Zealand Pharma announces positive results from Part 1 of multiple ascending dose trial with amylin analog ZP8396

Company announcement – No. 27 / 2023

Zealand Pharma announces positive results from Part 1 of multiple ascending dose trial with amylin analog ZP8396

  • Doses of 0.6 and 1.2 mg ZP8396 administered once-weekly for six weeks led to 5.3% and 5.1% mean weight loss as compared to 2.6%, 3.6% and 4.2% weight loss following single doses of 0.7, 1.4 and 2.4 mg ZP8396, already reported
  • Part 2 investigates once-weekly dosing for 16 weeks and has been initiated, exploring significantly higher doses of ZP8396 based on the mild adverse event profile observed in Part 1 of the trial
  • Results support continued development of ZP8396 as an alternative to GLP-1-based therapies for the management of overweight and obesity

Copenhagen, Denmark, July 3, 2023 – Zealand Pharma A/S (Nasdaq: ZEAL) (CVR-no. 20045078), a biotechnology company focused on the discovery and development of innovative peptide-based medicines, today announced results from Part 1 of a multiple ascending dose (MAD) trial for ZP8396, the company's long-acting amylin analog with potential for the management of overweight and obesity. Part 1 of the MAD trial was designed to investigate safety, tolerability, and clinical effects of 6 weeks of dosing with ZP8396 in healthy lean and overweight people.

“We are very encouraged by the reductions in body weight seen after six weeks of treatment at lower doses of ZP8396. We have initiated the second part of this multiple ascending dose clinical trial assessing both a longer duration of treatment and higher doses of ZP8396,” said David Kendall, MD, Chief Medical Officer of Zealand Pharma. “We are excited about the different opportunities with amylin, both as an alternative, non-incretin treatment for overweight and obesity and as a potential combination with incretin-based therapy, such as GLP-1”.

In Part 1 of this MAD trial, a total of 20 participants with a median BMI of 25 (kg/m2) were randomized (7:3) within two dose cohorts to receive either subcutaneous ZP8396 or placebo. Mean body weight reductions of 5.3% and 5.1% from baseline were observed following 6 once-weekly doses of 0.6 mg and 1.2 mg ZP8396, respectively. Participants who received placebo showed a body weight decrease of 0.4%.

ZP8396 was judged to be well tolerated, with no serious or severe adverse events (AEs) and no withdrawals. The most common AEs were related to the gastrointestinal system, were all mild and most occurred within two days of the first dose. Based on this mild adverse event profile, Zealand Pharma has moved swiftly into 16 weeks of dosing in Part 2 of the trial to explore significantly higher exposure levels of ZP8396. The company expects to present detailed results from the 6-week Part 1 at a scientific conference later this year and to report topline results from the 16-week Part 2 in 2024.

About the MAD trial
The MAD trial is a single-center, randomized, double-blind, placebo-controlled clinical trial in normal weight and overweight but otherwise healthy participants, investigating safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of ZP8396 (NCT05613387). The MAD trial consists of Part 1 and Part 2. Part 1 includes 20 participants receiving 6 once-weekly doses of ZP8396 or placebo as subcutaneous injections. Part 2 of the trial includes 48 participants receiving 16 once-weekly doses of ZP8396 or placebo using a dose up-titration scheme.

About ZP8396
ZP8396 is an investigational, potent long-acting amylin analog designed to improve solubility, minimize fibrillation, and to allow for co-formulation with other peptides, including GLP-1 analogs. Amylin analogs hold potential as both single agents as well as combination therapies for the treatment of obesity. ZP8936 has demonstrated the potential to reduce body weight and improve glycemia in preclinical models of obesity and diabetes. Results from the SAD trial showed dose-dependent, consistent and well-sustained body weight reductions of up to a mean of 4.2% from baseline (4.8% placebo-corrected) after one 2.4 mg dose. ZP8396 was well tolerated in the trial, with no serious or severe adverse events (AEs) and no withdrawals. The most frequent related AEs were decreased appetite, early satiety, nausea, and vomiting. Most AEs were mild and transient. No anti-drug antibodies were detected. The plasma half-life was approximately 10 days, suitable for once-weekly administration. These results were presented at the American Diabetes Association’s Scientific Sessions in June 2023.

About Zealand Pharma
Zealand Pharma A/S (Nasdaq: ZEAL) ("Zealand") is a biotechnology company focused on the discovery and development of peptide-based medicines. More than 10 drug candidates invented by Zealand have advanced into clinical development, of which two have reached the market and three candidates are in late-stage development. The company has development partnerships with a number of pharma companies as well as commercial partnerships for its marketed products.

Zealand was founded in 1998 and is headquartered in Copenhagen, Denmark, with a presence in the U.S. that includes Boston. For more information about Zealand’s business and activities, please visit www.zealandpharma.com.

Forward looking statements
This company announcement contains forward-looking statements that provide Zealand Pharma’s expectations or forecasts of future events regarding the research, development and commercialization of pharmaceutical products. These forward-looking statements may be identified by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would” and other words and terms of similar meaning. You should not place undue reliance on these statements, or the scientific data presented. The reader is cautioned not to rely on these forward-looking statements. Such forward-looking statements are subject to risks, uncertainties and inaccurate assumptions, which may cause actual results to differ materially from expectations set forth herein and may cause any or all of such forward-looking statements to be incorrect, and which include, but are not limited to, the occurrence of adverse safety events; risks of unexpected costs or delays; unexpected concerns that may arise from additional data, analysis or results obtained during clinical trials; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates or expansion of product labelling; failure to obtain regulatory approvals in other jurisdictions; and product liability claims. If any or all of such forward-looking statements prove to be incorrect, our actual results could differ materially and adversely from those anticipated or implied by such statements. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. All such forward-looking statements speak only as of the date of this company announcement and are based on information available to Zealand Pharma as of the date of this announcement. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. Information concerning pharmaceuticals (including compounds under development) contained within this material is not intended as advertising or medical advice.

Further information/contact

Adam Lange (Investors)
Investor Relations Officer
Zealand Pharma

Anna Krassowska, PhD (Investors and Media)
Vice President, Investor Relations & Corporate Communications
Zealand Pharma