tilpisertib (GS-4875) / Gilead - LARVOL DELTA

Falcon: Study to Evaluate the Efficacy and Safety of Tilpisertib in Adults With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P2 | N=19 | Terminated | Sponsor: Gilead Sciences | Completed ➔ Terminated; Sponsor terminated the study since a new molecular entity was able to achieve greater target coverage

Trial termination • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Falcon: Study to Evaluate the Efficacy and Safety of Tilpisertib in Adults With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P2; N=19; Completed; Sponsor: Gilead Sciences; Active, not recruiting ➔ Completed

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

Falcon: Study to Evaluate the Efficacy and Safety of GS-4875 in Adults With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P2; N=19; Active, not recruiting; Sponsor: Gilead Sciences; Recruiting ➔ Active, not recruiting; N=180 ➔ 19; Trial completion date: Oct 2021 ➔ Feb 2022

Clinical • Enrollment change • Enrollment closed • Trial completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

APPLICATION OF A WHOLE BLOOD PHARMACODYNAMIC BIOMARKER ASSAY TO QUANTIFY TPL2 ANTAGONIST, GS-4875 IN PRE-CLINICAL RAT STUDIES (DDW 2020) - "This work describes a novel PD biomarker to monitor TPL2 inhibition in whole blood. With this assay, GS-4875 demonstrated dose-dependent and reversible inhibition of the TPL2 pathway following oral administration in healthy rats"

Biomarker Assay • PK/PD data • Gastroenterology • Gene Therapies • Genetic Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • Primary Immunodeficiency • CXCL8 • IL1B • IL6

Falcon: Study to Evaluate the Efficacy and Safety of GS-4875 in Adults With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P2; N=180; Recruiting; Sponsor: Gilead Sciences; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

GS-4875, a First-in-Class TPL2 Inhibitor Suppresses MEK-ERK Inflammatory Signaling and Proinflammatory Cytokine Production in Primary Human Monocytes (ACR-ARHP 2019) - "Background/Purpose: Tumor progression locus 2 (TPL2, also known as MAP3K8) is a mitogen-activated protein kinase kinase kinase and the primary regulator of ERK-mediated gene transcription downstream of multiple proinflammatory stimuli including bacterial products (eg, LPS and bacterial peptidoglycans), damage-associated molecular patterns (DAMPs), TNFα, and IL-1β.1 TPL2 regulates the expression of several proinflammatory cytokines, including TNFα, IL-1β, IL-6 and IL-8. This work demonstrates the selective effects of TPL2 inhibition on ERK-mediated signaling and proinflammatory cytokine production and highlights the potential for TPL2 inhibition to treat diseases associated with dysregulated inflammatory signaling and chronic inflammation."

GS-4875, A FIRST-IN-CLASS TPL2 INHIBITOR SUPPRESSES MEK-ERK INFLAMMATORY SIGNALING AND PROINFLAMMATORY CYTOKINE PRODUCTION IN PRIMARY HUMAN MONOCYTES (UEGW 2019) - "Introduction: Tumor progression locus 2 (TPL2, also known as MAP3K8) is a mitogen-activated protein kinase kinase kinase and the primary regulator of ERK-mediated gene transcription downstream of multiple proinflammatory stimuli including bacterial products (eg, LPS and bacterial peptidoglycans), damage-associated molecular patterns (DAMPs), TNFα, and IL-1β.1 TPL2 regulates the expression of several proinflammatory cytokines, including TNFα, IL-1β, IL-6 and IL-8. This work demonstrates the selective effects of TPL2 inhibition on ERK-mediated signaling and proinflammatory cytokine production and highlights the potential for TPL2 inhibition to treat IBD and other chronic inflammatory and autoimmune diseases."

Falcon: Study to Evaluate the Efficacy and Safety of GS-4875 in Adults With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P2; N=180; Not yet recruiting; Sponsor: Gilead Sciences

Clinical • New P2 trial