Taysha Gene Therapies, Inc.

Data from an analysis of five NHP studies showed lumbar IT administration led to widespread and consistent biodistribution of AAV9 gene therapy vectors across brain and spinal cord regions IT and ICM administration achieved comparable biodistribution across brain and spinal cord regions in NHPs Findings from the analysis reaffirm the clinical potential of IT administration as an effective, safe and minimally invasive approach to deliver AAV-based gene therapies designed to treat CNS diseases in both children and adults DALLAS, Oct. 22, 2024 (GLOBE NEWSWIRE) -- Taysha Gene Therapies, Inc. (Nasdaq: TSHA) (Taysha or the Company), a clinical-stage biotechnology company focused on advancing adeno-associated virus (AAV)-based gene therapies for severe monogenic diseases of the central nervous system (CNS), today announced that it will present biodistribution data from an analysis of 28 non-human primates (NHP) evaluating the delivery of AAV9 gene therapy vectors across five different studies using intrathecal (IT) delivery by lumbar puncture (four studies) or intra-cisterna magna (ICM) injection (one study). The data will be presented during a poster presentation at the upcoming 31st Annual Congress of the European Society of Gene & Cell Therapy (ESGCT), taking place in Rome, Italy from October 22-25, 2024. These findings reinforce Taysha’s clinical development approach utilizing IT administration to deliver AAV-based gene therapies designed to treat the genetic root cause of CNS diseases, including the TSHA-102 program in clinical evaluation for children, adolescents and adults living with Rett syndrome. “Findings from an analysis across five NHP studies showed that both IT and ICM administration led to comparable, consistent and widespread biodistribution of AAV9 vector throughout the brain and spinal cord regions,” said Sukumar Nagendran, M.D., President and Head of Research & Development at Taysha. “Importantly, these findings further support the clinical potential of IT administration as an effective, safe and minimally invasive delivery approach for broad targeting of the CNS that has potential for outpatient use in both children and adults. We believe the NHP biodistribution data, together with our additional preclinical data, reaffirm our clinical development strategy utilizing IT administration and provide translational support for the broad clinical effect reported following treatment with TSHA-102 in both our REVEAL adolescent/adult trial and REVEAL pediatric trial." Poster presentation details are as follows: Title: Broad CNS Biodistribution of AAV9-based Gene Therapies Delivered by Intrathecal Lumbar Puncture in Non-Human Primates Presenters: Nino Devidze, MS, Ph.D., Clinical Development Lead and Emdadul Haque, Ph.D., Senior Director, Translational Sciences at Taysha Gene Therapies Date and Time: Wednesday October 23, 2024, from 13:30 to 15:00 CEST Poster Session: CNS & Sensory Diseases Poster Number: P0284 Additional details on the meeting can be found at the 31st Annual ESGCT Congress website. About TSHA-102TSHA-102 is a self-complementary intrathecally delivered AAV9 investigational gene transfer therapy in clinical evaluation for Rett syndrome. Designed as a one-time treatment, TSHA-102 aims to address the genetic root cause of the disease by delivering a functional form of MECP2 to cells in the CNS. TSHA-102 utilizes a novel miRNA-Responsive Auto-Regulatory Element (miRARE) technology designed to mediate levels of MECP2 in the CNS on a cell-by-cell basis without risk of overexpression. TSHA-102 has received Regenerative Medicine Advanced Therapy, Fast Track and Orphan Drug and Rare Pediatric Disease designations from the FDA, Orphan Drug designation from the European Commission and Innovative Licensing and Access Pathway designation from the Medicines and Healthcare products Regulatory Agency. About Rett SyndromeRett syndrome is a rare neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene encoding methyl CpG-binding protein 2 (MeCP2), which is essential for regulating neuronal and synaptic function in the brain. The disorder is characterized by loss of communication and hand function, slowing and/or regression of development, motor and respiratory impairment, seizures, intellectual disabilities and shortened life expectancy. Rett syndrome progression is divided into four key stages, beginning with early onset stagnation at 6 to 18 months of age followed by rapid regression, plateau and late motor deterioration. Rett syndrome primarily occurs in females and is one of the most common genetic causes of severe intellectual disability. Currently, there are no approved disease-modifying therapies that treat the genetic root cause of the disease. Rett syndrome caused by a pathogenic/likely pathogenic MECP2 mutation is estimated to affect