Company Overview and Business Update Crinetics Pharmaceuticals advances PALSONIFY™ regulatory review, progresses atumelnant development, and maintains a strong financial position [Executive Summary](index=1&type=section&id=Executive%20Summary) Crinetics Pharmaceuticals reported Q2 2025 financial results, highlighting significant progress towards becoming a fully-integrated, commercial-stage company - Crinetics is making significant progress towards becoming a fully-integrated, commercial-stage company, with regulatory and commercial preparations for PALSONIFY™ (paltusotine) on track[3](index=3&type=chunk) - The New Drug Application (NDA) for PALSONIFY™ (paltusotine) has a PDUFA target action date of **September 25, 2025**[1](index=1&type=chunk) - The company holds **$1.2 billion** in cash, cash equivalents, and investment securities as of June 30, 2025, anticipated to provide a financial runway into **2029**[1](index=1&type=chunk) [Recent Highlights](index=1&type=section&id=Recent%20Highlights) Recent highlights include the ongoing review of paltusotine's NDA for acromegaly, validation of its Marketing Authorization Application (MAA) by the EMA, and continued progress in the global development program for atumelnant - The review process for paltusotine's New Drug Application (NDA) for acromegaly remains on track with consistent and productive engagement with the FDA[4](index=4&type=chunk) - Paltusotine's Marketing Authorization Application (MAA) for acromegaly was validated by the European Medicines Agency (EMA), with a potential decision in the **first half of 2026**[4](index=4&type=chunk) - Enrollment for Cohort 4 of the adult Phase 2 study for atumelnant has been completed, with data expected **early in 2026**[4](index=4&type=chunk) - Crinetics presented eight abstracts from its novel clinical development programs, including paltusotine, atumelnant, and CRN12755, at the Endocrine Society's Annual Meeting, ENDO 2025[7](index=7&type=chunk) [Key Upcoming Milestones](index=2&type=section&id=Key%20Upcoming%20Milestones) Upcoming milestones include the FDA PDUFA date for paltusotine in September 2025, initiation of multiple Phase 3 trials for paltusotine (carcinoid syndrome) and atumelnant (adult and pediatric CAH) in H2 2025, and the start of a Phase 1/2 study for CRN09682 - FDA PDUFA target action date of **September 25, 2025**, for paltusotine NDA for the treatment of acromegaly[7](index=7&type=chunk) - Crinetics expects to initiate the CAREFNDR Phase 3 trial of paltusotine in carcinoid syndrome in the **second half of 2025**[7](index=7&type=chunk) - Crinetics expects to initiate the CALM-CAH Phase 3 study in adults with CAH and the BALANCE-CAH Phase 2/3 study in pediatrics in the **second half of 2025**[7](index=7&type=chunk) - Initiation of a Phase 2/3 study for atumelnant in ACTH-dependent Cushing's syndrome is expected in the **first half of 2026**[7](index=7&type=chunk) - Crinetics expects to initiate a Phase 1/2 dose escalation study for CRN09682, the first candidate from the nonpeptide drug conjugate (NDC) platform, for SST2-positive neuroendocrine tumors and other SST2-expressing solid tumors[7](index=7&type=chunk) Second Quarter 2025 Financial Results Crinetics reported increased Q2 2025 revenues and higher operating expenses, resulting in a larger net loss, but maintains a strong cash position [Financial Performance Overview](index=2&type=section&id=Financial%20Performance%20Overview) Crinetics reported increased revenues for Q2 2025, primarily from licensing agreements, but significantly increased operating expenses led to a higher net loss compared to the prior year Revenues (in thousands) | Metric | Q2 2025 | Q2 2024 | YoY Change | | :------------------------ | :--------------------- | :--------------------- | :--------- | | Revenues | $1,031 | $399 | +158.4% | Operating Expenses (in thousands) | Metric | Q2 2025 | Q2 2024 | YoY Change | | :------------------------- | :--------------------- | :--------------------- | :--------- | | Research and development | $80,301 | $58,344 | +37.6% | | Selling, general and administrative | $49,842 | $24,838 | +100.7% | - Increase in R&D expenses was primarily due to a **$9.6 million** increase in personnel costs and a **$7.9 million** increase in clinical and manufacturing activities costs, driven by clinical program advancement and preclinical portfolio expansion[7](index=7&type=chunk) - Increase in SG&A expenses was primarily driven by a **$12.0 million** increase in personnel costs (due to headcount increase) and a **$10.3 million** increase in outside services costs for commercial planning for PALSONIFY™[7](index=7&type=chunk) Net Loss (in thousands) | Metric | Q2 2025 | Q2 2024 | YoY Change | | :-------- | :--------------------- | :--------------------- | :--------- | | Net loss | $(115,637) | $(74,055) | +56.1% | [Financial Position and Outlook](index=2&type=section&id=Financial%20Position%20and%20Outlook) As of June 30, 2025, Crinetics held $1.2 billion in cash, cash equivalents, and investments, projecting these resources will fund operations into 2029, with an updated anticipated cash used in operations for 2025 between $340 million and $370 million Cash, Cash Equivalents and Investments (in thousands) | Metric | June 30, 2025 | December 31, 2024 | | :----------------------------------- | :------------ | :---------------- | | Cash, cash equivalents and investments | $1,196,360 | $1,354,069 | - Based on current projections, Crinetics expects its cash, cash