Ivonescimab

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.

REDWOOD CITY, CA & MIAMI, FL, USA I June 30, 2025 I Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers and Summit Therapeutics Inc. (Nasdaq: SMMT), a biopharmaceutical oncology company focused on patient-friendly medicinal therapies intended to improve quality of life, increase potential duration of life, and resolve serious unmet medical needs, today announced the companies have entered into a clinical collaboration in multiple solid tumor settings to evaluate the safety and efficacy of each of Revolution Medicines’ clinical-stage RAS(ON) inhibitors, including the multi-selective inhibitor daraxonrasib (RMC-6236), G12D-selective inhibitor zoldonrasib (RMC-9805) and G12C-selective inhibitor elironrasib (RMC-6291), in combination with Summit Therapeutics’ ivonescimab, a PD-1 / VEGF bispecific antibody. “We’ve disclosed promising initial evidence that each of daraxonrasib and elironrasib can deliver additive antitumor activity safely when combined with a PD-1 antibody in first-line treatment of patients with RAS mutant non-small cell lung cancer,” said Mark A. Goldsmith, M.D., Ph.D., Chairman and Chief Executive Officer of Revolution Medicines. “Combinations with novel PD-1 bispecific inhibitors could unlock further therapeutic potential. We are eager to evaluate combinations of investigational drugs from our RAS(ON) inhibitor portfolio with ivonescimab, an advanced PD-1 / VEGF bispecific inhibitor with a differentiated profile, in a range of common RAS mutant cancers.” The clinical collaboration aims to evaluate these combinations across three priority tumor types including RAS mutant non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC). Under the terms of the agreement, Summit Therapeutics will supply ivonescimab for clinical research and Revolution Medicines will be the study sponsor. Each company will retain commercial rights to their respective compounds, and the agreement is mutually non-exclusive. “We’re thrilled to partner with Revolution Medicines to evaluate in a clinical setting how our highly promising ivonescimab combined with their compelling RAS(ON) inhibitors could potentially improve outcomes for patients with lung and gastrointestinal cancers,” said Robert W. Duggan, Chairman and Co-Chief Executive Officer and Dr. Maky Zanganeh, President and Co-Chief Executive Officer of Summit Therapeutics. “As we continue to rapidly advance the clinical development of ivonescimab across non-small cell lung cancer and other solid tumors, we believe that it is critically important to combine ivonescimab with some of the most promising medicines and drug candidates as we seek to provide innovative therapy options to patients facing high unmet needs.” About Revolution Medicines, Inc. Revolution Medicines is a late-stage clinical oncology company developing novel targeted therapies for patients with RAS-addicted cancers. The company’s R&D pipeline comprises RAS(ON) inhibitors designed to suppress diverse oncogenic variants of RAS proteins. The company’s RAS(ON) inhibitors daraxonrasib (RMC-6236), a RAS(ON) multi-selective inhibitor; elironrasib (RMC-6291), a RAS(ON) G12C-selective inhibitor; and zoldonrasib (RMC-9805), a RAS(ON) G12D-selective inhibitor, are currently in clinical development. The company anticipates that RMC-5127, a RAS(ON) G12V-selective inhibitor, will be its next RAS(ON) inhibitor to enter clinical development. Additional development opportunities in the company’s pipeline focus on RAS(ON) mutant-selective inhibitors, including RMC-0708 (Q61H) and RMC-8839 (G13C). For more information, please visit www.revmed.com and follow us on LinkedIn . About Summit Therapeutics Inc. Summit Therapeutics Inc. is a biopharmaceutical oncology company focused on the discovery, development, and commercialization of patient-, physician-, caregiver- and societal-friendly medicinal therapies intended to improve quality of life, increase potential duration of life, and resolve serious unmet medical needs. Summit was founded in 2003 and its shares are listed on the Nasdaq Global Market (symbol “SMMT”). It is headquartered in Miami, Florida, and has additional offices in Menlo Park, California, and Oxford, UK. For more information, please visit https://www.smmttx.com and follow us on X @SMMT_TX . About Ivonescimab Ivonescimab, known as SMT112 in Summit’s license territories, North America, South America, Europe, the Middle East, Africa, and Japan, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity to PD-1 when in the presence of VEGF. This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al, SITC, 2023). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days after the first dose (Zhong, et al, SITC, 2023), is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets. Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 2,300 patients have been treated with ivonescimab in clinical studies globally. Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two multiregional Phase III clinical trials, HARMONi and HARMONi-3, and the Company has begun to enroll patients in the United States for HARMONi-7. HARMONi is a Phase III clinical trial which is evaluating ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a 3rd generation EGFR TKI (e.g., osimertinib). Top-line results were announced in May 2025, which included a statistically significant and clinically meaningful benefit in progression-free survival and a positive trend in overall survival, the trial’s two primary endpoints. Consistent results were noted between the single region HARMONi-A study and the multiregional HARMONi study. HARMONi-3 is a Phase III clinical trial which is intended to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic, squamous and non-squamous NSCLC. HARMONi-7 is a Phase III clinical trial which is intended to evaluate ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression. In addition, Akeso has recently had positive read-outs in three single-region (China), randomized Phase III clinical trials for ivonescimab in NSCLC: HARMONi-A, HARMONi-2, and HARMONi-6. HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI. Approximately 85% of patients received a 3 rd generation EGFR-TKI prior to randomization in the study. HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression. HARMONi-6 is a Phase III clinical trial evaluating ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous NSCLC, irrespective of PD-L1 expression. Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was initially approved for marketing authorization in China in May 2024, and its label was expanded in China in April 2025. Ivonescimab was granted Fast Track designation by the US Food & Drug Administration (“FDA”) for the HARMONi clinical trial setting. SOURCE: Summit Therapeutics