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Nurix says protein degrader shows potential in Waldenstrom’s patients in early trial

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Nurix Therapeutics’ BTK degrader has elicited responses in a small group of patients with certain cancers, supporting the biotech’s claim that the drug could potentially offer a better alternative to BTK inhibitors.

The Phase 1a/1b trial tested Nurix’s candidate, NX-5948, in 13 people with Waldenstrom’s macroglobulinemia, nine of whom were evaluable for response at data cutoff. Seven patients had an objective response within the first eight weeks, and the remaining two had stable disease. The responses were seen regardless of mutation status, Nurix said.

All 13 patients had an average three prior lines of treatment, including both BTK inhibitors and chemotherapy or chemo-immunotherapy, according to results presented Saturday at the International Workshop on Waldenstrom’s Macroglobulinemia in Prague. Five patients are still taking NX-5948, including two who have remained on the treatment for more than a year.

Although the evaluable patients had a limited duration of follow-up, the data trend “further advances the impressive durability of response narrative building around NX-5948,” Stifel analysts said Monday.

BTK inhibitors, such as BeiGene’s Brukinsa and AstraZeneca’s Calquence, made more than $10 billion in sales last year combined.

Nurix said the data support its decision to advance NX-5948 into an ongoing Phase 1b expansion cohort in Waldenstrom’s patients who have had at least one prior line of therapy, and those with a rare form of the disease called Bing-Neel syndrome that affects the central nervous system.

The Waldenstrom’s results come several months after the drug achieved a 69% objective response rate in 26 patients with relapsed or refractory chronic lymphocytic leukemia in the same study, including those who had become resistant to treatment with BTK inhibitors.

NX-5948 is a small-molecule protein degrader, meaning it could have higher potency than BTK inhibitors, according to Nurix. Degraders could also be favorable due to their potentially “broad coverage of resistance mutations,” Jefferies analysts said.


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