ALBANY, New York, United States and SHANGHAI, China – May 7, 2026
Drug Farm announced new ophthalmologic and central nervous system (CNS) findings from its ongoing Phase 1b clinical study of DF-003, a first-in-class oral ALPK1 inhibitor being developed for ROSAH syndrome, will be presented at the ARVO 2026 Annual Meeting in Denver, Colorado. The early clinical data demonstrated improvements in visual function, optic nerve pathology, headache severity, and systemic inflammatory symptoms in patients with the ultra-rare genetic autoinflammatory disease. The results strengthen the clinical potential of DF-003 as a possible disease-modifying therapy for ROSAH syndrome, an area where no approved targeted treatments currently exist.
Phase 1b Data Show Improvements in Vision and Neurological Symptoms
The open-label Phase 1b study enrolled six adult patients with genetically confirmed ROSAH syndrome who received once-daily oral DF-003 treatment for 28 days followed by a post-treatment observation period. According to the company, all six patients demonstrated improvement in at least one clinical domain during treatment. Ophthalmologic assessments revealed reductions in optic disc swelling and peripapillary retinal thickness, measured using optical coherence tomography (OCT), with signs of improvement observed as early as Day 29. One patient experienced measurable gains in visual function, including improvements of +12 letters in the left eye and +5 letters in the right eye in best-corrected visual acuity after only eight days of treatment. Importantly, clinical improvements reversed after treatment discontinuation, supporting a direct pharmacologic effect of DF-003 on disease activity.
Systemic Anti-Inflammatory Effects Support Disease Modification
Beyond ocular outcomes, investigators reported improvements in several systemic and neurological manifestations associated with ROSAH syndrome. Headache severity improved during treatment based on the validated HIT-6 questionnaire, while worsening again after discontinuation of therapy. Additional clinical improvements included reversal of anhidrosis and reductions in arthralgia, supporting broader anti-inflammatory activity linked to ALPK1 inhibition. DF-003 also demonstrated a favorable safety profile, with no serious adverse events or treatment-emergent adverse events reported during the 28-day dosing period. Researchers observed no clinically significant abnormalities in liver, kidney, hematologic, or coagulation parameters. Adverse events occurring after treatment cessation were consistent with recurrence of underlying disease symptoms rather than drug-related toxicity.
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First-in-Class ALPK1 Inhibition Targets Rare Genetic Disease
DF-003 is designed as a potent and selective inhibitor of disease-causing ALPK1 mutations, including T237M variants associated with ROSAH syndrome. The therapy is capable of penetrating both the blood-retina barrier and blood-brain barrier, allowing it to target inflammatory signaling pathways involved in both ocular and neurological disease manifestations. Mechanistically, DF-003 suppresses phosphorylation of TIFA, a key regulator of innate immune signaling and NF-κB activation. Drug Farm stated that the reversibility of clinical improvements after treatment discontinuation provides strong evidence that the observed therapeutic effects result from direct on-target ALPK1 inhibition. The findings further validate ALPK1 as a novel therapeutic target for inflammatory and rare genetic diseases.
Regulatory Momentum Supports Further Development
DF-003 has already received multiple regulatory designations from the FDA, including Fast Track, Orphan Drug, Rare Pediatric Disease, and Rare Disease Evidence Principles designations. The company confirmed plans to advance DF-003 into a pivotal Phase 3 clinical trial to further evaluate efficacy and safety in patients with ROSAH syndrome. Beyond this indication, Drug Farm believes ALPK1 inhibition may also have therapeutic potential in heart disease, kidney disease, and hepatitis B, based on encouraging preclinical findings. The company’s broader research platform combines genetics and artificial intelligence through its proprietary IDInVivo platform to identify novel drug targets across immune-mediated diseases.
Rare Disease Focus Expands Precision Immunology Pipeline
ROSAH syndrome is an ultra-rare autosomal dominant inflammatory disease characterized by progressive retinal degeneration, optic nerve edema, splenomegaly, anhidrosis, and severe headaches caused by activating mutations in the ALPK1 gene. Because no disease-modifying therapies currently exist, successful development of DF-003 could represent a major breakthrough for patients with this debilitating condition. The new clinical findings position Drug Farm among a growing group of biotechnology companies advancing precision therapies targeting genetically defined inflammatory pathways in rare diseases.
Source: Drug Farm press release
