Slide 1: Pemvidutide (ALT-801) results of first-in-human clinical trial
Pemvidutide (ALT-801), a novel GLP-1/glucagon dual receptor agonist, achieves rapid and potent reductions in body weight and liver fat: Results of a placebo-controlled, double-blind, first-in-human (FIH) clinical trial Stephen A. Harrison1, John Nestor2, Sarah K. Browne3, Jacques D. Payne3, Staci M.
Slide 2: Presenter Disclosures
Presenter Disclosures Stephen Harrison • Scientific advisor or consultant to: Akero, Alentis, Altimmune, Arrowhead, Axcella, BMS, Echosens, Galectin, Gilead, Hepion, Hepagene, HistoIndex, Intercept, Madrigal, Medpace, Metacrine, NGM Bio, Northsea, Novartis, Novo Nordisk, PathAI, Perspectum, Poxel, S
Slide 3: Pemvidutide (ALT-801)
Pemvidutide (ALT-801) Balanced (1:1) GLP-1:glucagon dual receptor agonist Slows gastric emptying COOH ↓ Food intake VVVVVVVVVVVVVVVVVV EuPort™ domain Weekly dosing, improved PK for improved GI tolerability GLP-1 Glucagon ↑ Insulin secretion Glucagon specificity GLP-1 specificity ↓ Glucagon secretion
Slide 4: Pemvidutide Phase 1 SAD/MAD Trial Design
Pemvidutide Phase 1 SAD/MAD Trial Design SAD/MAD Design Randomized, double-blind placebo-controlled study 70 subjects with overweight/obesity (BMI 25 - 40 kg/m2) Multiple ascending dose (MAD) phase (n = 34) 4:1 randomization (pemvidutide: placebo), with placebos pooled No caloric restriction or life
Slide 5: Characteristics of Study Participants (MAD Phase)
Characteristics of Study Participants (MAD Phase) Treatment Baseline Characteristics 1.2 mg 1.8 mg 2.4 mg Pooled placebo (n=7) (n=9) (n=11) (n=7) Age, years mean (SD) 27.7 (11) 32.0 (11) 31.4 (12) 35.3 (12) BMI, kg/m2 mean (SD) 30.0 (4) 30.1 (4) 31.8 (3) 31.0 (4) Sex female, n (%) 1 (14%) 4 (44%) 7
Slide 6: Study Disposition (MAD Phase)
Study Disposition (MAD Phase) No withdrawals for adverse events Treatment Characteristic Pooled 1.2 mg 1.8 mg 2.4 mg placebo Safety population1 n (%) 7 (100%) 9 (100%) 11 (91.7%) 7 (100%) Completed study n (%) 6 (86%) 9 (100%) 9 (82%) 5 (71%) Early withdrawal n (%) 1 (14%) 0 (0%) 2 (18%) 2 (29%) Los
Slide 7: Pemvidutide PK Profile
Pemvidutide PK Profile Long half-life supports weekly dosing Lower Cmax and delayed Tmax may enhance tolerability ALT-801 PK PARAMETER 1.8 mg SC Peak concentration (Cmax) 27.1 nmol/L Area under curve (AUC) 0-168 3400 nmol•hr Half-life (t1/2) 110 hrs Time to peak concentration (Tmax) 70 hrs 7
Slide 8: Weight Loss at Week 12 – Group Responses
Weight Loss at Week 12 – Group Responses 8
Slide 9: Weight Loss at Week 12 – Individual Responses
Weight Loss at Week 12 – Individual Responses 9
Slide 10: No Decline in Rate of Weight Loss at 12 weeks
No Decline in Rate of Weight Loss at 12 weeks 10
Slide 11: Changes in Serum Lipids at Week 12
Changes in Serum Lipids at Week 12 11
Slide 12: Effects on Lipid Metabolism
Effects on Lipid Metabolism Increased lipid oxidation and decreased lipid synthesis 12
Slide 13: Robust Decreases in Lipids Implicated in NASH Inflammation
Robust Decreases in Lipids Implicated in NASH Inflammation 13
Slide 14: Reduction of Liver Fat to Below Limit of Detection by Week 6
Reduction of Liver Fat to Below Limit of Detection (LOD) by Week 6 Greater than 90% reduction at 1.8 mg and 2.4 mg Individual Subjects with MRI-PDFF ≥ 5% at Baseline MRI-PDFF (%) Treatment Group Relative ∆ at Week 6 Baseline Week 6 Individual Mean Placebo 5.2 3.7 28.8 28.8 19.1 14.0 26.7 Pemvidutide
Slide 15: Robust Reduction of Liver Fat Content by MRI-PDFF
Robust Reduction of Liver Fat Content by MRI-PDFF From 19.5% to below limit of detection (LOD) by Week 6 Subject at 2.4 mg dose 19.5% Below LOD 15
Slide 16: Safety Overview (MAD Phase)
Safety Overview (MAD Phase) No serious AEs, severe AEs or AEs leading to treatment discontinuation Treatment Characteristic Pooled 1.2 mg 1.8 mg 2.4 mg placebo (n = 7) (n = 9) (n = 12) (n = 7) Serious or severe AEs n (%) 0 (%) 0 (%) 0 (%) 0 (%) AEs leading to treatment discontinuation n (%) 0 (%) 0
Slide 17: Summary
Summary Weight loss • 10.3% mean weight loss achieved at 1.8 mg dose at 12 weeks • The trajectory suggests that the rate of weight loss will continue beyond 12 weeks Lipids • Reduction of liver fat content to below LOD, equivalent to a greater than 90% decrease • Robust improvements in lipids specie
Slide 18: Conclusions and Next Steps
Conclusions and Next Steps • Pemvidutide represents a promising new agent for the treatment of obesity and NASH • Upcoming data: • NAFLD and obesity trial • 72 subjects with obesity or overweight plus baseline MRI-PDFF ≥ 10%, with endpoints of liver fat reduction and weight loss • Data readouts expe