Drug Farm announced positive results from its Phase 1 first-in-human trial of DF-003, a first-in-class alpha-kinase 1 (ALPK1) inhibitor designed to treat ROSAH syndrome, a rare genetic disease with no approved therapies. The data, presented at the American Society for Clinical Pharmacology & Therapeutics meeting in Washington, DC, demonstrated excellent safety and favorable pharmacokinetics across all tested doses.
Phase 1 Trial Design and Results
The randomized, placebo-controlled, double-blinded study (NCT05997641) evaluated DF-003 in 48 healthy volunteers across two phases. In the first portion, single ascending doses ranging from 3 mg to 150 mg were administered orally in five cohorts with 3:1 randomization (DF-003 to placebo). The second portion tested 50 mg of DF-003 administered daily for 14 consecutive days in eight healthy volunteers using the same randomization scheme.
The primary objective focused on evaluating safety, tolerability, and pharmacokinetic properties of DF-003. Results showed the drug was safe at all doses tested, with no serious adverse events reported. Treatment emergent adverse events occurred at similar rates between active and placebo groups, and no adverse events required dose modification or interruption.
"We are happy to share the results from our Phase 1 study that demonstrate the excellent safety of DF-003," said Neil Solomons, MD, Head of Clinical Development at Drug Farm. "We are also pleased that the pharmacokinetic profile of DF-003 leads to trough concentrations in blood that are consistent with efficacy in preclinical models of ROSAH syndrome and cardio-renal disease."
Pharmacokinetic Profile Supports Clinical Development
The pharmacokinetic analysis revealed DF-003 exhibited largely dose-proportional behavior, supporting its development as a once-daily oral medication. The blood concentrations achieved align with efficacy levels observed in preclinical models for both ROSAH syndrome and cardio-renal disease, providing confidence for upcoming patient trials.
"The dose ranges explored in this Phase 1 trial will be used in our upcoming proof of concept trials in ROSAH syndrome and cardio-renal disease patient populations," Solomons added.
Addressing Unmet Medical Need in ROSAH Syndrome
ROSAH syndrome is a rare, autosomal dominant autoinflammatory genetic disease characterized by retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache. Disease-causing mutations in ALPK1 lead to the syndrome, with the most common presenting symptom being progressive decline in visual acuity typically beginning before age 20. Ophthalmologic examination often reveals optic disc elevation, uveitis, and retinal nerve degeneration.
Most ROSAH patients exhibit inflammatory features including non-infectious low-grade fevers, arthralgia, headaches, and persistently elevated levels of inflammatory cytokines such as tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), and IL-1β.
"There are no approved drugs for ROSAH syndrome, and we are excited about the potential of DF-003 to save sight and to ameliorate other debilitating inflammatory symptoms associated with this disease," said Henri Lichenstein, PhD, Chief Executive Officer at Drug Farm.
Next Steps in Clinical Development
DF-003 represents a precision medicine approach, specifically targeting the disease-causing mutations of ROSAH syndrome and the excessive activation of the ALPK1 pathway found in cardio-renal disease. The company has already initiated patient enrollment in a Phase 1b trial (NCT06395285) for ROSAH syndrome patients.
Drug Farm developed DF-003 using its proprietary IDInVivo platform, which combines genetics and artificial intelligence technologies to discover immune-modulating therapies. The platform allows direct assessment of gene targets in living animals with intact immune systems, enabling the identification of novel innate immunity pathways and targets.
"This is a major inflection point for Drug Farm in our quest to advance DF-003, a first-in-class, immune-modulating drug that precision targets the disease-causing mutations of ROSAH syndrome," Lichenstein stated.
