bexobrutideg (NX-5948) / Nurix Therap - LARVOL DELTA

BEXOBRUTIDEG (NX-5948), A NOVEL BRUTON'S TYROSINE KINASE DEGRADER, SHOWS HIGH CLINICAL ACTIVITY AND TOLERABLE SAFETY IN AN ONGOING PHASE 1A/B STUDY IN PATIENTS WITH WALDENSTRÖM MACROGLOBULINEMIA (EHA 2025) - "Bexobrutideg was well tolerated in patients with WM, consistent with previous disclosures in the overall study population. Bexobrutideg demonstrated a notably high level of clinical activity with steady reduction in IgM levels and deepening responses in heavily pre-treated patients with WM despite all patients having prior BTKi exposure. Favorable outcomes were seen independent of baseline mutational status, including patients whose tumors had MYD88 and CXCR4 mutations."

Clinical • IO biomarker • P1 data • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Oncology • Targeted Protein Degradation • Thrombocytopenia • Waldenstrom Macroglobulinemia • BTK • CRBN • CXCR4 • MYD88

BEXOBRUTIDEG (NX-5948), A NOVEL BRUTON'S TYROSINE KINASE (BTK) DEGRADER, DEMONSTRATES RAPID AND DURABLE CLINICAL RESPONSES IN RELAPSED/REFRACTORY CLL: UPDATED FINDINGS FROM AN ONGOING PHASE 1A STUDY (EHA 2025) - "Bexobrutideg was well tolerated in patients with R/R CLL, including those with longer duration of treatment and higher doses. In this fully enrolled Phase 1a cohort, bexobrutideg showed rapid and durable responses independent of prior treatment or high-risk features such as double refractory status and unfavorable genetic profile. Phase 1b dose expansion (200 and 600 mg cohorts) is underway with plans to initiate pivotal trials in 2025."

Clinical • IO biomarker • P1 data • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Fatigue • Hematological Disorders • Hematological Malignancies • Infectious Disease • Neutropenia • Oncology • Pulmonary Embolism • Respiratory Diseases • Targeted Protein Degradation • BCL2 • BTK • CRBN • PLCG2 • TP53

BTK-A428D IS A CROSS-RESISTANT MUTATION TO BOTH BTK INHIBITORS AND DEGRADERS (EHA 2025) - "BTK-A428D is a mutation that exhibits cross-resistance to multiple BTK degraders (BGB-16673, NX-2127, NX-5948, Abbv Compound 1) and inhibitors (ibrutinib, acalabrutinib, zanubrutinib, and pirtobrutinib) both in vitro and in vivo, as supported by evidence from multiple aspects. In the future, BTK-A428D mutated cancer cells may be treated by other targeted therapies."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • PLCG2

Bexobrutideg (NX-5948), a novel BTK degrader, demonstrates rapid and durable clinical responses in relapsed/refractory CLL: updated findings from ongoing Phase 1a study (ICML 2025) - No abstract available

Clinical • P1 data • Chronic Lymphocytic Leukemia • Lymphoma

BEXOBRUTIDEG (NX-5948), A NOVEL BTK DEGRADER, SHOWS HIGH CLINICAL ACTIVITY AND TOLERABLE SAFETY IN AN ONGOING PHASE 1A/B STUDY IN WALDENSTRÖM MACROGLOBULINEMIA (ICML 2025) - "Bexobrutideg was well tolerated in pts with WM, consistent with previous disclosures in the overall study population. Bexobrutideg demonstrated a notably high level of clinical activity with steady reduction in IgM levels and deepening responses in heavily pre-treated pts, and in pts whose tumors had MYD88 and CXCR4 mutations. Bexobrutideg Phase 1b dose expansion is underway."

