Key Takeaways

• Interim phase 1b findings showed ophthalmic responses in 3 of 5 evaluable Chinese participants, with individual patients demonstrating improvements in visual acuity, color vision, and microperimetry
• DF-003 treatment was associated with improvements in systemic ROSAH manifestations and reductions in multiple inflammatory biomarkers, with some effects partially reversing after treatment ended
• Drug Farm plans to advance the oral ALPK1 inhibitor into a Phase 3 pivotal trial

Drug Farm reported positive interim findings from an international phase 1b study of DF-003, an investigational oral ALPK1 inhibitor, showing improvements in visual function and several systemic manifestations among adults with ROSAH syndrome.

The findings were presented by Ruifang Sui, MD, PhD, at the Asia-Pacific Vitreo-retina Society 2026 Congress in Gold Coast, Australia. According to the company, the results support continued clinical development of DF-003, including a planned phase 3 pivotal trial.

ROSAH syndrome is a rare genetic autoinflammatory disorder caused by activating mutations in ALPK1. The disease is characterized by progressive retinal degeneration as well as systemic inflammatory manifestations.

The open-label phase 1b study enrolled 11 adults with genetically confirmed ROSAH syndrome at 3 clinical sites in China, Australia, and the United States. Participants received DF-003 at 140 mg orally once daily for 3 days, followed by 45 mg once daily through Day 28. At the time of the presentation, 9 participants had completed follow-up through Day 78, while 2 remained in follow-up.

The APVRS presentation included detailed findings from 5 participants treated at Peking Union Medical College Hospital in China. Investigators reported improvements across ophthalmic function, anhidrosis, headache, arthralgia, and quality of life that were consistent with observations among participants enrolled in the United States and Australia.

For the presented analysis, an ophthalmic response was defined as an improvement of at least 2 lines in best-corrected visual acuity (BCVA) or low-luminance BCVA in at least 1 eye, or an improvement of at least 5 dB on microperimetry at 5 or more loci that was consistent with the direction of the BCVA change.

Three of the 5 Chinese participants met these response criteria. The other 2 had advanced visual impairment that limited assessment using the prespecified measures, according to Drug Farm.

One 20-year-old participant experienced an 11-letter improvement in BCVA. Color vision improved from 20 of 25 Ishihara plates at baseline to 25 of 25 by Day 15, with the improvement maintained through Day 78. The same participant experienced improvement in anhidrosis, with sweating returning beginning on Day 15. Objective testing demonstrated increased sweat production, and the patient reported improved heat tolerance. Weekly fever was absent during treatment but returned following treatment cessation. High-sensitivity C-reactive protein (hsCRP) in this participant decreased from 100 mg/L on Day 2 to 1.64 mg/L on Day 29. Improvements in mobility, fatigue, sleep quality, and arthralgia were also reported.

A second participant, who had advanced ocular disease, severe visual impairment, and a complicated cataract, also demonstrated an 11-letter improvement in visual acuity. Microperimetry showed improvements of at least 5 dB at 17 of 68 matched loci in the right eye and 15 of 68 matched loci in the left eye. These included spatially coherent clusters of at least 5 contiguous loci in each eye, according to Drug Farm. Intermittent fever was absent during treatment in this participant, while hsCRP decreased from 19.8 mg/L at baseline to 0.63 mg/L by Day 15.

Across the 5 Chinese participants, improvements in anhidrosis were observed through both objective sweat testing and patient-reported assessments. Improvements in headache burden, arthralgia, and quality of life were also reported among evaluable participants.

“These interim findings are encouraging because improvements were observed across both ocular and systemic manifestations of ROSAH syndrome,” Dr. Sui, chief physician and professor at Peking Union Medical College Hospital, said in a company announcement. “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.”

DF-003 was reported to be well tolerated in the interim analysis. No serious adverse events were observed, and no adverse events occurred during the 28-day treatment period. Drug Farm said all recorded adverse events occurred after treatment ended and were primarily associated with the reemergence of ROSAH symptoms.

No clinically meaningful treatment-emergent laboratory abnormalities were identified. Pharmacokinetic findings were generally consistent among participants enrolled in China and elsewhere and supported once-daily oral administration, according to the company.

Drug Farm plans to advance DF-003 into a phase 3 pivotal trial in patients with ROSAH syndrome. Longer treatment and evaluation in a larger patient population will be needed to determine the durability and magnitude of the ophthalmic and systemic effects suggested by the small, open-label phase 1b study.