Key Takeaways

  • Drug Farm reported early evidence that DF-003, a first-in-class oral ALPK1 inhibitor, improved visual function, optic nerve pathology, headaches, and systemic inflammatory symptoms in patients with ROSAH syndrome 
  • All six treated patients showed improvement in at least one clinical domain, with benefits reversing after treatment discontinuation, supporting a direct pharmacologic effect of ALPK1 inhibition
  • DF-003 was well tolerated with no serious adverse events during treatment, and Drug Farm plans to advance the therapy into a pivotal phase 3 trial

Drug Farm announced new ophthalmologic and central nervous system (CNS) findings from its Phase 1b clinical study of DF-003, a first-in-class oral ALPK1 inhibitor, at the Association for Research in Vision and Ophthalmology (ARVO) 2026 annual meeting in Denver, Colorado.

The presentation featured preliminary clinical outcomes from patients with ROSAH syndrome, a rare inherited autoinflammatory disease caused by activating mutations in the ALPK1 gene. The condition is characterized by progressive retinal degeneration, optic nerve pathology, and systemic inflammatory manifestations.

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,” was presented during Poster Session 537: Retina/RPE: New drugs, mechanisms of action, metabolism, and toxicity on May 7, 2026, from 11:45 a.m. to 1:30 p.m.

The open-label Phase 1b study (NCT06395285) enrolled six adult patients with genetically confirmed ROSAH syndrome. Participants 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. Notably, these improvements diminished after treatment discontinuation, providing evidence of a direct pharmacologic effect of DF-003.

Ophthalmologic evaluations showed encouraging signs of disease modulation in both the optic nerve and retina. Optical coherence tomography (OCT) assessments revealed reductions in optic disc swelling and peripapillary retinal thickness, with measurable changes observed as early as Day 29. One evaluable patient experienced clinically meaningful gains in visual function, including improvements in best-corrected visual acuity of +12 letters in the left eye and +5 letters in the right eye after only 8 days of treatment.

Beyond ocular outcomes, patients also demonstrated improvements in neurological and systemic symptoms. Headache severity improved during treatment as measured by the validated HIT-6 questionnaire, while symptoms worsened after therapy cessation. Investigators additionally reported reversal of anhidrosis and improvements in arthralgia, findings consistent with systemic anti-inflammatory activity.

DF-003 was reported to be well tolerated throughout the 28-day dosing period. No serious adverse events or treatment-emergent adverse events were observed during active treatment. The company also reported no clinically significant abnormalities in liver, renal, hematologic, or coagulation parameters. Adverse events occurring after discontinuation were described as consistent with recurrence of underlying ROSAH syndrome symptoms.

DF-003 is designed as a potent and selective inhibitor of disease-causing ALPK1 mutants, including T237M. The therapy is capable of penetrating both the blood-retina and blood-brain barriers and suppresses phosphorylation of TIFA, a key mediator of innate immune signaling and NF-κB activation.

Drug Farm said the reversibility of clinical and biomarker responses following discontinuation provides strong mechanistic evidence that the observed therapeutic effects are driven by on-target inhibition of the ALPK1 pathway.

“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.”

Based on the phase 1b findings, Drug Farm plans to advance DF-003 into a pivotal phase 3 clinical trial to further evaluate its efficacy and safety across both systemic and ophthalmologic manifestations of ROSAH syndrome.