Press release – No. 7 / 2022
Zealand Pharma Announces Presentations at The Obesity Society Annual Meeting
Results from the phase 2 clinical trial of GCGR/GLP-1R dual agonist BI 456906 showing bodyweight reductions of up to 9% after 16 weeks in people with type 2 diabetes to be presented
Four preclinical presentations highlighting effects of Zealand Pharma’s three wholly owned peptide therapeutic candidates (dapiglutide, ZP8396, ZP6590) on body weight, food intake, tolerability and co-formulation
Copenhagen, Denmark and Boston MA, U.S. November 1, 2022 – Zealand Pharma A/S (Nasdaq: ZEAL) (“Zealand”) (CVR-no. 20045078) a biotechnology company focused on the discovery and development of innovative peptide-based medicines, today announced presentations at the Obesity Society Annual Meeting (Obesity Week) being held in San Diego, California from November 1-4, 2022. Presentations include preclinical data on Zealand’s amylin analogue (ZP8396), its first-in-class GLP-1R/GLP-2R dual agonist (dapiglutide) and from the company’s GIP analogue (ZP6590). Clinical data from a Phase 2 trial of the GCGR/GLP-1R dual agonist BI 456906, being developed by Boehringer Ingelheim and co-invented with Zealand, will also be presented at Obesity Week.
“The science and data that we will present at this year’s Obesity Week highlight our pipeline of therapeutic peptide candidates under study for the potential treatment of obesity. We have designed these novel peptides with complementary modes of action to maximize the effect on weight management and to address various clinical conditions associated with obesity, while maintaining tolerability, by potentiating or adding to incretin effects through either dual receptor targeting or by engineering single receptor agonists that can be co-formulated with other peptides. The preclinical data to be presented deepen our understanding of the effects on body weight and food intake as well as tolerability and the combination or co-formulation of dapiglutide, our GLP-1R/GLP-2R dual agonist, and our amylin analogue which are both in early phase clinical trials, as well as our GIP analogue in late preclinical development,” said David Kendall, MD, Chief Medical Officer of Zealand Pharma. “Clinical results from the dual glucagon/GLP-1 receptor agonist BI 456906 from Boehringer Ingelheim’s Phase 2 trial in people with type 2 diabetes will be presented at Obesity Week. In the trial, bodyweight reductions of up to 9% were observed after treatment with BI 456906 for 16 weeks compared to 5.4% observed following open-label treatment with the GLP-1 receptor agonist semaglutide. We are extremely encouraged by the clinical data and the potential of this molecule in patients with overweight or obesity.”
The presentation abstracts are available at https://obesityweek.org/abstracts/ and are summarized as follows:
Title: Amylin Analog ZP8396 Co-formulated With Semaglutide Provides Additive Anti-obesity Effect in DIO Rat
Authors: P. Eriksson, J. Lundqvist, J. Griffin, C. Wenander, J. Skarbaliene, and D. Kendall
Date and Time: Friday November 4, 2022, 11:45am - 1:15pm PT
Presentation Highlights: Amylin analogue ZP8396 has been designed to allow co-formulation with other peptides. Using an in vivo model of diet induced obesity, treatment with ZP8396 co-formulated with GLP-1 analogue semaglutide achieved a sustained and greater cumulative reduction in food intake and resulted in sustained and greater body weight loss when compared to monotherapy with either agent alone. The body weight reduction was similar with ZP8396 and semaglutide administered as separate injections (loose combinations) compared with co-formulation (-17.7 ±1.0 with co-formulation, -16.1% ±0.7 with loose combinations, -4.7% ±0.8 with ZP8396 alone, -8.0% ±0.8 with semaglutide alone, +7.0% ±1.1 with vehicle). These preclinical data confirm the feasibility of administering ZP8396 co-formulated with semaglutide for the management of overweight and obesity and achieving greater body weight loss when compared to monotherapy with either agent.
Title: Anti-obesity Effect of Dapiglutide Alone and in Combination With the Amylin Analog ZP8396 in DIO Rat
Authors: P. Eriksson, J. Griffin, A. Nansen, J. Skarbaliene, and D. Kendall
Date and Time: Wednesday November 2, 2022, 01:30pm - 1:45pm PT
Presentation Highlights: GLP-1R/GLP-2R dual agonist dapiglutide and amylin analogue ZP8396 are currently both being evaluated as monotherapy in clinical trials. In the current study using an in vivo model of diet induced obesity, combination therapy with dapiglutide and ZP8396, achieved a significant, sustained and greater cumulative reduction in food intake and resulted in significant, sustained and greater body weight reduction compared to when either treatment was given as monotherapy (-18.9% ±1.8 with combination therapy, -12.4% ±0.9 with dapiglutide, -5.9% ±0.4 with ZP8396).
