On April 13, 2022 CStone Pharmaceuticals ("CStone", HKEX: 2616), a leading biopharmaceutical company focused on the research, development, and commercialization of innovative immuno-oncology therapies and precision medicines, reported that the preclinical data of multi-specific antibody CS2006/NM21-1480 has been presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 (Press release, CStone Pharmaceauticals, APR 13, 2022, View Source [SID1234612149]).

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Session: PO.IM02.09 – Therapeutic Antibodies 1
Date: April 12, 2022, 9:00 AM – 12:30 PM ET
Format: E-posters
Title: 2870/13-Dose selection investigations and combination strategies of NM21-1480, a PD-L1/4-1BB/HSA trispecific MATCH3 therapeutic clinical candidate
Presenter: Dr. Dan Snell

CS2006/NM21-1480 is a monovalent, tri-specific antibody-based molecule targeting PD-L1, 4-1BB, and human serum albumin (HSA). CS2006/NM21-1480 represents a leading class of broadly acting next-generation anti-PD-1/PD-L1 cancer immunotherapies and a new backbone molecule for tumor-specific combination therapies. CS2006/NM21-1480 is designed to bind to the immune co-stimulatory receptor 4-1BB and conditionally activate T cells only when engaging and blocking the checkpoint receptor ligand PD-L1 on the surface of tumor cells, potentially preventing the liver toxicities observed with previous anti-4-1BB agonistic antibodies.

Compared to other PD-L1/4-1BB bispecific antibody candidates, CS2006/NM21-1480’s unique monovalent structure and ultra-high-affinity PD-L1-binding are designed to tap the synergistic potential of tumor-localized modulation of PD-L1 and 4-1BB. Furthermore, half-life extension via the HSA-binding is designed to enable convenient dosing schedules for patients. CS2006/NM21-1480 is anticipated to be effective against tumors with a wide range of PD-L1 expression levels and may overcome primary and/or acquired resistance to anti-PD-1/PD-L1 therapies.

"The preclinical data of CS2006/NM21-1480 are encouraging and further demonstrate its potential to become a best-in-class anti-4-1BB agonist and next-generation immune checkpoint inhibitor. The bell-shape dose-response curve associated with this class of agents presents a unique challenge with dose-selection in the clinic. However, this concern seems to be alleviated by the fine affinity balance engineered in CS2006/NM21-1480 which allows optimal PD-L1 blockade and 4-1BB activation at the same time." Dr. Archie Tse, Chief Scientific Officer of CStone, said, "The first-in-human dose escalation study is ongoing in the United States, and patient enrollment has commenced in Taiwan, China. In addition, the investigational new drug application has been approved by the National Medical Products Administration of China and the clinical trial is underway. Moving forward, we will step up our efforts to drive research and development of CS2006/NM21-1480, and other pipeline assets to provide high-quality treatments for a wider range of cancer patients as soon as possible."

CS2006/NM21-1480 was discovered and engineered by Numab Therapeutics ("Numab"), CStone’s partner, using its proprietary λcap technology and MATCH platform. CStone and Numab signed an exclusive regional licensing agreement for the development and commercialization of the drug candidate. Pursuant to the terms of the licensing agreement, CStone will fund the research and development of CS2006/NM21-1480 up to completion of an initial Phase 1b clinical trial. In exchange, CStone obtains exclusive rights from Numab to develop and commercialize CS2006/NM21-1480 in Greater China (including Mainland China, Hong Kong, Macau, and Taiwan), South Korea, and Singapore. Numab retains all CS2006/NM21-1480 rights for the rest of the world. Upon completion of CStone’s funding period, no further financial obligations will be owed by either party.