Slide 1: Topline Results from the ACROBAT Phase 2 Program in Acromegaly
TOPLINE RESULTS FROM THE ACROBAT PHASE 2 PROGRAM IN ACROMEGALY October 26, 2020
Slide 2: Safe Harbor Statement
Safe Harbor Statement This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation are forward-looking statements, including statements regarding: the potential benefits of paltusotine for acromegaly patients; the plan
Slide 3: Summary of ACROBAT Phase 2 Results
Summary of ACROBAT Phase 2 Results • Primary endpoint achieved in Edge: Once daily oral paltusotine maintained insulin- like growth factor-1 (IGF-1) levels at week 13 after switching from injected somatostatin receptor ligand (SRL) depots of octreotide or lanreotide [∆IGF-1 =-0.034 (-0.107, 0.107),
Slide 4: Acromegaly and NETs are Currently Treated with Injected SRL Depots
Acromegaly and NETS are Currently Treated with Injected Somatostatin Receptor Ligand (SRL) Depots Acromegaly Neuroendocrine Tumors (NETs) • Benign pituitary tumor • NETs arise from aberrant • Secretes excess growth enteroendocrine cells hormone (GH) Liver • Excess GH causes excess SST2 Stomach • In
Slide 5: ~$3.1B (2019) Market, Despite Limitations of Injectables
~$3.1B (2019) Market, Despite Limitations of Injectables Sandostatin Somatuline Somavert Signifor (octreotide) (lanreotide) (pegvisomant) (pasireotide) $1.6B $1.2B $264M $75M Monthly intramuscular Monthly deep subcutaneous Daily injections 1 ml; 28 – 31- Monthly intramuscular 5-mL vial; 1½” 19-gauge
Slide 6: ACROBAT Edge Study Design
ACROBAT Edge Study Design A global clinical trial conducted at 45 clinical sites in 13 countries Screening Paltusotine Treatment Washout WEEK -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Key Eligibility Criteria: Dose Titration Period Washout Patients not controlled Last (IGF-1 > 1.0,
Slide 7: ACROBAT Edge Patient Groups
ACROBAT Edge Patient Groups Group Pre-Trial Therapy Baseline IGF-1 Total (x ULN) Enrolled SRL monotherapy Prespecified Primary 1 > 1.0 ≤ 2.5 25 (octreotide or lanreotide) Analysis Population 2 SRL + cabergoline > 1.0 ≤ 2.5 10 3 SRL + cabergoline ≤ 1.0 5 Exploratory 4 Pasireotide ≤ 1.0 4 Populations
Slide 8: ACROBAT Edge Patient Disposition
ACROBAT Edge Patient Disposition 89% of patients completed the study Total Enrolled n=47 Group 1 Group 2 Group 3 Group 4 Group 5 SRL Monotherapy SRL + Cabergoline (IGF>1) SRL + Cabergoline(IGF≤1.0) Pasireotide SRL + Pegvisomant n=25 (53.2%) n=10 n=5 n=4 n=3 Completers Completers Completers Completer
Slide 9: ACROBAT Edge Patient Characteristics
ACROBAT Edge Patient Characteristics Group 1 Group 2 Group 3 Group 4 Group 5 Total (N=25) (N=10) (N=5) (N=4) (N=3) (N=47) Demographics Median Age, years (Min, Max) 52 (31, 71) 53 (31, 70) 51 (43, 69) 56 (46, 67) 38 (35, 66) 51 (31, 71) Median Weight, kg (Min, Max) 91 (61, 155) 85 (56, 136) 87 (57, 9
Slide 10: Paltusotine Maintained IGF-1 and GH Levels After Switching From Injected SRL Depots
Paltusotine Maintained IGF-1 and GH Levels After Switching From Injected SRL Peptide Depots Hormone levels observed in primary analysis population (Group 1) 3.0 3.0 p<0.0001 IGF-1 p<0.0001 GH 2.5 2.5 p>0.6 p=0.6285 2.0 2.0 GH (ng/mL) IGF-1 (× ULN) p>0.6 p=0.6285 1.5 1.5 1.0 1.0 0.5 0.5 0.0 0.0 Basel
Slide 11: Paltusotine Maintained IGF-1 Levels After Switching From Injected SRL Peptide Depots
Paltusotine Maintained IGF-1 Levels After Switching From Injected SRL Peptide Depots Conclusions 1. IGF-1 levels after 13 weeks of paltusotine treatment did not significantly change from baseline in patients previously treated with injected SRL depots (Group 1) 2. Rise in IGF-1 after withdrawal (wit
Slide 12: Paltusotine Maintained GH Levels After Switching From Injected SRL Peptide Depots
Paltusotine Maintained GH Levels After Switching From Injected SRL Peptide Depots Conclusions 1. GH levels after 13 weeks of paltusotine treatment did not significantly change from baseline levels when patients were previously treated with injected SRL depots (Group 1) 2. Rise in GH after withdrawal
Slide 13: ACROBAT Edge Dose Titration
ACROBAT Edge Dose Titration Most Group 1 patients up-titrated to the highest dose (40 mg) Screening Paltusotine Treatment Washout WEEK -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Switch to paltusotine qd Number of patients at each dose level IGF at week 2 IGF at week 5 IGF at week 8
Slide 14: IGF-1 Levels Were Maintained After Switching to Paltusotine
