Nurix Presents the Discovery and Chemical Structure of First-in-Class CBL-B Inhibitor NX-1607 at the American Chemical Society (ACS) Meeting
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Insights
The advancement of NX-1607 into clinical studies is a significant milestone in the field of immuno-oncology. This inhibitor targets CBL-B, an E3 ligase implicated in T-cell activation, which is a critical component of the body's immune response against cancer cells. By inhibiting CBL-B, NX-1607 could potentially enhance the immune system's ability to fight tumors. The ongoing Phase 1 trial is important to assess not only the safety and tolerability of NX-1607 but also its pharmacokinetics and pharmacodynamics, which will inform the optimal dosing strategy. If the data are positive, this could lead to a new class of immuno-oncology drugs with a mechanism distinct from current PD-1/PD-L1 inhibitors.
The disclosure of NX-1607's structure and the initiation of its Phase 1 trial represent a combination of innovative drug design and strategic clinical development. As a first-in-class inhibitor, NX-1607's progression into clinical trials underscores the potential for a new wave of targeted protein modulation therapies. The biopharmaceutical industry is keenly interested in such advancements as they may offer alternative treatment options and expand the market for cancer therapies. The success of NX-1607 could also validate Nurix's platform and potentially lead to increased investor confidence in the company's pipeline.
From a market perspective, Nurix's presentation at the American Chemical Society meeting enhances the company's visibility within the scientific and investment communities. The novelty of NX-1607's mechanism—acting as an intramolecular glue rather than targeting a classic enzymatic active site—positions Nurix at the forefront of ligase inhibition research. The market is always responsive to such innovation, particularly in the high-stakes oncology sector. As the trial progresses, positive results could have a favorable impact on Nurix's stock value and attract partnerships or funding for further development. Conversely, any setbacks in the trial could pose risks to the company's valuation and future prospects.
Presentation highlights Nurix’s innovation and leadership in targeted protein modulation, including ligase inhibition
Unique mechanism of action, an intramolecular glue, locks the E3 ligase Casitas B-lineage lymphoma proto-oncogene B (CBL-B) in a closed inactive state
Phase 1 trial ongoing as monotherapy and in combination with paclitaxel in patients with a range of oncology indications
SAN FRANCISCO, March 20, 2024 (GLOBE NEWSWIRE) -- Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with cancer and inflammatory diseases, today disclosed the discovery and structure of NX-1607 in the First Time Disclosures session at the American Chemical Society Spring 2024 meeting in New Orleans, LA. This is the first inhibitor of CBL-B to advance into clinical studies and a prime example of Nurix’s ability to target previously undruggable E3 ligases.
“Today’s presentation at the ACS meeting showcases Nurix’s innovative combination of structure-based-drug-design and industry-leading expertise in the biochemistry of E3 ligases,” noted Gwenn Hansen, Ph.D., Nurix’s chief scientific officer. “Our unique approach to drug discovery enables us to design novel drugs that either inhibit E3 ligases, such as NX-1607, or harness E3 ligases for targeted protein degradation.”
In an oral presentation at the American Chemical Society Spring meeting entitled NX-1607: a First-In-Class Inhibitor of Casitas B-lineage Lymphoma B (CBL-B) for Immuno-Oncology, Nurix disclosed the structure of NX-1607 and its discovery history. NX-1607 acts as a specific intramolecular glue of the CBL-B protein, locking it in a closed and inactive conformation that lowers the threshold for T-cell activation. This mechanism of action is notable because CBL-B lacks a classic enzymatic active site binding pocket, preventing typical inhibitor design and thereby requiring a novel drug discovery approach. A copy of the presentation is available on the Posters and Presentations section of the scientific resources page of Nurix’s website.
Nurix is testing NX-1607 in an ongoing, first-in-human, multicenter, open-label, Phase 1a/1b dose-escalation/expansion trial to evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics (PK/PD), and preliminary anti-tumor activity of NX-1607 in patients with advanced malignancies, including solid tumors and lymphoma. The trial includes both a monotherapy and a combination cohort utilizing paclitaxel. In 2024, Nurix expects to present data from the Phase 1a dose-escalation portion of the trial of NX-1607 and to define dose(s) to enable Phase 1b cohort expansion. Additional information on the clinical trial can be accessed at www.clinicaltrials.gov (NCT05107674).
About CBL-B
CBL-B is an E3 ubiquitin ligase expressed in immune cells that regulates T-cell activation. CBL-B inhibition reduces T-cell exhaustion and increases cytokine production upon T cell receptor stimulation, overcoming suppressive signals in the tumor microenvironment. Furthermore, lack of CBL-B allows T-cell activation despite low target antigen expression on tumor cells, potentially reversing the tumor escape mechanism of resistance. Nurix is pursuing inhibition of CBL-B as a means to increase anti-tumor immune responses and potentially improve outcomes in patients with solid tumors and hematologic malignancies.
About Nurix Therapeutics, Inc.
Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of innovative small molecules and antibody therapies based on the modulation of cellular protein levels as a novel treatment approach for cancer, inflammatory conditions, 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, clinical stage 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 activation of multiple immune cell types including T cell and NK cells. Nurix is headquartered in San Francisco, California. For additional information visit http://www.nurixtx.com.
Forward-Looking Statements
This press release contains statements that relate to future events and expectations and as such constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. When or if used in this press release, the words “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “may,” “outlook,” “plan,” “predict,” “should,” “will,” and similar expressions and their variants, as they relate to Nurix, may identify forward-looking statements. All statements that reflect Nurix’s expectations, assumptions or projections about the future, other than statements of historical fact, are forward-looking statements, including, without limitation, statements regarding: Nurix’s plans and expectations for its drug candidates, including its plans to present data from the Phase 1a dose-escalation portion of the trial of NX-1607 and its plan to define dose(s) to enable Phase 1b cohort expansion; the extent to which Nurix’s drug candidates, including NX-1607, may address a range of diseases; and the potential advantages of Nurix’s scientific approach and DELigase™ platform. Forward-looking statements reflect Nurix’s current beliefs, expectations, and assumptions regarding the future. Although Nurix believes the expectations and assumptions reflected in such forward-looking statements are reasonable, Nurix can give no 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, which could cause Nurix’s actual activities and results to differ materially from those expressed in any forward-looking statement. Such risks and uncertainties include, but are not limited to: (i) whether Nurix will be able to successfully conduct and complete clinical development and commercialization of any of its drug candidates, including NX-1607; (ii) the risks inherent in the drug development process, including the unexpected emergence of adverse events or other undesirable side effects during clinical development; (iii) whether Nurix will be able to fund development activities and achieve development goals; (iv) risks and uncertainties relating to the timing and results of clinical trials; and (v) other risks and uncertainties described under the heading “Risk Factors” in Nurix’s Annual Report on Form 10-K for the fiscal year ended November 30, 2023, and other SEC filings. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. The statements in this press release speak only as of the date of this press release, even if subsequently made available by Nurix on its website or otherwise. Nurix disclaims any intention or obligation to update publicly any forward-looking statements, whether in response to new information, future events, or otherwise, except as required by applicable law.
Contacts:
Investors
Jason Kantor, Ph.D.
Nurix Therapeutics
ir@nurixtx.com
Elizabeth Wolffe, Ph.D.
Wheelhouse Life Science Advisors
lwolffe@wheelhouselsa.com
Media
Aljanae Reynolds
Wheelhouse Life Science Advisors
areynolds@wheelhouselsa.com
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