Slide 1: Topline Results from Paltusotine Phase 3 PATHFNDR-2 Study
Topline Results from Paltusotine Phase 3 PATHFNDR-2 Study A Randomized, Placebo-Controlled, Multicenter Study to Evaluate the Safety And Efficacy of Paltusotine in Subjects with Non- pharmacologically Treated Acromegaly March 19, 2024 1
Slide 2: Safe Harbor Statement
Safe Harbor Statement This presentation contains forward-looking statements. Crinetics Pharmaceuticals, Inc. (“Crinetics,” the “company,” “we,” “us,” or “our”) cautions you that statements contained in this presentation regarding matters that are not historical facts are forward-looking statements.
Slide 3: Phase 3 Study Met the Primary and All Secondary Endpoints
Phase 3 Study Met the Primary and All Secondary Endpoints and Paltusotine Was Well-Tolerated PRIMARY ENDPOINT ✓ 56% of participants achieved IGF-1 ≤ 1.0xULN vs 5% on placebo (p<0.0001) SECONDARY ENDPOINTS ✓ Change from baseline in IGF-1 (p<0.0001) – Key secondary endpoint ✓ 67% achieved IGF-1 <1.3×U
Slide 4: Paltusotine: Designed to Allow People with Acromegaly and Carcinoid Syndrome to Focus on Living
Paltusotine: Designed to Allow People with Acromegaly and Carcinoid Syndrome to Focus on Living CURRENT PALTUSOTINE STANDARD TARGET PRODUCT Inconsistent Reliable, Symptom OF CARE PROFILE* consistent, Control and durable control 77% report injection site VS Well- tolerated reactions Painful, Once-dai
Slide 5: What is Acromegaly?
What is Acromegaly? • Changed Facial • Hypertension • Headache Acromegaly is caused by a benign pituitary tumor Features • Hypopituitarism • Vision Defects Hepatomegaly secreting excess growth hormone (GH) • Prognathism • • Impaired Glucose • Perspiration • Enlarged Hands • Joint Pain Uncontrolled a
Slide 6: Evaluated Once Daily Oral Paltusotine in Non-pharmacologically Treated Acromegaly
Evaluated Once Daily Oral Paltusotine in Non-pharmacologically Treated Acromegaly Screening Participants: Randomized Control Phase OLE (Open Label (up to 16 weeks) Not Medically (24 Weeks) Extension) Treated Eligibility Criteria: (Stratum 1) n=111 Not Medically Treated - N=82 Paltusotine (n=54) Palt
Slide 7: 95% of Participants Completed the Randomized Control Phase
95% of Participants Completed the Randomized Control Phase of PATHFNDR-2 and 97% Enrolled in the Open Label Extension PATHFNDR-2 Participant Disposition Total Participants Randomized N=111* Paltusotine Placebo N=54 N=57 Not Medically Treated Washed Out Not Medically Treated Washed Out (Stratum 1) (S
Slide 8: Participant Characteristics
Participant Characteristics Paltusotine Placebo Overall Participant Characteristics N=54 N=57 N=111 Female, n (%) 26 (48%) 33 (58%) 59 (53%) Age at informed consent - Mean (SD), years 47.5 (13.6) 45.9 (12.3) 46.7 (12.9) Weight - Mean (SD), kg 86.1 (19.9) 82.4 (18.7) 84.2 (19.3) BMI - Mean (SD), kg/m
Slide 9: Disease Characteristics and Previous Treatment
Disease Characteristics and Previous Treatment Paltusotine Placebo Overall Disease Characteristics and Previous Treatment N=54 N=57 N=111 Duration since acromegaly diagnosis - Mean (SD), months 97.9 (95.7) 77.1 (69.4) 87.2 (83.5) Pituitary surgery performed - n (%) 50 (93%) 49 (86%) 99 (89%) Pituita
