Drug Farm today announced ophthalmologic and central nervous system (CNS) findings from its Phase 1b study of DF-003, a first-in-class oral ALPK1 inhibitor, will be presented at the Association for Research in Vision and Ophthalmology (ARVO) 2026 annual meeting in Denver, CO.
The presentation will highlight early evidence of improvements in visual function, optic nerve pathology, and neurological symptoms in patients with ROSAH syndrome, a rare genetic autoinflammatory disease caused by activating mutations in ALPK1 and characterized by progressive retinal degeneration and systemic inflammation.
Presentation Details
The poster, titled “ROSAH Syndrome – an ALPK1-related autoinflammatory disease: Preliminary CNS and ophthalmic clinical outcomes from the first six patients in a Phase 1b study treated with DF-003,” will be presented during Poster Session 537: Retina/RPE: New drugs, mechanisms of action, metabolism, and toxicity. The session will take place on May 7, 2026, from 11:45 AM to 1:30 PM.
Key Findings from Phase 1b Study
In this open-label Phase 1b study (NCT06395285), six adult patients with genetically confirmed ROSAH syndrome completed 28 days of once-daily oral DF-003 treatment followed by post-treatment observation. Clinical improvements were observed across multiple disease manifestations during the treatment period, with all six patients demonstrating improvement in at least one clinical domain. Notably, these improvements reversed after stopping treatment, supporting a direct pharmacologic effect of DF-003.
Ophthalmologic assessments demonstrated evidence of disease modulation at the level of the optic nerve and retina. Reductions in optic disc swelling and peripapillary retinal thickness were observed by optical coherence tomography (OCT), with improvements evident as early as Day 29. In one evaluable patient, measurable gains in visual function were observed, including improvements in best-corrected visual acuity of +12 letters in the left eye and +5 letters in the right eye after only eight days of treatment.
In addition, improvements were observed in neurological and systemic manifestations of disease. Headache severity improved during the treatment period as measured by the HIT-6 validated questionnaire and worsened following treatment discontinuation. Reversal of anhidrosis and improvements in arthralgia were also observed, consistent with the systemic anti-inflammatory effects of ALPK1 inhibition.
DF-003 was well tolerated, with no serious adverse events or treatment-emergent adverse events reported during the 28-day dosing period. No clinically significant abnormalities in liver, renal, hematologic, or coagulation parameters were observed. Adverse events were observed after treatment cessation and were consistent with recurrence of underlying ROSAH symptoms.
Mechanistic Insights
DF-003 is a potent and selective inhibitor of disease-causing mutants of ALPK1 (e.g. T237M) that can penetrate the blood-retina and blood -brain barriers and suppress phosphorylation of TIFA, a key mediator of innate immune signaling and NF-κB activation. The observed reversibility of clinical, ophthalmologic, and biomarker responses following DF-003 treatment discontinuation provides strong evidence that the therapeutic effects are mediated through on-target inhibition of the ALPK1 pathway.
KOL Perspective
“These early findings provide encouraging evidence that targeting ALPK1 may address both systemic and ocular manifestations of ROSAH syndrome,” said John Grigg, Professor of Clinical and Experimental Ophthalmology at the Save Sight Institute, University of Sydney. “The observed improvements in optic nerve pathology, visual function, and overall symptom burden, together with a favorable safety profile, support further clinical development of DF-003.”
Company Statement
“These data extend our clinical findings by demonstrating that selective inhibition of ALPK1 can translate into measurable improvements in ophthalmologic and neurological outcomes in patients with ROSAH syndrome,” said Henri Lichenstein, PhD, Chief Executive Officer of Drug Farm. “The consistency of response across patients, along with the reversibility of effects following treatment discontinuation, provides strong support for a direct pharmacologic mechanism and reinforces the potential of DF-003 as a disease-modifying therapy.”
Next Steps
Based on these findings, Drug Farm plans to advance DF-003 into a pivotal Phase 3 trial to further evaluate its efficacy, safety, and potential to address both systemic and ophthalmologic manifestations of ROSAH syndrome.
About DF-003
DF-003 is a proprietary, first-in-class drug developed by Drug Farm that inhibits the activity of ALPK1 and its disease-causing variants. It has therapeutic potential for ROSAH syndrome as well as heart and kidney diseases, based on efficacy observed in preclinical models. DF-003 has completed a Phase 1 clinical trial (NCT05997641) in healthy volunteers and is currently enrolling patients with ROSAH syndrome in an ongoing Phase 1b study (NCT06395285). DF-003 has received Fast Track, Orphan Drug, Rare Pediatric Disease, Rare Disease Evidence Principles designations from the FDA.
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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