Clinical • IO biomarker • P1 data • Chronic Lymphocytic Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Waldenstrom Macroglobulinemia • CRBN • CXCR4 • MYD88

Nurix Therapeutics Presents Updated Positive Data Demonstrating Durable, Deepening Responses in Ongoing Clinical Trial of Bexobrutideg (NX-5948) Monotherapy in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) and Waldenström Macroglobulinemia (WM) (GlobeNewswire) - P1a/b | N=572 | NCT05131022 | Sponsor: Nurix Therapeutics, Inc. | "Nurix Therapeutics, Inc...announced positive clinical data from the Company’s ongoing NX-5948-301 study, a Phase 1a/b clinical trial of bexobrutideg (NX-5948) in patients with relapsed or refractory B-cell malignancies....Objective response was observed in 16 patients (84.2%), including two patients (10.5%) with very good partial response (VGPR), 11 patients (57.9%) with partial response (PR), and three patients (15.8%) with minor response (MR). Three patients (15.9%) had a best response of stable disease (SD). Responses were observed in patients regardless of their baseline mutations in MYD88 and CXCR4....Nurix remains on track to initiate pivotal trials of bexobrutideg in 2025."

New trial • P1 data • Chronic Lymphocytic Leukemia • Waldenstrom Macroglobulinemia

Nurix Therapeutics to Host a Webcast Conference Call to Discuss Data from the Ongoing Phase 1 Clinical Trial of Bexobrutideg (NX-5948) Being Presented at the 30th European Hematology Association Congress (EHA2025) (GlobeNewswire) - "Nurix Therapeutics, Inc...announced that the company will host a webcast conference call at 8:00 a.m., ET, on Thursday, June 12, 2025, to discuss new data from the ongoing Phase 1 clinical trial of bexobrutideg (NX-5948) that will be presented at the European Hematology Association Congress in Milan, Italy."

P1 data • Chronic Lymphocytic Leukemia

Nurix Therapeutics Announces Presentations of Clinical Data at the 30th European Hematology Association Congress and the 18th International Conference on Malignant Lymphoma (GlobeNewswire) - "Nurix Therapeutics, Inc...today announced that data from the Company’s ongoing Phase 1a/b clinical trial of bexobrutideg (NX-5948) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and Waldenström macroglobulinemia will be presented at two major upcoming scientific conferences."

P1 data • Chronic Lymphocytic Leukemia • Waldenstrom Macroglobulinemia

NX-5948 is a CNS-penetrant catalytic Bruton's tyrosine kinase (BTK) degrader that breaks established design rules for CNS drugs (AACR 2025) - "In the clinic, NX-5948 is detectable in cerebrospinal fluid of patients with CNS-involved B-cell malignancies, with concentrations that exceed the minimum free plasma level that correlates with BTK degradation. NX-5948 has also demonstrated clinically meaningful responses in patients with primary CNS lymphoma or chronic lymphocytic leukemia with CNS involvement (Hansen, G., AACR San Diego, 2024; Linton, K., EHA Hybrid Congress, Madrid, Spain, 2024), supporting the therapeutic potential of NX-5948 in B-cell malignancies with CNS involvement."

Chronic Lymphocytic Leukemia • CNS Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • BTK

An oral BTK degrader TGRX-3911 overcomes resistance conferred by kinase-proficient and kinase-impaired mutations (AACR 2025) - "TGRX-3911 potently inhibited proliferation of TMD8 parental cells and those harboring knock-in BTK mutations that are resistant to currently approved ibrutinib, zanubrutinib and/or pirtobrutinib, including C481S, T474I, L528W, V416L, A428D, T474I/C481S, T474I/L528W and C481S/L528W (IC50 from 0.4 to 9.9 nM). Remarkably, TGRX-3911 potently inhibited the A428D mutant which is still resistant to current BTK degraders, NX-5948, BGB-16673 and ABBV-101...By eliminating both the catalytic and scaffold functions of BTK, TGRX-3911 has the potential to overcome clinical resistance which can hardly be achieved by conventional BTKi. The potential clinical application of TGRX-3911 for patients with B-cell malignancies is worth exploring."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD86 • PLCG2

HP-002: A brain-penetrant PROTAC that demonstrated potent anti-proliferation activities on multiple BTK mutant (AACR 2025) - "In lymphoma cells e.g. REC-1 and TMD8, HP-002 demonstrated 2-digit pM IC50 with up to ~10-fold more potent than NX-5948 and BGB-16673. HP-002 is a potent and highly selective BTK degrader against BTK-WT and multiple BTK inhibitor-resistant mutations. Brain penetration was observed in the TMD8 xenograft tumor model with deeper BTK down-regulation on the HP-002 treatment and robust tumor growth inhibition. With no significant safety risk findings in the preliminary rat and NHP DRF studies, HP-002 is currently under IND-enabling development."

Late-breaking abstract • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • BTK • CRBN • GSPT1 • SALL4

Nurix Therapeutics Presents Positive Preclinical Data at the AACR 2025 Annual Meeting from Multiple Orally Available, Brain Penetrant Degraders Against Three High Value Oncology Targets (GlobeNewswire) - "In a poster titled: 'NX-5948 is a CNS-penetrant catalytic Bruton’s tyrosine kinase (BTK) degrader that breaks established design rules for CNS drugs,' data were presented that highlight the unique physico-chemical properties of NX-5948, now called bexobrutideg, that differentiate it from traditional brain penetrant drugs. Bexobrutideg exhibits CNS exposure in several preclinical models and, most importantly, is detectable in the cerebrospinal fluid of patients where it has demonstrated clinically meaningful responses in patients with primary CNS lymphoma or chronic lymphocytic leukemia with CNS involvement."

Preclinical • Chronic Lymphocytic Leukemia • CNS Lymphoma

Efficacy/Safety of the BTK Degrader NX-5948 in Chronic Lymphocytic Leukemia: An Ongoing Phase 1a/b Study (BSH 2025) - No abstract available

Clinical • P1 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Upcoming Program Highlights: Bexobrutideg (NX-5948) (GlobeNewswire) - "In 2025, Nurix plans to commence a suite of clinical trials designed to support global registration of bexobrutideg for the treatment of patients with CLL. In addition, Nurix anticipates moving into autoimmune and inflammatory diseases and expects to open a new Phase 1b cohort for patients with CLL and associated autoimmune hemolytic anemia and is exploring the filing of a non-malignant hematology IND for autoimmune cytopenias in 2025. Future clinical updates in patients with both CLL and non-Hodgkin’s lymphoma are anticipated in 2025."

IND • New trial • Trial status • Autoimmune Hemolytic Anemia • Chronic Lymphocytic Leukemia • Non-Hodgkin’s Lymphoma

Nurix Therapeutics Announces Multiple Presentations at the American Association for Cancer Research (AACR) 2025 Annual Meeting (GlobeNewswire) - "Nurix Therapeutics...announced that company scientists will present preclinical data from its proprietary DEL-AI platform and several degrader programs in two oral presentations and two poster presentations at the American Association for Cancer Research (AACR) 2025 Annual Meeting..."

Preclinical • Oncology

A Food-Effect, Drug-Drug Interaction, and Pharmacokinetics Study of NX-5948 in Healthy Adult Subjects (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Nurix Therapeutics, Inc. | Active, not recruiting ➔ Completed

Trial completion

NX-5948-303: Absolute Bioavailability, Absorption, Metabolism, Excretion, and Mass Balance Study of [14C] NX-5948 (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Nurix Therapeutics, Inc. | Recruiting ➔ Completed

Trial completion

Nurix Announces U.S. FDA Orphan Drug Designation Granted to Bexobrutideg (NX-5948) for the Treatment of Waldenström Macroglobulinemia (GlobeNewswire) - "Nurix Therapeutics, Inc...announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to bexobrutideg (NX-5948) for the treatment of Waldenström macroglobulinemia (WM)....In collaboration with the national naming authority, United States Adopted Name (USAN) Council, Nurix’s lead BTK degrader, NX-5948, was assigned the nonproprietary name 'bexobrutideg'....Nurix continues to enroll patients with WM in an ongoing Phase 1b expansion cohort and anticipates sharing additional clinical data in 2025."

Commercial • Orphan drug • P1 data • Waldenstrom Macroglobulinemia

Breakthroughs in treatment for hematological malignancies: latest updates on molecular glue, PROTACs and RNA degraders from ASH 2024. (PubMed, J Hematol Oncol) - "Currently, the main categories developed based on degraders include molecular glue (such as Cemsidomide, NX-5948), PROTACs (such as BGB-16673, AC-676, KT-333 ), and RNA degraders (such as SKY-1214). This correspondence summarizes the preclinical and clinical updates on degrader therapies presented at the ASH 2024 annual meeting."

Journal • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation

Bruton Tyrosine Kinase Degraders: Current Concepts. (PubMed, Am J Clin Oncol) - "While BTK inhibitors (BTKi), such as ibrutinib, have been effective, resistance-both intrinsic and acquired-poses a significant challenge, often associated with BTK mutations like C481S...Agents such as NRX-0492, BGB-16673, NX-5948, NX-2127, HZ-Q1060, ABBV-101, and AC676 have shown significant BTK degradation in preclinical and early clinical trials...These BTK degraders have demonstrated favorable safety profiles, with manageable adverse events, and offer a novel therapeutic avenue for patients with BTKi-resistant malignancies. As clinical trials progress, these degraders hold the potential to significantly enhance treatment outcomes, offering a new frontier in personalized cancer therapy."

Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • BTK

BTK Is the Target That Keeps on Giving: A Review of BTK-Degrader Drug Development, Clinical Data, and Future Directions in CLL. (PubMed, Cancers (Basel)) - "We focus on four agents which are under investigation in B-cell malignancies in early clinical trials: BGB-16673, NX-2127, NX-5948, and AC676. Further trials investigating these agents in combination with other targeted CLL agents may help to further understand their applicability. An effective, tolerable oral class of drugs would be invaluable in the treatment of patients with multiply relapsed CLL/SLL."

Clinical data • Journal • Review • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Targeted Protein Degradation • BCL2

A Validated Liquid Chromatography-Tandem Mass Spectrometry Assay for the Determination of NX-5948 in Beagle Dog Plasma: Application to a Pharmacokinetic Study. (PubMed, Biomed Chromatogr) - "NX-5948 was demonstrated to be stable under the present storage conditions. After validation, the method was successfully applied for the quantification of NX-5948 in beagle dog plasma after oral and intravenous administration of the NX-5948."

Journal • PK/PD data • Oncology • Targeted Protein Degradation • BTK

BTK Is the Target That Keeps on Giving: A Review of BTK-Degrader Drug Development, Clinical Data, and Future Directions in CLL (Multidisciplinary Digital Publishing Institute) - "Encouraging pre-clinical data show that this MOA allows BTK protein degraders to overcome common BTK mutations. We focus on four agents which are under investigation in B-cell malignancies in early clinical trials: BGB-16673, NX-2127, NX-5948, and AC676. Preliminary data suggest a comparable safety and toxicity profile between agents across this drug class with many patients on phase 1 trials deriving durable clinical benefit. Optimal sequencing of BTK degraders in the therapeutic landscape of CLL/SLL treatment is yet to be established."

Review • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

Nurix Therapeutics Reports Fourth Quarter and Fiscal Year 2024 Financial Results and Provides a Corporate Update (GlobeNewswire) - "Upcoming Program Highlights: NX-5948:...Nurix...expects to open a new Phase 1b cohort for patients with CLL and associated autoimmune hemolytic anemia...in 2025. Future clinical updates in patients with both CLL and non-Hodgkin’s lymphoma are anticipated in 2025."

Clinical protocol • P1 data • Chronic Lymphocytic Leukemia • Non-Hodgkin’s Lymphoma

Nurix Therapeutics Reports Fourth Quarter and Fiscal Year 2024 Financial Results and Provides a Corporate Update (GlobeNewswire) - "Upcoming Program Highlights: NX-5948:...Nurix anticipates moving into autoimmune and inflammatory diseases...and is exploring the filing of a non-malignant hematology IND for autoimmune cytopenias in 2025."

IND • Hematological Disorders • Immunology • Inflammation