between 15,000 and 20,000 patients in the U.S., EU, and U.K. About Taysha Gene TherapiesTaysha Gene Therapies (Nasdaq: TSHA) is a clinical-stage biotechnology company focused on advancing adeno-associated virus (AAV)-based gene therapies for severe monogenic diseases of the central nervous system. Its lead clinical program TSHA-102 is in development for Rett syndrome, a rare neurodevelopmental disorder with no approved disease-modifying therapies that address the genetic root cause of the disease. With a singular focus on developing transformative medicines, Taysha aims to address severe unmet medical needs and dramatically improve the lives of patients and their caregivers. The Company’s management team has proven experience in gene therapy development and commercialization. Taysha leverages this experience, its manufacturing process and a clinically and commercially proven AAV9 capsid in an effort to rapidly translate treatments from bench to bedside. For more information, please visit www.tayshagtx.com. Forward-Looking StatementsThis 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,” “plans,” and “future” or similar expressions are intended to identify forward-looking statements. Forward-looking statements include, but are not limited to, statements concerning the potential of TSHA-102 and Taysha’s other product candidates to positively impact quality of life and alter the course of disease in the patients Taysha seeks to treat, its research, development and regulatory plans for its 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 Taysha’s product candidates. Forward-looking statements are based on management’s 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 Taysha’s business are described in detail in its SEC filings, including in Taysha’s Annual Report on Form 10-K for the full-year ended December 31, 2023 and Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, which are available on the SEC’s website at www.sec.gov. Additional information will be made available in other filings that Taysha makes from time to time with the SEC. These forward-looking statements speak only as of the date hereof, and Taysha disclaims any obligation to update these statements except as may be required by law. Company Contact:Hayleigh Collins Director, Head of Corporate Communications and Investor RelationsTaysha Gene Therapies, Inc.hcollins@tayshagtx.com Media Contact:Carolyn HawleyInizio EvokeCarolyn.hawley@inizioevoke.com

A gene therapy pioneer thinks he has a solution to the field’s struggle to commercialize breakthrough cures: Go global. Jim Wilson’s Philadelphia-based company GemmaBio on Tuesday announced up to $100 million in funding to manufacture and test six gene therapies in Brazil. The company’s plan, funded by Brazil’s Ministry of Health, looks to produce the potential medicines at a fraction of the millions of dollars that they often cost. Drugmakers big and small have found that the price tag for gene therapies made them a tough sell, or impractical to develop. In an interview, Wilson told Endpoints News that he’ll soon board flights to Korea, Saudi Arabia and other countries in hopes of making similar partnerships with organizations there. “What I’d like to be remembered for, and this is the chapter that we’re working on now that we have not yet achieved, is to be an advocate for global access of genetic medicines,” Wilson said. Wilson, initially known for a tragedy that halted the gene therapy field 25 years ago, managed a comeback by leading an influential group at the University of Pennsylvania. His academic unit developed methods for delivering genes to cells, a major step in breakthrough therapies, like Novartis’ therapy Zolgensma for spinal muscular atrophy. That progress, however, couldn’t overcome another trend: Companies began to abandon rare disease medicines that were deemed commercially unviable. Endpoints reported last year that dozens of companies had shelved dozens of treatments for rare conditions, often citing the cost of development and commercial uncertainty. Those failures led Wilson to conclude that the existing model for those rare diseases and their tiny groups of patients had reached its limit. “We had sort of run our course of what we can do in an academic setting,” Wilson said. In late July, the University of Pennsylvania board of trustees approved a spinout of Wilson’s research group that became GemmaBio. The company is initially working on eight therapies, three of them licensed from Passage Bio, a company Wilson co-founded in 2018. Under a licensing deal reached in August, GemmaBio paid Passage Bio $10 million upfront, and the agreement calls for additional milestone payments. Many drugmakers have turned away from gene therapies aimed at rare conditions because of the limited size of the markets. Wilson believes that GemmaBio’s