Bexobrutideg

Roche could pay Nurix up to $2.3 billion in milestones.\n Roche is paying Nurix Therapeutics $700 million upfront for rights to bexobrutideg, securing a stake in a BTK degrader that is set to go head-to-head against Eli Lilly’s Jaypirca in a phase 3 trial.Multiple BTK inhibitors are already on the market, with Lilly’s non-covalent Jaypirca providing an option to blood cancer patients who progress on covalent drugs, including AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeOne Medicines’ Brukinsa. Nurix has predicted that molecules that degrade BTK, rather than inhibit the kinase, will have advantages over existing products. Roche agrees. The Swiss drugmaker is paying $700 million upfront and committing up to $2.3 billion in milestones to co-develop and co-commercialize bexobrutideg. Roche will pay 60% of development costs and split U.S. profits equally. Nurix will co-commercialize bexobrutideg with Roche in the U.S., supporting its ambition to develop into a biotech that funds its other pipeline programs through product revenue. Roche will commercialize the BTK degrader outside the U.S. and pay Nurix royalties ranging from the low- to high-teens.In October, Nurix dosed the first patient in a potentially pivotal phase 2 trial. Participants have previously received covalent and non-covalent BTK inhibitors, plus a BCL-2 inhibitor such as AbbVie’s Venclexta, to treat chronic or small lymphocytic leukemia (CLL/SLL). A planned phase 3 confirmatory trial will compare bexobrutideg to Jaypirca in CLL and SLL patients previously treated with a covalent BTK inhibitor. Jaypirca’s effectiveness in patients failed by covalent BTK inhibitors helped Lilly secure an expanded FDA label and full approval in December. Nurix is betting that its molecule’s ability to remove BTK enzymatic activity and scaffolding functions and degrade thousands of BTK proteins per hour will lead to improved survival compared to Jaypirca.A cross-trial comparison, with the caveats that entails, supports the hypothesis. Nurix reported median progression-free survival of 22.1 months in a phase 1a trial, versus 14 months in Lilly’s phase 3 trial of Jaypirca. The patients in Nurix’s trial had, on average, received more lines of therapy before joining the study than their counterparts enrolled by Lilly.Competition in the blockbuster market is intense, with rival protein degraders potentially challenging bexobrutideg even if Roche and Nurix vanquish Jaypirca. BeOne started three phase 3 trials of a BTK degrader, BGB-16673, last year. AbbVie took a rival molecule, ABBV-101, into phase 1 in 2023. Nurix has identified bexobrutideg’s selectivity and ability to cross the blood-brain barrier as potential advantages.  Partnering with Roche positions Nurix to fully explore bexobrutideg’s potential. The clinical development plan includes monotherapy and combination blood cancer studies, plus phase 2 trials in neurology and immunology indications, such as multiple sclerosis and chronic spontaneous urticaria. Novartis and Sanofi are among the companies developing BTK inhibitors in neurology and immunology.Roche’s expertise in the therapeutic areas, plus its deep pockets, could benefit the expanded R&D plan. Those benefits of the deal speak to comments Jason Kantor, Ph.D., chief business officer of Nurix, made at an RBC Capital Markets event last month. Nurix was open to a deal that enhanced the therapeutic and commercial reach of the drug while allowing the biotech to become a commercial company, Kantor said at the time.