Zealand Pharma A/s · OMXCOP:ZEAL
Zealand Pharma A/s — Investor Day (March 2021)
59 slides from Zealand Pharma A/s's investor day presentation, Mar 4, 2021
Slide 1: R&D Day: Delivering on our commitment to patients
R&D Day Delivering on our commitment to patients March 2021
Slide 2: Welcome
Welcome 2 ##soft-page##
Slide 3: Agenda
@B080 Agenda “ Welcome Emmanuel Dulac Chief Executive Officer i Zealand today and 2025 ambition Emmanuel Dulac Chief Executive Officer R&D focus and strategy Adam Steensberg CMO and Head of R&D Metabolic portfolio Danilo Verge Head of Medical Affairs Steven Russel Associate Professor of Medicine, Ha
Slide 4: Forward looking statement
Forward looking statement This presentation contains information pertaining to Zealand Pharma A/S (“Zealand”). Neither Zealand nor its management, directors, employees or representatives make any representation or warranty, express or implied, as to the accuracy or completeness of any of the informa
Slide 5: Zealand today and 2025 ambition
Zealand today and 2025 ambition 5
Slide 6: Zealand Pharma is entering an exciting 2021
Zealand Pharma is entering an exciting 2021 Plan for a successful launch of Dasiglucagon HypoPal® rescue pen and optimize commercialization Execute on our robust late-stage clinical pipeline Advance our early-stage programs into the clinic Maintain a strong financial and organizational position 6
Slide 7: Ambition as a fully integrated biotech: 5x25
We are boldly pursuing our ambition as a fully integrated biotech 5x25 Have 5 commercialized products by 2025 Invest in innovative peptide research platform and robust pipeline Optimize commercial operationsSecure strong financial situation1 Fully operational US infrastructure High prescriber covera
Slide 8: R&D focus and strategy
R&D focus and strategy ; _
Slide 9: Zealand Pharma pioneers engineering of novel peptide drugs
Zealand Pharma pioneers engineering of novel peptide drugs Amylin and GIP analogs Acylated long-acting peptides α4β7 inhibitor In silico design Engineered for Dasiglucagon Stabilization Designed for co-formulation oral bioavailability Prevention of aggregation Glepaglutide Stabilized and long-acting
Slide 10: Zealand Pharma's Peptide Platform video
Zealand Pharma’s Peptide Platform Learn about Zealand Pharma’s Peptide Platform in this short video 10
Slide 11: Our talented team works diligently on our commitment to patients
Our talented team works diligently on realizing our commitment to patients 193 employees in R&D functions 11
Slide 12: Significant pipeline evolution over the last years
Significant pipeline evolution over the last years and a commitment to continue to deliver Product CandidatePreclinicalPhase 1Phase 2Phase 3RegistrationMarketed Dasiglucagon HypoPal® Rescue Pen Dasiglucagon S.C. Continuous Infusion Metabolic BI 456906 GLP-1/GLU Dual Agonist1 ZP 8396 Amylin Analog ZP
Slide 13: In 2021 we have three main focus areas for R&D
In 2021 we have three main focus areas for R&D 1 Deliver on late-stage assets HypoPal® rescue pen NDA approval Dasiglucagon CHI Phase 3 completion Glepaglutide Phase 3 execution Dasiglucagon BHAP Phase 3 initiation 2 Progress next value drivers Dasiglucagon minidose Phase 2 initiation in PBH and T1D
Slide 14: Our ambition: Leader in next generation peptide therapeutics
Our ambition: Leader in next generation peptide therapeutics with a high-value product pipeline to drive continued growth Next generation peptide platform In silico design Molecular display Oral formulation technologies Expanding therapeutic focus High-value product pipeline From hypoglycemia and T1
Slide 15: Metabolic Portfolio
Metabolic Portfolio Targeting the spectrum of hypoglycemia Advancing the promise of a bionic pancreas Expanding to Obesity 15
Slide 16: Metabolic portfolio pipeline
Metabolic Glepaglutide GLP-2 AnalogShort Bowel Syndrome on atiDapiglutide GLP-1/GLP-2 Dual AgonistSBS+ ammZP 9830 Kv1.3 Ion Channel BlockerIBD+ nfl &ZP 10000 ɑ4β7 Integrin InhibitorIBD I I GComplement C3 Inhibitor2Undisclosed Product Candidate Preclinical Phase 1 Phase 2 Phase 3 Registration Markete
Slide 17: Hypoglycemia can occur as a result of different conditions
Hypoglycemia can occur as a result of different conditions and Zealand is developing solutions for each 1 2 3 with recurrent and/or severe hypoglycemia 4 17
Slide 18: Patients are not comfortable with glucagon administration
Despite 2020 ADA recommendations, patients are not comfortable with glucagon administration Glucagon should be prescribed for all individuals at increased risk of level 2 hypoglycemia (BG<54mg/dl) so it is available should it be needed1 1/3 1/3 ~1/3 did not have a current prescription for glucagon d
Slide 19: Underappreciation of the risk of severe hypoglycemia in adults
There’s an underappreciation of the risk of severe hypoglycemia in adults Monthly Glucagon Rescue Prescriptions by Patient Age1 18,000 16,000 14,000 12,000 10,000 8,000 6,000 4,000 2,000 Most prescriptions are for children and seasonal (back-to-school period) Unmet Medical Need Despite ADA guideline
Slide 20: Dasiglucagon HypoPal rescue pen under FDA review
To address this, we have developed the Dasiglucagon HypoPal® rescue pen for treatment of severe hypoglycemia Under FDA review: PDUFA date March 27th, 2021 Dasiglucagon H2N 1 His 29 SerGlnGlyThrPheThrSerAspTyrSerLysTyr Leu Ala Asp COOH Thr Ser GluLeu TrpLysValPheGluGlu AlaArg Ala αMe Amino acid subst
Slide 21: Dasiglucagon rapid plasma glucose recovery across Phase 3
Dasiglucagon results in consistent & rapid plasma glucose recovery (PGR) across Phase 3 program 1st Pivotal 2nd Pivotal Pediatric Time to PG recovery (minutes)* 10 min 10 min 10 min % of Patients with PG increase of ≥20 mg/dL 10 minutes 65 62 65 20 minutes 99 94 100 30 minutes 100 97 100 Time to PGR
Slide 22: Congenital Hyperinsulinism is an ultra-rare disorder
Congenital Hyperinsulinism (CHI) is an ultra-rare but devastating disorder in neonates and children A disease that affects 1:30,000 - 1:50,000 births ~300 newborns are diagnosed every year with genetically determined CHI in the U.S. and EU1,2 Persistent episodes of hypoglycemia Most common cause of
Slide 23: Comprehensive Phase 3 program in CHI
Zealand has a comprehensive Phase 3 program to address the unmet need in CHI 32 patients, age 3 months-12 years. 12 patients, age 7 days-12 months. Maximum 44 patients, age 1 month onwards Hypo-prone, maximum therapy, incl. Pancreatic surgery Newly diagnosed, dependent on IV glucose Patients from 17
Slide 24: Mini-doses of dasiglucagon in Post Bariatric Hypoglycemia
Potential use of mini-doses of Dasiglucagon in other hypoglycemic conditions – Post Bariatric Hypoglycemia PBH is an under-recognized condition affecting 5-15% of patients with RYGB Positive topline results in phase 2 trial with Dasiglucagon in individuals who have undergone bariatric surgery Placeb
Slide 25: Mini-doses of dasiglucagon increased blood glucose
Mini-doses of Dasiglucagon consistently increased blood Plasma glucose (mg/dl) --30 ug--80 ug --200 ug --600 ug Time (min) “Free living” study in Type 1 diabetes planned for H1 2021 Patients will be required to exercise regularly during the study Dasi will be used to prevent or treat hypo events as
Slide 26: Dasiglucagon in Type 1 Diabetes Management: Bihormonal Bionic Pancreas
R&D Day: Metabolic Portfolio Dasiglucagon in Type 1 Diabetes Management The Bihormonal Bionic Pancreas ” Diabetes affects me all the time, and I have to think about it no matter what I do 26
Slide 27: Steven Russell on the Bihormonal Bionic Pancreas
R&D Days: Metabolic Portfolio Steven Russell, MD, PhD and Associate Professor of Medicine, Harvard Medical School about the Bihormonal Bionic Pancreas Listen to Steven Russel, MD, PhD talking about the Bihormonal Bionic Pancreas in this short video* *The iLet® bionic pancreas is an investigational d
Slide 28: Pre-pivotal studies with bihormonal bionic pancreas
Pre-pivotal studies indicate potential to normalize glycemia with bihormonal bionic pancreas 12 12% achieve goal 218 ± 63 mg/dl 11 10 HbA1c (%) 19% achieve goal 194 ± 51 mg/dl 24% achieve goal 180 ± 41 mg/dl Significant diabetes management workload 40% achieve goal 161 ± 28 mg/dl 1.9% < 60 mg/dl 34%
Slide 29: Phase 2 data supports move to phase 3
Glycemic data from phase 2 study supports decision to move to phase 3 with bihormonal bionic pancreas Phase 2 home-use clinical trial testing the iLet® bionic pancreas using Dasiglucagon1 Phase 3 trial initiation expected in H2 2021 based on positive EoP2 meeting with the FDA Insulin-Only Bihormonal
Slide 30: Bihormonal Bionic Pancreas Pivotal Trial
The Bihormonal Bionic Pancreas Pivotal Trial (BH BPPT) Bihormonal iLet with Dasiglucagon (BHBP) Insulin-Only iLet (IOBP) Usual Care BHBP BHBP Usual Care Insulin-Only iLet (IOBP) Bihormonal iLet with Dasiglucagon (BHBP) BHBP ADULTS (≥ 18y) n ~ 350 Primary endpoint A1C superiority of BH iLet versus IO
Slide 31: Obesity and associated metabolic diseases
Obesity and associated metabolic diseases The global prevalence of obesity has tripled since the mid-1970s 650 million adults and 124 million children and adolescents suffering from obesity -New England Journal of Medicine, Nov 20201 1 Kumanyika S et al., N Engl J Med (2020) 383:2197-220031
Slide 32: Dual pharmacology to address obesity
Dual pharmacology has the potential to effectively address obesity – Zealand Pharma is pursuing this from several angles Obesity is a complex metabolic disease modulated by several molecular pathways Monotherapy or single receptor-agonism is insufficient to induce changes in line with bariatric surg
Slide 33: GLP-1/glucagon dual agonism in obesity and NASH
GLP-1/glucagon dual agonism is being evaluated in obesity and NASH Boehringer-Ingelheim is progressing the development of Zealand’s dual agonist BI 456906 Phase 1: PK/safety Japanese HV Phase 1b: MAD Obese/OW; 16 weeks Phase 1a: SAD trial Healthy Volunteers Sanchez-Garrido MA et al. Diabetologia 201
Slide 34: Amylin analog with GLP-1 in preclinical obesity model
Amylin analog in combination with GLP-1 induces more weight loss vs. GLP-1 alone in preclinical obesity model 700 Start of ZP Amylin analogue treatment Vehicle ZP8396 allows for co-formulation with other peptides, including GLP-1 and GIP Once weekly dosing; Phase 1 anticipated in 2021 GLP-1 analogue
Slide 35: GIP agonist ZP6590 with GLP-1 in preclinical obesity model
GIP agonist (ZP6590) in combination with GLP-1 induces more weight loss vs. GLP-1 alone in preclinical obesity model ZP6590 allows for co-formulation with other peptides, including amylin and GLP-1 Predicted once weekly subcutaneous dosing; In IND enabling toxicology studies 4GLP-1 2GLP-1 + ZP GIP 0
Slide 36: Summary
Summary ” Robert, living with Type 1 diabetes, on the experience of severe hypoglycemia: It hit me like a ton of bricks. No warnings, one minute I was fine, next minute I wasn’t. Phase 3 studies for the bihormonal bionic pancreas are due to start towards the end of 2021 Zealand’s focus is expanding
Slide 37: Gastrointestinal and inflammatory disease portfolio
Gastrointestinal and inflammatory disease portfolio Targeting SBS Expanding to IBD and other chronic inflammatory diseases 37
Slide 38: Gastrointestinal and inflammatory disease portfolio pipeline
Gastrointestinal and inflammatory disease portfolio Dasiglucagon HypoPal® Rescue PenSevere hypoglycemia Dasiglucagon S.C. Continuous InfusionCongenital hyperinsulinism cDasiglucagon Bi-Hormonal Artificial Pancreas PumpType 1 Diabetes management i l etaboDasiglucagon Adjustable Mini-DosePBH/ T1D exer
Slide 39: Short bowel syndrome
Short bowel syndrome Patients with SBS have undergone massive intestinal surgery resulting in significantly reduced or complete loss of intestinal function Read more of Marianne’s story at zealandpharma.com/marianne-story ”My worst fear was to become what I am today: a short bowel patient.” Marianne
Slide 40: Long-term commitment to improve SBS treatment
We have a long-term commitment to improve SBS-treatment for the benefit of patients High unmet medical need Rare and severe disease affecting up to 40,000 people in the U.S. and Europe1,2 that impairs intestinal absorption, and leads to diarrhea and metabolic complications Life-long dependency Compl
Slide 41: Glepaglutide is our lead candidate for SBS
Glepaglutide is our lead candidate for treatment of SBS Glepaglutide1 – Long-acting stable GLP-2 analog Phase 2 data with increases in intestinal absorption following 3 weeks treatment Forms depot at injection site with effective half-life of ~50 hours Mean Baseline Wet Weight Absorption (g/day) 525
Slide 42: Increase in urine output bridges to Phase 3 endpoint
Increase in urine output in Phase 2 provides bridge to Phase 3 primary endpoint 71% (10 of 14 subjects) would have met the PS reduction criteria Applying the Phase 3 algorithm for parenteral support (PS) changes to the 1 & 10 mg dose groups in Phase22 57% (8 of 14 subjects) would have met the respon
Slide 43: Glepaglutide pivotal Phase 3 trial
Glepaglutide – Pivotal Phase 3 trial progressing toward results in 2022 Trial design Double-blind, placebo controlled trial in 129 SBS patients evaluating safety and efficacy of once and twice weekly dosing over 24 weeks Primary and key secondary endpoints Reduction in weekly parenteral support (PS
Slide 44: Glepaglutide Phase 3 trial program
Glepaglutide Phase 3 trial program Introducing EASE 3 Phase 3 extension trial utilizing the autoinjector EASE 4 Phase 3b trial evaluating intestinal absorption of fluid & energy over 24 weeks NEW NEW 44
Slide 45: Dapiglutide potential in SBS and GI diseases
Dapiglutide has potential to treat SBS as well as a wider range of gastrointestinal diseases Dapiglutide1,2 - Long-acting GLP-1/GLP-2 a e r a e c a f r u s ) l M a E t o S T - 2 e m n c i ( t s e t n i l l a m S *** Clinical progress Phase 1a (SAD) 800 600 400 200 0 p<0.001 p<0.001 *** Dapiglutide w
Slide 46: Expanding into IBD and chronic inflammatory diseases
Expanding into IBD and other chronic inflammatory diseases New era with superior peptide drug opportunities High-profile biological targets central to autoimmunity and chronic inflammation Kv1.3 ion channel Complement C3 Oral peptide inhibitors of biological targets with proven clinical efficacy α4β
Slide 47: Kv1.3 blocker for IBD and chronic inflammatory diseases
Kv1.3 blocker for IBD and other chronic inflammatory diseases T effector memory (TEM) cells drive auto-immunity and chronic inflammation through release of pro-inflammatory cytokines TEM cells are dependent on Kv1.3 ion channels whereas naïve and central memory T cells are dependent on Kca3.1 ion ch
Slide 48: ZP9830 for IBD and T cell driven diseases
ZP9830 for IBD and other T cell driven chronic inflammatory diseases ZP9830 is a potent and selective Kv1.3 ion channel blocker Optimized for selectivity, potency and stability In preparation for IND enabling toxicology studies Concentration-dependent inhibition of pro-inflammatory cytokine release
Slide 49: Orally-delivered α4β7 integrin inhibitor for IBD
Orally-delivered α4β7 integrin inhibitor for inflammatory bowel disease ZP10000, an α4β7 integrin inhibitor for oral delivery Oral dosing of ZP10000 reduces colonic lesion & inflammation in pre-clinical IBD disease model* Binding kinetics on par with antibodies Potential for improved tissue penetrat
Slide 50: Summary
Summary ” Mike, SBS patient, on the experience of living with a GI disease: Being tough, being strong. These are decisions that you make. Dapiglutide, a long-acting GLP-1/GLP-2 dual receptor agonist progressing towards phase 1 completion 2021 Zealand’s therapeutic focus is expanding to IBD and other
Slide 51: Zealand Peptide platform
Zealand Peptide platform 51
Slide 52: Zealand Pharma pioneers engineering of novel peptide drugs
Zealand Pharma pioneers engineering of novel Amylin and GIP analogs •Acylated long-acting peptides •Designed for co-formulation Dasiglucagon Stabilization Glepaglutide •Stabilized and long-acting GLP-2 analog α4β7 inhibitor In silico design Engineered for oral bioavailability Lixisenatide •First SIP
Slide 53: Peptides and our innovative peptide discovery platform
Peptides and our innovative peptide discovery platform Peptides are made from nature’s building blocks Our peptide discovery platform Agonist/Antagonist of biological function Mono/Dual pharmacology Inhibition of protein:protein interactions In silico modeling Formulation technologies Rational desig
Slide 54: Dasiglucagon demonstrates ability to improve peptide drug properties
Dasiglugacon is a demonstration of our ability to improve drug properties of peptides Dasiglucagon optimized to address poor stability and solubility of glucagon Avoid fibrillation in aqueous solutions 7 of the 29 amino acids in glucagon replaced – more charged molecule prevents aggregation Dasigluc
Slide 55: Dapiglutide: dual pharmacology with long plasma half-life
Dapiglutide – engineering dual pharmacology with long plasma half-life Balanced receptor potencyPlasma half-life of ~120 hours in humans Native GLP-1 & GLP-2 have 33% sequence homology Rational designed dual acting peptide with 10 AA substitutions in the GLP-2 sequence to add GLP-1 activity Rapid cl
Slide 56: Kv1.3 blocker: from venom to anti-inflammatory treatment
Kv1.3 blocker – from venom to anti-inflammatory treatment Ion channel drug target – Kv1.3 No native human Kv1.3 ion channel ligands exists Selectivity is key for drugs that target ion channels Venom library provided starting point for Kv1.3 blocker From venom to ZP9830 Venom starting points were hig
Slide 57: C3 peptide inhibitor designed to be best-in-class
C3 peptide inhibitor – designed to be best-in-class C3 is a part of the innate immune systemPeptides are ideal for C3 inhibition Complement system is a part of the innate immune system – high concentrations of peptide needed for efficient inhibition No natural peptide inhibitor of C3 exists – attrac
Slide 58: α4β7 integrin inhibitor using in silico design
α4β7 integrin inhibitor – utilizing in silico design for optimal binding and oral availability Validated target – oral treatment ZP10000 binding on par with antibodies α4β7 interaction with MAdCAM1 –immune cell recruitment to intestine Oral bioavailability is not possible for antibodies The interact
Slide 59: Our next generation peptide platform
Our next generation peptide platform builds on solid know-how and new innovative technologies Computational chemistry Library starting points Next generation peptide drugs Rational design Molecular display Formulation technologies 59