global approach will maximize the number of patients treated. To reach them, the company is zeroing in on countries that look to benefit the most from its potential medicines. One of the diseases it’s targeting — a fatal disorder called GM1 gangliosidosis that destroys neurons in the brain and spinal cord — is 10 times as common in Brazil compared to the rest of the world. “You have to go to where the prevalence is higher to conduct the clinical trials,” Wilson said. For GemmaBio, Brazil made sense in additional ways. The company is partnering with Fiocruz, a division of Brazil’s Ministry of Health, that has built up the country’s biomanufacturing sector to lessen costs and be closer to patients. During the pandemic, Fiocruz partnered with AstraZeneca to locally produce the company’s Covid-19 vaccine. Fiocruz has also worked with a nonprofit to domestically manufactur e CAR-T therapies. Fiocruz’s up to $100 million in funding to GemmaBio will go toward clinical trials and manufacturing, with an eye toward securing approval for the six therapies in the region and potentially other countries. “Brazil could be a foothold to gain broader access throughout Latin America,” Wilson said. In exchange for Fiocruz’s financial support, the organization has the option to license related treatments to supply the Brazilian public health system. Often, drugmakers first worry about FDA clearance, which quickens approvals in other countries. But Wilson said he’s encouraged by an FDA pilot program that looks to develop uniform standards across countries. “While we’re focusing this announcement on Brazil, we’re thinking globally,” Wilson said. GemmaBio’s mission aligns with calls to make gene therapies accessible. “Researchers, drug developers and drug manufacturers are squandering the chance to make gene therapies viable even in wealthier countries, let alone transformative for the world,” co-authors Evelyn Mwesigwa Harlow and Jennifer Adair wrote earlier this year in Nature . “To seize the opportunity, they must take into account the populations most in need, as well as the global market for treatments — both when developing and when valuing the drugs.” It was once unthinkable that Wilson could be at the forefront of bringing gene therapies to the world. In 1999, he led a first-of-its-kind experiment in which 18-year-old Jesse Gelsinger died because of a gene therapy that triggered an immune system reaction. The death was a major setback for the field and for Wilson, whose gene therapy center was disbanded, and he was barred from working on clinical trials for five years. In a comeback over the intervening years, Wilson’s lab discovered a family of viruses that could be engineered to shuttle gene therapies to cells, leading to a resurgence of the field. GemmaBio’s mission is being cheered on by rare disease advocates, who have watched drugmakers leave the space en masse . “You don’t do that unless you really care,” Christine Waggoner, the co-founder of the Cure GM1 Foundation, which jumpstarted one of the therapies that was paused by Passage Bio and licensed by GemmaBio. GemmaBio still faces a major challenge. Companies like Taysha Gene Therapies have tried to standardize gene therapy development only for their plans to crumble. A cash crunch at Taysha led the company to scrap most of its work, and it has been slow to offload paused programs that were initially funded by families. Wilson said GemmaBio distinguishes itself through both a global strategy and a focus on diseases with a smoother path for regulatory approval. “Many of the diseases that they selected were complicated,” Wilson said of other efforts. “Clinical development wasn’t clear. Endpoints weren’t clear. Natural history wasn’t clear. Potential for accelerated approval wasn’t clear.” Beyond just disease selection, GemmaBio could benefit from the FDA’s increasing openness to accelerated approval for gene therapies. And the agency is developing a so-called platform policy that could allow drug developers to simultaneously target multiple diseases without redoing critical work. Alongside GemmaBio, Wilson founded Franklin Biolabs, a contract research organization that specializes in viral vectors for gene therapies. It has received an undisclosed amount in funding from Savanne Life Sciences, the investment arm of Bioculture Group, a breeder of non-human primates for research. Plans call for soon disclosing how much GemmaBio received in seed funding, and from whom, according to Wilson. Besides venture capital, he’s hoping for a long-term extension of a federal voucher program that’s designed to incentivize the development of rare disease drugs. And the $100 million from Fiocruz is the first, he hopes, of more government partnerships. “It sends a message there is a different way for all of us to succeed in our business,” Wilson said.

