Adagrasib

The rise of the PD-(L)1xVEGF class offers checkpoint leader wannabes an opportunity to make up for lost PD-1 opportunities and potentially leapfrog makers of anti-PD-1 cancer drugs.\n As Merck & Co., Bristol Myers Squibb and Pfizer have hopped on the PD-(L)1xVEGF bispecific bandwagon, the question becomes how far the fanfare will spread.It’s more than just existing PD-1/L1 players potentially looking for bispecifics to bolster their positions; whether checkpoint inhibitor wannabes will use these next-generation antibodies to make up for lost PD-1 opportunities—and potentially leapfrog makers of anti-PD-1 drugs—remains an open topic for discussion.Both Eli Lilly and Novartis once had their eyes on PD-1 inhibitors but abandoned their plans after the market became increasingly crowded and their regulatory paths became trickier. What’s more, both Lilly and Novartis know the VEGF approach well. Lilly’s VEGFR2 inhibitor Cyramza is approved in certain patients with stomach cancer, colorectal cancer, liver cancer and EGFR-mutant non-small cell lung cancer (NSCLC). Novartis has Beovu, a not-so-successful anti-VEGF agent for certain eye conditions like wet age-related macular degeneration.“It’s a pretty hot topic,” Jake Van Naarden, president of Lilly Oncology, said in an interview on the sidelines of the 2025 American Society of Clinical Oncology (ASCO) annual meeting in Chicago. The conversation was conducted before BMS’ announcement of its $1.5 billion upfront deal for BioNTech’s PD-L1xVEGF candidate.Data from the PD-(L)1xVEGF class have so far been “provocative,” he said.“But, at the same time, a lot of the data we’ve seen from these studies have been early looks at important endpoints,” Van Naarden said. “I’m not prognosticating how those data will mature over time, but I think that’s really, really important.”“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 said. “We have no religion about A, where the medicine comes from, or B, what the medicine targets, or how it’s constructed,” he said. “All we care about is delivering really, really great new medicines to cancer patients.”The Lilly exec pointed out how the Indianapolis drugmaker is a bigger company than it’s ever been and has more resources than ever to bring such an agent in house and carry it through clinical development.Thanks to the success of its GLP-1 diabetes and weight loss meds, Lilly is currently the world’s largest pharma company by market cap. As of the end of March, the company had about $3.1 billion in cash and cash equivalents on its balance sheet.To Novartis, PD-(L)1xVEGF is clearly on the rise, and “it’s clearly an area that we evaluate carefully and looking at all the options,” the company’s president of development and chief medical officer, Shreeram Aradhye, M.D., said in a separate interview with Fierce Pharma shortly after Pfizer’s $1.25 billion upfront deal for 3SBio’s PD-1xVEGF candidate.A PD-(L)1xVEGF bispecific could offer Novartis a set of opportunities beyond the company’s internal work on radioligand therapies, and Novartis is looking at the area more like a “potential hedge,” Aradhye said.“To that end, it is an area of interest that we look at. I think it’s under evaluation,” he said. Novartis’ way of working allows it to not get trapped in fear of missing out while also making sure that it evaluates properly what added value that the PD-(L)1xVEGF biology might bring, he said.More broadly speaking, Novartis continues to be interested in external clinical-stage assets that are aligned with its areas of interest, Aradhye said. These include breast, prostate and lung cancers as well as adjacent areas such as ovarian and bladder cancers. While the execs with Lilly and Novartis appeared curious but cautious about PD-(L)1xVEGF bispecifics, it’s worth noting that biopharma companies often present a degree of impartiality on hot topics so they don’t reveal their intentions before going public with a deal.For example, when asked the same question of whether a PD-1xVEGF bispecific would be a fit for BMS the day before the BioNTech deal announcement, BMS Chief Medical Officer Samit Hirawat, M.D., didn’t show any special interest in the field.“Certainly very interesting data, and we have to continue to observe where it goes, and then we’ll make our call as we go along,” Hirawat said during a June 1 interview with Fierce on the sidelines of ASCO 2025.The BMS exec instead pointed to the company’s existing projects in NSCLC. On the commercial side, these include the FDA-approved Augtyro for ROS1-mutated NSCLC and Krazati for KRAS G12C-mutated NSCLC. On the clinical side, a phase 3 study is ongoing for Opdivo and a higher dose of the LAG-3 inhibitor relatlimab in first-line PD-L1-positive NSCLC, and BMS is examining its PRMT5 inhibitor in MTAP-deleted cancers, including NSCLC.