Ivonescimab Overview

Designed to potentially improve 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., Canada, Europe, Japan & Latin America and is an investigational therapy that is not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA). It brings two validated mechanisms in oncology3-5 into ONE novel tetravalent molecule. Ivonescimab simultaneously engages both PD-1 & VEGF. Globally over 2,300+ have been treated with ivonescimab across all clinical trials to date.

Mechanism of Action (MOA) based on in vitro studies6

Simultaneous interaction of PD-1 & VEGF blockades have the potential to drive synergistic anti-tumor activity
Inhibiting VEGF can help improve the effect of immunotherapy by modulating the tumor microenvironment (TME).
Enhancing the PD-1 blockade helps activate T cells.

COOPERATIVE BINDING
Increased Binding Strength (Affinity)
Presence of VEGF increases PD-1 binding strength by >18X
Presence of PD-1 increases VEGF binding strength by >4X

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 cells

Ivonescimab MOA Overview

Tumor Microenvironment

Images for illustrative purposes only.

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 where there are higher levels of PD-1 and VEGF vs. healthy tissue.1,2,6

Half-life (T1/2) of 6-7 days6
Provides blockade of both PD-1 and VEGF targets with its affiliated clearance, which could potentially lead to a favorable safety profile1,2

Clinical Trials

For additional information on the HARMONi or the HARMONi-3 clinical trials, please visit clinicaltrials.gov or contact medinfo@smmttx.com

Phase 3 Study: NCT063960654

A Randomized, Double-blind, Multi-center, Phase III Clinical Study of AK112 or Placebo Combined with Pemetrexed and Carboplatin in Patients With EGFR-mutant Locally Advanced or Metastatic Non-small Cell Lung Cancer Who Have Progressed on or Following Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment.
Learn more.

HARMONi Fact Sheet

Phase 3 Study: NCT058996085

A Randomized, Double-blinded, Multiregional Phase 3 Study of ivonescimab Combined with Chemotherapy versus pembrolizumab Combined with Chemotherapy for the First-line Treatment of Metastatic Non-small Cell Lung Cancer.
Learn more.

HARMONi-3 Fact Sheet

Phase 3 Study: NCT067675146

A Randomized, Double-blinded, Multiregional Phase 3 Study of Ivonescimab Versus Pembrolizumab for the First-line Treatment of Metastatic Non-small Cell Lung Cancer in Patients Whose Tumors Demonstrate High PD-L1 Expression (TPS ≥ 50%)
Learn more.

References

  1. Zhao Y. et al. eClinicalMedicine. 2023; 3(62): 102106.
  2. Wang L, et al. J Thorac Oncol. 2024 Mar;19(3):465-475.
  3. Manegold C, et al. J Thorac Oncol 2017;12(2):194-207.
  1. Tamura R, et al. Med Oncol 2020;37(1):2.
  2. Zhong T, et al. AACR-NCI-EORTC International Conference 2023.
    Poster #B123, Abstract #35333, Boston, MA, USA.
  3. HARMONi-7. ClinicalTrials.gov identifier: NCT06767514. (Updated Jan 10, 2025)

Abbreviations: PD-1, programmed death-1; VEGF, vascular endothelial growth factor; TPS, tumor proportion score; TME, tumor microenvironment, PD-L1, programmed death-ligand 1; EGFR-mutant, epidermal growth factor receptor mutation; EGFR-TKI, epidermal growth factor receptor- tyrosine kinase inhibitor; NSCLC, non-small cell lung cancer.

Ivonescimab is an investigational therapy that is not presently approved by any regulatory authority other than China’s National Medical Products Administration (NMPA).

*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”).