Biallelic RPE65 mutation associated retinal dystrophy

ROSAH syndrome is caused by mutations in the ALPK1 gene. Credit: Gorodenkoff via Shutterstock. Drug Farm has been granted a rare paediatric disease (RPD) designation from the US Food and Drug Administration (FDA) for DF-003 to treat retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis and headache (ROSAH) syndrome. DF-003 is an alpha-kinase 1 (ALPK1) indicated for the treatment of the rare autosomal dominant disorder ROSAH syndrome. The condition is caused by mutations in the ALPK1 gene, characterised by the symptoms listed in its name. ROSAH syndrome currently has no approved treatments. Drug Farm received FDA clearance of its investigational new drug (IND) application to initiate Phase I studies for the candidate in June 2023, after pre-clinical studies in ROSAH syndrome transgenic mouse models showed significant activity and favourable drug-like properties. If a new drug application for DF-003 is approved by the FDA, the company may be eligible to receive a priority review voucher (PRV) that can be redeemed to receive for any later marketing application. The double-blind, placebo-controlled Phase I trial (NCT05997641) is evaluating the safety, tolerability, and pharmacokinetics of DF-003 on 96 healthy subjects.  The study is expected to conclude in Q1 2025. The company has other candidates in the pipeline, including another ALPK1 agonist DF-006, which is under investigation in the third part of a Phase I study for the treatment of chronic hepatitis B infection. The trial is assessing the levels of DF-006 and its related compounds in the blood following doses of the formulation. In May 2023, Drug Farm generated $27m in a Series C funding round led by Betta Capital. The company, which has offices in both the US and China, also raised $56m in February 2021 in a Series A lead by BVCF. In the announcement accompanying the designation, Drug Farm’s chief medical officer Jeysen Yogaratnam said: “Obtaining Rare Pediatric Disease Designation recognizes the serious and debilitating complications of this rare disease and upholds our goal to provide DF-003 as the first targeted drug for potential treatment in patients afflicted with ROSAH syndrome.”

GUILFORD, Conn.--( BUSINESS WIRE )-- Drug Farm , a clinical-stage biopharmaceutical company announced that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease (RPD) Designation for the company’s alpha-kinase 1 (ALPK1) inhibitor, DF-003, to treat patients with ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis and headache) Syndrome. DF-003 is currently being evaluated in a Phase 1 trial ( NCT05997641 ) to assess safety and pharmacokinetics in normal healthy volunteers. “Pediatric patients living with ROSAH Syndrome face a significant unmet need with limited options to treat vision loss,” said Jeysen Yogaratnam, Chief Medical Officer, Drug Farm. “Obtaining Rare Pediatric Disease Designation recognizes the serious and debilitating complications of this rare disease and upholds our goal to provide DF-003 as the first targeted drug for potential treatment in patients afflicted with ROSAH Syndrome.” About Rare Pediatric Disease Designation Rare Pediatric Disease (RPD) Designation is granted by the FDA for serious or life-threatening diseases which affect fewer than 200,000 people in the United States and in which the serious or life-threatening manifestations primarily affect individuals less than 18 years of age. If a New Drug Application (NDA) for DF-003 to treat ROSAH Syndrome is approved by the FDA, Drug Farm may be eligible to receive a Priority Review Voucher (PRV) that can be redeemed to receive a priority review for any subsequent marketing application or may be sold or transferred. The FDA has implemented this program to encourage development of new drugs for treatment of rare pediatric diseases. About ROSAH Syndrome ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis and headache) Syndrome is a rare, autosomal dominant autoinflammatory disease named according to the characteristic symptoms exhibited by affected patients (1, 2). The disease is caused by a genetic gain-of-function mutation in ALPK1. The most common presenting symptom is a progressive decline in visual acuity that typically begins before 20 years of age, with ophthalmologic examination often revealing optic disc elevation, uveitis, and retinal nerve degeneration (2, 3). Most ROSAH patients also exhibit inflammatory features such as non-infectious low-grade fevers, arthralgia, headaches, and persistently elevated levels of inflammatory cytokines including tumor necrosis factor α (TNFα), interleukin 6 (IL-6), and IL-1β (3). Tantravahi SK, et al. An inherited disorder with splenomegaly, cytopenias, and vision loss. Am J Med Genet A. 2012;158(3):475-81. Williams LB, et al. ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder. Genet Med. 2019;21(9):2103-15. Kozycki CT, et al. Gain-of-function mutations in ALPK1 cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome. Ann Rheum Dis. 2022;81(10):1453-64. About DF-003 DF-003 is a first-in-class drug developed by Drug Farm that inhibits the activity of ALPK1 and variants of ALPK1 that have a gain-of-function mutation and cause ROSAH Syndrome. DF-003 currently is in a Phase 1 clinical trial (NCT05997641) in normal healthy volunteers. About Drug Farm Drug Farm is a private biotechnology Company developing innovative treatments targeting innate immunity for hepatitis B, heart and kidney diseases, and ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis and headache) syndrome. Drug Farm's unique IDInVivo platform combines breakthrough technologies in genetics and AI to discover new treatments. IDInVivo technology allows the direct assessment of gene targets in living animals with intact immune systems. Using the IDInVivo platform, Drug Farm has identified novel innate immunity pathways and targets and is now rapidly advancing multiple first-in-class drug candidates into clinical development. For more information please visit: https://www.drug-farm.com

