Crinetics Pharmaceuticals, Inc. · NASDAQ:CRNX
Crinetics Pharmaceuticals — Investor Day (June 2025)
75 slides from Crinetics Pharmaceuticals's investor day presentation, Jun 26, 2025
Slide 1: Research & Development Day
RESEARCH & DEVELOPMENT DAY June 26, 2025 – New York
Slide 2: Safe Harbor Statement
Safe Harbor Statement This presentation contains forward-looking statements. Crinetics Pharmaceuticals, Inc. (“Crinetics,” the “company,” “we,” “us,” or “our”) cautions you that all statements other than statements of historical facts contained in this presentation are forward-looking statements, in
Slide 3: Speakers
Speakers SCOTT STRUTHERS, Ph.D. STEPHEN BETZ, Ph.D. Founder and Founder and Chief Executive Officer Chief Scientific Officer RICK GRIMES STACEY HARTE DAVID C. METZ, MBBCH Global Product Global Product Professor of Medicine (retired) Leader, TSH Leader, NDC Neuroendocrinologist CRINETICS PHARMACEUTIC
Slide 4: Agenda
INTRODUCTION • Strategic Focus • Discovery Overview SESSION 1 • CRN12755: TSH Grave’s Hyperthyroidism, Graves’ Orbitopathy (TED) • CRN10329: SST3 AGENDA Autosomal Dominant Polycystic Kidney Disease (ADPKD) SESSION 2 • CRN09682: SST2 + NDC - Non-Peptide Drug Conjugate (NDC) Platform and CRN09682 - Ne
Slide 5: Introductory Remarks
INTRODUCTORY REMARKS Scott Struthers, Ph.D. Founder & Chief Executive Officer CRINETICS PHARMACEUTICALS | 5
Slide 6: Serving our Patients
Serving our Patients Our mission is to build the world’s leading endocrine company that consistently pioneers new therapeutics to help patients better control their disease and improve their daily lives. We made a commitment to the acromegaly community And we stand by it Traci Acromegaly Patient CRI
Slide 7: Our Passion for This Work Runs Deep
Our Passion for This Work Runs Deep CRINETICS PHARMACEUTICALS | 7
Slide 8: A Brief History of Crinetics
A Brief History of Crinetics Founding of Series A IPO Venture Round Opened Laboratories Bootstrapping Era Private Financed Era Modern Era (Technology Creation) (Initial Pipeline Creation) (Pipeline Advancement & Expansion) 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 20
Slide 9: Crinetics is Well-Positioned to Advance Standards of Care With Endocrine Science
Crinetics is Well-Positioned to Advance Standards of Care With Endocrine Science First anticipated Deep pipeline with World-class R&D IP rights commercial launch 2 late-stage programs in capabilities, 4 candidates into 2040s this year 4 indications in preclinical $1.3B of cash, cash Extensive intern
Slide 10: Exploring New Frontiers With Our Science to Expand Patient Reach
Exploring New Frontiers With Our Science to Expand Patient Reach > 1M > 100K Preclinical > 10K Obesity IND Enabling Clinical-Stage Approximate US Graves’ Patients Hyperthyroidism Graves’ Disease Other GPCR- Graves’ Orbitopathy driven Oncology (TED) Acromegaly Polycystic Hyperparathyroidism Kidney Di
Slide 11: Exploring New Frontiers With Our Science to Expand Patient Reach
Exploring New Frontiers With Our Science to Expand Patient Reach > 1M > 100K Preclinical > 10K Obesity IND Enabling TODAY’S TOPICS Clinical-Stage Approximate US Graves’ Patients Hyperthyroidism Graves’ Disease Other GPCR- Graves’ Orbitopathy driven Oncology (TED) Acromegaly Polycystic Hyperparathyro
Slide 12: Discovery Overview
DISCOVERY OVERVIEW Stephen Betz, Ph.D. Founder & Chief Scientific Officer CRINETICS PHARMACEUTICALS | 12
Slide 13: Crinetics' Target Selection Focuses on Endocrinology and Peptide Hormone GPCR Pharmacology
