Crinetics Pharmaceuticals, Inc. · NASDAQ:CRNX
Crinetics Pharmaceuticals — Investor Presentation (October 2018)
35 slides from Crinetics Pharmaceuticals's investor presentation, Oct 1, 2018
Slide 1: October 2018 Corporate Presentation
October 2018 Corporate Presentation Exhibit 99.1
Slide 2: Forward-looking statements
This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, business strategy, prospective products, product approvals, research
Slide 3: Our Vision
OUR VISION To build the leading endocrine company that consistently pioneers new therapeutics to help patients better control their disease and improve their daily lives
Slide 4: Focused on oral nonpeptide therapeutics for rare endocrine diseases
Focused on developing oral nonpeptide therapeutics for rare endocrine diseases and related tumors Targeting peptide G-protein coupled receptors (GPCRs) with validated biomarkers Unlocking new targets with high therapeutic potential Lead product candidate: CRN00808 Potential first-in-class oral, nonp
Slide 5: Experienced leadership team
Experienced leadership team Scott Struthers, PhD CEO, Founder & Director Frank Zhu, PhD VP of Chemistry & Founder Ajay Madan, PhD VP of Development Steve Betz, PhD VP of Biology & Founder Marc Wilson CFO Alan Krasner, MD CMO We have a long history of successfully discovering and developing important
Slide 6: Significant opportunities across multiple rare endocrine diseases and tumors
Significant opportunities across multiple rare endocrine diseases and endocrine-related tumors Endocrine pathways function to maintain homeostasis and commonly use peptide hormones acting through GPCRs to regulate many aspects of physiology including growth, energy, metabolism, gastrointestinal func
Slide 7: Understanding of GPCR signaling pathways enables oral small molecule candidates
Our understanding of the complex GPCR signaling pathways enables us to develop oral, small molecule, product candidates that modulate GPCR dynamic behaviors Our approach: Tailor ligands to regulate dynamic GPCR behaviors and ultimately improve patient outcomes b g O4P cAMP IP3 AC Ga GTP bArrestin bA
Slide 8: The somatostatin receptor family of peptide GPCRs
ECL2 TM1 TM3 TM5 TM4 TM7 TM2 The somatostatin receptor family of peptide GPCRs The peptide hormone somatostatin is produced by a variety of cell types and has pleiotropic effects throughout the body, many of which are related to the inhibition of secretion of other hormones or neurotransmitters The
Slide 9: Pipeline: potential to build a rare disease franchise in endocrinology
PROGRAM DISCOVERY PRECLIN PHASE 1 PHASE 2 PHASE 3 CRN00808 (Oral sst2 Agonist) Acromegaly CRN01941 (Oral sst2 Agonist) Neuroendocrine Tumors (NETs) CRN02481 Oral sst5 Agonist Hyperinsulinemia Oral ACTH Antagonist Cushing’s Disease Pipeline: Potential to build a rare disease franchise in endocrinolog
Slide 10: CRN00808 for the treatment of acromegaly
CRN00808 for the treatment of acromegaly
Slide 11: Limitations of injected somatostatin peptides and established commercial opportunity
Painful intramuscular/deep sc injections every month (octreotide, lanreotide) Hardness, bruising and swelling at injection site Inconvenient / frequent physician office visits Complex reconstitution of depot dosing regimens and prone to error Limited efficacy – only half of patients are fully contro
Slide 12: Acromegaly: disease overview and treatment paradigm
Acromegaly: disease overview and treatment paradigm ~25,000 people in the U.S. suffer from acromegaly Acromegaly is caused by a benign pituitary tumor Increased GH results in excess downstream secretion of IGF-1 from the liver GH and IGF-1 promote tissue growth and other metabolic effects Perspirati
Slide 13: CRN00808 target product candidate profile
CRN00808 – Target product candidate profile A new class of oral selective nonpeptide sst2 biased agonist designed for the treatment of acromegaly First agent in its class with reported clinical results Orally bioavailable nonpeptide (small molecule) Lack of injections/pain Administration at home Rap
Slide 14: CRN00808 is a potent and selective nonpeptide sst2 agonist
CRN00808 is a potent and selective nonpeptide sst2 agonist... sst2 EC50 = 0.3 nM sst4 sst3 sst1 sst5 In vitro selectivity profile at all five somatostatin receptor subtypes for CRN00808 AGONIST Human EC50 (nM) sst2 sst1 sst3 sst4 sst5 CRN00808 0.25 >10000 3300 1100 >10000 lanreotide 0.10 1900 200 82
Slide 15: Designed with Gi bias to reduce internalization and desensitization of sst2
…designed with Gi bias to reduce internalization and desensitization of sst2 sst2 Activity sst2 Internalization sst2 Activity sst2 Internalization Gi Bias Dose response curves are shown from individual representative experiments. All points are the mean ± standard error of either triplicate or quadr
Slide 16: Phase 1 SAD arm: PK/PD analysis
Phase 1 SAD arm: PK/PD analysis PK/PD analysis of the single-ascending dose arm. Top chart: Suppression of GHRH stimulated GH by 10 mg of CRN00808 administered as an oral solution on day 1 (filled circles, right), compared to day -1 (open circles, left). The plasma exposure of CRN00808 is shown in b
Slide 17: Phase 1 MAD arm: PK/PD analysis
