PM-8002

After trading up 8.5% Thursday following a Bloomberg report of a potential licensing deal with AstraZeneca, Summit Therapeutics\' stock price on Monday erased most of its prior gains. \n After several PD-1xVEGF competitors forged alliances with Big Pharma players, Summit Therapeutics, the frontrunner in this hot cancer drug field, is reportedly seeking its own deal.AstraZeneca is in talks with Summit Therapeutics over a potential licensing deal for the U.S. biotech’s ivonescimab, Bloomberg reported Thursday, citing people familiar with the matter.The deal could be worth $15 billion, including a multibillion-dollar upfront payment and several performance-based milestones, according to Bloomberg. The specific terms were not settled, and Summit has also talked to other large pharma companies, the people told the financial news outlet.Summit’s stock price traded up 8.5% Thursday, reflecting investors’ receptiveness to a Big Pharma collaborator, even though the company itself in-licensed ivonescimab from China’s Akeso. The Florida biotech’s market cap now stands at about $17.4 billion, as its stock nearly erased Thursday’s gains in Monday trading.To really excite investors, Summit will need a deal structure that features at least $7.7 billion in upfront cash, combined with $10 billion in biobucks, a Leerink Partners team led by Daina Graybosch, Ph.D., said in a Thursday note. While any deal could give Summit’s a much-needed injection of cash, Graybosch’s team doubted any Big Pharma company would be willing to pay that much initially.Leerink came up with the number by benchmarking investor expectations with ivonescimab’s first-in-class status and Bristol Myers Squibb’s potential $11 billion partnership around BioNTech’s PD-L1xVEGF bispecific BNT327, which is second in line in development in the drug class. To co-develop and co-commercialize BNT327 in a 50-50 profit-sharing deal structure, BMS agreed to pay BioNTech $1.5 billion upfront and $2 billion in unconditional anniversary payments through 2028.However, BioNTech already has a portfolio of internal assets to test with BNT327, while ivonescimab is currently Summit’s sole project, Leerink noted. Concerns have been brewing among Summit investors after competitor PD-(L)1xVEGF assets have been picked up by Merck & Co., BMS and Pfizer, all with the intention to combine with other drugs in the Big Pharma companies’ portfolios. The lack of cash power at the biotech has fed into investor anxieties that Summit might lose out in the long game if it can’t aggressively expand ivoenscimab’s clinical program.To Leerink, PD-(L)1xVEGF bispecifics are “bio-better” PD-(L)1 inhibitors, which will find most success when combined with other drugs. Therefore, the competition should also be judged by each drug’s portfolio of combo partners, and Summit is losing in that respect, Graybosch’s team wrote in a June note.A large pharma company would also be less willing to pay a hefty upfront payment given that numerous, presumably cheaper, PD-(L)1xVEGF assets are being developed in China, the Leerink team added in its Thursday note. For those earlier-stage candidates, a large pharma licensee may mold the clinical development plan to their will rather than inheriting Summit’s high-risk phase 3 HARMONi-3 trial that’s pitting ivonescimab against Merck’s Keytruda in their respective chemo combinations in a broad first-line non-small cell lung cancer population, the analysts said.AstraZeneca would be an ideal partner for Summit, Evercore ISI analysts wrote in a separate note Thursday. The British pharma has become a leading oncology player with a large internal pipeline that could “offer the kind of combo capabilities we believe will be needed to maximize ivo’s potential,” the Evercore team wrote.AZ is apparently interested in bispecifics around the PD-(L)1 checkpoint axis, with two assets—the PD-1xCTLA-4 agent volrustomig and the PD-1xTIGIT drug rilvegostomig. But Leerink analysts said they would be surprised if AZ enters the PD-(L)1xVEGF space given how much the British pharma has invested in those existing assets as potential backbones for combo therapies.An AZ spokesperson declined to comment on the Summit deal report. Meanwhile, ivonescimab’s clinical data have caused some turbulence in Summit’s stock price lately. The company in May reported that ivonescimab significantly reduced the risk of progression or death in patients with previously treated EGFR-mutated nonsquamous NSCLC in the drug’s first global phase 3 readout. However, because data on whether the drug may prolong patients’ lives didn’t reach statistical significance at that point, Summit said it needs to consider the timing of a potential filing with the FDA.Summit expects to present detailed results from that study, coded HARMONi, at a medical conference this year. 

AstraZeneca may be gearing up for a major move in cancer immunotherapy. The pharma is said to be in talks with Summit Therapeutics over a potential deal worth as much as $15 billion for rights to the biotech's PD-1/VEGF bispecific antibody ivonescimab, according to a Bloomberg report Thursday citing unnamed sources.Some of the sources said an agreement could feature an upfront payment in the billions, plus milestones down the line — though terms remain under negotiation and talks could still collapse. Summit has also held discussions with other major pharmaceutical firms and it could ultimately decide to partner with them instead, the sources said.Ivonescimab has been generating excitement as a next-generation cancer therapy. Developed with Summit's Chinese partner Akeso, the drug has shown the potential to outperform Merck & Co.'s Keytruda (pembrolizumab). Ivonescimab is already approved in China for previously treated EGFR-mutated lung cancer and recently expanded its label there to include first-line PD-L1-positive non–small-cell lung cancer (NSCLC).Results from the Phase III HARMONi-2 trial made waves in 2024 when the drug cut the risk of disease progression or death by nearly half compared to Keytruda in first-line Chinese patients with PD-L1 positive advanced NSCLC.More recent studies have kept the spotlight on ivonescimab — with mixed results. A Phase III trial outside China showed the drug significantly slowed disease progression compared to chemotherapy in EGFR-mutated lung cancer, but its overall survival benefit fell short of statistical significance, rattling investors and clouding US approval timelines (see – Spotlight On: Investors unimpressed by Summit's ASCO gatecrash).Meanwhile, ivonescimab recently scored another win, besting BeOne Medicine's anti-PD-1 antibody Tevimbra (tislelizumab) in the Phase III HARMONi-6 trial for squamous lung cancer patients.While the readouts may provide a blend of both encouragement and caution, the promise of PD-(L)1/VEGF inhibitors as a potential new cornerstone of cancer treatment appears to be too big for large pharmas to overlook, despite uncertainties about their ability to deliver consistently strong survival outcomes (see – Spotlight On: Biopharma's next immuno-oncology goldrush is already under way).A deal with Summit looks like it would mark AstraZeneca's first foray into the PD-(L)1/VEGF space, although other large pharma's have already thrown their hat in the ring.Merck struck a licensing deal last November for LaNova Medicines' LM-299 that includes an upfront payment of $588 million, with the Chinese biotech eligible for further milestones of up to $2.7 billion. More recently, Bristol Myers Squibb committed over $11 billion for rights to co-develop BioNTech's BNT327, while Pfizer has agreed to pay $1.25 billion upfront to in-license ex-China rights to 3SBio's PD-1/VEGF bispecific SSGJ-707.