Drug Farm today announced positive ophthalmologic and systemic findings from its international Phase 1b study of DF-003, a first-in-class oral ALPK1 inhibitor, presented at the Asia-Pacific Vitreo-retina Society (APVRS) 2026 Congress in Gold Coast, Australia.
The presentation highlighted early evidence of improvements across multiple major manifestations of ROSAH syndrome, including visual function, anhidrosis, headache, arthralgia, quality of life, and inflammatory biomarkers. ROSAH syndrome is a rare genetic autoinflammatory disease caused by activating mutations in ALPK1 and characterized by progressive retinal degeneration and systemic inflammation.
Presentation Details
The presentation, titled “Early Ophthalmic and Systemic Clinical Outcomes of DF-003, a Novel ALPK1 Inhibitor, in an International Phase 1b Study of Patients with ROSAH Syndrome,” was presented by Prof. Ruifang Sui during Rapid Fire 1 – AI, Big Data and Registries, Retina (Medical) 1, Session 1069, on Friday, August 28, 2026, at the APVRS 2026 Congress in Gold Coast, Australia.
The presentation reported interim findings from an open-label international Phase 1b study that enrolled 11 adults with genetically confirmed ROSAH syndrome across three clinical sites in China, Australia, and the United States. Participants received DF-003 at 140 mg orally once daily for three days followed by 45 mg once daily through Day 28. At the time of the presentation, nine participants had completed Day 78 follow-up and two remained in follow-up.
Key Findings from Phase 1b Study
Interim findings demonstrated improvements across multiple major clinical manifestations of ROSAH syndrome. Results from five patients enrolled at Peking Union Medical College Hospital in China showed improvements in ophthalmic function, anhidrosis, headache, arthralgia, and quality of life, consistent with observations in patients enrolled in the United States and Australia.
Ophthalmologic assessments demonstrated clinically meaningful changes in visual function. For the analyses presented, ophthalmic response was defined as a ≥2-line improvement in best-corrected visual acuity (BCVA) or low-luminance BCVA in at least one eye, or a ≥5 dB improvement by microperimetry at ≥5 loci consistent with the direction of change in BCVA. Three of five Chinese patients met the ophthalmic response criteria, while the remaining two patients had advanced visual impairment that limited evaluation using these criteria.
In one 20-year-old patient, BCVA improved by 11 letters during the study. Color vision improved from 20 of 25 Ishihara plates at baseline to 25 of 25 by Day 15 and was maintained through Day 78. The same patient experienced an improvement in baseline anhidrosis, with a return of sweating beginning on Day 15, accompanied by increased objectively measured sweat production and improved heat tolerance. Weekly fever, a component of this patient’s disease course, was absent during treatment and subsequently recurred after treatment cessation. High-sensitivity C-reactive protein (hsCRP) declined from 100 mg/L on Day 2 to 1.64 mg/L on Day 29, and the patient reported improvements in mobility, fatigue, sleep quality, and arthralgia.
A second patient with advanced ocular disease, severe visual impairment, and complicated cataract demonstrated an 11-letter improvement in visual acuity. Microperimetry showed ≥5 dB improvements at 17 of 68 matched loci in the right eye and 15 of 68 matched loci in the left eye, including spatially coherent clusters involving at least five contiguous loci in both eyes. Intermittent fever was absent during treatment, and hsCRP declined from 19.8 mg/L at baseline to 0.63 mg/L by Day 15.
Across the five Chinese patients, all demonstrated improvement in anhidrosis based on objectively measured sweat testing, and patient-reported assessments. Improvements were also observed in headache burden, arthralgia, and quality of life among evaluable patients.
DF-003 was well tolerated, with no serious adverse events reported and no adverse events occurring during the 28-day dosing period. All recorded adverse events occurred after DF-003 cessation and were primarily associated with reemergence of ROSAH symptoms. No clinically meaningful treatment-emergent laboratory abnormalities were observed. Pharmacokinetic profiles were generally consistent across global and Chinese participants and supported once-daily oral dosing in patients with ROSAH syndrome.
