Crinetics Pharmaceuticals, Inc. · NASDAQ:CRNX
Crinetics Pharmaceuticals — Investor Presentation (January 2023)
36 slides from Crinetics Pharmaceuticals's investor presentation, Jan 9, 2023
Slide 1: Developing GPCR-targeted oral small molecules for endocrine disorders and endocrine-related tumors
Developing GPCR-targeted oral small molecules for endocrine disorders and endocrine-related tumors Corporate presentation January 2023 Exhibit 99.1
Slide 2: Safe Harbor Statement
SAFE HARBOR STATEMENT This presentation contains forward-looking statements. Crinetics Pharmaceuticals, Inc. (“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 com
Slide 3: Building the World's Premier Fully-Integrated Endocrine Company
Building the World’s Premier Fully-Integrated Endocrine Company Leading GPCR drug discovery platform Global endocrinology clinical trial capabilities Two Phase 3 readouts expected in 2023 Pipeline: 3 product candidates with clinical POC Clinical POC in highly prevalent indications Global approvals f
Slide 4: Crinetics' Endocrine GPCR Discovery and Development Engine
Identify endocrine indications with unmet needs and well-understood targets Craft high quality, orally bioavailable, small molecule drug candidates Select best candidates with predictive endocrine biomarkers in preclinical models De-risk in healthy volunteers and then prove in patients with accepted
Slide 5: Crinetics' Discovery Laboratory Has Reproducibly Crafted Drug Candidates That Work
Crinetics’ Discovery Laboratory Has Reproducibly Crafted Drug Candidates That Work Differentiation, speed and probability of success in drug discovery are determined by the teams operating these tools, the integrated strategies they employ, and the culture that drives them. Focused Team Med Chem In
Slide 6: Endocrine GPCRs: Wide Open Field with Many High Value Opportunities
Approximately one-third of all approved drugs target GPCRs, but the majority of GPCR targets have been inaccessible.1 Many of these historically inaccessible endocrine GPCR targets possess: High-probability biology based on well characterized endocrine systems that are conserved across species, givi
Slide 7: Building a Synergistic Commercial Product Portfolio With Growing Stream of Catalysts
Building a Synergistic Commercial Product Portfolio With Growing Stream of Catalysts Program Discovery Preclin. Phase 1 Phase 2 Phase 3 Anticipated Milestones Paltusotine (SST2 agonist)* CRN04777 (SST5 agonist) CRN04894 (ACTH antagonist) PTH antagonist Undisclosed TSH antagonist Undisclosed (multipl
Slide 8: Extending Discovery Engine to Novel Precision Targeted Radiopharmaceuticals
Technology spun out of CRNX in 2021 $30 million funding from 5AM Ventures and Frazier CRNX retains significant ownership Milestones in excess of $1B and single-digit royalties on net sales from technology license Emerging broad clinical pipeline in oncology Target 1: IND filing in an endocrine cance
Slide 9: Paltusotine: A First-in-Class, Oral Small Molecule Somatostatin Receptor Ligand
Paltusotine: A First-in-Class, Oral Small Molecule Somatostatin Receptor Ligand for Acromegaly and Carcinoid syndrome Building Development and Commercial Capabilities
Slide 10: What is Acromegaly?
What is Acromegaly? Acromegaly is caused by a benign pituitary tumor secreting excess growth hormone (GH) IGF-I GH Liver Somatotroph Adenoma Excess GH secretion by the pituitary gland causes excess IGF-1 secretion by the liver Somatostatin Receptor Ligands (SRLs) inhibit GH secretion Sources: http:/
Slide 11: What are Neuroendocrine Tumors and Carcinoid Syndrome?
