Toronto, Canada, February 8, 2022 – Zucara Therapeutics Inc., a diabetes life sciences company developing the first once-daily therapeutic to prevent insulin-induced hypoglycemia (low blood glucose levels), today announced that the peer-reviewed journal, Diabetes, Obesity and Metabolism, has published a paper reporting positive preclinical data showing the effect and pharmacokinetics of ZT-01, which is currently in a Phase 1b proof-of-concept trial for the treatment of insulin-induced hypoglycemia in patients with Type 1 diabetes (“T1D”).

The paper, entitled, “ZT-01 – A Novel Somatostatin Receptor 2 Antagonist for Restoring the Glucagon Response to Hypoglycemia in Type 1 Diabetes,” was co-authored by members of Zucara Therapeutics in collaboration with Michael C. Riddell at York University and the lab of senior author Owen Chan at the University of Utah. The study reports that ZT-01, a somatostatin receptor 2 antagonist (“SSTR2a”), stimulates glucagon release and reduces hypoglycemia in rats with T1D. The study also compares ZT-01’s performance with an earlier prototype SSTR2a, PRL-2903.

“We are thrilled with the positive results of this preclinical study, whose efficacy portion employed a similar methodology to that of our ongoing Phase 1b clinical trial,” said Richard Liggins, Zucara Therapeutics’ Chief Scientific Officer. “This study demonstrated that ZT-01 significantly increased glucagon secretion in rats with T1D, and reduced the frequency and severity of hypoglycemia, suggesting ZT-01’s potential to reduce hypoglycemia exposure in humans with T1D.”

The results of the preclinical efficacy study demonstrate that ZT-01 was much more effective at preventing hypoglycemia onset compared to PRL-2903 and exhibited superior pharmacokinetic and pharmacodynamic properties when administered by subcutaneous or intraperitoneal injection. When administered one hour prior to the induction of hypoglycemia, treatment with either ZT-01 or PRL-2903 slowed the onset and reduced overall severity of hypoglycemia, but to varying degrees: treatment with PRL-2903 delayed hypoglycemia – which, for the purposes of this study, was a decline in blood glucose concentration to 3.0 mM – by approximately 10 minutes compared to more than one hour with ZT-01. In addition, PRL-2903 failed to prevent blood glucose concentrations from reaching the same nadir (approximately 2.0 mM) as the vehicle-treated animals. Average blood glucose levels following ZT-01 treatment reached a nadir of 3.8 mM, with more than 60% of rats completely avoiding significant hypoglycemia below the 3.0 mM threshold.

The data show the novel SSTR2a, ZT-01, exhibited greater exposure following subcutaneous dosing compared to PRL-2903 and significantly increased glucagon secretion in rats with T1D, an improvement in counter regulation that was associated with reduced severity and frequency of hypoglycemia. These results suggest that SSTR2 antagonism may be a suitable therapeutic strategy to reduce hypoglycemia exposure in humans with T1D. Zucara is currently conducting a Phase 1b proof-of-concept clinical trial in people with T1D, with results anticipated in Q2 2022.

The article may be accessed at https://dom-pubs.onlinelibrary.wiley.com/doi/abs/10.1111/dom.14652

About Zucara Therapeutics Inc.

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 secretion 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.

For additional information, please contact:

Zucara Therapeutics: Michael Midmer, mmidmer@zucara.ca