Zealand Pharma announces positive topline results from the Phase 1b 16-week multiple ascending dose clinical trial with long-acting amylin analog petrelintide

Company announcement – No. 32 / 2024

Zealand Pharma announces positive topline results from the Phase 1b 16-week multiple ascending dose clinical trial with long-acting amylin analog petrelintide

• Body weight reductions of up to a mean of 8.6% with high dose petrelintide after 16 weekly doses (1.7% with placebo)
• Petrelintide was judged to be safe and well tolerated at all dose levels
• Results provide robust support of the potential of petrelintide as an effective alternative to GLP-1RA-based therapies for weight management
• Zealand Pharma anticipates initiation of a Phase 2b clinical trial in H2 2024
• Conference call today at 8:00 p.m. CET / 2:00 p.m. ET

Copenhagen, Denmark, June 20, 2024 – Zealand Pharma A/S (Nasdaq: ZEAL) (CVR-no. 20045078), a biotechnology company focused on the discovery and development of innovative peptide-based medicines, today announces positive topline clinical results from Part 2 of a Phase 1b multiple ascending dose (MAD) trial, investigating safety, tolerability, and clinical effects of 16 weeks of dosing with petrelintide, a long-acting amylin analog in development for weight management¹.

"The data reported from this 16-week trial are both exciting and compelling, demonstrating significant and clinically meaningful reductions in body weight with a very favorable tolerability profile. These results support our conviction that petrelintide is very well tolerated and can potentially play an important role as an alternative to incretin-based therapies for the management of overweight and obesity,” said David Kendall, MD, Chief Medical Officer of Zealand Pharma. "These data pave the way for rapid progression to Phase 2b trials of petrelintide and further support the potential of this long-acting amylin analog to deliver weight loss comparable to GLP-1 receptor agonists with a better patient experience. We look forward to initiation of the Phase 2b clinical trial of petrelintide in people living with overweight and obesity later in 2024.”

In Part 2 of the Phase 1b MAD trial, a total of 48 (~80% male) participants with a median age of 49 years and a median baseline BMI of 29 kg/m², were randomized to receive 16 weekly doses of either petrelintide or placebo (3:1) within three dose cohorts. The mean body weight decreased by 8.6% from baseline among participants completing treatment with high dose petrelintide while placebo resulted in a mean body weight decrease of 1.7% from baseline.

Petrelintide was assessed to be well tolerated in the trial, with no serious or severe adverse events (AEs). All gastrointestinal (GI) AEs were mild except for two moderate events (nausea and vomiting) reported by one participant who discontinued treatment after the third dose. Notably, no other participants discontinued treatment due to AEs. No other participants reported vomiting and there were only two reports of diarrhea, both of which were mild. Nausea was reported by 16.7-33.3% for active groups and 16.7% for placebo. A low number of participants reported injection site reactions, all of which were mild. No anti-drug antibodies were observed.

These topline results are from an interim data cut. The final results will be based on all collected data including complete post-treatment follow-up from the third cohort. Zealand expects to present more details on the 16-week results from Part 2 of the MAD trial at a scientific conference later this year. The company also plans to rapidly progress the clinical development of petrelintide and initiate a Phase 2b clinical trial later in 2024.

About the MAD trial
The MAD trial is a single-center, randomized, double-blind, placebo-controlled clinical trial in healthy participants, investigating safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of petrelintide (NCT05613387). The MAD trial consists of Part 1 and Part 2. Part 1 includes 20 participants (eligible BMI 21.0–29.9 kg/m²) receiving 6 once-weekly doses of 0.6 mg and 1.2 mg petrelintide or placebo as subcutaneous injections. Part 2 of the trial includes 48 participants (eligible BMI 27.0–39.9 kg/m²) receiving 16 once-weekly doses of petrelintide or placebo within three dose cohorts using a dose escalation scheme. Part 2 of the MAD trial is exploring higher doses of petrelintide than in Part 1. Participants randomized to the two higher dose cohorts received the maximum assigned maintenance dose for a period of eight and six weeks, respectively.

About Petrelintide
Petrelintide (ZP8396) is a long-acting amylin analog suitable for once-weekly subcutaneous administration that has been designed with chemical and physical stability at neutral pH, minimizing fibrillation and allowing for co-formulation with other peptides. Amylin is produced in the pancreatic beta cells and co-secreted with insulin in response to ingested nutrients. Current clinical or preclinical data suggest a potential of petrelintide to deliver weight loss comparable to GLP-1 receptor agonists but with improved tolerability for a better patient experience and high-quality weight loss by preserving lean mass.

Conference call and webcast information
Zealand will host a conference call today, June 20, at 8:00 PM CET / 2:00 PM ET to review the topline results. Participating in the call will be Chief Executive Officer, Adam Steensberg; Chief Medical Officer, David Kendall; and Chief Financial Officer, Henriette Wennicke. The conference call will be conducted in English.

The live listen-only audio webcast of the call and accompanying slide presentation will be accessible at https://edge.media-server.com/mmc/p/2z723z92. To receive telephone dial-in information and a unique personal access PIN, please register at https://register.vevent.com/register/BIa06232d64c3d4367a7e0e5962b9e8433. Participants are advised to register for the call or webcast approximately 10 minutes before the start. A recording of the event will be available following the call on the Investor section of Zealand’s website at https://www.zealandpharma.com/investors/events-presentations/.

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. For more information about Zealand’s, please visit www.zealandpharma.com.

Forward looking statements
This company announcement contains "forward-looking statements”, as that term is defined in the Private Securities Litigation Reform Act of 1995 in the United States, as amended, even though no longer listed in the United States this is used as a definition to provide Zealand Pharma’s expectations or forecasts of future events regarding the research, development and commercialization of pharmaceutical products, the timing of the company’s pre-clinical and clinical trials and the reporting of data therefrom. 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, unexpected costs or delays in clinical trials and other development activities due to adverse safety events, patient recruitment or otherwise; unexpected concerns that may arise from additional data, analysis or results obtained during clinical trials; our ability to successfully market both new and existing products; changes in reimbursement rules and governmental laws and related interpretation thereof; government-mandated or market-driven price decreases for our products; introduction of competing products; production problems at third party manufacturers; dependency on third parties, for instance contract research or development organizations; unexpected growth in costs and expenses; our ability to effect the strategic reorganization of our businesses in the manner planned; 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 reject, fail to approve or may delay approval of our drug candidates or expansion of product labeling; failure to obtain regulatory approvals in other jurisdictions; exposure to product liability and other claims; interest rate and currency exchange rate fluctuations; unexpected contract breaches or terminations; inflationary pressures on the global economy; and political uncertainty, including the ongoing military conflict in Ukraine and the uncertainty surrounding upcoming elections in the US. 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.

Contacts:

Sources
1. ClinicalTrials.gov. A Research Study Looking at the Safety of Multiple Doses of ZP8396 and How it Works in the Body of Healthy Participants. Available at https://clinicaltrials.gov/study/NCT05613387. Last accessed June 2024.