Nurix Therapeutics Presents New Translational Data from First-in-Human Clinical Trial of Oral CBL-B Inhibitor NX-1607 Demonstrating Immune Activation and Tumor Microenvironment Remodeling

Rhea-AI Summary

Nurix Therapeutics (Nasdaq: NRIX) presented translational data on Nov 7, 2025 from its ongoing Phase 1a study of oral CBL-B inhibitor NX-1607 at SITC 2025.

Key findings show dose-dependent pharmacology and target engagement (pHS1 modulation), peripheral T cell activation and proliferation correlated with stable disease versus progressive disease, and a case study in metastatic castration-resistant prostate cancer (5 prior therapies) showing stable disease with increased CD8+ TIL density and upregulated interferon and cytotoxic pathways. RNA sequencing showed dose-dependent enrichment of immune signaling pathways, linking systemic immune activation to tumor microenvironment remodeling.

Positive

• Dose-dependent pharmacology and pHS1 biomarker modulation confirming target engagement
• Peripheral T cell activation correlated with patients achieving stable disease
• mCRPC case study: increased CD8+ TIL density and upregulated interferon/cytotoxic pathways
• RNA sequencing showed dose-dependent enrichment of antigen presentation and effector T cell pathways

Negative

• Clinical data are early-stage from an ongoing Phase 1a study (no late‑stage confirmation)
• Best reported objective outcome in presented data was stable disease, not tumor regression
• Key translational benefit illustrated by a single mCRPC case study (single‑patient paired biopsy)

Insights

Translational Immuno-oncology Expert

Phase 1 translational data show dose-dependent target engagement and immune activation but clinical efficacy remains preliminary.

NX-1607, an oral CBL-B inhibitor, produced dose-dependent pharmacokinetics and modulation of the proximal biomarker pHS1, consistent with target engagement and downstream immune signaling. Peripheral blood showed increased PD-1+ CD8+ T cells with Ki67+ and ICOS+ markers in patients with stable disease versus progressive disease, indicating systemic T‑cell activation linked to clinical status.

Paired pre/post tumor biopsies from a single heavily pretreated metastatic castration‑resistant prostate cancer patient showed increased CD8+ TIL density, upregulation of cytotoxic and interferon-response pathways, and reduced regulatory T‑cell signatures, consistent with remodeling of the tumor microenvironment and concordant transcriptomic enrichment of antigen presentation and effector T‑cell pathways.

Key dependencies and risks include the limited sample size, reliance on biomarker and a single case of best response as stable disease, and the early Phase 1 status of the program presented at the Society for Immunotherapy of Cancer meeting on Nov 07, 2025. Watch for expansion cohort response rates, objective response data and durability endpoints, and any prespecified biomarker-response correlations reported in future Phase 1 updates or subsequent trials; timelines for those readouts were not disclosed in this release.

Data are being presented at the 2025 Society for Immunotherapy of Cancer (SITC) Annual Meeting

SAN FRANCISCO, Nov. 07, 2025 (GLOBE NEWSWIRE) -- Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company developing targeted protein modulation therapies to treat cancer and immune disorders, today announced the presentation of new translational data from its ongoing Phase 1 study of NX-1607, an oral, first-in-class inhibitor of Casitas B-lineage lymphoma proto-oncogene B (CBL-B), at the Society for Immunotherapy of Cancer (SITC) 2025 Annual Meeting which is being held November 5–9, 2025, in National Harbor, MD.

The poster, titled Translational Insights from a First-in-Human Study of an Oral CBL-B Inhibitor in Advanced Solid Tumors, expands upon data presented at the recent European Society for Medical Oncology (ESMO) Congress from heavily pretreated patients with a variety of tumor types who were treated with NX-1607 in an ongoing Phase 1a clinical trial. The new data presented at SITC demonstrate that treatment with NX-1607 resulted in dose dependent pharmacologic activity consistent with target engagement and downstream immune modulation. Treatment with NX-1607 led to increased peripheral T cell activation and proliferation, which were statistically significantly greater in patients with stable disease (SD) compared with those with progressive disease (PD), indicative of active T-cell receptor (TCR) engagement and immune responsiveness to treatment.

The poster also highlights a case study of a patient with metastatic castration-resistant prostate cancer (mCRPC) who achieved a best response of stable disease while receiving NX-1607. Treatment was associated with expansion of activated peripheral memory T cell subsets, an increase in CD8+ tumor infiltrating lymphocyte (TIL) density and enhanced immune activation gene signatures in paired metastatic lymph node tumor biopsies. Collectively, these findings indicate that NX-1607 induced peripheral immune activation is associated with remodeling of the tumor microenvironment (TME), linking systemic immune activation to local tumor control.

“These translational findings further support the biological rationale for CBL-B inhibition as a novel immune-oncology therapy,” said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix Therapeutics. “NX-1607 has demonstrated encouraging signs of immune activation and disease control in heavily pretreated patients, supporting its potential as a novel next generation checkpoint inhibitor therapy and its continued development as a monotherapy and in combination with other anticancer agents for the treatment of advanced solid tumors.”

