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
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. Zealand Pharma company announcement – 23 May 2017; 2., Zealand Pharma company announcement – 22 June 2017 Ready for Phase 2b out-patient trial in T1D patients together with leading device developer Beta Bionics
Recently expanded collaboration with Beta Bionics
• Non-exclusive development agreement
• Preparing for Phase 2b trial with dasiglucagon in the iLetTM in 2018
The iLet™ device1 GEN 4
24 1. In development by Beta Bionics – Not approved by FDA
A potential paradigm shift with fully automated dual hormone pumps
of glucose control glucose of
automatization Level of of Level
25 1. Examples: MiniMed 530G System and MiniMed 670G System; 2. Example : Beta Bionics iLet device Significant market potential for glucagon in dual hormone pumps
Potential 2025 glucagon value in Estimated no. of T1D patients on pumps in the U.S. dual hormone pumps in U.S.5
Dual Hormone share of Estimated glucagon total pump market net sales5
~700k3 5.0% At 10% penetration USD ~0.3 billion CAGR
At 30% penetration USD ~1.0 billion 7.0% 560k2 CAGR At 50% penetration USD ~1.5 billion 400k1 Increasing prevalence of ~3% T1D patients/year4
Broader patient segment
Improving technology / integration
2015 2020 2025
1. American Association of Diabetes Educators; 2. Meddevicetracker, Informa, March 2017; 3. Zealand projections based on 5% annual growth; 4. JDRF 26 5. Scenarios of 10%, 30% and 50% use of dual hormone systems on forecasted pump users. Glucagon net price of USD 10/day at launch + 3% annual price growth Next steps: Dasiglucagon in cartridge for dual hormone pumps
Phase 2b trial in iLet™
in 2018
INSULIN Dasiglucagon Additional development and + commercial partnerships in 2018-2020
For illustration only
Launch dasiglucagon cartridge in 2022/2023
27 Dasiglucagon holds potential to change the life of millions of people living with metabolic diseases
Zealand dasiglucagon franchise Status
Rare disease
Pump treatment for recurrent low blood glucose Phase 3 ready - Congenital hyperinsulinism
Diabetes care
HypoPal® rescue pen for severe Phase 3 ongoing hypoglycemia
Automated diabetes care with a Phase 2b ready dual hormone pump
28