Artax Biopharma’s oral Nck modulator AX-158 performed well in a Phase 2a study of patients with mild-to-moderate plaque psoriasis.
Nck modulators are a new class of oral small molecules that inhibit Nck from binding to the T cell receptor (or TCR), blocking TCR activation to treat autoimmune diseases without causing broad immunosuppression.
Learn more about this new approach to autoimmunity from Christopher VanDeusen, PhD, Chief Scientific Officer of Artax Biopharma
About the Study and Its Findings
AX-158 was evaluated in a Phase 2a trial in participants with mild to moderate plaque psoriasis in multiple centers in the UK. Participants were randomized 2:1 to receive a single daily dose of 10mg AX-158 or placebo. A total of 31 participants were treated for 28 days. The primary endpoint of the study was safety, with secondary endpoints to demonstrate proof of mechanism.
When administered every day at a 10mg dose, AX-158 was found to be safe and well-tolerated.
o No Grade ≥ 3 treatment-related adverse effects (TEAEs)
o No discontinuation due to TEAEs
o No serious or opportunistic infections
- Longitudinal skin biopsies showed a trend of reduction in the number of CD8+ T cells in patients treated with AX-158.
- Biomarker analyses revealed statistically significant impacts on IL-17 and IL-12 signalling pathways.
- Statistically significant modulation of multiple psoriasis-related gene sets was observed.
- At the end of the study, only patients who received AX-158 achieved Psoriasis Area and Severity Index (PASI) 150 or greater.
A Clear Impact on T Cells
“From my blinded analysis of the patient samples in this phase 2a study, it is clear that AX-158 shows a clear impact on T cells and related biomarkers in this patient population,” says James Krueger, MD, PhD, Head of Laboratory for Investigative Dermatology at the Rockefeller University and member of the Scientific Advisory Board at Artax Biopharma, in a news release.
“We’re highly encouraged by the safety profile observed in our Phase 2a study and the notable impact of our oral Nck modulator AX-158 on key disease biomarkers and clinical severity scores,” adds Rob Armstrong, PhD, Chief Executive Officer of Artax Biopharma. “These results further support the potential of AX-158 to offer a truly novel mechanism to modulate TCR signaling rather than inhibit it, and we’re committed to continuing to advance this promising candidate to meet the unmet needs of patients with T cell-mediated autoimmune diseases.”
