Summary of Crinetics Pharmaceuticals FY Conference Call Company Overview - **Company**: Crinetics Pharmaceuticals (NasdaqGS:CRNX) - **Founded**: 2008 with a mission to be the world's leading endocrine company - **First Drug**: Approved for acromegaly, launched in 2025, generating $5.4 million in revenue from over 200 start forms [4][6] - **Pipeline**: Diverse pipeline including drugs for carcinoid syndrome, congenital adrenal hyperplasia (CAH), and Cushing's disease [5][19] Key Points Product Launch and Revenue - **PALSONIFY**: First drug launched, expected to be the standard of care for acromegaly, with strong early demand and over 200 enrollments [6][8] - **Revenue Generation**: $5 million in product revenue in the first quarter, with a pricing of $290,000 for a year of therapy [9][37] - **Reimbursement Process**: Over 50% of patients quickly reimbursed through medical exemption forms; average duration for prior authorizations is about 12 months [9][30] Clinical Trials and Pipeline - **Atumelnant**: An ACTH receptor antagonist in advanced clinical trials for CAH and Cushing's disease, with promising phase 2 data [7][19] - **Paltusotine**: Being studied for carcinoid syndrome, with phase 3 trials initiated; aims to simplify treatment compared to traditional painful injections [20][22] - **CRN09682**: A novel small molecule targeting neuroendocrine tumors, currently in first-in-human phase 1 dose escalation [24][80] Market Potential and Strategy - **Market Size**: Global market for somatostatin receptor ligands (SRLs) is approximately $2.5 billion, with $800 million to $900 million attributed to acromegaly [54] - **Patient Retention**: 80% of patients on SRLs discontinue or switch within five years, indicating a significant opportunity for PALSONIFY to retain patients [64] - **European Approval**: Positive recommendation from CHMP for European approval expected by mid-2026; plans to launch country-by-country [39][40] Future Milestones - **Upcoming Data**: Additional data from ongoing studies expected throughout the year, including updates on atumelnant and CRN09682 [25][81] - **Preclinical Programs**: Progress on TSH receptor antagonist and PTH receptor antagonist, with potential IND filings anticipated next year [84] Additional Insights - **Patient Experience**: Paltusotine offers a once-a-day oral administration, significantly improving patient experience compared to traditional therapies [20][41] - **Regulatory Landscape**: The company is navigating a changing regulatory environment, particularly concerning pricing and reimbursement strategies [39][40] - **Market Execution**: The success of PALSONIFY's launch and the ability to convert patients to paid drug status will be critical for market capture [61][62]

Group 1 - NTT Data plans to increase its workforce in India by 5,000 employees this year, focusing on software programming, consulting, and IT support [1] - The company has seen a doubling of large IT contracts exceeding $100 million in the past year, particularly in manufacturing, logistics, and the public sector [1] - NTT Data is currently constructing four data centers in India as part of a $1.5 billion investment, with a current workforce of 40,000 in the country [2] Group 2 - The Indian data center market is attractive due to the country hosting 20% of the world's data but having less than 6% of global data center capacity [2] - Clients' technology budgets are projected to increase by 7% to 9% this year, up from 6% to 7% last year, driven by investments beyond AI [3]

Core Insights - Crinetics Pharmaceuticals is experiencing early commercial momentum with its product PALSONIFY, which has been adopted by over 125 unique prescribers and has received more than 200 enrollment forms from clinical studies [1][6][2] - The company is transitioning from building a pipeline to establishing a commercial business, with PALSONIFY being its first commercial product launched in the U.S. [2][3] - Crinetics plans to initiate a global phase II/III study for atumelnant in ACTH-dependent Cushing's syndrome, which is characterized as a rare and difficult-to-treat condition [5][12] Commercial Performance - In Q4 2025, Crinetics reported total revenue of $6.2 million, with $5.4 million coming from PALSONIFY [4][16] - The company has seen encouraging formulary momentum, with several top payers adding PALSONIFY to their formularies, often with label-aligned prior authorizations and no step edits [1][6] - Approximately half of the patients are currently reimbursed through commercial or government coverage, while the other half are utilizing the company's Quick Start program [7][6] Financial Overview - Crinetics utilized $326.2 million in cash during 2025, which was favorable compared to the guidance range of $340 million to $370 million [19] - The company ended 2025 with over $1 billion in cash and investments, and after a public offering in January 2026, this amount increased to approximately $1.4 billion [20] - For 2026, the company expects GAAP operating expenses to be between $600 million and $650 million, reflecting increased clinical trials and commercialization activities [21] Pipeline Developments - Atumelnant is the first ACTH receptor antagonist tested in humans and has shown rapid and significant reductions in 24-hour urinary free cortisol in preliminary studies [5][10] - The upcoming EQUILIBRIUM ADCS trial will evaluate safety and efficacy across a range of doses, with a focus on establishing a glucocorticoid replacement strategy [12][13] - Crinetics is also advancing other candidates, including paltusotine for carcinoid syndrome and CRN09682 in oncology, with ongoing clinical trials [14][22] Regulatory Updates - Crinetics received a positive opinion from the CHMP in Europe for PALSONIFY, marking a significant milestone in its global regulatory strategy [22]

分组1 - Crinetics Pharmaceuticals, Inc. reported a quarterly loss of $1.29 per share, which was better than the Zacks Consensus Estimate of a loss of $1.37, representing an earnings surprise of +6.01% [1] - The company posted revenues of $6.16 million for the quarter ended December 2025, exceeding the Zacks Consensus Estimate by 38.05%, compared to zero revenues a year ago [2] - The stock has underperformed, losing about 6.8% since the beginning of the year, while the S&P 500 has gained 1.5% [3] 分组2 - The current consensus EPS estimate for the coming quarter is -$1.25 on revenues of $7.61 million, and for the current fiscal year, it is -$5.05 on revenues of $62.05 million [7] - The Zacks Industry Rank for Medical - Drugs is in the bottom 44% of over 250 Zacks industries, indicating potential challenges for stocks in this sector [8]

Financial Data and Key Metrics Changes - In Q4 2025, the company recognized $6.2 million in total net revenue, comprising $5.4 million from the U.S. launch of PALSONIFY and $0.8 million from a licensing agreement with SKK in Japan [25] - Total revenue for the full year 2025 was $7.7 million, with a cost of product revenue of $1.1 million in Q4 [25][26] - The company ended 2025 with over $1 billion in cash equivalents and investments, excluding $380 million from a public offering in January 2026, bringing total cash to approximately $1.4 billion post-offering [28] Business Line Data and Key Metrics Changes - The launch of PALSONIFY has seen over 200 enrollment forms received in Q4, with more than 125 unique prescribers involved [8][9] - The company is focusing on building a commercial enterprise around PALSONIFY, with a fully integrated team in place to support its launch [10][11] Market Data and Key Metrics Changes - The company is experiencing encouraging formulary momentum with payers, securing wins with top plans in the U.S. for PALSONIFY [9] - Approximately 50% of claims have been pre-reimbursed, with 60% moving into the QuickStart program [63] Company Strategy and Development Direction - Crinetics is transitioning from building a pipeline to establishing a commercial business, aiming to become a leading endocrinology company [7] - The company is focused on launching multiple innovative pharmaceuticals from its pipeline, including paltusotine and atumelnant, while also advancing its nonpeptide drug conjugate program [11][30] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about 2026, highlighting the successful launch of PALSONIFY and ongoing clinical trials for other products [31] - The company is committed to transforming the lives of patients with endocrine diseases and creating long-term sustainable value for stakeholders [31] Other Important Information - The company expects GAAP operating expenses for 2026 to be between $600 million and $650 million, reflecting ongoing investments in clinical trials and commercialization activities [29] - The anticipated increase in operating expenses is due to a full year of commercialization activities supporting PALSONIFY [29] Q&A Session Summary Question: Insights from Phase 2/3 design and previous studies - Management indicated that the structure of the Cushing's disease study is well established, with normalization of urine-free cortisol as a primary endpoint [36][68] Question: Trends in PALSONIFY prescriptions - Management noted positive feedback from prescribers and patients, but refrained from providing specific quantitative trends for the quarter [41][44] Question: Enrollment forms and commercial therapy timeline - Management stated that it is premature to extrapolate the 200 enrollment forms as a consistent run rate, with 50% of patients reimbursed and the other 50% on QuickStart [49][50] Question: Payer dynamics for PALSONIFY - Management reported no significant barriers to treatment access, with most coverage based on labels and a commitment to expedite the QuickStart process [63] Question: ADCS study design and endpoints - Management confirmed that the primary endpoint for the phase 3 study is set by the FDA, focusing on the percentage of patients achieving normal urine-free cortisol [68]

