tilpisertib fosmecarbil (GS-5290) / Gilead - LARVOL DELTA

PALEKONA: Study of Tilpisertib Fosmecarbil in Participants With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P2 | N=176 | Active, not recruiting | Sponsor: Gilead Sciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

First-In-Human Evaluation of the Pharmacokinetics, Pharmacodynamics, and Safety of Tilpisertib Fosmecarbil (GS-5290), an Oral Prodrug of a Tumor Progression Locus 2 Inhibitor in Healthy Participants. (PubMed, J Clin Pharmacol) - P2 | "GS-4875 and TIP reduced creatinine-based estimated glomerular filtration rate (GFR; day 10 baseline-adjusted geometric least-squares means ratio [90% CI] for GS-4875/placebo: 83.3% [79.2-87.5%]); this was attributed to renal transporter inhibition rather than GFR impairment as cystatin C- and iohexol-based GFR were unchanged. These data support further development of TIP in an ongoing phase 2 trial in UC (NCT06029972)."

Clinical • First-in-human • Journal • P1 data • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis • CST3 • MAP3K8

Validation of pERK as a robust pharmacodynamic biomarker for first-in-class TPL2 inhibitors, GS-4875 and TIP, in non-clinical and clinical studies (ECCO-IBD 2026) - P2 | "GS-4875 is a highly selective, first-in-class small molecule inhibitor of TPL2, and tilpisertib fosmecarbil (TIP; GS-5290) is an intestinally cleaved prodrug of GS-4875 in development for moderately to severely active UC (NCT06029972). Given the durable and robust effect of TIP on inhibition of TPL2 pathway demonstrated in blood, and the elevated TPL2 pathway activity observed in UC and CD tissue, TPL2 inhibition represents a promising therapeutic strategy for IBD. TIP is currently in evaluation in a Phase 2 clinical trial in UC."

Biomarker • Clinical • First-in-human • PK/PD data • Crohn's disease • Inflammatory Bowel Disease • Ulcerative Colitis • MAP3K8 • TNFA

PALEKONA: Study of Tilpisertib Fosmecarbil in Participants With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P2 | N=176 | Recruiting | Sponsor: Gilead Sciences | Trial completion date: May 2027 ➔ Feb 2028 | Trial primary completion date: Apr 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

PALEKONA: Study of Tilpisertib Fosmecarbil in Participants With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P2 | N=176 | Recruiting | Sponsor: Gilead Sciences | Trial completion date: Jun 2026 ➔ May 2027 | Trial primary completion date: Jun 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

PALEKONA: Study of Tilpisertib Fosmecarbil in Participants With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P2 | N=176 | Recruiting | Sponsor: Gilead Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

PALEKONA: Study of Tilpisertib Fosmecarbil in Participants With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P2 | N=176 | Not yet recruiting | Sponsor: Gilead Sciences

New P2 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis