NX-1607 / Nurix Therap - LARVOL DELTA

Upcoming Program Highlights: NX-1607 (GlobeNewswire) - "Nurix currently is evaluating NX-1607 in an ongoing Phase 1 trial in monotherapy and in a combination cohort utilizing paclitaxel in adults in a range of oncology indications. This study includes a thorough investigation of both dose and schedule in Phase 1a. Future clinical updates are anticipated in 2025."

Trial status • Lymphoma • Solid Tumor

Revisiting the Role of CBL in Liver Fibrosis: Unveiling the Antifibrotic Potential of CBLB inhibitor NX-1607. (PubMed, J Hepatol) - No abstract available

Journal • Fibrosis • Hepatology • Immunology • Liver Cirrhosis

Rational design, optimization, and biological evaluation of novel pyrrolo-pyridone derivatives as potent and orally active Cbl-b inhibitors. (PubMed, Eur J Med Chem) - "Notably, compound B2 stands out, showing superior potency in stimulating IL-2 production in T cells and modulating phosphorylation of key proteins in T-cell receptor signaling. Furthermore, B2 demonstrates favorable pharmacokinetics and significantly inhibits tumor growth in vivo, outperforming NX-1607, which is currently in clinical trials."

Journal • Hematological Malignancies • Lymphoma • Oncology • Targeted Protein Degradation • IL2

Cbl-b inhibition improves manufacturing efficiency and antitumoral efficacy of anti-CD19 CAR-T cells. (PubMed, Int Immunopharmacol) - "In vivo, NX-1607-treated CAR-T cells exhibited superior efficacy against hematological malignancies. These findings highlight Cbl-b as a therapeutic target for enhancing CAR-T cell manufacturing efficiency and antitumor efficacy, underscoring its potential for clinical applications."

Journal • B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Nurix Therapeutics Outlines 2025 Goals and Objectives for Advancement of Its Robust Pipeline in Cancer and Autoimmune Diseases (GlobeNewswire) - "Initiate a suite of clinical trials in 2025 intended to support global registration of NX-5948 for the treatment of chronic lymphocytic leukemia....Drive NX-2127 to proof-of-concept data: Nurix is focusing development on aggressive lymphomas where the combination of BTK degradation and IKZF1/3 degradation have the potential for synergy and significant therapeutic benefit. The company plans to complete dose escalation with new chirally controlled drug product and select recommended Phase 1b dose for selected indications and expects to share additional clinical data after selection of a Phase 1b expansion dose(s) and indication(s). Drive NX-1607 to proof-of-concept data: Nurix is testing both once daily (QD) and twice daily (BID) dosing of NX-1607. With additional patients in the BID dosing arms, Nurix plans to establish a Phase 1b monotherapy dose and expects to share additional clinical data after selection of a Phase 1b expansion dose(s) and indication(s)."

New trial • P1 data • Breast Cancer • Cervical Cancer • Chronic Lymphocytic Leukemia • Colorectal Cancer • Diffuse Large B Cell Lymphoma • Melanoma • Non Small Cell Lung Cancer • Prostate Cancer • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

NX-1607-101: A Study of NX-1607 in Adults With Advanced Malignancies (clinicaltrials.gov) - P1 | N=345 | Recruiting | Sponsor: Nurix Therapeutics, Inc. | Trial completion date: Feb 2026 ➔ Feb 2028 | Trial primary completion date: Aug 2024 ➔ Aug 2026

Trial completion date • Trial primary completion date • B Cell Lymphoma • Breast Cancer • Castration-Resistant Prostate Cancer • Cervical Cancer • Colorectal Cancer • Diffuse Large B Cell Lymphoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hematological Malignancies • Lung Cancer • Lymphoma • Malignant Pleural Mesothelioma • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Pleural Mesothelioma • Prostate Cancer • Richter's Syndrome • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer

Nurix Therapeutics Reports Third Quarter Fiscal 2024 Financial Results and Provides a Corporate Update (GlobeNewswire) - "NX-5948 is an investigational, orally bioavailable degrader of BTK that is currently being evaluated in the Phase 1b portion of a Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies. By year-end 2024, Nurix plans to present additional clinical data from this study for patients with CLL...Nurix recently introduced a new chirally controlled drug product, which is being evaluated in a dose escalation within this Phase 1a/b trial. Future clinical updates are anticipated in 2025...Nurix is evaluating NX-1607 in an ongoing Phase 1 trial in monotherapy and in a combination cohort utilizing paclitaxel in adults in a range of oncology indications...Nurix anticipates providing a program update by year-end 2024."

P1 data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Lymphoma • Mantle Cell Lymphoma • Oncology • Solid Tumor

Nurix Therapeutics Reports Second Quarter Fiscal 2024 Financial Results and Provides a Corporate Update (GlobeNewswire) - "Upcoming Program Highlights:...NX-2127:...Nurix plans to reinitiate enrollment with the new chirally controlled drug product in a standard dose escalation study within the current Phase 1a/1b trial in the second half of 2024....NX-1607:...In the second half of 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."

