Navlimetostat

The changes come amid the drugmaker’s cost-saving initiative designed to save $1.5 billion by the end of the year. \n Bristol Myers Squibb is shedding two clinical programs from its in-house pipeline, one from its 2023 Mirati buyout and another from a partnership with U.K. biotech Exscientia, now known as Recursion.The changes were shared in third-quarter earnings slides presented Oct. 30 (PDF).The Mirati program was an SOS1 inhibitor previously coded as MRTX0902. The asset was being studied in a phase 1/2 solid tumor trial that launched in 2022 and has a primary readout slated for mid-2026, according to ClinicalTrials.gov.As of publication, BMS has not responded to Fierce’s request for comment or questions about the trial’s status.The candidate was being evaluated as both a monotherapy and in combination with Mirati’s adagrasib (Krazati), which first nabbed accelerated approval in 2022 as a treatment for certain patients with advanced non-small cell lung cancer, and later secured a regulatory green light paired with Erbitux in colorectal cancer.Both MRTX0902 and adagrasib stem from BMS’s up-to-$5.8 billion acquisition for California-based cancer drug developer Mirati. The pharma has also continued development of MRTX1719, another Mirati program that is currently in phase 1 testing for solid tumors with MTAP deletion.The second asset removed from Bristol\'s internal pipeline is a PKC-theta inhibitor known as EXS4318. The immunology and inflammation asset had come from Exscientia, which has since merged with Recursion. The program had first-in-class potential and entered in-human testing in 2023.BMS got its hand on the candidate in 2021 after penning a $1.2 billion biobucks discovery deal and later licensing the rights to EXS4318.  As of publication, BMS did not respond to Fierce’s questions about the status of the partnership.BMS\'s earnings materials only identified the testing phase and drug mechanisms for the affected pipeline assets. A look at the company\'s prior pipeline developments indicates that the candidates came from the Mirati and Exscientia deals. The pipeline changes come on the heels of a leadership transition at BMS, with former Chief Medical Officer Samit Hirawat, M.D., succeeded by AstraZeneca’s Cristian Massacesi, M.D.On Thursday’s call, Massacesi highlighted the pharma’s neuro work, specifically that related to approved schizophrenia treatment Cobenfy. The new CMO counted 14 studies that are either ongoing or in the process of being launched—including 10 pivotal studies—related to the drug.The changes also come amid the drugmaker’s cost-saving initiative designed to save $1.5 billion by the end of the year. 

Tango Therapeutics reported data for its experimental pancreatic cancer drug that are strong enough for the company to move it into a Phase 3 study while concurrently raising $225 million to get things going. In a study of pancreatic cancer patients with a common mutation called MTAP deletion, Tango said Thursday that vopimetostat (formerly TNG462) achieved a 25% objective response rate in 39 patients with at least six months of follow-up. These patients, who had received one prior therapy, had a median progression-free survival of 7.2 months. Pancreatic cancer is one of the most difficult kinds of cancers to treat, and prognoses are poor. Though a 25% response rate would not move the needle much in other tumor types, Tango said it represents more than double the rate seen in historical controls. Tango estimates about 35% of all pancreatic cancer patients have the MTAP deletion mutation. Tango now plans to start a global Phase 3 study for the PRMT5 inhibitor in second-line pancreatic cancer with MTAP deletion in 2026, but it will have to discuss the results with the FDA later this year. The study will aim to enroll about 300 patients and compare vopimetostat to standard chemotherapy regimens. Tango raised $225 million along with the data, netting $210 million from an underwritten offering and $15 million from a PIPE financing. Tango’s shares $TNGX rose about 25% in premarket trading, but fell roughly 15% after Thursday’s opening bell. Analysts expect Tango’s vopimetostat to compete with programs from Bristol Myers Squibb, which is also researching a PRMT5 inhibitor, and Ideaya Biosciences, which is developing a MAT2A inhibitor. During Tango’s call on Thursday morning, one analyst noted that patients responded to vopimetostat in a median of 3.5 months, compared to five months for Bristol Myers’ BMS-986504, which is in multiple mid- and late-stage studies. In response, Tango CEO Barbara Weber said it’s difficult to know what’s driving that difference. “We do believe that vopimetostat has substantively better target coverage at 250 mg than BMS-986504 does at 400 or 600 mg,” Weber said. “So it’s possible that is partly what’s driving it. It’s hard to say for sure.” The pancreatic cancer cohort only represented some of Tango’s data. The company also set up a study group in lung cancer and for another cohort of patients who have a variety of tumors but all have MTAP deletions. In total, 179 patients received the drug, 94 of whom were evaluable for efficacy with at least six months of follow-up. The ORR among the 94 patients was 27%, with a median PFS of 6.4 months. The lung cancer data were not yet mature, but about 15% of all lung cancer patients have the MTAP deletion mutation, Tango said. In the third group, which Tango referred to as “histology agnostic,” 49% of 41 patients saw a response after six months. Median PFS was 9.1 months. There were 13 different kinds of cancer observed in the group, including mesothelioma, esophageal and head and neck. The analysis of the 41 patients did not include nine sarcoma patients, none of whom responded to the drug. There were no life-threatening side effects or deaths caused by the drug in the study. Severe side effects were “rare,” Tango said, except for severe anemia, which occurred in 13% of all patients.