SSGJ-707

Pfizer's first wave of PD-1xVEGF trials, Akeso's first overall survival win from ivonescimab and more deals from Eli Lilly made our news this week. Pfizer is launching the first clinical trials for its PD-1xVEGF drug, while Akeso detailed the first overall survival win for its first-in-class ivonescimab. Eli Lilly signed two more drug discovery pacts, continuing a dealmaking spree. And more.1. With Summit leading the pack in PD-1xVEGF bispecifics, Pfizer lays out its own plan to replace KeytrudaPfizer unveiled the first clinical trials for its PD-1xVEGF bispecific licensed from China’s 3SBio. One of the first two phase 3 trials is a head-to-head study against Keytruda in the two drugs’ respective combinations with chemotherapy in patients with first-line non-small cell lung cancer. A phase 1/2 will combine the drug, coded PF-08634404, with Pfizer’s antibody-drug conjugates.2. Akeso details ivonescimab's 1st overall survival win. Should Summit celebrate?Akeso provided detailed results for ivonescimab’s first positive overall survival readout, showing that the addition of the PD-1xVEGF drug to chemotherapy reduced the risk of death by 25% in Chinese patients with previously treated EGFR-mutated NSCLC. The OS win marked another validation of the drug class but did not necessarily secure ivonescimab a top spot in this particular indication.3. Eli Lilly pens $1.2B pact with Sanegene to better target metabolic RNA medsLilly continues AI push, inking $100M-plus research pact with InsilicoEli Lilly continued its recent deal spree by inking a research pact worth up to $1.2 billion with Sino-American biotech SanegeneBio focused on cardiometabolic RNA interference medicines and a separate $100 million-plus deal with artificial intelligence drug discovery outfit Insilico Medicine. The Indianapolis pharma had just signed another AI drug design deal with XtalPi last week.4. Neurocrine's depression drug is latest asset from Takeda pact to flunk a phase 2 trialA phase 2 major depressive disorder trial of a candidate Neurocrine Biosciences licensed from Takeda has failed. The drug, a negative allosteric modulator of the NMDA NR2B receptor, failed to beat placebo on change in depression severity by Day 5 as measured on the Montgomery-Åsberg Depression Rating Scale.5. Lyell hands over $70M-plus in cash, equity for 'impressive' phase 1-stage colorectal cancer CAR-TLyell Immunopharma is paying Sino-American firm Innovative Cellular Therapeutics $40 million upfront, plus 1.9 million of its own shares, for ex-China rights to a CAR-T therapy. In an ongoing U.S. study in 12 pretreated colorectal cancer patients, a high dose of the guanylyl cyclase-C-targeted CAR-T has shown a 67% overall response rate and median progression-free survival of 7.8 months.6. Third Arc Bio pens back-loaded $840M pact for Adagene's masking T-cell engager techIn a heavily back-loaded deal, Third Arc Bio is tapping Adagene to develop T-cell engagers against tumor-associated antigens. The pact includes $5 million upfront and up to $840 million in milestones. The Adagene platform involved is designed to activate an antigen when it reaches the tumor microenvironment, improving safety and widening therapeutic index.Other News of Note:7. JSF divests CRO Crown Biosciences for $204M (release, release)8. Recall roundup: Fresenius, Sun and Teva among drugmakers pulling products in recent weeks9. Lundbeck, Otsuka back survey uncovering ‘blind spot’ around Alzheimer’s agitation10. Boryung breaks ground on penicillin plant expansion in South Korea11. China allocates $60M to procure 15.4M bivalent HPV shots for national immunization scheme (Jiemian, Chinese)

The competitive landscape for PD-(L)1xVEGF bispecifics is finally taking shape. For the last couple years, much of the attention has focused on Summit Therapeutics and its lead drug ivonescimab. Now, two other challengers are revving their engines, setting up a race that may shape the future of immuno-oncology. If successful, the companies could bring new treatments to a plethora of cancer patients in the next decade. The biggest impact will likely be in areas like colorectal cancer, where PD-(L)1 checkpoint inhibitors are not widely used and some experts see untapped potential . But each bispecific will also be attempting to replace those PD-(L)1 drugs, like Merck’s $30-billion-a-year blockbuster Keytruda, in certain cancers where they’ve long been the standard. Summit’s first rival is the team of Pfizer and 3SBio, which signed a licensing deal for a PD-1xVEGF bispecific called SSGJ-707 earlier this year. Pfizer unveiled the first look at its clinical development plan in a presentation with analysts on Monday for the newly named PF’4404. Among other trials, that candidate will be in a Phase 3 study in first-line metastatic colorectal cancer and a Phase 3 non-small cell lung cancer study evaluating both squamous and non-squamous tumors. Jeff Legos, Pfizer’s chief oncology officer, took note of the “substantial opportunity” in colorectal cancer on the analyst call. He also emphasized roughly 95% of colorectal cancer patients aren’t eligible to receive checkpoint inhibitors like Keytruda. “These patients will be the focus of our planned ‘4404 Phase 3 studies in metastatic CRC,” Legos said. The other main competitors, Bristol Myers Squibb and BioNTech, teamed up this past June for a deal worth up to $11.1 billion. The pair is advancing a PD-L1xVEGF program called pumitamig that BioNTech acquired in its Biotheus buyout . After Bristol Myers outlined a suite of five mid- and late-stage studies during an earnings call last month, BioNTech went further at its R&D Day on Tuesday and provided perhaps the most in-depth look at what’s coming next. Beyond colorectal and triple-negative breast cancer — where other companies have not disclosed trial plans — BioNTech is looking at an amalgam of studies in difficult indications. That includes pancreatic cancer, ovarian cancer and glioblastoma, where BioNTech plans to start Phase 1 or Phase 2 studies in the coming years. Both the Pfizer-3SBio and BMS-BioNTech groups are planning to use their respective pipelines at their disposal to create what they hope are potent combination therapies. Pfizer is planning on testing PF’4404 with the antibody-drug conjugates it got from Seagen, Endpoints News previously reported , while BMS and BioNTech have flexibility in their deal to run studies combining pumitamig with experimental drugs in each of their portfolios. For pumitamig, that will involve combo therapies with BioNTech’s in-house assets, as well as other partnered drugs from DualityBio, OncoC4 and MediLink, BioNTech CEO Uğur Şahin told Endpoints in an interview on Tuesday. Bristol Myers will also be able to run trials with pumitamig and some of its own pipeline programs. “Both parties have the opportunity to develop, and even do registrational trials, with their own compound combinations,” Şahin said. “But both partners have also the ability to join into existing combination trials of the other party. So this is a really permissive approach for drug development, and does not rely on having to discuss everything and agree on every detail before you start something.” Despite all the momentum this year, whether these development plans work may not be known for a while. Summit plans to file for an ivonescimab approval in a certain form of non-small cell lung cancer, though the market size is estimated to be about just $500 million. Summit also announced last month it would start its own colorectal cancer trial and plot a course of combination therapy studies; enrollment in colorectal cancer is slated to start by the end of the year. Meanwhile, the earliest Phase 3 pumitamig data from BMS-BioNTech are not expected until 2028. Additionally, results from the two PF’4404 Phase 3 trials Pfizer announced won’t come until 2029 or 2030 , according to the ClinicalTrials.gov database. Although those data are a few years away, they are coincidentally timed to read out around when Keytruda will fall off-patent in 2028. (Merck also has its own PD-1xVEGF bispecific partnership with LaNova Medicines, but that program is in a much earlier stage of development — it just started a Phase 1 China trial last year.) Other earlier-stage trials for PF’4404 may report results in the meantime, potentially giving the industry its first clues as to whether this new class of drugs can work outside lung cancer. Pfizer didn’t provide an exact timeline for data, saying only that Phase 1/2 studies in liver, urothelial and kidney cancers will start in 2026. Pumitamig, however, will certainly have additional data by the time Keytruda falls off-patent. Phase 2 results in first-line lung cancer are expected next year, and a Phase 3 China study in triple-negative breast cancer should also read out in 2026. Even though positive China data might not correlate to a similar result in Western patients — Summit faced scrutiny over this issue in its lung cancer studies — BioNTech executives are confident breast cancer can be different. “We believe there should be no difference in other indications,” Ilhan Celik, VP of clinical development, said at the BioNTech R&D Day on Tuesday. “This will be, again, guided by the data, but there is no reason to believe that there are significant differences regarding the response and the efficacy. Safety, by the way, is also very similar.” TD Cowen analyst Yaron Werber wrote in a note to investors Wednesday morning that the key for BioNTech will be ensuring it can stay on these timelines, particularly since most of the spaces they’re playing in are very competitive. “There is a lot here to drive interest, but we note that the company has historically had some slippage of timelines (including global dose finding readouts for pumi) or outright attrition for pipeline assets,” Werber wrote. “Hence, we will be looking to see whether mgmt will be able to keep to the schedule they set forward.” Editor’s note: This article has been updated to correct that the total value of BioNTech and Bristol Myers’ collaboration is $11.1 billion, not $10.6 billion.