Structure Therapeutics, Inc. · NASDAQ:GPCR
Structure Therapeutics — Corporate Update (December 2023)
35 slides from Structure Therapeutics's corporate update, Dec 18, 2023
Slide 1: Comprehensive Program Update
GSBR - 1290 Comprehensive Program Update CONFIDENTIAL December 18, 2023
Slide 2: Attendees
2 Attendees • Raymond Stevens, Ph.D., Chief Executive Officer • Mark Bach, M.D., Ph.D., Chief Medical Officer • Blai Coll, M.D., Ph.D., VP Clinical Development • Jun Yoon, Chief Financial Officer • Danielle Keatley, Investor Relations Confidential
Slide 3: Forward looking statements
3 Forward looking statements This presentation contains “forward - looking statements” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Re form Act of 1995. All statements other than statements of historical fact are statements that could be deemed forward - lo
Slide 4: Agenda
4 Agenda • Opening Remarks and Overview (Ray Stevens) • GSBR - 1290 Program Update (Blai Coll) − Phase 2a Safety and Tolerability Summary − Phase 2a Efficacy Summary − Phase 2b - enabling studies − Japanese Bridging Study − 6 and 9 month Toxicology Update • Overall Profile and Next Steps ( Mark Bach
Slide 5: Program Update and Phase 2a Proof-of-Concept Data Summary of Key Findings
5 GSBR - 1290 Program Update and Phase 2a Proof - of - Concept Data Summary of Key Findings • Encouraging efficacy, safety and tolerability results • Generally well - tolerated with no serious adverse events (SAEs) related to drug up to 12 weeks, very low discontinuations • Results support once - a
Slide 6: Program Update
6 GSBR - 1290 Program Update Blai Coll, M.D., Ph.D., VP Clinical Development Confidential
Slide 7: Our Journey Towards a Potentially Best in Class Oral GLP-1RA
7 Our Journey Towards a Potentially Best in Class Oral GLP - 1RA Phase 2a in T2DM x Initial study in T2DM over 12 wk x Favorable s afety and tolerability x Active drug at 45mg and 90mg Phase 2a Obesity x Second study in obesity over 12 wk x Favorable s afety and tolerability x Active drug at 120mg a
Slide 8: Phase 2a Study Design in T2DM and Obesity
8 GSBR - 1290 Phase 2a Study Design in T2DM and Obesity Top line data at 12 weeks Primary endpoint: S afety and tolerability Secondary endpoints: Demonstrate decrease in HbA1c Demonstrate decrease in weight Demonstrate changes in metabolic parameters after a Mixed Meal Tolerance Test Interim results
Slide 9: Phase 2a baseline characteristics
9 Phase 2a (12 wk) Phase 2a (12 wk) Characteristics N (%) T2DM Obesity without T2DM 45 mg (N=10) 90 mg (N=26) Placebo (N=18) 120 mg (N=24) Placebo (N=16) Age, years 60.5 (7.5) 55.9 (11.0) 59.4 (9.3) 45.8 (14) 46 (14) Sex, female N (%) 4 (40) 12 (46) 7 (39) 13 (54) 4 (25) Hispanic or Latino, N(%) 8 (
Slide 10: Phase 2a Study: Participant disposition
10 GSBR - 1290 Phase 2a Study: Participant disposition Phase 2a (12 wk) Phase 2a (12 wk) N (%) T2DM Obesity without T2DM 45 mg (N=10) 90mg (N=26) Placebo (N=18) 120mg (N=24) Placebo (N=16) Discontinued study due to AEs 2 (20)* 0 0 0 0 Discontinued study due to AEs related to study drug 1 (10)** 0 0
Slide 11: Safety and Tolerability Summary
11 GSBR - 1290 Program Update Safety and Tolerability Summary Phase 2a – Topline data from first study in T2DM Phase 2a – Interim results in Obesity Confidential
Slide 12: Phase 2a Study: Safety and Tolerability Overview of TEAEs
12 Phase 2a (12 wk) Phase 2a (12 wk) Event N (%) T2DM Obesity without T2DM 45 mg (N=10) 90 mg (N=26) Placebo (N=18) 120 mg (N=24) Placebo (N=16) Any TEAE 10 (100) 25 (96.2) 8 (44.4) 23 (95.8) 11 (68.8) Any TEAE by maximum severity Mild 2 (20) 6 (23.1) 6 (33.3) 6 (25) 9 (56.3) Moderate 7 (70) 17 (65.
