Slide 1: Topline Results from Paltusotine Phase 3 PATHFNDR-1 Study
TOPLINE RESULTS FROM PALTUSOTINE PHASE 3 PATHFNDR-1 STUDY A Randomized, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Paltusotine in Subjects with Acromegaly Treated with Long-acting Somatostatin Receptor Ligands
Slide 2: Safe Harbor Statement
SAFE HARBOR STATEMENT This presentation contains forward-looking statements. Crinetics Pharmaceuticals, Inc. (“Crinetics”) cautions you that statements contained in this presentation regarding matters that are not historical facts are forward-looking statements. These statements are based on the com
Slide 3: Met the Primary and All Secondary Endpoints and Paltusotine Was Well-Tolerated
Met the Primary and All Secondary Endpoints and Paltusotine Was Well-Tolerated PRIMARY ENDPOINT ✓ 83% of participants on paltusotine maintained IGF-1 ≤ 1.0xULN vs 4% on placebo (p<0.0001) SECONDARY ENDPOINTS (paltusotine arm vs. placebo) ✓ Change from baseline in IGF-1 (p<0.0001) ✓ Change from basel
Slide 4: What is Acromegaly?
What is Acromegaly? Acromegaly is caused by a benign pituitary tumor secreting excess growth hormone (GH) • Changed Facial • Hypertension • Headache Features • Hypopituitarism • Vision Defects Uncontrolled acromegaly is debilitating and increases risk of early death • Hepatomegaly • Prognathism • Pe
Slide 5: Paltusotine Was Designed as the First Once-Daily, Oral, Selectively Targeted SST2 Agonist
Paltusotine Was Designed as the First Once-Daily, Oral, Selectively Targeted SST2 Agonist octreotide (peptide) paltusotine (nonpeptide) Peptides and nonpeptides share a common receptor binding site Proteases Intrinsically permeable oral bioavailability 0.5% oral bioavailability 70% SST2 Receptor Blo
Slide 6: Goal for Paltusotine: Help People to Focus on Living Life
Goal for Paltusotine: Help People to Focus on Living Life Current Standard of Care Disease Control Tolerability Patient Experience Treatment-related Depot SRL injections Poor symptom injection site reactions are painful and often control: worsening of reported by 77% of need to be administered sympt
Slide 7: Evaluated Participants Switching from Standard of Care Depots to Once Daily Oral Paltusotine
Evaluated Participants Switching from Standard of Care Depots to Once Daily Oral Paltusotine Screening Randomized Controlled Phase Open Label (up to 12 weeks) (36 Weeks, 11 planned Visits) Extension Phase Participants: Entry Criteria: IGF-1 ≤1.0 xULN Paltusotine (n=30) on octreotide or n=58 R Paltus
Slide 8: Participant Disposition
98% of Participants Completed the Randomized Controlled Phase of PATHFNDR-1 and 91% Enrolled in the Open Label Extension (OLE) Phase PATHFNDR-1 Participant Disposition Total Participants Randomized N=58 Paltusotine Placebo N=30 N=28 Study Discontinuation Study Discontinuation N=0 N=1 (patient decisi
Slide 9: Participant Characteristics
Participant Characteristics Paltusotine Placebo Overall Participant Characteristics N=30 N=28 N=58 Female, n (%) 15 (50%) 17 (61%) 32 (55%) Age at informed consent - Mean (SD), years 55.9 (14.6) 53.9 (12.9) 54.9 (13.7) Weight - Mean (SD), kg 83.7 (18.6) 73.2 (16.0) 78.6 (18.1) BMI - Mean (SD), kg/m2
Slide 10: Disease Characteristics
Disease Characteristics Paltusotine Placebo Overall Disease Characteristics and Previous Treatment N=30 N=28 N=58 Duration since acromegaly diagnosis - Mean (SD), months 187 (88) 121 (82) 155 (91) Pituitary surgery performed - n (%) 26 (87%) 24 (86%) 50 (86%) Duration since pituitary surgery - Mean
Slide 11: Primary Endpoint Achieved
Primary Endpoint Achieved: 83% of Participants on Paltusotine Maintained IGF-1 ≤1.0 xULN 100% 83% (25/30) p<0.0001 Participants Achieving 80% Primary Endpoint (%) 60% 40% 20% 4% (1/28) 0% Paltusotine Placebo Participants who were rescued or stopped the assigned treatment before week 34 did not meet
Slide 12: Secondary Endpoint #1 Achieved: IGF-1 Change from Baseline
Secondary Endpoint #1 Achieved: Paltusotine Treatment Maintained Control of IGF-1 1.0 p<0.0001 0.83 xULN IGF-1 Change from Baseline 0.8 (x ULN ± SE) 0.6 0.4 0.2 0.04 xULN 0.0 Paltusotine Placebo (n=30) (n=28) -0.2 Least Squares (LS) Mean (± SE) is shown and estimated based on an analysis of covarian
Slide 13: Participants on Paltusotine Maintained IGF-1 Levels
Participants on Paltusotine Maintained IGF-1 Levels IGF-1 xULN at Baseline and End of Randomized Controlled Phase (EOR) for Each Participant Paltusotine Placebo 4.0 4.0 Rescued Rescued 3.5 3.5 3.0 3.0 IGF-1 (x ULN) IGF-1 (x ULN) 2.5 2.5 2.0 2.0 1.5 1.5 1.0 1.0 0.5 0.5 0.0 0.0 BL 4 8 12 16 20 24 28 3
Slide 14: Patients Reported Symptom Severity Using the Acromegaly Symptoms Diary
Patients Reported Symptom Severity Using the Acromegaly Symptoms Diary (ASD) Symptoms Evaluated in the ASD • ASD was developed in accordance with FDA Headache pain guidance to evaluate symptoms of acromegaly in Joint pain clinical studies* Sweating • Seven symptoms were rated from 0 (no symptom) Fat
Slide 15: Secondary Endpoint #2 Achieved
Secondary Endpoint #2 Achieved: Paltusotine Treatment Maintained Control of Acromegaly Symptoms Change from Baseline to EOR in Total ASD Score 7 6 p=0.02 +4.6 Change from Baseline (± SE) 5 4 ASD Score 3 2 1 -1 -0.6 -2 -3 Paltusotine Placebo (n=30) (n=28) EOR: End of Randomized Controlled Phase. ASD
Slide 16: Paltusotine Maintained Control Across All Individual Symptom Components of ASD
Paltusotine Treatment Maintained Control Across All Individual Symptom Components of ASD Change from Baseline in ASD Score by Item 2.0 Paltusotine Placebo 1.3 1.6 Change in ASD Score (+SE) 1.1 0.9 1.2 0.5 0.8 0.4 0.3 0.1 0.1 0.03 0.4 0.0 -0.4 -0.1 -0.03 -0.03 -0.3 -0.8 -0.3 Headache Joint Pain Sweat
Slide 17: Secondary Endpoint #3 Achieved
Secondary Endpoint #3 Achieved: Paltusotine Treatment Maintained Growth Hormone Control Participants with Baseline GH <1.0 ng/mL* who Maintained GH <1.0 ng/mL at EOR 100% 87% Percentage Meeting Endpoint (20/23) p=0.0003 80% 60% 40% 28% (5/18) 20% 0% Paltusotine Placebo *Endocrine Society Clinical Pr
Slide 18: Paltusotine was Well-Tolerated with No Severe or Serious Adverse Events
Paltusotine was Well-Tolerated with No Severe or Serious Adverse Events Paltusotine Placebo N=30 N=28 Treatment-Emergent Adverse Events n (%) n (%) Any 24 (80%) 28 (100%) Mild 14 (47%) 10 (36%) Moderate 10 (33%) 15 (54%) Severe 0 3 (11%) Treatment-related 11 (37%) 4 (14%) Serious Not treatment-relat
Slide 19: PATHFNDR-1 Adverse Events Summary
PATHFNDR-1 Adverse Events Summary Paltusotine Placebo Treatment Emergent N=30 N=28 Adverse Events ≥5% n (%) n (%) Common Acromegaly Symptoms Arthralgia 8 (27%) 16 (57%) Headache 6 (20%) 10 (36%) Peripheral swelling 2 (7%) 10 (36%) Fatigue 2 (7%) 5 (18%) Muscular weakness 1 (3%) 3 (11%) Paraesthesia
Slide 20: PATHFNDR-1 Safety Summary
PATHFNDR-1 Safety Summary • Paltusotine was well-tolerated with no severe or serious adverse events reported in the active arm • The most frequently (>10%) reported adverse events included arthralgia, diarrhea, headache, abdominal pain and nausea • No safety signals were observed in vital signs, ECG
Slide 21: Crinetics' Approach to Address Unmet Needs of People with Acromegaly
Crinetics’ Approach to Address Unmet Needs of People with Acromegaly, Prescribers, and Healthcare Systems As a trusted member of the global endocrine community, Crinetics aspires to bring the first once daily, oral selectively targeted SST2 agonist* to patients Efficacy The Crinetics Approach Commer
Slide 22: Paltusotine: Initial Multi-Billion Dollar U.S. Market Opportunity
Paltusotine: Initial Multi-Billion Dollar U.S. Market Opportunity in Acromegaly and Carcinoid Syndrome (U.S. Patients) (U.S. Patients) Carcinoid Syndrome Diagnosed Acromegaly 33,000 Prevalence 27,000 Not cured Addressable Patients 33,000 11,000 (Candidates for SRL) surgically Current Patients 10,000
Slide 23: Anticipated Paltusotine Milestones
Anticipated Paltusotine Milestones • 4Q23 Preliminary results from carcinoid syndrome Phase 2 study • 1Q24 Results from PATHFNDR-2 Phase 3 study in untreated acromegaly patients • 2024 Acromegaly NDA submission • 2024 Anticipated carcinoid syndrome Phase 3 start • Ongoing: Acromegaly open label exte
Slide 24: Q&A
Q&A Scott Struthers, Ph.D. Founder and Chief Executive Officer Dana Pizzuti, M.D. Chief Development Officer Alan Krasner, M.D. Chief Medical Officer