Nurix Therapeutics Presents Data at American Congress

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

The poster presentation highlighted the specificity and potency of NX-5948 and the superior cellular activity against BTKi resistance mutations of both NX-2127 and NX-5948 compared to others. Published BTK Degrader

SAN FRANCISCO, April 17, 2023 (GLOBE NEWSWIRE) — Nurix Therapeutics, Inc. (Nasdaq: NRIX) announces a clinical-stage development of targeted protein modulators designed to treat patients with hematologic malignancies and solid tumors. A biopharmaceutical company and, today, a targeted protein degradation program that includes structural disclosure of NX-2127 and new preclinical data for NX-2127 and NX-5948. B-cell malignancy. These data will be presented at the American Association for Cancer Research (AACR) Annual Meeting, April 14-19, 2023 in Orlando, Florida.

President and Chief Executive Officer Arthur T. Sands, M.D., said: of Nurix. “Nurix represents an excellent class of targets with broad potency against wild-type BTK and all mutations tested to date, with the potential to provide novel therapeutics for patients for whom there are no existing options. Leading the field in developing proteolytic drug candidates. Failed.”

AACR presentation details
in a poster presentation titled NX-5948 selectively promotes subnanomolar degradation of inhibitor-resistant BTK mutants. Preclinical data demonstrating potent tumor cell killing activity of Nurix’s BTK degradants (NX-5948 and NX-2127) against a wide range of acquired BTK inhibitor resistance mutations and their superiority compared to other reported degradants was presented. Specifically, NX-5948 was shown to target and promote potent degradation of V416L, T474I, and L528W BTKi resistance mutations that reduce or eliminate the activity of next-generation noncovalent BTK inhibitors such as pirtbrutinib. it was done. The broad-spectrum activity of NX-2127 and NX-5948 against BTK mutations, compared to BTK inhibitors and other BTK-degrading agents, adds additional mechanisms to ongoing clinical trials in patients with advanced B-cell malignancies. provide rationale.

“Presentation at the AACR and ACS conferences demonstrates Nurix’s approach of combining a deep understanding of the biochemistry of E3 ligases and the pharmacodynamics of target proteases with the principles of rational drug design,” said Dr. Gwenn Hansen. said. , Chief Scientific Officer of Nurix. “With our unique drug discovery expertise, we have the potential to design targeted protein modulators that can address one or more important therapeutic targets and combine their activities into a single molecule that may benefit specific diseases. I have.”

The mechanistic basis for overcoming mutation resistance is that NX-5948 cooperatively binds to BTK and the E3 ligase cereblon and maintains a stable ternary complex despite reduced binding affinity to the mutant and is supported by data showing that it can retain degradative activity against specific BTKi resistance mutations. BTK protein. BTK degradation by NX-5948 was shown to be highly selective in proteomic assessments, with significant off-target activity observed in primary T cells, TMD8 cells, or MM-1R cells treated with NX-5948. did not.

In an oral presentation entitled First Disclosure of NX-2127, an Oral Targeted Degradation Agent of Bruton’s Tyrosine Kinase (BTK) with Concomitant Immunomodulatory Activity for the Treatment of B Cell MalignanciesThe structure of NX-2127 was disclosed to a broader oncology audience at AACR following initial disclosure in an oral presentation at the American Chemical Society Spring Meeting on March 29, 2023. The presentation also included preclinical characterization and early pharmacokinetic and pharmacodynamic data. in humans.

Registered attendees will be able to view all presentations and posters on demand on the AACR website. Nurix’s AACR presentation is also available in 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 the cerebroneogenic substrates Icarus (IKZF1) and Aeolus (IKZF3). NX-2127 is currently being evaluated in Phase 1 clinical trials in patients with relapsed or refractory B-cell malignancies. Additional information about ongoing clinical trials can be accessed at www.clinicaltrials.gov (NCT04830137).

About NX-5948
NX-5948 is an investigational, orally bioavailable, small-molecule degrader of BTK that, unlike NX-2127, is designed as a single-targeted degrader. NX-5948 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B-cell malignancies. Additional information about ongoing clinical trials 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 molecules and cell therapies based on modulation of cellular protein levels as novel therapeutic approaches for cancer and other challenging diseases. Nurix will leverage its extensive expertise in E3 ligases and proprietary DNA-encoded libraries to identify and advance drug candidates that target E3 ligases, a broad class of enzymes that can regulate proteins within cells. built DELigase, an integrated discovery platform for Nurix’s drug discovery approach is to exploit 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 a targeted proteolytic agent for Bruton’s tyrosine kinase, a B-cell signaling protein, and inhibition of Casitas B-lineage lymphoma proto-oncogene B, an E3 ligase that regulates T-cell activation Includes drug. Nurix is ​​headquartered in San Francisco, California. For more information, see:
http://www.nurixtx.com.

forward-looking statement
This press release contains statements relating to future events and expectations, which constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. , “may”, “estimate”, “expect”, “intend”, “may”, “prospect”, “plan”, “predict”, “should” , “will” and similar expressions and variations thereof relate to Nurix and may identify forward-looking statements. All statements other than statements of historical fact that reflect Nurix’s expectations, assumptions or projections regarding the future are forward-looking statements, including, but not limited to, statements regarding future plans, prospects and strategies. . current and future drug candidates; the timing of clinical updates and planned delivery of initial findings from our clinical research; the potential benefits of our drug candidates; and the extent to which our scientific approaches can potentially address a wide range of diseases. Forward-looking statements reflect Nurix’s current beliefs, expectations and assumptions. Nurix believes that the expectations and assumptions reflected in such forward-looking statements are reasonable, but Nurix cannot give any assurance that they will prove to be correct. Forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and changes in circumstances that are difficult to predict. They may differ materially from those expressed in the description. Such risks and uncertainties include, but are not limited to: (ii) the timing and results of clinical trials; (iii) Nurix’s ability to fund development activities and achieve development objectives; (iv) the impact of macroeconomic conditions on Nurix’s business, clinical trials, financial condition, liquidity and results of operations; (v) Nurix’s ability to protect its intellectual property; and (vi) Nurix’s Quarterly Report on Form 10-Q for the fiscal quarter ended February 28, 2023 and other SEC filings under “Risk Factors. and other risks and uncertainties described under the heading Readers are therefore cautioned not to place undue reliance on these forward-looking statements. The statements in this press release are made as of the date of this press release, even if Nurix subsequently makes them available on its website or otherwise. Except, we disclaim any intention or obligation to publicly update any forward-looking statements, whether in response to new information, future events or otherwise.

contact address:
Investor
cylinder neo
Neulix Therapeutics
ir@nurixtx.com

Dr. Elizabeth Wolfe
Wheelhouse Life Science Advisor
lwolffe@wheelhouselsa.com

media
Arjanay Reynolds
Wheelhouse Life Science Advisor
areynolds@wheelhouselsa.com



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