Slide 10: Primary Endpoint Met: 56% of Participants on Paltusotine Achieved IGF-1 ≤1.0xULN
Primary Endpoint Met: 56% of Participants on Paltusotine Achieved IGF-1 ≤1.0xULN 100% p<0.0001 Participants Achieving Primary Endpoint (%) 80% 56% 60% (30/54) 40% 20% 5% (3/57) 0% Paltusotine Placebo 10 Participants who were rescued or stopped the assigned treatment before week 24 were considered no
Slide 11: Paltusotine Achieved Statistically Significant Responses in Both Patient Populations
Paltusotine Achieved Statistically Significant Responses (IGF-1 ≤1.0xULN) in Both Patient Populations Not Medically Treated Washed Out (Stratum 1) (Stratum 2) p<0.0001 p<0.0001 93% 100% 100% (13/14) 80% 80% Participants Achieving Participants Achieving Primary Endpoint (%) Primary Endpoint (%) 60% 6
Slide 12: Paltusotine Reduced IGF-1 Levels in 50/54 of Participants
Paltusotine Reduced IGF-1 Levels in 50/54 (93%) of Participants IGF-1 x ULN at Baseline and End of Randomized Control Phase (EoR) for Each Participant Paltusotine (N=54) Placebo (N=57) 8 8 Rescued Rescued N=2 N=13 7 7 6 6 IGF-1 (x ULN) IGF-1 (x ULN) 5 5 4 4 3 3 2 2 1 1 0 0 BL 2 4 6 8 12 16 20 22 24
Slide 13: Key Secondary Endpoint: Paltusotine Significantly Decreased IGF-1 Levels
Key Secondary Endpoint Achieved: Paltusotine Treatment Significantly Decreased IGF-1 Levels Change from Baseline in IGF-1 x ULN Treatment Difference (95% CI): -0.91 (-1.11, -0.71) 0.4 p<0.0001 IGF-1 Change from Baseline 0.2 0.09 xULN 0.0 (xULN ± SE) -0.2 -0.4 -0.6 -0.8 -0.82 xULN -1.0 Paltusotine Pl
Slide 14: Paltusotine Treatment Rapidly and Durably Decreased IGF-1 Levels
Paltusotine Treatment Rapidly (Within 2-4 Weeks) and Durably Decreased IGF-1 Levels Percent Change from Baseline in IGF-1 Level by Visit 10 Paltusotine (N=54) Placebo (N=57) IGF-1 Mean Percent Change 0 from Baseline (± SE) -10 Rapid 93% of Durable ↓IGF-1 participants ↓IGF-1 -0.82 xULN -20 (2-4 weeks
Slide 15: Secondary Endpoint #2 Met: 67% Achieved IGF-1 <1.3×ULN
Secondary Endpoint #2 Met: 67% of Participants Achieved IGF-1 <1.3×ULN with Paltusotine Participants who Achieved IGF-1 <1.3×ULN at EoR Overall Paltusotine Placebo p<0.0001 p<0.0001 in both strata vs. placebo 100% (14/14) Percentage Achieving Endpoint Percentage Achieving Endpoint 100% 100% 80% 67%
Slide 16: Participants Reported Symptom Severity Using the Acromegaly Symptoms Diary
Participants Reported Symptom Severity Using the Acromegaly Symptoms Diary (ASD) Symptoms Evaluated in the ASD Headache pain • ASD was developed in accordance with Joint pain FDA guidance to evaluate symptoms of Sweating acromegaly in clinical trials* Fatigue • Each symptom was rated from 0 (no Leg
Slide 17: Secondary Endpoint #3 Achieved: Paltusotine Treatment Improved Acromegaly Symptoms
Secondary Endpoint #3 Achieved: Paltusotine Treatment Improved Acromegaly Symptoms Change from Baseline to EoR in Total ASD Score Change from Baseline (± SE) Not Medically Treated (Stratum 1) 8 p=0.004 p=0.06 7 8 6 Change from Baseline (± SE) 6 ASD Score 4 5 2 +0.16 0 4 -2 +2.75 -4 ASD Score 3 -6 -4
