Roche is preparing to file one BTK-targeting drug for approval, and has just added another with potential across oncology, immunology, and neurology via a deal with Nurix Therapeutics.
The licensing agreement includes a $700 million upfront payment, with the remainder tied to development, regulatory, and sales milestones, and gives Roche rights to bexobrutideg (NX-5948), an oral BTK degrader due to start phase 3 testing this summer in previously-treated chronic lymphocytic leukaemia.
Under the terms, Roche will share commercial rights to the drug with Nurix in the US, with responsibility for 60% of development costs, and have exclusive rights elsewhere.
The agreement comes as Roche is gearing up for the first filings of its oral BTK inhibitor fenebrutinib in relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS).
The BTK class has a long history in oncology as well and, with bexobrutideg, Roche thinks it has a "potential best-in-class" candidate that could overcome resistance seen with current drugs in the class, with potential in other indications like chronic spontaneous urticaria (CSU) and MS, also.
In CLL, many patients experience disease progression due to acquired resistance mutations, incomplete pathway suppression, or intolerance that limits long-term use, according to the Swiss pharma group.
Moreover, treatment options remain limited once patients relapse following treatment with current drugs in the class, which include AbbVie/Johnson & Johnson's Imbruvica (ibrutinib), AstraZeneca's Calquence (acalabrutinib), BeOne's Brukinsa (zanubrutinib), and Eli Lilly's Jaypirca (pirtobrutinib).
There's a massive market to target in blood cancers, according to Roche, which has cited market research figures it could reach $41 billion in 2031, with BTK drugs accounting for around $19 billion of that total, and CLL alone representing a $16 billion market by 2035.
"As a single agent, bexobrutideg has shown highly promising results in B-cell malignancy clinical trials to date, and we can now rapidly expand our phase 3 programme enhanced by Roche's global reach," said Nurix's chief executive, Arthur Sands.
He also suggested that the alliance raises the possibility of starting combination trials of the BTK degrader with other drugs developed by Roche for blood cancers, which include AbbVie-partnered BCL-2 inhibitor Venclexta/Venclyxto (venetoclax) and anti-CD20 antibody Gazyva/Gazyvaro (obinutuzumab).
Nurix is also working on another oral BTK degrader, zelebrudomide, which also targets IKZF1 and IKZF4 and is in phase 1a/1b testing in patients with diffuse large B-cell lymphoma and mantle cell lymphoma.
Roche is the latest in a series of big pharmas to partner with Brisbane, California-based Nurix, which signed a wide-ranging degrader-antibody conjugate (DAC) alliance with Pfizer in 2023 and has also licensed rights to Sanofi for a STAT6 degrader with potential in diseases like atopic dermatitis and asthma and to Gilead for an IRAK4 degrader for rheumatoid arthritis.
https://pharmaphorum.com/news/roche-doubles-down-btk-23bn-nurix-deal
