Asahi Kasei Therapeutics Corp., has initiated a Phase I clinical trial for AK1940, a peptide-based selective antagonist of tumor necrosis factor receptor 1 (TNFR1), marking the compound's first entry into human testing. The trial (jRCT2071250141) began April 19, 2026 in Japan and will evaluate single and multiple ascending subcutaneous doses in healthy volunteers, with pharmacokinetics, safety, and tolerability as primary endpoints. AK1940 was discovered through a joint research program with PeptiDream Inc., a specialist in constrained peptide platforms, and will be developed independently by Asahi Kasei Therapeutics, the pharmaceutical subsidiary of the diversified parent group Asahi Kasei.
The compound's mechanism sets it apart from the five approved pan-TNF inhibitors — adalimumab, etanercept, infliximab, certolizumab pegol, and golimumab — that collectively dominate the TNF-targeted market in rheumatoid arthritis and related conditions. All existing agents block TNF ligand or both receptor subtypes simultaneously. TNFR2, which those agents also suppress, mediates regulatory T-cell function and tissue repair signaling. AK1940 targets only TNFR1, the receptor subtype that drives the pro-inflammatory arm of TNF biology, leaving TNFR2 intact.
Research context
The biological rationale for selective TNFR1 antagonism has accumulated over more than a decade. A 2021 study published in Frontiers in Immunology demonstrated that atrosimab, a TNFR1-selective antagonist, produced therapeutic activity across multiple acute and chronic inflammatory mouse models — providing class-level preclinical validation for the approach (AllSci link. Work published in Blood in 2019 showed that TNFR1 blockade, not TNFR2 blockade, reduced chronic inflammation in a JAK2-V617F mouse model), and a 2021 Blood Advances follow-up reinforced that the two receptor subtypes are not interchangeable therapeutic nodes. More recently, a 2024 Nature Communications paper documented dichotomous immune outcomes from TNFR1 versus TNFR2 signaling in NK cell responses, strengthening the conceptual basis for receptor-selective intervention.