ocadusertib (LY3871801) / Rigel Pharmaceuticals - LARVOL DELTA

Ocadusertib, a Novel Oral Selective Receptor-Interacting Serine/Threonine-Protein Kinase 1 Inhibitor, Demonstrates Target Engagement but Limited Clinical Efficacy in Moderately-to-Severely Active Rheumatoid Arthritis: Results from a Phase 2a Trial (ACR Convergence 2026) - P2 | "Background/Purpose: Ocadusertib (ocadu; LY3871801; R552) is a novel, selective inhibitor of receptor-interacting serine/threonine-protein kinase (RIPK1), a regulator of inflammatory signaling downstream of TNF receptor activation implicated in synovial inflammation and tissue damage in RA... Ocadu demonstrated evidence of RIPK1 target engagement and biological activity, but consistent clinical efficacy was not observed across endpoints. Most TEAEs were mild or moderate, and no dose-limiting safety signals were identified. These findings provide important insight into RIPK1 biology in RA and may inform future therapeutic development strategies."

Clinical • P2a data • Cardiovascular • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CDK7 • CRP • RIPK1 • S100A8

An Adaptive Phase 2a/2b Study of LY3871801 in Adult Participants With Rheumatoid Arthritis (clinicaltrials.gov) - P2 | N=164 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

An Adaptive Phase 2a/2b Study of LY3871801 in Adult Participants With Rheumatoid Arthritis (clinicaltrials.gov) - P2 | N=164 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting | N=380 ➔ 164 | Trial completion date: Jul 2026 ➔ Apr 2026

Enrollment change • Enrollment closed • Trial completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

Eli Lilly ends Rigel (RIGL) RIPK1 licensing deal, no future milestones (StockTitan.net) - "Rigel Pharmaceuticals reports that Eli Lilly and Company has elected to terminate their License and Collaboration Agreement covering ocadusertib (previously R552) and other RIPK1 inhibitors. Lilly’s termination is in its entirety and becomes effective June 15, 2026....After termination, Lilly’s rights to the licensed compounds will cease, subject to transition provisions, and Rigel expects to regain full rights to these programs. Rigel is evaluating the impact of the termination and, following this step and the earlier end of the CNS disease program effective in November 2025, does not expect to receive future milestones or royalties under the agreement."

Commercial • Rheumatoid Arthritis

Early Development of Ocadusertib, a Selective Receptor-Interacting Serine/Threonine-Protein Kinase 1 Inhibitor. (PubMed, Clin Transl Sci) - "Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) inhibitors are being investigated for chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis...In a phase 1, double-blind, randomized, multiple-dose study in healthy participants, greater than 90% RIPK1 target engagement was achieved at Day 14 with ocadusertib treatment. Taken together, these findings support further assessment of ocadusertib for the treatment of chronic inflammatory diseases."

First-in-human • Journal • Dermatitis • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Arthritis • Inflammatory Bowel Disease • Oncology • Psoriasis • Rheumatoid Arthritis • Rheumatology • CDK7 • RIPK1 • TNFA

Ocadusertib: Completion of P2 trial (NCT05848258) for moderately to rheumatoid arthritis in Jul 2026 (Eli Lilly) - Q4 2025 Results

Trial completion date • Rheumatoid Arthritis

However, Rigel disclosed in its third-quarter earnings release yesterday that the biopharma received notification from Lilly in early October that the pharma is now terminating this CNS collaboration. (FierceBiotech)

Commercial • Rheumatoid Arthritis

Rigel Reports First Quarter 2025 Financial Results and Provides Business Update (Rigel Press Release) - "In late April, Rigel notified Eli Lilly and Company (Lilly) that it will not exercise its opt-in right related to the development and commercialization of ocadusertib (previously R552) for the treatment of non-central nervous system (CNS) diseases. As a result of this notification, in the second quarter of 2025, Rigel expects to recognize approximately $40.0 million in non-cash revenue resulting from the release of the remaining cost share liability currently on the balance sheet. Per the agreement with Lilly, Rigel will continue to be entitled to receive milestone and tiered royalty payments on future net sales of ocadusertib and its CNS penetrant program."

Commercial • Rheumatoid Arthritis

CDSCO Panel Approves Eli Lilly Proposal To Increase Patients Number From India 37 To 57 For LY3871801 Study (Medical Dialogues) - "The Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has approved pharmaceutical major Eli Lilly's proposal to increase the number of patients from India from 37 to 57 for phase 2a part of the study of anti-rheumatoid drug LY3871801...This came after Eli Lilly and Company presented an increase in the number of patients from India from 37 to 57 for phase 2a study Protocol No: J3P-MC-FTAF8....After detailed deliberation, the committee recommended approval of an increase in the number of patients from India from 37 to 57 for phase 2a part of the study as presented by the firm."

Trial status • Rheumatoid Arthritis

Ocadusertib: Primary completion of P2 trial (NCT05848258) for rheumatoid arthritis in Feb 2026 (Eli Lilly) - Q1 2025 Results: Completion of P2 trial for rheumatoid arthritis in Jul 2026

Trial completion date • Trial primary completion date • Rheumatoid Arthritis

Early Development of Ocadusertib, a Selective Receptor-Interacting Serine/Threonine-Protein Kinase 1 Inhibitor (ACR Convergence 2024) - "Ocadusertib (LY3871801; R552) is a potent and selective allosteric inhibitor of RIPK1 that blocks inflammatory cell death and is currently being studied in clinical trials. Preclinical studies have demonstrated ocadusertib to be a potent and selective allosteric inhibitor of RIPK1 inhibitor. In a Phase 1 study, ocadusertib had a long t1/2, was well tolerated, and had an acceptable safety profile. These findings support further assessment of ocadusertib in chronic inflammatory diseases including rheumatoid arthritis."

Dermatitis • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Psoriasis • Rheumatoid Arthritis • Rheumatology • CDK7 • RIPK1

Ocadusertib: Primary completion of P2 trial (NCT05848258) for rheumatoid arthritis in Feb 2026 (Eli Lilly) - Q2 2024 Results: Completion of P2 trial for rheumatoid arthritis in Jul 2026

Trial completion date • Trial primary completion date • Rheumatoid Arthritis

An Adaptive Phase 2a/2b Study of LY3871801 in Adult Participants With Rheumatoid Arthritis (clinicaltrials.gov) - P2 | N=380 | Recruiting | Sponsor: Eli Lilly and Company | Phase classification: P2a/2b ➔ P2 | Trial primary completion date: Jun 2024 ➔ Feb 2026

Phase classification • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

A Study of LY3871801 in Healthy Asian and Non-Asian Participants (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion

A Study of Carbon-14-Labelled [14C] LY3871801 in Healthy Male Participants (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Eli Lilly and Company | Recruiting ➔ Completed

Trial completion

A Study of LY3871801 in Healthy Asian and Non-Asian Participants (clinicaltrials.gov) - P1 | N=32 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed

An Adaptive Phase 2a/2b Study of LY3871801 in Adult Participants With Rheumatoid Arthritis (clinicaltrials.gov) - P2a/2b | N=380 | Recruiting | Sponsor: Eli Lilly and Company | Trial primary completion date: Feb 2026 ➔ Jun 2024

Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

A Study of Carbon-14-Labelled [14C] LY3871801 in Healthy Male Participants (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open

A Study of Carbon-14-Labelled [14C] LY3871801 in Healthy Male Participants (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P1 trial

A Study of LY3871801 in Healthy Asian and Non-Asian Participants (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open

A Study of LY3871801 in Healthy Asian and Non-Asian Participants (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P1 trial

An Adaptive Phase 2a/2b Study of LY3871801 in Adult Participants With Rheumatoid Arthritis (clinicaltrials.gov) - P2a/2b | N=380 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

Rigel Pharmaceuticals Provides Business Update (PRNewswire) - "R552, a potent and selective RIPK1 inhibitor, will advance into Phase 2 development in psoriasis in 1H 2022 with partner Lilly"

New P2 trial • Immunology • Psoriasis