Zealand Pharma Announces Oral Presentation of Phase 2 Data for BI 456906 at the 58th Annual ...

Press release – No. 6 / 2022

Zealand Pharma Announces Oral Presentation of Phase 2 Data for BI 456906 at the 58th Annual Meeting of the European Association for the Study of Diabetes (EASD)

• BI 456906 effectively lowered HbA1c up to -1.88% at week 16 in patients with type 2 diabetes in the Phase 2 clinical trial
• Preclinical pharmacology of BI 456906 supports ongoing Phase 2 studies in obesity or non-alcoholic steatohepatitis

Copenhagen, Denmark and Boston MA, U.S. September 21, 2022 – Zealand Pharma A/S (CVR-no. 20045078) a biotechnology company focused on the discovery and development of innovative peptide-based medicines, today announced the presentation of data from the Boehringer Ingelheim-sponsored Phase 2 clinical trial of BI 456906, a glucagon receptor/glucagon-like peptide-1 receptor (GCGR/GLP-1R) dual agonist, in patients with type 2 diabetes at the 58th Annual Meeting of the European Association for the Study of Diabetes (EASD) being held in Stockholm September 19 – 23, 2022. Preclinical data on BI 456906 will also be presented at the EASD annual meeting. BI 456906 is being developed by Boehringer Ingelheim and was co-invented with Zealand Pharma.

“We are delighted with the data presented at EASD from Boehringer Ingelheim’s Phase 2 trial of the dual glucagon/GLP-1 receptor agonist BI 456906 that showed effective lowering of HbA1c of up to -1.88% in people with type 2 diabetes at 16 weeks compared to -1.47% observed following open-label treatment with the GLP-1 receptor agonist semaglutide,” said David Kendall, MD, Chief Medical Officer of Zealand Pharma. “We look forward to the results from this Phase 2 trial’s secondary endpoints related to the changes in bodyweight following treatment with BI 456906 to be reported at Obesity Week 2022 later this year.”

The abstracts of the oral presentations are available at https://www.easd.org/programme-2022.html and the data are summarized as follows:

Title: Multiple dose-ranging study of the novel glucagon/GLP-1 receptor dual agonist BI 456906 vs placebo and open-label weekly semaglutide reference control in type 2 diabetes (Abstract number: 613)
Authors: J. Rosenstock, M. Blüher, B. Schmid, J. Hoefler, A. Hennige
Session: Short Oral Discussions Event D – SO 46 Incretins everywhere
Date and Time: Wednesday, 21 September 2022, 1:15 - 2:15 PM CET

Presentation Highlights: Treatment with BI 456906 resulted in dose-dependent HbA1c reductions, up to a maximum of -1.88% at Week 16 in people with type 2 diabetes (T2D) and showed greater HbA1c lowering than with open-label semaglutide 1.0mg in the Phase 2 trial. The safety and tolerability profile that included gastrointestinal (GI) disorders, such as nausea and vomiting, as the most frequently reported adverse events, was as is expected with higher increasing doses of GLP-1 receptor agonists. Most adverse events were reported during the dose-escalation phase of the trial, and therefore slower escalation schemes may mitigate the frequency.

• The Phase 2 placebo-controlled, double-blind trial enrolled people with T2D on stable metformin background therapy. Participants were randomized to receive multiple rising doses of BI 456906 in one of six dose groups, placebo or open-label weekly semaglutide 1.0mg for 16 weeks. More information about the design of the Phase 2 trial is at ClinicalTrials.gov ( NCT04153929 ).
• Different doses of BI 456906 were escalated every 1–2 weeks to ensure that 10 weeks were spent on a maintenance dose.
• The primary endpoint was the change from baseline in HbA1c after 16 weeks of treatment. Secondary endpoints related to the changes in bodyweight from baseline are expected to be reported later this year.
• Treatment with BI 456906 led to dose-dependent decreases in HbA1c, with mean reductions of -0.93% to -1.88% at 16 weeks across the six dose groups, compared with -0.25% seen with placebo. Treatment with open-label weekly semaglutide at 1.0mg led to a decrease in HbA1c of -1.47%.
• Adverse events were reported in 78% of all participants receiving BI 456906. Drug-related adverse events were reported for 59% of BI 456906-treated participants and 38% of participants treated with open-label semaglutide. These were most frequently GI disorders such as nausea and vomiting.
• Drug-related serious adverse events were reported for four participants treated with BI 456906 across dose groups, all of which resolved once treatment was stopped, and for no participants receiving placebo.
• Adverse events led to treatment discontinuation in 16% of patients receiving BI 456906, 5% receiving placebo and 4% receiving open-label semaglutide.
• Slower dose escalations over a longer duration are expected to mitigate GI adverse events.

Title: BI 456906, structural properties and pharmacology of the novel glucagon and glucagon-like peptide-1 receptor (GCGR/GLP1R) dual agonist (Abstract number 570)
Authors: R. Augustin, T. Zimmermann, L. Thomas, T. Baader-Pagler, P. Haebel, E. Simon, H. Klein, R. Santhanam, W. Reindl, B. Bajrami, W. Rist, I. Uphues, D. Hamprecht, H. Neubauer
Session: Short Oral Discussions Event E – SO 41 Incretins: basic science
Date and Time: Thursday, 22 September 2022, 12:00 - 1:00 PM CET

Presentation Highlights: BI 456906, by simultaneous activation of the GCGR and GLP-1R, achieved a body weight lowering efficacy that is superior to GLP-1R agonist semaglutide and is attributed to an increase in energy expenditure. Transcriptional profiling provided insights into the mechanism of action for BI 456906 in the liver with potential human relevance for patients with NASH. Taken together, the pharmacology of BI 456906 suggests clinical benefits for patients with obesity and patients with NASH which is in support of the current clinical programs.

About BI 456906

BI 456906 is a dual agonist, acting on glucagon (GCG) receptors and glucagon-like peptide-1 (GLP-1) receptors to regulate energy and glucose homeostasis, and which is expected to improve the metabolic profile of treated individuals. BI 456906 has been shown to reduce bodyweight in preclinical and clinical studies.

BI 456906 was co-invented by Boehringer Ingelheim through a collaboration agreement with Zealand Pharma. Boehringer Ingelheim is currently investigating the GCGR/GLP-1R dual agonist in two phase 2 trials for people with obesity or who are overweight ( NCT04667377 ) and for people with non-alcoholic steatohepatitis (NASH; NCT04771273 ). Under the terms of the agreement, Boehringer Ingelheim funds all research, development and commercialization activities related to BI 456906. Zealand Pharma is eligible to receive up to EUR 345 million in outstanding milestone payments, and high-single to low-double digit royalties on global sales.

About Zealand Pharma A/S 

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 and partnerships with a number of blue-chip pharma companies as well as commercial partnerships for its marketed products.

Founded in 1998 and headquartered in Copenhagen, Denmark, Zealand has a team in the U.S. For more information about Zealand’s business and activities, please visit http://www.zealandpharma.com.

Forward-Looking Statements

This press release contains “forward-looking statements”, as that term is defined in the Private Securities Litigation Reform Act of 1995, as amended, 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; product liability claims; and the direct and indirect impacts of the ongoing COVID-19 pandemic on our business, results of operations and financial condition. 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 press release and are based on information available to Zealand Pharma as of the date of this release. 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:

Anna Krassowska, PhD
Vice President, Investor Relations & Corporate Communications
Zealand Pharma A/S
ank@zealandpharma.com

David Rosen (U.S. Media)
Argot Partners
media@zealandpharma.com