Preliminary results from a small study of heavily treated patients with blood cancer suggest that an experimental protein degrader, which removes problematic proteins instead of just inhibiting them, could have benefits over existing small molecule drugs.
Nurix Therapeutics said that its degrader of Bruton’s tyrosine kinase, or BTK, spurred a 69% objective response rate in 26 patients with relapsed or refractory chronic lymphocytic leukemia, including those whose cancer had become resistant to approved BTK inhibitors.
The patients had undergone an average of four prior lines of therapy, and 43% of them had resistance mutations to BTK inhibitors. One patient who had been treated with all four commercial BTK inhibitors and seven other therapies responded to Nurix’s treatment and continued to improve during six months of follow-up.
“We are very excited to see this high proportion of patients respond at this stage of development,” Nurix CEO Arthur Sands told Endpoints News in an interview. “We have patients approaching complete responses, and we are excited to continue monitoring their deepening of benefit.”
BTK inhibitors have become a major commercial class, with drugs on the market from BeiGene (Brukinsa), Eli Lilly (Jaypirca), Johnson & Johnson (Imbruvica) and AstraZeneca (Calquence). Collectively, they brought in more than $10 billion last year.
San Francisco-based Nurix announced the data in a press release and presented it at the European Hematology Association Congress on Sunday. The Phase 1 study is ongoing and includes several patients with non-Hodgkin lymphoma. Sands said the company would report efficacy data for those patients later this year and is preparing to begin a pivotal study of the drug in 2025.
The drug, NX-5948, is Nurix’s most advanced program. In April, the company announced glimpses of efficacy, showing that the complex molecule could cross the blood-brain barrier and target cancer that had spread to the nervous system. That led the company to raise $188.6 million in a public offering that month.
Sunday’s results showed that one patient treated with the drug had cancer cells eliminated from their cerebrospinal fluid by 24 weeks.
“That’s important for the category of protein degraders, because it was thought it would be very difficult for these molecules to cross the blood-brain barrier,” Sands said.
The company’s press release was light on details about safety. Sands said the drug was “so far very well tolerated” and that the most common adverse events were low blood cell counts. He said there was also a “very low rate” of atrial fibrillation and other cardiovascular events that have been seen with BTK inhibition.
Sands believes that using a degrader will have a favorable safety and efficacy profile, including a potentially higher potency and the elimination of other roles that BTK enzymes play in cancer not addressed by inhibitors.
“One drug can destroy thousands of target proteins, unlike inhibitors which are one-to-one, and this translates to increased potency,” Sands said. “Degraders eliminate a protein from a cell extremely efficiently. Anyone working with RNAi or antisense would envy the level of protein removal that we can achieve with these small molecules.”