SRT-015 / Seal Rock Therapeutics - LARVOL DELTA

Efficacy of the apoptosis-signal-regulating kinase 1 (ASK1) inhibitor SRT-015 in in vivo and in vitro pathogen-associated molecular patterns (PAMPs)-induced disease models (EASL 2025) - "Although further experiments are needed to fully understand how SRT-015 improved survival in septic mice, it seems to be at least mediated by regulation of the innate immune response. These results further support the development of SRT-015 in advanced liver disease and ACLF."

Preclinical • Fibrosis • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Liver Failure • Septic Shock • IL1B • IL6 • MAPK8 • TLR2 • TLR4 • TNFA

INTRAVENOUS ADMINISTRATION WITH THE ASK1 INHIBITOR SRT-015 ALLEVIATES LIVER INJURY AND SYSTEMIC INFLAMMATION IN DISEASE MODELS OF LIVER FAILURE (AASLD 2024) - "These results demonstrate that i.v. SRT-015 administration alleviates liver injury and counteracts systemic inflammation in curative settings in acute liver failure models, which support its development for the treatment of patients with ACLF."

Addiction (Opioid and Alcohol) • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • IL6 • TNFA

SRT-015: Novel therapeutic for cholestatic liver diseases (EASL-ILC 2024) - "SRT-015 significantly, and dose-dependently, decreased BDL-induced fibrosis shown by multiple endpoints after 14 days of treatment in this robust model. These antifibrotic data, with previously demonstrated anti-inflammatory activity, suggests that SRT-015 is a promising therapeutic for human cholestatic liver diseases with an established safe clinical dosing regimen."

Addiction (Opioid and Alcohol) • Cholestasis • Fibrosis • Hepatology • Immunology • Liver Failure • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

SRT-015: A Second-Generation ASK1 Inhibitor for Liver Diseases Including NASH (NASH Summit-US 2023) - "Synopsis SRT-015 treatment results in direct inhibition of apoptosis, inflammation and fibrosis in vitro and in vivo Liver-selective small molecule efficacious in a chronic, therapeutic DIO-NASH preclinical model and in multiple acute liver models Demonstrated safety in Phase 1 clinical trials; ideal single or combination therapy"

Fibrosis • Hepatology • Immunology • Inflammation • Non-alcoholic Steatohepatitis

Development of physiologically based pharmacokinetic model to predict liver exposure of SRT-015, a next-generation inhibitor of apoptosis signal-regulating kinase 1 (EASL-ILC 2023) - P1 | "We have established a highly predictive PBPK model of SRT-015 exposure in human liver. The model indicates efficacious exposure in the liver with all oral doses tested in the phase 1 clinical trial in healthy participants and will help in the dose selection for Phase 2 trials. The model also indicates the feasibility to attain efficacious exposure via IV infusion, which could be a preferred administration route in ACLF patients with impaired consciousness or otherwise unable to swallow an oral drug."

PK/PD data • Addiction (Opioid and Alcohol) • CNS Disorders • Hepatology • Inflammation • Liver Failure • Non-alcoholic Steatohepatitis

SRT-015, best-in-class apoptosis signal-regulating kinase 1 inhibitor, demonstrates preclinical efficacy in acute models of liver injury (EASL-ILC 2023) - "SRT-015 treatment significantly, and dose-dependently, decreased the liver injury marker ALT in two models of acute hepatotoxicity. These data support the advancement of SRT-015 to chronic AH models and suggest that SRT-015 is a promising therapeutic for both APAP overdose and AH."

Preclinical • Addiction (Opioid and Alcohol) • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Non-alcoholic Steatohepatitis • CYP2E1

PHASE 1, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, SINGLE- AND MULTIPLE-ASCENDING DOSE STUDY OF THE SAFETY, TOLERABILITY AND PHARMACOKINETICS OF THE ASK1 INHIBITOR SRT-015 IN HEALTHY ADULTS (AASLD 2022) - "SRT-015 was well tolerated with single doses up to 640mg and repeat doses of 320mg for 7 days. Exposure achieved in the healthy volunteers exceeded that observed with efficacious doses of SRT-015 in non-clinical studies."

Clinical • P1 data • PK/PD data • Fibrosis • Hepatology • Immunology • Inflammation • Non-alcoholic Steatohepatitis • Pain

ANTI-INFLAMMATORY MECHANISMS OF NOVEL ASK1 INHIBITOR SRT-015 (AASLD 2022) - "These data demonstrate SRT-015’s anti-inflammatory MOA and target engagement in human whole blood assays and anti-inflammatory efficacy in a preclinical therapeutic model. These data support the continued advancement of SRT-015 as a possible therapeutic for liver diseases including NASH."

Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Non-alcoholic Steatohepatitis • CD14 • CD68 • CD86 • IL1B • LGALS3 • TNFA

First-in-Human Study of SRT-015 in Healthy Subjects. (clinicaltrials.gov) - P1 | N=81 | Completed | Sponsor: Syneos Health | Recruiting ➔ Completed

Trial completion • Hepatology • Non-alcoholic Steatohepatitis

First-in-Human Study of SRT-015 in Healthy Subjects. (clinicaltrials.gov) - P1; N=96; Recruiting; Sponsor: Syneos Health

Clinical • New P1 trial • Hepatology • Non-alcoholic Steatohepatitis