Crinetics Pharmaceuticals, Inc. · NASDAQ:CRNX
Crinetics Pharmaceuticals — 10th Annual SVB Leerink Global Healthcare Conference 2021
35 slides from Crinetics Pharmaceuticals's conference presentation, Feb 24, 2021
Slide 1: Corporate Presentation
CORPORATE PRESENTATION Leerink Global Healthcare Conference, February 24, 2021
Slide 2: Safe Harbor Statement
SAFE HARBOR STATEMENT This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation are forward-looking statements, including statements regarding: the potential benefits of paltusotine for acromegaly patients and patie
Slide 3: Mission
Mission: To build the leading endocrine company that consistently pioneers new therapeutics to help patients better control their disease and improve their daily lives CRINETICS PHARMACEUTICALS | 3
Slide 4: Strategy: Drugs Built from Scratch for Purpose
Strategy: Drugs Built from Scratch for Purpose We aim to discover, develop and commercialize drugs for endocrine indications with: High Unmet Medical Needs Well established biology Biomarkers as registrational endpoints 1 Clinical proof of concept achieved (POC) in Phase 1 studies Small registration
Slide 5: Endocrinology: Early Derisking and Value Creation
Endocrinology: Early Derisking and Value Creation Phase 2 Disease Efficacy Preclinical POC ∆Hormones, ∆Hormones, PROs, PK, PK, Safety Safety Phase 1 Healthy Phase 2 Trials Phase 3 Trials Volunteers (Patients) (Patients) Phase 1 Phase 3 Healthy Registration Volunteer POC Data ∆Hormones, ∆Hormones, PK
Slide 6: Pipeline Targets Indications with Unmet Need
Pipeline Targets Indications with Unmet Need Well established endocrinology has the potential to allow for the use of biomarkers as registration endpoints Development Stage Prevalence Registrational PROGRAM Preclin Phase 1 Phase 2 Phase 3 Endpoint Global Range US Total per 100,000 Paltusotine (SST2
Slide 7: Paltusotine: An Investigational, Potential First-in-Class, Oral Nonpeptide SST2 Agonist
PALTUSOTINE: AN INVESTIGATIONAL, POTENTIAL FIRST-IN-CLASS, ORAL NONPEPTIDE SST2 AGONIST Acromegaly Carcinoid syndrome Nonfunctional neuroendocrine tumors CRINETICS PHARMACEUTICALS | 7
Slide 8: Acromegaly and NETs are Currently Treated with Injected SST2 Peptide Agonists
Acromegaly and NETS are Currently Treated with Injected SST2 Peptide Agonists Acromegaly Neuroendocrine Tumors (NETs) • Caused by benign pituitary • NETs arise from aberrant Liver enteroendocrine cells in GI, tumor that secretes excess growth hormone (GH) SST2 Stomach pancreas or lungs • Excess GH c
Slide 9: Paltusotine: In Vivo Proof-of-Concept in Healthy Rats
Paltusotine: In Vivo Proof-of-Concept in Healthy Rats Healthy Rat Suppression of GHRH stimulated GH secretion in male and GHRH female rats with oral paltusotine Paltusotine GH Liver IGF-1 GHRH: Growth Hormone-Releasing Hormone CRINETICS PHARMACEUTICALS | 9
Slide 10: Paltusotine: Phase 1 Proof-of-Concept in Healthy Volunteers
Paltusotine: Phase 1 Proof-of-Concept in Healthy Volunteers Healthy Volunteer Suppression of GHRH stimulated GH secretion in healthy GHRH volunteers with oral paltusotine Predose + 10 mg paltusotine Plasma (day 1) Plasma [paltusotine] ng/mL (day -1) [paltusotine] Paltusotine Stimulate GH with GHRH (
Slide 11: Paltusotine: GH and IGF-1 Suppression in Acromegaly Patients
Paltusotine: GH and IGF-1 Suppression in Acromegaly Patients Acromegaly Patients GH and IGF-1 suppression maintained after switching from injected SOC to oral paltusotine 3.0 p<0.0001 GH 3.0 Pituitary tumor IGF-1 p<0.0001 secretes 2.5 2.5 excess GH p>0.6 p=0.6285 2.0 2.0 GH (ng/mL) IGF-1 (× ULN) p>0
Slide 12: CRN04894: An Investigational, Potential First-in-Class, Oral Nonpeptide ACTH Antagonist
CRN04894: AN INVESTIGATIONAL, POTENTIAL FIRST-IN-CLASS, ORAL NONPEPTIDE ACTH ANTAGONIST Congenital adrenal hyperplasia (CAH) Cushing’s disease (CD) Other conditions of ACTH excess CRINETICS PHARMACEUTICALS | 12
Slide 13: The HPA Axis is the Body's Emergency Response System for Stress
The Hypothalamic-Pituitary-Adrenal (HPA) Axis is the Body’s Emergency Response System for Stress Adrenal Gland Adrenocorticotrophic hormone (ACTH) Stress cholesterol Hypothalamus MC2/MRAP CRF Cortisol Adrenal Cortical Cell Pituitary 21-hydroxylase X Adrenal Androgens AVP cortisol (17-OHP, A4) mutate
Slide 14: CRN04894, an ACTH Antagonist Designed to Block Excess ACTH Action in CAH Patients
CRN04894, an ACTH Antagonist Designed to Block Excess ACTH Action in CAH Patients CAH Patients Loss of cortisol in CAH patients results in: 1. Adrenal insufficiency, loss of negative feedback to pituitary 2. Excess ACTH resulting in excess adrenal androgens 3. Precocious puberty, short stature, infe
Slide 15: CRN04894, an ACTH Antagonist Designed to Block Excess ACTH Action in Cushing's Disease
CRN04894, an ACTH Antagonist Designed to Block Excess ACTH Action in Cushing’s Disease Cushing’s Disease Patients Excess cortisol in Cushing’s Disease patients results in: 1. Central obesity and round face 2.Dorsal and supraclavicular fat pads 3.Hypertension; Stretch marks; Bone loss; Hyperglycemi
Slide 16: Pituitary Corticotroph Tumors Cause Cushing's Disease
Pituitary Corticotroph Tumors Cause Cushing’s Disease, an ACTH Dependent Cushing’s Syndrome Cushing’s Disease Patients Time course of plasma cortisol levels over a diurnal cycle Plasma Cortisol, mcg/dL Pituitary tumor 30 secretes excess ACTH Cushing’s Disease Patients1 20 CRN04894 Excess ACTH 10 Adr
Slide 17: CRN04894: In Vivo Proof-of-Concept in Healthy Rats with Induced Hypercortisolism
CRN04894: In Vivo Proof-of-Concept in Healthy Rats with Induced Hypercortisolism CRN04894 suppression of ACTH-induced Healthy Rat corticosterone secretion in rats Vehicle CRN04894 (1 mg/kg) CRN04894 (3 mg/kg) CRN04894 (10 mg/kg) ACTH CRN04894 ACTH Adrenal Experiment designed to mimic disease: • CRN0
Slide 18: CRN04894: Phase 1 Proof-of-Concept in Healthy Volunteers with Induced Hypercortisolism
CRN04894: Phase 1 Proof-of-Concept in Healthy Volunteers with Induced Hypercortisolism Healthy Volunteers Evaluation of CRN04894 suppression of ACTH-induced cortisol secretion in healthy volunteers ACTH Stimulation Test Baseline (day -1) Treated (SAD day 1; MAD day 10) ACTH ‘4894 (po) ACTH ACTH day
Slide 19: CRN04894: Ongoing Phase 1 Proof-of-Concept in Healthy Volunteers
CRN04894: Ongoing Phase 1 Proof-of-Concept in Healthy Volunteers Single Ascending Dose (SAD) Cohorts S1 S6 S7 S8 S2 S3 S4 S5 (10 mg) (optional) (optional) (optional) SAD Cohorts Key Endpoint • ACTH stimulated peak cortisol Day 1 vs. baseline (± CRN04894) MAD Cohorts Additional Efficacy Endpoints Key
Slide 20: CRN04777: An Investigational, Potential First-in-Class, Oral Nonpeptide SST5 Agonist
CRN04777: AN INVESTIGATIONAL, POTENTIAL FIRST-IN-CLASS, ORAL NONPEPTIDE SST5 AGONIST Congenital hyperinsulinism (CHI) CRINETICS PHARMACEUTICALS | 20
Slide 21: Inappropriate Insulin Secretion Causes Life Threatening Recurrent Hypoglycemia in CHI
Inappropriate Insulin Secretion Causes Life Threatening Recurrent Hypoglycemia in CHI Normal Glucose Control Congenital Hyperinsulinism 0.64-1.3/ ~2-4K 100,000 U.S. Total Prevalence Globally Blood • Genetic defect results in excess insulin Liver Glucose secretion when blood glucose is low Glucagon C
Slide 22: Excruciating Unmet Medical Needs in CHI
Excruciating Unmet Medical Needs in CHI Intensive 24h-glucose management (monitoring, feeding, glucose tube) Current Standard of Care for CHI Patient & Parent Goals Put child to bed knowing they will wake up in the morning Focal Diffuse Avoid neurological damage Eliminate the glucose tube and
Slide 23: CHI Patient Care is a High Burden on Healthcare Systems
CHI Patient Care is a High Burden on Healthcare Systems Current Challenges • Variable time to diagnosis Healthcare utilization by a baby girl with CHI • Constant dextrose infusion to maintain normal blood sugar levels Born 2014, Original CHI diagnosis 12/2014, First Diazoxide Tx 3/161 • Surgical rem
Slide 24: SST5 Agonists Should Be Universally Effective Against Various Forms of Congenital HI
SST5 Agonists Should Be Universally Effective Against Various Forms of Congenital HI Healthy pancreatic β-cells Congenital HI pancreatic β-cells Common mutations that X cause congenital HI CRN04777 Depolarization Depolarization KATP channel Ca2+ channel SST5 receptor KATP channel Ca2+ channel activa
Slide 25: CRN04777: Ex-Vivo Proof-of-Concept with Pancreatic Islets from CHI Donor
CRN04777: Ex-Vivo Proof-of-Concept with Pancreatic Islets from CHI Donor Congenital HI pancreas CRNX SST5 agonist suppressed insulin from islets isolated from patient with Beckwith-Wiedemann Syndrome Pancreatectomy Islet isolation Glucose KCl Insulin CRNX SST5 agonist Islet data was obtained using a
Slide 26: CRN04777: In Vivo Proof-of-Concept in Healthy Rats with Induced Hyperinsulinism
CRN04777: In Vivo Proof-of-Concept in Healthy Rats with Induced Hyperinsulinism Healthy Rat CRN04777 suppression of sulfonylurea-induced insulin secretion and hypoglycemia in rats Stimulate insulin secretion with Administer Administer sulfonylurea sulfonylurea (glyburide) vehicle or CRN04777 Blood L
Slide 27: CRN04777: Phase 1 Proof-of-Concept in Healthy Volunteers with Induced Hyperinsulinism
CRN04777: Phase 1 Proof-of-Concept in Healthy Volunteers with Induced Hyperinsulinism Healthy Volunteer Evaluation of CRN04777 suppression of glucose and sulphonylurea induced insulin secretion in healthy volunteers Stimulate insulin secretion with 1. IV Glucose Tolerance Test (IVGTT) sulfonylurea B
Slide 28: CRN04777: Ongoing Phase 1 Proof-of-Concept in Healthy Volunteers
CRN04777: Ongoing Phase 1 Proof-of-Concept in Healthy Volunteers Single Ascending Dose (SAD) Cohorts Sa1 (0.5 mg) Sa2 Sa3 Sa4 Sa5 Sa6 IV Glucose Tolerance Test (IVGTT) SAD (3 parts) Sb1 Sb2 Sulfonylurea SAD A (n=8/cohort, up to 6 cohorts) challenge • IVGTT: Measure plasma glucose, insulin, C-peptide
Slide 29: 2020 Accomplishments and Anticipated 2021-2022 Milestones
2020 Accomplishments and Anticipated 2021-2022 Milestones 2020 Accomplishments 2021 Anticipated Milestones 2022 Goals ✓ Positive paltusotine acromegaly Phase 2 data CRN04894 SAD POC data in 1H2021 Paltusotine Phase 3 enrollment complete for ✓ acromegaly Improved paltusotine CRN04777 SAD POC data in
Slide 30: CRINETICS PHARMACEUTICALS | 30
CRINETICS PHARMACEUTICALS | 30
Slide 31: Appendices
APPENDICES CRINETICS PHARMACEUTICALS | 31
Slide 32: Key Patent Families Anchor a Robust IP Portfolio
Key Patent Families Anchor a Robust IP Portfolio Paltusotine Portfolio Patent Family Subject Patent Nos. Status Priority Date Estimated Expiration Matter U.S. 10,562,884 Granted in: U.S. AU U.S. 10,604,507 Pending in: EA, EP, BR, CA, CN, IL, IN, Composition of Matter July 2016 July 2037 U.S. 10,766,
Slide 33: Leadership Team
Leadership Team Scott Struthers, PhD President & CEO, Founder Frank Zhu, PhD VP of Chemistry, Founder Steve Betz, PhD VP of Biology, Founder Ajay Madan, PhD Chief Development Officer Marc Wilson Chief Financial Officer Alan Krasner Chief Medical Officer VP, Corporate Strategy Gina Ford & Commercial
Slide 34: Board of Directors
Board of Directors Wendell Wierenga, PhD Chairman (Former EVP R&D, Santarus) Scott Struthers, PhD Founder & CEO Steve Kaldor, PhD Former CEO, Quanticel Matt Fust, MBA Former CFO, Onyx Weston Nichols, PhD Founder & Managing Partner, Lynx1 Capital Stephanie Okey, MS Former SVP, Genzyme Corporation Cam
Slide 35: Scientific Advisory Board
Scientific Advisory Board David Clemmons, MD Professor of Medicine at UNC, Chapel Hill President & CEO, Partners Healthcare Anne Klibanski, MD Former Chief of Neuroendocrine Unit at MGH & Professor of Medicine at Harvard Philip Harris, FRCP, PhD Chief Medical Officer, Isotopen Technologien München C
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