JNJ-4681 / J&J - LARVOL DELTA

A Rollover Study for Continued Study Treatment and Ongoing Safety Monitoring (clinicaltrials.gov) - P1 | N=120 | Enrolling by invitation | Sponsor: Janssen Research & Development, LLC | N=52 ➔ 120

Enrollment change • Acute Myelogenous Leukemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer • Solid Tumor

A Rollover Study for Continued Study Treatment and Ongoing Safety Monitoring (clinicaltrials.gov) - P1 | N=52 | Enrolling by invitation | Sponsor: Janssen Research & Development, LLC | N=35 ➔ 52

Enrollment change • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Rollover Study for Continued Study Treatment and Ongoing Safety Monitoring (clinicaltrials.gov) - P1 | N=120 | Enrolling by invitation | Sponsor: Janssen Research & Development, LLC | N=80 ➔ 120

Enrollment change • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Rollover Study for Continued Study Treatment and Ongoing Safety Monitoring (clinicaltrials.gov) - P1 | N=80 | Enrolling by invitation | Sponsor: Janssen Research & Development, LLC | Trial completion date: Jan 2028 ➔ Oct 2028

Trial completion date • Acute Myelogenous Leukemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer • Solid Tumor

Challenges and innovative solutions for kinase inhibitor discovery in immunology (ACS-Fall 2025) - "The discovery and profiling of a GI-restricted JAK inhibitor clinical candidate, JNJ-64251330, for treating IBD will be discussed.Covalent inhibition of kinases by targeting a unique cysteine residue can achieve selectivity versus kinases that that do not have an analogous nucleophile. Bruton's tyrosine kinase (BTK) is a therapeutic target for B-cell malignancies and has potential for treating autoimmune diseases. We identified a highly selective covalent BTK inhibitor clinical candidate JNJ-64264681 that has advanced into human clinical studies."

Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Immunology • Inflammatory Bowel Disease

A Study of JNJ-64264681 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1 | N=85 | Completed | Sponsor: Janssen Research & Development, LLC | Active, not recruiting ➔ Completed

Trial completion • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1 | N=75 | Completed | Sponsor: Janssen Research & Development, LLC | Active, not recruiting ➔ Completed | Trial completion date: Apr 2025 ➔ Jan 2025 | Trial primary completion date: Apr 2025 ➔ Jan 2025

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

A Rollover Study for Continued Study Treatment and Ongoing Safety Monitoring (clinicaltrials.gov) - P1 | N=80 | Enrolling by invitation | Sponsor: Janssen Research & Development, LLC

New P1 trial • Acute Myelogenous Leukemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Castration-Resistant Prostate Cancer • Chronic Lymphocytic Leukemia • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer • Solid Tumor

A Study of JNJ-64264681 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1 | N=85 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Dec 2026 ➔ Apr 2025 | Trial primary completion date: Apr 2026 ➔ Apr 2025

Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1 | N=75 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Dec 2026 ➔ Jul 2025

Combination therapy • Trial completion date • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1 | N=75 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Jul 2025 ➔ Dec 2026

Combination therapy • Trial completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of JNJ-64264681 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1 | N=85 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Apr 2026 ➔ Dec 2026

Trial completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of JNJ-64264681 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1 | N=85 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Apr 2025 ➔ Apr 2026

Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1 | N=75 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Jul 2024 ➔ Jul 2025

Combination therapy • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1 | N=75 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Phase classification: P1b ➔ P1

Combination therapy • Phase classification • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1b | N=75 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Apr 2026 ➔ Jul 2025

Combination therapy • Trial completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of JNJ-64264681 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1 | N=85 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2025 ➔ Apr 2026

Enrollment closed • Trial completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1b | N=75 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Dec 2024 ➔ Apr 2026

Combination therapy • Trial completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Phase 1 First-in-Human Pharmacokinetic and Pharmacodynamic Study of JNJ-64264681, a Covalent Inhibitor of Bruton's Tyrosine Kinase. (PubMed, Clin Pharmacol Drug Dev) - "JNJ-64264681 showed no safety signals of concern. Overall, safety, tolerability, PK, BTKO, and PK/PD modeling guided the rationale for dose selection for the subsequent first-in-patient lymphoma studies."

Journal • P1 data • PK/PD data • Hematological Malignancies • Lymphoma • Oncology

A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1b | N=75 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Dec 2023 ➔ Jul 2024

Combination therapy • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of JNJ-64264681 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1 | N=85 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Dec 2024 ➔ Apr 2025

Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

[VIRTUAL] DISCOVERY AND PRECLINICAL PROPERTIES OF JNJ-64264681, A POTENT AND SELECTIVE COVALENT BTK INHIBITOR FOR THE TREATMENT OF B CELL MALIGNANCIES (EHA 2021) - P1, P1b | "BTK inhibitors have been widely studied in B-cell hematologic malignancies and 3 inhibitors, including the first-in-class BTK inhibitor ibrutinib, are currently approved. Conclusion The preclinical results confirm that JNJ-64264681 is a highly selective and potent BTK inhibitor and provide proof-of-concept for human trials in patients with B cell malignancies driven by the classical NF-κB pathway. JNJ-64264681 is currently in human clinical trials (NCT04210219 and NCT04657224) as single agent to establish dose and pharmacokinetics and to evaluate efficacy in combination with the first-in-class MALT1 inhibitor JNJ-67856633."

Preclinical • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • CD79B • MALT1

A Study of JNJ-64264681 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1 | N=85 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Dec 2024 ➔ Apr 2025

Trial completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Discovery of JNJ-64264681: A Potent and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. (PubMed, J Med Chem) - "We report the discovery and preclinical properties of JNJ-64264681 (13), a covalent, irreversible BTK inhibitor with potent whole blood activity and exceptional kinome selectivity. JNJ-64264681 demonstrated excellent oral efficacy in both cancer and autoimmune models with sustained in vivo target coverage amenable to once daily dosing and has advanced into human clinical studies to investigate safety and pharmacokinetics."

Journal • Hematological Disorders • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lupus • Oncology • Rheumatoid Arthritis • Rheumatology • Systemic Lupus Erythematosus

A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1b | N=75 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Jul 2024 ➔ Dec 2023

Combination therapy • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology