On July 25, 2024 Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") and The University of Texas MD Anderson Cancer Center (MD Anderson) reported a strategic five-year collaboration agreement for the purpose of accelerating the development of ivonescimab (Press release, Summit Therapeutics, JUL 25, 2024, View Source [SID1234645099]).
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Leveraging MD Anderson’s clinical infrastructure and research expertise together with Summit’s innovative, investigational, potential first-in-class PD-1 / VEGF bispecific antibody, the collaboration is designed to quickly discover additional opportunities for ivonescimab, including several tumors outside of its current development plan. MD Anderson will lead multiple clinical trials in several tumor types to evaluate the safety and potential clinical benefit of ivonescimab, including the possibility of identifying biomarkers through additional research activities.
"We are excited to collaborate with MD Anderson to provide unique insights and expertise to further broaden the development of ivonescimab," stated Allen S. Yang, MD, PhD, Chief Medical Officer of Summit. "This collaboration will help accelerate the growing clinical development efforts for ivonescimab and help bring this innovative advancement on immunotherapy and anti-angiogenic standards to as many patients who may benefit as possible."
Early work may include certain types of renal cell carcinoma, colorectal cancer, skin cancer, and breast cancer and glioblastoma, which has the potential to rapidly expand the breadth and depth of the ivonescimab development program. The bispecific antibody has shown significant promise in recent read-outs from the randomized Phase III non-small cell lung cancer clinical trials, HARMONi-A and HARMONi-2, conducted by Summit’s partner, Akeso, in addition to promising Phase II data in other solid tumors.
"Through our extensive clinical research efforts, we are committed to bringing impactful new medicines to patients in need as rapidly as possible," said Christopher Flowers, M.D., Division Head of Cancer Medicine at MD Anderson. "We are pleased to be collaborating with Summit to broaden the clinical development efforts of ivonescimab and its unique mechanism of action to support our mutual goal to improve the therapeutic options for patients with cancer."
MD Anderson and Summit will collaborate on the design and conduct of preclinical and clinical studies with oversight from a joint steering committee. This research is expected to begin later this year.
About Ivonescimab
Ivonescimab, known as SMT112 in Summit’s license territories, the United States, Canada, Europe, Japan, Latin America, including Mexico and all countries in Central America, South America, and the Caribbean, the Middle East, and Africa, 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. Ivonescimab displays unique cooperative binding to each of its intended targets with multifold 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 (Zhong, et al, SITC (Free SITC Whitepaper), 2023). 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, together with a half-life of 6 to 7 days (Zhong, et. al., SITC (Free SITC Whitepaper), 2023), is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.
Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 1,800 patients have been treated with ivonescimab in clinical studies globally.
Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two multi-regional Phase III clinical trials, HARMONi and HARMONi-3.
HARMONi is a Phase III clinical trial which intends to evaluate ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a 3rd generation EGFR TKI (e.g., osimertinib).
HARMONi-3 is a Phase III clinical trial which is designed to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic squamous NSCLC.
In addition, Akeso has recently had positive read-outs in two single-region (China), randomized Phase III clinical trials for ivonescimab in NSCLC, HARMONi-A and HARMONi-2.
HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI.
HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression (PD-L1 TPS >1%).
Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was approved for marketing authorization in China in May 2024.