Zealand Pharma A/S Stock

Zealand Pharma A/S, a biotechnology company, focuses on the discovery, design and development of peptide-based medicines.

The company focuses on specialty medicines for metabolic and gastrointestinal diseases and other specialty disease areas with significant unmet medical needs.

The company’s pipeline of internally developed product candidates is concentrated on potential treatments for specialty gastrointestinal and metabolic diseases. In addition, it is looking to focus its efforts on drug candidates that may qualify for orphan/rare disease status.

The company has the following programs in late clinical development:

ZEGALOGUE (dasiglucagon) single use syringe or autoinjector for severe hypoglycemia. ZEGALOGUE (dasiglucagon) injection was approved by the U.S. Food and Drug Administration (FDA) in March 2021 for the treatment of severe hypoglycemia in people with diabetes aged 6 and over. ZEGALOGUE (dasiglucagon) single use syringe or autoinjector offers diabetes patients and their families a fast treatment solution for severe hypoglycemia. ZEGALOGUE (dasiglucagon) is a glucagon analogue for the treatment of severe hypoglycemia in patients with diabetes aged six and above.

V-Go Wearable Insulin Delivery Device: The V-Go is an affordable, all-in-one basal-bolus insulin delivery device option for adult patients requiring insulin that is worn like a patch and can eliminate the need for taking multiple daily shots.

The company has the following programs in late clinical development:

Glepaglutide, a long-acting GLP-2 analog in development for the treatment of short bowel syndrome (SBS). Orphan drug designation has been granted in the U.S. The company has published the results of a Phase 2 trial where glepaglutide was dosed for three weeks in 18 patients with SBS. The trial demonstrates significant positive effects on gastrointestinal absorption and other efficacy parameters with the two highest doses, whilst the lowest dose was non-effective. Based on the findings of this trial, the pivotal Phase 3 trial in 129 SBS patients was initiated in 2018 and patient enrollment was completed in 2021. Full results from the trial are expected in the third quarter of 2022. This study will evaluate the ability to reduce patient dependency on parenteral (intravenous) support when treated with glepaglutide over 26 weeks.

Dasiglucagon dual-hormone artificial pancreas for automated diabetes management. In a non-exclusive collaboration with Beta Bionics Inc. (Beta Bionics), the company is developing dasiglucagon for use in an artificial pancreas device, including both insulin and dasiglucagon. Breakthrough Device designation was received from the FDA in December 2019. Guided by an algorithm, this device is designed to maintain and control blood glucose levels with minimal patient intervention. The company has already reported positive results from two Phase 2a trials during the second quarter of 2017, and top-line results from a small home-use Phase 2 trial in iLet gen 3.2 dual-hormone artificial pancreas system were announced in June 2019. Beta Bionics has begun test run screening for the iLet bihormonal pivotal Phase 3 trial, utilizing dasiglucagon and insulin, and is on track to commence a Phase 3 trial of patients by the end of 2022. Overall, the program is designed to demonstrate the clinical outcome of utilizing dasiglucagon in the bihormonal iLet versus an insulin-only iLet, while also comparing these results to intensified usual care.

Dasiglucagon for congenital hyperinsulinism. Congenital hyperinsulinism (CHI) is an ultra-rare but devastating disease caused by inappropriately elevated insulin secretion irrespective of glucose levels. This leads to frequent and often severe hypoglycemia and long-term irreversible damage to health. In 2017, the FDA and the European Commission both granted orphan drug designation to dasiglucagon for the treatment of CHI. The company signed a collaboration agreement with DEKA Research & Development Corp. to develop a continuous infusion pump to be used in combination with dasiglucagon for the treatment of CHI.

Dasiglucagon for post bariatric surgery hypoglycemia. In March 2020, the company reported positive topline results from its Phase 2 dose-finding clinical proof-of-concept trial that explore the potential benefits of mini-doses of dasiglucagon in correcting serious hypoglycemic events following meal ingestions in some patients who have undergone bariatric surgery. Subjects were randomly assigned to be treated with two different subcutaneous administered doses of dasiglucagon (80 µg and 200 µg) and placebo (saline injection) after the meal. Results of the trial demonstrate that both dasiglucagon doses significantly reduced meal-induced hypoglycemia compared to placebo.

The company’s other internally developed product candidate programs include:

Dapiglutide (INN): This product candidate is a long-acting GLP-1R/GLP-2R dual agonist. The Phase 1a single-ascending dose, safety and tolerability trial investigating dapiglutide in healthy volunteers was completed in the third quarter of 2020 and dapiglutide was found to have an acceptable safety and tolerability profile. Results showed a plasma half-life allowing for once weekly dosing. Based on the results of the Phase 1a trial, the company initiated a Phase 1b (multiple ascending dose) safety and tolerability trial. In November 2021, it announced that dapiglutide was assessed to be safe and well tolerated in the study. Dapiglutide displayed a linear dose-response for the pharmacokinetics parameters with a half-life of approximately 120 hours giving the possibility for once weekly dosing. For pharmacodynamics, a dose-response relationship was found for several biomarkers suggesting that clinically relevant exposures of dapiglutide were achieved in the study. The company will be exploring several potential indications in gastrointestinal and metabolic diseases where dapiglutide’s profile could provide new treatment options including Short Bowel Syndrome.

ZP 7570: This product candidate is a potential once-weekly GLP-1-/GLP-2 agonist for the treatment of SBS in Phase 2 development.

ZP 6590 GIP Agonist: This program is in preclinical development as a potential treatment for obesity.

ZP 8396 Amylin Analog: This product candidate is being developed as a potential once-weekly treatment for obesity and type 2 diabetes. The company has initiated patient dosing in a Phase 1 clinical trial with ZP8396 for potential treatment of obesity. The Phase 1, first-in-human, randomized, single ascending dose trial will assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of ZP8396 administered to healthy subjects. Preclinical data on ZP8396 was presented at The Obesity Society Annual Meeting, which showed anti-obesity effects of ZP8396 in in vivo models, with up to 20% weight loss when combined with GLP1 analogue semaglutide.

Additional Pre-clinical Programs: The company is also working on several additional preclinical programs that include an ion channel blocker and an a4ß7 integrin inhibitor that may enter the clinic in the years to come.

The company engages in joint development efforts under the following programs:

Boehringer Ingelheim (BI): The company has a clinical license collaboration with Boehringer Ingelheim targeting treatments for type 2 diabetes, obesity, and non-alcoholic steatohepatitis (NASH). In June 2021, the FDA granted Fast Track Designation to the GLP-1/glucagon dual agonist BI 456906 in development under this program for the treatment of NASH in adults. The GLP-1/glucagon dual agonist activates two key gut hormone receptors simultaneously.

Three parallel Phase 2 trials are ongoing. All subjects have been randomized in the first phase 2 trial, which evaluates the dose-relationship of BI 456906 on HbA1c from baseline to 16 weeks relative to placebo in 410 people with diabetes. Secondary objectives are to assess the effect on change in body weight and an open-label comparator (semaglutide) will allow for the comparison of the effects against a pure GLP-1R agonist. The second Phase 2 randomized double-blind placebo-controlled dose-finding trial will evaluate BI 456906 in people with obesity or who are overweight with a BMI 27 kg/m2 or higher without diabetes. Participants will receive a subcutaneous injection of either BI 456906 or placebo once a week for the duration of the trial. The primary endpoint of this trial is the percentage change in body weight at week 46 compared to placebo. The third Phase 2 randomized double-blind placebo-controlled dose-finding trial will evaluate BI 456906 in people with NASH and liver fibrosis (F2/F3) with and without diabetes. The primary endpoint of this trial is the histological improvement of steatohepatitis without worsening of fibrosis after 48 weeks of treatment. Participants will receive a weekly subcutaneous injection of either different doses of BI 456906 or placebo for the duration of the trial. Boehringer Ingelheim is funding all research, development and commercialization activities related to the treatment.

Alexion Pharmaceuticals, Inc. (Alexion): The company has a pre-clinical license collaboration with Alexion that targets Complement C3, which has the potential to treat a range of complement mediated diseases. The complement system is part of the immune system that protects the body against, among other things, infection. This system can become dysregulated, which leads to certain auto-immune diseases. The company and Alexion are pursuing certain peptide-based therapeutic candidates that may be able to treat some of these diseases. The company will lead the joint discovery and research efforts through the preclinical stage, and Alexion will lead development efforts beginning with IND filing and Phase 1 trials. The company is looking to initiate a Phase 1 trial of the C3 inhibitor in 2022.

Deka Research, Development and Supply Agreements for the Deka pump

In November 2021, the company entered into a research & development agreement with DEKA Research & Development Corp. and DEKA Products Limited Partnership (DEKA) for the development of a pump that can be used with dasiglucagon for the treatment of CHI (Congenital Hyperinsulisum) in pediatric patients.

Seasonality

Although the sales of some of the products that are on the market in the United States are sensitive to seasonal sales trends the company’s financial performance, financial position and cash flows are not subject to significant seasonality. However, it is noted that the sales of ZEGALOGUE (dasiglucagon) for school aged children are likely to be increased in the period leading up to the start of the school year.

Patents

For most patent families, the company files a patent application under the International Patent System (PCT), which can be entered for examination into the patent office in any of the countries that are signatories to the PCT. In some cases, it files national applications directly in the major jurisdictions, which include Europe, the United States and Japan. For certain patent families, the company files in parallel an application under the PCT and national applications in certain jurisdictions, such as the United States.

Patent and Patent Application Portfolio

The company owns one patent family covering lixisenatide. This entire family is licensed exclusively to Sanofi S.A. (Sanofi). It owns five patent families covering its proprietary GLP-2 analog glepaglutide or backup candidates. Although the disclosures of one of these patent families encompass both elsiglutide and glepaglutide, it has been possible to claim the subject matter relating to glepaglutide in separate patents in the United States for its internal compound dasiglucagon, a glucagon analog that has a favorable stability profile.

Glepaglutide

The company owns seven patent families that cover glepaglutide. These patent families include granted patents in Australia, Brazil, Canada, China, Europe, Eurasia, Hong Kong, Israel, India, Japan, South Korea, Mexico, New Zealand, Norway, Ukraine, South Africa and the U.S. The granted U.S. patents include the composition of matter claims covering both the peptide and the composition of glepaglutide and related compounds. The granted European patent includes claims drawn to the composition of matter of a genus of compounds that encompasses glepaglutide, as well as analogs thereof and methods of using glepaglutide.

Dasiglucagon

The company owns five patent families covering dasiglucagon, including patents and applications in the United States and non-U.S. jurisdictions, including Australia, Brazil, Canada, China, Egypt, Eurasia, Europe, India, Israel, Japan, South Korea, Mexico, Malaysia, the Philippines, Singapore, Thailand, Taiwan, Ukraine, and Vietnam. The pending claims in one family cover the dasiglucagon compound and a group of structurally related compounds having glucagon agonist activity and increased solubility and/or stability relative to the native glucagon, as well as pharmaceutical compositions, including such compounds and related uses for treating a variety of diseases, including hypoglycemia, type 1 and 2 diabetes and other metabolic conditions, and nucleic acid molecules for expression of the compounds in host cells. The patent applications in the family that protect the compound itself, when issued, will have a nominal expiration date in July 2033. A United States patent in this family granted with claims covering the dasiglucagon compound. This patent received a patent term adjustment of 560 days, and is scheduled to expire in February 2035.

ZP 10,000 a4ß7 Integrin Inhibitor

This is an asset that was acquired with the company’s acquisition of Encycle Therapeutics, Inc. (Encycle). This includes the acquisition of seven patent families, including granted patents and patent applications in various territories, including two patent families that are co-owned with the University of Montreal and two patent families that are licensed from the University of Toronto. The remaining two families are wholly owned by Encycle, including the family that includes the composition of matter patent application.

Other Assets

The company also has patents and patent applications that encompass or relate to other pre-clinical and clinical assets that include its GLP-1/GLP-2 agonist (11 families), Amylin (two families), GIP agonist (four families), Kv1.3 (two families), glucagon dualacting peptide receptor agonist (GGDA) (five families) and C3 (three families).

The company (or the company’s wholly owned subsidiaries that include ZP Holding SPV K/S and ZP SPV 3 K/S) own all the patents and applications.

Research and Development

The company’s research and development expenses were Danish kroner 588.5 million in 2021.

Government Regulation

The FDA and comparable regulatory authorities in state and local jurisdictions and in other countries impose substantial and burdensome requirements upon companies involved in the clinical development, manufacture, marketing and distribution of drugs, such as those that the company is developing.

Competition

The company competes with companies that are producing drugs for, among other disease indications, short bowel syndrome (SBS), such as Takeda plc, which markets and distributes Gattex, and hypoglycemia, such as Novo Nordisk, Xeris and Eli Lilly & Co, which each market and distribute glucagon rescue kits.

History

Zealand Pharma A/S was founded in 1997. The company was incorporated in Denmark in 1998.