4D Molecular Therapeutics, Inc.

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

Preclinical data for 4D-710 for cystic fibrosis lung disease in combination with CFTR modulators to be presented in a poster presentationEMERYVILLE, Calif., Sept. 23, 2024 (GLOBE NEWSWIRE) -- 4D Molecular Therapeutics (Nasdaq: FDMT, 4DMT or the Company), a leading clinical-stage genetic medicines company focused on unlocking the full potential of genetic medicines to treat large market diseases, today announced a poster presentation at the 2024 North American Cystic Fibrosis Conference (NACFC) in Boston, Massachusetts on September 26-28, 2024. 2024 NACFC Poster Presentation Details: Title:Transgene expression and CFTR channel function in human bronchial epithelial cells following addition of CFTR modulators and 4D-710Poster Session:Poster 344Date/Time:Friday, September 27, 2024 (1:15 – 2:15 p.m. ET)Presenter:Melissa A. Calton, Ph.D., VP, Early-Stage Product Development at 4DMT The presentation will also be available on the 4DMT website: https://4dmoleculartherapeutics.com/pipeline/#posters-and-publications About 4DMT 4DMT is a leading clinical-stage genetic medicines company focused on unlocking the full potential of genetic medicines to treat large market diseases in ophthalmology and pulmonology. 4DMT’s proprietary invention platform, Therapeutic Vector Evolution, combines the power of the Nobel Prize-winning technology, directed evolution, with approximately one billion synthetic AAV capsid-derived sequences to invent customized and evolved vectors for use in our wholly owned and partnered product candidates. Our product design, development, and manufacturing engine helps us efficiently create and advance our diverse product pipeline with the goal of revolutionizing medicine with potential curative therapies for millions of patients. Currently, 4DMT is advancing six clinical-stage and one preclinical product candidate, each tailored to address rare and large market diseases in ophthalmology, pulmonology and cardiology. In addition, 4DMT is also advancing programs in CNS through a gene editing partnership. 4D Molecular Therapeutics™, 4DMT™, Therapeutic Vector Evolution™, and the 4DMT logo are trademarks of 4DMT. All of our product candidates are in clinical or preclinical development and have not yet been approved for marketing by the U.S. Food and Drug Administration (FDA) or any other regulatory authority. No representation is made as to the safety or effectiveness of our product candidates for the therapeutic uses for which they are being studied. Learn more at www.4DMT.com and follow us on LinkedIn. Contacts: Media: Katherine SmithInizio Evoke CommsMedia@4DMT.com Investors: Julian PeiHead of Investor Relations and Corporate FinanceInvestor.Relations@4DMT.com

4D Molecular Therapeutics’ one-time gene therapy reduced the need for annual injections in patients with age-related blindness in a mid-stage trial. The company on Wednesday reported updated Phase 1/2 data for its lead candidate, 4D-150, finding that 70% of treated patients in a broad Phase 2b population did not need an annualized injection of Regeneron’s Eylea. In that 30-patient group, 4DMT reported an 89% reduction in annualized injections through 52 weeks and said that 80% of patients received zero or one injection. The findings were even more pronounced in a 15-person cohort of patients who were recently diagnosed with wet age-related macular degeneration. 4DMT reported similar data in a Phase 1/2 population with more severe patients, including an 83% reduction in annual injections. More than half of patients had zero or one injection through 52 weeks and 44% were injection-free. In an interview, CEO David Kirn said the results are substantial evidence that its intravitreal injection — meaning it’s injected directly into the eye — is just as effective as other anti-VEGF candidates that require subretinal shots. Intravitreal injections are easier to perform than subretinal, which require surgery. “We’re thrilled to say we now have that,” he said. Though regulators only ask for data through 52 weeks, Kirn expects the effects of the therapy to be durable for five or more years. Investors were evidently less thrilled, with the company’s shares down 22% after the market opened Thursday. The injection did not lead to any new side effects and fit the safety profile of other anti-VEGF options, according to the California biotech. Roughly 3% of patients experienced intraocular inflammation, and all but one patient completed their steroid prophylaxis taper on time. All eyes are now on the company’s pivotal trials set for 2025. The first, a US-based study, is set to begin in the first quarter of next year. Kirn said that “we’re all aligned with FDA already.” He added that the company is “almost there” with European regulators and is hashing out final study details. That study would launch three or four months after the US one, Kirn said. Equipped with $578 million at the end of June , Kirn said there are no plans for a follow-on offering, a staple action for today’s public biotechs following positive readouts. “But we’ll be opportunistic and smart about how we build the business,” he said, adding that the company’s current runway extends through the first Phase 3 readout. Kirn also believes the company will have enough money to continue to advance earlier-stage candidates while prioritizing late-stage development of 4D-150. It has two other clinical-stage ophthalmology candidates in the pipeline, plus one that’s received IND clearance. 4DMT also has one clinical-stage candidate apiece for its pulmonary and cardiology wings. “We’re very rapidly shifting from a diversified company to what we hope to be the leader in large-market ophthalmology for genetic medicine,” Kirn said.