Crinetics’ Target Selection Focuses on the Intersection of Endocrinology and Peptide Hormone GPCR Pharmacology The GPCR Superfamily Crinetics Current Indications • Acromegaly • Carcinoid Syndrome • Congenital Adrenal Hyperplasia • ACTH-dependent Cushing’s >80 peptide Syndrome (ADCS) hormones acting
Slide 14: Our Strategy: Early Derisking with Biomarker Validation from Discovery through Approval
Our Strategy: Early Derisking with Biomarker Validation from Discovery through Approval Preclinical Models Phase 1 Phase 2/3 POC (Healthy Volunteers) (Patients) Safety, POC Safety, Disease Efficacy ∆Hormones ∆Hormones ∆Hormones PK, Safety PK, Safety PK, Safety PROs POC: Proof-of-Concept, PK: Pharmac
Slide 15: Our Approach: Tailor Ligands to Regulate Dynamic GPCR Behaviors
Our Approach: Tailor Ligands to Regulate Dynamic GPCR Behaviors to Ultimately Improve Patient Outcomes Atumelnant SST3 Agonist Antagonist Agonist TSH Antagonist Paltusotine β-arrestin complex cAMP Nonpeptide Drug Conjugate (NDC) IP3 Ligand binding kinetics Biased receptor Alternative Receptor traffi
Slide 16: Every Assay Cascade Must Be Optimized for Receptor Specifics
Despite Similarities, Every Assay Cascade Must Be Optimized for Receptor Specifics and Desired Drug Characteristics SST2 Agonist Assay Cascade SST2 cAMP and Internalization EC50 (human) Properties Criteria SST cAMP Selectivity SST cAMP Chemical Structure New IP (human) (mouse, rat, dog) Potent and S
Slide 17: Early Leads Show the Way to Finding Clinical Class Compounds
Early Leads Show the Way to Finding Clinical Class Compounds Rat Healthy Volunteer Early Lead GHRH Challenge GHRH Challenge % Stimulated GH Suppression 100 80 1500 Vehicle 60 [GH], ng/mL CRN00351 1 mg/Kg, sc CRN00808 1000 CRN00351 10 mg/Kg, sc 40 Octreotide, 0.1 mg/Kg, sc 500 20 Ongoing 0 0 Discover
Slide 18: Medicinal Chemistry
Medicinal Chemistry 50 g 30-300 mg Dog CV Induction (rat) (human) Non-Rodent PK CYP Inhibition / Madan A, Endocr Abstr. 2020;70:AEP627. GHRH Challenge Non-Rodent Safety SST cAMP Selectivity Plasma Protein Binding Rat Tox (human) hERG SST2 cAMP and Internalization EC50 (rat) Rodent PK Metabolite ID S
Slide 19: Every Atom in Paltusotine (CRN00808) Was Optimized
Every Atom in Paltusotine (CRN00808) Was Optimized For Pharmacologic and Pharmaceutical Properties 2-OH, 3-CN combo “Top” Diamine Removes hERG activity Defines SST2 selectivity Synergistic SST2 potency Symmetry reduces chirality and conformational issues -F, -Cl increase hERG activity 3,5 substituti
Slide 20: Discovery Is (Almost) Never a One-and-Done Process
SST2 ACTH Agonist Antagonist hSST2 EC50 (nM) 10000 0.1 100 1000 0.01 10 1 1436 1429 1422 1415 1408 1401 1394 1387 1380 1373 1366 1359 1352 1345 1338 1331 1324 1317 1310 1303 1296 1289 1282 1275 1268 1261 1254 1247 1240 1233 1226 1219 1212 1205 1198 1191 1184 1177 1170 1163 1156 1149 1142 1135 1128 1
Slide 21: Patients Play a Fundamental Role in Discovery and Development
Patients Play a Fundamental Role in Discovery and Development We engage in patient advocacy starting in the Discovery phase Feedback on patient journey is incorporated into overall strategy and trial designs Early input optimizes enrollment and positions candidates for success to address unmet need
Slide 22: TSHR Antagonist: Graves' Disease
TSHR ANTAGONIST GRAVES’ DISEASE: Graves’ Hyperthyroidism Graves’ Orbitopathy (Thyroid Eye Disease, TED) Rick Grimes Global Product Leader, TSH CRINETICS PHARMACEUTICALS | 22
Slide 23: Graves' Hyperthyroidism and Orbitopathy (TED) Have Significant Negative Effects on Patients
Graves’ Hyperthyroidism and Orbitopathy (TED) Have Significant Negative Effects on Patients Graves’ Hyperthyroidism • Graves’ disease is one of the most common Significant Impact on Patients endocrine diseases, affecting ~3 million • Emotional, mental and physical fatigue individuals in the U.S. 1 •
Slide 24: Graves' Hyperthyroidism: Standard of Care Has Been Stagnant for Decades
Graves’ Hyperthyroidism: Standard of Care Has Been Stagnant for Decades and Has Significant Limitations ATDs have become the highly preferred 1L treatment in the US (~90%) due to risks associated with ablative therapies Antithyroid Drugs (ATDs) Ablative Therapy MOA MOA • Inhibits thyroid hormone syn
Slide 25: Graves' Orbitopathy (TED): Need for a Safer Therapy
Graves’ Orbitopathy (TED): Anti-IGF-1R Has Changed the Treatment Paradigm but There is a Need for a Safer Therapy Teprotumumab (anti-IGF-1R mAb) • Inhibition of IGF-1R improves proptosis associated with TED • Teprotumumab reduces proptosis with up to 80% response1 but many experience relapse (>30%)2
Slide 26: The Core Driver of Both Graves' Hyperthyroidism and TED is Over-Stimulation of TSHR
The Core Driver of Both Graves’ Hyperthyroidism and Orbitopathy (TED) is Over-Stimulation of TSHR by TSHR Stimulating Auto-Antibodies (TSAbs) Graves’ Disease has two major manifestations: • Hyperthyroidism • Orbitopathy (also known as Thyroid Eye Disease or TED) TSHR – Thyroid Stimulating Hormone Re
Slide 27: TSHR Antagonism: A Targeted, Novel Mechanism to Treat Graves' Disease
TSHR Antagonism: A Targeted, Novel Mechanism to Treat Both Major Manifestations of Graves’ Disease CRINETICS PHARMACEUTICALS | 27
Slide 28: Crinetics Has Developed Potent and Selective Small Molecule TSH Receptor Antagonists
Crinetics Has Developed Potent and Selective Small Molecule, TSH Receptor Antagonists CRNX TSHR Antagonists CRN12755 Is Potent Functional Antagonist • Structurally diverse of Human TSHR • Potent and selective for TSHR 125 • Good ADME properties Human pIC50 8.06 ± 0.07 (8.8 nM) 100 Rat pIC50 7.31 ± 0
Slide 29: CRN12755 Reduced Thyroid Hormone Levels in a Stimulated Rat Model
Graves’ Hyperthyroidism: CRN12755, a TSHR Antagonist, Reduced Thyroid Hormone Levels in a Stimulated Rat Hyperthyroidism Model RAT HYPERTHYROIDISM MODEL Total T4 Oral administration of CRN12755 dose dependently reduced TSAb (M22) stimulated thyroid hormone (T4) levels Vehicle or CRN12755 PO 60 Total
Slide 30: CRN12755 Suppressed TSAb-Stimulated Hyaluronic Acid Production in TED Patient-Derived GOFs
Graves’ Orbitopathy (TED): CRN12755 Suppressed TSAb-Stimulated Hyaluronic Acid Production in TED Patient-Derived GOFs IGF1R Graves’ orbital fibroblasts (GOFs) are obtained from TED patients TSAb TSHR undergoing orbital decompression surgery and differentiated into orbital adipocytes Orbital Fibrobla
Slide 31: CRN12755 Suppressed TSAb-Stimulated Production of IL-6 in Orbital Adipocytes
Graves’ Orbitopathy (TED): CRN12755 Suppressed TSAb-Stimulated Production of IL-6 in TED Patient-Derived Orbital Adipocytes IGF1R TSAb TSHR Graves Orbital Fibroblasts (GOFs) from TED patients are differentiated into orbital adipocytes and stimulated with TSAbs Orbital Fibroblast IL-6 Increase cytoki
Slide 32: TSHR Antagonist: Potential Single, Oral Therapy for Graves' Hyperthyroidism and TED
TSHR Antagonist: Has Potential to Be a Single, Oral Therapy to Treat Graves’ Hyperthyroidism and Treat/Prevent Orbitopathy (TED) Product Vision Graves’ Hyperthyroidism • Oral, once daily • Rapid control of hyperthyroidism and symptoms • Simultaneous treatment and prevention of orbitopathy • No risks
Slide 33: A TSHR Antagonist Has Potential Advantages Over Emerging New Therapies
