ZT-01 / Zucara Therapeutics - LARVOL DELTA

Zucara Therapeutics Announces Second and Final Closing of US$25 Million Series B Financing (PRNewswire) - "Zucara Therapeutics Inc...announced that it has completed the second and final closing of its US$25 million Series B Financing....'We are thrilled to close our Series B financing, which will enable us to complete our Phase 2a clinical trial and the nonclinical activities to support a once-weekly version of ZT-01.'"

Financing • Hypoglycemia • Type 1 Diabetes Mellitus

Comparing a Somatostatin Receptor 2 Antagonist (SSTR2a) to Exogenous Glucagon (EG) for the Treatment of Severe Insulin-Induced Hypoglycemia (ADA 2024) - "Here, we tested the use of SSTR2a as a rescue treatment for SH. After 3 episodes of insulin-induced hypoglycemia to impair glucagon counterregulation, healthy male rats received an overdose of regular insulin before a SC injection of vehicle, EG (0.15 mg) or SSTR2a (10 mg/kg ZT-01) at the onset of level 2 hypoglycemia... SSTR2a provided more gradual and sustained recovery from SH than EG without causing systemic hyperglucagonemia."

Late-breaking abstract • Hypoglycemia • Metabolic Disorders • Severe Hypoglycemia • SSTR • SSTR2

The Glucagon Stimulating Effect in Hypoglycemia of Somatostatin Receptor 2 Antagonist (SSTR2a) Is Maintained with Repeat Dosing (ADA 2024) - "Introduction: A single dose of SSTR2a, ZT-01, reduces hypoglycemia exposure in diabetic rat models... Daily dosing of SSTR2a resulted in a consistent increase in glucagon during repeated hypoglycemic challenges, and reduced hypoglycemia exposure in initial challenges. It may also improve overall glycemia in this T2D rat model of recurrent hypoglycemia."

Late-breaking abstract • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus • SSTR • SSTR2

Impact of SSTR2a Treatment in Hypoglycemia in Male (M) and Female (F) Rat Models of Type 2 Diabetes (T2D) (ADA 2024) - "We observed apparent sex-related differences to the hormonal responses to hyper- and hypoglycemia, and SSTR2a may increase glucagon responses more so in F rats with T2D."

Late-breaking abstract • Preclinical • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

ZONE: A Study of the Effect of ZT-01 on Night-time Hypoglycemia in Type 1 Diabetes (clinicaltrials.gov) - P2 | N=168 | Recruiting | Sponsor: Zucara Therapeutics Inc. | Trial completion date: Jul 2024 ➔ Jul 2025 | Trial primary completion date: Jul 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

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

ZONE: A Study of the Effect of ZT-01 on Night-time Hypoglycemia in Type 1 Diabetes (clinicaltrials.gov) - P2 | N=168 | Recruiting | Sponsor: Zucara Therapeutics Inc. | Phase classification: P2a ➔ P2

Phase classification • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Zucara Therapeutics Doses First Patient in Phase 2a 'ZONE' Trial (PRNewswire) - "Zucara Therapeutics Inc...today announced that it has dosed the first patient in its Phase 2a trial of the effect of ZT-01 On Nocturnal hypoglycemia Events in Type 1 diabetes ('T1D') mellitus ('ZONE')....The ZONE study is a multi-centre, randomized, double-blinded, placebo-controlled, multiple-dose, crossover study designed to evaluate the effect of ZT-01 on the frequency of nocturnal hypoglycemia in patients with T1D....Patients will be monitored for hypoglycemia events using a continuous glucose monitor. The study's primary endpoint is the rate of nocturnal hypoglycemic events, compared to placebo. Secondary endpoints include the number of patients experiencing adverse events and time spent in hypoglycemia compared to placebo....The ZONE study is actively recruiting and will enroll patients at as many as 15 clinical sites across Canada and the U.S. Recruitment is expected to be completed in 2024."

Enrollment status • Trial status • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

ZT-01, a somatostatin receptor 2 antagonist (SSTR2a), increases pulsatile glucagon release during hypoglycaemia in type 1 diabetes (EASD 2023) - P1 | "ZT-01 enhanced the magnitude, amplitude and onset of glucagon pulsatility during hypoglycemia in adults with T1D, a novel finding associated with observations of glucose counterregulation."

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

ZONE: A Study of the Effect of ZT-01 on Night-time Hypoglycemia in Type 1 Diabetes (clinicaltrials.gov) - P2a | N=168 | Recruiting | Sponsor: Zucara Therapeutics Inc. | Not yet recruiting ➔ Recruiting | Initiation date: Mar 2023 ➔ Jul 2023

Enrollment open • Trial initiation date • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Zucara Therapeutics Receives IND Clearance for Phase 2 Clinical Trial of ZT-01 (PRNewswire) - "Zucara Therapeutics Inc...announced that the U.S. Food and Drug Administration ('FDA') has cleared the Company's Investigational New Drug ('IND') application for ZT-01 for the prevention of night-time (nocturnal) hypoglycemia in patients with Type 1 Diabetes ('T1D'). The FDA's clearance enables Zucara to initiate its planned trial titled A Phase 2a study of effect of ZT-01 On Nocturnal hypoglycemia Events in Type 1 diabetes mellitus (ZONE), with first patient dosing expected to occur in the third quarter of 2023."

IND • New P2a trial • Diabetes • Hypoglycemia • Metabolic Disorders

ZONE: A Study of the Effect of ZT-01 on Night-time Hypoglycemia in Type 1 Diabetes (clinicaltrials.gov) - P2a | N=168 | Not yet recruiting | Sponsor: Zucara Therapeutics Inc.

New P2a trial • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Effects of Somatostatin Receptor Type 2 Antagonism During Insulin-Induced Hypoglycaemia in Male Rats with Pre-Diabetes. (PubMed, Diabetes Obes Metab) - "SSTR2a treatment increases glucagon responsiveness and delays the onset of insulin-induced hypoglycaemia in this rat model of pre-T2D where only a modest deficiency in glucagon counterregulation exists."

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

Effect of ZT-01 on Glucagon During Hypoglycemia in Type 1 Diabetes Mellitus (clinicaltrials.gov) - P1 | N=24 | Terminated | Sponsor: Zucara Therapeutics Inc. | Recruiting ➔ Terminated; The study was completed following review of the assumptions underlying the power calculation and it was deemed that enough subjects had been recruited to complete enrollment

Trial termination • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

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

Effect of ZT-01 on Glucagon During Hypoglycemia in Type 1 Diabetes Mellitus (clinicaltrials.gov) - P1; N=25; Recruiting; Sponsor: Zucara Therapeutics Inc.

New P1 trial • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus