Zealand Pharma A/s · OMXCOP:ZEAL
Zealand Pharma A/s — ObesityWeek 2024
17 slides from Zealand Pharma A/s's conference presentation, 2024
Slide 1: Safety, Tolerability, and Clinical Effects of Petrelintide (ZP8396), A Long-acting Amylin Analog
Safety, Tolerability, and Clinical Effects of Petrelintide (ZP8396), A Long-acting Amylin Analog Tim Heise1 On behalf of: Minna Brændholt Olsen2, Jon Griffin2, Ulrike Hövelmann1, Stanislava Macura2, Thue Johansen2, Berith Fredsted Hagen2, Helle Frimer-Larsen2, Evan Charles Frary2, Dan Hesse2 1Profil
Slide 2: GLP-1RA-based therapies are efficacious for weight loss, but have been associated with GI tolerability issues
GLP-1RA-based therapies are efficacious for weight loss, but have been associated with GI tolerability issues1 Rx Currently, two once-weekly (OW) GLP-1RA-based therapies are approved for weight management,2,3 offering mean weight loss of ~15–21%4,5 GI adverse events, such as nausea, vomiting, and di
Slide 3: What is petrelintide?
What is petrelintide? Petrelintide (ZP8396) is a 36-amino-acid acylated peptide, based on the peptide sequence of human amylin1 Long-acting acylated amylin analog suitable for OW administration in humans1,2 Chemically and physically stable at neutral pH, minimizing fibrillation3 Potent agonistic eff
Slide 4: Objectives: Petrelintide Phase 1b MAD
Objectives: Petrelintide Phase 1b MAD Primary objective Primary endpoint • To evaluate the safety and tolerability of • Incidence of TEAEs petrelintide administered as multiple SC injections in overweight and obese, but otherwise healthy, subjects in order to identify the maximum tolerated dose with
Slide 5: Trial design: Petrelintide Phase 1b MAD
Trial design: Petrelintide Phase 1b MAD A randomized, double-blind, placebo-controlled, Phase 1b, MAD trial of petrelintide1,2 Dose escalation within 1.0 2.0 4.0 6.0 7.5 9.0 mg (6 weeks) cohorts every second week 0.6 1.2 2.4 3.6 4.8 mg (8 weeks) 3 cohortsa N=48 • Adults 18–64 0.6 1.2 2.4 mg (12 week
Slide 6: Demographics and clinical characteristics
Demographics and clinical characteristics Petrelintide Phase 1b MAD trial: baseline characteristics1,2 Placebo Petrelintide 2.4 mg Petrelintide 4.8 mg Petrelintide 9.0 mg Total (N=12) (N=12) (N=12) (N=12) (N=48) Male sex, 10 (83) 10 (83) 9 (75) 9 (75) 38 (79) n (%) Age (years), 46 (23–63) 48 (26–57)
Slide 7: Participants
Treatment completion and compliance with dose escalation within cohorts 0.6 1.2 2.4 mg 0.6 1.2 2.4 3.6 4.8 mg 1.0 2.0 4.0 6.0 7.5 9.0 mg Due to other Due to AEs 1 reasons 2 Due to other 3 reasons 4 Participants 5 6 7 8 9 10 11 12 0 2 4 6 8 10 12 14 16 0 2 4 6 8 10 12 14 16 0 2 4 6 8 10 12 14 16 • Th
Slide 8: Summary of treatment emergent adverse events (TEAEs)
Summary of treatment emergent adverse events (TEAEs) 100% 100% 92% E=58 92% E=95 12 Placebo (N=12) E=62 12 E=63 12 11 11 Petrelintide 2.4 mg (N=12) 10 Number of participants Petrelintide 4.8 mg (N=12) 8 Petrelintide 9.0 mg (N=12) 6 4 17% 17% 8% E=2 E=3 8% 2 E=2 E=2 2 2 1 0 0 0 0 1 0 ≥1 TEAE Moderate
Slide 9: TEAEs by System Organ Class
TEAEs by System Organ Class Placebo Petrelintide 2.4 mg Petrelintide 4.8 mg Petrelintide 9.0 mg SOC n (%) E n (%) E n (%) E n (%) E Total TEAEs 11 (91.7) 62 12 (100) 58 11 (91.7) 63 12 (100) 95 Metabolism and nutrition disorders 6 (50.0) 9 10 (83.3) 12 8 (66.7) 12 9 (75.0) 13 Respiratory, thoracic a
Slide 10: Selected Gastrointestinal TEAEs
Selected Gastrointestinal TEAEs All GI TEAEs were mild, except for one event of moderate nausea and one event on moderate vomiting in a single participant 12 12 Number of participants Nausea Vomiting 10 10 8 8 6 33% 33% 6 E=6 E=11 8% 4 17% 17% 4 E=2 E=2 E=2 4 4 2 2 1 2 2 0 0 0 0 0 Placebo Petrelinti
Slide 11: Summary of additional safety parameters
Summary of additional safety parameters No clinically significant findings for vital signs, ECG, physical examinations, or clinical laboratory assessments Mean pulse rate decreased for all cohorts compared to placebo and was approximately 5 bpm lower than baseline towards the end of treatment Trend
Slide 12: Summary of pharmacokinetics
Summary of pharmacokinetics 1.5E +05 AUCtau at steady state (nmol/L*h) 1E +05 • Petrelintide shows dose proportional pharmacokinetics from 0.6 mg to 9.0 mg • Both for Cmax and AUCtau 5E +04 • Tmax was observed at 24 hours • Terminal half-life of approximately 240 hours (10 days) was confirmed • Petr
Slide 13: Change in body weight
Change in body weight Observed mean (95% CI) percent change from baseline in body weight 2 Petrelintide 2.4 mg Petrelintide 4.8 mg 0 -2 -8.6% -4 Change from baseline (%) -6 -8 -4.8% -10 Baseline: 98.1 kg Baseline: 89.5 kg -12 2 Petrelintide 9.0 mgb Placebo 0 -2 -8.3% -4 -6 -8 -1.7% -10 Baseline: 87.
Slide 14: STEP – semaglutide SC Phase clinical trial
STEP 1 – semaglutide SC Phase 3 clinical trial Mean (95% CI) percent change from baseline in body weight – observed in-trial data 0 -2 Change from baseline (%) Placebo (N=655) -4 -6 -8 -10 -12 -14 -16 Semaglutide (N=1306) -18 0 4 8 12 16 20 28 36 44 52 60 68 Weeks since randomization Semaglutide 0.2
Slide 15: Summary
Summary Safety • 16 weeks of treatment with petrelintide maintenance doses up to 9.0 mg was well tolerated and safe • The vast majority of TEAEs reported by petrelintide-treated participants were mild; only one participant reported moderate GI AEs • Of 36 petrelintide-treated participants, one parti
Slide 16: Overall conclusions
Overall conclusions This Phase 1 trial demonstrated excellent tolerability of petrelintide and achievement of clinically relevant weight loss after 16 weeks Petrelintide will be further investigated in a Phase 2 obesity trial
Slide 17: Access this presentation here
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