equivalents, and investments to be sufficient to fund its current operating plan into **2029**[7](index=7&type=chunk)[8](index=8&type=chunk) - For 2025, the company now anticipates cash used in operations to be between **$340 million** and **$370 million**[8](index=8&type=chunk) Corporate Information This section covers Q2 2025 conference call details, Crinetics Pharmaceuticals' therapeutic focus, and forward-looking statement disclaimers [Conference Call and Webcast Details](index=3&type=section&id=Conference%20Call%20and%20Webcast%20Details) Management hosted a live conference call and webcast on August 7, 2025, at 4:30 p.m. ET to discuss the financial results and business update - Management held a live conference call and webcast on **Thursday, August 7, 2025, at 4:30 p.m. ET**[9](index=9&type=chunk) - Access details for the conference call were **1-833-470-1428** (domestic) or **1-404-975-4839** (international) with Access Code **899803**[9](index=9&type=chunk) [About Crinetics Pharmaceuticals](index=3&type=section&id=About%20Crinetics%20Pharmaceuticals) Crinetics Pharmaceuticals is a clinical-stage company focused on discovering, developing, and commercializing novel therapeutics for endocrine diseases and related tumors - Crinetics Pharmaceuticals is a clinical-stage company focused on the discovery, development, and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumors[10](index=10&type=chunk) - PALSONIFY (paltusotine) is the lead investigational once-daily, oral, selective somatostatin receptor type 2 (SST2) nonpeptide agonist in clinical development for acromegaly and carcinoid syndrome[10](index=10&type=chunk) - Atumelnant is currently in development for congenital adrenal hyperplasia and ACTH-dependent Cushing's syndrome[10](index=10&type=chunk) - The company's pipeline includes additional discovery programs for hyperparathyroidism, polycystic kidney disease, Graves' disease, diabetes, obesity, and GPCR-targeted oncology indications[10](index=10&type=chunk) [Forward-Looking Statements](index=3&type=section&id=Forward-Looking%20Statements) This section contains a standard disclaimer regarding forward-looking statements, emphasizing that actual results may differ materially from projections due to various risks and uncertainties - The press release contains forward-looking statements regarding clinical development plans, regulatory timelines, commercial launch plans, therapeutic potential, and financial runway[11](index=11&type=chunk) - Key risks and uncertainties include potential changes in reported data, regulatory authorities disagreeing with interpretations, inability to obtain/enforce intellectual property rights, geopolitical disruptions, unexpected adverse side effects, dependence on third parties, and the timing/outcome of research and development[11](index=11&type=chunk)[12](index=12&type=chunk) - Readers are cautioned not to place undue reliance on these statements, which speak only as of the date of the press release, and Crinetics does not plan to publicly update or revise them[12](index=12&type=chunk) Condensed Consolidated Financial Statement Data This section presents unaudited condensed consolidated financial statements, detailing statements of operations and balance sheet data [Statements of Operations Data](index=5&type=section&id=Statements%20of%20Operations%20Data) This section provides the unaudited condensed consolidated statements of operations for the three and six months ended June 30, 2025, and 2024, detailing revenues, operating expenses, loss from operations, other income, and net loss STATEMENTS OF OPERATIONS DATA (in thousands) | STATEMENTS OF OPERATIONS DATA: | Three months ended June 30, | | | Six months ended June 30, | | | :----------------------------- | :-------------------------- | :-- | :-- | :------------------------ | :-- | | | 2025 | | 2024 | 2025 | 2024 | | Revenues | $1,031 | | $399 | $1,392 | $1,039 | | Operating expenses: | | | | | | | Research and development | 80,301 | | 58,344 | 156,541 | 111,685 | | Selling, general and administrative | 49,842 | | 24,838 | 85,368 | 45,666 | | Total operating expenses | 130,143 | | 83,182 | 241,909 | 157,351 | | Loss from operations | (129,112) | | (82,783) | (240,517) | (156,312) | | Total other income, net | 13,475 | | 8,728 | 28,106 | 15,797 | | Loss before equity method investment | (115,637) | | (74,055) | (212,411) | (140,515) | | Loss on equity method investment | — | | — | — | (470) | | Net loss | $(115,637) | | $(74,055) | $(212,411) | $(140,985) | | Net loss per share - basic and diluted | $(1.23) | | $(0.94) | $(2.27) | $(1.86) | | Weighted-average shares - basic and diluted | 93,791 | | 79,008 | 93,448 | 75,690 | [Balance Sheet Data](index=5&type=section&id=Balance%20Sheet%20Data) This section presents the unaudited condensed consolidated balance sheet data as of June 30, 2025, and December 31, 2024, including cash, cash equivalents and investments, working capital, total assets, total liabilities, accumulated deficit, and total stockholders' equity BALANCE SHEET DATA (in thousands) | BALANCE SHEET DATA: | June 30, 2025 | December 31, 2024 | | :----------------------------- | :------------ | :---------------- | | Cash, cash equivalents and investments | $1,196,360 | $1,354,069 | | Working capital | $1,148,868 | $1,315,704 | | Total assets | $1,289,574 | $1,434,592 | | Total liabilities | $118,048 | $109,787 | | Accumulated deficit | $(1,164,521) | $(952,110) | | Total stockholders' equity | $1,171,526 | $1,324,805 |