Astellas Pharma is spreading its bets in neurodegenerative disorders, committing $50 million to AviadoBio for the opportunity to license its lead program, an experimental gene therapy for a type of dementia with no FDA-approved drugs. The sum breaks down to a $20 million equity investment and up to $30 million in upfront payments. The deal announced Tuesday grants Astellas an exclusive option to license global rights to the London-based startup’s AVB-101, which is currently in early clinical development as a potential treatment for a certain form of frontotemporal dementia (FTD). FTD is a type of early-onset dementia that leads to rapid decline in functions such as attention control, working memory, and problem solving. It typically causes death within three to 13 years of diagnosis, according to AviadoBio. The company aims to specifically treat this dementia when it is driven by a mutation to the gene that encodes progranulin (PGN), a protein that regulates immune activity in the brain. presented by Health IT Accelerating Claim Processing: Strategies to Shorten the Life of a Claim These strategies and practices can significantly shorten the life cycle of claims, leading to quicker resolutions and improved financial outcomes. By Greenway Health AVB-101 delivers to the central nervous system a functioning copy of the gene that provides instructions for making progranulin. The goal of the one-time treatment is to bring levels of that protein into the range of normal. Administered into the thalamus of the brain, AviadoBio’s therapy is transported to its cellular targets aboard an adeno-associated virus (AAV), an engineered virus widely as a delivery vehicle for genetic medicines. AviadoBio’s science is based on research from King’s College London. The startup emerged from stealth in 2021, backed by $80 million in Series A financing. In preclinical research conducted with progranulin-deficient mice, AviadoBio has reported its experimental FTD-PGN therapy led to expression of progranulin in the brain and a reduction in disease pathology. A Phase 1/2 ascending-dose clinical trial treated its first patient earlier this year. The open-label study has a targeted enrollment of nine participants. There are other efforts underway to try and restore progranulin levels as a way to treat FTD-PGN. Passage Bio’s PBFT02 is a gene therapy intended to boost levels of the key protein in the central nervous system. This program has reached Phase 1/2 testing. Alector is taking a different approach with AL100, an antibody drug designed to bind to a protein that leads to degradation of progranulin. This program has reached Phase 3 testing under a partnership with GSK, which has rights to share in the development and commercialization of this experimental therapy. Gene therapy is one of the areas Astellas has identified for growth, Richard Wilson, the company’s senior vice president for genetic regulation, told MedCity News last year. Within gene therapy, the company is focusing on neuromuscular disorders, central nervous system conditions, and ophthalmology. Astellas’s gene therapy division formed from the 2020 acquisition of Audentes Therapeutics, which brought a pipeline of gene therapies in various stages of development for rare inherited disorders. presented by Health Tech What’s Keeping Healthcare CIOs Up at Night: How to Improve Patient Satisfaction by Handling Calls More Efficiently Health systems have spent billions on portals while investments in modernizing the voice channel — the dominant preference of healthcare consumers — have taken a backseat. By Stephanie Baum Some of the Audentes programs have encountered setbacks. The FDA in 2021 placed a clinical hold on an experimental gene therapy for the enzyme deficiency Pompe disease. That hold was lifted in early 2023. Three gene therapy programs for Duchenne muscular dystrophy were terminated in 2022 based on preclinical data. A gene therapy for the rare neuromuscular disorder X-linked myotubular myopathy was placed under a clinical hold in 2020 following three patient deaths. Though it later was cleared to resume, a fourth patient death in 2021 led to another clinical hold that is still in place. Astellas has prior experience with option deals for gene therapies. Two years ago, Astellas made an equity investment in Taysha Gene Therapies, securing exclusive options to license gene therapies for the rare neurodegenerative disorders giant axonal neuropathy (GAN) and Rett syndrome. Following the report of Phase 1/2 data for the GAN gene therapy last year, Astellas said it would not exercise its option on that program. A key Rett study is ongoing and the option for this program remains open. Astellas has struck other deals to fill its gene therapy pipeline. Last year, the company licensed a preclinical Kate Therapeutics gene therapy in development for X-linked myotubular myopathy. Following that deal, Astellas licensed the rights to use a 4D Molecular Therapeutics AAV vector for ophthalmic diseases. The option agreement with AviadoBio covers the application of AVB-101 to FTD-GRN and other indications. The trigger for the option and the option exercise period were not disclosed. But if Astellas exercises it, AviadoBio could receive up to $2.18 billion in license fees and milestone payments, plus royalties from sales of a commercialized product. “As we complete dosing of the first cohort of patients in our Phase 1/2 ASPIRE-FTD trial of AVB-101, we are excited about the potential of this collaboration to help address the unmet need that exists today in frontotemporal dementia,” AviadoBio CEO Lisa Deschamps said in a prepared statement. “This strategic collaboration will combine our promising gene therapy candidate for FTD-GRN and delivery expertise with Astellas’s global capabilities in development and commercialization of gene therapies.” Public domain image by Flickr user SciTechTrend