Crinetics Pharmaceuticals, Inc. · NASDAQ:CRNX
Crinetics Pharmaceuticals — Investor Presentation (September 2025)
38 slides from Crinetics Pharmaceuticals's investor presentation, September 2025
Slide 1: Corporate Presentation
Corporate Presentation September 2025
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 all statements other than statements of historical facts contained in this presentation are forward-looking statements.
Slide 3: Our Mission
To be the world’s leading endocrine company that Our Mission: consistently pioneers new therapeutics to help patients better control their disease and improve their daily lives Acromegaly Carcinoid Syndrome Congenital Adrenal Hyperplasia ACTH-Dependent Cushing’s Syndrome Tony Ellen Wendy NETs and SS
Slide 4: Transforming Endocrine Disease Treatment from Discovery to Commercialization
Transforming Endocrine Disease Treatment from Discovery to Commercialization In-House Discovery Proven Development Commercial Execution ✓ Proven drug-hunters in ✓ Demonstrated execution ✓ Building global the difficult GPCR space with 5 positive global commercial Phase 2 or 3 readouts in capabilities
Slide 5: Continued Value Creation with Deep Pipeline of Transformative Drug Candidates
Continued Value Creation with Deep Pipeline of Transformative Drug Candidates PRODUCT CANDIDATE INDICATION DISCOVERY IND-ENABLING PHASE 1 PHASE 2 PHASE 3 REGISTRATIONAL APPROVED Paltusotine (Oral SST2 Acromegaly (US) Agonist) Paltusotine (Oral SST2 Acromegaly (EU) Agonist) Paltusotine (Oral SST2 Car
Slide 6: World-class Development Leading to Global Commercialization
World-class Development Leading to Global Commercialization Paltusotine: Lead Clinical Candidate for Acromegaly and Carcinoid Syndrome PATHFNDR-1 PATHFNDR-2 CARCINOID SYNDROME PHASE 3 RESULTS PHASE 3 RESULTS PHASE 2 RESULTS CRINETICS PHARMACEUTICALS | 6
Slide 7: Acromegaly Symptoms Take a Toll on Patients
Acromegaly Symptoms Take a Toll on Patients Acromegaly is a rare chronic disease caused by a pituitary adenoma that secretes excess GH, resulting in hypersecretion of IGF-I1,2 Effects of Prolonged Exposure to IGF-I and GH1,2 Patient Symptoms3-4 LOCAL TUMOR EFFECTS PHYSICAL CHANGES Headache | Visual
Slide 8: Acromegaly Patient Reach
Acromegaly Patient Reach 36,000 People Living with 11,500 Actively Managed and Acromegaly in the US Addressable in Short-Term 7,500 No Active Follow-up 15% 40% Treatment Treatment Discontinued Naive 17,000+ Undiagnosed 20% 11,500 Other Therapies Actively 25% Managed Injectable SRL 1,500/yr diagnosed
Slide 9: Acromegaly Patients Face Significant Unmet Need, Presenting a Compelling Market Opportunity
Acromegaly Patients Face Significant Unmet Need, Presenting a Compelling Market Opportunity Reported injection site reactions 77% after SRL treatment1 Had acromegaly symptoms worsen 79% at end of SRL injection cycle2 64% Felt upset for being dependent on others for treatment1 “It's urgent because sy
Slide 10: PALSONIFY Achieved Rapid, Reliable Biochemical Control in Switch Patients
In Phase 3 Studies, PALSONIFY Achieved Rapid, Reliable and Consistent Biochemical Control in Switch Patients Patients switching from PALSONIFY Treatment Maintained IGF-1 Control standard-of-care in Patients who Switched from SRL Injections 2.0 Mean (±SE) IGF-I (× ULN) 83% 1.5 1.0 p<0.0001 4% 0.5 Pal
Slide 11: PALSONIFY Achieved Rapid, Reliable Biochemical Control in Naïve Patients
In Phase 3 Studies, PALSONIFY Achieved Rapid, Reliable and Consistent Biochemical Control in Naïve Patients Non-pharmacologically- Percent Change from Baseline in IGF-1 Level by Visit treated patients 10 PALSONIFY (N=54) Placebo (N=57) IGF-1 Mean Percent Change 0 from Baseline (± SE) 56% -10 Rapid 9
Slide 12: PALSONIFY Results in Long-Term Stable Biochemical Control
PALSONIFY Treatment Results in Long-Term Stable Biochemical Control Across a Range of Acromegaly Patients Evolve/ Edge ACROBAT Advance 3.0 LA- Wash SRL -out Median IGF-I ± IQR 2.0 IGF-I (x ULN) 1.0 ULN 4 0.0 years W3 W15 W39 W51 W77 W103 W129 W155 W181 W207 N 43 43 43 42 39 40 37 37 35 33 28 20 PATH
Slide 13: PALSONIFY Achieved Consistent Control of Symptoms and Reduced Exacerbations
In Phase 3 Studies, PALSONIFY Achieved Consistent Control of Symptoms and Reduced Frequency of Symptom Exacerbations Label includes trend towards reduced severity of 7 key symptoms in both randomized trials PALSONIFY PALSONIFY Placebo Placebo Change from Baseline in ASD Score by Item Change from Bas
Slide 14: PALSONIFY was Well-Tolerated with No Severe or Serious Adverse Events
PALSONIFY was Well-Tolerated with No Severe or Serious Adverse Events Key safety outcomes from the randomized control period of Phase 3 studies • No serious adverse events None occurred with PALSONIFY vs 2.4% with placebo • GI AEs resolved Most GI AEs occurred within the first 2 months (median durat
Slide 15: Four Pillars to Optimize the Launch of PALSONIFY
Four Pillars to Optimize the Launch of PALSONIFY ACTIVATE ADOPT ACCESS ADHERE SHIFT THE WIN ON ENSURE DRIVE ADHERENCE MINDSET EFFICACY ACCESS Success isn’t just Switch and naïve Removing friction to With the right about IGF-1 control, patients deserve a help more patients support, patients it’s abou
Slide 16: Carcinoid Syndrome: Second Indication for Paltusotine
Carcinoid Syndrome: Second Indication for Paltusotine Serotonin + Other Carcinoid Syndrome Lung Factors Facial flushing in a patient Severe flushing episodes can be debilitating and potentially with carcinoid syndrome NETs dangerous Goal: reduce frequency and severity (normal is < 1/day) Excess bowe
Slide 17: Carcinoid Syndrome: Paltusotine Reduced Frequency of Key Symptoms in Phase 2
Carcinoid Syndrome: Paltusotine Reduced Frequency of Key Symptoms in Phase 2 Study Flushing Frequency For Patients with Excess Bowel Movement* Frequency >1/day at Baseline For Patients with >3/day at Baseline 3.0 Excess (>3/day) Daily Frequency (7d avg) 4.0 P<0.0001 P=0.02 (N=24) (N=16) Daily Freque
Slide 18: Carcinoid Syndrome: CAREFNDR Phase 3 Study
Carcinoid Syndrome: CAREFNDR Phase 3 Study Trial Size: 141 patients, 2:1 randomization Key Eligibility Criteria: • Treatment naïve or currently untreated and actively symptomatic –OR- controlled on SRL therapy and symptom worsening upon washing out of treatment • Grade 1 or 2 NET, Positive SSTR expr
Slide 19: World-class Development to Grow the Late-Stage Pipeline
World-class Development to Grow the Late-Stage Pipeline Atumelnant: In Development for Congenital Adrenal Hyperplasia and Cushing’s Disease CUSHING’S DISEASE CAH PHASE 2 PHASE 2 INITIAL TOPLINE RESULTS FINDINGS RELEASE CRINETICS PHARMACEUTICALS | 19
Slide 20: Atumelnant: First Oral, Daily ACTH Antagonist in Development for CAH
Atumelnant: The First Oral, Daily ACTH Antagonist is in Development for Congenital Adrenal Hyperplasia Disruptions in the HPA Axis Causing CAH Atumelnant Mechanism of Action in CAH Hypothalamic-Pituitary-Adrenal Axis Hypothalamic-Pituitary-Adrenal Axis Hypothalamus 21-OH deficiency blocks Hypothalam
Slide 21: 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 • S
Slide 22: Atumelnant Vision: Healthier Hormone Levels for People Living with CAH
Atumelnant Vision: Healthier Hormone Levels for People Living with CAH 3000 2500 High A4 High A4 Androstenedione Level + + 2000 Normal GC High GC (A4) (ng/dL) 1500 1000 Normal A4 500 + Normal A4 + GC High GC 0 0 5 10 15 20 25 30 35 40 45 GC Dose (Hydrocortisone Equivalent) (mg/m2/day) A single pill
Slide 23: Rapid, Substantial and Sustained A4 Reductions
Rapid, Substantial and Sustained A4 Reductions, the Key Biomarker for CAH Disease Control 1600 40 mg 80 mg 120 mg Observations from Mean Mean Morning Serum A4 (SE) (ng/dL) 1400 Morning Serum A4 Declines 1200 • Across each cohort, baseline A4 1000 levels were significantly elevated (>1,000 ng/dL) -58
Slide 24: Atumelnant Positive Phase 2 Results in CAH
Atumelnant Positive Phase 2 Results: Demonstrated Strong Effect on Both Biomarkers and Clinical Outcomes in CAH EFFICACY ✓ Rapid, substantial, sustained statistically significant reduction of A4 in all dose groups: Up to 80% mean reduction in A4 on atumelnant as soon as 2 weeks, sustained at 12 week
Slide 25: Updated Design and Status: Phase 2 Atumelnant in CAH
Updated Design and Status: Phase 2 Atumelnant in Congenital Adrenal Hyperplasia (CAH) Treatment Arms: Key Eligibility Criteria • 4 cohorts, each 12 weeks (N=6-12) N=34-40 • Male or female 80 mg Once Daily (PM Dosing) (n=11) participants ≥18 to 75 years. Age: ≥16 years (US) 40 mg Once Daily (PM Dosin
Slide 26: Global Phase 3 CAH Trial Design
Global Phase 3 CAH Trial Designed to Assess Normalization of Androgen and Glucocorticoids Key Eligibility Criteria (N = 150): • Male or female participants ≥ 18 to 75 years. • A4 > ULN1 with supraphysiologic GC dose (≥11 mg/m2/day) • Classic 21-hydroxylase deficiency • A4 > ULN1 with physiologic GC
Slide 27: Global Phase 2/3 Pediatric CAH Trial Design
Global Phase 2/3 Pediatric CAH Trial Designed to Assess Normalization of Androgens and Glucocorticoids Operationally Seamless Phase 2/3 Study Design Part A (Phase 2) Part B (Phase 3) • Open-label, semi-sequential cohorts • Double-blind, Placebo controlled • Dose Determination for Part B • Confirmato
Slide 28: Establishing Uncompromising CAH Treatment Goals
Establishing Uncompromising CAH Treatment Goals Androgen and GC Establishing the uncompromising treatment goal of normal adrenal androgens (A4 ≤ULN) Normalization with physiologic glucocorticoid replacement Early and extended period for glucocorticoid reduction designed to achieve GC as Replacement,
Slide 29: ACTH Dependent Cushing's Syndrome: Second Indication for Atumelnant
ACTH Dependent Cushing’s Syndrome (ADCS): Second Indication for Atumelnant Disruptions in the HPA Axis Causing ADCS Atumelnant Mechanism of Action in ADCS Hypothalamic-Pituitary-Adrenal Axis Hypothalamic-Pituitary-Adrenal Axis Hypothalamus Hypothalamus Adenoma* secretes AVP ACTH leading to AVP CRF a
Slide 30: ADCS Medical Treatment Remains a Significant Unmet Need
ADCS Medical Treatment Remains a Significant Unmet Need for the Endocrinology Field Unpredictable outcomes Unacceptable delay to Multiple with existing therapies cortisol normalization Limiting Adverse events Goal is to control cortisol Titration every 2+ weeks • Hepatotoxicity levels (serum and uri
Slide 31: Morning Serum Cortisol: All Participants Rapidly Achieved Levels <5 µg/dL
In Phase 1b/2a, Morning Serum Cortisol: All Participants Rapidly Achieved Cortisol Levels <5 µg/dL Participant 1 Participant 2 Participant 3 Participant 4 Participant 5 30 Serum Cortisol 25 (µg/dL) 20 15 10 5 5 µg/dL* 0 Biochemical Adrenal Insufficiency 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 350 300 Uri
Slide 32: Atumelnant Showed Profound, Rapid and Sustained Reduction of Excess Cortisol
ACTH Dependent Cushing’s Syndrome: Atumelnant Showed Profound, Rapid and Sustained Reduction of Excess Cortisol ✓ EFFICACY • Morning Serum Cortisol: All Participants Rapidly Achieved Serum Cortisol Levels <5 µg/dL • 24-hour Urine Free Cortisol: Sustained at or Below the ULN with Hydrocortisone Add-B
Slide 33: World-class Discovery to Grow the Clinical Pipeline
World-class Discovery to Grow the Clinical Pipeline Following the Crinetics way to create medicines to help increasingly larger numbers of people CRINETICS PHARMACEUTICALS | 33
Slide 34: Multiple INDs Driving Next Wave of Innovation
Multiple INDs Driving Next Wave of Innovation Indication Neuroendocrine Hyperparathyroidism Graves / TED ADPKD Tumors (NETs) Target SST2+ NDC PTH antagonist TSH antagonist SST3 agonist (CRN09682) 200K incident 3M+ patients Approximate 140K patients with 300K+ patients with Graves, US Patient SST2+ N
Slide 35: CRN09682 Designed to Selectively Target SST2-Expressing Tumor Cells
CRN09682 is Designed to Selectively Target and Deliver Cytotoxic Payload to SST2-Expressing Tumor Cells Differentiation vs. Current Modalities • Non-cytotoxic when linked Anticancer Agents MMAE • Highly potent when free (Chemotherapies, PROTAC) • Interchangeable payload for future development X Not
Slide 36: IND Accepted for CRN09682, Progressing Toward Phase 1/2
IND Accepted for CRN09682, Progressing Toward Phase 1/2 Initiation in NETs and SST2-Expressing Solid Tumors CRN09682 Selectively Delivers MMAE to Tumors With CRN09682 Induces Rapid Regression of SST2+ Small Cell Minimal Systemic Exposure to Free MMAE in Mice Lung Tumors in Nude Mice with High Tumor
Slide 37: Exploring New Frontiers With Our Science to Expand Patient Reach
Exploring New Frontiers With Our Science to Expand Patient Reach > 1M > 100K Preclinical > 10K IND Enabling Obesity Clinical-Stage Approximate US Patients Graves’ Disease Other GPCR- driven Oncology Thyroid Ophthalmopathy Acromegaly Hyperparathyroidism Polycystic Kidney Disease Cushing’s Disease Car
Slide 38: Crinetics: Building a Premier Endocrine-Focused Global Biopharmaceutical Company
Crinetics: Building a Premier Endocrine-Focused Global Biopharmaceutical Company Plans for 2025: ADVANCE Pipeline for 2026+: EXPAND Launch Paltusotine Grow Commercial Engine • PDUFA date September 25, 2025 • Launch of paltusotine in 2nd indication • EU regulatory filing 1H2025 • Launch of atumelnant
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