# EDGAR Filing Document

**Accession Number:** 0001658247
**File Stem:** 0000950170-25-090405
**Filing Date:** 2025-6
**Character Count:** 58099
**Document Hash:** cceef3069a54ba7e69ed6314acee0314
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0000950170-25-090405.hdr.sgml**: 20250626

**ACCESSION NUMBER**: 0000950170-25-090405

**CONFORMED SUBMISSION TYPE**: 8-K

**PUBLIC DOCUMENT COUNT**: 86

**CONFORMED PERIOD OF REPORT**: 20250626

**ITEM INFORMATION**: Regulation FD Disclosure

**ITEM INFORMATION**: Other Events

**ITEM INFORMATION**: Financial Statements and Exhibits

**FILED AS OF DATE**: 20250626

**DATE AS OF CHANGE**: 20250626

**FILER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** Crinetics Pharmaceuticals, Inc.
- **CENTRAL INDEX KEY:** 0001658247
- **STANDARD INDUSTRIAL CLASSIFICATION:** PHARMACEUTICAL PREPARATIONS [2834]
- **ORGANIZATION NAME:** 03 Life Sciences
- **EIN:** 263744114
- **STATE OF INCORPORATION:** DE
- **FISCAL YEAR END:** 1231

**FILING VALUES:**
- **FORM TYPE:** 8-K
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 001-38583
- **FILM NUMBER:** 251080548

**BUSINESS ADDRESS:**
- **STREET 1:** 6055 LUSK BLVD.
- **CITY:** SAN DIEGO
- **STATE:** CA
- **ZIP:** 92121
- **BUSINESS PHONE:** 858-450-6464

**MAIL ADDRESS:**
- **STREET 1:** 6055 LUSK BLVD.
- **CITY:** SAN DIEGO
- **STATE:** CA
- **ZIP:** 92121

?xml version='1.0' encoding='ASCII'? 8-K

**UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549**

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## **FORM** 8-K

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**CURRENT REPORT**

**Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934**

**Date of Report (Date of earliest event reported):** June 26, 2025<br>

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Crinetics Pharmaceuticals, Inc.

**(Exact name of Registrant as Specified in Its Charter)**

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| | | |
|:---|:---|:---|
| Delaware | 001-38583 | 26-3744114 |
| **(State or Other Jurisdiction<br>of Incorporation)** | **(Commission File Number)** | **(IRS Employer<br>Identification No.)** |
| 6055 Lusk Boulevard |  |  |
| San Diego**,** California |  | 92121 |
| **(Address of Principal Executive Offices)** |  | **(Zip Code)** |

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**Registrant's Telephone Number, Including Area Code:** (858) 450-6464<br>

**(Former Name or Former Address, if Changed Since Last Report)**

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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

**Securities registered pursuant to Section 12(b) of the Act:**

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| | | |
|:---|:---|:---|
| **<br>Title of each class** | **Trading<br>Symbol(s)** | **<br>Name of each exchange on which registered** |
| Common Stock, par value $0.001 per share | CRNX | Nasdaq Global Select Market |

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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

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## **Item 7.01 Regulation FD Disclosure.** 
On June 26, 2025, at 9:00 am Eastern Time, Crinetics Pharmaceuticals, Inc. (the "Company") hosted an in-person and virtual Research and Development Day ("R&D Day") in New York. The R&D Day included a presentation that provided an update, including preclinical data on the Company's early-stage pipeline assets, next steps and portfolio strategy to drive long-term value. Key topics included:

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•CRN12755, a Thyroid Stimulating Hormone Receptor ("TSHR") antagonist, for Graves' disease, including Graves' hyperthyroidism and Graves' orbitopathy (Thyroid Eye Disease, or "TED")

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•CRN10329, an SST3 agonist, for autosomal dominant polycystic kidney disease ("ADPKD")

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•Nonpeptide drug conjugate (NDC) platform, including CRN09682 for NETs and other SST2+ tumors

During the presentation, the Company referenced the slide presentation attached as Exhibit 99.1 to this Current Report on Form 8-K, which is incorporated herein by reference. The slide presentation and a live audio webcast of the presentation have been made available under the "Investors" section of the Company's website.

The information contained in this Item 7.01, including in Exhibit 99.1 hereto, is being "furnished" and shall not be deemed "filed" for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the "Exchange Act"), is not subject to the liabilities of that section and is not deemed incorporated by reference in any filing under the Securities Act of 1933, as amended (the "Securities Act"), or the Exchange Act, except as shall be expressly set forth by specific reference in such a filing.

**Item 8.01 Other Events.**

The R&D Day presentation included the following updates on the Company's pre-clinical development pipeline:

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•*CRN12755*: The Company provided preclinical data on its lead candidate CRN12755 in the thyroid-stimulating hormone receptor ("TSHR") antagonist program for the treatment of Graves' disease, including the two major manifestations Graves' hyperthyroidism and Graves' orbitopathy (Thyroid Eye Disease or "TED"). CRN12755 was observed to decrease TSAb-stimulated thyroid hormone (T4) in a rat model, and was observed to decrease hyaluronic acid and IL-6 production in Graves Orbital Fibroblasts (GOFs) from TED patients. The Company also provided an overview of the clinical development strategy for CRN12755, including key biomarkers and other data to be captured in the Phase 1 trial.

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•*CRN10329*: The Company identified CRN10329 as a preclinical leading development candidate for a selective SST3 nonpeptide agonist for the treatment of autosomal dominant polycystic kidney disease (ADPKD). CRN10329 was observed to decrease cystic index, cellular proliferation, kidney weight and aberrant expression of renal tubular injury markers in a mouse model of ADPKD. The Company also shared data highlighting that SST3 is highly and consistently expressed in cyst-lining cells in ADPKD.

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•*CRN09682:* 

oThe Company shared data on CRN09682 previously presented at medical conferences. Data show the potency, selectivity and internalization of CRN09682. CRN09682 in tumor and plasma and free MMAE in plasma are not observed after 24 hours in a mouse tumor model, while free MMAE cleaved from CRN09682 persists within the tumor for at least 240 hours. The Company also demonstrated that CRN09682 induced anti-tumor activity in a dose-dependent manner in different mouse tumor growth models without a decrease in body weight.

oThe Company provided additional details regarding the trial design of its Phase 1/2 study, BRAVESST2, of CRN09682 for the treatment of metastatic or locally advanced SST2-positive neuroendocrine tumors and other SST2-expressing solid tumors. In the Phase 1 dose escalation phase, the Company expects to enroll 3-6 patients per cohort until the minimum tolerated dose is confirmed. Data from the dose escalation will inform the recommended expansion dose for the Phase 2 dose expansion phase and confirm the tumor sub-types that will be enrolled in the expansion cohorts. The Company expects to enroll up to 150 participants across both Phase 1 and Phase 2 of the trial.