Slide 13: Phase 2a Study: Safety and Tolerability
13 Phase 2a (12 wk) Phase 2a (12 wk) Event N (%) T2DM Obesity without T2DM 45 mg (N=10) 90 mg (N=26) Placebo (N=18) 120 mg (N=24) Placebo (N=16) Nausea 7 (70) 19 (73) 2 (11) 21 (87) 2 (12) Vomiting 4 (40) 13 (50) 0 15 (62) 1 (6) Diarrhea 6 (60) 9 (34) 3 (16) 14 (58) 3 (18) Decreased appetite 2 (20)
Slide 14: Tolerability over time - Most common GI-related TEAEs
GSBR - 1290 tolerability over time - Most common GI - related TEAEs 14 Confidential Highest incidences of events during the titration phase with attenuation trend over time GSBR - 1290 in T2DM (12 wk) GSBR - 1290 in Obesity (12 wk) Dose Titration Phase Dose Titration Phase Nausea Vomiting 0% 5% 10%
Slide 15: Phase 2a study (12 wk): Changes in heart rate
GSBR - 1290 Phase 2a study (12 wk): Changes in heart rate 15 Confidential • Higher pulse rate observed (5 to 8 bpm) with GSBR - 1290 as expected for the class • Increases consistent with other GLP - 1RAs 1,2 1,2 Granhall C, Donsmark M, Blicher TM, et al. Clin Pharmacokinet. 2019;58(6):781 - 791. Pra
Slide 16: Efficacy Summary
16 GSBR - 1290 Program Update Efficacy Summary Phase 2a – Topline data from first study in T2DM patients Phase 2a – Interim results in Obesity patients Confidential
Slide 17: Phase 2a First Study in T2DM: HbA1c Reduction
GSBR1290 Phase 2a First Study in T2DM (12 wk) Efficacy EndpointHbA1c ReductionStatisticallysignificant reduction in HbA1c placebo adjusted at day 84 ( 1.01% to 1.02%)Early separation observed at day 3517HbA1c change from baseline to Day 84 (%)HbA1c change from baseline (%), over time-1.4-1.2-1-0.8-0
Slide 18: Phase 2a First Study in T2DM: Weight Reduction
18GSBR129045 mg (N=6)GSBR129090 mg (N=16)Least Square MeanDifference (LSM), Changein BW (%) vs Placebo-3.51 -3.2695% CI-5.58 to 1.43 -5.17 to 1.36Pvalue vs placebo 0.00190.0013Weight change from baseline (kg), over timeWeight change from baseline (%), Day 84*LSM, CI and p value from Mixed Model for
Slide 19: Phase 2a First Study in T2DM: Fasting Plasma Glucose
-1.61-1.281.21-2.00-1.50-1.00-0.500.000.501.001.50GSBR 45 mg GSBR 90 mg Placebo-4-3-2-10120 20 40 60 80Fasting plasma glucose change from baseline (mmol/L)(LSM SEM)Study daysGSBR1290 45 mg GSBR-1290 90 mg PlaceboGSBR1290 Phase 2a: First Study in T2DM (12 wk) Efficacy EndpointFasting Plasma GlucoseSt
Slide 20: Phase 2a T2DM: Mixed Meal Tolerance Test
GSBR - 1290 Phase 2a: First Study in T2DM (12 wk) – Efficacy Endpoint Mixed Meal Tolerance Test placebo adjusted change from BL at Day 84 (LSM) GSBR - 1290 demonstrated improvements in postprandial glucose, insulin and marker of insulin resistance Plasma glucose (mmol/L*hour), AUC 0 - 4 Insulin (mIU
Slide 21: Phase 2a Obesity Study: Interim Analysis (8 wk) Weight reduction
21 GSBR - 1290 Phase 2a: Obesity Study – Interim Analysis (8 wk) Weight reduction Weight change from baseline (kg), over time * LSM, CI and p value from Mixed Model for Repeated Measures. -6 -5 -4 -3 -2 -1 0 1 0 10 20 30 40 50 60 Weight change from baseline (kg) (LSM ± SEM) Study days GSBR-1290 120
Slide 22: Summary of Weight Reduction
22 GSBR - 1290 Summary of Weight Reduction Clinically meaningful and statistically significant weight reduction observed in T2DM and Obesity 22 % change from baseline Confidential -6 -5 -4 -3 -2 -1 0 1 0 10 20 30 40 50 60 70 80 90 Weight change from baseline (%) Obesity 90mg (Ph1b) Obesity 120mg (Ph
Slide 23: GSBR-1290 in Context of Oral Small Molecule GLP-1RA
