Slide 1: Topline Phase 2 Results from Atumelnant in Congenital Adrenal Hyperplasia (CAH)
Topline Phase 2 Results from Atumelnant in Congenital Adrenal Hyperplasia (CAH) January 10, 2025 Exhibit 99.2
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.
Slide 3: Atumelnant Positive Phase 2 Results: Strong Effect on Biomarkers and Clinical Outcomes in CAH
Atumelnant Positive Phase 2 Results: Demonstrated Strong Effect on Both Biomarkers and Clinical Outcomes in CAH A4: Androstenedione; 17-OHP: 17-hydroxyprogesterone. Atumelnant is an investigational drug. The safety and efficacy of atumelnant have not been established. In clinical studies, atumelnant
Slide 4: Atumelnant is the First and Only ACTH Antagonist in Clinical Development for CAH
Atumelnant is the First and Only ACTH Antagonist in Clinical Development for Congenital Adrenal Hyperplasia Reference: Kim SH, Han S, Zhao J, et al. Discovery of CRN04894: A novel potent selective MC2R antagonist. ACS Med Chem Lett. 2024;15(4):478-485. Abbreviations: ACTH, adrenocorticotrophic hormo
Slide 5: CAH Affects ~17,000 Addressable Adult and Pediatric Patients in the US
CAH Affects ~17,000 Addressable Adult and Pediatric Patients in the US Treatment Goals in Adults with CAH Reduction of A4 and other androgens to address hyperandrogenism, which can manifest as excessive facial hair, acne and polycythemia Restore normal menstrual cycles and fertility in women Shrink
Slide 6: Phase 2 Open-Label Study of Atumelnant in CAH
Male or female participants ≥16 years (≥18 years ex-US) and ≤75 years Classic 21-hydroxylase deficiency On ≥15mg Hydrocortisone equivalent daily dose A4 >1.5xULN Phase 2 Open-Label Study of Atumelnant in CAH Designed to Evaluate Safety, Efficacy and Pharmacokinetics A4: Androstenedione; ULN: Upper l
Slide 7: Demographics and Baseline Characteristics
Demographics and Baseline Characteristics * One participant in 80mg had no height assessment at baseline and was excluded in the summary. ** Central laboratory data reported. 2 participants entered the study based on elevated A4 levels measured locally that were >1.5 ULN. Upper limit of normal (ULN)
Slide 8: 12 Weeks of Treatment with Atumelnant Was Well Tolerated
Once daily dosing of 40, 80 and 120 mg of atumelnant generally well tolerated No severe or serious adverse events observed to date TEAEs mild to moderate in nature, most were transient and did not require intervention No negative clinical trends relative to vital signs, physical examination or elect
Slide 9: Overview of Treatment-Emergent Adverse Events
40 mg N=11 n (%) 80 mg N=11 n (%) 120 mg N=6 n (%) All Participants N=28 n (%) Any Treatment-Emergent Adverse Events (TEAE) 8 (72.7%) 7 (63.6%) 5 (83.3%) 20 (71.4%) Mild 5 (45.5%) 4 (36.4%) 4 (66.7%) 13 (46.4%) Moderate 3 (27.3%) 3 (27.3%) 1 (16.7%) 7 (25.0%) Severe 0 0 0 0 Any Related TEAE 4 (36.4%
Slide 10: Atumelnant Was Well Tolerated: Summary of TEAEs by Preferred Term
Atumelnant Was Well Tolerated Preferred Term 40 mg N=11 n (%) 80 mg N=11 n (%) 120 mg N=6 n (%) All Participants N=28 n (%) Participants with at least 1 TEAE 8 (72.7%) 7 (63.6%) 5 (83.3%) 20 (71.4%) Headache 2 (18.2%) 3 (27.3%) 2 (33.3%) 7 (25.0%) Fatigue 3 (27.3%) 1 (9.1%) 1 (16.7%) 5 (17.9%) Decre
Slide 11: Rapid, Substantial and Sustained A4 Reductions
Rapid, Substantial and Sustained A4 Reductions, the Key Biomarker for CAH Disease Control Participants At Baseline: 40 mg N=11; 80 mg N=11; 120 mg N=6. Participants At Week 12: 40 mg N=10; 80 mg N=11; 120 mg N=6. CFB: change from baseline, LSM: Least-square-mean Across each cohort, baseline A4 level
Slide 12: Majority of Participants at 80mg and 120mg Achieved A4<ULN by Week 2
Female ULN Male ULN 2 BL 6 12 (EOT) 14 The Majority of Participants at 80mg and 120 mg* Achieved A4<ULN by Week 2 40 mg Morning Serum A4 (ng/dL) 80 mg Week 120 mg 2 BL 6 12 (EOT) 14 2 BL 6 12 (EOT) 14 *7/11 participants at 80 mg and 4/6 at 120 mg achieved A4<ULN by week 2
Slide 13: Rapid, Substantial and Sustained Reductions in 17-OHP
Rapid, Substantial and Sustained Reductions in 17-OHP, a Confirmatory Secondary Biomarker of Disease Control Serum 17-Hydroxyprogesterone (SE) (ng/dL) BL W12 (EOT) BL W12 (EOT) BL W12 (EOT) 2 BL 6 12 (EOT) 14 Serum 17-Hydroxyprogesterone (ng/dL) Week 2 BL 6 12 (EOT) 14 2 BL 6 12 (EOT) 14 40 mg 80 mg
Slide 14: Many Participants Resumed Menses While Enrolled in the Study
Many Participants Resumed Menses While Enrolled in the Study 6/11 female participants (not on hormonal contraceptives with intact uterus) resumed menses during the study Includes 3 previously amenorrheic female participants, and 3 participants with previous irregular menses 8/13 female participants
Slide 15: Case Study: Lifelong Adrenal Enlargement Improved on Atumelnant within 12 weeks
Case Study: Lifelong Adrenal Enlargement Improved on Atumelnant within 12 weeks * In patients with evaluable MRIs at baseline and at 12 Weeks. **77% reduction observed in the left adrenal (not shown). CONFIDENTIAL Example 120mg Participant -79% Reduction Consistent Decrease in Adrenal Volume Across
Slide 16: Significant Clinical Improvements Achieved with Atumelnant Treatment
Significant Clinical Improvements Achieved with Atumelnant Treatment CAH Manifestations Achieved following 12 weeks of treatment with atumelnant Overproduction of androgens, and androgen precursors Normalization of A4 in many participants and substantial reduction in 17-OHP levels (across dose group
Slide 17: Summary of Results and Next Steps
Summary of Results and Next Steps Summary: Successful Phase 2 Results Rapid and sustained treatment effect, including in participants with high baseline A4 Clinical activity observed across all doses (once daily 40, 80 and 120 mg) Dose response demonstrated 80 mg and 120 mg as the likely therapeutic
Slide 18: Atumelnant Vision: Healthier Hormone Levels for People Living with CAH
A single pill taken once a day, that eliminates excess ACTH driven adrenal activation and its clinical sequalae for people struggling with Congenital Adrenal Hyperplasia Normal A4 + GC High A4 + Normal GC High A4 + High GC Normal A4 + High GC Atumelnant Vision: Healthier Hormone Levels for People Li
Slide 19: 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 Marc Wilson Chief Financial Officer
Slide 20: Abbreviations
Abbreviations CAH Congenital adrenal hyperplasia CRF Corticotropin releasing factor EOT End of treatment GC Glucocorticoid TEAE Treatment emergent adverse event TART Testicular adrenal rests tumors ULN Upper limit of normal 17-OHP 17-hydroxyprogesterone A4 Androstenedione ACTH Adrenocorticotrophic h