PD-(L)1xVEGF Bispecific Antibodies: The New Frontier in Cancer Immunotherapy

In a rapidly evolving landscape of cancer immunotherapy, pharmaceutical giants are racing to secure their positions in the promising field of PD-(L)1xVEGF bispecific antibodies. Recent developments have seen major players like Bristol Myers Squibb (BMS), Pfizer, and Merck & Co. making significant moves, while others such as Eli Lilly and Novartis are closely monitoring the situation.

Big Pharma's Big Moves

Bristol Myers Squibb has made headlines with its $1.5 billion upfront deal to acquire BioNTech's PD-L1xVEGF candidate, signaling a strong commitment to this emerging class of therapeutics. Not to be outdone, Pfizer has invested $1.25 billion upfront in a deal with 3SBio for their PD-1xVEGF bispecific candidate. These substantial investments underscore the industry's confidence in the potential of these novel therapies.

Merck & Co., already a leader in the PD-1 inhibitor space with Keytruda, has also joined the bispecific race, although specific details of their program remain undisclosed. The involvement of these pharmaceutical powerhouses has sparked intense interest in the field, with many wondering who might be next to enter the fray.

Cautious Optimism from Potential Entrants

Eli Lilly and Novartis, both of which previously abandoned plans for PD-1 inhibitors due to market saturation and regulatory challenges, are now carefully evaluating their options in the PD-(L)1xVEGF bispecific space.

Jake Van Naarden, president of Lilly Oncology, described the data from the PD-(L)1xVEGF class as "provocative" but emphasized the importance of waiting for more mature data. "If ultimately it seems obvious that this will be an important class of medicines, of course it would make sense for Lilly to have a PD-(L)1xVEGF program of its own," Van Naarden stated.

Novartis' chief medical officer, Shreeram Aradhye, M.D., echoed this sentiment, noting that PD-(L)1xVEGF is "clearly an area that we evaluate carefully and looking at all the options." Aradhye described Novartis' interest in the field as a "potential hedge," suggesting that the company is considering how these bispecifics might complement their existing oncology portfolio, particularly their work in radioligand therapies.

The Promise and Challenges of Bispecific Antibodies

PD-(L)1xVEGF bispecific antibodies represent a novel approach to cancer immunotherapy, combining the immune-activating properties of PD-1/PD-L1 inhibition with anti-angiogenic effects targeting VEGF. This dual-action mechanism is believed to potentially enhance efficacy compared to individual checkpoint inhibitors or anti-VEGF therapies.

However, industry experts caution that while early data are promising, more comprehensive clinical results are needed to fully understand the potential of this new class of drugs. The field is still young, and questions remain about long-term efficacy, safety profiles, and how these bispecifics will compare to established treatment regimens across various cancer types.

As the race intensifies, pharmaceutical companies must balance the potential rewards of being early movers in this space against the risks of investing heavily in an still-unproven technology. The coming months and years will likely see continued dealmaking, clinical trial announcements, and potentially, the emergence of new players in this exciting and rapidly evolving field of cancer immunotherapy.