Slide 18: Paltusotine Treatment Improved All Individual Symptom Components of ASD
Paltusotine Treatment Improved All Individual Symptom Components of ASD Change from Baseline to EoR in ASD Score by Item Paltusotine Placebo * * * * * 1.0 0.6 0.4 0.5 0.4 Change in ASD Score (+SE) 0.3 0.3 0.6 0.2 0.2 -0.2 -0.1 -0.6 -0.3 -0.3 -0.3 -0.3 -1.0 -0.6 -0.7 -1.4 Headache Joint Pain Sweating
Slide 19: Secondary Endpoint #4 Met: Target Growth Hormone Levels in 57% of Subjects
Secondary Endpoint #4 Met: Paltusotine Treatment Achieved Target Growth Hormone Levels in 57% of Subjects Participants who Achieved GH < 1.0 ng/mL at EoR 100% p<0.0001 Percentage Achieving Endpoint 80% 57% (31/54) 60% 40% 18% 20% (10/57) 0% Paltusotine Placebo Participants who are rescued or stop th
Slide 20: Paltusotine was Generally Well-Tolerated with No Serious Adverse Events
Paltusotine was Generally Well-Tolerated with No Serious Adverse Events Paltusotine Placebo N=54 N=57 Treatment-Emergent Adverse Events (TEAEs) n (%) n (%) Any 49 (91%) 49 (86%) Mild 47 (87%) 45 (79%) Moderate 15 (28%) 26 (46%) Severe 2 (4%) 5 (9%) Treatment-related 26 (48%) 15 (26%) Serious 0 1 (2%
Slide 21: Paltusotine Demonstrated No New Safety Signals
Paltusotine Demonstrated No New Safety Signals TEAEs with an Incidence of ≥5% in Total Participants Paltusotine Placebo N=54 N=57 TEAE n (%) n (%) Diarrhoea 18 (33%) 10 (18%) Headache 11 (20%) 19 (33%) • Safety profile in PATHFNDR-2 Arthralgia 6 (11%) 13 (23%) Abdominal pain 6 (11%) 2 (4%) comparabl
Slide 22: PATHFNDR-2 Safety Summary
PATHFNDR-2 Safety Summary • Paltusotine was generally well-tolerated with no serious adverse events reported • The most frequently (>10%) reported adverse events included diarrhoea, headache, arthralgia, and abdominal pain • No new safety signals were observed in adverse events, vital signs, ECGs, o
Slide 23: PATHFNDR Program Provides a Uniquely Rich Data Set
PATHFNDR Program Provides a Uniquely Rich Data Set Assessing BOTH Biochemical AND Symptom Control in Acromegaly Paltusotine data now support NDA filing for First commercial launch for Crinetics, broad use in acromegaly pending FDA approval of paltusotine for acromegaly • Previously, PATHFNDR-1 met a
Slide 24: Crinetics is Building the Premier Fully Integrated Endocrine-focused Pharmaceutical Company
Crinetics is Building the Premier Fully Integrated Endocrine-focused Pharmaceutical Company • ✓ 1Q Carcinoid Syndrome • 1H Commence CAH Phase 3* Phase 2 data readout • 2H Paltusotine acromegaly • ✓ 1Q Acromegaly PATHFNDR-2 PDUFA** and launch** Phase 3 data readout • Human POC from new drug • 2Q Init
Slide 25: Q&A
Scott Struthers, Ph.D. Founder and Chief Executive Officer Q&A Dana Pizzuti, M.D. Chief Medical & Development Officer Alan Krasner, M.D. Chief Endocrinologist Marc Wilson Chief Financial Officer Jim Hassard Chief Commercial Officer 25
Slide 26: Thank You
Pharmaceuticals Thank You