Crinetics Pharmaceuticals, Inc. · NASDAQ:CRNX

Crinetics Pharmaceuticals — Investor Presentation (June 2024)

32 slides from Crinetics Pharmaceuticals's investor presentation, Jun 3, 2024

  1. Slide 1: Initial Phase 2 Results From Atumelnant in CAH and ADCS

    Initial Phase 2 Results From Atumelnant* (CRN04894) in Congenital Adrenal Hyperplasia (CAH) and ACTH- dependent Cushing’s Syndrome (ADCS) June 3rd, 2024 * Proposed international nonproprietary name under review

  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: Crinetics' Vision for Atumelnant

    Crinetics’ Vision for Atumelnant* A single pill, taken once a day, that reliably enables people struggling with either CAH or ADCS to achieve normal, healthy hormone levels that will improve their daily lives. OUR MISSION To revolutionize the treatment paradigm for CAH and ADCS with an unprecedented

  4. Slide 4: Profound, Rapid and Sustained Reductions of A4 and 17-OHP in CAH with Atumelnant

    Profound, Rapid and Sustained Reductions of A4 and 17-OHP in Congenital Adrenal Hyperplasia with Atumelnant EFFICACY ✓ 100% (n=6/6) of participants maintained androstenedione (A4) <ULN at all time points on atumelnant (80 mg) • A4 and related androgens are key drivers of disease pathophysiology • A4

  5. Slide 5: Profound, Rapid and Sustained Reduction of Excess Cortisol in ADCS with Atumelnant

    Profound, Rapid and Sustained Reduction of Excess Cortisol in ACTH-dependent Cushing’s Syndrome with Atumelnant EFFICACY ✓ 100% (n=5/5) of participants achieved normal 24h Urinary Free Cortisol (UFC) on atumelnant (80 mg) • UFC normalization has been recommended by FDA as a primary endpoint ✓ ALL pa

  6. Slide 6: Disruptions in the HPA Axis Lead to Diseases of Excess ACTH and Excess Adrenal Activation

    Disruptions in the HPA Axis Lead to Diseases of Excess ACTH and Excess Adrenal Activation Normal Cushing’s Disease (CD) Congenital Adrenal Hyperplasia (CAH) Circadian Hypothalamus Hypothalamus Hypothalamus Negative Clock AVP Feedback AVP AVP CRF CRF CRF Stress Unable to Regulate Negative Loss of Exc

  7. Slide 7: Congenital Adrenal Hyperplasia

    CONGENITAL ADRENAL HYPERPLASIA

  8. Slide 8: Atumelnant: Second Clinical Asset in Late-Stage Development

    Atumelnant: Second Clinical Asset in Late-Stage Development Skillfully Crafted to Help Subjects Reach Their Treatment Goals Stress Hypothalamus Lead Indication: Congenital Adrenal Hyperplasia (CAH) CRF Circadian Estimated ~27,000 people in the US based on genetic prevalence CRF Clock AVP AVP Treatme

  9. Slide 9: Atumelnant: The First Oral, Selective ACTH Antagonist

    Atumelnant: The First Oral, Selective ACTH Antagonist Atumelnant is an investigational drug being evaluated in clinical studies for CAH. Atumelnant has not yet been approved by any regulatory authority. 9 A4: Androstenedione; 17-OHP: 17-hydroxyprogesterone, ACTH: Adrenocorticotropic hormone. MC2R: M

  10. Slide 10: Updated Design and Status: Phase 2 Atumelnant in CAH (TouCAHn)

    Updated Design and Status: Phase 2 Atumelnant in Congenital Adrenal Hyperplasia (CAH) (TouCAHn) Key Eligibility Criteria Treatment Arms: N=24 • 3 cohorts, each 12 weeks (N=6-12) • Male or female participants ≥18 to 75 years. Age: ≥16 years (US) 80 mg Once Daily (n=9) • Classic 21-hydroxylase deficie

  11. Slide 11: Demographics and Baseline Characteristics

    Demographics and Baseline Characteristics 40 mg 80 mg All Participants N=4 N=6 N=10 Age (yrs), mean (range) 24.3 (22-27) 35.2 (25-42) 30.8 (22-42) Female, n (%) 0 5 (83%) 5 (50%) BMI (kg/m2)*, mean (range) 26.5 (21.7-30.2) 30.9 (22.3-35.8) 29.0 (21.7-35.8) Baseline Biomarker levels A4 (ng/dL), mean

  12. Slide 12: No Significant Safety Signals Reported

    No Significant Safety Signals Reported Summary of TEAEs by Preferred Term (Reported by ≥2 of Total Participants) 40 mg 80 mg All N=4 N=6 N=10 Preferred Term n (%) n (%) n (%) Participants with at least 1 TEAE 3 (75%) 4 (67%) 7 (70%) Fatigue 2 (50%) 1 (17%) 3 (30%) Headache 2 (50%) 0 2 (20%) Upper re

  13. Slide 13: Atumelnant (80 mg) Profoundly and Rapidly Reduced Mean A4, Sustained at 12 Weeks

    Atumelnant (80 mg) Profoundly and Rapidly Reduced Mean A4, Sustained at 12 Weeks Atumelnant 2000 1800 Mean (SE) of Morning Serum A4 1600 80 mg 1400 1200 (ng/dL) 1000 800 -91%* -96%* (at the earliest 600 (sustained at 12wks) timepoint measured) 400 200 Female ULN Male ULN 0 Baseline 2 6 12 (EOT) 14 W

  14. Slide 14: Atumelnant (80 mg) Induced Rapid, Profound and Sustained Reduction of A4 in all Participants

    Atumelnant (80 mg) Induced Rapid, Profound and Sustained Reduction of A4 in all Participants Participant 1 (M) Participant 2 (F) Participant 3 (F) Participant 4 (F) Participant 5 (F) Participant 6 (F) 2800 Atumelnant 2600 1000 Morning Serum A4 (ng/dL) 800 600 Two female subjects had first menstruati

  15. Slide 15: Atumelnant (40 mg) Also Lowered A4 Levels

    Atumelnant (40 mg) Also Lowered A4 Levels Atumelnant 2000 1800 Mean (SE) of Morning Serum A4 1600 40 mg 80 mg 1400 1200 (ng/dL) 1000 800 -91%* -96%* (at the earliest (sustained at 12wks) 600 timepoint measured) 400 200 Female ULN Male ULN 0 Baseline 2 6 12 (EOT) 14 Week Number of Participants: 40 mg

  16. Slide 16: Atumelnant (80 mg) Profoundly and Rapidly Reduced Mean 17-OHP, Sustained at 12 Weeks

    Atumelnant (80 mg) Profoundly and Rapidly Reduced Mean 17-OHP, Sustained at 12 Weeks Atumelnant 18000 17-Hydroxyprogesterone (ng/dL) 16000 14000 80 mg Mean (SE) of Serum 12000 10000 8000 6000 -97%* -94%* (at the earliest 4000 timepoint measured) (sustained at 12wks) 2000 Female ULN 0 Male ULN Baseli

  17. Slide 17: Atumelnant (80 mg) Induced Rapid, Profound and Sustained Reduction of 17-OHP in all Participants

    Atumelnant (80 mg) Induced Rapid, Profound and Sustained Reduction of 17-OHP in all Participants Participant 1 (M) Participant 2 (F) Participant 3 (F) Participant 4 (F) Participant 5 (F) Subject 6 (F) Atumelnant 25000 Serum 17-Hydroxyprogesterone 20000 15000 (ng/dL) 10000 5000 Female ULN 0 Male ULN

  18. Slide 18: Atumelnant (40 mg) Also Lowered 17-OHP Levels

    Atumelnant (40 mg) Also Lowered 17-OHP Levels Atumelnant 18000 17-Hydroxyprogesterone (ng/dL) 16000 40 mg 80 mg 14000 Mean (SE) of Serum 12000 10000 8000 6000 -97%* -94%* (at the earliest 4000 (sustained at 12wks) timepoint measured) 2000 Female ULN 0 Male ULN Baseline 2 6 12 (EOT) 14 Week Number of

  19. Slide 19: Goal: Achieving Healthy Hormone Levels with Atumelnant

    Goal: Achieving Healthy Hormone Levels with Atumelnant Normalize A4 at Physiologic Glucocorticoid Replacement Phase 3 study to be designed to benefit all patients with unhealthy hormone levels (A4 or GC) Phase 2 Participants: 900 High A4, High GC High A4, Normal GC 800 Phase 2 700 Androstenedione Le

  20. Slide 20: ACTH Dependent Cushing's Syndrome

    ACTH DEPENDENT CUSHING’S SYNDROME

  21. Slide 21: Atumelnant in ACTH-dependent Cushing's Syndrome

    Atumelnant in ACTH-dependent Cushing’s Syndrome ACTH-dependent Cushing’s Syndrome (ADCS) Treatment Goals • Control cortisol levels and reduce associated complications (e.g., cardiovascular disease, infections, thromboembolism, diabetes, fractures) • Correct ADCS symptoms and patient reported outcome

  22. Slide 22: Despite Recent Medical Advances, Optimal ADCS Medical Treatment Remains Elusive

    Despite Recent Medical Advances, Optimal ADCS Medical Treatment Remains Elusive Unpredictable Unacceptable delay to cortisol Multiple Limiting outcomes with normalization Adverse events existing therapies ~50-80% efficacy but with Laborious Titration schedules • Hepatotoxicity unpredictable effects

  23. Slide 23: Open-Label Trial of Atumelnant in ACTH-dependent Cushing's Syndrome (ADCS)

    Open-Label Trial of Atumelnant in ACTH-dependent Cushing’s Syndrome (ADCS) Sequential Multiple Ascending Dose Cohorts Key Eligibility Criteria Treatment Arms: • 3 cohorts, 10 days treatment N=18 • Male or female, aged 18- 80 mg Once Daily (n=6) 75 years • ADCS or Ectopic ACTH syndrome 120 mg Once Da

  24. Slide 24: Demographics and Baseline Characteristics

    Demographics and Baseline Characteristics 80 mg N=5 Age (yrs), median (range) 47 (34-55) Male, n (%) 4 (80%) BMI (kg/m2), median, (range) 36 (24-43) 24h mUFC (ug/24h), median (range) 252 (99-293) ACTH (pg/mL), median (range) 49 (26-1,504) Reference range (RR): <45 ug/24h for mUFC and 5-46 pg/mL for

  25. Slide 25: Safety and Tolerability

    Safety and Tolerability • Atumelnant 80 mg was generally well tolerated in this study • Predefined biochemical adrenal insufficiency (serum cortisol <5 µg/dL) observed in all patients treated to date. Consistent with the known mechanism and pharmacology • Two participants with pre-existing steatosis

  26. Slide 26: Morning Serum Cortisol: All Participants Rapidly Achieved Serum Cortisol Levels <5 µg/dL

    Morning Serum Cortisol: All Participants Rapidly Achieved Serum Cortisol Levels <5 µg/dL Participant 1 Participant 2 Participant 3 Participant 4 Participant 5 30 Atumelnant 25 Serum Cortisol (µg/dL) 20 15 10 5 5 µg/dL* Biochemical Adrenal 0 Insufficiency 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Day HC Add

  27. Slide 27: 24h Urine Free Cortisol: Sustained at or Below the ULN with HC Add Back

    24h Urine Free Cortisol: Sustained at or Below the ULN and Maintained Control with Hydrocortisone (HC) Add Back Participant 1 Participant 2 Participant 3 Participant 4 Participant 5 350 Atumelnant 300 Urine Free Cortisol (µg/24 hr) 250 200 150 100 50 ULN 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Day HC A

  28. Slide 28: Every Participant Experienced Improvement in Multiple Clinical and/or Cushing's Lab Features

    Every Participant Experienced Improvement in Multiple Clinical and/or Cushing’s Lab Features Participant 1 2 3 4 5 Total Insomnia   -   4/4 Irritability -  -   3/3 Malaise - - - -  1/1 Poor concentration      4/5 Anxiety/depression -     3/4 Clinical Features Fatigue  - -   2/3 L

  29. Slide 29: Atumelnant Program: Summary of Results and Next Steps

    Atumelnant Program: Summary of Results and Next Steps Summary: Phase 2 Data Exceeded Expectations with Unprecedented Effects • Profound, rapid and sustained biomarker reduction in both CAH and ADCS • Generally safe and well-tolerated • Early signs of clinical symptom improvement in both CAH and ADCS

  30. Slide 30: Crinetics is Building the Premier Fully Integrated Endocrine-Focused Pharmaceutical Company

    Crinetics is Building the Premier Fully Integrated Endocrine- Focused Pharmaceutical Company • 1H Commence CAH Phase 3* • ✓ 1Q Carcinoid Syndrome Phase 2 data readout • 2H Paltusotine acromegaly PDUFA** and launch** • ✓ 1Q Acromegaly PATHFNDR-2 Phase 3 data readout • Later-stage ADCS development* •

  31. Slide 31: 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 31

  32. Slide 32: Atumelnant Maintained Cortisol Below Normal Levels After ACTH Challenge Test

    Atumelnant Maintained Cortisol Below Normal Levels After ACTH Challenge Test on Top of Sustained Elevated ACTH ACTH Challenge ‘4894 ACTH Elevated or PBO Challenge Cortisol PBO (n=12) (1 mcg) 20 '4894 80 mg nighttime (n=5) [Cortisol] (mcg/dL) 15 Suppression Normal range for Healthy of response Volunt

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