JNJ-6665 / J&J - LARVOL DELTA

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

Identification of isoquinolinone DHODH inhibitor isosteres. (PubMed, Bioorg Med Chem Lett) - "In a previous communication, we described our efforts leading to the discovery of compound 3 (JNJ-74856665), an orally bioavailable, potent, and selective DHODH inhibitor for clinical development...The correct positioning of the nitrogen in these core systems proved to be essential in modulating potency. Herein is described the synthesis of these complexly functionalized cores and their profiling, leading to DHODH inhibitors that possess favorable properties suitable for further development."

Journal • Acute Myelogenous Leukemia

A Study of JNJ-74856665 in Participants With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1 | N=153 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Jul 2024 ➔ Jul 2025 | Trial primary completion date: Jul 2024 ➔ Jul 2025

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • BCL2

Discovery of JNJ-74856665: A Novel Isoquinolinone DHODH Inhibitor for the Treatment of AML. (PubMed, J Med Chem) - "As a result of virtual screening and structure-based drug design approaches, a novel series of isoquinolinone DHODH inhibitors was identified. Further lead optimization afforded JNJ-74856665 as an orally bioavailable, potent, and selective DHODH inhibitor with favorable physicochemical properties selected for clinical development in patients with AML and myelodysplastic syndromes (MDS)."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

A Study of JNJ-74856665 in Participants With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1 | N=155 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Dec 2023 ➔ Jul 2024 | Trial primary completion date: Dec 2023 ➔ Jul 2024

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • BCL2

A Study of JNJ-74856665 in Participants With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1 | N=157 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Aug 2023 ➔ Dec 2023 | Trial primary completion date: Feb 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • BCL2

Discovery of JNJ 74856665: A novel Isoquinolinone DHODH inhibitor for the treatment of AML (ACS-Sp 2023) - "As a result of virtual screening and structure-based drug design approaches, a novel series of isoquinolinone DHODH inhibitors was identified. Further lead optimization afforded JNJ 74856665 as an orally bioavailable, potent and selective DHODH inhibitor with favorable physicochemical properties selected for clinical development in patients with AML and MDS."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

J&J, flush with blood cancer assets, cuts one from the pipeline (FierceBiotech) - "The company has cut JNJ-6665—a dihydroorotate dehydrogenase inhibitor—according to an updated pipeline (PDF) revised for the company’s third-quarter report on Tuesday. A spokesperson for J&J told Fierce Biotech the asset had been axed 'as part of a strategic portfolio decision.' JNJ-6665 had been in the middle of a phase 1 trial for patients with acute myeloid leukemia and myelodysplastic syndrome."

Discontinued • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

A Study of JNJ-74856665 in Participants With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1 | N=157 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Dec 2024 ➔ Aug 2023 | Trial primary completion date: Sep 2023 ➔ Feb 2023

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • BCL2

A Study of JNJ-74856665 in Participants With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1 | N=157 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Active, not recruiting | N=281 ➔ 157

Enrollment change • Enrollment closed • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • BCL2

A Study of JNJ-74856665 in Participants With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1 | N=281 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Jun 2024 ➔ Dec 2024

Trial completion date • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • BCL2

Discovery of JNJ 74856665: A Novel Isoquinolinone DHODH Inhibitor for the Treatment of AML (ACS-Sp 2022) - "As a result of virtual screening and structure-based drug design approaches, a novel series of isoquinolinone DHODH inhibitors was identified. Further lead optimization afforded JNJ 74856665 as an orally bioavailable, potent and selective DHODH inhibitor with favorable physicochemical properties selected for clinical development in patients with AML and myelodysplastic syndromes (MDS)."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

A Study of JNJ-74856665 in Participants With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1; N=281; Recruiting; Sponsor: Janssen Research & Development, LLC; N=120 ➔ 281; Trial completion date: Sep 2023 ➔ Jun 2024

Enrollment change • Trial completion date • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • BCL2

[VIRTUAL] JNJ-74856665, a novel DHODH inhibitor, mediates potent anti-leukemic activity and differentiation in vitro and in vivo (AACR 2021) - "Combination of JNJ-74856665 with azacitidine in vivo demonstrated lack of antagonism in the anti-leukemic activity.The results described herein demonstrate that JNJ-74856665 exerts potent anti-leukemic activity in vitro and in vivo and warrant further investigation. To that end, a phase 1 clinical trial assessing the safety and efficacy of JNJ-74856665 in patients with AML and MDS is planned to initiate shortly."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD14 • ITGAM

A Study of JNJ-74856665 in Participants With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1; N=120; Recruiting; Sponsor: Janssen Research & Development, LLC; Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

A Study of JNJ-74856665 in Participants With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1; N=120; Not yet recruiting; Sponsor: Janssen Research & Development, LLC

New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology