Slide 1: Analyst and Investor Call to Review Oral GLP-1 Data: Scientific Data
Analyst and Investor Call to Review Oral GLP-1 Data: Scientific Data The European Association for the Study of Diabetes (EASD) Annual Meeting, Stockholm September 21, 2022 Breakthroughs that change patients’ lives 1
Slide 2: Forward-Looking Statements and Other Notices
Forward-Looking Statements and Other Notices This presentation and our discussions during this conference call will include forward-looking statements that are subject to substantial risks and uncertainties, many of which are beyond our control, that could cause actual results to differ materially f
Slide 3: Danuglipron Phase 2b study in adults with Type 2 diabetes
Oral small molecule GLP-1 receptor agonist danuglipron (PF-06882961) results in glucose lowering and body weight loss over 16 weeks in a Phase 2b study in adults with Type 2 diabetes mellitus Aditi R Saxena1, Juan Frias 2, Lisa S Brown3, Donal N Gorman4, Nikolaos Tsamandouras 1, Morris J Birnbaum1*
Slide 4: Introduction, Objectives and Study Design
Introduction, Objectives and Study Design • Objectives and study design: Phase 2b, randomized, placebo-controlled, parallel group, dose-ranging study to examine the effect of danuglipron on efficacy, safety, tolerability and pharmacokinetics over 16 weeks in adults with T2D (NCT03985293) • Primary e
Slide 5: Eligibility Criteria and Baseline Characteristics
Eligibility Criteria and Baseline Characteristics Key Eligibility Criteria Demographics and Baseline Characteristics of the Overall Populationa • T2D treated with diet and exercise, with or • Age: 58.6 ± 9.33 years without metformin • Female: 49.1% • HbA1c ≥7% and ≤10.5% • Race: White 83.5%, other 1
Slide 6: Significant, Dose-responsive Declines in HbA1c
Significant, Dose-responsive Declines in HbA1c All danuglipron groups demonstrated statistically significant dose-responsive declines from baseline in HbA1c at Week 16 compared with placebo (all P<0.0001, except 2.5 mg BID which was P<0.01) HbA1c: Change from Baseline at Week 16 HbA1c: Change from B
Slide 7: Significant Reduction in Fasting Plasma Glucose Over Weeks
Significant Reduction in Fasting Plasma Glucose Over 16 weeks At Week 16, FPG was statistically significantly reduced with all Danuglipron doses compared with placebo (P<0.001 for all doses ≥10 mg BID; P<0.1 for 2.5 mg BID) FPG: Change from baseline at Week 16 FPG: Change from Baseline Through The S
Slide 8: Significant Decline in Body Weight Over Weeks
Significant Decline in Body Weight Over 16 Weeks Body weight was statistically significantly reduced at Week 16 in the Danuglipron 80 mg BID and 120 mg BID groups (both P<0.001), compared with placebo Body Weight: Change from Baseline at Week 16 Body Weight: Change from Baseline Through the Study 2
Slide 9: Safety & Tolerability Profile Consistent with Mechanism
Safety & Tolerability Profile Consistent with Mechanism • The majority of AEs were mild, with nausea, diarrhoea and vomiting most common • No episodes of severe hypoglycemia • No clinically significant, adverse trends in laboratory measures, electrocardiogram or vital sign abnormalities Danuglipron
Slide 10: Danuglipron 12-week Phase 2a study in adults with Type 2 diabetes
Efficacy, safety and tolerability of danuglipron (PF-06882961) over 12 weeks in Phase 2a study in adults with Type 2 diabetes mellitus Donal N Gorman1, Aditi R Saxena2, Juan Frias3, Rene N Lopez4, Nikolaos Tsamandouras2, Morris J Birnbaum2* 1 Pfizer Worldwide Research and Development, Cambridge, UK;
Slide 11: Danuglipron 12-Week Phase 2a Study Overview
Danuglipron 12-Week Phase 2a Study Overview • Danuglipron: an oral small molecule GLP-1R agonist being investigated for T2D and/or obesity • Objectives and study design: phase 2a, randomised, double-blind, placebo-controlled, parallel-group study to assess the tolerability, safety and pharmacodynami
Slide 12: Declines in HbA1c and FPG with Danuglipron at Week 12 in T2D
Declines in HbA1c and FPG with Danuglipron at Week 12 in T2D Statistically significant reductions from baseline in HbA1c in all Danuglipron groups, and FPG across most groups, at Week 12 were demonstrated compared with placebo HbA1c: Change from baseline at week 12 in T2D FPG: Change from baseline a
Slide 13: Declines in Body Weight with Danuglipron at Week 12
Declines in Body Weight with Danuglipron at Week 12 Body weight: Change from baseline at week 12 in T2D • T2D 2 • Statistically significant reductions in body weight Least squares mean (90% CI) change from baseline at Week 12 in body weight (kg) in all Danuglipron groups at Week 12 were 0 demonstrat
Slide 14: Tolerability and Safety of Danuglipron in 12 Week Phase 2 Study
Tolerability and Safety of Danuglipron in 12 Week Phase 2 Study • Majority of AEs were mild, with nausea, vomiting and diarrhoea most commonly reported; incidence of nausea and vomiting was generally greater at higher doses T2D Obesity without T2D Danuglipron Danuglipron Danuglipron Danuglipron Danu
Slide 15: Summary of Danuglipron Phase 2 Data
Summary of Danuglipron Phase 2 Data • These Phase 2 clinical data with an oral small molecule GLP-1R agonist demonstrate that danuglipron was generally safe, with a tolerability profile consistent with the mechanism of action1,2 • Danuglipron reduced HbA1c, FPG and body weight in T2DM at multiple do
Slide 16: Once-daily oral GLP-1R agonist PF-07081532 Phase 1b
Once-daily oral small molecule GLP-1R agonist PF-07081532 robustly reduces glucose and body weight within 4-6 weeks in a Phase 1b in adults with Type 2 diabetes and non-diabetic adults with obesity Clare Buckeridge1, Nikolaos Tsamandouras1, Santos Carvajal-Gonzalez1, Lisa S Brown2, Kristin L Chidsey
Slide 17: Study Design Overview
Study Design Overview • Inpatient study (NCT05158244) conducted at 2 clinical research units in the United States • 6 cohorts were enrolled: 5 cohorts of participants with T2D and 1 cohort with obesity • PF-07081532 or placebo administered once daily, with breakfast • Rapid titration used to achieve
Slide 18: Population and Key Endpoints
Population and Key Endpoints Adult Participants Key Safety and Tolerability Endpoints With type 2 diabetes: • Adverse events (AEs), discontinuations due to AEs • T2D • Laboratory tests, vital signs, 12-lead ECGs (stable metformin ≥ 500 mg) • HbA1c 7%–10.5% • BMI 24.5–45.5 kg/m2 Other Assessments Wit
Slide 19: Key Baseline Demographic and Disease Characteristics
Key Baseline Demographic and Disease Characteristics A total of 66 participants were randomised T2D: 51 participants; 40 for dosing duration of 28 days and 11 for dosing duration of 42 days Obesity: 15 participants for dosing duration of 42 days T2D Obesity Age, years 58.6 (8.3) 53.3 (9.1) Male, % 5
Slide 20: Robust Declines in Mean Daily Glucose with Once-daily PF-07081532
Robust Declines in Mean Daily Glucose with Once-daily PF-07081532 in Participants with T2D 0 baseline in MDG (mg/dL) at end of treatment Posterior mean (90% CI) change from Observed mean reductions from baseline in -40 -29.1 MDG were dose-dependent -47.8 Each of the PF-07081532 doses were -80 -64.2
Slide 21: Fasting Plasma Glucose Approaching Non-diabetic Thresholds with PF-07081532
Fasting Plasma Glucose Approaching Non-diabetic Thresholds with Once-daily PF-07081532 in Participants with T2D 0 LS mean (SE) change from baseline in FPG (mg/dL) at end of treatment Observed average reductions from baseline in FPG were up to -79 mg/dL over 28 days and -40 up to -102 mg/dL over 42 d
Slide 22: HbA1c Reduction with Once-daily PF-07081532 for 4 to 6 Weeks
HbA1c Reduction with Once-daily PF-07081532 for 4 to 6 Weeks in Participants with T2D 0 LS mean (SE) change from baseline in HbA1c (%) at end of treatment While longer duration of intervention is -0.50 required to assess the effect of treatment on -0.60 HbA1c, reductions were observed following -1 -
Slide 23: Dose-responsive Weight Reduction with Once-daily PF-07081532
Dose-responsive Weight Reduction with Once-daily PF-07081532 for 4 to 6 Weeks 0 LS mean (SE) change from baseline in weight (kg) at end of treatment -1 While longer duration of intervention is -2 required to assess the effect of treatment on body weight, reductions were observed -3 following dosing
Slide 24: Observed Adverse Effect Profile of PF-07081532 in Phase 1b Study
Observed Adverse Effect Profile of PF-07081532 in Phase 1b Study is Consistent with the Mechanism of Action Adverse Events: Most events (87% for T2D; 94% for obesity) were reported as mild in intensity, with gastrointestinal disorders most common across groups, in line with the mechanism of action.
Slide 25: PF-07081532 Pharmacokinetic Profile Following Last Dose
PF-07081532 Pharmacokinetic Profile Following Last Dose • PF-07081532 exposure (AUC24 and Cmax) generally increased in an approximately dose-proportional manner across the dose range studied • Observed half-life is supportive of once-daily administration • No substantial differences in exposure obse
Slide 26: Phase 1b Data with PF-07081532 Support Potential Best-in-Class Profile
Phase 1b Data with PF-07081532 Over 4-6 Weeks in T2D and Obesity Support Potential Best-in-Class in Efficacy and Tolerability • Dose-dependent reductions from baseline in MDG, FPG and HbA1c in participants with T2D • Declines in body weight, with higher doses of PF-07081532 demonstrating greater red