Astrazeneca Plc · LSE:AZN
Astrazeneca — Investor Day (November 2024)
40 slides from Astrazeneca's investor day presentation, Nov 4, 2024
Slide 1: Meet the Management: Weight Management Virtual Event
AZN Meet the Management: Weight Management Virtual Event Webinar for investors and analysts 4 November 2024 1
Slide 2: Forward-looking statements
Forward-looking statements In order, among other things, to utilise the ‘safe harbour’ provisions of the US Private Securities Litigation Reform Act of 1995, AstraZeneca (hereafter ‘the Group’) provides the following cautionary statement: This document contains certain forward-looking statements wit
Slide 3: Weight Management @ AstraZeneca
Weight Management @ AstraZeneca Sharon Barr I. Weight Management @ AZN EVP, BioPharmaceuticals R&D ― Introduction and growth ambitions ― Weight management landscape Mikhail Kosiborod, MD ― Our weight management strategy VP, Research @ Saint Luke’s Health System, Kansas City Elisabeth Björk II. Pipel
Slide 4: Ambition – $80bn Total Revenue by 2030 & sustained 2030+ growth
Ambition – $80bn Total Revenue by 2030 & sustained 2030+ growth Working on “today, tomorrow and the day after" Beyond 2030 Illustrative only, not to scale ADCs and Radioconjugates Cell therapy and T-cell engagers Launching key NMEs $80bn Gene therapy AZD0120 rilvegostomig AZD0486 saruparib Next-gene
Slide 5: BioPharmaceuticals – next wave of growth to 2030 and beyond
BioPharmaceuticals – next wave of growth to 2030 and beyond Illustrative only, not to scale Launching NMEs Beyond 2030 baxdrostat dapa FDCs Amyloidosis combinations to address full spectrum tozorakimab of disease Existing portfolio IVX-A12 Weight management and risk factors Expanding modalities in r
Slide 6: Mikhail Kosiborod, MD
Mikhail Kosiborod, MD VP, Research @ Saint Luke’s Health System, Kansas City ― Physician leader overseeing strategic direction for all activities across the Academic Research Organization ― Designed and led clinical trials that made critical contributions to understanding the impact of SGLT2 inhibit
Slide 7: Sustainable weight management is essential for cardiometabolic organ protection
Landscape and Strategy Sustainable weight management is essential for cardiometabolic organ protection The weight management Underlying Multi-organ Obesity landscape continues to evolve Risk factors conditions effects BMI: >30 63% Insulin resistance Chronic kidney disease of obesity population has 1
Slide 8: Going beyond obesity to improve quality of weight loss and manage key co-morbidities
Landscape and Strategy Going beyond obesity to improve quality of weight loss and manage key co-morbidities overweight obesity 63% of patients diagnosed with obesity also suffer Population (millions) >50% of global from one or more comorbidities2 population will suffer from 1,914 overweight or 988 1
Slide 9: Delivering durable weight loss, addressing cardiometabolic risk and protecting organs
Landscape and Strategy Delivering durable weight loss, addressing cardiometabolic risk and protecting organs Obesity Overweight T2D ( obesity/ ( other severe (+ organ overweight + co-morbidities) protection) organ protection) AZD5004 AZD5004 AZD5004 oGLP-1 RA oGLP-1 RA oGLP-1 RA AZD6234 Potential
