Nurix Therapeutics Reports Dosing of First Patient in Phase 1 Clinical Trial of a Selective BTK Degrader in Development for B-cell Leukemias & Lymphomas

Nurix Therapeutics, Inc. recently announced the first patient has been dosed in its Phase 1a/1b study to evaluate orally available small molecule NX-5948, a potent and selective degrader of Bruton’s tyrosine kinase (BTK) in patients with relapsed B-cell malignancies.

Nurix is conducting the open-label, dose escalation and expansion trial at multiple centers in the UK. The trial is designed to evaluate the safety and tolerability of NX-5948 in adults with relapsed or refractory B-cell malignancies. Nurix expects to have initial safety and pharmacokinetic and pharmacodynamic data from the Phase 1a portion of the study in the second half of 2022.

“We are excited to have initiated the trial of a second highly selective and potent BTK degrader, that has the additional feature of being able to cross the blood brain barrier,” said Robert J. Brown, MD, Executive Vice President of Clinical Development of Nurix. “NX-5948 has the potential to offer a differentiated clinical profile for patients with relapsed or refractory B cell malignancies.”

In preclinical studies presented at the 2021 American Society of Hematology (ASH) Annual Meeting, NX-5948 demonstrated potent anti-tumor activity in models of both ibrutinib-sensitive and ibrutinib-resistant (C481S mutant BTK) lymphoma. NX-5948 was able to cross the blood brain barrier in preclinical models, degrade BTK in both microglia and central nervous system (CNS) resident lymphoma cells, and exert anti-lymphoma activity in a model of primary central nervous system lymphoma (PCNSL).

“Our BTK degraders, NX-2127 and NX-5948, provide potentially complementary solutions to the growing problem of resistance, which has been noted with all BTK inhibitors currently in use and leads to disease relapse,” said Arthur T. Sands, MD, PhD, President and Chief Executive Officer of Nurix. “Our ongoing clinical trials of these two differentiated molecules, NX-2127, with additional cereblon immunomodulatory activity, and NX-5948 which is central nervous system penetrant, are expected to provide key data that will inform each molecule’s optimal development path in oncology. With the new Phase 1 trial with NX-5948, we currently have four clinical trials ongoing, positioning us for a number of important data catalysts over the next 12 months.”

NX-5948 is an investigational, orally bioavailable, small molecule degrader of BTK that, unlike NX-2127, has been designed to lack cereblon immunomodulatory activity for potential applications in indications where sparing immunomodulatory activity may be beneficial. Additional information on the ongoing clinical trial in the UK of NX-5948 in adults with advanced B-cell malignancies can be accessed at ClinicalTrials.gov (NCT05131022). Additional information on the ongoing clinical trial of NX-2127 in the US in adults with advanced B-cell malignancies can be accessed at ClinicalTrials.gov (NCT04830137).

Nurix Therapeutics is a biopharmaceutical company focused on the discovery, development, and commercialization of small molecule therapies designed to modulate cellular protein levels as a novel treatment approach for cancer and other challenging diseases. Leveraging Nurix’s extensive expertise in E3 ligases together with its proprietary DNA-encoded libraries, Nurix has built DELigase, an integrated discovery platform to identify and advance novel drug candidates targeting E3 ligases, a broad class of enzymes that can modulate proteins within the cell. Nurix’s drug discovery approach is to either harness or inhibit the natural function of E3 ligases within the ubiquitin proteasome system to selectively decrease or increase cellular protein levels. Nurix’s wholly owned pipeline includes targeted protein degraders of Bruton’s tyrosine kinase, a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene B, an E3 ligase that regulates T cell activation. Nurix is headquartered in San Francisco, CA. For more information, visit http://www.nurixtx.com/.