Financial Data and Key Metrics Changes - In Q4 2025, Crinetics Pharmaceuticals recognized $6.2 million in total net revenue, comprising $5.4 million from the U.S. commercial launch of PALSONIFY and $0.8 million from a licensing agreement with SKK in Japan [26] - Total revenue for the full year 2025 was $7.7 million, with a cost of product revenue of $1.1 million in Q4 [26][27] - The company ended 2025 with over $1 billion in cash equivalents and investments, excluding $380 million from a public offering in January 2026, bringing total cash equivalents to approximately $1.4 billion post-offering [29][30] Business Line Data and Key Metrics Changes - The launch of PALSONIFY has seen over 200 enrollment forms received in Q4, with more than 125 unique prescribers involved [8][9] - The company is focusing on building a commercial enterprise around PALSONIFY, with a fully integrated team in place to support its launch [10][11] Market Data and Key Metrics Changes - The company is experiencing encouraging formulary momentum with payers, securing wins with top plans in the U.S. for PALSONIFY [9] - Approximately 50% of claims have been pre-reimbursed, with 60% moving into a Quick Start program [64] Company Strategy and Development Direction - Crinetics is transitioning from building a pipeline to building a business, aiming to establish itself as a leading endocrinology company [7] - The company is focused on launching multiple innovative pharmaceuticals from its pipeline, including paltusotine and Atumelnant, while also advancing its nonpeptide drug conjugate program [11][12] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the growth trajectory for PALSONIFY and the potential for Atumelnant to address significant unmet needs in treating Cushing's disease [11][25] - The company anticipates that existing cash and investments will be sufficient to fund operations into 2030, allowing for continued investment in clinical trials and commercialization activities [30] Other Important Information - The company has received a positive CHMP opinion for PALSONIFY in the treatment of acromegaly, marking a significant milestone for its European regulatory path [32] - The EQUILIBRIUM ADCS study is designed to efficiently assess the safety and efficacy of Atumelnant in treating ACTH-dependent Cushing's syndrome [25] Q&A Session Summary Question: Insights from phase II/III design and previous studies - Management noted that the structure of the Cushing's disease study is well precedented, with normalization of urine-free cortisol as a primary endpoint [34][37] Question: Trends in PALSONIFY prescriptions - Management expressed satisfaction with the launch and noted positive feedback from prescribers and patients, but refrained from providing specific quantitative trends [41][42] Question: Enrollment forms and commercial therapy timeline - Management indicated that it is premature to extrapolate the 200 enrollment forms as a run rate, and about 50% of patients are reimbursed for commercial therapy [49][50] Question: Payer dynamics for PALSONIFY - Management reported positive progress in market access with no significant barriers to treatment, and ongoing engagement with payers [63][64] Question: ADCS study design and endpoints - Management confirmed that the primary endpoint for the phase III study is set by the FDA, focusing on the percentage of patients achieving normal urine-free cortisol [68][69]

Financial Data and Key Metrics Changes - In Q4 2025, the company recognized $6.2 million in total net revenue, with $5.4 million from the U.S. commercial launch of PALSONIFY and $0.8 million from a licensing agreement with SKK [24] - Total revenue for the full year 2025 was $7.7 million, with a cost of product revenue of $1.1 million in Q4 [24][25] - Research and development expenses for Q4 were $85.1 million, down from $90.5 million in Q3, while selling, general, and administrative expenses were $53.7 million, relatively stable compared to $52.3 million in Q3 [25] - The company ended 2025 with over $1 billion in cash equivalents and investments, which does not include $380 million from a public offering in January 2026 [26] Business Line Data and Key Metrics Changes - The launch of PALSONIFY has seen over 200 enrollment forms in Q4, with more than 125 unique prescribers involved [6][7] - The company is focusing on building a fully integrated commercial enterprise to support PALSONIFY, including sales professionals and patient support services [8][9] Market Data and Key Metrics Changes - The company is experiencing encouraging formulary momentum with payers, securing wins with top plans in the U.S. for PALSONIFY [7] - Approximately 50% of patients