Core Insights - Crinetics Pharmaceuticals announced new data on PALSONIFY (paltusotine) for acromegaly, highlighting its potential as a next-generation treatment option with a consistent safety profile and durable IGF-1 control [2][9] Group 1: Clinical Data and Results - The PATHFNDR-1 trial showed that 53 out of 58 participants (91%) entered the ongoing open-label extension after a 36-week randomized, placebo-controlled period, with interim analysis data available through Week 96 [3] - In the PATHFNDR-2 trial, 103 of 106 completers (97.2%) transitioned to the ongoing open-label extension after a 24-week randomized controlled period, with efficacy data from 88 patients through Week 84 [5] - Mean IGF-1 levels remained stable at 0.81 ± 0.21 times the upper limit of normal (ULN) at Week 96, demonstrating durable biochemical control [6][7] Group 2: Symptom Control and Patient Outcomes - Patients switching from injected somatostatin receptor ligands (SRLs) to PALSONIFY experienced a significant reduction in symptom exacerbations, from over 30% of days on SRLs to just 6.2% during stable PALSONIFY dosing (p < 0.0001) [8] - A pooled analysis of Acromegaly Symptom Diary (ASD) scores indicated that a greater proportion of patients treated with PALSONIFY reported less symptom burden compared to those on placebo [8] Group 3: Company Overview and Future Prospects - Crinetics Pharmaceuticals is focused on developing novel therapeutics for endocrine diseases, with PALSONIFY being the first investigational once-daily oral SST2 nonpeptide agonist in Phase 3 clinical development for acromegaly and carcinoid syndrome [9][10] - The company is also developing Atumelnant for congenital adrenal hyperplasia and ACTH-dependent Cushing's syndrome, with all drug candidates being orally delivered small molecules [10]

Group 1 - Crinetics Pharmaceuticals, Inc. will report its second quarter 2025 financial results on August 7, 2025, after market close [1] - A conference call will be held at 4:30 p.m. ET on the same day to discuss the financial results and provide a business update [1][2] - The conference call can be accessed via dial-in numbers or a live webcast, with a recommendation to connect 15 minutes prior to the start [2] Group 2 - Crinetics Pharmaceuticals is a clinical stage pharmaceutical company focused on developing novel therapeutics for endocrine diseases and related tumors [4] - The lead development candidate, PALSONIFY (paltusotine), is in clinical development for acromegaly and carcinoid syndrome associated with neuroendocrine tumors [4] - Other drug candidates include Atumelnant, which is in development for congenital adrenal hyperplasia and ACTH-dependent Cushing's syndrome, with all candidates being orally delivered small molecules [4]

Company Overview and Financial Status - Crinetics has a strong financial position with $1.3 billion in cash, cash equivalents, and investments[31] - The company anticipates its first commercial launch this year and holds IP rights into the 2040s[31] Pipeline Programs and Focus - Crinetics is developing paltusotine, with a PDUFA date in September 2025, for acromegaly[27] - The company is developing CRN12755, a TSHR antagonist, for Graves' Hyperthyroidism and Graves' Orbitopathy (TED), with plans for an IND submission[123] - Crinetics is advancing CRN10329, an SST3 agonist, for Autosomal Dominant Polycystic Kidney Disease (ADPKD), with IND-enabling studies ongoing[150] - The company is developing CRN09682, a nonpeptide drug conjugate (NDC), targeting SST2-expressing tumors, currently in Phase 1/2 study[254] Market and Patient Reach - Graves' Hyperthyroidism affects over 3 million individuals in the US, with a significant portion developing TED[75] - ADPKD affects approximately 145,000 diagnosed patients in the US, with 50% developing end-stage kidney disease[130, 131] - The addressable patient population for Graves' Orbitopathy (TED) is up to approximately 170,000 incident cases[120]

Core Points - Crinetics Pharmaceuticals granted non-qualified stock option awards for 102,350 shares and restricted stock unit (RSU) awards for 77,875 shares to 46 new non-executive employees as part of the 2021 Employment Inducement Incentive Award Plan [1][2] - The stock options have an exercise price of $31.99 per share, equal to the closing price on July 10, 2025, and will vest over four years [2] - Crinetics Pharmaceuticals is focused on developing novel therapeutics for endocrine diseases and related tumors, with lead candidate paltusotine in clinical development for acromegaly and carcinoid syndrome [3] Summary by Category Stock Options and RSUs - The stock options and RSUs were granted as inducements for new employees under the 2021 Inducement Plan, in compliance with Nasdaq Listing Rule 5635(c)(4) [1][2] - Stock options will vest 25% after one year, with the remainder vesting in 36 equal monthly installments, contingent on continued employment [2] - RSUs will vest in equal annual installments over four years, also dependent on continued employment [2] Company Overview - Crinetics Pharmaceuticals is a clinical stage pharmaceutical company specializing in endocrine diseases and tumors [3] - The company’s lead candidate, paltusotine, is the first investigational oral selective somatostatin receptor type 2 nonpeptide agonist [3] - Other drug candidates in development include treatments for congenital adrenal hyperplasia and ACTH-dependent Cushing's syndrome, with a focus on orally delivered small molecules [3]

Core Insights - Crinetics Pharmaceuticals is set to present long-term efficacy and safety data for its investigational drug PALSONIFY (paltusotine) in acromegaly, demonstrating both biochemical and symptom control with a well-tolerated safety profile [1][2] - The company will also showcase Phase 2 trial results for atumelnant in congenital adrenal hyperplasia (CAH) and data from early-stage development programs in Graves' hyperthyroidism and orbitopathy at the Endocrine Society's Annual Meeting, ENDO 2025 [1][3] PALSONIFY Presentations - Four abstracts will report results from the PALSONIFY development program, including an oral presentation on long-term efficacy, safety, and symptom control in acromegaly patients switching from injectable somatostatin receptor ligands to once-daily oral PALSONIFY [2][4] - Three poster presentations will cover symptom stability in acromegaly, patient-reported outcomes from PATHFNDR-1 and PATHFNDR-2, and open-label extension data from PATHFNDR-2 [2] Atumelnant Presentations - Three abstracts will focus on atumelnant, including an oral presentation of Phase 2 trial results in CAH, highlighting reductions in adrenal volume and significant decreases in potent 11-oxygenated androgens [3][7] Early-Stage Pipeline - Crinetics will present new data from its early-stage pipeline, including findings related to CRN12755 for Graves' hyperthyroidism and orbitopathy [4][8] Company Overview - Crinetics Pharmaceuticals is a clinical-stage pharmaceutical company focused on developing novel therapeutics for endocrine diseases and related tumors, with PALSONIFY and atumelnant as its lead candidates [11]

Summary of Crinetics Pharmaceuticals (CRNX) 2025 Update / Briefing Company Overview - **Company**: Crinetics Pharmaceuticals (CRNX) - **Focus**: Development of novel therapies for endocrine diseases, particularly targeting underserved patient populations Key Points and Arguments Strategic Focus and Pipeline Development - Crinetics was founded to address the needs of patients with endocrine disorders, emphasizing the importance of understanding patient experiences and needs in drug development [10][12][53] - The company has transitioned from a discovery-focused entity to a development and commercialization company, with a pipeline that includes several promising candidates [22][24] Pipeline Highlights - **Paltusotine**: A first-in-class somatostatin receptor agonist for acromegaly, which has progressed through clinical trials and is currently in the NDA process with a PDUFA date set for September 25 [12][22] - **Atomelanet**: An ACTH receptor antagonist for congenital adrenal hyperplasia (CAH) and Cushing's disease, which entered clinical trials in 2021 [20][22] - **CRN 12,755**: A TSH receptor antagonist in development for Graves' disease, which is expected to address both hyperthyroidism and Graves' orbitopathy [55][70] TSH Receptor Antagonist Program - **Graves' Disease**: Affects approximately 1% of the U.S. population (about 3 million people), with significant symptoms including hyperthyroidism and thyroid eye disease [56][81] - Current treatments have limitations, including risks associated with ablative therapies and adverse effects from antithyroid drugs [60][61] - **CRN 12,755**: Demonstrated efficacy in preclinical models, showing potential to suppress thyroid hormone production and mitigate symptoms of orbitopathy [70][72] Market Opportunity - The addressable patient population for Graves' disease therapies is substantial, with an annual incidence of new diagnoses up to 170,000 and a significant number of patients suffering from moderate to severe orbitopathy [81][82] - The company aims to provide a single oral therapy that effectively treats both hyperthyroidism and orbitopathy without the adverse effects associated with current treatments [77] Future Directions - Upcoming poster presentation at the ENDO conference to share additional data on CRN 12,755 [82] - Progressing through IND enabling activities with plans for a Phase 1 healthy volunteer study to establish safety and pharmacokinetics [82] Other Important Content - Emphasis on the company's culture and commitment to patient engagement, which informs their drug development process [12][53] - The importance of having backup candidates in development to mitigate risks associated with lead compounds [46][50] - The dynamic nature of GPCRs and the complexity of drug discovery, highlighting the challenges and strategies in developing effective therapies [33][36] This summary encapsulates the key points from the Crinetics Pharmaceuticals briefing, focusing on the company's strategic direction, pipeline developments, market opportunities, and future plans.

Company Overview - Crinetics Pharmaceuticals is a clinical stage pharmaceutical company focused on discovering, developing, and commercializing novel therapeutics for endocrine diseases and endocrine-related tumors [2] - The lead development candidate, paltusotine, is the first investigational once-daily, oral, selective somatostatin receptor type 2 (SST2) nonpeptide agonist in clinical development for acromegaly and carcinoid syndrome associated with neuroendocrine tumors [2] - Other candidates in development include Atumelnant for congenital adrenal hyperplasia and ACTH-dependent Cushing's syndrome, with a focus on orally delivered, small molecule, new chemical entities [2] Upcoming Event - Crinetics Pharmaceuticals will host an in-person and virtual R&D Day in New York on June 26, 2025, from 9:00 AM to 12:00 PM ET [1] - The event will provide updates on early-stage pipeline assets, next steps, and portfolio strategy aimed at driving long-term value [1] - A live question-and-answer session will follow the formal presentations during the event [1]

Core Viewpoint - Crinetics Pharmaceuticals has granted stock options and restricted stock units to new non-executive employees as part of its 2021 Employment Inducement Incentive Award Plan to attract talent [1][2]. Group 1: Stock Options and RSUs - The Compensation Committee granted a total of 74,000 stock options and 48,850 RSUs to 20 new employees [1]. - The stock options have an exercise price of $33.08 per share, equal to the closing price on June 10, 2025 [2]. - Stock options will vest over four years, with 25% vesting after one year and the remainder vesting in 36 equal monthly installments [2]. Group 2: Company Overview - Crinetics Pharmaceuticals is a clinical stage pharmaceutical company focused on developing therapeutics for endocrine diseases and related tumors [3]. - The lead candidate, paltusotine, is in clinical development for acromegaly and carcinoid syndrome [3]. - Other drug candidates are being developed for conditions such as congenital adrenal hyperplasia and ACTH-dependent Cushing's syndrome, with a focus on orally delivered small molecules [3].

Core Points - Crinetics Pharmaceuticals granted stock options and restricted stock units (RSUs) to new non-executive employees as part of its 2021 Employment Inducement Incentive Award Plan [1][2] - The stock options total 74,000 shares with an exercise price of $33.08, equal to the closing price on June 10, 2025, and will vest over four years [2] - The RSUs total 48,850 shares and will also vest over four years in equal annual installments [2] Company Overview - Crinetics Pharmaceuticals is a clinical stage pharmaceutical company focused on developing novel therapeutics for endocrine diseases and related tumors [3] - The lead candidate, paltusotine, is in clinical development for acromegaly and carcinoid syndrome associated with neuroendocrine tumors [3] - Other drug candidates include Atumelnant, targeting congenital adrenal hyperplasia and ACTH-dependent Cushing's syndrome, with a focus on orally delivered small molecules for various endocrine conditions [3]