bexobrutideg (RG6191) / Nurix Therap, Roche - LARVOL DELTA

Study of NX-5948 in Combination With Other Agents in Adults With B-cell Malignancies (clinicaltrials.gov) - P1/2 | N=150 | Recruiting | Sponsor: Nurix Therapeutics, Inc. | Not yet recruiting ➔ Recruiting | Initiation date: May 2026 ➔ Aug 2026

Enrollment open • Trial initiation date • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Discovery of BTK degraders for the treatment of B-cell malignancies (ACS-Fall 2026) - "Covalent BTK inhibitors (e.g., ibrutinib, acalabrutinib) have demonstrated efficacy across diseases including CLL, MCL, MZL, and WM, but long-term benefit is frequently limited by resistance mutations, most commonly at BTKC481, that abrogate covalent binding and drive progression, and additional mutations may also reduce the activity of emerging noncovalent inhibitors, such as pirtobrutinib. Together, these data support BTK degraders as a promising modality to overcome BTK inhibitor resistance and broaden therapeutic impact, including in CNS disease. This presentation will describe the discovery of NX-2127 and NX-5948, pre-clinical characterization and translation to clinical effects in lymphoma and leukemia patients."

Chronic Lymphocytic Leukemia • CNS Disorders • Hematological Malignancies • Leukemia • Lymphoma • Marginal Zone Lymphoma • Oncology • Targeted Protein Degradation • CRBN • IKZF1 • IKZF3

Molecular and Structural Basis of Pan-Resistance to BTK Degraders and Inhibitors. (PubMed, Cancer Discov) - "Here we sequenced serial CLL samples from patients enrolled in the phase I trials of zelebrudomide and bexobrutideg and observed recurrent expansion of preexisting BTK A428D mutations at relapse. Combining BTK degraders with venetoclax mitigated the expansion of BTK A428D. These results provide the molecular basis for clinical resistance to BTK degraders and will inform the development of next-generation BTK degrader therapies."

Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

DAYBreak CLL-306: A Phase 3 Randomized Open-Label Trial of the Novel Bruton Tyrosine Kinase Degrader Bexobrutideg (NX-5948) vs Pirtobrutinib in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (SOHO 2026) - P1, P3 | "Enrollment is planned to open in July 2026. BTK: Bruton tyrosine kinase; BTKi: Bruton tyrosine kinase inhibitor; CLL: chronic lymphocytic leukemia; ECOG PS: Eastern Cooperative Oncology Group performance status; IRC: independent review committee; iwCLL: International Workshop on Chronic Lymphocytic Leukemia; PFS: progression-free survival; SLL: small lymphocytic lymphoma; TP53; tumor protein p53 gene."

Clinical • P3 data • B Cell Lymphoma • Chronic Lymphocytic Leukemia • CNS Lymphoma • Leukemia • Lymphoma • Oncology • Prolymphocytic Leukemia • Richter's Syndrome • Small Lymphocytic Lymphoma • BCL2 • BTK • TP53

Efficacy and Safety of the Bruton's Tyrosine Kinase (BTK) Degrader NX-5948 in Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL): Updated Results from an Ongoing Phase 1a/b Study (ASH 2024) - "Prior therapies : BTKi (97.1%), pirtobrutinib (23.5%), BCL2i (91.2%), BTKi + BCL2i (88.2%), chemo/chemoimmunotherapy (79.4%), PI3Ki (32.4%), CAR-T (5.9%). Responses observed in pts with PLCG2 mutations support a mechanism whereby NX-5948 disrupts the BTK signaling complex, potentiating broader targeting of oncogenic pathways downstream of BTK. The Phase 1b dose-expansion portion of the study is underway; data from additional pts are expected for the presentation."

Clinical • IO biomarker • P1 data • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Fatigue • Hematological Disorders • Hematological Malignancies • Hypertension • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pulmonary Embolism • Respiratory Diseases • Targeted Protein Degradation • Thrombocytopenia • BCL2 • BTK • CRBN • PLCG2 • TP53

Updated Efficacy and Safety Data From an Ongoing Phase 1a/b Trial of the Bruton's Tyrosine Kinase Degrader Bexobrutideg (NX-5948) in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Across Lines of Therapy (SOHO 2026) - P1, P2 | "Bexobrutideg is being evaluated in the Ph2 DAYBreak-201 study (NCT07221500), and a Ph3 DAYBreak-306 study investigating bexobrutideg vs pirtobrutinib is planned. BCL2i: B-cell leukemia/lymphoma 2 inhibitor, BTKi: Bruton's tyrosine kinase inhibitor, CLL: chronic lymphocytic leukemia, ORR: objective response rate, SLL: small lymphocytic lymphoma."