A TSHR Antagonist Has Potential Advantages Over Emerging New Therapies TSHR Antagonist Potential Attributes • Oral, once daily • Rapid control of hyperthyroidism with thyroid preservation • Simultaneous treatment and prevention of orbitopathy • No adverse effects of ATDs or anti-IGF-1R and no non-sp
Slide 34: Large Patient Population in Graves' Hyperthyroidism and Orbitopathy with High Unmet Need
Large Patient Population in the US in Both Graves’ Hyperthyroidism and Orbitopathy (TED) with High Unmet Need GRAVES’ HYPERTHYROIDISM GRAVES’ ORBITOPATHY (TED) ~30k >3M prevalent patients1 * ~500,000 prevalent patients4 * incident4,5 ~150k ~25k Sight- Up to ~1.2M with active Graves’ ~325k Mild Moder
Slide 35: Next Steps for the TSH Antagonist Program
Next Steps for the TSH Antagonist Program ENDO 2025: IND Submission Phase 1 Healthy Poster Volunteer Study Presentation Early Proof-of-Concept in Phase 1 with Thyroid Biomarkers (TSH, T3, and T4) IND: Investigational New Drug; POC: proof of concept. CRINETICS PHARMACEUTICALS | 35
Slide 36: SST3 Agonist: ADPKD
SST3 AGONIST AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD) Stephen Betz, Ph.D. Founder & Chief Scientific Officer CRINETICS PHARMACEUTICALS | 36
Slide 37: ADPKD is a Genetic Disease That Significantly Impacts Quality of Life
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a Genetic Disease That Significantly Impacts Quality of Life Normal Hyperfiltration Impairment Failure Leads to kidney failure and dysfunction • 50% of patients develop end stage kidney disease (ESKD), requiring dialysis or kidney transplant To
Slide 38: ADPKD is a Disease of Disrupted Ca2+ and cAMP Ciliary Signaling
ADPKD is a Disease of Disrupted Ca2+ and cAMP Ciliary Signaling Healthy Human Kidney ADPKD Patient Kidney SST3 Receptor SST3 Receptor PC1/PC2 PC1/PC2 Adenylyl X Adenylyl Cyclase Cyclase AQP2 AQP2 Channel SST3 Receptor Channel SST3 Receptor cAMP cAMP Cystogenesis genes Cystogenesis genes PKD1 enables
Slide 39: Tolvaptan Improves Kidney Function in ADPKD, but Causes Increased Urination and Hypernatremia
Tolvaptan Improves Kidney Function in ADPKD, but Causes Increased Urination and Hypernatremia Collecting duct Risks epithelial cells Collecting duct lumen Blood vessel lumen Decreases insertion of AQP2 Decreased urine osmolality AQP2 ↑ insertion Channel Increased water excretion Tolvaptan of AQP2 H2
Slide 40: SST3 is Expressed in Renal Epithelia in ADPKD Patients
SST3, a G𝛼i-Coupled Receptor, is Expressed in Renal Epithelia in ADPKD Patients Activation of SST3 localized in cilia and apical membrane SST3 is expressed in cysts emerging from both of cyst-lining cells decreases cAMP and cystogenesis proximal tubules and collecting ducts Collecting duct Proximal
Slide 41: SST3 Agonism Represents an Effective Somatostatin-Targeted Strategy in ADPKD
SST3 Agonism Represents an Effective Somatostatin- Targeted Strategy in ADPKD SST3 is highly and consistently expressed in cyst-lining cells in ADPKD Mouse Human Control Pkd2WS25 Healthy human ADPKD (n=5) (n=6) (n=5) (n=4) Waning efficacy: SST2 agonists have shown some SST2 Cy Cy efficacy in ADPKD t
Slide 42: Crinetics Has Developed Potent and Selective SST3 Small Molecule Agonists
Crinetics Has Developed Potent and Selective SST3 Small Molecule Agonists LOY-003 Paltusotine 10000 CRNX SST3 Agonists • Structurally diverse 1000 • Potent and selective at hSST3 hSST3 EC50 nM • Good ADME properties 100 10 CRN10329 (Leading Development Candidate) 1 • Predicted human PK supports QD d
Slide 43: Aggressive Conditional PKD1-KO Mouse Model of ADPKD
Aggressive Conditional PKD1-KO Mouse Model of ADPKD Allows for Rapid Compound Evaluation Localization and segment identity of renal cysts in ADPKD mouse model DBA - Collecting Ducts (CDs) LTL - Proximal Tubules (PTs) Medulla Medulla Kidney Weight Cystic Index ✱✱✱✱ Cortex Cortex Kidney Cystic Index (
Slide 44: A Multi-level Approach to Characterize Efficacy in ADPKD Mouse Model
A Multi-level Approach to Characterize Efficacy in ADPKD Mouse Model Biomarkers used to interrogate efficacy of advanced SST3 agonists Level Organ Tissue Cellular Molecular miRNA Gene Regulation Cyst size Proliferation RNA pathway Biomarker Kidney Weight markers profile miRNA: microRNA CRINETICS PHA
Slide 45: CRN10329 Inhibits Cyst Growth and Decreases Proliferation in an Aggressive Mouse Model
Exposure to CRN10329 Inhibits Cyst Growth and Decreases Proliferation in an Aggressive Mouse Model of ADPKD Cystic Index Decreased Cellular Proliferation Decreased CRN10329 concentration Cyst Cyst Proliferating cells Collecting ducts H&E CRN10329 Merge 3 ✱✱ Kidney Weight Proximal tubules LKW/BW (%)
Slide 46: CRN10329 Corrects Aberrant Expression of Renal Tubular Injury Markers
CRN10329 Corrects Aberrant Expression of Renal Tubular Injury Markers PKD1 KO Periostin miR30a Periostin Periostin miR30a CRN10329 Cell Proliferation Treatment Cyst Growth LTBP1 KO reduces cystogenesis Kidney Int. 2014 Apr;85(4):845-54; Am J Physiol Renal Physiol. 2018 Dec 1;315(6):F1695-F1707; Neph
Slide 47: CRN10329 has the Potential to be Standard of Care for ADPKD
CRN10329 has the Potential to be Standard of Care for ADPKD TPP Tolvaptan miRNA 17 inhibitor CRN10329 V2R antagonist SST3 agonist Comparison Ph2/3 Current SOC Preclinical ADPKD at risk of rapid ADPKD at risk of moderate ADPKD at any risk of Target Indication progression to very rapid progression, pr
Slide 48: SST3 Agonist: First-In-Class Novel Therapy for the Majority of ADPKD Patients and Beyond
SST3 Agonist: First-In-Class Novel Therapy for the Majority of ADPKD Patients and Beyond Vision Product Vision To be the first-in-class, oral, once-daily, SST3 agonist that provides long-term kidney function protection, improves the quality of life, and becomes the standard of care for people living
Slide 49: Next Steps for the SST3 Agonist Program
Next Steps for the SST3 Agonist Program IND Enabling Studies IND Clearance Phase 1 Healthy and Activities Volunteer Study CRINETICS PHARMACEUTICALS | 49
Slide 50: Nonpeptide Drug Conjugates (NDC) Platform
NONPEPTIDE DRUG CONJUGATES (NDC) PLATFORM Stephen Betz, Ph.D. Founder & Chief Scientific Officer CRINETICS PHARMACEUTICALS | 50
Slide 51: Crinetics' Unique SST2-NDC Approach Integrates Two Validated Strategies in Oncology
Crinetics’ Unique SST2-NDC Approach Integrates Two Validated Strategies in Oncology SST2 is a well-established MMAE is a well-established, target for imaging and PRRT effective, and easily sourced anti-tumor payload Broad Indication Potential Meningioma Brain Head & Neck MMAE Skin Breast Lung Liver
Slide 52: NDCs Are Designed to Selectively Target and Deliver Cytotoxic Payloads
NDCs Are Designed to Selectively Target and Deliver Cytotoxic Payloads to Cells of Interest Differentiation vs. Current Modalities • Non-cytotoxic when linked Anticancer Agents (Chemotherapies) Payload • Highly potent when free • Interchangeable payload for X Not tumor specific future development X
Slide 53: CRN09682 is the First of Many Potential NDCs from this Platform
CRN09682 is the First of Many Potential NDCs from this Platform Each Component is Optimized • Known to kill cells of interest MMAE • Not toxic when conjugated • Long in-tumor stability • Stable in plasma • Rapidly and specifically cleaved when Linker internalized • Does not interfere with pharmacolo