Slide 10: Three high potential assets progressing to Phase IIb
Landscape and Strategy $5bn+* Three high potential assets progressing to Phase IIb AZD5004 AZD6234 AZD6234 + AZD9550 oGLP-1 long-acting amylin long-acting amylin + GLP-1/glucagon • Small molecule • Selective amylin agonist • Triple mechanism • Strong target engagement • Once-weekly s.c. dosing • Onc
Slide 11: AZD5004 Oral GLP-1 RA
AZD5004 Oral GLP-1 RA Elisabeth Björk SVP, LATE CVRM 11
Slide 12: AZD5004 is a potent oral GLP-1 small molecule
AZD5004 | oGLP-1 AZD5004 is a potent oral GLP-1 small molecule No adverse effects in preclinical 9-month trial1 and dose- Intravenous glucose tolerance test1 confirms target dependent difference in body weight gain vs. controls engagement across range of doses tested in Phase I trial 60000 25mg* (ch
Slide 13: Phase I first-in-human SAD/MAD trial conducted in controlled in-patient setting
AZD5004 | oGLP-1 Phase I first-in-human SAD/MAD trial conducted in controlled in-patient setting with fasting requirements Controlled in-patient setting included 14-hour fasting window and 1,800 average daily caloric intake Part 1 – SAD in healthy participants Primary endpoint: Cohort A1 (N=8; A/P=6
Slide 14: SAD/MAD PK supports potential for improved tolerability profile and once-daily dosing
AZD5004 | oGLP-1 SAD/MAD PK supports potential for improved tolerability profile and once-daily dosing Flat SAD PK profile MAD PK consistent with SAD PK 1mg 4mg 10mg 25mg Day 1 Day 2 – 27 Day 28 40 MAD – 5mg 103 30 20 102 AZD5004 concentration (ng/mL) 10 Weight normalised AZD5004 0 101 concentration
Slide 15: AZD5004 may be administered with or without food
AZD5004 | oGLP-1 AZD5004 may be administered with or without food No significant food effect observed in food effect trial 1000 500 AZD5004 concentration (ng/mL) 250 100 Half-life at 50mg: 10 20.7h fed 21.2h fasted 1 0 24 48 72 96 120 Fed Fasted Time (hours) SAD = single ascending dose; PK = pharmac
Slide 16: Doses 50mg or below well-tolerated in healthy volunteer SAD trial
AZD5004 | oGLP-1 Doses 50mg or below well-tolerated in healthy volunteer SAD trial Cohort A1 Cohort A2 AZD5004 AZD5004 Placebo Total AZD5004 AZD5004 AZD5004 AZD5004 Placebo Total 10mg 25mg 50mg 100mg 200mg 300mg N=6 N=6 N=8 N=9 N=6 N=6 N=6 N=6 N=8 N=9 Variables, n (%) TEAEs 1 (17) 0 2 (25) 4 (44) 4
Slide 17: Tolerability supports limited need for titration in MAD trial
AZD5004 | oGLP-1 Tolerability supports limited need for titration in MAD trial AZD5004 AZD5004 AZD5004 AZD5004 Placebo Total 5mg 10mg 30mg 50mg (uptitrated) Variables, n (%) N=9 N=9 N=10 N=10 N=13 N=51 TEAEs 7 (78) 3 (33) 10 (100) 9 (90) 8 (62) 37 (73) Drug-related 4 (44) 2 (22) 10 (100) 9 (90) 8 (6
Slide 18: Exploratory PD data from SAD trial confirm target engagement of GLP-1R
AZD5004 | oGLP-1 Exploratory PD data from SAD trial confirm target engagement of GLP-1R Reduction in glucose in healthy volunteers during oral glucose tolerance test from doses ≥4mg Glucose AUC percent change from D-1 to D1 20 Percent change (%) 0 -20 -40 Placebo 1mg 4mg 10mg 25mg 50mg 100mg 200mg 3
