Crinetics Pharmaceuticals, Inc. · NASDAQ:CRNX
Crinetics Pharmaceuticals — Investor Presentation (August 2021)
44 slides from Crinetics Pharmaceuticals's investor presentation, August 2021
Slide 1: Corporate Presentation August 2021
CORPORATE PRESENTATION August 2021
Slide 2: Safe Harbor Statement
SAFE HARBOR STATEMENT This presentation contains forward-looking statements. Crinetics cautions you that statements contained in this presentation regarding matters that are not historical facts are forward-looking statements. These statements are based on the company’s current beliefs and expectati
Slide 3: Mission: To build the leading endocrine company
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! Pharmacologic POC in Phase 1
Endocrinology Invented Biomarkers! Pharmacologic POC 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] Serum [GH]
Slide 8: Paltusotine: Investigational 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 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: ~$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 11: 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 12: 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 13: 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 14: 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 15: Phase 3 Program: Potential for Broad First-Line 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 16: 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 17: 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 18: 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 19: CRN04894: Investigational 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 | 20
Slide 20: The HPA Axis is the Body's Emergency Response System
The Hypothalamic-Pituitary-Adrenal (HPA) Axis is the Body’s Emergency Response System for Stress Adrenal Gland ACTH Stress cholesterol Hypothalamus MC2/MRAP CRF Cortisol Adrenal Cortical Cell Pituitary 21-hydroxylase Adrenal Androgens AVP cortisol (17-OHP, A4) peripheral target tissues (Glucocortico
Slide 21: Hypothesis: Oral Selective ACTH Antagonist for ACTH Excess Diseases
Hypothesis: An Oral, Selective ACTH Antagonist Will Have Utility in Treating Diseases of ACTH Excess Normal Cushing’s Disease (CD) Hypothalamus Congenital Adrenal Hyperplasia (CAH) Hypothalamus Hypothalamus CRF CRF stress CRF Pituitary Pituitary Pituitary negative feedback AVP X AVP Loss of adenoma
Slide 22: CRN04894: First-in-Class ACTH Antagonist
CRN04894: First-in-Class ACTH Antagonist for ACTH Driven Diseases Pituitary Gland Adrenal Gland Target Cells ACTH Cortisol Pituitary Directed ACTH Adrenal GC Agents to Suppress Receptor Steroidogenesis Receptor ACTH Secretion Antagonist Inhibitors Antagonist • Limited efficacy • Limited Efficacy • E
Slide 23: No ACTH Receptor Blocking Agents Available
There Are No ACTH Receptor Blocking Agents Available to Treat ACTH Driven Diseases All currently approved agents and agents in development act upstream or downstream of ACTH ACTH Cortisol Pituitary Gland Adrenal Gland Target Cells Pituitary Directed Agents to Adrenal Steroidogenesis Inhibitors Gluco
Slide 24: CRN04894 is the Only ACTH Antagonist in Clinical Development
CRN04894 is the Only ACTH Antagonist in Clinical Development CRN04894 was carefully crafted by Crinetics in-house discovery team CRN04894 is a potent (Kb= 0.4 nM) competitive Acute suppression of ACTH-induced antagonist of ACTH signaling corticosterone observed in rats Vehicle CRN04894 (1 mg/kg) CRN
Slide 25: CRN04894 SAD Study Design for Proof-of-Concept
CRN04894 SAD Study Design to Establish Pharmacologic Proof-of-Concept Follows Crinetics’ core endocrine strategy of using hormonal biomarkers to drive development Study Goals ACTH Challenge Test • Evaluate safety [ 10-80 mg] Baseline (Day -1) Treated (Day 1) • Evaluate pharmacokinetics: oral absorpt