**Forward-Looking Statements**

This Current Report on Form 8-K contains forward-looking statements within the meaning of Section 27A of the Securities Act and Section 21E of the Exchange Act. All statements other than statements of historical facts contained in this Current Report on Form 8-K are forward-looking statements, including statements regarding the Company's pipeline development and clinical trial programs, clinical development strategy, and trial design and expected enrollment for the Company's Phase 1/2 study BRAVESST2 of CRN09682. These forward-looking statements speak only as of the date of this Current Report on Form 8-K and are subject to a number of known and unknown risks, uncertainties, assumptions, and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, without limitation, the risks and uncertainties described in the Company's periodic filings with the SEC. The events and circumstances reflected in the Company's forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Additional information on risks facing the Company can be found under the heading "Risk Factors" in the Company's periodic filings with the SEC, including its annual report on Form 10-K for the year

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ended December 31, 2024 and quarterly report on Form 10-Q for the quarter ended March 31, 2025. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Except as required by applicable law, the Company does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

## **Item 9.01 Financial Statements and Exhibits.** 
(d) Exhibits

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| | |
|:---|:---|
| **Exhibit No.** | **Description** |
| 99.1 | [<u>Slide Presentation.</u>](crnx-ex99_1.htm) |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) |

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**SIGNATURES**

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.

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| | | | |
|:---|:---|:---|:---|
|  |  |  | Crinetics Pharmaceuticals, Inc. |
| Date: | June 26, 2025 | By:  | /s/ R. Scott Struthers, Ph.D. |
|  |  |  | R. Scott Struthers, Ph.D.<br>President and Chief Executive Officer<br>(Principal Executive Officer) |

---

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## Exhibit 99.1

![Slide 1](crnx-ex99_1s1.jpg)

Research & Development Day June 26, 2025 – New York Exhibit 99.1

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![Slide 2](crnx-ex99_1s2.jpg)

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, including, but not limited to, statements regarding: the potential for any of our ongoing clinical trials to demonstrate safety or efficacy, plans and timing for CRN09682 trials targeting the treatment of patients with NETs, the potential expansion to further indications and complementary treatment with paltusotine; the potential clinical benefits of our TSHR antagonist, CRN12755, in patients across multiple indications, and the plans for advancement of such program, including future updates and potential studies; the potential benefits, safety and tolerability of our SST3 agonist, CRN10329, for autosomal dominant polycystic kidney disease, and the plans for advancement and growth of such program, including potential future public updates, studies, approval timeline, and expansion of treatment; development plans for our SST2 nonpeptide drug conjugates platform; development of possible new therapeutic options for neuroendocrine neoplasms; the anticipated timing of upcoming milestones of our development programs, clinical trials and registration applications of our product candidates; and the direction or trajectory of the Company's potential future growth, and our expected plans and timing for commercialization of paltusotine and other product candidates pending regulatory approval. In some cases, you can identify forward-looking statements by terms such as "may," "believe," "anticipate," "could," "should," "estimate," "expect," "intend," "plan," "project," "will," "predict," "forecast," "continue," "lead to," "designed to," "goal," "target," and similar terms or the negatives thereof. These statements speak only as of the date of this presentation, involve known and unknown risks, uncertainties, assumptions, and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, without limitation: topline and initial data that we report may change following a more comprehensive review of the data related to the clinical studies and such data may not accurately reflect the complete results of a clinical study, and the FDA and other regulatory authorities may not agree with our interpretation of such results; the risk that interim or preclinical results of a clinical trial do not necessarily predict final results and that one or more of the clinical outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data, and as more patient data become available; the possibility of unfavorable new clinical data and further analyses of existing clinical data; potential delays in the commencement, enrollment and completion of clinical trials and the reporting of data therefrom; our dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; the success of our clinical trials and nonclinical studies for paltusotine and our other product candidates; regulatory developments in the United States and foreign countries; unexpected adverse side effects or inadequate efficacy of our product candidates that may limit their development, regulatory approval and/or commercialization; our ability to obtain and maintain intellectual property protection for our product candidates; we may use our capital resources sooner than we expect; and other risks described under the heading "Risk Factors" in documents we file from time to time with the Securities and Exchange Commission. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and, except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions, and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. Safe Harbor Statement

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![Slide 3](crnx-ex99_1s3.jpg)

Speakers RICK GRIMES Global Product Leader, TSH DAVID C. METZ, MBBCH Professor of Medicine (retired) Neuroendocrinologist STACEY HARTE Global Product Leader, NDC SCOTT STRUTHERS, Ph.D. Founder andChief Executive Officer STEPHEN BETZ, Ph.D. Founder andChief Scientific Officer

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![Slide 4](crnx-ex99_1s4.jpg)

Agenda INTRODUCTION Strategic Focus Discovery Overview SESSION 1 CRN12755: TSHGrave's Hyperthyroidism, Graves' Orbitopathy (TED) CRN10329: SST3Autosomal Dominant Polycystic Kidney Disease (ADPKD) BREAK SESSION 2 CRN09682: SST2 + NDC Non-Peptide Drug Conjugate (NDC) Platform and CRN09682 Neuroendocrine Tumors (NETs) and Carcinoid Syndrome CLOSING Q&A

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![Slide 5](crnx-ex99_1s5.jpg)

Introductory Remarks Scott Struthers, Ph.D. Founder & Chief Executive Officer IR team QC final

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![Slide 6](crnx-ex99_1s6.jpg)

CRINETICS PHARMACEUTICALS \| 6 IR team QC final

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![Slide 7](crnx-ex99_1s7.jpg)

CRINETICS PHARMACEUTICALS \| 7 IR team QC final

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![Slide 8](crnx-ex99_1s8.jpg)

A Brief History of Crinetics CONFIDENTIAL 2012 2014 2013 2015 2016 2017 2018 2019 2022 2024 2025 2020 2021 2023 2011 2010 2008 Private Financed Era (Initial Pipeline Creation) Modern Era (Pipeline Advancement & Expansion) 2009 Bootstrapping Era (Technology Creation) Company Founded November Opened Laboratories Series A Venture Round Paltusotine Phase 2 Data IPO Paltusotine Acromegaly Phase 3 Readouts Paltusotine CS Phase 2 Data Atumelnant Phase 2 Data CRINETICS PHARMACEUTICALS \| 8 CS: Carcinoid Syndrome Paltusotine Sep. 2025 PDUFA DATE Paltusotine Phase 1 Data Paltusotine (CRN00808) IR team QC final Atumelnant Phase 1 Data Atumelnant (CRN04894) Founding of

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![Slide 9](crnx-ex99_1s9.jpg)

Crinetics is Well-Positioned to Advance Standards of Care With Endocrine Science Deep pipeline with 2 late-stage programs in 4 indications First anticipated commercial launch this year Culture dedicated to patients and science $1.3B of cash, cash equivalents & investments IP rights into 2040s World-class R&D capabilities, 4 candidates in preclinical Extensive internal endocrinology expertise CRINETICS PHARMACEUTICALS \| 9 IR team QC final

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![Slide 10](crnx-ex99_1s10.jpg)

Obesity Congenital Adrenal Hyperplasia Other GPCR-driven Oncology Hyperparathyroidism Pituitary Acromegaly Pituitary Endocrinology-Adjacent Graves' Disease Polycystic Kidney Disease Neuroendocrine & Other SST2+ Tumors Exploring New Frontiers With Our Science to Expand Patient Reach Endocrinology > 100K Approximate US Patients > 1M > 10K Preclinical IND Enabling Clinical-Stage Paltusotine Atumelnant Cushing's Disease SST targeting Carcinoid Syndrome SST2 targeting Acromegaly IR team QC final Graves' Hyperthyroidism Graves' Orbitopathy (TED)

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![Slide 11](crnx-ex99_1s11.jpg)

Obesity Congenital Adrenal Hyperplasia Other GPCR-driven Oncology Hyperparathyroidism Pituitary Acromegaly Pituitary Endocrinology-Adjacent Endocrinology > 100K Approximate US Patients > 1M > 10K Preclinical IND Enabling Clinical-Stage Paltusotine Atumelnant Cushing's Disease SST targeting Carcinoid Syndrome SST2 targeting Acromegaly IR team QC final Exploring New Frontiers With Our Science to Expand Patient Reach Graves' Hyperthyroidism Graves' Orbitopathy (TED) Polycystic Kidney Disease Neuroendocrine & Other SST2+ Tumors TODAY'S TOPICS Graves' Disease

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![Slide 12](crnx-ex99_1s12.jpg)

DISCOVERY OVERVIEW Stephen Betz, Ph.D. Founder & Chief Scientific Officer IR team QC final

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![Slide 13](crnx-ex99_1s13.jpg)

Crinetics' Target Selection Focuses on the Intersection of Endocrinology and Peptide Hormone GPCR Pharmacology Crinetics Current Indications Hauser et al, Nature Reviews, Drug Discovery 2017 The GPCR Superfamily >800 Human GPCRs Acromegaly Carcinoid Syndrome Congenital Adrenal Hyperplasia ACTH-dependent Cushing's Syndrome (ADCS) NETs & Other SST2+ Tumors Polycystic Kidney Disease Graves' Disease (including Graves' Hyperthyroidism and Graves' Orbitopathy) Hyperparathyroidism Obesity

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![Slide 14](crnx-ex99_1s14.jpg)

Our Strategy: Early Derisking with Biomarker Validation from Discovery through Approval POC: Proof-of-Concept, PK: Pharmacokinetics, PROs: Patient Reported Outcomes Preclinical Models POC Phase 1(Healthy Volunteers) Safety, POC Phase 2/3(Patients) Safety, Disease Efficacy IR team QC final ∆Hormones PK, Safety ∆Hormones PK, Safety ∆Hormones PK, SafetyPROs

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![Slide 15](crnx-ex99_1s15.jpg)

Alternative signaling Our Approach: Tailor Ligands to Regulate Dynamic GPCR Behaviors to Ultimately Improve Patient Outcomes Biased receptor signaling Receptor trafficking Ligand binding kinetics conformational changes Paltusotine SST3 Agonist Atumelnant Nonpeptide DrugConjugate (NDC) TSH Antagonist Our understanding of complex GPCR signaling pathways enables us to develop product candidates that target specific GPCR dynamic behaviors cAMP IP3 β-arrestin complex Agonist Antagonist

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![Slide 16](crnx-ex99_1s16.jpg)

Despite Similarities, Every Assay Cascade Must Be Optimized for Receptor Specifics and Desired Drug Characteristics Properties Criteria Chemical Structure New IP In Vitro Pharmacology Potent and SST2-selective Bias for cAMP over internalization In Vitro ADME Profile Acceptable drug-like properties Brain Penetration Minimal Pharmacokinetics Species PK Acceptable exposures for PD / tox studies Predicted Human PK Half-life compatible for QD dosing In Vivo Efficacy Suppression of growth axis Rodent and Non-Rodent Toxicity Acceptable NOAEL Genotoxicity Negative Cardiovascular Toxicity Acceptable NOAEL Non-Rodent PK Rodent PK Rat Tox Genotox Assessment 30-300 mg Medicinal Chemistry 50 g Non-Rodent Tox Plasma Protein Binding Dog CV GHRH Challenge(rat) In Vitro CV Safety Assessment Metabolite ID SST2 cAMP and Internalization EC50 (human) CYP Inhibition/Induction hERG Microsomal Stability SST cAMP Selectivity (human) SST cAMP (mouse, rat, dog) IGF-1 Repeat Dose(rat) SST2 Agonist Assay Cascade IR team QC final

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![Slide 17](crnx-ex99_1s17.jpg)

Early Leads Show the Way to Finding Clinical Class Compounds CRN00351 hSST2 EC50=0.45 nM hSST4 EC50=0.47 nM Early Lead Healthy Volunteer GHRH Challenge Every molecule Crinetics moves into the clinic is designed to exceed a high bar for selectivity, drug exposure and drug-like properties Rat GHRH Challenge Ongoing Discovery CRN00808 IR team QC final

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![Slide 18](crnx-ex99_1s18.jpg)

The Ultimate Clinical Compound Is a Balance of Multiple Inputs and Evaluations Zhao J, et al. ACS Med Chem Lett. 2023;14(1):66-74. Madan A, et al. Pituitary. 2022;25(2):328-339. Madan A, Endocr Abstr. 2020;70:AEP627. hSST2 EC50 (nM) More Potent Less Potent CRN00808 (paltusotine) Synthesis Order Non-Rodent PK Rodent PK Rat Tox Genotox 30-300 mg Medicinal Chemistry 50 g Non-Rodent Safety Plasma Protein Binding Dog CV GHRH Challenge(rat) In Vitro CV Safety Assessment Metabolite ID SST2 cAMP and Internalization EC50 (human) CYP Inhibition / Induction hERG Microsomal Stability SST cAMP Selectivity (human) SST cAMP EC50 (mouse, rat, dog) IGF-1 Repeat Dose(rat) IR team QC final

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![Slide 19](crnx-ex99_1s19.jpg)

Every Atom in Paltusotine (CRN00808) Was Optimized For Pharmacologic and Pharmaceutical Properties Zhao et al. (2022) ACS Medicinal Chemistry Letters, https://pubs.acs.org/doi/full/10.1021/acsmedchemlett.2c00431 2-OH, 3-CN combo Removes hERG activity Synergistic SST2 potency -F, -Cl increase hERG activity 5-pos SST2 activity increase Poorer SST selectivity Increased hERG activity 6-pos SST2, SST3, and SST4 activity increase Typically lowers metabolic stability Quinoline core N improves SST2 potency Good synthetic accessibility Overall acceptable bioavailability Overall acceptable stability "Top" Diamine Defines SST2 selectivity Symmetry reduces chirality and conformational issues 3,5 substitution Most potent and selective for SST2 -OCH3, -CH3 increases CYP and hERG activities Difluoro = optimal drug-like properties 7-pos Substitution lowers SST2 potency IR team QC final

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![Slide 20](crnx-ex99_1s20.jpg)

License CRN01941 Pivot to CRN04894 Discovery Is (Almost) Never a One-and-Done Process Backup Molecules Provide Insurance and Opportunity CRN00808 CRN01941 hSST2 EC50 (nM) Synthesis Order SST2 Agonist Initial Candidate CRN04599 ACTH Antagonist IR team QC final

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![Slide 21](crnx-ex99_1s21.jpg)

Patients Play a Fundamental Role in Discovery and Development Patient engagement is in our DNA, with nearly two decades of relationship building that began well before our work in the clinic 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 Awareness initiatives build network, develop insights, and support communities Acromegaly Awareness Day November 1, 2019 IR team QC final

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![Slide 22](crnx-ex99_1s22.jpg)

TSHR Antagonist Rick Grimes Global Product Leader, TSH Graves' disease: Graves' Hyperthyroidism Graves' Orbitopathy (Thyroid Eye Disease, TED)

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![Slide 23](crnx-ex99_1s23.jpg)

Graves' Orbitopathy (TED) Graves' Hyperthyroidism and Orbitopathy (TED) Have Significant Negative Effects on Patients Significant Impact on Patients Emotional, mental and physical fatigue Anxiety Difficulty concentrating due to "brain fog" Reduced performance on daily living and work activities Graves' disease is one of the most common endocrine diseases, affecting ~3 million individuals in the U.S. 1 Symptoms include irritability, tremor, fatigue, weight loss, dyspnea and heat intolerance Major complications include atrial fibrillation, heart failure and thyroid storm Significant Impact on Patients Significant physical discomfort including ocular pain, double vision and proptosis Can lead to psychosocial distress, such as anxiety and depression Difficulty with daily tasks such as driving, reading and social interactions ~500,000 prevalent patients in the U.S.2 Causes inflammation and damage to the tissues around the eye, including muscles, fatty tissue, and connective tissue Typically follows a biphasic course: active inflammatory phase (1-3 years) followed by a chronic, fibrotic phase Can lead to vision loss and blindness Lee et al. 2023 Bartalena et al. 2020 Graves' Hyperthyroidism Healthy Eye TED Eye

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![Slide 24](crnx-ex99_1s24.jpg)

MOA Inhibits thyroid hormone synthesis in the thyroid gland Limitations Does not prevent or treat Graves' Orbitopathy 30-50% of Graves' patients develop TED1 Typically develop TED within 18 months of onset of Graves' Hyperthyroidism Potential for serious side effects including liver injury (~3%)2 and agranulocytosis (~0.3%)3 Other adverse effects including Itching, rash, hives, arthralgias, arthritis, fever, abnormal taste sensation, nausea, or vomiting in up to 13% of patients2 Graves' Hyperthyroidism: Standard of Care Has Been Stagnant for Decades and Has Significant Limitations Chin et al. 2020 Sundaresh et al. 2013 Wanabe et al. 2012t al. 2013 Antithyroid Drugs (ATDs) MOA Ablation of thyroid function, either with Radioactive iodine (RAI), which destroys the thyroid cells Thyroidectomy (surgical thyroid removal) Limitations Permanent hypothyroidism and lifelong thyroid hormone replacement therapy Thyroidectomy risks parathyroid gland and laryngeal nerve damage RAI has risk of radiation thyroiditis or secondary malignancies RAI has increased risk of incidence or exacerbation of TED Ablative Therapy ATDs have become the highly preferred 1L treatment in the US (~90%) due to risks associated with ablative therapies

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![Slide 25](crnx-ex99_1s25.jpg)

Graves' Orbitopathy (TED): Anti-IGF-1R Has Changed the Treatment Paradigm but There is a Need for a Safer Therapy Douglas et al. 2020 Couch 2022 Kahaly et al. 2021 Inhibition of IGF-1R improves proptosis associated with TED Teprotumumab reduces proptosis with up to 80% response1 but many experience relapse (>30%)2 Risks of therapy include: On target risk of hearing impairment (10-20%)3,4 and hyperglycemia (10%)3,5 Other safety risks including muscle spasms (32%), alopecia (15%), nausea (12%) and fatigue (10%)6 Requires burdensome IV dosing in an infusion center Not suitable for all patients – precautions for those with inflammatory bowel disease, diabetes and pre-existing hearing conditions Teprotumumab (anti-IGF-1R mAb) Douglas et al. 2023 Smith et al. 2024 Teprotumumab FDA briefing document Dec. 13, 2019

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![Slide 26](crnx-ex99_1s26.jpg)

The Core Driver of Both Graves' Hyperthyroidism and Orbitopathy (TED) is Over-Stimulation of TSHR by TSHR Stimulating Auto-Antibodies (TSAbs) CRINETICS PHARMACEUTICALS \| 26 Graves' Disease has two major manifestations: Hyperthyroidism Orbitopathy (also known as Thyroid Eye Disease or TED) TSHR – Thyroid Stimulating Hormone Receptor

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![Slide 27](crnx-ex99_1s27.jpg)

TSHR Antagonism: A Targeted, Novel Mechanism to Treat Both Major Manifestations of Graves' Disease CRINETICS PHARMACEUTICALS \| 27

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![Slide 28](crnx-ex99_1s28.jpg)

Crinetics Has Developed Potent and Selective Small Molecule, TSH Receptor Antagonists CRNX TSHR Antagonists Structurally diverse Potent and selective for TSHR Good ADME properties CRN12755 (leading development candidate) Predicted human PK to support QD dosing Efficacious in Graves' Hyperthyroidism rat model Inhibits TSAb stimulation in human Graves' patient orbital fibroblasts IND-enabling safety studies in progress CRN12755 Is Potent Functional Antagonist of Human TSHR

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![Slide 29](crnx-ex99_1s29.jpg)

Graves' Hyperthyroidism: CRN12755, a TSHR Antagonist, Reduced Thyroid Hormone Levels in a Stimulated Rat Hyperthyroidism Model M22: TSAb derived from Graves' patient RAT HYPERTHYROIDISM MODEL Oral administration of CRN12755 dose dependently reduced TSAb (M22) stimulated thyroid hormone (T4) levels

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![Slide 30](crnx-ex99_1s30.jpg)

Graves' Orbitopathy (TED): CRN12755 Suppressed TSAb-Stimulated Hyaluronic Acid Production in TED Patient-Derived GOFs Graves' orbital fibroblasts (GOFs) are obtained from TED patients undergoing orbital decompression surgery and differentiated into orbital adipocytes Hyaluronic Acid TSHR IGF1R Orbital Fibroblast Hyaluronic acid attracts and binds to water, increasing the volume of orbital tissue Dose Response Demonstrated in Model with M22 Antibody Stimulation TSAb Fowler, M. (2025)

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![Slide 31](crnx-ex99_1s31.jpg)

