Crinetics Pharmaceuticals, Inc. · NASDAQ:CRNX
Crinetics Pharmaceuticals — Investor Presentation (June 2021)
43 slides from Crinetics Pharmaceuticals's investor presentation, June 2021
Slide 1: Corporate Presentation
CORPORATE PRESENTATION June 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 Development Strategy: Focus on Hormone Levels
Endocrinology Development Strategy: Focus on Hormone Levels from Preclinical to Approval Phase 2/3 Safety, Preclinical POC Disease Efficacy ∆Hormones, ∆Hormones, PROs, PK, Safety PK, Safety Phase 1 Healthy Phase 2/3 Trials Volunteers (Patients) Phase 1 Healthy Volunteer Safety, POC ∆Hormones, PK, Sa
Slide 6: Pipeline Targets Indications with Unmet Need
Pipeline Targets Indications with Unmet Need Well established biology 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 agonis
Slide 7: Endocrinology Invented Biomarkers: Clinical Proof-of-Concept in Phase 1
Endocrinology Invented Biomarkers! Clinical Proof-of-Concept in Phase 1 is Our Goal Acromegaly Predose + 10 mg paltusotine (day 1) Plasma Plasma [paltusotine] ng/mL (day -1) [paltusotine] Suppression of GH Phase 1 SAD Data: Stimulate GH with Stimulate GH with GHRH (50 µg) GHRH (50 µg) Serum [GH] Ser
Slide 8: Paltusotine: 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 | 8
Slide 9: Acromegaly and NETs 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 10: NETs Treatment Considerations and Opportunities to Improve Standard of Care
NETs Treatment Considerations and Opportunities to Improve Current Standard of Care First line intervention Common additional interventions NET prevalence Symptom control Anti-tumor activity in US Tumor removal (Carcinoid Syndrome) (Nonfunctional + CS) 171K 62% eligibility PRRT: SST2 targeted 19% oc
Slide 11: ~$3B Market Despite Limitations of Current Therapies
~$3B Market Despite Limitations of Current Therapies Sandostatin Somatuline Somavert MYCAPSSA (octreotide) (lanreotide) (pegvisomant) (oral octreotide) $1.4B $1.4B $277M $1M Monthly intramuscular Monthly deep subcutaneous Daily injections 1 ml; 28 – 31- Twice daily oral capsule 5-mL vial; 1½” 19-gau
Slide 12: Paltusotine Showed High Intrinsic Oral Bioavailability
Paltusotine Showed High Intrinsic Oral Bioavailability Peptide: Octreotide Nonpeptide: paltusotine Survive proteolysis Diffuse through lipid bilayer Paltusotine Aided by gut (CRN00808) permeabilizing Intrinsically agents permeable Oral Bioavailability 70% Observed Half Life 42-50 hr. Intestinal epit
Slide 13: Paltusotine Designed to Avoid Drug-Drug Interactions
Paltusotine was Designed to Avoid Drug-Drug Interactions and Be Easy to Prescribe Mass-balance (14C) study in healthy volunteers 250 Paltusotine has not shown clinically Paltuostine meaningful inhibition or induction of drug Total radioactivity metabolizing enzymes Plasma concentration 200 TRA (ng/m
Slide 14: Phase 2 ACROBAT Edge Study Met Primary Endpoint
Phase 2 ACROBAT Edge Study Met Primary Endpoint Hormone suppression maintained after switching from injected SOC to oral paltusotine 3.0 3.0 p<0.0001 IGF-1 p<0.0001 GH 2.5 2.5 p>0.6 p=0.6285 2.0 2.0 GH (ng/mL) IGF-1 (× ULN) p>0.6 p=0.6285 1.5 1.5 1.0 1.0 0.5 0.5 0.0 0.0 Baseline Paltusotine 4 Wks Ba
Slide 15: Evidence of Dose Response from Phase 2 Program
Evidence of Dose Response from Phase 2 Program Results from Switching to Paltusotine: Change in IGF-1 Magnitude of Paltusotine Activity: Change in IGF-1 from from Baseline to Steady State at Indicated Dose Steady State to 4 Weeks After Withdrawal Post-hoc analysis of data from EDGE primary analysis
Slide 16: Paltusotine New Tablet Formulation Incorporates Multiple Improvements
Paltusotine New Tablet Formulation Incorporates Multiple Improvements New tablet formulation to be used in Phase 3 (and commercially, if approved) Expected ambient shipping and storage Acid lowering agents include proton pump inhibitors, H2 blockers, antacids Data to be presented at ENDO (March 20-2
Slide 17: Improved Performance of New Tablet Formulation in Healthy Volunteers
Improved Performance of New Tablet Formulation Observed in Healthy Volunteers Post dose fast of 0.5 – 1 hr was sufficient Dose proportional exposure observed Observed minimal effect of acid up to 80mg lowering agents 1500 4000 1500 AUC0-24 ng*hr/mL AUC0-24 (ng*hr/mL) AUC0-24 ng*hr/mL 3000 1000 1000
Slide 18: Phase 3 Program: Potential for Broad First-Line Medical Therapy
Phase 3 Program: Designed to Support Potential for Broad First-Line Medical Therapy Two double-blind, placebo-controlled studies planned to support broad labeling in the U.S. and Europe for use in all acromegaly patients who require pharmacotherapy PATHFNDR-1: Switching from SOC Evaluate safety and
Slide 19: PATHFNDR-1: Enabling Switching from SOC
PATHFNDR-1: Enabling Switching from SOC Placebo (n = 26) Endpoints Key Eligibility Criteria R Total Treatment Period: 9 months Patients controlled on Paltusotine (n= 26) Primary: octreotide or lanreotide • Percent responders vs. placebo depot monotherapy • Start on 40 mg QD or placebo • IGF-1 assess
Slide 20: PATHFNDR-2: Enabling Use in Untreated Patients
PATHFNDR-2: Enabling Use in Untreated Patients Placebo (n = 37) Endpoints Key Eligibility Criteria R Total Treatment Period: 12 weeks Medication naïve Paltusotine (n= 37) Primary: (or untreated ≥4 mo.) • Percent responders vs. placebo • Starting dose: 20 mg QD or placebo OR • Weeks 1-2: Initial forc
Slide 21: Anticipated Paltusotine Milestones
Anticipated Paltusotine Milestones 1 Initiate PATHFNDR-1: switching from SOC ✓ Initiate PATHFNDR-2: use in untreated patients 2 (anticipated in 2H 2021) Initiation of Phase 2 NETs trial in carcinoid syndrome 3 (end of 2021) Report topline data from PATHFNDR-1 & 2 trials 4 (expected in 2023) CRINETIC
Slide 22: CRN04894: 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 | 22
Slide 23: 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 Adrenocorticotrophic Gland hormone (ACTH) is secreted by pituitary and acts at MC2 receptor on adrenal Stress cholesterol Hypothalamus MC2/MRAP CRF Cortisol Adrenal Cortical Cell Pituitary 21-hyd
Slide 24: CRN04894, an ACTH Antagonist Designed to Treat Cushing's Disease at the Source
CRN04894, an ACTH Antagonist Designed to Treat Cushing’s Disease at the Source Cushing’s Disease Excess ACTH in Cushing’s Disease patients results in: 1. Central obesity and round face 2. Dorsal and supraclavicular fat pads Hypothalamus 3. Hypertension; Stretch marks; Bone loss; Hyperglycemia CRF
Slide 25: 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 26: CRN04894 Designed to Provide Predictable Steroid Administration for CAH Patients
CRN04894, an ACTH Antagonist Designed to Provide Predictable Steroid Administration for CAH Patients Congenital Adrenal Hyperplasia 6.7-10/ Hypothalamus 27,000 100,000 Total Prevalence CRF U.S. of Classic CAH Globally Pituitary AVP Cause: Inability to produce No approved 0 cortisol due to genetic de
Slide 27: CRN04894 Showed Activity in Preclinical Models
