Ivonescimab Overview
Designed to optimize the balance of anti-tumor activity and safety1,2
Ivonescimab is the most advanced PD-1/VEGF bispecific antibody in clinical development in the U.S. & EU* and is an investigational drug that is not approved by any regulatory authority. It brings two validated mechanisms in oncology3,4,5 into ONE novel tetravalent molecule. Ivonescimab simultaneously engages both PD-1 & VEGF. To-date over 1,600 patients have been treated with ivonescimab in clinical trials in China and Australia. Summit is actively recruiting 100+ patients in the U.S., Canada and Europe; the overall study will include over 400 patients worldwide.
Mechanism of Action (MOA) based on in vitro studies
Simultaneous interaction of PD-1 & VEGF blockades have the potential to drive synergistic anti-tumor activity.1,3,6
Inhibiting VEGF can help improve the effect of immunotherapy by modulating the tumor microenvironment1
Enhancing the PD-1 blockade helps activate T cells.4
COOPERATIVE BINDING
Increased Binding Strength (Affinity)
Presence of VEGF increases PD-1 binding strength by >18X7
Presence of PD-1 increases VEGF binding strength by >4X7
Increased Binding of T Cells
VEGF dimer leads to potential interconnection or daisy chaining of multiple ivonescimab molecules, which may lead to increased binding of T cells7,8
Tumor Microenvironment
Tumor Microenvironment with Ivonescimab Cooperative Binding
VEGF Dimer
PD-1 Receptor in T Cell
Potential Safety Benefits
Ivonescimab has the potential to accumulate in the Tumor Microenvironment (TME) where there are higher levels of PD-1 and VEGF vs. healthy tissue.1,2,7,8
Half-life (T1/2) of 6-7 days9
Provides blockade of both PD-1 and VEGF targets with its affiliated clearance, which could potentially lead to a favorable safety profile4,5
Clinical Trials
For additional information on the HARMONi or the HARMONi-3 clinical trials, please visit clinicaltrials.gov or contact medinfo@smmttx.com
References
- Zhao Y. et al. eClinicalMedicine. 2023; 3(62): 102106.
- Zhou C. et al. J Clin Oncol. 2022;40:16_suppl, 9040.
- Manegold C, et al. J Thorac Oncol 2017;12(2):194-207.
- Pardoll, D. Nat Rev Cancer 2012;12(4):252-64.
- Tamura R, et al. Med Oncol 2020;37(1):2.
- Data on File. [14, 15] Summit Therapeutics Inc.
- Zhong T, et al. AACR-NCI-EORTC International Conference 2023.
Poster #B123, Abstract #35333, Boston, MA, USA. - Zhong T, et al. JITC 2022;10(2):521.
- Zhang L, et al. ASCO 2023 poster #9087.
Ivonescimab is an investigational therapy that is not approved by any regulatory authority.
Ivonescimab is currently being investigated in global Phase III clinical trials. Phase I and II data generated and analyzed by Akeso.
*There are no known PD-1-based bispecific antibodies approved by the U.S. Food and Drug Administration (“FDA”) or the European Medicines Agency (“EMA”).
