On November 2, 2023 Akeso (9926.HK) reported that its collaboration and licensing partner, Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit") will present data for the novel, potential first-in-class investigational bispecific antibody, ivonescimab (AK112/SMT112), at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in San Diego, CA (Press release, Akeso Biopharma, NOV 2, 2023, View Source [SID1234636829]). The poster with updated data describing ivonescimab’s mechanism of action will be displayed on Saturday November 4, 2023, from 11:55am to 1:25pm Pacific Time. This mechanism of action of ivonescimab was also presented at the 2023 AACR (Free AACR Whitepaper)-NCI-EORTC (American Association for Cancer Research-National Cancer Institute-European Organization for Research and Treatment of Cancer) Conference on Molecular Targets and Cancer Therapeutics.

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Ivonescimab is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. The poster describes how ivonescimab displays unique cooperative binding to each of its intended targets with higher affinity when in the presence of both PD-1 and VEGF.

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the tumor microenvironment with over 18 fold increased binding affinity to PD-1 in the presence of VEGF in vitro, and over 4 times increased binding affinity to VEGF in the presence of PD-1 in vitro. This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.

The marketing application for one indication of ivonescimab was accepted by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) with priority review. Currently, there are four registrational phase III clinical trials being conducted globally, which include three head-to-head trials with PD-1 monoclonal antibody as the positive control drug, and two international multicenter clinical trials.

Summit has begun its clinical development of ivonescimab in order to establish its efficacy and safety in two proposed NSCLC indications:

Ivonescimab combined with chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a third-generation EGFR tyrosine kinase inhibitor (TKI) (HARMONi trial)
Ivonescimab combined with chemotherapy in first-line metastatic squamous NSCLC patients (HARMONi-3 trial)
Earlier this year, the first patient was treated in Summit’s license territories in the Phase III HARMONi clinical trial. Summit has opened clinical trial sites in the HARMONi-3 trial and expects to begin dosing patients in the current fiscal quarter.

About Ivonescimab (PD-1/VEGF bispecific antibody)
Ivonescimab is a potential first-in-class investigational PD-1/VEGF bi-specific antibody discovered by Akeso. It combines the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab is currently engaged in multiple Phase III clinical trials worldwide.

In December 2022, Akeso entered into a collaboration and license agreement for up to US$5 billion with Summit Therapeutics ("Summit"). Akeso out-licensed to Summit exclusive rights to ivonescimab (PD-1/VEGF) for the development and commercialization in the United States, Canada, Europe, and Japan. Akeso will retain development and commercialization rights for the rest of the world including China. Ivonescimab is known as AK112 for Akeso’ R&D code at China and Australia, and as SMT112 for Summit’s license territories.