CRN04894 Showed Activity in Preclinical Models Acute suppression of ACTH-induced Repeat CRN04894 dosing (7d) prevented adrenal corticosterone observed in rats hypertrophy from chronic ACTH infusion Vehicle 0.8 Adrenal gland weight (g) CRN04894 (1 mg/kg) CRN04894 (3 mg/kg) 0.6 CRN04894 (10 mg/kg) 0.4
Slide 28: CRN04894 Phase 1 Clinical POC: Adrenal Suppression
CRN04894 Phase 1 Clinical POC Cushing’s Disease and CAH – Adrenal Suppression Healthy volunteers: SAD data expected mid-2021; MAD data expected 2H 2021 Objectives ACTH Stimulation Test Baseline (day -1) Treated (SAD day 1; MAD day 10) • Safety and tolerability ACTH ‘4894 (po) ACTH • Pharmacokinetics
Slide 29: Recent and Anticipated CRN04894 Milestones
Recent and Anticipated CRN04894 Milestones 1 Open US IND ✓ ✓ (complete) 2 Initiate Phase 1 FIH healthy volunteer POC study Report Phase 1 SAD data 3 (expected mid-2021) Report Phase 1 MAD data 4 (expected 2H 2021) CRINETICS PHARMACEUTICALS | 29
Slide 30: CRN04777: 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 | 30
Slide 31: Inappropriate Insulin Secretion Causes 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 Liver CHI patients Blood • Genetic defect results in excess insulin secrete excess Glucose secretion when blo
Slide 32: 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 33: CHI Patient Care is a High Burden on Healthcare Systems
CHI Patient Care is a High Burden on Healthcare Systems Current Challenges Healthcare utilization by a baby girl with CHI • Variable time to diagnosis • Constant dextrose infusion to maintain normal blood sugar levels Born 2014, Original CHI diagnosis 12/2014, First Diazoxide Tx 3/161 • Surgical rem
Slide 34: SST5 Agonists Should Be Universally Effective Against 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 35: Proof of Mechanism Achieved in Animal Models and Patient Islets
Proof of Mechanism Achieved in Animal Models and Patient Islets CRN04777 rescued sulfonylurea-induced CRNX SST5 agonist suppressed insulin from islets isolated hypoglycemia in rats from patient with Beckwith-Wiedemann Syndrome Administer Administer sulfonylurea vehicle or (glyburide) CRN04777 CRNX S
Slide 36: CRN04777 Phase 1 Clinical POC: Insulin Suppression
CRN04777 Phase 1 Clinical POC Congenital Hyperinsulinism – Insulin Suppression Healthy volunteers: SAD data expected mid-2021; MAD data expected 2H 2021 Objectives 1. IV Glucose Tolerance Test (IVGTT) Baseline (day -1) Treated (SAD day 1) • Safety and tolerability IV glucose ‘4777 (po) IV glucose •
Slide 37: Recent and Anticipated CRN04777 Milestones
✓ Recent and Anticipated CRN04777 Milestones US Rare Pediatric Disease and EU Orphan Drug Designations 1 ✓ (received; CRNX may be eligible for priority review voucher in the US) 2 Initiate Phase 1 FIH healthy volunteer POC study Report Phase 1 SAD data 3 (expected mid-2021) Report Phase 1 MAD data 4
Slide 38: 2021 Goal: Three Programs with Clinical POC
2021 Goal: Three Programs with Clinical POC Poised for steady cadence of milestones in 2021 Q1 Q2 Q3 Q4 Initiate PATHFNDR-1 Initiate PATHFNDR-2 Paltusotine SST2 Agonist for Acromegaly & NETs Initiate Phase 2 NETs Trial in Carcinoid Syndrome Initiate Phase 1 Phase 1 SAD Data CRN04894 ACTH Antagonist
Slide 39: Appendices
APPENDICES CRINETICS PHARMACEUTICALS | 39
Slide 40: 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 41: 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 42: 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 43: 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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