IGF-1 Levels Were Maintained After Switching to Paltusotine from Injected SRL Depots Screening Paltusotine Treatment Washout 2.6 2.4 2.2 Last Depot 2.0 Dose Rec’d 1.8 1.6 IGF-1 (× ULN) 1.4 1.2 1.0 n = 25 n = 23 n = 18 0.8 n = 20 Number of patients 0.6 in Group 1 at each 40 mg dose level 0.4 0.2 30 m
Slide 15: Switching to Once Daily Oral Paltusotine Maintained IGF-1 Levels in 87% of Group 1 Patients
Switching to Once Daily Oral Paltusotine Maintained IGF-1 Levels in 87% of Group 1 Patients Individual patient percent change in IGF-1 at end of treatment vs. baseline and change at 4 weeks after withdrawal of paltusotine • 20/231 patients (87%) who completed the dosing period achieved IGF-1 levels
Slide 16: Paltusotine Suppressed IGF-1 in Patients Previously Receiving Combination Therapy with Cabergoline
Paltusotine Suppressed IGF-1 in Patients Previously Receiving Combination Therapy with Cabergoline Patients on SRL depots + oral cabergoline (Groups 2 and 3) 3.5 p=0.0166 • Paltusotine contributed to IGF-1 3.0 lowering in patients previously treated with injected SRL peptide depots + oral 2.5 p=0.00
Slide 17: ACROBAT Evolve Trial Design
ACROBAT Evolve Trial Design Randomized, double-blind global clinical trial conducted at 44 clinical sites in 13 countries Randomized Screening Paltusotine Treatment Withdrawal Washout WEEK -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 paltusotine Key Eligibility Criteria: Dose Titratio
Slide 18: ACROBAT Evolve Dose Titration
ACROBAT Evolve Dose Titration Most patients did not reach the highest dose (30 mg) Randomized Screening Paltusotine Treatment Withdrawal Washout WEEK -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Number of patients at each dose level Switch to paltusotine qd paltusotine IGF at week 2 I
Slide 19: Evolve Results Provided Additional Response Data at the Low End of the Dose Range
Evolve Results Provided Additional Response Data at the Low End of the Dose Range Randomized Screening Titration Period Washout Withdrawal 2.0 Last Depot Dose Rec’d Randomize if IGF ≤ 1.0 at wk 8 1.5 IGF-1 (× ULN) 1.0 Number of patients at each dose level 0.5 n= 13 n=9 n= 3 30 mg Not Randomized (N=5
Slide 20: Post-Hoc Analysis of Edge (Group 1) and Evolve Provide Evidence of a Dose Response
Post-Hoc Analysis of Edge (Group 1) and Evolve Provide Evidence of a Dose Response Results from Switching to Paltusotine: Change in IGF-1 Magnitude of Paltusotine Activity: Change in IGF-1 from from Baseline to Steady State at Indicated Dose Steady State to 4 Weeks After Withdrawal Steady state IGF-
Slide 21: Paltusotine was Generally Well Tolerated Across Clinical Trials
Paltusotine was Generally Well Tolerated Across Clinical Trials Treatment Emergent Edge/Evolve Patients Healthy Acrobat Edge and Evolve volunteers Adverse Events ≥ 5%* (N=60) n (%) • No study discontinuations due to adverse events (N=128^) n (%) Common Acromegaly Symptoms • No patients required res
Slide 22: Summary of ACROBAT Phase 2 Results
Summary of ACROBAT Phase 2 Results • Primary endpoint achieved in Edge: Once daily oral paltusotine maintained IGF-1 levels at week 13 after switching from injected somatostatin receptor ligand (SRL) depots of octreotide or lanreotide [∆IGF-1 =-0.034 (-0.107, 0.107), median (IQR1)] • Both IGF-1 and
Slide 23: Paltusotine Development Program Plans
Paltusotine Development Program Plans • KOL webinar on November 20th to discuss acromegaly and ACROBAT results • Update on improved formulation of paltusotine planned for use in Phase 3 • Additional analysis of ACROBAT data including exposure/response and patient reported outcome (PRO) instruments t
Slide 24: Paltusotine is Protected by a Strong IP Portfolio
Paltusotine is Protected by a Strong IP Portfolio Multiple U.S. patents granted; national stage applications filed in 2017 2010 2015 2020 2025 2030 2035 2040 2045 2050 Granted Composition of Matter Expiration U.S. 9,896,432; U.S. 10,351,547; U.S. 10,597,377 July 2037 Pending Pending in foreign juris
Slide 25: Pipeline: Rare Disease Franchise in Endocrinology
Pipeline: Rare Disease Franchise in Endocrinology ANTICIPATED NEXT PROGRAM DISCOVERY PRECLIN PHASE 1 PHASE 2 PHASE 3 MILESTONE End-of-Phase 2 meeting Paltusotine with FDA 1Q2021 Acromegaly Initiate Phase 3 acromegaly 1H 2021 Neuroendocrine Tumors (NETs) Initiate Phase 2 in 2021 Oral ACTH Antagonist
Slide 26: Crinetics Pharmaceuticals
CRINETICS PHARMACEUTICALS | 26
Slide 27: Thank You
‘Crinetics Pharmac THANK YOU