MSD, the maker of the global "king of medicine" - Keytruda, made headlines at the end of last year by investing USD 588 million in an advance payment and USD 2.7 billion in potential milestone payments to acquire the tumor immunotherapy LM-299 from the Chinese company LaNova Medicines. This deal highlights the growing attention in the pharmaceutical development field towards oncology targeting the dual PD-(L)1 and VEGF pathways. PD-(L)1 and VEGF (vascular endothelial growth factor) bispecific antibody therapies are considered a key direction for future tumor treatments, attracting increasing global interest due to their unique mechanism of action and promising clinical data. As a result, more and more pharmaceutical companies worldwide are focusing on this area, with China playing a crucial role in its field.
1. Mechanism of Action of PD-(L)1 and VEGF Combination Therapy
PD-(L)1 inhibitors restore the immune system's ability to recognize and attack tumor cells by blocking the interaction between the PD-L1 molecules expressed on tumor cells and the PD-1 receptors on immune cells. However, the abnormal blood vessel development in the tumor microenvironment can inhibit immune cell infiltration and provide nutritional support to tumor cells. VEGF, as a major regulator of angiogenesis, plays a crucial role in this process. By inhibiting VEGF, the normal blood vessel structure of the tumor tissue can be restored, enhancing immune cell penetration into the tumor and synergizing with PD-(L)1 inhibitors to strengthen the anti-tumor immune response.
For this reason, PD-(L)1 and VEGF dual-target bispecific antibody therapies have garnered widespread attention. These therapies combine immune checkpoint inhibition with anti-angiogenesis, not only directly targeting the tumor but also optimizing the tumor microenvironment from multiple angles to create a synergistic anti-cancer effect. Particularly in patient groups where PD-(L)1 inhibitor single-drug is not highly effective, PD-(L)1/VEGF bispecific antibody has the potential to significantly improve therapeutic effect. Currently, more than 10 PD-(L)1/VEGF bispecific antibody projects are in clinical trials, and early data has shown promising efficacy across various solid tumors, demonstrating significant tumor inhibition effects and the potential for prolonged survival.
2. Position of Chinese Assets in the Global PD-(L)1/VEGF Competitive Landscape
Globally, the R&D of PD-(L)1 and VEGF bispecific antibody therapies has entered a highly competitive phase. Major pharmaceutical giants and biotech companies have increased their investments to advance the development of related drugs.
Currently, several PD-(L)1 and VEGF bispecific antibody assets targeting different tumor types have entered clinical trials. Among them, the key assets from Summit Therapeutics and BioNTech stand out. MSD's acquisition of LM-299 asset of LaNova Medicines was, to some extent, inspired by Summit Therapeutics, which also licensed the PD1-VEGF drug ivonescimab from another Chinese company, Akeso, Inc. A clinical trial of Ivonescimab showed that it outperformed MSD's "king of medicine" Keytruda in the treatment of non-small cell lung carcinoma (NSCLC), one of the most important indications for which Keytruda has been approved. Ivonescimab's success in this field highlights the potential for PD1-VEGF mechanism drugs to "replace" existing therapies in the future.
In addition to Ivonescimab, BioNTech's PD-L1/VEGF candidate BNT-327 has demonstrated consistent efficacy across various tumors and subgroups, with particularly optimistic data in breast cancer. Not coincidentally, BNT-327 was also an asset acquired through BioNTech's USD 800 million acquisition of the Chinese enterprise Biotheus, with an additional potential performance payment of USD 150 million. This deal was officially completed in February of this year. To date, more than 750 patients have received BNT-327 treatment in clinical trials. Multiple clinical trials are underway to evaluate the effects of BNT-327 as a monotherapy or in combination with other treatments targeting various oncogenic pathways for so...
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