What are Neuroendocrine Tumors (NETs) and Carcinoid Syndrome? Diarrhea Flushing Difficulty breathing Tachycardia Carcinoid heart disease (valvulopathy) Carcinoid crisis (life threatening) Stomach Liver Pancreas Intestine NETs arise from neuroendocrine cells in GI tract, pancreas or lungs serotonin +
Slide 12: Somatostatin Receptor Ligands Are a $2.7B Established Market
Sandostatin (octreotide) Somatuline (lanreotide) Sponsor Administration Monthly intramuscular injections 5-mL vial; 1½” 19-gauge needle Monthly deep subcutaneous injections .2-.5ml; 18-gauge needle Global Net Sales (2021) $1,400M1 $1,300M1 U.S. Net Sales (2021) $843M1 $893M2 Approval date(s) 1988, 1
Slide 13: Paltusotine: Initial Multi-Billion Dollar U.S. Market Opportunity
19-30% of NETs patients have Carcinoid Syndrome Paltusotine: Initial Multi-Billion Dollar U.S. Market Opportunity in Acromegaly and Carcinoid Syndrome Current Patients (On Endocrine Therapy*) Diagnosed Prevalence Addressable Patients (Candidates for SRL) Acromegaly (U.S. Patients) 27,000 11,000 10,0
Slide 14: Treatment Challenges and High Burden of Care with Currently Available SRLs
There are Treatment Challenges and a High Burden of Care with Currently Available SRLs Poor symptom control: 33 – 55% of acromegaly patients on injectable SRLs (octreotide/lanreotide) report worsening of symptoms at the end of each injection cycle1,2 Poor disease control: 42% of participants in a pi
Slide 15: Aspiring to bring the only once daily oral SRL to patients
Aspiring to bring the only once daily oral SRL to patients as a trusted member of the global endocrine community Properly Resourcing Commercial Functions Began building commercial team in Q1 2022 Making continued investments to inform a targeted and nimble market access plan Providing Value to Healt
Slide 16: Concentrated Prescriber Bases at Key Stages of the Acromegaly Patient Journey
Diagnosis and Surgery Initiation of Pharmacotherapy Ongoing Assessment of Pharmacotherapy Concentrated Prescriber Bases at Key Stages of the Acromegaly Patient Journey in U.S. 200 endocrinologists in 40 pituitary centers write 80% of initial Rx’s 1,000 local endos write 80% of subsequent Rx’s for 10
Slide 17: Acromegaly Patients on Paltusotine Maintained IGF-1 Levels for Up to Two Years
SOC Injected SRL1 Untreated 2 Phase 2 Paltusotine Open Label Extension (OLE) Median IGF-1 ± IQR (x ULN) Acromegaly Patients on Paltusotine Maintained IGF-1 Levels for Up to Two Years in Open Label Study for Phase 2 Patients Eligible Phase 2 study participants opted to continue into the open label ex
Slide 18: The Paltusotine Development Program: PATHFNDR Phase 3
The Paltusotine Development Program Has Built a Global Development Capability for All Future Programs The Paltusotine Acromegaly Phase 3 Program is Designed to Support Potential, Broad First-Line Medical Therapy Label. Underway at ~100+ sites in Countries Around the World PATHFNDR-1: Switching from
Slide 19: Carcinoid Syndrome: Label Expansion Opportunity for Paltusotine
Carcinoid Syndrome: Label Expansion Opportunity for Paltusotine Key Eligibility Criteria Naïve or treated with octreotide or lanreotide Grade 1 or 2 NET Starting Dose: 40 mg Paltusotine (n=15) Starting Dose: 80 mg Paltusotine (n=15) Randomized Treatment Period: 8 weeks R 50 Week Extension Phase Dose
Slide 20: Endocrine Franchise Expanding: CRN04894 and CRN04777
Our Endocrine Franchise Is Expanding with Additional Product Candidates Entering Patient Trials CRN04894: A First-in-Class, Oral Small Molecule ACTH antagonist for Cushing’s Disease (CD) & Congenital Adrenal Hyperplasia (CAH) CRN04777: A First-in-Class, Oral Small Molecule SST5 Agonist for Hyperinsu
Slide 21: What is Cushing's Disease?
What is Cushing’s Disease? Cortisol ACTH Corticotroph Adenoma Excess ACTH secretion causes excess cortisol secretion by the adrenal Adrenal ACTH antagonist blocks the action of ACTH Cushing’s disease is caused by a benign pituitary tumor secreting excess ACTH Weight gain and fatty tissue deposits (m
Slide 22: What is Congenital Adrenal Hyperplasia (CAH)?