Enrollment status • P1 data • Hematological Malignancies • Solid Tumor

Nurix Therapeutics Reports First Quarter Fiscal 2024 Financial Results and Provides a Corporate Update (GlobeNewswire) - "NX-1607: 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."

P1 data • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

Nurix Presents the Discovery and Chemical Structure of First-in-Class CBL-B Inhibitor NX-1607 at the American Chemical Society (ACS) Meeting (GlobeNewswire) - "Nurix Therapeutics, Inc...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....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."

Commercial • P1 data • Oncology • Solid Tumor

First disclosure of NX-1607, a first-in-class inhibitor of Casitas B-lineage lymphoma b (CBL-B) for immuno-oncology (ACS-Sp 2024) - P1 | "Currently, NX-1607 is undergoing evaluation in a phase I clinical trial across multiple oncology indications (NCT05107674). We present pharmacokinetic-pharmacodynamic (PK-PD) data from this trial."

Immuno-oncology • Hematological Malignancies • Lymphoma • Oncology • Targeted Protein Degradation

Nurix Therapeutics Reports Fourth Quarter and Fiscal Year 2023 Financial Results and Provides a Corporate Update (GlobeNewswire) - "NX-1607: 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."

P1 data • Oncology • Solid Tumor

NX-1607-101: A Study of NX-1607 in Adults With Advanced Malignancies (clinicaltrials.gov) - P1 | N=345 | Recruiting | Sponsor: Nurix Therapeutics, Inc. | Phase classification: P1b ➔ P1 | Trial completion date: Feb 2025 ➔ Feb 2026

Metastases • Phase classification • Trial completion date • Breast Cancer • Cervical Cancer • Colorectal Cancer • Diffuse Large B Cell Lymphoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hematological Malignancies • Lung Adenocarcinoma • Lung Cancer • Lymphoma • Malignant Pleural Mesothelioma • Melanoma • Mesothelioma • Metastatic Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Prostate Cancer • Richter's Syndrome • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer

Nurix Therapeutics Outlines 2024 Strategic Priorities with Advancement of Targeted Protein Modulation Pipeline in Cancer and Autoimmune Diseases (BioSpace) - "The company plans to accelerate Phase 1 clinical trial enrollment to enable pivotal trials. In addition, Nurix expects to complete ongoing preclinical studies that can enable an investigational new drug (IND) application for NX-5948 in autoimmune indications. NX-2127: Nurix expects to resolve the partial clinical hold on the Phase 1 clinical trial to enable the introduction of newly manufactured drug product into the ongoing Phase 1 clinical trial. NX-1607: Nurix expects to present data from the Phase 1a stage of the monotherapy and paclitaxel combination cohorts in its clinical trial of NX-1607 in a range of oncology indications, and to define plans and dose(s) for Phase 1b cohort expansion."

Enrollment status • P1 data • Preclinical • Castration-Resistant Prostate Cancer • Chronic Lymphocytic Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Hematological Malignancies • Leukemia • Lung Cancer • Lymphoma • Metastatic Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

The co-crystal structure of Cbl-b and a small-molecule inhibitor reveals the mechanism of Cbl-b inhibition. (PubMed, Commun Biol) - "A Cbl-b inhibitor, Nx-1607, is currently in phase I clinical trials for advanced solid tumor malignancies...To further elucidate its mechanism of inhibition, we determined the co-crystal structure of Cbl-b with C7683, revealing the compound's interaction with both the TKBD and LHR, but not the RING domain. Here, we provide structural insights into a novel mechanism of Cbl-b inhibition by a small-molecule inhibitor that locks the protein in an inactive conformation by acting as an intramolecular glue."

Journal • Oncology • Solid Tumor • Targeted Protein Degradation

A First-in-Human Phase 1 Trial of NX-1607, a First-in-Class Oral CBL-B Inhibitor, in Patients with Advanced Malignancies Including DLBCL (ASH 2023) - P1b | "Clinical trial information: NCT05107674. Study contact: nx1607101@nurixtx.com"

Clinical • IO biomarker • Metastases • P1 data • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation

Dose-Escalation/Expansion Trial Evaluates NX-1607 Across Cancer Settings (Targeted Oncology) - "An ongoing phase 1a/1b trial (NCT05107674) is set to evaluate NX-1607-101, an oral small-molecule inhibitor of casitas B-lineage lymphoma B (CBL-B) designed to enhance innate and adaptive immune responses and demonstrate antitumor activity and long-term survival in patients with persistent lymphoma including those with diffuse large B-cell lymphoma (DBCL)....The primary objectives for phase 1a are safety, tolerability, maximum tolerated dose (MTD), and/or recommended phase 1b dose (RP1bD), and the primary objectives for phase 1b will be safety, tolerability, preliminary antitumor activity measured using RECIST v1.1, modified RECIST, and the PK and PD of NX-1607."

