Usher Syndromes

There’s still money to be raised by gene therapy startups with good clinical data. On Wednesday, North Carolina biotech Atsena Therapeutics said it had raised a $150 million Series C to try and be the first to treat a rare form of ocular disease that leads to blindness. Bain Capital Life Sciences led the financing. Another new Atsena investor, Wellington Management, also took part as did all existing backers, including Lightstone Ventures, Sofinnova Investments and Abingworth, among others. “There is a place here for programs and companies that do have compelling clinical data in diseases with high unmet clinical needs,” Atsena CEO Patrick Ritschel said in an interview. The gene therapy field has been held back by struggles with commercialization, pipeline cuts and funding pullbacks. Only a few ocular gene therapy companies have been able to secure nine-figure financings since 2022, including Beacon , Ray and Frontera . Atsena last disclosed a $24.5 million Series B in October 2023. Atsena is working on Part B of a Phase 1/2 study of ATSN-201, a gene therapy that it hopes will treat a genetic ocular disease called X-linked retinoschisis, or XLRS. The condition is usually found in childhood and impacts about 30,000 men in the US and European Union, the biotech said. “In a majority of the nine patients treated, we see anatomic resolution of disease and we see functional improvement in the majority. So it’s not often you can get that kind of convincing signal on a small dataset ,” Leonard Feiner, a principal at Bain Capital Life Sciences, said in an interview. The disease causes an abnormal split in the retinal layers and can’t be fixed by glasses, eventually leading to blindness. “The interesting thing about this disease, XLRS, is that in addition to having functionally decreased vision, these patients also have an anatomic problem, which is a lack of adhesion between the layers of the retina,” Feiner said. The therapy is a subretinal injection and uses an adeno-associated virus. The new funding is slated to carry Atsena all the way through a biologics license application at the FDA “and beyond,” Ritschel said. The startup will meet with the FDA later this year to clarify if the Phase 1/2 could support an accelerated approval, or if the biotech would need to run an additional study. The future of cell and gene therapy decisions at the FDA is now in limbo as top leadership, most notably Peter Marks, has been forced out or resigned in recent days . “We’ve seen others in this space in [the past] 12 months or so obtain accelerated approval alignment with the FDA in rare disease, genetic therapy environments, so we would be hopeful for that as well,” Ritschel said. It’s not the first company to try and treat the disease. Biogen had a $1 billion-plus pact with Applied Genetic Technologies Corporation, but their gene therapy failed a Phase 1/2 study in 2018 . Atsena is also working on ATSN-101 for Leber congenital amaurosis type 1, or LCA1. The biotech began searching for a partner for the former Sanofi gene therapy in 2023 and shortly after presented one-year data from a Phase 1/2 trial. It secured a licensing agreement with Kyoto-based Nippon Shinyaku last fall. Ritschel said the pivotal study has yet to begin and declined to disclose any expected timing. The Series C will also support a preclinical pipeline of gene therapies for inherited retinal diseases like MYO7A-associated Usher syndrome, or USH1B, the company said. Atsena employs “just over 20 people today,” Ritschel said. Prior to joining the company in 2020, he was involved in other gene therapy upstarts as co-founder of StrideBio and an angel investor in Bamboo Therapeutics. Ginkgo bought AAV capsid assets from StrideBio in 2023 and Pfizer acquired Bamboo for up to $645 million in 2016.

