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. Conclusion 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.