Drug Farm Announces FDA Rare Pediatric Disease Designation for First-in-Class ALPK1 Inhibitor DF-003 in ROSAH Syndrome

Drug Farm, a biopharmaceutical company dedicated to the development of innovative drugs, recently announced that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation (RPDD) to its First-in-class ALPK1 inhibitor DF-003 for the treatment of ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome. DF-003 is currently undergoing Phase 1 clinical trials (NCT05997641) to evaluate the safety and pharmacokinetics in healthy volunteers.

"Pediatric patients with ROSAH syndrome have significant unmet clinical needs, with a lack of treatment options for vision loss," commented Dr. Jeysen Yogaratnam, Chief Medical Officer of Drug Farm. "The Rare Pediatric Disease designation recognizes the clinical necessity to address the severe and debilitating complications of this rare disease and supports our goal of developing DF-003 as the first targeted therapy for patients with ROSAH syndrome."

Pediatric Rare Disease Designation (RPDD) is granted by the FDA for the treatment of serious or life-threatening diseases affecting children under the age of 18 in the United States and fewer than 200,000 patients. If Drug Farm's DF-003 New Drug Application (NDA) for the treatment of ROSAH syndrome receives FDA approval, Drug Farm will be eligible to receive a Priority Review Voucher (PRV). This voucher can be redeemed to obtain priority review for any subsequent marketing application, or it can be sold or transferred at a price of approximately $100 million. The FDA introduced this program to encourage the development of new drugs for treating rare pediatric diseases. To qualify for RPDD designation, three main criteria must be met: the drug must be intended for the prevention or treatment of a rare pediatric disease; there must be sufficient data or prevalence information demonstrating that the rare pediatric disease meets the rare disease criteria; and there must be adequate supportive data showing the drug’s efficacy in treating the rare pediatric disease.

ROSAH (Retinal dystrophy, Optic nerve edema, Splenomegaly, Anhidrosis, and Headache) syndrome is a rare autosomal dominant hereditary autoinflammatory disease, named based on the characteristic symptoms exhibited by affected patients (1, 2). The disease is caused by gain-of-function mutations in ALPK1. The most common symptom is progressive vision loss, which usually begins before the age of 20. Ophthalmologic examination typically reveals optic disc elevation, uveitis, and retinal neurodegeneration.^{[2， 3，4]}Most ROSAH patients also exhibit inflammatory features, such as non-infectious low-grade fever, arthralgia, headache, and persistently elevated levels of inflammatory cytokines, including tumor necrosis factor α (TNFα), interleukin 6 (IL-6), and IL-1β (4).

DF-003 is a First-in-class novel drug developed by Drug Farm. It can inhibit ALPK1 and ALPK1 mutant activity, where high-activity mutations of these variants lead to ROSAH syndrome. DF-003 is currently in Phase 1 clinical trials (NCT05997641) involving normal healthy volunteers.

Drug Farm is a biotechnology company dedicated to the discovery of targets and the development of original new drugs (first-in-class), focusing on innovative therapies for hepatitis B, heart and kidney diseases, and ROSAH syndrome, among other autoimmune diseases. Drug Farm's unique IDInVivo+ platform combines breakthrough technologies in genetics and artificial intelligence to discover new treatments, allowing for the direct selection of genetic targets in animal models with intact immune systems. Using the IDInVivo+ platform, Drug Farm has discovered multiple novel innate immune pathways and targets, and is rapidly advancing several original new drugs into clinical development.

* References:

1. Tantravahi SK, et al. An inherited disorder with splenomegaly, cytopenias, and vision loss. Am J Med Genet A. 2012;158(3):475-81.

2. 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.

3. Zhong L, et al. Juvenile Onset Splenomegaly and Oculopathy Due to Germline Mutation in ALPK1. J Clin Immunol. 2020 Feb;40(2):350-358

4. 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.