Zucara Therapeutics Reports Positive Results from Phase 1b Trial of ZT-01

– Proof-of-Concept Trial Confirms ZT-01's Mechanism of Action in Restoring Glucagon Release in Patients with Type 1 Diabetes –

– First-in-Class ZT-01 has the Potential to Become the First Therapeutic to Prevent Hypoglycemia in Patients with Insulin-Dependent Diabetes –

TORONTO, June 22, 2022 /PRNewswire/ - Zucara Therapeutics Inc., a diabetes life sciences company developing the first therapeutic to prevent insulin-induced hypoglycemia (low blood glucose levels), today announced that its Phase 1b proof-of-concept trial demonstrated ZT-01's ability to restore glucagon release in people with Type 1 diabetes ("T1D").

Data from 18 subjects that completed all three hypoglycemic challenge (clamp) procedures demonstrated that nearly 90% of subjects had a meaningful increase in glucagon following ZT-01 compared to placebo. Compared to placebo, ZT-01 at 3 mg and 20 mg resulted in a mean 14 pg/mL and a 20 pg/mL change in peak glucagon from baseline, respectively (p<0.0001); while, on average, ZT-01 doubled the number of counter-regulatory events (an increase in blood glucose in hypoglycemia despite increasing insulin infusion). Of the 18 subjects completing 3 clamps, 16 showed a greater than 10 pg/mL increase in glucagon higher than placebo following one or both doses of ZT-01. There were no serious adverse events observed.

Michael Midmer, Zucara Therapeutics' Chief Executive Officer, added, "We are thrilled that results of this Phase 1b study establish proof of concept by demonstrating that our somatostatin receptor antagonist increases glucagon during hypoglycemia in people with diabetes. ZT-01 is a first-in-class molecule and could help many people with diabetes that suffer from disruptive hypoglycemia. We are working to file regulatory applications by the end of this year for a multi-center Phase 2 trial in the U.S. and Canada and look forward to evaluating ZT-01's ability to prevent hypoglycemia that challenges the lives of people with T1D."

Conducted at Centricity Research (formerly LMC Manna Research), the study employed a crossover design in people with T1D undergoing hypoglycemic clamp procedures to cause clinically significant Level 2 hypoglycemia. The procedure was performed on three separate occasions to assess the effects of subcutaneous ZT-01 at doses of 3 mg and 20 mg versus placebo, given before hypoglycemia was initiated. The main objective of the study was to evaluate the effect of ZT-01 on glucagon levels. Zucara would like to thank all study participants and we recognize how committed you were to our study and have greatly helped move this important research forward.

Dr. Alex Abitbol, the study's principal investigator, commented, "We are pleased to have demonstrated that ZT-01 acts to increase glucagon during hypoglycemia. In many patients undergoing the study's hypoglycemic clamp procedure, we not only observed a rise in glucagon but also a corresponding rise in glucose suggesting that ZT-01 may prevent hypoglycemia, further demonstrating proof-of-concept. This is the first treatment that aims to restore the normal physiology of glucagon secretion and could greatly impact the quality-of-life of patients living with diabetes, as well as their caregivers."

In people without diabetes, insulin secretion decreases while glucagon secretion increases to prevent hypoglycemia. However, in people with insulin-dependent diabetes, this response is dysregulated due to elevated secretion of pancreatic somatostatin ("SST"). Zucara has demonstrated that, in people with T1D, the glucagon response can be restored by inhibiting SST with ZT-01, a first-in-class SST receptor 2 antagonist.

Zucara Therapeutics is developing ZT-01, a first-in-class therapeutic to prevent insulin-induced hypoglycemia in patients using insulin therapy. ZT-01 is designed to inhibit somatostatin, a pancreatic hormone that impairs the glucagon response to hypoglycemia in people with insulin-dependent diabetes. ZT-01 restores glucagon release to prevent hypoglycemia, which could dramatically change diabetes disease management and improve both patient health and quality of life. For more information, visit www.zucara.ca.

SOURCE Zucara Therapeutics Inc.