Slide 1: Initial Phase 2 Results From Atumelnant in CAH and ADCS
Exhibit 99.3 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
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: 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
Slide 4: Profound, Rapid and Sustained Reductions of A4 and 17-OHP in CAH
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
Slide 5: Profound, Rapid and Sustained Reduction of Excess Cortisol in ADCS
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
Slide 6: Disruptions in the HPA Axis Lead to Diseases of Excess ACTH
Disruptions in the HPA Axis Lead to Diseases of Excess ACTH and Excess Adrenal Activation Normal Cushing’s Disease (CD) Congenital Adrenal Hyperplasia (CAH) Hypothalamus Hypothalamus Hypothalamus Circadian Negative Clock AVP Feedback AVP AVP CRF CRF CRF Stress Unable to Regulate Loss of Negative Exc
Slide 7: Congenital Adrenal Hyperplasia
CONGENITAL ADRENAL HYPERPLASIA
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) Circadian Estimated ~27,000 people in the US based on genetic prevalence CRF CRF Clock AVP AVP Treatme
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
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 80 mg Once Daily (n=9) years. Age: ≥16 years (US) • Classic 21-hydroxylase deficie
Slide 11: Demographics and Baseline Characteristics
Demographics and Baseline Characteristics 40 mg 80 mg All Participants N=4 N=6 N=10 24.3 (22-27) 35.2 (25-42) 30.8 (22-42) Age (yrs), mean (range) Female, n (%) 0 5 (83%) 5 (50%) 2 BMI (kg/m )*, 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), mea
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 n (%) n (%) n (%) Preferred Term 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
Slide 13: Atumelnant (80 mg) Profoundly and Rapidly Reduced Mean A4
Atumelnant (80 mg) Profoundly and Rapidly Reduced Mean A4, Sustained at 12 Weeks Atumelnant 2000 1800 1600 80 mg 1400 1200 1000 -91%* 800 -96%* (at the earliest (sustained at 12wks) 600 timepoint measured) 400 Female ULN 200 Male ULN 0 Baseline 2 6 12 (EOT) 14 Week Number of Participants: 80 mg 6 6
Slide 14: Atumelnant (80 mg) Induced 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) Atumelnant 2800 2600 1000 800 600 Two female subjects had first menstruation in >2 years. Regular m
Slide 15: Atumelnant (40 mg) Also Lowered A4 Levels
Atumelnant (40 mg) Also Lowered A4 Levels Atumelnant 2000 1800 1600 40 mg 80 mg 1400 1200 1000 -91%* -96%* 800 (at the earliest (sustained at 12wks) 600 timepoint measured) 400 Female ULN 200 Male ULN 0 Baseline 2 6 12 (EOT) 14 Week Number of Participants: 40 mg 4 4 0 0 0 80 mg 6 6 6 4 4 * Percent c
Slide 16: Atumelnant (80 mg) Profoundly and Rapidly Reduced Mean 17-OHP
Atumelnant (80 mg) Profoundly and Rapidly Reduced Mean 17-OHP, Sustained at 12 Weeks Atumelnant 18000 16000 14000 80 mg 12000 10000 8000 -97%* 6000 -94%* (at the earliest (sustained at 12wks) 4000 timepoint measured) 2000 Female ULN 0 Male ULN Baseline 2 6 12 (EOT) 14 Week Number of Participants: 80
Slide 17: Atumelnant (80 mg) Induced 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 20000 15000 10000 5000 Female ULN 0 Male ULN Baseline 2 6 12 (EOT) 14 Week EOT: En
Slide 18: Atumelnant (40 mg) Also Lowered 17-OHP Levels
Atumelnant (40 mg) Also Lowered 17-OHP Levels Atumelnant 18000 16000 40 mg 80 mg 14000 12000 10000 8000 -97%* 6000 -94%* (at the earliest (sustained at 12wks) 4000 timepoint measured) 2000 Female ULN 0 Male ULN Baseline 2 6 12 (EOT) 14 Week Number of Participants: 40 mg 4 4 0 0 0 80 mg 6 6 6 4 3 * P
Slide 19: Phase 3 Goal: Achieving Healthy Hormone Levels with Atumelnant
Phase 2 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 800 700 600 91% A4* Unheal
Slide 20: ACTH Dependent Cushing's Syndrome
ACTH DEPENDENT CUSHING’S SYNDROME
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
Slide 22: Optimal ADCS Medical Treatment Remains Elusive
Despite Recent Medical Advances, Optimal ADCS Medical Treatment Remains Elusive Unacceptable Unpredictable Multiple Limiting delay to cortisol outcomes with Adverse events normalization existing therapies Laborious Titration schedules • Hepatotoxicity ~50-80% efficacy but with (every 2+ weeks or lon
Slide 23: Open-Label Trial of Atumelnant in ADCS
Open-Label Trial of Atumelnant in ACTH-dependent Cushing’s Syndrome (ADCS) Sequential Multiple Ascending Dose Cohorts Treatment Arms: Key Eligibility Criteria • 3 cohorts, 10 days treatment N=18 • Male or female, aged 18- 80 mg Once Daily (n=6) 75 years • ADCS or Ectopic ACTH 120 mg Once Daily (n=6)
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%) 2 BMI (kg/m ), 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 fo
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
Slide 26: Morning Serum Cortisol: All Participants Achieved 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 20 15 10 5 5 µg/dL* Biochemical Adrenal Insufficiency 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Day HC Add Back Started 26 HC: Hy
Slide 27: 24h Urine Free Cortisol: Sustained at or Below the ULN
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 300 250 200 150 100 50 ULN 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Day HC Add Back Started 27 ULN: Upper l
Slide 28: Every Participant Experienced Improvement in Multiple Clinical 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 ˜ - -˜˜ Low Libido 2/3 ˜˜
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
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 • 2H Paltusotine acromegaly data readout ** ** PDUFA and launch •✓ 1Q Acromegaly PATHFNDR-2 Phase • Later-stage ADCS development* 3 data readout •
Slide 31: 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 Jim Hassard Chief Commercial Officer 31