23GSBR1290 in Context of Oral Small Molecule GLP 1RA-14-12-10-8-6-4-2020.0 4.0 8.0 12.0 16.0 20.0 24.0 28.0 32.0 36.0Body weight change from baseline (%)Study Time (weeks)Weight change from baseline (%)GSBR1290 120mgObesityGSBR1290 45/90mgT2DMOrforglipron 24/45mg2ObesityOrforglipron 12mg1T2DMOrforgl
Slide 24: Phase 2b-enabling Activities
GSBR - 1290 Program Update Phase 2b - enabling Activities Phase 1 – Japanese Bridging Study Preclinical GLP - Toxicology Studies 24 Confidential
Slide 25: Japanese and Non-Japanese Bridging Study
25 GSBR - 1290 Phase 1 (4 wk): Japanese and Non - Japanese Bridging Study • All participants completed the study • No discontinuations or dose reductions • No SAEs N (%) Japanese cohort Non - Japanese cohort 60mg (N=9) Placebo (N=3) 60mg (N=6) Nausea 6 (66.7) 0 3 (50.0) Decreased appetite 6 (66.7) 0
Slide 26: 6/9 Month GLP-Toxicology Study Preliminary Results
26 6/9 Month GLP - Toxicology Study Preliminary Results x 6 - month study in rodents (N=216) • Daily oral dosing for 6 - month (10, 100, 1000 mg/kg/day), plus 1 month recovery • Animals per group (treatment + recovery): N=15+5/group/sex • NOAEL is 1000 mg/kg/day, leading to >100 fold safety window a
Slide 27: Overall Profile and Next Steps
27 GSBR - 1290 Overall Profile and Next Steps Mark Bach, M.D., Ph.D., CMO Confidential
Slide 28: Overview of Phase 2a Clinical Data
28 GSBR - 1290 – Overview of Phase 2a Clinical Data Efficacy: Statistically significant weight reduction (4.74%) at 8 weeks on 120 mg daily. Study ongoing to 12 weeks. Safety: No SAEs; No discontinuations due to AEs up to 12 weeks Tolerability: Most AEs (96%) mild – moderate Confidential Obesity : P
Slide 29: Next Steps: Formulation Bridging and Titration Optimization Study
29 Next Steps: Formulation Bridging and Titration Optimization Study Capsule to Tablet Formulation and Explore Additional Titration Schemes Part 2: • To assess the tolerability at different titration schemes with the tablet • To study the comparative bioavailability of capsules and tablets at a ther
Slide 30: Closing
30 GSBR - 1290 Closing Raymond Stevens, Ph.D., CEO Confidential
Slide 31: Program Progress and Anticipated Milestones
31 GSBR - 1290: Program Progress and Anticipated Milestones 2023 2024 x Phase 1b/MAD data (4 wk) • N=24, healthy overweight/obese participants, up to 90 mg • No adverse event - related discontinuations up to 90 mg • Statistically significant reductions in weight (up to 4.9% placebo - adjusted) at 60
Slide 32: Our Journey Towards a Potentially Best-in-Class Oral GLP-1R Agonist
32 Our Journey Towards a Potentially Best - in - Class Oral GLP - 1R Agonist x Phase 2a T2DM (12wk) x Phase 2a Obesity (interim) x Phase 1b MAD (4wk) Sep 2023 Phase 2b Obesity (~36wk) Proof - of - Concept Phase 2b T2DM (~26wk) Dose - range finding/ Optimization Phase 3 Obesity (>52wk) Phase 3 T2DM (
Slide 33: Next Steps: Continue To Execute On Oral Incretin Franchise Strategy
33 Next Steps: Continue To Execute On Oral Incretin Franchise Strategy GLP - 1R+ Combo GIPR GLP - 1R+ Combo Amylin GLP - 1R+ Combo Apelin/APJR GLP - 1R+ Combo GCGR Osteo - arthritis Fatty Liver Disease Obesity Type 2 Diabetes CKD Alzheimer’s Heart Failure Sleep Apnea Other Incretins Selective Weight
Slide 34: GSBR-1290 in context
34 GSBR - 1290 in context • Significant future market opportunity for oral GLP - 1 agonists to treat cardiometabolic diseases such as obesity, type 2 diabetes, chronic kidney disease, MASH and others • Oral GLP - 1 agonists have the potential to be foundational and a backbone for future combinations
Slide 35: Thank you!
Thank you! CONTACT US FOR ADDITIONAL INFORMATION: Email: ir@structuretx.com http://www.structuretx.com Confidential
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