Clinical • First-in-human • P1 data • Tumor mutational burden • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • BCL2 • BTK • TMB

Study of NX-5948 Versus Pirtobrutinib in R/R CLL/SLL (clinicaltrials.gov) - P3 | N=620 | Recruiting | Sponsor: Nurix Therapeutics, Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Jun 2032 ➔ Aug 2033

Enrollment open • Trial completion date • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

LATEST RESULTS FROM AN ONGOING FIRST-IN-HUMAN PHASE 1A/B STUDY OF NX-5948, A SELECTIVE BRUTON’S TYROSINE KINASE (BTK) DEGRADER, IN PATIENTS WITH RELAPSED/REFRACTORY CLL AND OTHER B-CELL MALIGNANCIES (EHA 2024) - "Preliminary findings from this ongoing first-in-human study of NX-5948 demonstrate a tolerable safety profileacross B-cell malignancies. Deep clinical responses were observed in a heavily pre-treated population of ptswith CLL and NHL, some with BTKi resistance mutations, high-risk molecular features, and CNS involvement. These data suggest a role for NX-5948 in the CLL treatment landscape and warrant its continued investigationin NHL, including subtypes where BTKi may not be sufficient."

Clinical • IO biomarker • P1 data • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • Thrombocytopenia • BTK • CRBN • PLCG2 • TP53

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 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 chronic lymphocytic leukemia (CLL): New and updated findings from an ongoing Phase 1a/b trial (ASH 2025) - "In the largest Ph1a/b cohort of pts with relapsed/refractory CLL treated with bexobrutidegreported to date, bexobrutideg was well tolerated across dose levels and treatment durations.Bexobrutideg showed rapid and durable responses in a heavily pre-treated population of pts with CLL,including those with baseline BTK mutations and high-risk molecular features. Additional follow-up andpreliminary results from the 200 mg vs 600 mg randomized dose-expansion cohorts will be presented."

Clinical • IO biomarker • P1 data • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Pneumonia • Respiratory Diseases • Septic Shock • Targeted Protein Degradation • Thrombocytopenia • BTK • CRBN • PLCG2 • TP53

BGB-16673, a Potent BTK Degrader in Human Blood and Cancer Cell Lines, Shows High Selectivity in Both Proteomics and Kinome Panel Analysis (SOHO 2026) - "BGB-16673 is a potent BTK degrader with high selectivity across key blood cell types by proteomic profiling. Both degraders reduce TEC in platelets, while BGB-16673 shows markedly higher selectivity of kinase inhibitions than NX-5948. The clinical relevance of these selectivity profiles warrants further validation."

Preclinical • Hematological Malignancies • Lymphoma • Oncology

Daybreak CLL-201: A Study of Bexobrutideg (NX-5948), a Bruton Tyrosine Kinase Degrader, in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Previously Treated With a Covalent BTK Inhibitor, a Noncovalent BTK Inhibitor, and a BCL2 Inhibitor (SOHO 2026) - P1, P2 | "Safety, pharmacokinetics, and health-related quality of life will also be evaluated. Enrollment is under way, and the study is expected to recruit approximately 100 patients globally."

Clinical • IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • CNS Lymphoma • Leukemia • Lymphoma • Oncology • Prolymphocytic Leukemia • Richter's Syndrome • Small Lymphocytic Lymphoma • BCL2 • CRBN

An ongoing first-in-human phase 1 trial of NX-5948, an oral Bruton’s tyrosine kinase (BTK) degrader, in patients with relapsed/refractory B cell malignancies, including chronic lymphocytic leukemia (CLL) (IWCLL 2023) - P1 | "Approximately 110 patients (30 in phase 1a, 80 in phase 1b) may be enrolled and treated until confirmed progression or unacceptable toxicity. Enrollment in the phase 1a portion of this study is underway in the UK and the US, and is anticipated to begin in the Netherlands in 2023."

Clinical • P1 data • Chronic Lymphocytic Leukemia • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Waldenstrom Macroglobulinemia • BTK • CRBN

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

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, shows high clinical activity and tolerable safety in patients with Waldenström macroglobulinemia: Updated results from an ongoing Phase 1a/b study (ASH 2025) - "Bexobrutideg was well tolerated in patients with WM, consistent with previous disclosuresin the overall study population. Bexobrutideg demonstrated a notably high level of clinical activity withsteady reduction in IgM levels and deepening responses over time in heavily pre-treated patients (all ofwhom had prior cBTKi exposure), and in patients whose tumors had MYD88 and CXCR4 mutations.Bexobrutideg Phase 1b dose expansion is underway."

Clinical • IO biomarker • P1 data • Chronic Lymphocytic Leukemia • CNS Disorders • Hematological Malignancies • Infectious Disease • Influenza • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Respiratory Diseases • Targeted Protein Degradation • Waldenstrom Macroglobulinemia • BTK • CRBN • CXCR4 • MYD88

UPDATED EFFICACY AND SAFETY DATA FROM AN ONGOING PHASE 1A/B TRIAL OF THE BTK DEGRADER BEXOBRUTIDEG (NX-5948) IN PATIENTS WITH CLL ACROSS LINES OF THERAPY (EHA 2026) - P1, P2 | "High response rates were observed across populations with different prior therapies, including in pts previously treated with BTKi and in BTKi-naïve pts, supporting further clinical development. Bexobrutideg is being evaluated in the Ph2 DAYBreak-201 study (NCT07221500) and a Ph3 DAYBreak-306 study investigating bexobrutideg vs pirtobrutinib is planned."

