PRL-2903 / Zucara Therapeutics - LARVOL DELTA

Evaluating the effectiveness of a novel somatostatin receptor 2 antagonist, ZT-01, for hypoglycemia prevention in a rodent model of type 2 diabetes. (PubMed, Front Pharmacol) - " High-fat fed (HFF), low dose streptozotocin (STZ, 35 mg/kg)-induced T2D and HFF only, nondiabetic (controls-no STZ) rats were treated with the SSTR2 antagonists ZT-01/PRL-2903 or vehicle (n = 9-11/group) 60 min before an insulin tolerance test (ITT; 2-12 U/kg insulin aspart) or an oral glucose tolerance test (OGTT; 2 g/kg glucose via oral gavage) on separate days. Treatment with SSTR2 antagonists increases glucagon responses in a rat model of T2D and results in less hypoglycemia exposure. Future studies are required to determine the best dosing periods for chronic SSTR2 antagonism treatment in T2D."

Journal • Preclinical • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus • SSTR • SSTR2

ZT-01 - A Novel Somatostatin Receptor Antagonist for Restoring the Glucagon Response to Hypoglycemia in Type 1 Diabetes. (PubMed, Diabetes Obes Metab) - "We conclude that ZT-01 may be effective in restoring glucagon responses and preventing the onset of hypoglycemia in patients with T1D."

Journal • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus • SSTR • SSTR2

Transdermal delivery of a somatostatin receptor type 2 antagonist using microneedle patch technology for hypoglycemia prevention. (PubMed, Drug Deliv Transl Res) - "Herein, we aimed to develop a microneedle (MN) patch for transdermal delivery of a peptide (PRL-2903) that antagonizes somatostatin receptor type 2 (SSTR2) in α-cells...The proposed MN patch is the first demonstration of a transdermal microneedle patch designed to deliver an SSTR2 antagonist for the prevention of hypoglycemia. This counter-regulatory peptide delivery system may be applied alongside with insulin delivery systems to provide a more effective and safer treatment for people with insulin-dependent diabetes."

Journal • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus • SSTR

[VIRTUAL] Subcutaneous Administration of the Novel Somatostatin Receptor 2 Antagonist ZT-01 Restores the Glucagon Response to Hypoglycemia in STZ-Diabetic Rats to Normal Levels (ADA 2020) - "We previously demonstrated that a novel SSTR2 antagonist, ZT-01, exhibited superior efficacy at restoring the glucagon response to hypoglycemia compared to an established SSTR2 antagonist, PRL-2903, when given intraperitoneally at a dose of 10 mg/kg...The glucagon response in this dose range was comparable to that observed in nondiabetic rats administered vehicle. We therefore conclude that ZT-01 at doses ranging from 0.3 to 1 mg/kg normalized the glucagon response to hypoglycemia in STZ-diabetic rats and may be an effective compound for the prevention hypoglycemia in patients with T1D."

Late-breaking abstract • Preclinical • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

[VIRTUAL] Novel Somatostatin Receptor 2 Antagonist ZT-01 Prevents Hypoglycemia Onset in STZ-Diabetic Rats by Improving Glucagon Secretion (ADA 2020) - "ZT-01 administration increased glucagon peak by 4-fold over the response to PRL-2903 (P<0.05). We conclude that ZT-01 may be an effective compound that can be used for the restoration of the glucagon response to hypoglycemia in patients with T1D."

Late-breaking abstract • Preclinical • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Somatostatin Receptor 2 Antagonism Enhances Plasma Glucagon Levels during Insulin-Induced Hypoglycemia in a Rodent Model of Type 2 Diabetes Mellitus (ADA 2019) - "Rats were then divided into SSTR2a treatment (PRL-2903, 10 mg/kg) or vehicle (n=9 for each) 1-hour before insulin-induced hypoglycemia (3 IU/kg NovoRapid). Compared with vehicle treatment, PRL-2903 promoted higher plasma glucagon counter-regulation, as indicated by area under curve (AUC) analysis (p < 0.05). Thus, SSTR2a treatment improves the attenuated glucagon response to hypoglycemia in T2DM rats."

Late-breaking abstract • Preclinical