Crinetics Pharmaceuticals, Inc. · NASDAQ:CRNX

Crinetics Pharmaceuticals — Technical Presentation (December 2023)

20 slides from Crinetics Pharmaceuticals's technical presentation, Dec 18, 2023

  1. Slide 1: Initial Results from Ongoing Paltusotine Carcinoid Syndrome Open Label Phase 2 Study

    INITIAL RESULTS FROM ONGOING 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

  2. 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.

  3. Slide 3: Once Daily Oral Paltusotine Showed Strong Initial Results in Carcinoid Syndrome Patients

    Once Daily Oral Paltusotine Showed Strong Initial Results in Carcinoid Syndrome Patients ✓ SAFETY • Paltusotine was well-tolerated with no severe or serious treatment ✓ PHARMACOKINETICS related adverse events and consistent with prior studies • Overall PK was generally consistent with expectations f

  4. Slide 4: Carcinoid Syndrome is a Serious Disease and Patients Need Better Treatment Options

    Carcinoid Syndrome is a Serious Disease and Patients Need Better Treatment Options 5-HT + Other Carcinoid Syndrome Lung Factors ~33,000 Patients Diagnosed with Carcinoid Syndrome (US) Facial Flushing in a patient NETs with carcinoid syndrome Excess bowel movements (>3/day) are highly disruptive Goal

  5. Slide 5: Phase 2 Study Design: Evaluating Safety, PK and Efficacy of Paltusotine in Carcinoid Syndrome

    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 Long Term Extension Key Eligibility Criteria: • Treatment naïve or currently untreated and actively symptomatic – OR – con

  6. Slide 6: Disposition and Dosing for the Initial Data Cut (N=27)

    Disposition and Dosing for the Initial Data Cut (N=27) Initial data cut1 N=27 <2 Weeks of Treatment Dose at Randomization (N=27 initial data cut) N=4 2+ weeks data available for 40mg 80mg Total initial efficacy analysis2 Naïve/ N=23 5 4 9 Untreated Discontinuations Ongoing in RTP Switching 8 10 18 N

  7. Slide 7: Baseline Demographics and Disease Characteristics

    Baseline Demographics and Disease Characteristics Naïve/Untreated Symptomatic Switching from SRL Overall N=9 N=18 N=27 Female, n(%) 6(67) 9(50) 15(56) Male, n(%) 3(33) 9(50) 12(44) Age at informed consent - Mean (SD), years 58.2 (19.5) 60.6(8.1) 59.8(12.7) BMI - Mean (SD), kg/m2 30.0(14.0) 29.6(5.7)

  8. Slide 8: 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 1000 Healthy Healthy Volunteer Volunteer Carcinoid Carcinoid Syndrome Patients Syndrome Paltusotine Concentration Mean (SD) Steady-State 750 (ng/mL) 500 250 0 40 mg 40 mg 80 mg 80 mg Tro

  9. Slide 9: Paltusotine was Well-Tolerated with No Severe or Serious Treatment-Related Adverse Events

    Paltusotine was Well-Tolerated with No Severe or Serious Treatment-Related Adverse Events Treatment-Emergent Paltusotine Adverse Events N = 27 Preliminary Safety Summary from Ongoing Any 18(66.7) Carcinoid Syndrome Phase 2 Study Mild 9(33.3) • Paltusotine was well-tolerated with no treatment Moderat

  10. Slide 10: Paltusotine Reduced the Frequency of Both Key Carcinoid Syndrome Core Symptoms

    Paltusotine Reduced the Frequency of Both Key Carcinoid Syndrome Core 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 p = 0.05 p < 0.01 Excess(>3/day) Daily Frequency N=11 3.0 N=19 Dail

  11. Slide 11: Paltusotine had Clear Benefit on Subjects with Elevated Bowel Movement Frequency

    Paltusotine had Clear Benefit on Subjects with Elevated Bowel Movement Frequency Change from Baseline to Last Week of Treatment (Patients Ordered by Baseline Value) 8 Average change -1.9 BM/day (N=11) Average change -0.1 BM/day 7 (From Baseline to Last Visit) Bowel Movement Daily 6 Excess BM >3 per

  12. Slide 12: Paltusotine Showed Improvements in Flushing Frequencies in Majority of Subjects

    Paltusotine Showed Improvements in Flushing Frequencies in Majority of Subjects Change from Baseline to Last Week, Frequencies at Baseline and Last Week (Patients Ordered by Baseline Value) 8 Average change was -2.0 flushing events / day (N=19) Average change was 7 0.1 flushing events / (From Baseli

  13. Slide 13: 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 Bowel Movement Frequency of All Participants (N=23) Whether Experiencing Excess BMs at Baseline or Not Untreated Participants Participants Switching From Prior SRL 6 6 Paltusotine Paltusotine 5 5 Bowel Movement

  14. Slide 14: Rapid Improvements in Flushing Frequency were Observed within 2 Weeks of Treatment

    Rapid Improvements in Flushing Frequency were Observed within 2 Weeks of Treatment Flushing Frequency of All Participants (N=23) Whether Experiencing Flushing at Baseline or Not Untreated Participants Participants Switching From Prior SRL 4 4 Paltusotine Paltusotine Flushing Frequency/Day Flushing F

  15. Slide 15: 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 2.0 6.0 Severity (0-10 numerical rating scale) p = 0.01 p = 0.001 5.0 Daily Frequency (7d avg) 1.5 4.0 4.2 1.0 3.0 1.1 2.0 0.5 N = 23 N = 23 1.0 0.5 N = 23 N1.3 = 23 0.0 0.0 Baseline Wee

  16. Slide 16: Example Study Participant #1: Elimination of Flushing and Normalization of BMs

    Example Study Participant #1: Elimination of Flushing and Normalization of BMs 10 9 8 Paltusotine 80 mg/day 7 Excess BM Frequency (per day) 6 >3/d BMs Flushes 5 4 3 2 No Prior Normal BM Therapy 3/w to 3d 1 0 -1 -30 -20 -10 0 10 20 30 40 50 60 Study Day BM = bowel movement CRINETICS PHARMACEUTICALS |

  17. Slide 17: Example Study Participant #2: Meaningful Improvements in BM and Flushing Frequencies

    Example Study Participant #2: Meaningful Improvements in BM and Flushing Frequencies 10 80 mg/day 9 Paltusotine 40 mg/day 8 7 Frequency (per day) BMs Flushes 6 Excess BM >3/d On 5 Octreotide 4 3 2 Normal BM 1 3/w to 3d Washout 0 Period -1 -30 -20 -10 0 10 20 30 40 50 60 Study Day BM = bowel movement

  18. Slide 18: Once Daily Oral Paltusotine Showed Strong Initial Results in Carcinoid Syndrome Patients

    Once Daily Oral Paltusotine Showed Strong Initial Results in Carcinoid Syndrome Patients Summary: Exceeded Initial Goals for the Study • Significant reductions of frequency and severity of bowel movements and flushing with 40mg and 80mg • Paltusotine was well-tolerated with no severe or serious trea

  19. Slide 19: Anticipated Paltusotine Milestones

    Anticipated Paltusotine Milestones • Results from PATHFNDR-2 • Acromegaly NDA submission Phase 3 study in untreated • Carcinoid syndrome Phase 3 start acromegaly patients pending alignment with FDA 1Q24 1H24 2H24 • Topline results from carcinoid syndrome Phase 2 study (N=36) Ongoing Open Label Exten

  20. Slide 20: Q&A

    Q&A Scott Struthers, Ph.D. Founder and Chief Executive Officer Dana Pizzuti, M.D. Chief Medical & Development Officer Alan Krasner, M.D. Chief Endocrinologist

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