Slide 1: Results from Paltusotine Carcinoid Syndrome Open Label Phase 2 Study
Results from Paltusotine Carcinoid Syndrome Open Label Phase 2 Study A Randomized, Parallel Group Study to Evaluate the Safety, Pharmacokinetics, and Dose Response of Paltusotine Treatment in Subjects with Carcinoid Syndrome March 12, 2024
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: Once Daily Oral Paltusotine Showed Positive Results in Carcinoid Syndrome Patients
Once Daily Oral Paltusotine Showed Positive Results in Carcinoid Syndrome Patients EFFICACY FINDINGS: Rapid and Sustained Reductions in Patient Symptoms ✓ Flushing: 63% reduction in frequency for patients with >1/day (p< 0.0001) ✓ Flushing Severity: 61% reduction in severity of episodes (p<0.0001) ✓
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 Phase 3 control design strategy 77% report injection site VS Well- tolerated rea
Slide 5: Carcinoid Syndrome is a Serious Disease and Patients Need Better Treatment Options
Carcinoid Syndrome is a Serious Disease and Patients Need Better Treatment Options Serotonin + Other Carcinoid Syndrome Lung Factors ~33,000 Patients Diagnosed with Carcinoid Syndrome (U.S.) Facial Flushing in a patient NETs with carcinoid syndrome Excess bowel movements (>3/day) are highly disrupti
Slide 6: Phase 2 Study Design: Evaluating Safety, PK and Efficacy of Paltusotine in Carcinoid Syndrome Patients
Phase 2 Study Design: Evaluating Safety, PK and Efficacy of Paltusotine in Carcinoid Syndrome Patients Protocol: 8-week, open-label, parallel, randomized 2-dose study followed by a Long Term Extension phase Key Eligibility Criteria: • Treatment naïve or currently untreated and actively symptomatic –
Slide 7: Subject Disposition and Dosing
Subject Disposition and Dosing Entered RTP Total N=36 n (%) Entered RTP 36 Naïve/Untreated 9 Early Termination1 Switching 27 N=6 Discontinued 6 (17) Withdrawal by subject 1 (3) Adverse event 2 (6) Completed RTP Investigator decision 2 (6) N=30 Need for administration of a prohibited concomitant medi
Slide 8: Baseline Demographics and Disease Characteristics were Consistent Across Patient Groups
Baseline Demographics and Disease Characteristics were Consistent Across Patient Groups Naïve/Untreated Symptomatic Switching from SRL Overall N=9 N=27 N=36 Female, n (%) 6 (67) 13 (48) 19 (53) Male, n (%) 3 (33) 14 (52) 17 (47) Age - Mean (SD), years 58.2 (19.5) 61.6 (10.3) 60.8 (13.0) BMI - Mean (
Slide 9: Paltusotine Exposure in Patients with Carcinoid Syndrome was Consistent with Expectations from Healthy Volunteers
Paltusotine Exposure in Patients with Carcinoid Syndrome was Consistent with Expectations from Healthy Volunteers Healthy Carcinoid Syndrome 1000 Paltusotine Concentration (ng/mL) 800 Mean (SD) Steady-State 600 400 598 200 405 284 202 223 107 110 0 55 40 mg 40 mg 80 mg 80 mg Trough Post-dose Trough
Slide 10: Paltusotine was Generally Well-Tolerated with No Severe or Serious Treatment-Related Adverse Events
Paltusotine was Generally Well-Tolerated with No Severe or Serious Treatment-Related Adverse Events Treatment-Emergent Paltusotine Preliminary Safety Summary from Ongoing Adverse Events, n (%) N=36 Carcinoid Syndrome Phase 2 Study Any 26 (72.2) • Paltusotine was generally well-tolerated with no Mild
Slide 11: Most Frequent Treatment-Emergent Adverse Events Observed were Mild to Moderate
Most Frequent Treatment-Emergent Adverse Events Observed were Mild to Moderate Treatment-Emergent Paltusotine Adverse Events, n (%) N=36 Diarrhea 14 (38.9) Abdominal Pain 7 (19.4) • Adverse event frequency was similar across Nausea 6 (16.7) both dose groups Headache 6 (16.7) Flushing 5 (13.9) • Most
Slide 12: Paltusotine Reduced Frequency of Key Carcinoid Syndrome Symptoms: Excess BM and Flushing
Paltusotine Reduced Frequency of Key Carcinoid Syndrome Symptoms: Excess BM and Flushing Excess Bowel Movement* Frequency Flushing Frequency For Patients For Patients with >3/day at Baseline with >1/day at Baseline 3.0 4.0 Excess (>3/day) Daily Frequency (7d avg) P=0.02 P<0.0001 (N=16) (N=24) Daily
Slide 13: Paltusotine Showed Improvements in Subjects with Elevated Bowel Movement Frequency
Paltusotine Showed Improvements in Subjects with Elevated Bowel Movement Frequency Change from Baseline to Last Week of Treatment (Patients with at least 2 Weeks of RTP Data, Ordered by Baseline Value) 8 Mean change -1.6 BM/day (N=19) Mean change -0.3 BM/day (N=16) Bowel Movement Daily Frequency 7 (
Slide 14: Paltusotine Showed Improvements in Flushing Frequency in Majority of Subjects
Paltusotine Showed Improvements in Flushing Frequency in Majority of Subjects Change from Baseline to Last Week of Treatment (Patients with at Least 2 Weeks of RTP Data, Ordered by Baseline Value) 8 Mean Change was -1.9 flushing/ day (N=25) Mean Change was –0.2 flushing/day (N=10) 7 (From Baseline t
Slide 15: Rapid Improvements in Bowel Movement Frequency Were Observed Within 2 Weeks of Treatment
Rapid Improvements in Bowel Movement Frequency Were Observed Within 2 Weeks of Treatment and Were Sustained Through Week 8 Naïve/Untreated (n = 9) Switching From Prior SRL (n = 27) 6 6 Bowel Movement Frequency/Day Bowel Movement Frequency/Day Paltusotine Paltusotine 5 5 4 4 Mean (SE) Mean (SE) 3 3 2
Slide 16: Rapid Improvements in Flushing Frequency Were Observed Within 2 Weeks of Treatment
Rapid Improvements in Flushing Frequency Were Observed Within 2 Weeks of Treatment and Were Sustained Through Week 8 Naïve/Untreated (n = 9) Switching From Prior SRL (n = 27) 4 Paltusotine 4 Paltusotine Flushing Frequency/Day Flushing Frequency/Day 3 3 Mean (SE) Mean (SE) 2 2 1 1 Washout Period 0 0
Slide 17: Paltusotine Also Reduced the Severity of Key Carcinoid Syndrome Symptoms
Paltusotine Also Reduced the Severity of Key Carcinoid Syndrome Symptoms Episodes of BM Urgency Flushing Severity 1.5 Severity (0-10 numerical rating scale) P<0.0001 4.0 P<0.0001 (N=31) (N=31) Daily Frequency (7d avg) 1.0 3.0 3.6 Mean (SE) Mean (SE) 1.1 -61% -64% 2.0 0.5 1.0 1.4 0.4 N = 23 N = 23 0.
Slide 18: Rapid Improvements in Episodes of BM Urgency Were Observed Within 2 Weeks of Treatment
Rapid Improvements in Episodes of BM Urgency Were Observed Within 2 Weeks of Treatment and Were Sustained Through Week 8 Naïve/Untreated (n = 9) Switching From Prior SRL (n = 27) 2.0 Paltusotine 2.0 Paltusotine Daily Frequency of Urgent Daily Frequency of Urgent Events (7d avg) Events (7d avg) 1.5 1
Slide 19: Rapid Improvements in Flushing Severity Were Observed Within 2 Weeks of Treatment
Rapid Improvements in Flushing Severity Were Observed Within 2 Weeks of Treatment and Were Sustained Through Week 8 Naïve/Untreated (n = 9) Switching From Prior SRL (n = 27) Severity (0-10 numerical rating scale) Severity (0-10 numerical rating scale) 6 6 Paltusotine Paltusotine 5 5 4 4 Mean (SE) Me
Slide 20: Paltusotine Suppressed Serotonin Levels, a Key Biomarker in Carcinoid Syndrome Patients
Paltusotine Suppressed Serotonin Levels, a Key Biomarker in Carcinoid Syndrome Patients Naïve Washout 40 40 20 20 Biomarker Percent Change Biomarker Percent Change from Baseline (% ± IQR) from Baseline (%± IQR) 0 0 -20 -20 -40 -40 -60 -60 -80 -80 Median Baseline Median Baseline Median Baseline Media
Slide 21: Once Daily Oral Paltusotine Showed Positive Results in Carcinoid Syndrome Patients
Once Daily Oral Paltusotine Showed Positive Results in Carcinoid Syndrome Patients Summary: Phase 2 Results Support Proceeding to a Phase 3 Program • Rapid and sustained reductions were observed in frequency and severity of bowel movements and flushing episodes with 40 mg and 80 mg • Paltusotine was
Slide 22: Market Research Supports that Paltusotine's Emerging Profile can Address Unmet Needs for Carcinoid Syndrome
Market Research Supports that Paltusotine’s Emerging Profile can Address Unmet Needs for Carcinoid Syndrome Oral Alternative Symptom Control Patient Preference • HCPs note the extensive training required for nurses to correctly prepare • HCPs predict they would offer • HCPs say the level of symptom
Slide 23: Strategy to Enable Paltusotine to Serve a Greater Number of Patients
Strategy to Enable Paltusotine to Serve a Greater Number of Patients • Build HCP Experience with Acromegaly Paltusotine • Phase 3 Study Design Supporting Both Switching and Untreated Carcinoid Syndrome Patients Strategic Objectives: • Build HCP Experience in Carcinoid Syndrome 50,000 45,000 40,000 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 Phase • 1H Commence CAH Phase 3* 2 data readout • 2H Paltusotine acromegaly • 1Q Acromegaly PATHFNDR-2 PDUFA** and launch** Phase 3 data readout • Human POC from new drug • 2Q Initial
Slide 25: Q&A
Scott Struthers, Ph.D. Q&A Founder and Chief Executive Officer Dana Pizzuti, M.D. Chief Medical & Development Officer Alan Krasner, M.D. Chief Endocrinologist Jim Hassard Chief Commercial Officer 25
Slide 26: Thank You
‘Crinetics Pharmaceuticals Thank You