Slide 19: Reduction in glucose and body weight observed in MAD T2D trial at 50mg
AZD5004 | oGLP-1 Reduction in glucose and body weight observed in MAD T2D trial at 50mg Fasting glucose Glucose AUC (MMMT) Body weight 0 0 0 % change from BL in MMTT glucose AUC Change from BL in fasting glucose at Day 28, mg/dL (Mean ± SD) -2 % change in body weight -50 at Day 28 (Mean ± SD) -20 fr
Slide 20: Dose-dependent reduction in glucose and body weight observed in MAD T2D trial
AZD5004 | oGLP-1 Dose-dependent reduction in glucose and body weight observed in MAD T2D trial Fasting glucose Glucose AUC (MMMT) Body weight 1500 0 plasma glucose at Day 28 (mg/dL) Change from baseline in body 0 Change from baseline in fasting weight at Day 28 (%) -38.5mg/dL 1200 -2.5 Glucose MMTT
Slide 21: Phase I data supports initiation of Phase II trials
AZD5004 | oGLP-1 AZD5004 Phase I data supports initiation of Phase II trials Proven mechanism Encouraging safety Favourable route and potency profile at range of doses of administration ― Evidence of GLP-1 receptor ― No serious adverse events ― Once-daily oral administration target engagement ― Favo
Slide 22: Phase IIb VISTA designed to evaluate body weight reduction
AZD5004 | oGLP-1 Phase IIb VISTA designed to evaluate body weight reduction Patient population: VISTA NCT06579092 | Randomised, ― ≥18 years old double-blind, placebo- Arm 1 | AZD5004 | Dose X controlled dose finding trial ― BMI ≥30kg/m2 or BMI Arm 2 | AZD5004 | Dose X ≥27kg/m2 and one obesity- Follo
Slide 23: Phase IIb SOLSTICE designed to evaluate effect on glycaemic control
AZD5004 | oGLP-1 Phase IIb SOLSTICE designed to evaluate effect on glycaemic control Patient population: SOLSTICE Arm 1 | AZD5004 | Dose X NCT06579105 | Randomised, ― ≥18 years old double-blind, placebo- Arm 2 | AZD5004 | Dose X controlled dose finding trial ― HbA1c ≥7.0% and ≤10.5% Arm 3 | AZD5004
Slide 24: Opportunity for additional cardiovascular benefit through small molecule combinations
AZD5004 | oGLP-1 Opportunity for additional cardiovascular benefit through small molecule combinations T2DM CKD HF Dyslipidaemia + dapagliflozin + dapagliflozin + dapagliflozin + AZD0780 (oSGLT2i) (oSGLT2i) (oSGLT2i) (oPCSK9) TYPE 2 AZD5004 Superior HbA1c Potential to deliver Potential to deliver Po
Slide 25: AZD6234 Long-acting amylin
AZD6234 Long-acting amylin Regina Fritsche Danielson SVP, EARLY CVRM 25
Slide 26: Amylin agonism promotes weight loss by reducing fat mass while retaining lean mass
AZD6234 | LA amylin Amylin agonism promotes weight loss by reducing fat mass while retaining lean mass in preclinical study Dose-dependent decrease driven by reduction in fat mass with lean mass preserved in obese rats treated with AZD6234 15-day once-daily treatment1 Change in mass from Day 0 to Da
Slide 27: Phase I SAD demonstrated efficacy with promising tolerability
AZD6234 | LA amylin Phase I SAD demonstrated efficacy with promising tolerability Body weight change after single dose of AZD6234 Exposure response for nausea/vomiting 0.4 Mean body weight change from baseline (%) 0.3 Cmax (mg/L) 0.2 Following single 2.7mg dose, a mean weight loss of 1.7% and 0.1 2.
