Summit Therapeutics and MD Anderson Announce Strategic Collaboration to Accelerate Development of Ivonescimab
Five Year Collaboration Intended to Advance PD-1 / VEGF Bispecific in Several Solid Tumors across Multiple Clinical Trials
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
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,
“Through our extensive clinical research efforts, we are committed to bringing impactful new medicines to patients in need as rapidly as possible,” said
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,
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, 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, 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
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,
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
About
Summit was founded in 2003 and our shares are listed on the Nasdaq Global Market (symbol "SMMT"). We are headquartered in
For more information, please visit https://www.smmttx.com and follow us on X @SMMT_TX.
About MD Anderson
Summit Forward-looking Statements
Any statements in this press release about the Company’s future expectations, plans and prospects, including but not limited to, statements about the clinical and preclinical development of the Company’s product candidates, entry into and actions related to the Company’s partnership with
Appendix: Glossary of Critical Terms Contained Herein
Affinity – Affinity is the strength of binding of a molecule, such as a protein or antibody, to another molecule, such as a ligand.
Avidity – Avidity is the accumulated strength of multiple binding interactions.
Angiogenesis – Angiogenesis is the development, formation, and maintenance of blood vessel structures. Without sufficient blood flow, tissue may experience hypoxia (insufficient oxygen) or lack of nutrition, which may cause cell death.1
Cooperative binding – Cooperative binding occurs when the number of binding sites on the molecule that can be occupied by a specific ligand (e.g., protein) is impacted by the ligand’s concentration. For example, this can be due to an affinity for the ligand that depends on the amount of ligand bound or the binding strength of the molecule to one ligand based on the concentration of another ligand, increasing the chance of another ligand binding to the compound.2
Immunotherapy – Immunotherapy is a type of treatment, including cancer treatments, that help a person’s immune system fight cancer. Examples include anti-PD-1 therapies.3
Intracranial - Within the cranium or skull.
PD-1 – Programmed cell Death protein 1 is a protein on the surface of T cells and other cells. PD-1 plays a key role in reducing the regulation of ineffective or harmful immune responses and maintaining immune tolerance. However, with respect to cancer tumor cells, PD-1 can act as a stopping mechanism (a brake or checkpoint) by binding to PD-L1 ligands that exist on tumor cells and preventing the T cells from targeting cancerous tumor cells.4
PD-L1 – Programmed cell Death Ligand 1 is expressed by cancerous tumor cells as an adaptive immune mechanism to escape anti-tumor responses, thus believed to suppress the immune system’s response to the presence of cancer cells.5
PD-L1 TPS – PD-L1 Tumor Proportion Score represents the percentage of tumor cells that express PD-L1 proteins.
PFS – Progression-Free Survival.
RANO –Response Assessment in Neuro-Oncology, the standard for assessing the response of a brain or spinal cord tumor to therapy.
SQ-NSCLC – Non-small cell lung cancer tumors of squamous histology.
T Cells – T cells are a type of white blood cell that is a component of the immune system that, in general, fights against infection and harmful cells like tumor cells.6
Tetravalent – A tetravalent molecule has four binding sites or regions.
Tumor Microenvironment – The tumor microenvironment is the ecosystem that surrounds a tumor inside the body. It includes immune cells, the extracellular matrix, blood vessels and other cells, like fibroblasts. A tumor and its microenvironment constantly interact and influence each other, either positively or negatively.7
VEGF – Vascular Endothelial Growth Factor is a signaling protein that promotes angiogenesis.8
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Shibuya M. Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies. Genes Cancer. 2011 Dec;2(12):1097-105 |
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Stefan MI, Le Novère N. Cooperative binding. PLoS |
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Han Y, et al. PD-1/PD-L1 Pathway: Current Researches in Cancer. Am J Cancer Res. 2020 |
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Han Y, et al. PD-1/PD-L1 Pathway: Current Researches in Cancer. Am J Cancer Res. 2020 |
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Shibuya M. Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies. Genes Cancer. 2011 Dec;2(12):1097-105. |
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Contact Summit Investor Relations:
Chief Business & Strategy Officer
Senior Director, Investor Relations
investors@smmttx.com
Contact MD Anderson:
1-713-792-9518
CRBoldt@MDAnderson.org
MD Anderson Public Relations Office
1-713-792-0655
PublicRelations@MDAnderson.org
@MDAndersonNews
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