FORT WORTH, Texas, Jan. 21, 2025 (GLOBE NEWSWIRE) -- Nacuity Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company developing treatments for retinitis pigmentosa, cataracts and other diseases caused by oxidative stress, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to NPI-001 (N-acetylcysteine amide) tablets, Nacuity’s proprietary investigational therapy for the treatment of patients with retinitis pigmentosa (RP). A drug may receive Fast Track designation if it is intended to treat a serious or life-threatening disease and demonstrates the potential to address an unmet medical need. “Fast Track Designation represents an objective assessment by the FDA for the potential of NPI-001 tablets as a treatment for RP, a severe blinding disease,” said G. Michael Wall, Ph.D., Senior Vice President and Chief Scientific Officer of Nacuity Pharmaceuticals. “We are committed to advancing NPI-001 to address this significant unmet medical need for patients suffering from RP.” A drug that receives Fast Track designation may benefit from more frequent interactions with the FDA throughout drug development. In addition, the Fast Track program allows for Accelerated Approval and Priority Review, if relevant criteria are met. About Retinitis PigmentosaOften diagnosed in childhood or adolescence, retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases involving over 3,000 different mutations in more than 50 genes (Daiger et al., 2013), causing progressive night and peripheral vision loss. RP often leads to legal and sometimes complete blindness. Forms of RP and related diseases include Usher syndrome, Leber congenital amaurosis and Bardet-Biedl syndrome. An estimated 100,000 people in the U.S. have RP (https://www.fightingblindness.org/diseases/retinitis-pigmentosa). There are no FDA-approved drugs or no standard treatments for RP. A curative gene therapy, voretigene neparvovec (LUXTURNA®), exists for patients with the RPE65 mutation, about 1-6% of patients with RP (Cross et al., 2022). Nacuity researchers are working to develop a gene-agnostic treatment for RP, a significant unmet medical need. About NPI-001NPI-001 is a proprietary, GMP-grade formulation of N-acetylcysteine amide (NACA) tablets being developed to target oxidative stress associated with diseases such as retinitis pigmentosa. Preclinical studies indicate that NPI-001 boosts glutathione, the body’s most powerful endogenous antioxidant, to stop chemically aggressive oxygen molecules from damaging retinal cells. NPI-001 and related small molecules are potent antioxidants in several preclinical models that may lead to additional indications. In addition to Fast Track Designation, NPI-001 has also been granted Orphan Drug Designation for RP which provides seven years of U.S. FDA regulatory exclusivity for the product upon regulatory approval. About Nacuity Pharmaceuticals, Inc.Nacuity Pharmaceuticals is a clinical-stage leader in innovative treatments for oxidative stress. The company’s powerful, targeted therapies aim to attenuate oxidative tissue damage, a driver of blinding eye diseases and a broad spectrum of serious chronic conditions. Nacuity has three highly differentiated clinical programs ongoing for retinitis pigmentosa, cataract and cystinosis. Nacuity has operations in Fort Worth, TX, USA, and Australia, and extensive managerial and scientific domain expertise as well as backing from Foundation Fighting Blindness (https://www.fightingblindness.org/) and its venture arm RD Fund (https://www.retinaldegenerationfund.org). For more information, please visit www.nacuity.com. Trademarks are the property of their owners. Nacuity Media ContactJulia Clements267.626.1085jclements@6degreespr.com References: Cross N, van Steen C, Zegaoui Y, Satherley A, Angelillo L. Retinitis Pigmentosa: Burden of Disease and Current Unmet Needs. Clin Ophthalmol. 2022 Jun 20;16:1993-2010. doi: 10.2147/OPTH.S365486. PMID: 35757022; PMCID: PMC9232096. Daiger SP, Sullivan LS, Bowne SJ. Genes and mutations causing retinitis pigmentosa. Clin Genet. 2013 Aug;84(2):132-41. doi: 10.1111/cge.12203. Epub 2013 Jun 19. PMID: 23701314; PMCID: PMC3856531 Guidance for Industry: Expedited Programs for Serious Conditions – Drugs and Biologics, May 2014. Wood JPM, Chidlow G, Wall GM, Casson RJ. N-acetylcysteine amide and di-N-acetylcysteine amide protect retinal cells in culture via an antioxidant action. Exp Eye Res. 2024 Nov; 248:110074. doi: 10.1016/j.exer.2024.110074. Epub 2024 Sep 7. PMID: 39251120.

MILAN, Dec. 09, 2024 (GLOBE NEWSWIRE) -- AAVantgarde Bio (AAVantgarde), an Italy-based global biotechnology company, presented preliminary safety data on the first two subjects dosed in the LUCE-1 trial, a Phase 1/2 open label clinical trial to assess safety and tolerability of AAVB-081, using the company’s proprietary dual hybrid gene therapy platform to deliver MYO7A protein in subjects with retinitis pigmentosa related to Usher Syndrome Type 1B (USH1B). The subretinal gene therapy procedure in the LUCE-1 study was supervised by Prof. Francesca Simonelli, Head of the Ophthalmology Unit at the University Hospital of Campania “Luigi Vanvitelli” (Naples), lead dosing site for the LUCE-1 study. Safety data for two low visual acuity (LVA) subjects (S1 & S2) in the low dose (LD) cohort was presented. The best corrected visual acuity (BCVA) returned to pre-treatment level within 2 weeks in both subjects. All adverse events (AEs) were mild and resolved without further intervention. To date, no dose-limiting toxicities have been observed. The independent Data Safety Monitoring Board has provided recommendation to continue the trial as planned. “I am delighted to be involved as Principal Investigator in this first-in-human Phase 1/2 clinical study of AAV-081 for patients with retinitis pigmentosa related to USH1B,” said Prof. Simonelli. “These preliminary safety results are very encouraging, and we are progressing with the dose escalation in this study. AAVB-081 shows a favourable safety profile, with no significant immune response and has potential for visual improvement, that I hope will help greatly improving the quality of life of these patients.” Dr. Natalia Misciattelli, CEO of AAVantgarde added “We are honoured to have Prof. Simonelli as Principal Investigator for this clinical study aimed at providing hope for USH1B patients that currently have no therapeutic options to prevent sight loss. We are excited about these preliminary results and look forward to sharing data of our dual AAV platform technology for MYO7A retinitis pigmentosa related to Usher syndrome in relevant forums.” About the AAVB-081 programAAVB-081 is an intra-retinal AAV8-based dual hybrid product targeting MYO7A-associated Usher syndrome (USH1B). AAVantgarde’s dual hybrid platform uses two AAV8 vectors, each containing one half of an expression cassette encoding for the Myo7A gene and works at the cell nucleus level, recombining the two halves of the transgene back into a single one within the cell. This technology translates into an efficient recombination that generates therapeutically meaningful protein levels in animal models. About the LUCE-1 Trial (NCT06591793)LUCE-1 is a Phase 1/2 multicenter, open-label, dose escalation study investigating safety, tolerability and preliminary efficacy of 3 dose levels of dual AAV8.MYO7A (AAVB-081) administered subretinally in subjects with retinitis pigmentosa associated with Usher Syndrome Type 1B. You can find further information on the LUCE-1 study in the link below:LUCE-1 clinical study About Usher syndrome type 1BUsher syndrome type 1B (Usher1B) is an inherited disease that affects the retina and the inner ear. Usher1B is caused by mutations in the MYO7A gene. The therapeutic gene to treat Usher1B is 6.7 kb long and is therefore too large to fit inside a standard AAV vector. Approximately 20,000 patients in the U.S. and E.U. have Usher1B. These children are born deaf, have vestibular dysfunction, and begin to progressively lose vision in their first decade of life. Although there are surgical treatments available to treat deafness in these patients, there are no treatments available to treat progressive vision loss and blindness in these patients. About AAVantgarde BioAAVantgarde Bio is a clinical stage, Italian headquartered, international biotechnology company that has developed two proprietary Adeno-Associated Viral (AAV) vector platforms to address the gene therapy cargo capacity limitations of AAV vectors. The AAVantgarde platforms could be used to deliver large genes to ocular and non-ocular tissues. Co-founded by Professor Alberto Auricchio at TIGEM (Telethon Institute of Genetics and Medicine) in Naples, Italy, and Telethon Foundation, AAVantgarde will initially validate the platform in the clinic in two inherited retinal diseases with clear unmet need. For more information, please visit: www.aavantgarde.com Contact:Dr. Magda Blanco – Head of Corporate DevelopmentEmail: info@aavantgarde.com