Key Findings

• Dose-dependent pharmacology and immune activation: NX-1607 demonstrated dose-dependent pharmacokinetics and pharmacodynamic modulation of the proximal biomarker pHS1, confirming target engagement and inhibition of CBL-B–mediated signaling.
• Peripheral immune activation linked to clinical benefit: Patients with stable disease exhibited a greater enrichment of circulating PD-1⁺ CD8⁺ T cells expressing Ki67⁺ (proliferation) and ICOS⁺(activation) markers compared with those with progressive disease, demonstrating active TCR engagement and antitumor immune responsiveness.
• Remodeling of the tumor microenvironment: In a case study of a heavily pretreated mCRPC patient (5 prior therapies), NX-1607 treatment achieved a best response of stable disease. Paired pre and post treatment metastatic lymph node tumor biopsy analyses showed an increase in CD8⁺ TIL density, upregulation of cytotoxic and interferon-response pathways, and reduced regulatory T-cell signatures, consistent with enhanced effector activity and immune activation within the TME.
• Transcriptomic evidence of immune pathway engagement: RNA sequencing analyses demonstrated dose-dependent enrichment of immune signaling pathways, including interferon response, antigen presentation, and effector T cell activation, further supporting a mechanistic link between NX-1607 exposure and immune activation.

About NX-1607
NX-1607 is an investigational first-in-class oral inhibitor of the E3 ligase Casitas B-lineage lymphoma proto-oncogene B (CBL-B) being developed for immuno-oncology indications, including a range of solid tumor types. CBL-B is a cytoplasmic E3 ubiquitin ligase that negatively regulates T cell activation, making it an attractive target for immuno-oncology and offering a novel therapeutic approach to treat solid tumors. Inhibition of CBL-B in preclinical studies reverses T cell exhaustion, alleviates tumor induced immunosuppression, and may also exert direct antitumor effects. Nurix is evaluating NX-1607 in an ongoing Phase 1 trial in adults in a range of oncology indications. This study includes a thorough investigation of both dose and schedule in the Phase 1a portion. Additional information on the NX-1607 clinical trial can be accessed at www.clinicaltrials.gov (NCT05107674).

About Nurix Therapeutics, Inc.
Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines, the next frontier in innovative drug design aimed at improving treatment options for patients with cancer and autoimmune diseases. Nurix’s wholly owned, clinical stage pipeline includes degraders of Bruton’s tyrosine kinase (BTK), a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene B (CBL-B), an E3 ligase that regulates activation of multiple immune cell types including T cells and NK cells. Nurix also is advancing multiple potentially first-in-class or best-in-class degraders and degrader antibody conjugates (DACs) in its preclinical pipeline. Nurix’s partnered drug discovery pipeline consists of a preclinical stage degrader of STAT6, a clinical stage degrader of IRAK4, and multiple additional programs under collaboration agreements with Gilead Sciences, Inc., Sanofi S.A. and Pfizer Inc., within which Nurix retains certain options for co-development, co-commercialization and profit sharing in the United States for multiple drug candidates. Powered by a fully AI-integrated discovery engine capable of tackling any protein class, and coupled with unparalleled ligase expertise, Nurix’s dedicated team has built a formidable advantage in translating the science of targeted protein degradation into clinical advancements. Nurix aims to establish degrader-based treatments at the forefront of patient care, writing medicine’s next chapter with a new script to outmatch disease. Nurix is headquartered in San Francisco, California. For additional information visit http://www.nurixtx.com.

Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 and other federal securities laws. Any statements contained herein that do not describe historical facts, including, but not limited to, statements regarding the Nurix’s intention to present new data from the clinical trial of NX-1607 at the SITC 2025 Annual Meeting, are forward-looking statements that involve risks and uncertainties that could cause actual results to differ materially from those discussed in such forward-looking statements. Such risks and uncertainties include, among others, the risks described under the heading “Risk Factors” in Nurix’s Quarterly Report on Form 10-Q for the period ended August 31, 2025, and subsequent filings with the SEC. Any of these risks and uncertainties could materially and adversely affect Nurix’s business and results of operations, which could, in turn, have a significant and adverse impact on Nurix’s stock price. Nurix cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. Nurix undertakes no obligation to update publicly any forward-looking statements to reflect new information, events or circumstances after the date they were made or to reflect the occurrence of unanticipated events.

Contacts:

Investors
Kris Fortner
Nurix Therapeutics, Inc.
ir@nurixtx.com

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

Media
Aljanae Reynolds
Wheelhouse Life Science Advisors
areynolds@wheelhouselsa.com

FAQ

What did Nurix announce about NX-1607 at SITC on November 7, 2025 (NRIX)?

Nurix presented Phase 1a translational data showing dose-dependent target engagement, peripheral T cell activation, and tumor microenvironment remodeling linked to clinical stable disease.

How did NX-1607 affect immune cells in patients in the NRIX Phase 1a study?

NX-1607 induced increased peripheral PD-1+ CD8+ T cell proliferation (Ki67+) and activation (ICOS+), with greater enrichment in patients with stable disease.

What tumor microenvironment changes were reported for NX-1607 (NRIX) in the mCRPC case study?

Paired biopsies showed higher CD8+ TIL density, reduced regulatory T‑cell signatures, and upregulated cytotoxic and interferon-response pathways.

Does the SITC 2025 data for NX-1607 (NRIX) show objective responses or approvals?

The presented data report immune activation and stable disease as the best response; no regulatory approvals or confirmed objective responses were reported.

What evidence links NX-1607 exposure to immune pathway activation in the NRIX data?

Dose-dependent RNA sequencing enrichment of interferon response, antigen presentation, and effector T cell activation pathways was reported.