Clinical • First-in-human • P1 data • Tumor mutational burden • Chronic Lymphocytic Leukemia • Hematological Malignancies • Neutropenia • Targeted Protein Degradation • CRBN • TMB

Nurix Therapeutics…announced that the first patient has been enrolled in the global Phase 3 DAYBreak CLL-306 study (NCT07516093) evaluating bexobrutideg…in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have previously received a covalent BTK inhibitor (GlobeNewswire) - "The global study is being conducted under the collaboration between Nurix and Roche and marks the first Phase 3 trial for bexobrutideg....The randomized Phase 3 trial is expected to enroll approximately 620 patients with relapsed/refractory CLL/SLL who have previously progressed on a covalent BTK inhibitor. Patients will be randomized 1:1 to receive either bexobrutideg 600 mg orally once per day or pirtobrutinib."

Enrollment open • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

A Single and Multiple Ascending Doses, Relative Bioavailability, Food Effect, and Drug-Drug Interaction Study of NX-5948 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=223 | Completed | Sponsor: Nurix Therapeutics, Inc. | Recruiting ➔ Completed | N=18 ➔ 223 | Trial completion date: Aug 2026 ➔ May 2026

Enrollment change • Trial completion • Trial completion date

Bexobrutideg: Regulatory submissions in US/EU for r/r CLL in 2029 and beyond (Roche) - H1 2026 Results

EMA filing • FDA filing • Chronic Lymphocytic Leukemia • Hematological Malignancies • Oncology

Nurix Therapeutics…announced the closing of its previously announced global collaboration agreement with Roche to co-develop and co-commercialize bexobrutideg, following expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 (GlobeNewswire) - "Under the terms of the agreement, Nurix will receive an upfront cash payment of $700 million and is eligible to receive development, regulatory and sales milestones for potential total payments of up to $2.3 billion. Development costs will be shared 40% by Nurix and 60% by Roche. The parties will equally split the profits and losses from U.S. commercialization. Nurix and Roche will co-commercialize bexobrutideg in the United States across all indications. Outside of the United States, Roche will be responsible for commercialization, with Nurix eligible to receive royalties ranging from the low- to high-teens. Nurix and Roche will jointly advance a broad clinical development program for bexobrutideg, including ongoing and planned studies in chronic lymphocytic leukemia (CLL), additional B-cell malignancies, multiple sclerosis (MS) and chronic spontaneous urticaria (CSU)."

Licensing / partnership • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Chronic Spontaneous Urticaria • Multiple Sclerosis

Expansion of Bexobrutideg Development into Immunology and Neurology (Nurix Press Release) - "Continued advancement of a healthy volunteer SAD/MAD study evaluating the new tablet formulation of bexobrutideg to support potential future development in immunology and neurology indications with planning underway for the initiation of Phase 2 trials in CSU and MS."

New P2 trial • Chronic Spontaneous Urticaria • Immunology • Multiple Sclerosis

Bexobrutideg Clinical Data Presented at EHA 2026 (Nurix Press Release) - "Updated Phase 1a results demonstrated: Median progression-free survival of 22.1 months; Objective response rate (ORR) of 83%; Responses observed across difficult-to-treat patient populations, including patients with BTK resistance mutations, high-risk molecular features and central nervous system involvement...New Phase 1b results demonstrated: ORR of 92.9% among evaluable patients with 18 of 19 patients remaining on treatment at data cutoff in Cohort; 5, evaluating patients previously treated with a BTK inhibitor but naïve to BCL2 inhibitor therapy ORR of 84.2% among evaluable patients with 19 of 20 patients remaining on treatment at data cutoff in Cohort 15, evaluating BTKi-naïve patients including treatment-naïve patients."

P1 data • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

Selective Degradation of Bruton's Tyrosine Kinase in Human Platelets Reveals a Signalling-Centric Strategy for Anti-thrombotic Therapy (ISTH 2026) - "Methods Human platelets were treated with two cereblon-recruiting BTK degraders NX-2127 and NX-5948 and BTK/TEC levels were assessed by immunoblotting. These findings establish protein degradation as a mechanistically precise strategy for platelet modulation and support BTK-directed PROTACs as a rational platform for next-generation anti-thrombotic therapy. Table or Figure Upload (1) Page 2 Table or Figure Upload (2) DOI*10.1016/j.rpth.2026.103597"

B Cell Lymphoma • Cardiovascular • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Targeted Protein Degradation • Thrombosis • BTK • CRBN • PLCG2 • PLEK • SYK