are reimbursed for commercial or government payers, while the other 50% are utilizing the QuickStart program [48][62] Company Strategy and Development Direction - The company is transitioning from building a pipeline to building a business, aiming to establish PALSONIFY as the new standard of care for acromegaly [5][10] - The focus is on expanding the commercial business and advancing clinical trials for other pipeline candidates, including atumelnant for CAH and Cushing's disease [10][30] - The company received a positive CHMP opinion for PALSONIFY in the EU, reflecting the strength of their data [30] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about 2026, highlighting simultaneous execution across the portfolio and ongoing advancements in clinical trials [30] - The company believes existing cash and investments will be sufficient to fund operations into 2030, providing a significant runway for commercialization and clinical development [27] Other Important Information - The company is committed to transforming the lives of people with endocrine diseases and creating long-term sustainable value for stakeholders [30] - The EQUILIBRIUM ADCS study is designed to assess the safety and efficacy of atumelnant in treating ADCS, with a seamless transition from phase 2 to phase 3 [20][23] Q&A Session Summary Question: Insights from Phase 2/3 design and learnings from other studies - Management noted that the structure of the Cushing's disease study is well precedented, with normalization of urine-free cortisol as a primary endpoint [34][66] Question: Trends in PALSONIFY prescriptions - Management is pleased with the launch and early positive experiences from prescribers and patients, but refrained from providing quantitative comments on trends [40][43] Question: Enrollment forms and commercial therapy timeline - Management indicated that it is premature to extrapolate the 200 enrollment forms but expressed satisfaction with the number [47] Question: Payer dynamics for PALSONIFY - Management reported positive progress in market access with no significant barriers to treatment, and most coverage is based on the product's label [62] Question: Phase 3 endpoints for ADCS study - The primary endpoint for phase 3 is set by the FDA, focusing on the percentage of patients achieving normal urine-free cortisol [66]

February 26, 2026 Fourth Quarter and Full Year 2025 Financial Results and Business Update Forward Looking Statements 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. Such forward-looking statements include, but are not limited to, statements regarding: our ability to effectively comme ...

Product Development and Approval - PALSONIFY is the first once-daily oral treatment approved by the FDA for adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option, launched commercially in October 2025[27][36][53]. - The first patient was enrolled in the Phase 3 study of paltusotine for CS in November 2025, with a positive opinion from the CHMP of the EMA in February 2026[30]. - The FDA approved PALSONIFY for first-line treatment of adults with acromegaly on September 25, 2025, granting orphan drug designation for paltusotine[61]. - The EMA granted orphan drug designation for paltusotine in February 2025, with a positive opinion for marketing authorization expected in the first half of 2026[62]. - The FDA review process for new drug applications (NDAs) typically takes about 10 to 12 months from submission to approval[137]. - The FDA may require Phase 4 testing after NDA approval to further assess a drug's safety and effectiveness[140]. - Orphan drug designation can provide seven years of exclusivity for products approved for rare diseases affecting fewer than 200,000 individuals in the U.S.[144]. - Fast track designation allows for expedited review of drugs intended to treat serious conditions, with opportunities for more frequent interactions with the FDA[145]. - Breakthrough therapy designation can expedite development for products showing substantial improvement over existing therapies[146]. - Priority review aims to evaluate applications within six months, compared to ten months for standard reviews, for drugs that significantly improve safety or efficacy[147]. - Accelerated approval may be granted based on effects on surrogate endpoints that predict clinical benefit, with confirmatory trials required post-approval[149]. - The FDCA provides five years of non-patent data exclusivity for new chemical entities, preventing approval of similar drugs during this period[155]. - Pediatric exclusivity can extend marketing exclusivity by an additional six months if clinical trials in children are conducted[157]. Clinical Trials and Research - The Phase 2 TouCAHn study of atumelnant in CAH reported positive results in January 2025, with further updates expected in 2026[35]. - The Phase 2 study of atumelnant in adult CAH patients