HG302 effectively generates stable genome editing with minimal off-target effects in-vitro and in-vivo A single intravenous injection of HG302 restores functional dystrophin protein expression HG302 demonstrates therapeutic effects by improving muscle functions in humanized DMD mice SHANGHAI and CLINTON, N.J., Dec. 19, 2023 /PRNewswire/ -- HuidaGene Therapeutics (辉大基因"HuidaGene") today announced the U.S. FDA granted Rare Pediatric Drug Designation (RPDD) to HG302, a novel CRISPR-Cas12 DNA-editing therapy, to treat Duchenne muscular dystrophy (DMD), affecting 1 in ~5,000 newborn boys. Continue Reading Unlike the in-vivo use of Cas9 system with limited genome-editing efficiency, high occurrence of off-targeting modifications, viral delivery packaging limitations, and complicated CRISPR-Cas9 patent dispute, HuidaGene identified novel Cas12i proteins using AI and deep machine-learning of DNA sequencing through the proprietary HG-PRECISE ® platform to develop high-fidelity Cas12i variant (hfCas12Max®). This hfCas12Max® is smaller in size than Cas9, thereby packaging it using one viral vector with the lowest off-targeting activity and highest editing efficiency in mammalian cells when compared to SpCas9 and LbCas12a. Furthermore, Cas12i was granted a patent by USPTO with a cleaner commercial landscape. HuidaGene Announces RPDD Granted to HG302, A Novel CRISPR DNA-editing Therapy, for the Treatment of DMD Post this "This is Company's third program receiving RPDD, suggesting the recognition of the importance of DMD and the preclinical safety and efficacy of hfCas12Max gene-editing therapy by FDA," said Alvin Luk, Ph.D., M.B.A., C.C.R.A., Co-founder and CEO of HuidaGene. "DMD patients are often wheelchair-bound before the age of 12 facing a significant unmet need. HG302 is designed specifically to target the DMD gene and enable the production of functional dystrophin protein. Time is muscle; we look forward to advancing HG302 into the clinic as soon as possible." The RPDD is granted for rare medical diseases affecting fewer than 200,000 people in the US and primarily for individuals aged under 18. If the HG302 Biologic Licensing Application (BLA) for DMD is approved by the FDA, HuidaGene may be eligible to receive a priority review voucher (PRV) that can be redeemed to receive a priority review for any subsequent marketing application or may be sold or transferred this high-value PRV. PRVs have historically commanded prices over US$ 100 million. About HG302 HG302 is a novel CRISPR DNA-editing therapy with high-fidelity Cas12 (hfCas12Max) and CRISPR RNA targeting human DMD exon 51 splice-donor (SD) site delivered by a single viral vector into the muscles. The human DMD exon 51 SD site will be disrupted by HG302, thereby allowing exon 51 skipping to form the correct open reading frame from exons 50 to 53, restoring functional dystrophin protein expression and improving muscle functions. About HuidaGene - 辉大基 因 HuidaGene Therapeutics (辉大基因), a global clinical-stage biotechnology company, utilizes its CRISPR-based HG-PRECISE® platform to discover, engineer, and develop potentially curative genomic medicine. The Company is advancing clinical programs of HG004 in RPE65-associated inherited retinal disease (granted both ODD and RPDD), HG202 CRISPR RNA-editing in neovascular age-related macular degeneration, and the preclinical pipeline, including HG301 CRISPR DNA-editing in retinitis pigmentosa, HG204 CRISPR RNA-editing in neurodevelopmental disease of MECP2 duplication syndrome (granted both ODD and RPDD), and HG302 CRISPR DNA-editing for Duchenne muscular dystrophy (granted RPDD) etc. The Company's extensive intellectual property portfolio positions it as a leader in unleashing the full potential of genome medicine. Learn more at huidagene.com or on LinkedIn. SOURCE HuidaGene Therapeutics