Graves' Orbitopathy (TED): CRN12755 Suppressed TSAb-Stimulated Production of IL-6 in TED Patient-Derived Orbital Adipocytes Murdock et al, Frontiers in Ophthalmology, 2025 Graves Orbital Fibroblasts (GOFs) from TED patients are differentiated into orbital adipocytes and stimulated with TSAbs TSHR IGF1R Orbital Fibroblast TSAb IL-6 Increase TRAb production Fowler, M. (2025) Increase proliferation, differentiation, and adipogenesis Increase cytokine production and inflammation

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![Slide 32](crnx-ex99_1s32.jpg)

TSHR Antagonist: Has Potential to Be a Single, Oral Therapy to Treat Graves' Hyperthyroidism and Treat/Prevent Orbitopathy (TED) Graves' Orbitopathy (TED) Prevent Orbitopathy Graves' Hyperthyroidism Oral, once daily Rapid control of hyperthyroidism and symptoms Simultaneous treatment and prevention of orbitopathy No risks associated with ATDs Thyroid preservation Oral, once daily Equivalent or better efficacy than approved IGF-1R mAb Improved safety No hearing impairment or hyperglycemia Enabling a more durable treatment Product Vision

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2nd Generation IGF-1R Inhibitors (SC or oral) Treat TED only Early data suggest subcutaneous are more efficacious than oral On-target side effects remain a concern (full data still pending) Reduce levels of TSAbs by promoting degradation Broad IgG degradation, not TSAb specific May require large reductions in IgG (>70%) High dose, once weekly subcutaneous injections A TSHR Antagonist Has Potential Advantages Over Emerging New Therapies TSHR Antagonist Product Vision A single, oral therapy to treat Graves' Hyperthyroidism and treat/prevent Graves' Orbitopathy ROA: route of administration. TSHR Antagonist Potential Attributes Anti-FcRn mAbs & Small Molecule Bispecific Degraders 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-specific immunomodulation

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Large Patient Population in the US in Both Graves' Hyperthyroidism and Orbitopathy (TED) with High Unmet Need ~500,000 prevalent patients4 \* Lee et al. 2023 Hallowell et al. 2002 Smith et al. 2016 Bartalena et al. 2020 GRAVES' ORBITOPATHY (TED) >3M prevalent patients1 \* GRAVES' HYPERTHYROIDISM Addressable patient population up to ~170k incident3 Bartley et al. 1994 Dosiou et al. 2021 Muralidhar et al. 2020 \*Theoretical prevalence ~30k incident4,5 Addressable patient population ~9k moderate to severe incident Up to ~1.2M with active Graves' hyperthyroidism2 ~325k Mild (55-75%) ~150k Moderate-to-severe(20-40%)6,7 ~25k Sight-threatening (<10%)

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Next Steps for the TSH Antagonist Program ENDO 2025: Poster Presentation IND Submission Phase 1 Healthy Volunteer Study IND: Investigational New Drug; POC: proof of concept. Early Proof-of-Concept in Phase 1 with Thyroid Biomarkers (TSH, T3, and T4)

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SST3 Agonist Stephen Betz, Ph.D. Founder & Chief Scientific Officer Autosomal Dominant Polycystic Kidney Disease (ADPKD) IR team QC final

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Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a Genetic Disease That Significantly Impacts Quality of Life Tolvaptan (current standard-of-care) only used by <10% of patients: Modest efficacy Boxed Warning: Acute liver injury Key adverse effects (mechanism-dependent): Increased frequency of urination Thirst Dehydration Willey C et al. Kidney Disease 2019; Sim et al. 2021 Most common inherited kidney disorder (~145K diagnosed patients in the US) Abnormal primary cilia function triggers cystogenesis, fluid-filled cysts that gradually enlarge Normal Hyperfiltration Impairment Failure Leads to kidney failure and dysfunction 50% of patients develop end stage kidney disease (ESKD), requiring dialysis or kidney transplant IR team QC final

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ADPKD is a Disease of Disrupted Ca2+ and cAMP Ciliary Signaling AQP2 Channel SST3 Receptor SST3 Receptor PC1/PC2 Adenylyl Cyclase Cystogenesis genes AQP2 Channel SST3 Receptor SST3 Receptor PC1/PC2 Adenylyl Cyclase Cystogenesis genes X PKD1 enables ciliary Ca2+ influx Inhibits adenylyl cyclase and reduces cAMP Healthy Human Kidney ADPKD Patient Kidney Low ciliary cAMP levels  No cystogenic signal Calcium unable to enter cell to reduce cAMP High ciliary cAMP levels  Cystogenic genes induced Hypothesis: Reducing ciliary cAMP levels is a novel approach for reducing cystogenesis IR team QC final cAMP cAMP

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Tolvaptan Improves Kidney Function in ADPKD, but Causes Increased Urination and Hypernatremia H2O H2O Decreases insertion of AQP2 Decreased urine osmolality Increased water excretion Increased serum sodium (hypernatremia) Reduces adenylyl cyclase activity, decreasing expression of cystogenesis genes Decreased cystogenesis Reduced kidney function decline Risks Benefit ↑ insertion of AQP2 Tolvaptan X Cystogenesis genes X X Collecting duct lumen Blood vessel lumen Collecting duct epithelial cells AQP2 Channel V2 Receptor SST3 Receptor SST3 Receptor PC1/PC2 Adenylyl Cyclase Adenylyl Cyclase IR team QC final AQP2: aquaporin-2

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&nbsp;&nbsp;&nbsp;&nbsp;H2O H2O ↑ insertion of AQP2 Collecting duct lumen Blood vessel lumen Collecting duct epithelial cells SST3 is expressed in cysts emerging from both proximal tubules and collecting ducts Tolvaptan acts only on cysts originating from collecting duct SST3 agonist should impact expansion of cysts originating from tubules and collecting duct Cy: cyst lumen Cy Cy Activation of SST3 localized in cilia and apical membrane of cyst-lining cells decreases cAMP and cystogenesis Cystogenesis genes X AQP2 Channel V2 Receptor SST3 Receptor SST3 Receptor PC1/PC2 Adenylyl Cyclase Adenylyl Cyclase IR team QC final

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Waning efficacy: SST2 agonists have shown some efficacy in ADPKD trials Hyperglycemia with SST5 activation Consistent expression in healthy and ADPKD kidneys SST3 Agonism Represents an Effective Somatostatin-Targeted Strategy in ADPKD Lancet 2013; 382: 1485–95; PLoS Med 16(4): e1002777; JAMA, 2018; 320 (19) Hepatology 2013; 58(1), 409-421 SST3 is highly and consistently expressed in cyst-lining cells in ADPKD Cy Cy Cy Cy Cy Cy Cy: cyst lumen Mouse Human Control (n=5) Pkd2WS25 (n=6) Healthy human (n=5) ADPKD (n=4) SST2 SST3 SST5 IR team QC final

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Crinetics Has Developed Potent and Selective SST3 Small Molecule Agonists CRNX SST3 Agonists Structurally diverse Potent and selective at hSST3 Good ADME properties CRN10329 (Leading Development Candidate) Predicted human PK supports QD dosing Efficacious in ADPKD mouse model IND-enabling safety studies ongoing Paltusotine CRN10329 LOY-003 IR team QC final

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Aggressive Conditional PKD1-KO Mouse Model of ADPKD Allows for Rapid Compound Evaluation DBA - Collecting Ducts (CDs) LTL - Proximal Tubules (PTs) Cortex Medulla Cortex Medulla DBA: dolichos biflorus agglutinin LTL: lotus tetragonolobus lectin Cysts derive from collecting ducts in medulla and from proximal tubules in cortex Localization and segment identity of renal cysts in ADPKD mouse model Kidney Weight Cystic Index WT CreERT2-; Pkd1fl/fl ADPKD CreERT2+; Pkd1fl/fl CRINETICS PHARMACEUTICALS \| 43 IR team QC final

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A Multi-level Approach to Characterize Efficacy in ADPKD Mouse Model Tissue Cellular Molecular Organ Cyst size Proliferation markers RNA pathway profile Kidney Weight Level Biomarker Biomarkers used to interrogate efficacy of advanced SST3 agonists miRNA: microRNA IR team QC final miRNA Gene Regulation

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Exposure to CRN10329 Inhibits Cyst Growth and Decreases Proliferation in an Aggressive Mouse Model of ADPKD Cyst Cyst CRN10329 concentration H&E CRN10329 Merge Proximal tubules Collecting ducts Kidney Weight Cystic Index Decreased Cellular Proliferation Decreased Total cells Proliferating cells IR team QC final LKW: left kidney weight; BW: body weight.

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CRN10329 Treatment CRN10329 Corrects Aberrant Expression of Renal Tubular Injury Markers LTBP1 KO reduces cystogenesis Kidney Int. 2014 Apr;85(4):845-54; Am J Physiol Renal Physiol. 2018 Dec 1;315(6):F1695-F1707; Nephrol Dial Transplant (2012) 27: 2702–2711; Ren Fail. 2020; 42(1): 1166–1172; Int J Oncol. 2016 Mar;48(3):1155-64 miR30a Periostin Cell Proliferation Cyst Growth PKD1 KO Periostin Periostin miR30a IR team QC final

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CRN10329 has the Potential to be Standard of Care for ADPKD TPP Comparison Tolvaptan V2R antagonist Current SOC miRNA 17 inhibitor Ph2/3 CRN10329 SST3 agonist Preclinical Target Indication ADPKD at risk of rapid progression ADPKD at risk of moderate to very rapid progression, ADPKD at any risk of progression Efficacy ~50% reduction in total kidney volume (TKV) growth, only in first year of treatment Potential for impact on TKV to be more effective than tolvaptan Potential for impact on TKV to be more effective than tolvaptan ~33% reduction in eGFR decline Potential for impact on eGFR to be more effective than tolvaptan Potential for impact on eGFR to be more effective than tolvaptan SAFETY Tolerability/Safety Black Box Warning: Requires continual liver monitoring Hypernatremia, dehydration and hypovolemia, polyuria and nocturia significantly impact patients' lives Mild to moderate AEs including injection site reaction, headache, and sinus infection Expected to be well tolerated DOSING Dosing Oral BID, requires titration SC, Q2W, no expected titration Oral, QD, no titration expected QD: Once daily BID: Twice daily Q2W: Once every two weeks SC: Subcutaneous IR team QC final

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1. Provide a new, superior SOC: Establish efficacy, improve safety/tolerability, first approval in ADPKD at high risk of rapid progression (Stage 2-3A) 2. Accelerated approval based on Phase 2 endpoint (TKV): Efficient clinical development plan to enable accelerated approval based on TKV endpoint 3. Expand to earlier, younger patients with superior safety / tolerability: Lifelong protection of kidney function to stop or delay renal function impairment (Stage 1) 4. Expand to more advanced patients (superior efficacy): The first treatment to stop or delay progression to ESRD (Stages 3B-4) 5. Exploit combination potential: Evaluate emerging preclinical and clinical data to identify potential additive or synergistic combination therapies 6. Indication expansion: Explore in polycystic liver disease (PLD) and non-functioning pituitary adenomas (NFPAs) 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 with ADPKD Strategies IR team QC final

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Next Steps for the SST3 Agonist Program IND Enabling Studies and Activities IND Clearance Phase 1 Healthy Volunteer Study IR team QC final

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NonPeptide Drug Conjugates (NDC) Platform Stephen Betz, Ph.D. Founder & Chief Scientific Officer IR team QC final

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Crinetics' Unique SST2-NDC Approach Integrates Two Validated Strategies in Oncology MMAE is a well-established, effective, and easily sourced anti-tumor payload 64Cu-dotatate PET scan of a patient with intestinal NET and multiple metastases Pauwels (2018) Am J Nuc Med 8, 311-331 SST2 is a well-established target for imaging and PRRT MMAE CRINETICS PHARMACEUTICALS \| 51 Broad Indication Potential Brain Lung Meningioma Liver GI Tract Breast Head & Neck Skin PET: positron emission tomography, NET: neuroendocrine tumor, PRRT: peptide receptor radionuclide therapy IR team QC final

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NDCs Are Designed to Selectively Target and Deliver Cytotoxic Payloads to Cells of Interest MMAE: monomethyl auristatin E; tubulin inactivator; PROTAC: proteolysis-targeting chimeras; PK: pharmacokinetics; ADME: absorption, distribution, metabolism, excretion. Stable in plasma Cleaved intracellularly High affinity and selectivity Optimized internalization Low molecular weight Traditional chemical synthesis Designed for substitution with other GPCR-targeting small molecules Differentiation vs. Current Modalities Limited number of cycles Radionuclide supply Treatment logistics Radiation safety Long half-life Poor tumor penetration Unspecific uptake Radioligand Therapies Antibody-Drug Conjugates Not tumor specific Unfavorable PK/ADME Narrow therapeutic index Anticancer Agents (Chemotherapies) Payload Applicability across multiple endocrinology and endocrine-adjacent therapeutic areas including oncology and immunology Linker Ligand Non-cytotoxic when linked Highly potent when free Interchangeable payload for future development IR team QC final

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CRN09682 is the First of Many Potential NDCs from this Platform SST2 Agonist MMAE Known to kill cells of interest Not toxic when conjugated Long in-tumor stability Stable in plasma Rapidly and specifically cleaved when internalized Does not interfere with pharmacology Potent SST2 agonist Selective for SST2 Optimized for internalization Stable in plasma Each Component is Optimized Linker IR team QC final

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Next Gen NDC Opportunities Wide array of specifically tailored molecules for areas of high unmet needs New Payloads New Targets Next Steps for the Crinetics NDC Platform: Leverage Tailoring of Components for Specific Patient Needs Novel payloads Multiple payloads per molecule Complementary with current therapies Other GPCRs in endocrinology and oncology Tailored half life Optimal tissue distribution IR team QC final

