Week 4, November 2024: The PD-1, PD-L1, and VEGF Train

This month, two high-profile deals for bispecific antibodies targeting the PD-1/PD-L1 and VEGF pathways were announced.  

The Deals

On November 14, Merck announced its licensing agreement with LaNova Medicines for LM-299, an investigational PD-1/VEGF bispecific antibody. Merck is committing up to $3.3 billion, with $588 million upfront, to develop and commercialize LM-299 globally. This therapy, now in Phase 1 trials for solid tumors in China, is designed to restore immune function while preventing tumor angiogenesis.  

Just a day prior, BioNTech announced its $800 million acquisition of Biotheus, securing global rights to BNT327/PM8002, a PD-L1/VEGF-A bispecific antibody. This acquisition aligns with BioNTech’s strategy to create combination therapies for solid tumors, leveraging BNT327/PM8002 as a backbone.

Why the PD-1/VEGF Mechanism? 

PD-1 plays a key role in programmed death signaling in order to regulate T- cell mediated reponses. PD-1 engagement can reduce cytokine secretion and cell proliferation through interfering with CD28-costimulatory signalling pathway. Keytruda (pembrolizumab) is a humanized IgG4 mAb that disrupts the PD-1/PD-L1 pathway. As Merck’s blockbuster drug, it will be facing biosimilar competition in the coming years. 

VEGF inhibitors, on the other hand, blocks angiogenesis in tumors but can also change or destroy tumor vessels. By combining these mechanisms, bispecific antibodies offer a synergistic approach, tackling cancer on multiple fronts. 

Meanwhile, early data from competitors like Summit Therapeutics’ ivonescimab has shown the potential of these therapies to outperform established treatments. As a PD-1/VEGF-A bispecific, ivonescimab demonstrated a nearly 50% reduction in the risk of disease progression or death in advanced non-small cell lung cancer compared to Keytruda.