Drug Farm to Present Positive Phase 1b Data for First-in-Class ALPK1 Inhibitor DF-003 in ROSAH Syndrome at IMMUNOLOGY2026™
Drug Farm has announced promising early clinical and immunologic data from its ongoing Phase 1b study evaluating DF-003, a first-in-class oral inhibitor targeting ALPK1. These preliminary findings are set to be presented in a podium session at IMMUNOLOGY2026, held from April 15–19, 2026, in Boston. The data provide an encouraging glimpse into the potential of a novel therapeutic approach for patients suffering from ROSAH syndrome, a rare and debilitating genetic autoinflammatory condition.
ROSAH syndrome is driven by mutations in the ALPK1 gene, particularly the T237M variant, which leads to dysregulated inflammatory signaling and a range of systemic symptoms. Currently, treatment options for this rare disorder are extremely limited, making the development of targeted therapies an urgent priority. DF-003 has been designed to selectively inhibit ALPK1, thereby addressing the root cause of inflammation in affected patients rather than merely managing symptoms.
The upcoming presentation, titled “Preliminary immunologic and clinical Phase 1b study outcomes from patients with ROSAH syndrome treated with the first-in-class ALPK1 inhibitor DF-003,” will be delivered during the session focused on chronic immunity and interventional strategies. It is scheduled for April 17, 2026, and will highlight both clinical outcomes and pharmacodynamic effects observed in the early-stage trial.
The Phase 1b study (NCT06395285) is a multicenter, open-label trial involving six adult patients with genetically confirmed ROSAH syndrome linked to the ALPK1 T237M mutation. Participants received once-daily oral dosing of DF-003 over a four-week treatment period. Despite the small sample size, the study has yielded notable findings that suggest meaningful clinical benefit.
Across multiple clinical assessments, improvements were observed in several hallmark symptoms of the disease. Four out of six patients experienced a reversal of anhidrosis, a condition characterized by the inability to sweat, which can significantly impair thermoregulation and quality of life. Additionally, patients reported reductions in arthralgia, or joint pain, and demonstrated improvements in overall well-being as measured by the standardized EQ-5D quality-of-life questionnaire.
A particularly important observation was that these clinical benefits diminished after discontinuation of DF-003 treatment. This reversibility strongly supports the conclusion that the improvements were directly attributable to the pharmacologic action of the drug, rather than external or unrelated factors. Such findings are especially valuable in early-phase studies, where establishing a clear drug-response relationship is critical.
Beyond clinical symptom relief, the study also demonstrated significant pharmacodynamic activity, providing evidence that DF-003 effectively modulates inflammatory pathways in humans. In one patient with elevated baseline inflammation, treatment led to normalization of several key biomarkers, including interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), interleukin-8 (IL-8), and CXCL10. These biomarkers are commonly associated with systemic inflammation, and their reduction indicates a meaningful impact on disease biology.
Further evidence of DF-003’s therapeutic potential was observed at the organ level. In one evaluable patient who had not undergone splenectomy, researchers documented an approximately 20% reduction in spleen volume after 28 days of treatment. Splenomegaly, or enlargement of the spleen, is often associated with chronic inflammatory conditions, and its reduction suggests a broader systemic effect of the therapy. As with other outcomes, this effect was reversed following treatment discontinuation, reinforcing the drug’s direct influence.
Safety and tolerability are critical considerations in early-stage drug development, and DF-003 demonstrated a favorable profile in this regard. No serious adverse events or treatment-emergent adverse events were reported during the 28-day dosing period. Additionally, key indicators of organ function, including renal and hepatic parameters, remained stable across all participants. Pharmacokinetic data further support the feasibility of once-daily oral dosing, which could offer a convenient and patient-friendly treatment option if the therapy progresses successfully through later-stage trials.
The significance of these findings has been recognized by clinical experts in the field. John Grigg, a leading specialist in clinical ophthalmology and eye health at the University of Sydney, highlighted the importance of the results, particularly in light of the limited treatment landscape for ROSAH syndrome. He noted that the observed improvements in symptoms such as anhidrosis and systemic inflammation, along with reductions in spleen size and a strong safety profile, underscore the promise of targeting ALPK1 as a therapeutic strategy.
From the company’s perspective, these early data represent a critical milestone. Henri Lichenstein, Chief Executive Officer of Drug Farm, emphasized that the study provides the first clinical evidence that selective inhibition of ALPK1 can translate into tangible clinical benefits for patients. He also pointed to the reversibility of both clinical and biomarker responses as further confirmation of the drug’s mechanism of action. The company plans to present additional data later in the year, including findings related to ophthalmological outcomes and headache symptoms, which are also key aspects of ROSAH syndrome.
Looking ahead, Drug Farm intends to build on these encouraging results by advancing DF-003 into a pivotal Phase 3 clinical trial. The goal of this next stage will be to more comprehensively evaluate the drug’s efficacy and safety in a larger patient population, while further exploring its potential to address the underlying biology of the disease.
In summary, the preliminary Phase 1b findings for DF-003 mark an important step forward in the development of targeted therapies for rare autoinflammatory diseases. By directly inhibiting ALPK1, the drug offers a novel mechanism of action that addresses the root cause of ROSAH syndrome. While additional research is needed to confirm these early results, the data presented at IMMUNOLOGY2026 provide a strong foundation for continued clinical development and raise hope for patients who currently have few effective treatment options.
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.
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