been added to ResearchAndMarkets.com's offering.

The global hemoglobinopathies market size is expected to reach USD 15.7 billion by 2028, expanding at a CAGR of 10.8%

Increasing awareness regarding hemoglobinopathies and government initiatives to diagnose the diseases at an early stage are expected to propel market growth over the forecast period. Moreover, increasing R&D investment, the presence of a promising drug pipeline, and technologically advanced diagnostics platforms are expected to boost the growth of the market.

The development of novel curative technologies, such as CRISPR/Cas9 and hematopoietic stem cell transplantation, coupled with a promising pipeline, is expected to propel market growth. Moreover, the presence of regulatory agencies, such as the FDA, which are working toward improving drug approval rate by granting accelerated approval for hemoglobinopathies drugs, is expected to drive the market.

Initiatives such as the Sickle Cell Awareness Initiative (SCAI) are working toward educating the people about the disease, which will increase the diagnosis and treatment rate. SCAI also raises funds for individuals affected with sickle cell diseases (SCDs) and provides research funding.

Moreover, governments of Middle Eastern and Asian countries provide funds for R&D of hemoglobinopathies treatment. For instance, various programs undertaken by governments, such as thalassemia screening in neonates and providing medicines, are impacting the market growth positively.

The high patient population in low-income countries has encouraged market players and non-profit organizations to launch several initiatives to improve the access to the therapy.

For instance, in February 2019, the Access to Excellent Care for Sickle Cell Patients Pilot Program (ACCEL) was launched by Global Blood Therapeutics, Inc. in order to provide research funding for novel SCD projects, with an aim to expand the access to optimal healthcare for sickle cell disease.

Biopharmaceutical companies are collaborating with nonprofit organizations to promote public awareness about hemoglobinopathies.

An increase in investment and funding for the development of novel therapies to treat hemoglobinopathies will further boost the market growth over the forecast period. The National Heart, Lung, and Blood Institute (NHLBI) has significantly invested in research & development in sickle cell disease.

The NHLBI supports research work through various initiatives. Furthermore, private funding such as the Bronx Blood Research Fund (BBRF) provides a platform for research and management of thalassemia and other hemoglobinopathies.

Gene therapy has emerged as a promising treatment option for managing hemoglobin disorder as it targets the underlying genetic cause of the condition through the administration of one-time gene therapy and significantly reduces the need for blood transfusions.

The current pipeline of gene therapy products includes CTX001 (CRISPR Therapeutics), BIVV003 (Sangamo Therapeutics, Inc. & Bioverativ Inc), and HGB-206 (bluebird bio, Inc).

Hemoglobinopathies Market Report Highlights

Global Hemoglobinopathies Market Variables, Trends & Scope

Penetration and Growth Prospect Mapping

Epidemiology Assessment of Hemoglobinopathies

Market Variable Analysis

Market Restraint Analysis

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/8dphl0

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Global Hemoglobinopathies Markets, 2021-2028 - High Unmet Needs / Increasing R&D Investment / Initiatives to Improve Disease Awareness -...

BrainStorm to Present at the 2021 Cell & Gene Meeting on the Mesa – WSAZ-TV

Published: Oct. 4, 2021 at 6:00 AM EDT

NEW YORK, Oct. 4, 2021 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of cellular therapies for neurodegenerative diseases, announced today that Stacy Lindborg, Ph.D., Executive Vice President and Head of Global Clinical Research, will deliver a presentation at the2021 Cell & Gene Meeting on the Mesa, being held as a hybrid conferenceOctober 12-14, and October 19-20, 2021.

Dr. Lindborg's presentation highlights the expansion of Brainstorm's technology portfolio to include autologous and allogeneic product candidates, covering multiple neurological diseases. The most progressed clinical development program, which includes a completed phase 3 trial of NurOwn in ALS patients, remains the highest priority for Brainstorm. Brainstorm is committed to pursuing the best and most expeditious path forward to enable patients to access NurOwn.

Dr. Lindborg's presentation will be in the form of an on-demand webinar that will be available beginning October 12. Those who wish to listen to the presentation are required to registerhere. At the conclusion of the 2021 Cell & Gene Meeting on the Mesa, a copy of the presentation will also be available in the "Investors and Media" section of the BrainStorm website underEvents and Presentations.

About the 2021 Cell & Gene Meeting on the Mesa

The meeting will feature sessions and workshops covering a mix of commercialization topics related to the cell and gene therapy sector including the latest updates on market access and reimbursement schemes, international regulation harmonization, manufacturing and CMC challenges, investment opportunities for the sector, among others. There will be over 135 presentations by leading public and private companies, highlighting technical and clinical achievements over the past 12 months in the areas of cell therapy, gene therapy, gene editing, tissue engineering and broader regenerative medicine technologies.

The conference will be delivered in a hybrid format to allow for an in-person experience as well as a virtual participation option. The in-person conference will take place October 12-14 in Carlsbad, CA. Virtual registrants will have access to all content via livestream during program dates. Additionally, all content will be available on-demand within 24 hours of the live program time. Virtual partnering meetings will take place October 19-20 via Zoom.

About NurOwn

The NurOwntechnology platform (autologous MSC-NTF cells) represents a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors (NTFs). Autologous MSC-NTF cells are designed to effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression.

About BrainStorm Cell Therapeutics Inc.

BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwntechnology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug designation status from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm has completed a Phase 3 pivotal trial in ALS (NCT03280056); this trial investigated the safety and efficacy of repeat-administration of autologous MSC-NTF cells and was supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). BrainStorm completed under an investigational new drug application a Phase 2 open-label multicenter trial (NCT03799718) of autologous MSC-NTF cells in progressive multiple sclerosis (MS) and was supported by a grant from the National MS Society (NMSS).

For more information, visit the company's website atwww.brainstorm-cell.com.

Safe-Harbor Statement

Statements in this announcement other than historical data and information, including statements regarding future NurOwnmanufacturing and clinical development plans, constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may," "should," "would," "could," "will," "expect,""likely," "believe," "plan," "estimate," "predict," "potential," and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, BrainStorm's need to raise additional capital, BrainStorm's ability to continue as a going concern, the prospects for regulatory approval of BrainStorm's NurOwntreatment candidate, the initiation, completion, and success of BrainStorm's product development programs and research, regulatory and personnel issues, development of a global market for our services, the ability to secure and maintain research institutions to conduct our clinical trials, the ability to generate significant revenue, the ability of BrainStorm's NurOwntreatment candidate to achieve broad acceptance as a treatment option for ALS or other neurodegenerative diseases, BrainStorm's ability to manufacture, or to use third parties to manufacture, and commercialize the NurOwntreatment candidate, obtaining patents that provide meaningful protection, competition and market developments, BrainStorm's ability to protect our intellectual property from infringement by third parties, heath reform legislation, demand for our services, currency exchange rates and product liability claims and litigation; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available athttp://www.sec.gov. These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements.

ContactsInvestor Relations:Eric GoldsteinLifeSci Advisors, LLCPhone: +1 646.791.9729egoldstein@lifesciadvisors.com

Media:Paul TyahlaSmithSolvePhone: + 1.973.713.3768Paul.tyahla@smithsolve.com

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The above press release was provided courtesy of PRNewswire. The views, opinions and statements in the press release are not endorsed by Gray Media Group nor do they necessarily state or reflect those of Gray Media Group, Inc.

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