On October 31, 2023 Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") reported that data for its novel, potential first-in-class investigational bispecific antibody, ivonescimab, will be presented at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in San Diego, CA (Press release, Summit Therapeutics, OCT 31, 2023, View Source [SID1234636600]). 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.
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The poster is a collaborative effort between Summit and our collaboration and licensing partner, Akeso, Inc. (HKEX Code: 9926.HK), who generated and analyzed the data. The senior author of the poster is Jing Min, PhD, Senior Vice President Drug Discovery and Preclinical Science at Akeso, and it will be presented at SITC (Free SITC Whitepaper) 2023 by Betty Y. Chang, PhD, Head of Research at Summit.1
Ivonescimab, known as SMT112 in the United States, Canada, Europe, and Japan, and as AK112 in China and Australia, 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,2 and over 4 times increased binding affinity to VEGF in the presence of PD-1 in vitro.3 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.
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.
Over 950 patients have been treated with ivonescimab across multiple clinical studies in different proposed indications in China and Australia, in addition to those recently enrolled in Summit’s license territories.
Lung cancer is believed to impact approximately 238,0004 people in the United States each year and approximately 477,0005 in Europe. NSCLC is the most prevalent type of lung cancer and represents approximately 80% to 85% of all incidences.6 Among patients with non-squamous NSCLC, approximately 15% have EGFR-sensitizing mutations in the United States and Europe.7 Patients with squamous histology represent approximately 25% to 30% of NSCLC patients.8
Ivonescimab is an investigational therapy that is not approved by any regulatory authority.
About the SITC (Free SITC Whitepaper) 2023 Poster
Poster Title: Mechanism of Action of Ivonescimab (AK112/SMT112): A First-in-Class Tetravalent Fc-silent Bispecific Antibody with Dual Blockade of PD-1 and VEGF that Promotes Cooperative Biological Effects
SITC Abstract No.: 1194
Session Date & Time: Saturday November 4, 2023, from 11:55am to 1:25pm PT