Title: Anti-obesity Effects of GIP Analogue ZP6590 in Combination with Semaglutide in DIO Mice
Authors: J. Skarbaliene, A. Nansen, and H. Rosenqvist
Date and Time: Wednesday November 2, 2022, 11:40am - 1:15pm PT
Presentation Highlights: GIP exhibits potent incretin activity and may impact weight regulation. In this study using an in vivo model of diet induced obesity, GIP analogue ZP6590 potentiated the body weight loss effects of GLP-1 monotherapy with semaglutide despite negligible effects of ZP6590 alone (-24.1% ±1.3 with combination of ZP6590 and semaglutide, -13.7% ±2.3 for semaglutide alone, 0.8% ±0.9 for ZP6590 alone). The potentiation of body weight loss resulting from combination therapy in this model was also observed if ZP6590 was added after maximal effect of GLP-1 monotherapy had been achieved. These preclinical results suggest a synergistic potential of this combination in treating obesity.
Title: Potent Antiemetic Effect of GIP Analogue ZP6590 in Ferrets, a Gold Standard Model for Emesis Testing
Authors: J. Skarbaliene, C. Wenander, and J. Griffin
Date and Time: Wednesday November 2, 2022, 11:40am - 1:15pm PT
Presentation Highlights: Some medications, including GLP-1 analogues, are known to induce nausea and vomiting in patients. GIP analogue ZP6590 exerted antiemetic effects in an in vivo model challenged with the emesis-inducing agents morphine or peptide YY3–36. These results suggest the potential therapeutic advantages of combination therapies targeting GIP with other drivers of malaise in the field of weight management, diabetes or in the management of opioid-induced emesis.
Title: Glucagon/GLP-1 Receptor Dual Agonist BI 456906 Reduces Bodyweight in Patients With Type 2 Diabetes
Authors: J. Rosenstock, M. Bluher, C. Schoelch, J. Hoefler, and A. Hennige
Date and Time: Thursday November 3, 2022, 10:15am - 10:30am PT
Presentation Highlights: Treatment with the GCGR/GLP-1R dual agonist BI 456906 resulted in dose-dependent bodyweight reductions, up to a maximum of -9.0% in people with type 2 diabetes (T2D) and showed greater bodyweight loss than with open-label semaglutide 1.0 mg 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 1.0 mg 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.
Baseline mean age was 57 years, bodyweight 97 kg and BMI 25-50 kg/m2.
Treatment with BI 456906 has dose-dependently reduced HbA1c in patients with T2D on stable metformin therapy.
Treatment with BI 456906 led to dose-dependent decreases in bodyweight, with mean reductions of -1.9% to -9.0% at 16 weeks across the six dose groups, compared with -1.2% seen with placebo. Treatment with open-label weekly semaglutide at 1.0 mg led to a decrease in bodyweight of -5.4%.
Adverse events were reported in 77.8% of all participants receiving BI 456906. These were most frequently GI disorders such as nausea and vomiting. Adverse events led to treatment discontinuation in 15.9% of patients receiving BI 456906.
Slower dose escalations over a longer duration are expected to mitigate GI adverse events.
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. Boehringer Ingelheim is currently investigating the GCGR/GLP-1R dual agonist in two phase 2 trials for people with obesity or 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 is eligible to receive up to EUR 345 million in outstanding milestone payments, and high-single to low-double digit royalties on global sales.
Dapiglutide is a long-acting GLP-1R/GLP-2R dual agonist for the potential treatment of obesity. In the Phase 1b multiple-ascending dose clinical trial in healthy volunteers, dapiglutide showed dose dependent weight loss over four weeks of treatment and was well-tolerated. Results showed a plasma half-life allowing for once weekly dosing and effects on several biomarkers suggest clinically relevant exposures of dapiglutide were achieved.
ZP8396 is an investigational, potent long-acting amylin analogue designed to improve solubility, minimize fibrillation and allow for co-formulation with other peptides, including GLP-1 analogues. Amylin analogues hold potential as both mono and combination therapies for obesity. In preclinical studies ZP8936 has shown potent anti-obesity effects. ZP8936 is currently being evaluated in a Phase 1 clinical trial.
ZP6590 is a long-acting glucose-dependent insulinotropic polypeptide (GIP) analogue with a predicted half-life supporting once-weekly dosing in humans. GIP exhibits potent incretin activity and may impact weight regulation. Recent findings show that GIP exerts antiemetic effects in models of GLP-1-induced emesis and suggests a potential therapeutic advantage of combining GIP with treatments known to induce emesis in patients.
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.
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.
Anna Krassowska, PhD
Vice President, Investor Relations & Corporate Communications
Zealand Pharma A/S
David Rosen (U.S. Media)