Slide 28: Encouraging Phase I data supported initiation of Phase IIb APRICUS trial
AZD6234 | LA amylin Encouraging Phase I data supported initiation of Phase IIb APRICUS obesity/overweight trial Encouraging safety Robust profile Phase IIb ongoing ― No safety concerns at ― Supports once-weekly dosing ― Phase IIb APRICUS trial ongoing doses up to 4.2mg ― Encouraging weight loss in p
Slide 29: Phase IIb APRICUS designed to evaluate body weight reduction
AZD6234 | LA amylin Phase IIb APRICUS designed to evaluate body weight reduction Patient population: APRICUS NCT06595238 | Randomised, ― ≥18 years old double-blind, placebo- controlled trial ― BMI ≥30kg/m2 or BMI Arm 1 | AZD6234 | Dose 1 ≥27kg/m2 and one obesity-related condition R Follow-up Arm 2 |
Slide 30: AZD9550 GLP-1/glucagon agonist
AZD9550 GLP-1/glucagon agonist Regina Fritsche Danielson SVP, EARLY CVRM 30
Slide 31: AZD9550 decreased body weight in preclinical model with clinical PK data
AZD9550 | GLP-1/glu AZD9550 decreased body weight in preclinical model with clinical PK data supporting once-weekly administration Body weight decrease seen in obese mice1 Mild-to-moderate drug-related GI adverse events 20 200 Body weight change (% Day 0-21) 10 175 160 AZD9550 concentration (ng/mL)
Slide 32: AZD9550 and AZD6234 potential once-weekly triple mechanism combination
AZD9550 | GLP-1/glu AZD9550 and AZD6234 potential once-weekly AZD6234 | LA amylin triple mechanism combination Combination of novel mechanisms to expand therapeutic options Incretin Incretin AZD6234 | LA amylin AZD9550 | GLP-1/glu tolerant intolerant BMI Overweight Obesity Promotes satiety, Reduces
Slide 33: Summary
Summary Sharon Barr EVP, BIOPHARMACEUTICALS R&D 33
Slide 34: Majority of cardiovascular, renal and metabolism patients have multi-organ risk factors
Majority of cardiovascular, renal and metabolism patients have multi-organ risk factors, benefitting from combination therapy Diabetes Obesity Consensus Metabolic opinion is shifting AHA PRESIDENTIAL ADVISORIES Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the AHA Renal Cardio
Slide 35: Three high potential assets progressing to Phase IIb
$5bn+* Three high potential assets progressing to Phase IIb AZD5004 AZD6234 AZD6234 + AZD9550 oGLP-1 long-acting amylin long-acting amylin + GLP-1/glucagon • Small molecule • Selective amylin agonist • Triple mechanism • Strong target engagement • Once-weekly s.c. dosing • Once-weekly s.c. dosing •
Slide 36: Q&A Session
Q&A Session Sharon Barr Ruud Dobber EVP, BIOPHARMACEUTICALS EVP, BIOPHARMACEUTICALS R&D BUSINESS Regina Fritsche Elisabeth Björk Danielson SVP, LATE CVRM SVP, EARLY CVRM Mikhail Kosiborod, MD Mina Makar VP, RESEARCH @ SAINT LUKE’S SVP, GLOBAL CVRM HEALTH SYSTEM, KANSAS CITY 36
Slide 37: Appendix
Appendix 37
Slide 38: Dose-dependent reductions in fasting glucose observed in MAD T2D trial
AZD5004 | oGLP-1 Dose-dependent reductions in fasting glucose observed in MAD T2D trial Change in fasting glucose at Day 28 at different doses of AZD5004 5mg 10mg 30mg 50mg plasma glucose at Day 28 (mg/dL) Change from baseline in fasting 0 -50 -100 -150 0 7 14 21 28 0 7 14 21 28 0 7 14 21 28 0 7 14
Slide 39: Dose-dependent reductions in post-prandial glucose observed in MAD T2D trial
AZD5004 | oGLP-1 Dose-dependent reductions in post-prandial glucose observed in MAD T2D trial Percentage change in glucose AUC following a MMTT at Day 28 at different doses of AZD5004 5mg 10mg 30mg 50mg Glucose MMTT AUC0-4 (h x mg/dL) 1500 1200 900 600 D-1 D14 D28 D-1 D14 D28 D-1 D14 D28 D-1 D14 D28
Slide 40: Dose-dependent reduction in body weight observed in MAD T2D trial
AZD5004 | oGLP-1 Dose-dependent reduction in body weight observed in MAD T2D trial Mean percentage change in body weight on Day 28 at different doses of AZD5004 5mg 10mg 30mg 50mg 0 Change from baseline in body weight at Day 28 (%) -2.5 -5.0 -7.5 -10.0 0 7 14 21 28 0 7 14 21 28 0 7 14 21 28 0 7 14 2