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NENsNeuroendocrine Neoplasms DAVID C. METZ, MBBCH Professor of Medicine (retired) Neuroendocrinologist

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Neuroendocrine Neoplasms (NENs): Rare Tumors Arising from Neuroendocrine Cells Throughout the Body 1. Baldelli R. et al. Somatostatin analogs therapy in gastroenteropancreatic neuroendocrine tumors: current aspects and new perspectives. doi: 10.3389/fendo.2014.00007; 2. Singh S et al. Patient reported burden of NET diagnosis: results from the first global survey of patients with NETs. J Glob Oncol. 2016; 2:43-53. Most common primary sites: Pancreas GI tract Lungs NENs originate in wide range of organs SST2 expressed on ~80% of tumors1 Spectrum of disease from well-differentiated, indolent neuroendocrine tumors (NETs) to poorly-differentiated, highly aggressive neuroendocrine carcinomas (NECs), including small-cell lung cancer (SCLC) Often present at advanced, incurable stage with >50% metastatic typically to liver2 Clinically, nonfunctional or functional based on symptoms of hormone hypersecretion (e.g. carcinoid syndrome) Extra-pancreatic Extra-pulmonary Hindgut Transverse, left, sigmoid colon Rectum Midgut Second part of duodenum Jejunum Ileum Right Colon Foregut Lungs Stomach First part of duodenum Pancreatic NETs (functional/non-functional) Gastrointestinal (GI) NETs (also referred to as carcinoid tumors)

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Incidence of Neuroendocrine Tumors is Increasing Over Time Dasari A, et al. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States. JAMA Oncol. 2017;3:1335-1342. NETs Incidence has Increased Faster than Other Malignancies The Increase Affects All Grades and Stages

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Well-differentiated NENs are Rare, Heterogenous and Treated Based on the Tumor Grade & Differentiation Grade 1 (Ki67 <3%) Grade 2 (Ki67 3-20%) Grade 3 (Ki67 >20%) High Grade (small/large-cell) Neuroendocrine Tumors (NETs) Neuroendocrine Carcinomas (NECs) Poorly-differentiated Tumor Aggressiveness SST2 Expression More Frequent/Common Less Frequent/Common Better Outcomes Poorer Outcomes Klimstra DS, et al. Digestive System Tumours. In: WHO Classification of Tumours. 5th edition. Vol 1. IARC, Lyon, 2019.

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Ex-Pancreatic NET NEN Treatment Algorithm is Complex Kinase / mTOR inhibitors include Cabozantinib, Everolimus, Sunitinib. Chemotherapies include CAPTEM, Folfox/iri/nox, platinum/etoposide, Lurbinectedin, I/O: Immunotherapies Treatments represent most commonly used but do not reflect full spectrum of available options. Locoregional/ Resectable Metastatic/Unresectable Chemotherapy Diagnosed with NET/NEC \*\* Progressive and/or Symptomatic There is no consensus on order of treatments for advanced metastatic disease Major Outcome Predictors\*: Stage (extent of disease) Grade and differentiation Primary tumor site Patient age (<50 yo vs. ≥50 yo) \* Borbath I. The ENET registry: A tool to assess the prognosis of NENs. EJ Cancer 2022;168:80 \*\* Figure adapted from: Kunz P, J Clin Oncol 33:1855-1863, 2015 & Mohamed A, ERC (2024)31 e240025; Weaver JMJ, Cancers (2023)15, 4951; McGarrah PW, Pancreas (2020)49, 529; Chan J, NEJM. 2025;392:653-665; Lee L. Expert Opin Pharmacother. 2018 May 24;19(8):909–928; Strosberg J N Engl J Med 2017;376:125-135. , Horn L. N Engl J Med 2018;379:2220-9. Mountzios G. DOI: 10.1056/NEJMoa2502099, June 2, 2025. SRL = Somatostatin Receptor Ligand Asymptomatic or Stable Disease Poorly-Differentiated Well-Differentiated Systemic Treatment Liver-Directed Therapy Pancreatic NET Surgery Chemotherapy PRRT Kinase / mTOR Inhibitors SRL Observe SRL I/O Therapy

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Kills tumor cells rapidly and effectively Improves efficacy for higher grade disease Addresses PRRT intolerance and cycle limitations Provides better benefit/risk profile after SRL use Improves quality of life and survival Cytotoxic Chemotherapy Peptide Receptor Radionuclide Therapy (PRRT) Somatostatin Receptor Ligand (SRL) Kinase / mTOR Inhibitors CRINETICS PHARMACEUTICALS \| 60 Neuroendocrine Neoplasms (NENs) are Incurable When Metastatic, Regardless of Grade Some Tumor Regression Moderately Well-Tolerated Longest DOR Some Tumor Regression Moderate Side Effects Variable DOR Good Tumor Regression Moderate/ Severe Side Effects Variable DOR Tumor Stability Well-Tolerated Variable DOR A significant opportunity exists for a new therapy that…. Expected Treatment Outcomes Treatments represent most commonly used, but do not reflect full spectrum of available options DOR: duration of response

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crn09682 Stacey Harte Global Product Leader, CRN09682 SST2+ Cancers: Neuroendocrine Tumors and Beyond

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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 IR team QC final

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CRN09682 was Purposefully Designed to be Selective for and Internalized by SST2 SST2 Internalization Endosomal trafficking assay Potency and Selectivity cAMP production assay SS14 is native somatostatin, peptide hormone agonist of SST2 CRINETICS PHARMACEUTICALS \| 63 Assays performed in SST-expressing CHO cells >400-fold IR team QC final

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Free MMAE CRN09682 Selectively Delivered MMAE into SST2+ Tumors with Minimal Systemic Exposure to Free MMAE Intact CRN09682 CDX: cell derived xenograft; SCLC: small cell lung cancer, MMAE: monomethyl auristatin E. Tumor PK in Nude Mice Bearing SCLC SST2-Expressing NCI-H524 Tumors Single IV dose of CRN09682 0.3 mg/kg administered to CDX mice CRINETICS PHARMACEUTICALS \| 64 Intact CRN09682 Free MMAE IR team QC final

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CRN09682 Inhibited Tumor Growth in Two SCLC SST2 Expressing CDX Mouse Models in a Dose-Dependent Manner CRN09682 Efficacy Study in NCI-H69 Tumor Model CRN09682 demonstrated anti-tumor activity in both models and induced tumor regression in NCI-H69 model CRN09682 had no effect on BW in NCI-H524 and induced minimal BW loss at 3 mg/kg in NCI-H69 model CRN10976 is an analog NDC with no SST2 agonist activity CRN09682 Efficacy Study in NCI-H524 Tumor Model BW: body weight; CDX: cell derived xenograft QW: every week; SCLC: small cell lung cancer; SST2: somatostatin receptor 2 IR team QC final Dosing QWx4 wks in both studies.

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CRN09682 Induced Rapid Tumor Regression in SCLC CDX Mice Bearing Large Tumors CRN09682 Efficacy Study & Body Weights in NCI-H524 Tumor Model BW: body weight; CDX: cell derived xenograft;; SCLC: small cell lung cancer; SST2: somatostatin receptor 2 CRN09682 demonstrated anti-tumor activity and induced tumor regression at 1 and 3 mg/kg Complete regression observed in 3/10 mice at 1 mg/kg and 7/10 mice at 3 mg/kg CRN09682 had no effect on BW loss in NCI-H524 model Tumor Volume Body Weight IR team QC final Dosing QWx4 wks.

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CRN09682 Phase 1/2 Study Key Endpoints Safety & tolerability of CRN09682 Define DLT/MTD and select Expansion Dose PK of CRN09682 and MMAE DLT: Dose limiting toxicity; DOR: duration of response; MTD: Maximum tolerated dose; MMAE: monomethyl auristatin E; NEC: Neuroendocrine carcinoma; NET: Neuroendocrine tumor; ORR: objective response rate; PFS: progression free survival; PK: pharmacokinetics; Q3W: every 3 weeks; SCLC: small cell lung cancer); SSTR: somatostatin receptor; WD: well-differentiated Efficacy Endpoints Measure preliminary anti-tumor activity of CRN09682: ORR, DOR, PFS by RECIST v1.1 Key Eligibility Criteria: Metastatic or locally advanced inoperable NETs, NECs or other solid tumors Tumor progression on or after last line of therapy Positive SSTR expression by FDA approved SSTR PET/CT No carcinoid syndrome Ph 1: Dose Escalation Ph 2: Dose Expansion\* Cohort 1: Pancreatic NET Well-differentiated Cohort 3: NEC Poorly Differentiated (includes SCLC) Cohort 2: ex-Pancreatic NET Well-differentiated Recommended Expansion Dose Dose Level 1 Q3W Cohort 4: Other Solid Tumors (e.g. Breast, Head-Neck) Dose Level 2 Dose Level 3 Dose Level 4 MTD FDA cleared starting dose Bayesian Optimal Interval design, n=3-6/cohort n=approximately 25/cohort \*representative of potential cohorts IR team QC final

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Expanding CRN09682 Opportunity into a Broad Set of Indications by Targeting SST2+ Tumors CRINETICS PHARMACEUTICALS \| 68 Glioblastoma2 (89-100%) ES Small Cell Lung Cancer8 (48-83%) Meningioma6 (92%) Hepatocellular Carcinoma4 (38% (IHC)) GEP-NEC1 (38%) ER+/HER2- Metastatic Breast7 (30%) Head & Neck Squamous Cell Carcinoma (inc. NPC)3 (97-100%) Metastatic Melanoma5 (45-61%) \* SST2 expression measured by SST2 Dotatate unless noted. ER+: estrogen positive; ES: extensive stage; GEP: Gastroenteropancreatic; IHC: immunohistochemistry; NPC: nasopharyngeal carcinoma NEC: neuroendocrine carcinoma; SST2: somatostatin receptor 2 (Approximate Percent of Tumors Expressing SST2) Sources in notes. IR team QC final

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Together, they may offer additional benefit through co-administration, potentially broadening therapeutic impact. Paltusotine and CRN09682 Have the Potential to be Distinct, Complementary Treatment Options for NETs Patients Anti-Tumor Response CRN09682 Progressive Disease Carcinoid Syndrome/Functional Tumors Paltusotine Triggers rapid cell death leading to tumor regression Disease Control Provides rapid and consistent symptom control Crinetics' Strategy Unlocks the Full Potential to Treat the Broadest Set of NETs Patients IR team QC final Paltusotine is an investigational compound.

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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 2024 SEER estimation^ (publication pending) ~208K Diagnosed / Seeking Care ^Source: SEER 17 & SEER 8 (Surveillance, Epidemiology, and End Results) Health Advances analysis, data on file. CRINETICS PHARMACEUTICALS \| 70 \* Segment refers to patients receiving pharmacotherapy including SRLs or antitumor agents. Includes combination use; sum of SRL treated patients and antitumor treated patients may be greater than the total treated population since they are not mutually exclusive. ~157-180K Not Undergoing Medical Management ~28-51K Undergoing Medical Management\* ~18-34K SRL Treatment ~11-21K Antitumor Agent Pharmacologically treated population for symptom and/or tumor control\* Patients with localized tumors removed by surgery "Watch and wait" patients with low grade or non-functional NETs Initial opportunity for paltusotine and CRN09682 NEN/Ts: neuroendocrine neoplasms/tumors; SRL: somatostatin receptor ligand IR team QC final

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Next Steps for the CRN09682 Program and NDC Platform Enrolling Patients in Phase 1/2 Study Exploring Additional Tumor Types with CRN09682 Beyond NETs Data from Dose Escalation Portion of Phase 1/2 Study Expansion of Crinetics NDC Discovery Pipeline IR team QC final

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Closing Remarks Scott Struthers, Ph.D. Founder & Chief Executive Officer

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Program Discovery IND-Enabling Phase 1 Phase 2 Phase 3 Registrational Upcoming Milestones Paltusotine (SST2 agonist) PDUFA Date (September 2025) CHMP Opinion (1H 2026) Phase 3 (2H 2025) Atumelnant (ACTH antagonist) Phase 3 in Adult (2H 2025) Phase 2/3 in Pediatric (2H 2025) Phase 2/3 (2H 2025) CRN09682 Nonpeptide drug conjugate Phase 1/2 TSH antagonist IND SST3 agonist IND PTH antagonist IND Oral GLP-1 nonpeptide Candidate Selection Oral GIP nonpeptide Candidate Selection Continued Value Creation with Deep Pipeline of Transformative Drug Candidates SST: somatostatin receptor type; ACTH: adrenocorticotropic hormone; NETs: Neuroendocrine tumors; TSH: thyroid-stimulating hormone; TED: thyroid eye disease; ADPKD: Autosomal dominant polycystic kidney disease; PTH: parathyroid hormone; GLP-1: glucagon-like peptide-1 receptor agonists; GIP: gastric inhibitory polypeptide; IND: Investigational New Drug Application; PDUFA: Prescription Drug User Fee Act; CHMP: Committee for Medicinal Products for Human Use Hyperparathyroidism ADPKD Obesity Obesity Graves' disease & TED NETs and SST2-expressing solid tumors Partners: Congenital adrenal hyperplasia (adult) Carcinoid syndrome Japan Development and Commercialization Partner for Paltusotine Licensee of targeted, nonpeptide radiopharmaceuticals Licensee of CRN01941 for veterinary use

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Crinetics of Tomorrow: A Premier, Endocrine-Focused Global Biopharmaceutical Company Sales Funded GrowthPipeline Expansion World Class R&D Strong Balance Sheet Multiple Pipeline Readouts Potential International Launches 2026 & Beyond Commercial Build Potential US Launch 2025

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Thank You