Slide 54: Next Steps for the Crinetics NDC Platform
Next Steps for the Crinetics NDC Platform: Leverage Tailoring of Components for Specific Patient Needs • Novel payloads • Multiple payloads per New Payloads molecule • Complementary with current therapies Next Gen NDC Opportunities • Tailored half life Wide array of • Optimal tissue distribution spe
Slide 55: Neuroendocrine Neoplasms
NENS NEUROENDOCRINE NEOPLASMS DAVID C. METZ, MBBCH Professor of Medicine (retired) Neuroendocrinologist CRINETICS PHARMACEUTICALS | 55
Slide 56: Neuroendocrine Neoplasms: Rare Tumors Arising from Neuroendocrine Cells
Neuroendocrine Neoplasms (NENs): Rare Tumors Arising from Neuroendocrine Cells Throughout the Body • NENs originate in wide range of organs Gastrointestinal (GI) NETs • SST2 expressed on ~80% of tumors1 (also referred to as carcinoid tumors) • Spectrum of disease from well-differentiated, indolent n
Slide 57: Incidence of Neuroendocrine Tumors is Increasing Over Time
Incidence of Neuroendocrine Tumors is Increasing Over Time NETs Incidence has Increased The Increase Affects All Faster than Other Malignancies Grades and Stages Dasari A, et al. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States. J
Slide 58: NENs are Rare, Heterogenous and Treated Based on Tumor Grade & Differentiation
NENs are Rare, Heterogenous and Treated Based on the Tumor Grade & Differentiation Neuroendocrine Neuroendocrine Tumors (NETs) Carcinomas (NECs) Well-differentiated Poorly-differentiated Grade 1 Grade 2 Grade 3 High Grade (Ki67 <3%) (Ki67 3-20%) (Ki67 >20%) (small/large-cell) Tumor Aggressiveness SS
Slide 59: NEN Treatment Algorithm is Complex
NEN Treatment Algorithm is Complex Diagnosed with NET/NEC ** There is no consensus Locoregional/ on order of treatments Resectable Metastatic/Unresectable for advanced metastatic disease Poorly- Well-Differentiated Differentiated Asymptomatic Major Outcome Predictors*: or Stable Progressive and/or S
Slide 60: NENs are Incurable When Metastatic, Regardless of Grade
Neuroendocrine Neoplasms (NENs) are Incurable When Metastatic, Regardless of Grade A significant opportunity exists for Expected Treatment Outcomes a new therapy that…. Somatostatin Peptide Kinase / Cytotoxic Receptor Receptor mTOR ✓ Kills tumor cells rapidly and effectively Chemotherapy Ligand (SRL
Slide 61: CRN09682: SST2+ Cancers
CRN09682 SST2+ CANCERS: Neuroendocrine Tumors and Beyond Stacey Harte Global Product Leader, CRN09682 CRINETICS PHARMACEUTICALS | 61
Slide 62: CRN09682 is a First-in-Class Therapy Designed to Deliver MMAE to SST2-Expressing Tumor Cells
CRN09682 is a First-in-Class Therapy Designed to Selectively Target and Deliver MMAE to SST2-Expressing Tumor Cells MMAE: monomethyl auristatin E, tubulin inactivator; NDC: non-peptide drug conjugate; SST2: somatostatin receptor 2 CRINETICS PHARMACEUTICALS | 62
Slide 63: CRN09682 Was Purposefully Designed to be Selective for and Internalized by SST2
CRN09682 was Purposefully Designed to be Selective for and Internalized by SST2 Potency and Selectivity SST2 Internalization cAMP production assay Endosomal trafficking assay 125 hSST1 % cAMP stimulation 100 hSST2 hSST3 75 hSST4 50 >400-fold hSST5 25 0 -12 -10 -8 -6 -4 log [CRN09682] M SS14 is nativ
Slide 64: CRN09682 Selectively Delivered MMAE into SST2+ Tumors with Minimal Systemic Exposure
CRN09682 Selectively Delivered MMAE into SST2+ Tumors with Minimal Systemic Exposure to Free MMAE Tumor PK in Nude Mice Bearing SCLC SST2-Expressing NCI-H524 Tumors Intact CRN09682 Free MMAE 1000 Intact CRN09682 1000 Free MMAE Concentration (nM) Concentration (nM) 100 100 10 10 1 Tumor CRN09682 1 Tu
Slide 65: CRN09682 Inhibited Tumor Growth in Two SCLC CDX Mouse Models
CRN09682 Inhibited Tumor Growth in Two SCLC SST2 Expressing CDX Mouse Models in a Dose-Dependent Manner CRN09682 Efficacy Study in NCI-H524 Tumor Model CRN09682 Efficacy Study in NCI-H69 Tumor Model CRN10976 is an analog NDC with no SST2 agonist activity Dosing QWx4 wks in both studies. • CRN09682 d
Slide 66: CRN09682 Induced Rapid Tumor Regression in SCLC CDX Mice Bearing Large Tumors
CRN09682 Induced Rapid Tumor Regression in SCLC CDX Mice Bearing Large Tumors CRN09682 Efficacy Study & Body Weights in NCI-H524 Tumor Model Tumor Volume Body Weight Dosing QWx4 wks. • CRN09682 demonstrated anti-tumor activity and induced tumor regression at 1 and 3 mg/kg • Complete regression obser
Slide 67: CRN09682 Phase 1/2 Study
CRN09682 Phase 1/2 Study Ph 1: Dose Escalation Ph 2: Dose Expansion* • Bayesian Optimal Interval design, n=3-6/cohort • n=approximately 25/cohort Key Eligibility Criteria: MTD Cohort 1: Pancreatic NET • Metastatic or locally advanced Well-differentiated inoperable NETs, NECs or other Expansion Dose
Slide 68: Expanding CRN09682 Opportunity into a Broad Set of Indications
Expanding CRN09682 Opportunity into a Broad Set of Indications by Targeting SST2+ Tumors Meningioma6 (92%) Glioblastoma2 (89-100%) Head & Neck Squamous Cell Carcinoma (inc. NPC)3 (97-100%) Metastatic Melanoma5 ER+/HER2- Metastatic Breast7 (45-61%) (30%) ES Small Cell Lung Cancer8 (48-83%) Hepatocell
Slide 69: Paltusotine and CRN09682 Have Potential to Be Complementary Treatment Options for NETs
Paltusotine and CRN09682 Have the Potential to be Distinct, Complementary Treatment Options for NETs Patients CRN09682 Progressive Disease Triggers rapid cell death leading to tumor regression Together, they may offer Anti-Tumor Response additional benefit through co-administration, potentially broa
Slide 70: Additional Treatment Options May Expand Limited Pharmacotherapy Use in NENs
Availability of Additional Treatment Options May Expand the Limited Pharmacotherapy Use in NENs ADDRESSABLE CS/NEN PATIENT POPULATION (US, 2024) 10-year prevalence of NENs based on ~208K 2024 SEER estimation^ (publication Diagnosed / Seeking Care pending) • Patients with localized tumors removed by
Slide 71: Next Steps for the CRN09682 Program and NDC Platform
Next Steps for the CRN09682 Program and NDC Platform Enrolling Patients Data from Exploring Expansion of in Phase 1/2 Study Dose Escalation Additional Tumor Crinetics NDC Portion of Phase Types with Discovery Pipeline 1/2 Study CRN09682 Beyond NETs CRINETICS PHARMACEUTICALS | 71
Slide 72: Closing Remarks
CLOSING REMARKS Scott Struthers, Ph.D. Founder & Chief Executive Officer CRINETICS PHARMACEUTICALS | 72
Slide 73: Continued Value Creation with Deep Pipeline of Transformative Drug Candidates
Continued Value Creation with Deep Pipeline of Transformative Drug Candidates Program Discovery IND-Enabling Phase 1 Phase 2 Phase 3 Registrational Upcoming Milestones Acromegaly (US) PDUFA Date (September 2025) Paltusotine Acromegaly (EU) CHMP Opinion (1H 2026) (SST2 agonist) Carcinoid syndrome Pha
Slide 74: Crinetics of Tomorrow: A Premier, Endocrine-Focused Global Biopharmaceutical Company
Crinetics of Tomorrow: A Premier, Endocrine- Focused Global Biopharmaceutical Company 2026 & Beyond 2025 Multiple Pipeline Readouts Commercial Build Potential International Potential US Launch Launches World Class R&D Sales Funded Growth Strong Balance Sheet Pipeline Expansion CRINETICS PHARMACEUTIC
Slide 75: Thank You
‘Crinetics jarmaceutica Thank You