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Dasiglucagon for Congenital Hyperinsulinism Moving Into Phase 3 with Orphan Designation in U.S

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Dasiglucagon for Congenital Hyperinsulinism Moving Into Phase 3 with Orphan Designation in U.S AGENDA Business highlights Britt Meelby Jensen Significant progress with late stage clinical programs heading towards filing The Zealand peptide platform Andrew Parker World leading expertise delivering differentiated peptide-based drug candidates Glepaglutide Adam Steensberg / David F. Mercer A potential best-in-class GLP-2 for treatment of short bowel syndrome Followed by Q&A session Dasiglucagon Adam Steensberg / Jessica Castle A novel glucagon analog with potential to disrupt diabetes care & rare diseases Followed by Q&A session Closing remarks Britt Meelby Jensen Driving success in 2018 and beyond with short and long term value drivers Followed by Q&A session 1 Dasiglucagon Glucagon analog in development for diabetes care and congenital hyperinsulinism 25 January, 2018 2 Our unique peptide-design capabilities behind dasiglucagon Native glucagon Dasiglucagon • An endogenous peptide hormone • Novel glucagon analog secreted from the pancreas in response to low glucose • Unique stability in liquid formulation • Main insulin counter-regulatory hormone • Fast onset-of-action • Highly unstable in solution 3 Creating an opportunity for people living with diabetes and congenital hyperinsulinism Zealand dasiglucagon franchise Status Rare disease Pump treatment for recurrent low blood glucose Phase 3 ready - Congenital hyperinsulinism (CHI) Diabetes care HypoPal® rescue pen for severe Phase 3 ongoing hypoglycemia Automated diabetes care with a Phase 2b ready dual hormone pump 4 Dasiglucagon for congenital hyperinsulinism moving into Phase 3 with orphan designation in U.S. and EU Improve the lives of children with congenital hyperinsulinism through a non-surgical treatment option For illustration only 5 Congenital hyperinsulinism – an ultra-rare disease in newborns with serious complications Congenital hyperinsulinism • Up to 300 newborns and children are diagnosed with genetically determined CHI in the U.S. and EU every year1,4 • Excessive plasma insulin due to genetic defect in the beta-cells4 • Persistent episodes of hypoglycemia4 • Associated with seizures and brain damage3 • Most severe cases end up with near-total pancreatectomy5 1. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=657 (not including transient cases due to perinatal stress or diabetic mother2. Arnoux JB et al. Orphanet Journal 6 of Rare Diseases 2011, 6:63; 3. Thornton PS et al. J Pediatr. 2015;167(2):238-45; ); 4. Congenital Hyperinsulinism International. Available at: http://congenitalhi.org; 5. Meissner T et al.. Long-term follow-up of 114 patients with congenital hyperinsulinism. Eur J Endocrinol 2003;149:43-51. Current treatments of CHI are frequently inadequate Current treatment algorithm for congenital hyperinsulinism 1. Glucose level stabilization • Diet management • Glucose infusion • Glucagon rescue or i.v.1 • Diazoxide3 2. Diagnostic workup Focal Diffuse Fast to partial Medical management Fast to near-total pancreatectomy • Diazoxide2 pancreatectomy • Octreotide CHI cured, no • Sirolimus CHI not CHI cured sequelae • Glucagon rescue cured (T1D develops3) 7 1. Not in label for glucagon; 2. Diazoxide only FDA approved medicine for CHI; 3. Arya VB, et al. PLoS One. 2014;9(5):e98054. Dasiglucagon could become a first-in-class glucagon analog for long-term treatment of congenital hyperinsulinism Clinical proof-of-concept in 9 children with Potential future treatment algorithm for CHI diffuse CHI using glucagon for reconstitution4 Dasiglucagon infusion • Reduction or discontinuation of i.v. glucose infusion in all children • Six children discharged home on the treatment • In three children glucagon was administered for 1–4 years Dasiglucagon infusion 8 1. Not in label for glucagon; 2. Diazoxide only FDA approved medicine for CHI; 3. Arya VB, et al. PLoS One. 2014;9(5):e98054. Phase 3 trials to be initiated in 2018 with ambition to launch product in 2020 Phase 2/3 trial in up to 16 neonates with CHI Key Inclusion criteria: • Age 7 days to 3 months • Diagnosed with hyperinsulinemia/hypoglycemia and diazoxide non-responsive Phase 3 trial in up to 32 children with CHI Key inclusion criteria: • Age 3 months to 12 years • Diagnosed with diffuse CHI (+/- near-total pancreatectomy) and more than 3 episodes of hypoglycemia per week Dasiglucagon delivered via a subcutaneous infusion pump • Short-term stabilization: Preventing hypoglycemia and discharge to home • Long-term treatment: Preventing recurrent hypoglycemia and need for near-total pancreatectomy in diffuse CHI 9 Next steps: Dasiglucagon for congenital hyperinsulinism (CHI) Phase 3 initiation in 2018 Phase 3 results in 2019 For illustration only Launch in 2020 10 Dasiglucagon HypoPal® rescue pen for treatment of severe hypoglycemia 0.6 mg dasiglucagon Offer millions of people with diabetes rescue from For illustration only severe hypoglycemia 11 Severe hypoglycemia is a constant risk and a major burden for diabetes patients on insulin • One of the most feared complications for patients on insulin therapy1 • Happens to up to 40% of patients with Type 1 diabetes every year2 • ~300,000 hospitalizations per year in the U.S.4 • High complexity of currently available glucagon rescue kits3 1. Kalra 2013, UK Hypoglycemia Study Group; 2. International Hypoglycemia Study Group. Diabetes Care. 2015;38:1583–1591; 3. *Research Commissioned by Zealand 12 Pharma n = 11,373 posts on hypoglycemia in diabetes. Results from human factor studies published by Locemia and Xeris; Center for Disease Control and Prevention.cdc.org; Harris et al. 2001, Practical Diabetes International; 4. National Diabetes Statistics Report. CDC. 2014. Opportunity to replace glucagon for reconstitution with dasiglucagon in an auto-injector for easy administration Currently available glucagon rescue kit The HypoPal® rescue pen For illustration only Glucagon Emergency kit, Eli Lilly1 More than 85% of trained caregivers failed Preferred mode of administration by patients, to deliver full dose of the emergency kit2 care givers and health care professionals3 13 1. Glucagon for injection Eli Lilly 2012; 2. ePoster # 867, EASD 2015, Stockholm; 3. Zealand commissioned market research Dasiglucagon provided rapid rescue from hypoglycemia in Phase 2 Rapid rescue from hypoglycemia in Phase 2 with dasiglucagon1 Median time to recovery2 • 9 min for dasiglucagon 0.6 mg • 10 min for GlucaGen® 1.0 mg 14 1. Diabetes Care 2017 Dec; dc171402; 2. 20 mg/dL increase in plasma glucose Confirmatory Phase 3 trial utilizing similar design as used in Phase 2 is on track to deliver results in 2018 ADA Phase 3 trial – results 2Q 2018 • Anti-Drug-Antibody assessment in 90 T1D patients • 3 repeat injections of dasiglucagon or GlucaGen in 45 subjects each Confirmatory Phase 3 – results 4Q 2018 • Hypoglycemic clamp in 156 T1D patients • Single injection of dasiglucagon, GlucaGen or placebo • Primary endpoint: Time to 20 mg/dL increase in plasma glucose V3 Follow Up Day 28 15 The glucagon hypoglycemia rescue market has significant growth potential The U.S. glucagon market for rescue treatment is expected to grow significantly Current volume Future market volume estimates > 2m 9% CAGR Rescue treatments4 Increased penetration ~ 1m Increased awareness Rescue 1 treatments Improved product3 2016 2025 Current value Potential value USD ~ 0.3 billion2 USD > 0.7 billion5 1. IMS Health data, 2016 volume of glucagon rescue kit market; 2. IMS Health data, 2016 value, including value from vials used for diagnostic use; 3. Vast majority of 16 parents of T1DM children or adolescents struggled to use the rescue kit. Source: Harris 2001; 4. 2016 U.S. volume (IMS Health) forecasted with an increase in T1D prevalence of 3% per year (JDRF), increased adoption of rescue treatments with new options available (+10-20% from 2019-22); 5. Estimated annual price increase of 5% Next steps for dasiglucagon HypoPal® rescue pen Phase 3 results and commercial partnerships in 2018/2019 NDA/MAA filing in 2019/20 Launch in US and EU in 2020/21 17 Dasiglucagon cartridge for dual hormone artificial pancreas pumps INSULIN Dasiglucagon A future with fully automated + diabetes care fueled by dasiglucagon in dual hormone pump systems For illustration only 18 Dr. Jessica Castle M.D. Associate Professor at Oregon Health and Science University and the Harold Schnitzer Diabetes Health Center Specialty in endocrinology and diabetes Principal Investigator of studies in artificial pancreas systems and novel pharmaceutical therapies in diabetes 19 Managing blood glucose in Type 1 diabetes is a constant struggle 20 Potential for tight glucose management with automated dual hormone pump control algorithms already proven Daily mean plasma glucose levels1 InsulinInsulin--onlyonly treatmenttreatment Blood glucose target level2 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 8 Day 9 Day 10 Day 11 Insulin and glucagon in a dual-hormone pump system Blood glucose target level2 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 8 Day 9 Day 10 Day 11 1. The Lancet, December 2016: S0140-6736(16)32567-3 and Elkhatib F, Buckingham BA, Buse JB, et al. Abstract 77-OR. at: ADA 76th Scientific Sessions; June 10-14, 21 2016; New Orleans, LA. Association. N=39 adults with type 1 diabetes, 24 hour daily treatment; 2. HbA1C of 7-4% Automated diabetes care fueled by dasiglucagon in fully integrated dual hormone pump systems 2 Glucose sensor/CGM2 Integrated insulin and glucagon 1 pump and infusion set1 3 Pre-filled insulin and glucagon cartridges INSULIN Dasiglucagon Dasiglucagon 4 mg/ml + 22 1. Example of pump devise – www.betabionics.com; 2. Example of sensor devise – www.dexcom.com Two Phase 2a trials and chronic toxicology studies concluded with dasiglucagon for pump use Phase 2a Microdose trial1 • 17 T1D patients at normal or low blood sugar • Dasiglucagon effective in doses from 0.03 to 0.6 mg • Optimal profile for pump use Phase 2a Pump trial2 Dasiglucagon Lilly Glucagon 80% • 10 T1D patients – challenged with fasting, high 71% basal insulin rate and exercise 60% 65% • iLet algorithm to maintain plasma glucose in range 40% 20% • Dasiglucagon as effective as old glucagon 18% 13% following reconstitution 0% Time with glucose < 60 mg/dl Time with glucose 70-180 mg/dl 23 1.
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