Crinetics Pharmaceuticals, Inc. · NASDAQ:CRNX
Crinetics Pharmaceuticals — Investor Presentation (January 2021)
38 slides from Crinetics Pharmaceuticals's investor presentation, January 2021
Slide 1: Corporate Presentation
CORPORATE PRESENTATION January 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: 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 6: Clinical Proof-of-Concept in Phase 1 is Our Goal
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] S
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: NETs Treatment Considerations and Opportunities to Improve Current 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 10: ~$3B Market Despite Limitations of Current Therapies
~$3B Market Despite Limitations of Current Therapies Sandostatin Somatuline Somavert MYCAPSSA (octreotide) (lanreotide) (pegvisomant) (oral octreotide) $1.6B $1.2B $264M Monthly intramuscular Monthly deep subcutaneous Daily injections 1 ml; 28 – 31- Twice daily oral capsule 5-mL vial; 1½” 19-gauge n
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 and Be Easy to Prescribe
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: 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 16: Improved Performance of New Tablet Formulation Observed 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 17: Recent and Anticipated Paltusotine Milestones
Recent and Anticipated Paltusotine Milestones 1 New tablet formulation (ready for phase 3) ✓ End of Phase 2 meeting with the FDA 2 (anticipated in 1Q 2021) Initiation of Phase 3 acromegaly program 3 (planned for 1H 2021) Initiation of NETs trial in carcinoid syndrome 4 (planned for 2021) CRINETICS P
Slide 18: 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 | 18
Slide 19: 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 20: 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 21: 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 22: 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 CRN04894 (3 mg/kg) CRN04894 (10 mg/kg) CRN04894 (30 mg/kg) ACTH ACTH + ACTH + ACTH + only CRN0
Slide 23: CRN04894 Phase 1 Study Designed to Evaluate Clinical Proof-of-Concept
1 CRN04894 Phase 1 Study Designed to Evaluate Clinical Proof-of-Concept SAD (N=8/cohort) U.S. IND open • Starting dose 10 mg • Design: Administer ACTH with and without CRN04894 ACTH Challenge Test • Key Endpoint: ACTH stimulated peak Baseline (day -1) Treated (SAD day 1; MAD day 10) cortisol day 1 v
Slide 24: 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 1H 2021) Report Phase 1 MAD data 4 (expected 2H 2021) CRINETICS PHARMACEUTICALS | 24
Slide 25: 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 | 25
Slide 26: 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 Liver CHI patients Blood • Genetic defect results in excess insulin secrete excess Glucose secretion when blo
Slide 27: 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 28: 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 29: 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 30: 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 31: CRN04777 Phase 1 Study Designed to Evaluate Clinical Proof-of-Concept
CRN04777 Phase 1 Study Designed to Evaluate Clinical Proof-of-Concept IV Glucose Tolerance Test (IVGTT) Proof-of-Concept: Dose dependent suppression of glucose-stimulated SAD (3 parts) insulin secretion with CRN04777 vs baseline SAD 1a (n=8/cohort, up to 6 cohorts) • IVGTT: Measure plasma glucose, i
Slide 32: 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 33: 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 1H21 Paltusotine Phase 3 enrollment complete for ✓ acromegaly Improved paltusotine CRN04777 SAD POC data in ta
Slide 34: Appendices
APPENDICES CRINETICS PHARMACEUTICALS | 34
Slide 35: 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. U.S. 10,604,507 Pending in: EA, EP, AU, BR, CA, CN, Composition of Matter July 2016 July 2037 U.S. 10,766,877 IL,
Slide 36: 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 37: 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 38: 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
Crinetics Pharmaceuticals — Investor Presentation (January 2021) on 6ix