lorpucitinib (JNJ-64251330) / J&J - LARVOL DELTA

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 Phase 1, Randomized, Multi-Dose Study to Evaluate the Enteric Selectivity and Safety of JAK Inhibitor, Lorpucitinib, in Healthy Participants. (PubMed, Clin Pharmacol Ther) - P1 | "In Part 1, 24 participants were randomized to one of four treatment arms receiving either lorpucitinib (30 mg daily, 30 mg every 12 hours [Q12H], or 75 mg Q12H) or tofacitinib (5 mg Q12H) for 5 days. In Part 2, lorpucitinib plasma concentrations were detectable but at low levels, with no statistical differences in PK parameters between the fed and fasted groups. Lorpucitinib was safe and well tolerated, and the data may be useful in designing studies to evaluate lorpucitinib in patients with JAK/STAT-driven gastrointestinal diseases."

Journal • P1 data • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Psoriasis • Rheumatoid Arthritis • Rheumatology • STAT3

Lorpucitinib (JNJ-64251330) in patients with familial adenomatous polyposis (FAP): Results from a phase 1b study. (ASCO 2023) - P1b | "These results show that lorpucitinib had no clear effect on polyp burden. The study found that lorpucitinib is safe and exhibits an enteric-selective distribution in FAP patients. Inhibition of JAK tyrosine kinase signaling was associated with reduced STAT-3 phosphorylation in mucosal biopsies from FAP patients."

Clinical • P1 data • Cardiovascular • Colon Cancer • Colonic Polyps • Colorectal Cancer • Gastrointestinal Cancer • Genetic Disorders • Infectious Disease • Oncology • Pain • Solid Tumor • Venous Thromboembolism • APC • CRP

A Study of JNJ-64251330 in Participants With Familial Adenomatous Polyposis (clinicaltrials.gov) - P1b | N=42 | Completed | Sponsor: Janssen Research & Development, LLC | Active, not recruiting ➔ Completed | Trial completion date: Oct 2024 ➔ Feb 2023

Trial completion • Trial completion date • Colon Cancer • Genetic Disorders • Solid Tumor • APC • STAT3

A Study of JNJ-64251330 in Participants With Familial Adenomatous Polyposis (clinicaltrials.gov) - P1b | N=42 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Colon Cancer • Genetic Disorders • Solid Tumor • APC • STAT3

A Study of JNJ-64251330 in Participants With Familial Adenomatous Polyposis (clinicaltrials.gov) - P1b | N=40 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: May 2024 ➔ Oct 2024

Trial completion date • Colon Cancer • Genetic Disorders • Solid Tumor • APC • STAT3

A Study of JNJ-64251330 in Participants With Familial Adenomatous Polyposis (clinicaltrials.gov) - P1b | N=40 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Jun 2023 ➔ May 2024

Trial completion date • Colon Cancer • Genetic Disorders • Solid Tumor • APC • STAT3

A Study of JNJ-64251330 in Participants With Familial Adenomatous Polyposis (clinicaltrials.gov) - P1b; N=40; Recruiting; Sponsor: Janssen Research & Development, LLC; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Genetic Disorders • APC • STAT3

A Study of JNJ-64251330 in Participants With Familial Adenomatous Polyposis (clinicaltrials.gov) - P1b; N=40; Not yet recruiting; Sponsor: Janssen Research & Development, LLC

Clinical • New P1 trial • Genetic Disorders • APC • STAT3

A Study of JNJ-64251330 in Healthy Participants (clinicaltrials.gov) - P1; N=36; Completed; Sponsor: Janssen Research & Development, LLC; Active, not recruiting ➔ Completed

Clinical • Trial completion

A Study of JNJ-64251330 in Healthy Participants (clinicaltrials.gov) - P1; N=36; Active, not recruiting; Sponsor: Janssen Research & Development, LLC; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed