Phase 1 study of balinatunfib, an oral inhibitor of TNFR1 signal in mild‐to‐moderate psoriasis

BACKGROUND: Activation of tumour necrosis factor receptor 1 (TNFR1) promotes inflammation in several autoimmune diseases. OBJECTIVES: To evaluate safety, tolerability and clinical efficacy of balinatunfib versus placebo in patients with mild-to-moderate psoriasis. METHODS: Phase-1, 4-week, randomized, double-blind, placebo-controlled pilot study, including patients aged 18-65 years with chronic plaque-type psoriasis with mild-to-moderate severity as defined by Psoriasis Area Severity Index (PASI ≤16) and ≥2 lesions with a Target Lesion Severity Score (TLSS) ≥4 at both screening and baseline. The primary endpoint was safety and tolerability of balinatunfib as assessed by the incidence of adverse events (AEs), treatment-emergent AEs (TEAEs) and AEs of special interest. Secondary endpoints were the percent change in TLSS from baseline to Weeks 2 and 4. Serum biomarkers, interleukin-22 (IL-22), IL-17F and percent change in PASI from baseline to Weeks 2 and 4, were also evaluated. RESULTS: 38 male patients (age [mean ± SD], 43 ± 10.6) were randomized to receive 200-mg balinatunfib (N = 26) or placebo (N = 12). No serious or severe TEAEs or adverse events of special interest were observed during the study. Dysgeusia (61.5% vs. 0%) and nausea (19.2% vs. 0%) were the most frequently reported TEAEs in the balinatunfib versus the placebo groups. Balinatunfib showed improvements from baseline in TLSS vs. placebo at Week 2 (17.06% vs. 6.29%, p = 0.032) and Week 4 (38.18% vs. 20.44%, p = 0.012). Exploratory analyses suggested an improvement in the total PASI scores at Week 2 (17.73% vs. 4.12%, nominal p = 0.005), Week 4 (35.09% vs. 15.71%, nominal p = 0.009) and decreased serum levels of IL-22 (nominal p = 0.0001) and IL-17F (nominal p = 0.0025) with balinatunfib treatment. CONCLUSIONS: Patients with mild-to-moderate psoriasis treated with balinatunfib reported no severe or serious TEAEs and showed promising clinical responses, suggesting that further evaluation of TNFR1 signal inhibition in inflammatory diseases is warranted.