Nurix Announces DeTIL-0255 Scientific Presentations at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) and Successful Completion of DeTIL-0255 Phase 1 Safety Run-in

SAN FRANCISCO, Nov. 10, 2022 (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, presented preclinical data supporting the utility of its CBL-B inhibitors to enhance cell therapy at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), which is being held November 8 – 12^th in Boston. Nurix also announced the successful completion of the safety run-in portion of the ongoing Phase 1 trial of DeTIL-0255 in patients with advanced gynecologic malignancies and revealed that it has received feedback from the FDA regarding the potential combination of DeTIL-0255 with the oral CBL-B inhibitor NX-1607. The FDA feedback, the preliminary safety profile of DeTIL-0255, and the potential benefits of combining DeTIL-0255 with in vivo pharmacologic inhibition of CBL-B with NX-1607 provide a path for a potential future combination trial to explore whether inhibiting CBL-B both ex vivo and in vivo may enhance the anti-tumor potential of adoptive cell therapy.

“We believe that our portfolio of first-in-class CBL-B inhibitors has the potential to improve outcomes for patients with solid tumors and enhance the field of cell therapy,” said Robert J. Brown, M.D., executive vice president of clinical development at Nurix. “Pending successful completion of Nurix’s NX-1607 Phase 1a dose escalation trial, we envision expanding the use of NX-1607 as a single agent in selected indications in 2023. We also can see a path to exploring the potential for a combination strategy with DeTIL-0255 in accordance with recent feedback from the FDA.”

The Phase 1 safety run-in includes three patients with advanced epithelial ovarian cancer (EOC) who have been dosed with DeTIL-0255 and have cleared the initial safety evaluation. Expansion of the Phase 1 trial will be postponed, pending potential inclusion of NX-1607 in future cohorts.

Summary of DeTIL-0255-related data presented at the SITC meeting:

Title: A novel small molecule inhibitor of CBL-B shows potent antitumor activity in combination with Pmel-1 adoptive cell transfer in an aggressive mouse melanoma model
Current adoptive cell transfer (ACT) treatment paradigms require application of high dose bolus infusions of IL-2 which are associated with acute toxicities, restricting the use of ACT in the clinic. The results presented in this poster demonstrate that production of ACT supported by ex vivo use of NX-0255 combined with in vivo oral treatment with NX-1607:

• Increases the antitumor activity of the transferred T cells when compared to ACT alone and
• Induces a more favorable anti-tumor activity phenotype of the adoptively transferred T cells compared to treatment with IL-2

These observed anti-tumor effects of NX-1607 support its potential use in combination with cell-based therapeutics.

Title: The CBL-B inhibitor, NX-0255, improves human drug enhanced tumor infiltrating lymphocyte (DeTIL-0255) expansion and T-cell function in full-scale runs
These studies demonstrate that addition of NX-0255, a highly potent CBL-B inhibitor, during ex-vivo TIL expansion results in a favorable TIL phenotype and higher cell yields at research scale. Data from six full-scale manufacturing runs of different tumor types are presented demonstrating that addition of NX-0255 in the cell expansion phase significantly increases the total number of CD8+ T cells with a central memory and ‘stem-like’ memory phenotype. In addition, the expression profile of genes associated with tumor killing activities was enhanced in NX-0255 treated cells when compared with conventional TIL.

Title: Universal expansion of CBL-B-inhibited tumor infiltrating lymphocytes, DeTIL-0255, from women with ovarian cancer: process validation 
In this poster, data are presented from both research and clinical scale manufacturing studies demonstrating that Nurix has developed a process in which cells are exposed to NX-0255 during the cell expansion phase of manufacturing that yields a superior TIL product for patients with ovarian cancer with a favorable phenotype amenable for adoptive cell therapy.

About DeTIL-0255
DeTIL-0255 is an autologous cell therapy consisting of T cells derived from a patient’s tumor expanded in culture with recombinant interleukin-2 and the small molecule CBL-B inhibitor NX-0255. DeTIL-0255 is designed to be a single administration autologous TIL therapy infused following non-myeloablative chemotherapy. DeTIL-0255 is currently being evaluated in a Phase 1 clinical trial in patients with advanced gynecologic tumors. Additional information on the ongoing clinical trial can be accessed at www.clinicaltrials.gov (NCT05107739).

About NX-1607
NX-1607 is an orally bioavailable inhibitor of Casitas B-lineage lymphoma proto-oncogene B (CBL-B) for immuno-oncology indications, including a range of solid tumor types. NX-1607 acts on T cells, NK cells, and dendritic cells to enhance anti-tumor immunity, and has demonstrated single-agent anti-tumor activity in multiple tumor models. Nurix is evaluating NX-1607 in an ongoing, Phase 1 dose escalation and expansion trial in adults with a variety of oncology indications at multiple clinical sites. Additional information on the clinical trial can be accessed at www.clinicaltrials.gov (NCT05107674).

About Nurix
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 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 future plans and strategies; the tolerability, safety profile, therapeutic potential and other advantages of Nurix’s drug candidates; the planned timing and conduct of the clinical trials for Nurix’s drug candidates; the planned timing for the provision of updates and findings from Nurix’s clinical trials; and the extent to which Nurix’s drug candidates and scientific approach and may potentially address a broad range of diseases. Forward-looking statements reflect Nurix’s current beliefs, expectations, and assumptions. 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 Phase 1 clinical trials for NX-1607, DeTIL-0255 and its other drug candidates and receive results on its expected timelines, or, at all; (ii) whether Nurix will be able to successfully complete clinical development for its drug candidates; (iii) the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; (iv) whether regulatory authorities will be satisfied with the results from Nurix’s clinical studies; (v) whether Nurix will be able to obtain regulatory approval of and ultimately commercialize its drug candidates; (vi) whether Nurix will be able to fund development activities and achieve development goals; (vii) the impact of the COVID-19 pandemic on Nurix’s clinical trials and operations; and (viii) other risks and uncertainties described under the heading “Risk Factors” in Nurix’s Quarterly Report on Form 10-Q for the fiscal quarter ended August 31, 2022, 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:
Silinda Neou 
Nurix Therapeutics 
ir@nurixtx.com 

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

Media 
Brett Whelan 
LifeSci Communications 
bwhelan@lifescicomms.com