Nurix Therapeutics Presents Data at the American Association for Cancer Research (AACR) Annual Meeting Highlighting Activity of its BTK Targeted Protein Degraders, NX-2127 and NX-5948, against a Broad Range of BTKi Resistance Mutations

Oral presentation features structural disclosure and preclinical characterization of NX-2127, Nurix’s lead BTK degrader for the treatment of B-cell malignancies

Poster presentation highlights specificity and potency of NX-5948 and superior cellular activity of both NX-2127 and NX-5948 against BTKi resistance mutations compared to other published BTK degraders

SAN FRANCISCO, April 17, 2023 (GLOBE NEWSWIRE) — Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with hematologic malignancies and solid tumors, today announced presentations covering its targeted protein degradation programs, including the structural disclosure of NX-2127 and new preclinical data for NX-2127 and NX-5948, highlighting their superior activity against acquired mutations in Bruton’s tyrosine kinase (BTK), a key therapeutic target in the treatment of B-cell malignancies. These data are being presented at the American Association for Cancer Research (AACR) Annual Meeting which is being held from April 14-19, 2023, in Orlando, FL.

“Our presentations at the AACR meeting highlight the features of our targeted BTK degraders that enable them to uniquely address a broad group of acquired BTK inhibitor resistance mutations,” said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. “Nurix is leading the field in developing a superior class of Targeted Protein Degrader drug candidates that have broad capabilities against both wild-type BTK and across all mutations thus far tested with the potential to provide a new treatment modality for patients for whom existing options have failed.”

Details of the AACR Presentations
In a poster presentation entitled NX-5948 promotes selective, sub-nanomolar degradation of inhibitor-resistant BTK mutants, preclinical data were presented demonstrating the potent tumor cell-killing activity of Nurix’s BTK degraders (NX-5948 and NX-2127) against a broad range of acquired BTK inhibitor resistance mutations and their superiority compared with other reported degraders. Specifically, NX-5948 was shown to target and promote potent degradation of the V416L, T474I, and L528W BTKi resistance mutations that reduce or eliminate the activity of next-generation non-covalent inhibitors of BTK, such as pirtobrutinib. The broad range of activity of NX-2127 and NX-5948 against BTK mutations relative to BTK inhibitors and other BTK degraders provides further mechanistic rationale for the ongoing clinical trials in patients with advanced B cell malignancies.

“The presentations at the AACR and ACS meetings illustrate Nurix’s approach which combines rational drug-design principles with a deep understanding of the biochemistry of E3 ligases and the pharmacodynamics of targeted protein degraders,” noted Gwenn Hansen, Ph.D. , Nurix’s chief scientific officer. “Our unique drug discovery expertise enables us to design targeted protein modulators that can address one or more key therapeutic targets, combining activities into a single molecule, which may have advantages in certain diseases.”

The mechanistic basis for overcoming mutational resistance is supported by data demonstrating that NX-5948 binds BTK and the E3 ligase cereblon cooperatively, enabling it to maintain a stable ternary complex and retain degradation activity against certain BTKi resistance mutations despite a reduction in binding affinity to mutant BTK proteins. BTK degradation by NX-5948 was shown to be highly selective in proteomics assessments with no significant off-target activity identified in primary T cells, TMD8 cells, or MM-1R cells treated with NX-5948.

In an oral presentation entitled First Disclosure of NX-2127, an oral targeted degrader of Bruton’s tyrosine kinase (BTK) with concurrent immunomodulatory activity for the treatment of B-cell malignancies, the structure of NX-2127 was disclosed to the broader oncology audience at AACR following its initial disclosure in an oral presentation at the American Chemical Society Spring meeting on March 29, 2023. The presentation also included the preclinical characterization and initial pharmacokinetic and pharmacodynamic data in humans.

All presentations and posters are available for registered attendees for on-demand viewing on the AACR website. Nurix’s AACR presentations are also available on the Posters and Presentations section of the scientific resources page of the Nurix website.

About NX-2127
NX-2127 is a novel bifunctional molecule that degrades Bruton’s tyrosine kinase (BTK) and cereblon neosubstrates Ikaros (IKZF1) and Aiolos (IKZF3). NX-2127 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies. Additional information on the ongoing clinical trial can be accessed at www.clinicaltrials.gov (NCT04830137).

About NX-5948
NX-5948 is an investigational, orally bioavailable, small molecule degrader of BTK that, differentiated from NX-2127, has been designed as a single target degrader. NX-5948 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies. Additional information on the ongoing clinical trial can be accessed at clinicaltrials.gov (NCT05131022).

About Nurix Therapeutics, Inc.
Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of small molecule and cell therapies based on the modulation of cellular protein levels as a novel treatment approach for cancer and other challenging diseases. Leveraging extensive expertise in E3 ligases together with 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, California. For additional information visit
http://www.nurixtx.com.

Forward Looking Statement
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Contacts:
Investors
Silinda Neou
Nurix Therapeutics
ir@nurixtx.com

Elizabeth Wolffe, Ph.D.
Wheelhouse Life Science Advisors
lwolffe@wheelhouselsa.com

Media
Aljanae Reynolds
Wheelhouse Life Science Advisors
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