Slide 1: Safety, tolerability, and clinical effects of dapiglutide, a once-weekly GLP-1R/GLP-2R agonist
Safety, tolerability, and clinical effects of dapiglutide, a once-weekly GLP-1R/GLP-2R agonist Tim Heise Stine Just Maarbjerg1, Rebecca Zachariae1, Ulrike Hövelmann2, Nicklas Järvelä Johansen1, Jonas Lundahl1, Lone Frost Larsen1, Nanna Skall Sørensen1, Theis Gondolf1, Tim Heise2 1Zealand Pharma A/S,
Slide 2: Disclosures
Disclosures • Received research funds from Adocia, Afon Technology, Astra Zeneca, Altimmune, Betagenon, Biocon, Bioton, Cass Pharmaceuticals, Civica Foundation, Corteria, Cytoki, Eli Lilly, Enyo Pharma, Gan&Lee Pharmaceuticals, Genova, Nanexa, Neodyne, Novo Nordisk, SamChunDang Pharm. Co., Spiden, S
Slide 3: What is dapiglutide?
What is dapiglutide? Dapiglutide (GLP-1/GLP-2): Potential first-in-class targeting obesity and low-grade inflammation Strong scientific rationale to be validated in clinical Design of the molecule trials Dapiglutide is derived from a 33-amino acid GLP-2 People with obesity have increased low-grade p
Slide 4: Objectives: Dapiglutide Phase 1b MAD – part 1 objectives and endpoints
Trial objectives and endpoints Objectives: Dapiglutide Phase 1b MAD – part 1 Primary objective Primary endpoint • To evaluate the safety and tolerability of • Incidence of TEAEs dapiglutide administered as multiple SC injections in overweight and obese, but otherwise healthy subjects in order to ide
Slide 5: Trial design: Dapiglutide Phase 1b MAD – part 1 design
Trial design Trial design: Dapiglutide Phase 1b MAD – part 1 A randomized, double-blind, placebo-controlled, Phase 1b, MAD trial of dapiglutide1 No lifestyle modifications, such as counselling on diet and exercise Part 1 Part 2 Dose escalation every 2 weeks Dose escalation every 4 weeks 14:4 dapiglu
Slide 6: Demographics and clinical characteristics
Trial results Demographics and clinical characteristics Dapiglutide Phase 1b MAD trial – baseline characteristics1,2 Placebo Dapiglutide 7.5 mg Dapiglutide 10 mg Dapiglutide 13 mg Total (N=12) (N=14) (N=14) (N=14) (N=54) Male sex, 10 (83%) 13 (93%) 10 (71%) 13 (93%) 46 (85%) n (%) Age (years), 54 (2
Slide 7: Safety summary of TEAEs
Trial results Safety summary of TEAEs 13-weeks dose escalation cohorts – dose escalation every 2nd week Placebo Dapiglutide 7.5 mg Dapiglutide 10 mg Dapiglutide 13 mg Adverse events (N=12) (N=14) (N=14) (N=14) N (%) E N (%) E N (%) E N (%) E Total 8 (66.7%) 17 14 (100%) 52 14 (100%) 135 13 (92.9%) 1
Slide 8: Most common TEAEs
Trial results Most common TEAEs 13-weeks dose escalation cohorts – dose escalation every 2nd week System Organ Class Placebo Dapiglutide 7.5 mg Dapiglutide 10 mg Dapiglutide 13 mg Preferred Term (N=12) (N=14) (N=14) (N=14) N (%) E N (%) E N (%) E N (%) E Gastrointestinal disorders 5 (41.7%) 8 10 (71
Slide 9: Summary of additional safety parameters
Trial results Summary of additional safety parameters No clinically significant findings for vital signs, ECG, physical examinations, or clinical laboratory assessments Mean pulse rate increased for all cohorts compared to placebo and was approximately 5–10 bpm higher than baseline towards the end o
Slide 10: Summary of pharmacokinetics
Trial results Summary of pharmacokinetics Dapi 7.5 mg Dapi 10 mg Dapi 13 mg (N=8) (N=10) (N=7) • Dapiglutide shows dose proportional pharmacokinetics from 7.5 mg to 13 mg • Both for Cmax and AUCtau • Tmax was observed at 24 hours • Terminal half-life of approximately 120 hours (5 days) was confirmed
Slide 11: Relative body weight change from baseline to week 13
Trial results Relative body weight change from baseline to week 13 Estimated mean percent change in body weight Dapi 7.5 mg (N=14) Dapi 10 mg (N=14) Dapi 7.5 mg (N=14) Dapi 10 mg (N=14) Dapi 13 mg (N=14) Dapi 13 mg (N=14) Placebo (N=12) 5 Dapi 7.5 mg Dapi 10.0 mg Dapi 13.0 mg Difference (mean and 95
Slide 12: Conclusions
Trial conclusion Conclusions Dapiglutide treatment appeared safe and well-tolerated with an AE profile similar to other incretin-based therapies Dapiglutide displayed dose proportional pharmacokinetics and is suitable for once-weekly dosing Placebo-adjusted reductions in body weight were up to a mea
Slide 13: Data from part 2 to be presented at future scientific conference
Data from part 2 to be presented at future scientific conference
Slide 14: Thank you
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