Trial status • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

NX-1607, a small molecule inhibitor of CBL-B, enhances anti-PD-1-mediated tumor growth inhibition by reshaping intratumoral innate and adaptive immune response (SITC 2023) - P1b | "These findings provide additional support for clinical development of this novel CBL-B inhibitor given as monotherapy or in combination with PD-1 blockade. A Phase 1 clinical trial of NX-1607 in patients with advanced tumors is ongoing (NCT05107674)."

IO biomarker • Colon Cancer • Colorectal Cancer • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • IFNG

Nurix Therapeutics Announces Presentations at the 65th American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - "Nurix Therapeutics, Inc...today announced that clinical data will be presented for its two BTK degrader programs, NX-5948 and NX-2127, in two posters at the 65th American Society of Hematology Annual Meeting and Exposition being held December 9-12, 2023, in San Diego, CA. Nurix will also present a trials in progress poster for its NX-1607 program."

P1 data • Trial status • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Nurix Therapeutics Reports Third Quarter Fiscal 2023 Financial Results and Provides a Corporate Update (GlobeNewswire) - "Upcoming Program Highlights:...NX-1607:...Nurix is evaluating NX-1607 in an ongoing, Phase 1a dose escalation trial in monotherapy and in a combination cohort utilizing paclitaxel in adults in a range of oncology indications. Nurix expects to present clinical data from the Phase 1a portion of the study and to define a dose for Phase 1b cohort expansion in the second half of 2023."

P1 data • Hematological Malignancies • Solid Tumor

Nurix Therapeutics Reports Second Quarter Fiscal 2023 Financial Results and Provides a Corporate Update (GlobeNewswire) - "Upcoming Program Highlights:...NX-1607:...Nurix is evaluating NX-1607 in an ongoing, Phase 1a dose escalation trial in monotherapy and in a combination cohort utilizing Paclitaxel in adults in a range of oncology indications and expects to present clinical data from the Phase 1a portion of the study and to define a dose for Phase 1b cohort expansion in the second half of 2023."

P1 data • Breast Cancer • Cervical Cancer • Colorectal Cancer • Diffuse Large B Cell Lymphoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Hematological Malignancies • Lung Cancer • Lymphoma • Malignant Pleural Mesothelioma • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Prostate Cancer • Richter's Syndrome • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • Triple Negative Breast Cancer • Urothelial Cancer

NX-1607-101: A Study of NX-1607 in Adults With Advanced Malignancies (clinicaltrials.gov) - P1b | N=363 | Recruiting | Sponsor: Nurix Therapeutics, Inc. | N=268 ➔ 363

Enrollment change • Metastases • Breast Cancer • Cervical Cancer • Colorectal Cancer • Diffuse Large B Cell Lymphoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hematological Malignancies • Lung Adenocarcinoma • Lung Cancer • Lymphoma • Malignant Pleural Mesothelioma • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Prostate Cancer • Richter's Syndrome • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer

NX-0255 AND NX-1607, SMALL MOLECULE INHIBITORS OF CBL-B, ARE EFFICACIOUS IN COMBINATION WITH ADOPTIVE CELL THERAPY OR RITUXIMAB IN PRECLINICAL MOUSE MODELS OF LYMPHOMA (ICML 2023) - P1, P1b | "We have initiated a clinical trial with NX-1607 (NCT05107674) in patients with advanced cancer including solid tumors and malignant lymphoma, including large B cell lymphoma. Nurix has also completed the safety run-in portion of a Phase 1 trial evaluating NX-0255 in the production of an investigational drug-enhanced TIL therapy, DeTIL-0255 (NCT05107739)."

Combination therapy • Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD8

NX-1607, a small molecule inhibitor of the CBL-B E3 ubiquitin ligase, promotes T and NK cell activation and enhances NK-mediated ADCC in a mouse lymphoma tumor model (SITC 2022) - P1b | "Methods Here we describe the effects of NX-1607, an orally bioavailable intramolecular glue inhibitor of CBL-B, on primary human T and NK cells and assess NX-1607 in combination with Rituximab in a murine xenograft model of Non-Hodgkin’s Lymphoma (NHL). These studies also provide support for clinical development of NX-1607 as a monotherapy or in combination with antibody therapeutics to enhance ADCC antitumor effects. We have initiated a clinical trial with NX-1607 in patients with advanced solid tumors NX-1607-101 ( NCT05107674 )."

Preclinical • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • CD4 • IFNG • IL2 • TGFB1 • TNFA

A FIRST-IN-HUMAN PHASE 1 TRIAL OF NX-1607, A FIRST-IN-CLASS ORAL CBL-B INHIBITOR, IN PATIENTS WITH ADVANCED MALIGNANCIES INCLUDING RICHTER TRANSFORMATION DLBCL (EHA 2022) - P1b | "Conclusion Accrual is ongoing. Clinical trial information: NCT05107674."

Clinical • P1 data • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Solid Tumor • Targeted Protein Degradation