showed statistically significant reductions in A4 levels, with effects sustained through the 12-week primary endpoint[77]. - The CALM-CAH Phase 3 study for atumelnant in adult CAH patients aims to demonstrate normalization of A4 levels while on physiological doses of glucocorticoids, with the first participant randomized in December 2025[80]. - The BALANCE-CAH pediatric study is a seamlessly-operational Phase 2/3 study, with the first patient dosed in January 2026, evaluating safety and efficacy in pediatric participants with classic CAH[82]. - Atumelnant is currently being studied in an open-label, multiple-ascending dose Phase 1b/2a trial for ACTH-dependent Cushing's syndrome, with positive initial findings reported in June 2024[86]. - The Phase 2/3 study of atumelnant (EQUILIBRIUM-ADCS) is expected to initiate in the first half of 2026, with a double-blind, placebo-controlled design[86]. - The company faces risks related to the lengthy and expensive process of clinical trials, which may not yield favorable results or regulatory approval[197]. - Delays in clinical trials can significantly affect product development costs and the ability to generate revenue[205]. - Conducting clinical trials in foreign countries presents additional risks that may delay completion or result in suspension or termination of trials[206]. - The company may experience delays in clinical trials due to various factors, including regulatory disagreements and funding issues, which could harm commercial prospects[208]. - The FDA's new guidance on informed consent published in August 2023 may impact patient recruitment and retention in clinical trials, potentially causing significant delays[210]. - The company may experience increased development costs and delays in obtaining regulatory approval if it cannot enroll a sufficient number of subjects for clinical trials, which could adversely affect its stock value[211]. - Adverse findings from clinical trials, whether from the company or competitors, could negatively impact the recruitment of patients and the commercial prospects of its investigational products[215]. - The company must demonstrate substantial evidence of safety and efficacy through well-controlled clinical trials to satisfy regulatory authorities, which may require additional studies if data requirements evolve[219]. - The company may face significant delays in obtaining regulatory approvals due to varying approval procedures in foreign markets and increased scrutiny following safety concerns with marketed pharmaceuticals[222]. - The company’s product candidates are subject to extensive regulation, which is costly and time-consuming, potentially leading to unanticipated delays in commercialization[218]. - If undesirable side effects are identified during clinical trials, the company may need to limit the development of its product candidates, adversely affecting their market acceptance and revenue potential[217]. Financial Performance and Projections - As of December 31, 2025, the company had an accumulated deficit of $1.4 billion, primarily due to research and development expenses and selling, general, and administrative costs[184]. - The company expects to continue incurring losses, particularly as it ramps up commercialization efforts for PALSONIFY and conducts ongoing clinical trials for other drug candidates[185]. - The company has incurred significant operating losses since its inception and may never achieve profitability, which could adversely affect its financial condition and stock price[184]. - The company will require substantial additional financing to support its ongoing operations and product development programs, with potential delays or terminations if capital is not secured[187]. - The company believes its existing cash and cash equivalents will fund operations for at least the next 12 months, but this estimate is based on assumptions that may prove incorrect[188]. - The commercial success of PALSONIFY is crucial and will depend on market acceptance by healthcare professionals and payors[184]. - The company has initiated commercial sales of PALSONIFY following FDA approval, but has not yet demonstrated the ability to sustain broader commercialization[183]. - The company is focused on developing additional product candidates for various indications, including NETs, hyperparathyroidism, and metabolic diseases[187]. - The company maintains limited product liability insurance coverage of $10 million per occurrence and in the aggregate, which may not be sufficient as insurance costs rise[179]. - The company may need to seek additional funds sooner than planned, including through public or private equity or debt financings, with a potential sale of up to $350.0 million of common stock[189]. Market and Competitive Landscape - Approximately 36,000 people in the U.S. are living with acromegaly, with 17,000 undiagnosed and 11,500 actively managed, of which 40% are treatment naïve[52]. - The prevalence of Cushing's disease in the U.S. is approximately 11,000 patients, often under-diagnosed due to symptom overlap with other disorders[85]. - The company has a robust pipeline focused on endocrine, metabolism, and targeted therapies, addressing unmet medical needs in various conditions[96]. - The company is continuously evaluating and prioritizing drug discovery efforts to address various endocrine diseases and related tumors[96]. - The trading price of the company's common stock could be highly volatile, potentially leading to substantial losses for investors[29]. - The reliance on third parties for raw materials and active pharmaceutical ingredients poses risks to the company's development and commercialization efforts[29]. - The FDA approved levoketoconazole in December 2021 for Cushing's syndrome, highlighting the competitive landscape for treatments in this area[108]. Corporate Culture and Workforce - The company is committed to maintaining a corporate culture that fosters scientific rigor and employee engagement to improve therapeutic options for patients[39]. - The company employs 594 full-time employees, with 150 holding advanced degrees (Ph.D. or M.D.), and has a good relationship with its workforce[176]. - Sanwa Kagaku Kenkyusho Co., Ltd. granted SKK an exclusive license to develop and commercialize paltusotine in Japan as of February 2022[112]. - The company entered into a Clinical Supply Agreement with SKK on June 14, 2022, to manufacture and supply materials for paltusotine[112]. - An exclusive license for CRN01941, a somatostatin receptor type 2 agonist for veterinary use, was granted to Loyal on March 24, 2023[113]. - The company holds multiple issued patents for paltusotine, with expiration dates estimated between 2037 and 2046, depending on the type of patent and jurisdiction[115][116]. - The drug substance for paltusotine is synthesized in India, optimized in Portugal, and tableted in the U.S.[123]. - The company relies on third-party manufacturers for the production of its products and does not own manufacturing facilities[121][122].

Core Insights - Crinetics Pharmaceuticals reported a significant increase in revenue for Q4 2025, with net product revenue of $5.4 million from the launch of PALSONIFY, marking a notable growth compared to previous periods [4][5][6] - The company is set to initiate a seamless Phase 2/3 study of atumelnant for ACTH-dependent Cushing's syndrome in the first half of 2026, indicating ongoing commitment to expanding its clinical pipeline [5][10] - Crinetics aims to build a multi-product company in the endocrinology space, leveraging its commercial infrastructure and pipeline depth [2] Financial Performance - Total revenue for Q4 2025 was $6.2 million, compared to $0.0 million in Q4 2024, and for the full year 2025, revenue reached $7.7 million, up from $1.0 million in 2024 [4][10] - The cost of product revenue for Q4 2025 was $1.1 million, primarily related to expanding commercial manufacturing capacity [10] - Research and development expenses increased to $85.1 million for Q4 2025 and $332.1 million for the full year, compared to $66.6 million and $240.2 million in 2024, reflecting ongoing investments in key programs [10][21] - Selling, general, and administrative expenses rose to $53.7 million for Q4 2025 and $191.3 million for the full year, compared to $28.2 million and $99.7 million in 2024, driven by the build-out of the commercial organization [10][21] - The net loss for Q4 2025 was $122.8 million, compared to a net loss of $80.6 million in Q4 2024, and for the full year, the net loss was $465.3 million, up from $298.4 million in 2024 [10][21] Product Development and Pipeline - PALSONIFY received FDA approval on September 25, 2025, as the first and only once-daily oral somatostatin receptor ligand for acromegaly, with over 200 enrollment forms submitted by the end of December 2025 [5][10] - The company initiated three pivotal trials, including the CAREFNDR Phase 3 trial for carcinoid syndrome and the CALM-CAH Phase 3 trial for congenital adrenal hyperplasia [5][10] - Positive data from the Phase 2 study of atumelnant showed that 88% of participants reduced glucocorticoid doses to physiological levels, supporting its potential as a leading oral ACTH antagonist [5][10] Cash Position and Future Outlook - As of December 31, 2025, Crinetics had $1.0 billion in cash, cash equivalents, and investment securities, down from $1.4 billion a year earlier [10][21] - The company completed a public offering on January 8, 2026, raising approximately $380 million, which increased its cash position to about $1.4 billion [10] - For 2026, Crinetics expects GAAP operating expenses to be between $600 million to $650 million, with non-GAAP operating expenses projected between $480 million to $520 million [10][21]