Trial initiation for Numab’s lead pipeline program marks entry of first proprietary tri-specific MATCH antibody into clinical development
Numab Therapeutics AG announced today the first patient has been dosed in its proprietary ND021 program, a next-generation tri-specific immuno-oncology approach targeting PD-L1, 4-1BB and Serum Albumin. The study will initially enroll up to 102 cancer patients at four major clinical sites across the United States and Taiwan and will expand to additional centers as the study progresses. In its first part, this international, multi-center Phase 1/2 clinical study will investigate the safety and tolerability of ascending doses of NM21-1480, the company’s clinical lead molecule in the ND021 program, in patients with various forms of solid tumors and establish a recommended dose for continued clinical development. The trial will subsequently explore the anti-tumor activity of the compound in patients suffering from selected tumor types.
“Advancing NM21-1480 into clinical trials is an exciting and transformative step for Numab Therapeutics,” said David Urech, Ph.D., Founder and Chief Executive Officer of Numab Therapeutics. “Our team has immense faith in the capability of NM21-1480 to invigorate anti-cancer immunity. The unique properties of this molecule are exemplary for our mission to deliver the highest quality of immuno-oncology drugs aiming at better patient outcomes.”
NM21-1480 represents a next-generation checkpoint modulator. Its mechanism of action and preclinical data suggest that it will overcome several limitations of current standard of care checkpoint modulator therapy. The differentiating profile of NM21-1480 over standard of care is based on its molecular design as a monovalent tri-specific antibody fragment. NM21-1480 binds and blocks immune-suppressive PD-(L)1 signaling with best-in-class potency and at the same time triggers 4-1BB-mediated T cell stimulation specifically in the tumor microenvironment to avoid systemic toxicities. NM21-1480 was optimized to bind selected epitopes of the respective targets with balanced affinities in order to maximize the synergistic effect of PD-L1 blockade and 4-1BB agonism in patients with varying PD-L1 expression levels.
“As we dose patients in the initial dose-escalation part of this clinical study, we look forward to study the pharmacodynamic profile of the compound, and establish a dose regimen suggested to provide an optimized benefit to cancer patients,” said Peter Lichtlen, M.D., Ph.D., Founder and Chief Medical Officer of Numab Therapeutics. “NM21-1480 was designed by Numab to overcome the limitations of current standard of care checkpoint inhibitors and also carries several unique mechanistic features as compared to other 4-1BB/PD-L1 bi-specifics that are at similar stage of development. In the subsequent part of the study following our initial dose-escalation we aim at demonstration of this differentiation vs. standard of care based on clinical anti-tumor activity.”
ND021 is a next generation tri-specific immuno-oncology drug targeting the tumor-immunity suppressive PD(L)-1 pathway and the tumor-immunity activating 4-1BB/CD137 pathway in a single therapeutic molecule. Targeting these two clinically validated pathways in a combinatorial approach is expected to provide patients suffering from a broad range of cancer types with a unique novel treatment opportunity characterized by an improved benefit-to-risk profile as compared to current standard of care as well as other combinatorial immunotherapy approaches currently in clinical development. Numab has formed a regional partnership for ND021 with its Chinese partner CStone Pharmaceuticals.