t1/2 = 42-50 hr 5 mg 10 mg 20 mg 30 mg Plasma concentration on the last day of dosing Phase 1 MAD arm: PK/PD analysis 10 mg selected as the initial dose in Phase 2 trials PK/PD analysis of the multiple-ascending dose arm. Left chart: Time-course of plasma CRN00808 trough concentrations (black square
Slide 18: CRN00808: Conclusions from Phase 1
CRN00808: Conclusions from Phase 1 Potent suppression of GH axis in Phase 1 provided clinical POC Clear exposure response relationship observed for GH suppression Maximum GH and IGF-1 suppression observed with 10 mg dose Pharmacokinetics data suggest suitability for once daily oral administration CR
Slide 19: Planned Acromegaly Phase 2 Trials: EVOLVE
CRN00808: Planned Acromegaly Phase 2 Trials: EVOLVE ACROBAT EVOLVE Study: Evaluation of CRN00808 vs placebo in patients controlled on injected SSA monotherapy WEEK -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 SSA Responders (n=36) Depot Last Dose PLACEBO ACTIVE WASHOUT AND RESUME OR
Slide 20: Planned Acromegaly Phase 2 Trials: EDGE
CRN00808: Planned Acromegaly Phase 2 Trials: EDGE ACROBAT EDGE Study: Exploration of CRN00808 in patients inadequately controlled on injected SSA monotherapy WEEK -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Partial Responders (n=45) Depot Last Dose WASHOUT AND RESUME ORIGINAL TREAT
Slide 21: Established clinical development strategy based on other approved products
CRN00808: Established clinical development strategy based on other approved products DRUG (TRIAL) COMPARATOR N PRIMARY ENDPOINT placebo 107 50% GH ê@ 4 weeks none 63 IGF normalization @ week 48 Oral octreotide baseline 155 IGF normalization @ month 7 placebo octreotide/lanreotide 50 130 IGF normaliz
Slide 22: CRN01941 for the treatment of neuroendocrine tumors
CRN01941 for the treatment of neuroendocrine tumors
Slide 23: SSAs: a growing standard of care in NETs
SSAs: a growing standard of care in NETs Prevalence: ~171,000 patients (U.S.)1 Arise from enteroendocrine cells in the GI tract, lung, more rarely, the pancreas NETs commonly overexpress sst2 receptors Somatostatin analogs (SSAs) are a standard of care - NCCN guidelines outline SSAs as first line fo
Slide 24: Goal: Initiate Phase 1 human proof-of-concept trial in first half of 2019
Goal: Initiate a Phase 1 human proof-of-concept clinical trial in the first half of 2019 with results expected in late 2019 / early 2020 CRN01941: Suppression of GHRH-induced GH in preclinical models Dose CRN01941 (mg/Kg) % GH suppression from vehicle hSST2 EC50 rSST2 EC50 In vivo EC50 CRN00808 0.27
Slide 25: CRN02481 for the treatment of hyperinsulinemia
CRN02481 for the treatment of hyperinsulinemia
Slide 26: CHI: disease overview and treatment limitations
CHI: disease overview and treatment limitations Indications Congenital hyperinsulinism (CHI) Genetic defects (eg. KATP channel) results in excess insulin secretion and profound hypoglycemia Incidence: 1:30,000 to 1:50,000 births (U.S.) Post-bariatric surgery hypoglycemia Insulinoma Insulin secreting
Slide 27: CHI hypothesis: an oral, selective-sst5 drug
CHI hypothesis: an oral, selective-sst5 drug is the optimal strategy for treating all HI patients Pancreatic Islet Cells GLUCAGON GLUCOSE sst2 sst5 b-cell INSULIN INSULIN a-cell GLUCAGON GLUCOSE Diazoxide Octreotide (inhibits insulin, glucagon, & pituitary GH secretion) sst2 KATP channel SST5 Agonis
Slide 28: Preclinical results
Preclinical results Rescue of hypoglycemia in rats induced by treatment with sulfonylurea glyburide …while maintaining glucagon levels Vehicle 5 mg/Kg CRN02481 sc In an OGTT, CRN02481 suppressed insulin… Vehicle 5 mg/Kg CRN02481 sc CRN02481 dosed 1 mg/Kg ACTH Iv bolus Glucose bolus CRN02481 dosed Gl
Slide 29: Cushing's Disease
Cushing’s Disease
Slide 30: Cushing's disease overview
Cushing’s disease overview Cushing’s disease is caused by a benign pituitary adenoma with excess adrenocorticotropic hormone (ACTH) secretion, resulting in excess cortisol Source: Dekkers et al (2007) 1210, 2006-2012 Adrenal Cortisol ACTH Standardized Mortality Ratio = 2.4 (95% CI, 1.2-3.9) TARGET E
Slide 31: A prototype antagonist of ACTH with high potency in vitro
A prototype antagonist of ACTH with high potency in vitro observed in preclinical studies K1 = 0.8 nM Kb = 0.4 nM Schild analysis of functional antagonism In vivo POC: acute suppression of ACTH-induced corticosterone in rats Antagonist dosed orally 1 mg/Kg ACTH Iv bolus [antagonist] Competition radi
Slide 32: Financial Overview
Financial Overview $174.8 million pro forma cash and cash equivalents based on $68.4 million in cash and cash equivalents as of June 30, 2018 $106.4 million net proceeds from IPO in July 2018 No debt 24,024,231 common shares outstanding as of August 24, 2018 Strong financial position
Slide 33: Crinetics Pharmaceuticals
'Crinetics Pharmaceuticals
Slide 34: ICS
ICS ‘Crineti 2 > < o a a <
Slide 35: Directors and Advisory Board
Directors and Advisory Board BOARD OF DIRECTORS Wendell Wierenga, PhD Chairman (Former EVP R&D, Santarus) Scott Struthers, PhD Founder & CEO Mason Freeman, MD Venture Partner, 5AM; Endocrinologist at MGH Steve Kaldor, PhD Former CEO, Quanticel Matt Fust Former CFO, Onyx Jack Nielsen Managing Directo
Crinetics Pharmaceuticals — Investor Presentation (October 2018) on 6ix