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

The Optimal Management of Waldenström Macroglobulinemia (SOHO 2025) - "Standard treatment options include alkylating agents (eg, bend-amustine or cyclophosphamide) or proteasome inhibitors (eg, bortezomib, carfilzomib, or ixazomib) in combination with anti-CD20 monoclonal antibody rituximab, covalent Bruton tyrosine kinase (BKT) inhibitors (eg ibrutinib, acalabrutinib, or zanubrutinib), BCL2 antagonists (eg, venetoclax), and non-covalent BTK inhibitors (eg, pirtobrutinib) 13–23...The combination of bendamustine and rituximab showed superior progression-free survival (PFS) to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in a study by the STiL group 13...The all-oral, non-chemo, fixed-duration combination of pirtobrutinib and venetoclax has shown promise in early relapse 29.Inlate relapse, multiple agents are under active development, including second-generation BCL2 antagonists (eg, sonrotoclax), BTK degraders (eg, BGB-16673 30, NX-5948), conjugated radioisotopes (eg, iopofosine I-131 31), antibody-drug conjugates..."

IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • B2M • BCL2 • CXCR4 • MYD88 • TP53

Advances in the Management of Relapsed/Refractory CLL and Richter Transformation (ICML 2025) - P=N/A, P2, P3 | "BRUIN CLL-321 is a phase 3, registrational study that evaluated pirtobrutinib compared to the investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) [23]...Nemtabrutinib is now being evaluated in the registrational, phase 3 BELLWAVE-010 trial (NCT05947851) for patients with R/R CLL, comparing nemtabrutinib plus venetoclax to venetoclax plus rituximab...An ongoing, open-label, first-in-human phase 1/2 study is evaluating the BTK degrader BGB-16673 as monotherapy in patients with R/R CLL [27, 28]...NX-2127 is an investigational, first-in-class BTK degrader currently being evaluated in a phase 1 trial for patients with relapsed or refractory B-cell malignancies, CLL [29, 30]...NX-5948 is another investigational and more selective BTK degrader in an ongoing Phase 1a/1b clinical trial...This trial aims to establish lisaftoclax plus acalabrutinib as a potential alternative to venetoclax-based BTKi combination..."

IO biomarker • Acute Myelogenous Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Small Lymphocytic Lymphoma • BCL2L1 • TP53

Bexobrutideg (NX-5948), a Novel Bruton's Tyrosine Kinase (BTK) Degrader, Shows High Clinical Activity and Tolerable Safety in an Ongoing Phase 1a/b Study in Patients With Waldenström Macroglobulinemia (WM) (SOHO 2025) - "Bexobrutideg was well tolerated in patients with WM, consistent with the overall study population. Bexobrutideg demonstrated a notably high level of clinical activity, with a steady reduction in IgM levels and deepening responses in heavily pre-treated patients with prior BTKi exposure. Favorable outcomes were seen independent of baseline mutational status, including MYD88 and CXCR4 mutations."

Clinical • IO biomarker • P1 data • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Oncology • Waldenstrom Macroglobulinemia • BTK • CRBN • CXCR4 • MYD88

New Targets and Drugs on the Horizon in Chronic Lymphocytic Leukemia (SOHO 2025) - P1, P1/2 | "12 Treatment planning for patients with " double refractory " CLL — CLL that is resistant to a covalent BTKi and venetoclax — is a relatively novel but emerging scenario in the clinic...Noncovalent (Reversible) BTK Inhibitors In the BRUIN-321 phase 3 randomized trial of pirtobrutinib monotherapy versus the control arm of the investigator's choice between idealisib plus rituximab or bendamustine plus rituximab, pirtobrutinib had improved PFS (14 vs 8.7 months, Hazard ratio [HR] 0.54, P = 0.0002) and a superior time to next treatment or death compared to the control arm (24 vs 10.9 months, HR 0.37, P < 0.0001)...Nemtabrutinib is another noncovalent BTKi under clinical investigation, demonstrating an overall response rate (ORR) of 36.4% in CLL patients in the phase 1 study (n = 22 patients)...23,24 Thus far, data for three orally administered BTK degraders — NX-2127, NX-5948 and BGB-16673 23–25— have been presented, and there are ongoing clinical..."

IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Leukemia • Lymphoma • Oncology • CD20 • PRKCB • PRKCH • ROR1

Bexobrutideg (NX-5948), a Novel Bruton's Tyrosine Kinase Degrader, Demonstrates Rapid and Durable Clinical Responses in Relapsed/ Refractory Chronic Lymphocytic Leukemia: Updated Findings from an Ongoing Phase 1a Study (SOHO 2025) - "Bexobrutideg was well tolerated in patients, including those with longer duration of treatment and higher doses. Rapid and durable responses observed independent of prior treatment or high-risk features. Phase 1b dose expansion (200 mg and 600 mg cohorts) is underway with plans to initiate pivotal trials in 2025."

Clinical • IO biomarker • P1 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • BCL2 • BTK • CRBN • PLCG2 • TP53

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 (IWCLL 2025) - No abstract available

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

Nurix Therapeutics Reports Second Quarter 2025 Financial Results and Provides a Corporate Update (GlobeNewswire) - "Upcoming Program Highlights: Bexobrutideg (NX-5948): Building on the recent positive data in CLL and WM, Nurix anticipates providing additional clinical updates for bexobrutideg and remains on track to initiate pivotal trials for bexobrutideg in CLL in the second half of 2025. To support future development of bexobrutideg in autoimmune and inflammatory diseases, Nurix has expanded a new Phase 1b cohort for patients with CLL and autoimmune hemolytic anemia and is exploring the filing of a non-malignant hematology IND for autoimmune cytopenias in 2025."

IND • New trial • P1 data • Trial status • Autoimmune Hemolytic Anemia • Chronic Lymphocytic Leukemia • Waldenstrom Macroglobulinemia

European Medicines Agency Grants Bexobrutideg (NX-5948) Orphan Drug Designation for the Treatment of Lymphoplasmacytic Lymphoma, also Known as Waldenström Macroglobulinemia (GlobeNewswire) - "Nurix Therapeutics, Inc...announced that the European Medicines Agency (EMA) has granted Orphan Drug Designation (ODD) to bexobrutideg (NX-5948) for the treatment of lymphoplasmacytic lymphoma. Bexobrutideg is an orally bioavailable, brain penetrant degrader of Bruton’s tyrosine kinase (BTK) which is being evaluated in an ongoing Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies, including lymphoplasmacytic lymphoma, also known as Waldenström macroglobulinemia (WM)."

Orphan drug • Lymphoplasmacytic Lymphoma • Waldenstrom Macroglobulinemia

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) - "Bexobrutideg was well tolerated in pts with R/R CLL, including those with longer duration of treatment and higher doses. Bexobrutideg showed rapid and durable responses independent of prior treatment or high-risk features. Phase 1b dose expansion (200 and 600 mg cohorts) is underway with plans to initiate pivotal trials in 2025."

Clinical • IO biomarker • P1 data • Chronic Lymphocytic Leukemia • Lymphoma • BCL2 • CRBN • PLCG2 • TP53

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 • Indolent Lymphoma • Lymphoma • Lymphoplasmacytic Lymphoma • Waldenstrom Macroglobulinemia • CRBN • CXCR4 • MYD88

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

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