Mechanistic Insights
DF-003 is a potent and highly selective inhibitor of ALPK1 designed to suppress mutation-driven inflammatory signaling underlying ROSAH syndrome. In biochemical assays, DF-003 demonstrated an IC50 of 1.5 nM against human ALPK1 and at least 860-fold selectivity relative to the closest non-ALPK1 kinase tested. In a ROSAH mouse model, oral DF-003 reduced retinal glial activation and inflammatory cytokine upregulation in ocular and central nervous system tissues.
Consistent with the proposed mechanism of action, treatment with DF-003 was associated with concordant reductions in multiple inflammatory biomarkers, including CCL3, CCL4, IP-10, serum amyloid A (SAA), hsCRP, and IL-6. Several inflammatory biomarkers showed partial rebound following treatment cessation, paralleling the reemergence of certain clinical manifestations after discontinuation of DF-003.
The concordance of ophthalmologic, systemic, and pharmacodynamic responses, together with partial reversal of certain effects after treatment cessation, provides supportive evidence that the observed clinical activity is related to pharmacologic inhibition of the ALPK1 pathway.
KOL Perspective
“These interim findings are encouraging because improvements were observed across both ocular and systemic manifestations of ROSAH syndrome,” said Prof. Ruifang Sui, Chief Physician; Professor; Head of the Ocular Genetics Group; Academic Leader in Ocular Genetics of the Department of Ophthalmology at Peking Union Medical College Hospital and presenter of the APVRS study results. “In particular, the changes observed in visual function together with improvements in sweating, systemic symptoms, and inflammatory biomarkers support continued evaluation of ALPK1 inhibition as a potential therapeutic approach for patients with ROSAH syndrome.”
Company Statement
“These data substantially extend our earlier clinical observations with DF-003 and demonstrate consistent activity across multiple clinically important manifestations of ROSAH syndrome in an international patient population,” said Henri Lichenstein, Ph.D., Chief Executive Officer of Drug Farm. “We are particularly encouraged by the ophthalmologic findings, including improvements in visual acuity and microperimetry, together with the concordant systemic and inflammatory biomarker responses. The consistency and multidomain nature of these findings reinforce our confidence in DF-003 as a potential disease-modifying therapy that directly targets the underlying genetic driver of ROSAH syndrome.”
Next Steps
Based on these findings, Drug Farm plans to continue advancing the clinical development of DF-003 in a Phase 3 pivotal trial in patients with ROSAH syndrome. The interim Phase 1b results support evaluation of DF-003 over longer treatment durations and in a larger patient population to further characterize its effects on visual function, anhidrosis, systemic manifestations, inflammatory biomarkers, and quality of life.
About DF-003
DF-003 is a proprietary, first-in-class drug developed by Drug Farm’s MedChem5 platform that inhibits the activity of ALPK1 and its disease-causing variants. DF-003 has demonstrated evidence of clinical improvement across multiple symptoms of ROSAH syndrome in an ongoing Phase 1b study (NCT06395285). DF-003 is amongst the first drugs developed with AI that will enter a Phase 3 trial. DF-003 also has therapeutic potential for heart and kidney diseases based on efficacy observed in preclinical models. DF-003 has received Fast Track, Orphan Drug, Rare Pediatric Disease, Rare Disease Evidence Principles designations from the FDA. The discovery of DF-003 has been published in Nature Communications.
About ROSAH Syndrome
ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome is a rare, autosomal dominant autoinflammatory genetic disease caused by activating mutations in the ALPK1 gene. It is characterized by progressive visual loss, optic nerve and retinal pathology, and systemic inflammatory manifestations, including elevated pro-inflammatory cytokines. Symptoms often begin in childhood or early adulthood, and there are currently no approved disease-modifying therapies.
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 syndrome. Its proprietary IDInVivo platform integrates genetics and artificial intelligence to identify and validate novel drug targets directly in living systems. Drug Farm is advancing multiple first-in-class drug candidates into clinical development.
For more information, please visit: https://www.drug-farm.com.
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