Slide 26: PK Results: Oral Bioavailability With Dose-Proportional Exposure
PK Results: CRN04894 Showed Oral Bioavailability With Dose-Proportional Exposure Half-life ~24 hour and tmax ~1 hour 80 mg (N=12) 40 mg (N=6) 20 mg (N=6) 10 mg (N=6) Data shown are mean±SEM CRINETICS PHARMACEUTICALS | 32
Slide 27: CRN04894 Rapidly Reduced Basal Cortisol Output
CRN04894 Rapidly Reduced Basal Cortisol Output from Adrenal Glands Acute reduction of basal cortisol (56% @ 80 mg) 2 hours after administration of CRN04894 17% Baseline (Day -1) -25% -35% -37% Full suppression of cortisol -56% production a Pbo 10 mg 20 mg 40 mg 80 mg (N=9) (N=6) (N=6) (N=6) (N=12) C
Slide 28: Dose-Dependent Cortisol Suppression Following ACTH Challenge (250 mcg)
Dose-Dependent Suppression of Cortisol Observed Following Supra-Pathophysiologic ACTH Challenge (250 mcg) CRN04894 resulted in strong cortisol suppression (41% @ 80 mg) despite anticipated ACTH exposure orders of magnitude higher than disease states ACTH Challenge (250 mcg) Placebo (N=7) 0% 80 mg CR
Slide 29: Cortisol Suppression in Disease-relevant ACTH Challenge (1 mcg)
Clinically Meaningful Cortisol Suppression Observed in Response to Disease-relevant ACTH Challenge (1 mcg) CRN04894 maintains normal cortisol levels for these subjects in face of disease-relevant ACTH (1 mcg) challenge CRN04894 ACTH Challenge 80 mg (1 mcg) Elevated 20 Cortisol [Cortisol] (mcg/dL) 15
Slide 30: Conclusions from CRN04894 SAD Results
Conclusions from CRN04894 SAD Results Objectives Generally safe and well tolerated at single doses from 10 to 80 mg • Safety and tolerability Achieved targeted pharmacokinetic profile • Drug-like • Rapidly absorbed after oral administration (tmax ~1 hr) Pharmacokinetics • Dose proportional exposure
Slide 31: Recent and Anticipated CRN04894 Milestones
Recent and Anticipated CRN04894 Milestones 1 Open US IND ✓ ✓ (complete) 2 Initiate Phase 1 FIH healthy volunteer POC study 3 Report Phase 1 SAD data ✓ Report Phase 1 MAD data 4 (expected 2H 2021) CRINETICS PHARMACEUTICALS | 37
Slide 32: CRN04777: Investigational Oral Nonpeptide SST5 Agonist
CRN04777: AN INVESTIGATIONAL, POTENTIAL FIRST-IN-CLASS, ORAL NONPEPTIDE SST5 AGONIST Congenital hyperinsulinism (CHI) CRINETICS PHARMACEUTICALS | 38
Slide 33: Inappropriate Insulin Secretion Causes 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 34: 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 35: 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 36: 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 37: Proof of Mechanism 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 38: 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 39: 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 September 2021) Report Phase 1 MAD
Slide 40: On Track to Achieve 2021 Goal of Three Programs with Proof-of-Concept
On Track to Achieve 2021 Goal of Three Programs with Proof-of-Concept Demonstrated in the Clinic Q1 Q2 Q3 Q4 Initiate Paltusotine Initiate PATHFNDR-2 PATHFNDR-1 SST2 Agonist for Acromegaly & NETs POC Achieved Initiate Phase 2 NETs Trial in Carcinoid Syndrome Initiate Phase 1 CRN04894 Phase 1 SAD Dat
Slide 41: Appendices
APPENDICES CRINETICS PHARMACEUTICALS | 47
Slide 42: 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 43: Board of Directors
Board of Directors Wendell Wierenga, PhD Chairman (Former EVP R&D, Santarus) Scott Struthers, PhD Founder & CEO Matt Fust, MBA Former CFO, Onyx Weston Nichols, PhD Founder & Managing Partner, Lynx1 Capital Stephanie Okey, MS Former SVP, Genzyme Corporation Camille Bedrosian, MD Chief Medical Officer
Slide 44: 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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