edecesertib (GS-5718) / Gilead - LARVOL DELTA

Study of Edecesertib in Participants With Cutaneous Lupus Erythematosus (CLE) (clinicaltrials.gov) - P2 | N=33 | Recruiting | Sponsor: Gilead Sciences | Trial completion date: Dec 2024 ➔ Sep 2025 | Trial primary completion date: Dec 2024 ➔ Aug 2025

Trial completion date • Trial primary completion date • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

Study of Edecesertib in Participants With Cutaneous Lupus Erythematosus (CLE) (clinicaltrials.gov) - P1 | N=3 | Terminated | Sponsor: Gilead Sciences | Phase classification: P1b ➔ P1

Phase classification • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

Study of Edecesertib in Participants With Cutaneous Lupus Erythematosus (CLE) (clinicaltrials.gov) - P2 | N=33 | Recruiting | Sponsor: Gilead Sciences

Trial completion date • Trial primary completion date • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

Study of Edecesertib in Participants With Cutaneous Lupus Erythematosus (CLE) (clinicaltrials.gov) - P2 | N=33 | Recruiting | Sponsor: Gilead Sciences | Phase classification: P2a ➔ P2

Phase classification • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

Study of Edecesertib in Participants With Cutaneous Lupus Erythematosus (CLE) (clinicaltrials.gov) - P2a | N=33 | Recruiting | Sponsor: Gilead Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

"First disclosure of Irak-4 degrader NX-0479 / GS-6791? $GILD just paid $NRIX $20m to exercise opt-in. GS-5718 study is now marked "withdrawn" $CRIS $PFE $RIGL $KYMR" (@JacobPlieth)

IRAK4

Study of GS-5718 in Participants With Cutaneous Lupus Erythematosus (CLE) (clinicaltrials.gov) - P1b | N=3 | Terminated | Sponsor: Gilead Sciences | N=12 ➔ 3 | Suspended ➔ Terminated; Sponsor decision to terminate study.

Enrollment change • Trial termination • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

Study of GS-5718 in Participants With Cutaneous Lupus Erythematosus (CLE) (clinicaltrials.gov) - P2a | N=33 | Not yet recruiting | Sponsor: Gilead Sciences

New P2a trial • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

Study to Evaluate Safety, Tolerability, and Efficacy of GS-5718 in Participants With Active Rheumatoid Arthritis Who Have an Inadequate Response to Disease-modifying Antirheumatic Drug(s) (bDMARDs) Treatment (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Gilead Sciences | N=120 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

Study to Evaluate Safety, Tolerability, and Efficacy of GS-5718 in Participants With Active Rheumatoid Arthritis Who Have an Inadequate Response to Disease-modifying Antirheumatic Drug(s) (bDMARDs) Treatment (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Gilead Sciences | Initiation date: Dec 2021 ➔ Jul 2022

Trial initiation date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

Study of GS-5718 in Participants With Cutaneous Lupus Erythematosus (CLE) (clinicaltrials.gov) - P1b | N=12 | Suspended | Sponsor: Gilead Sciences | Recruiting ➔ Suspended

Trial suspension • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

Study to Evaluate Safety, Tolerability, and Efficacy of GS-5718 in Participants With Active Rheumatoid Arthritis Who Have an Inadequate Response to Disease-modifying Antirheumatic Drug(s) (bDMARDs) Treatment (clinicaltrials.gov) - P2; N=120; Not yet recruiting; Sponsor: Gilead Sciences

Clinical • New P2 trial • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

[VIRTUAL] The Clinical, Oral Small Molecule IRAK4 Inhibitor, GS-5718, Improves Survival and Reduces Disease Pathologies by Modulating Multiple Inflammatory Endpoints in the Murine NZB/W Model of Spontaneous Lupus (ACR-CONVERGENCE 2021) - "Current standard of care treatments, including methotrexate, cyclophosphamide, mycophenolate mofetil, and blockers of B-cell activating factor (BAFF) have demonstrated efficacy (e.g. improved survival and/or clinical pathologies) in this model2,3. GS-5718 treatment showed statistically significant improvements in survival and disease progression in a murine NZB/W spontaneous lupus model accompanied by improvements in pharmacodynamic inflammatory endpoints. These results suggest a pathological role for IRAK4 signaling in a pre-clinical mouse lupus model and supports further evaluation of GS-5718 for therapeutic intervention in lupus patients."

IO biomarker • Preclinical • Immunology • Inflammatory Arthritis • Lupus • Renal Disease • Rheumatology • IRAK4 • TLR7 • TLR9

[VIRTUAL] Phase 1 Study Results of GS-5718, an Oral IRAK4-Inhibitor: Pharmacodynamics of Single and Multiple Doses of GS-5718 in Healthy Subjects (ACR-CONVERGENCE 2021) - "GS-5718, administered once daily, resulted in significant and sustained inhibition of ex-vivo stimulated secretion of TNF-α, the main PD biomarker. The PD profile of GS-5718 supports once daily dosing and further development in patients with RA and LE."

Clinical • IO biomarker • P1 data • PK/PD data • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Rheumatoid Arthritis • Rheumatology • IRAK4 • TLR7 • TNFA

Study of GS-5718 in Participants With Cutaneous Lupus Erythematosus (CLE) (clinicaltrials.gov) - P1b; N=12; Recruiting; Sponsor: Gilead Sciences; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

[VIRTUAL] FIRST-IN-HUMAN STUDY OF GS-5718, AN ORAL IRAK-4 INHIBITOR, IN HEALTHY SUBJECTS: PHARMACOKINETICS, SAFETY, TOLERABILITY, AND ASSESSMENT OF EFFECT OF FOOD AND ACID REDUCING AGENTS ON EXPOSURE (EULAR 2021) - "The effects of a high-fat meal and omeprazole (a representative ARA) on GS-5718 50 mg dose pharmacokinetics were also evaluated. GS-5718, administered once daily, was well tolerated following single or multiple dosing up to 150 mg. The pharmacokinetic and safety profile of GS-5718 support the further development in inflammatory diseases with once-daily administrations."

Clinical • P1 data • PK/PD data • Inflammation • IRAK4

Study of GS-5718 in Participants With Cutaneous Lupus Erythematosus (CLE) (clinicaltrials.gov) - P1b; N=12; Not yet recruiting; Sponsor: Gilead Sciences

Clinical • New P1 trial • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus