netazepide (YF476) / Trio Medicines - LARVOL DELTA

Randomized controlled trial of an oral Gastrin Receptor Antagonist for the treatment of postmenopausal osteoporosis. (PubMed, J Bone Miner Res) - "Based on this study it appears that short term gastrin receptor antagonism is unlikely to be a successful strategy in the prevention of osteoporosis. However, this a preliminary exploration of a novel hypothesis and larger studies might be needed."

Clinical • Journal • Gastrointestinal Disorder • Hematological Disorders • Osteoporosis • Rheumatology

A cholecystokinin 2 receptor antagonist alleviates seizure severity in a mouse and miniature pig model of temporal lobe epilepsy. (PubMed, Epilepsy Behav) - "Administration of CCK-2 receptor antagonist YF476 significantly suppressed convulsive seizure frequency during and post-treatment in TLE mice and was also effective in alleviating the frequency of severe and mild seizures in TLE miniature pigs when compared with phenytoin and carbamazepine. This study reveals a novel strategy for treating TLE and it provides the possibility of YF476 being adopted as a new anti-seizure drug."

Journal • Preclinical • CNS Disorders • Epilepsy

Gastrin: a new branch of the gastropancreatic axis that can explain the effect of sleeve gastrectomy on glucose metabolism. (PubMed, J Gastrointest Surg) - "Gastrin plays a central role in glucose improvement after SG. It stimulates a medium-term strong insulin response but also causes long-term beta-cell mass depletion and a loss of insulin response. These effects are prevented by gastrin antagonists such as netazepide."

Journal • Diabetes • Gastrointestinal Disorder • Metabolic Disorders • Type 2 Diabetes Mellitus • GAST

Trial of a Gastrin Receptor Antagonist in Barrett's Esophagus (clinicaltrials.gov) - P2; N=27; Completed; Sponsor: Columbia University; N=20 ➔ 27

Clinical • Enrollment change • Barrett Esophagus • Gastrointestinal Disorder

YF476 in Barrett's Esophagus (clinicaltrials.gov) - P2; N=27; Completed; Sponsor: Trio Medicines Ltd.; Enrolling by invitation ➔ Completed

Trial completion • Barrett Esophagus • Gastrointestinal Disorder

Potential clinical indications for a CCK2 receptor antagonist. (PubMed) - Curr Opin Pharmacol - "Netazepide and Z-360 are currently undergoing clinical development, for treatment of gastric neuroendocrine tumours and pancreatic cancer, respectively. There are several other potential indications for a CCK2RA and an unmet need."

Journal • Review • Biosimilar • Gastrointestinal Cancer • Oncology • Pancreatic Cancer

Netazepide Inhibits Expression of Pappalysin 2 in Type-1 Gastric Neuroendocrine Tumors. (PubMed, Cell Mol Gastroenterol Hepatol) - "In an analysis of human gNETS and mice, we found that gastrin upregulates expression of gastric PAPPA2. Increased PAPPA2 alters IGF bioavailability, cell migration, and tissue remodeling, which are involved in type-1 gNET development. These effects are inhibited by netazepide."

Journal • GAST • IGFBP3

Targeting cholecystokinin-2 receptor for pancreatic cancer chemoprevention. (PubMed, Mol Carcinog) - "Overall, JNJ-26070109 showed better chemopreventive efficacy than YF476. However, caution is recommended when selecting doses, as the agents appeared to exhibit gender-specific effects."

Journal

YF476 and Type I Gastric Carcinoids (clinicaltrials.gov) - P2; N=8; Completed; Sponsor: Trio Medicines Ltd.; Active, not recruiting ➔ Completed

Clinical • Trial completion

YF476 and Type II Gastric Carcinoids (clinicaltrials.gov) - P2; N=3; Terminated; Sponsor: Trio Medicines Ltd.; N=30 ➔ 3; Enrolling by invitation ➔ Terminated; Poor recruitment

Clinical • Enrollment change • Trial termination

Targeting cholecystokinin-2 receptor (CCK2R) for pancreatic ductal adenocarcinoma prevention in p48Cre/+-LSL-KrasG12D/+ mice model (AACR 2019) - "...Two CCK2R antagonists, netazepide (YF476) and JNJ-26070109, were tested for their effect on PanINs and their progression to PDAC in p48Cre/+-LSL-KrasG12D/+ mice...However, caution is recommended while selecting the doses as the agents appeared to exhibit gender-specific effects. [Supported by NCICN25001-26}"

Preclinical

Trial of a Gastrin Receptor Antagonist in Barrett's Esophagus (clinicaltrials.gov) - P2; N=20; Completed; Sponsor: Julian A Abrams, MD; Active, not recruiting ➔ Completed; Trial completion date: Jun 2018 ➔ Dec 2017

Clinical • Trial completion • Trial completion date