What is Congenital Adrenal Hyperplasia (CAH)? CAH patients have too little cortisol resulting in excess ACTH and excess androgens Cortisol ACTH ACTH antagonist blocks the action of ACTH Adrenal X Androgens Low Cortisol: Low blood pressure, blood sugar, energy Adrenal crisis can be life threatening A
Slide 23: CRN04894: Multi-Billion Dollar U.S. Market Opportunity in Cushing's Disease and CAH
Requiring adjunct to GCs *No approved therapies to-date CRN04894: Initial Multi-Billion Dollar U.S. Market Opportunity in Cushing’s Disease and CAH $1,500M Current Patients (On Marketed Therapy) Diagnosed Prevalence Addressable Patients (Candidates for ‘4894) Cushing’s (U.S. Patients) 11,200 5,000 1
Slide 24: Current Therapeutics Have Limited Efficacy and/or Safety Issues
Cortisol ACTH Pituitary Gland Pituitary Directed Agents to Suppress ACTH Secretion Available: glucocorticoids, pasireotide, cabergoline Limited efficacy Safety issues Target Cells Glucocorticoid Receptor Antagonist Available: mifepristone Efficacy difficult to assess Safety issues Adrenal Gland Adre
Slide 25: CRN04894 Target Product Profile
CRN04894 Target Product Profile: Normalize Adrenal Cortisol Levels and Symptoms The only once daily oral ACTH receptor antagonist to normalize adrenal cortisol levels and get patients back to normal without toxicity monitoring requirements Cushing’s Disease Normalize cortisol levels (UFC) & symptoms
Slide 26: CRN04894 Potently Suppressed Adrenal Activity as Measured by Urinary Free Cortisol
PBO (n=9) 40 mg (n=6) 60 mg (n=6) 80 mg (n=6) CRN04894 Potently Suppressed Adrenal Activity as Measured by Urinary Free Cortisol* 24-Hour Urinary Free Cortisol (day 9) Normalization of 24-hour urinary free cortisol has been the registrational endpoint for Cushing’s disease drugs -31% -72% -75% 3% *R
Slide 27: Open-Label Trial of CRN04894 in Patients with ACTH-Dependent Cushing's Syndrome
Open-Label Trial of CRN04894 in Patients with ACTH-Dependent Cushing’s Syndrome (ADCS) Screening/Washout: 14 Days Key Eligibility Criteria N = 18 ADCS: Cushing’s disease Ectopic ACTH syndrome Failed surgery or are awaiting surgery Treatment Periods: 3 cohorts, each 10 days Company-sponsored trial is
Slide 28: Proposed Open-Label Trial of CRN04894 in Patients with CAH
Proposed Open-Label Trial of CRN04894 in Patients with Congenital Adrenal Hyperplasia (CAH) Screening: 4 weeks Key Eligibility Criteria N = 18-30 Participants with CAH and high A4 (≥1.5xULN) at screening Age: ≥16 years Treatment Periods: 3 cohorts (one optional), each 12 weeks SRC review of 3 patien
Slide 29: What is Congenital Hyperinsulinism (CHI)?
What is Congenital Hyperinsulinism (CHI)? Excess insulin produces life-threatening hypoglycemia (low blood glucose) Pancreas Liver Tissues Insulin (b-cells) Glucose Release Glucose Uptake Glucagon (a-cells) X Pancreatic Beta-cell mutations cause inappropriate insulin secretion Inappropriate insulin
Slide 30: CRN04777: Market Opportunity in Congenital and Syndromic Hyperinsulinism
CRN04777: Initial Meaningful Market Opportunity in Congenital and Syndromic Hyperinsulinism Source: Company data on file Diagnosed Prevalence Addressable Congenital HI (U.S. Patients) 2,200 1,500 ? Not cured surgically ? Syndromic HI (U.S. Patients) 1,700 1,700 Diagnosed Prevalence CHI Hypoglycemia
Slide 31: Treatment Challenges and High Burden of Care with Currently Available CHI Therapies
Treatment Challenges and High Burden of Care with Currently Available CHI Therapies Safety, efficacy, & route of administration all need better options Medical Diazoxide Ineffective in ~50% of patients; black box warning Injectable SST2 agonists Tachyphylaxis, no pediatric dosing guidelines, painful
Slide 32: CRN04777 Target Product Profile
CRN04777 Target Product Profile Designed for Kids, Their Caregivers, and the Healthcare System Bringing the only kid friendly, once daily oral therapy to patients as a trusted member of the global CHI community Kid and Family Friendly Raspberry flavored sweetened syrup taken orally Take with breakfa
Slide 33: CRN04777 Reduced Insulin Secretion & IV Glucose Support in Healthy Volunteer Model
CRN04777 Reduced Insulin Secretion & IV Glucose Support in Healthy Volunteer Model of HI# -76% -83% -97% Change in Glucose Infusion Rate % Insulin Reduction Compared to Baseline Change in Insulin %Glucose Infusion Rate Reduction Compared to Baseline * * #Data on file from a Phase 1 trial in healthy
Slide 34: Our GPCR Discovery and Development Engine Is Continuing to Craft and Advance New Assets
Our GPCR Discovery and Development Engine Is Continuing to Craft and advance new assets Targeting highly prevalent endocrine disorders with a favorable probability of success
Slide 35: Growing Franchise Addresses Multi-Billion Dollar Market Opportunity Across Endocrinology
* The portion of each market that could be addressable will depend on relevant indication subpopulations and clinical development plans pursued Sources: Company data on file Current Clinical Pipeline Future Opportunity Paltusotine ‘4777 ‘4894 $820Mn $3,200Mn $960Mn $1,500Mn $2,500Mn $23Bn $84Bn $16B
Slide 36: Investment Highlights: Expected Milestones and Financial Position
Investment Highlights: Expected Milestones and Financial Position Strong Financial Position to Execute Through 2024 $368.4 million in cash & investments as of September 30, 2022 3Q23 PATHFNDR-1 Topline Data 4Q23 PATHFNDR-2 Topline Data 2H23 Carcinoid syndrome P2 data 2023 New drug candidates from di
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