Drug Farm Announces Positive Safety and Pharmacokinetic Data for ALPK1 Inhibitor DF-003 from Phase 1 Trial

From May 28 to 31, 2025, at the 126th American Society for Clinical Pharmacology and Therapeutics (ASCPT) Annual Meeting held in Washington, D.C., USA, Drug Farm presented positive results from the Phase 1 clinical study (NCT05997641) of DF-003 completed in healthy volunteers.DF-003, as a new drug inhibiting α-kinase 1 (ALPK1), aims to provide a novel treatment approach targeting the root cause of the rare genetic disorder ROSAH syndrome.

This randomized, double-blind, placebo-controlled study completed the safety, tolerability, and pharmacokinetic analysis of DF-003 in 48 healthy volunteers. Volunteers were randomly assigned in a 6:2 ratio to receive oral DF-003 or corresponding placebo under fasting conditions across 5 single ascending dose (SAD) groups (doses ranging from 3 to 150 mg) and one 14-day multiple dose (MD) group (50 mg once daily). The primary objective of the study was to evaluate the safety, tolerability, and pharmacokinetic profile of DF-003.

Key Results

Safety:The DF-003 group demonstrated good safety at all administered doses without any serious adverse events (SAE). The incidence of treatment-emergent adverse events (TEAE) was similar between participants receiving the drug treatment and those receiving the placebo, and no dose adjustment or intervention was required.

Pharmacokinetics:The pharmacokinetic characteristics of DF-003 are largely dose-proportional, and clinical data support once-daily oral administration.

"We are excited to share the results of our Phase I study, which demonstrate the excellent safety profile of DF-003," said Neil Solomons, M.D., Chief Medical Officer of Drug Farm. "We are also pleased to see that the trough drug exposure levels of DF-003 in blood align with the effective drug concentrations in preclinical models of ROSAH syndrome and cardio-renal diseases. The dose range explored in this trial will be used in the upcoming proof-of-concept trials for patients with ROSAH syndrome and cardio-renal diseases."

Drug Farm CEO Dr. Henri Lichenstein stated: "This is a significant milestone in advancing DF-003, a potential first-in-class immunomodulatory new drug.Can precisely target the pathogenic mutations of ROSAH syndrome and the overactivated ALPK1 pathway in cardiorenal diseases."There are currently no drugs approved for the treatment of ROSAH syndrome, and the potential of DF-003 to save vision and improve disease-related inflammatory symptoms is exciting."

DF-003 is a potential “first-in-class” new drug developed by Drug Farm. It can inhibit ALPK1 and the activity of ALPK1 mutants that cause ROSAH syndrome. DF-003 has the potential to treat ROSAH syndrome and cardio-renal diseases, showing efficacy in preclinical models for these disease indications. DF-003 has completed a Phase 1 clinical trial (NCT05997641) in healthy volunteers and is currently recruiting ROSAH syndrome patients for a Phase 1b/2a trial (NCT06395285).

ROSAH (Retinal dystrophy, Optic nerve edema, Splenomegaly, Anhidrosis, and Headache) syndrome is a rare autosomal dominant hereditary autoinflammatory disease, named according to the characteristic symptoms exhibited by affected patients.[1、2]. This disease is caused by highly active genetic mutations in ALPK1. The most common symptom is progressive vision loss, typically beginning before the age of 20. Ophthalmic examinations often reveal optic disc elevation, uveitis, and retinal neurodegeneration.[2、3]Most ROSAH patients also exhibit inflammatory characteristics, 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 interleukin 1β (IL-1β).[3]。

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. 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.