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]

Summary of Crinetics Pharmaceuticals (CRNX) Conference Call Company Overview - **Company**: Crinetics Pharmaceuticals (CRNX) - **Event**: Jefferies Healthcare Conference, June 5, 2025 - **Key Speaker**: CEO Scott Struthers Core Points and Arguments Product Pipeline and Milestones - Crinetics is preparing for a PDUFA date on September 25 for its first molecule, paltusotine, aimed at treating acromegaly [2][3] - The company has a robust pipeline, including a second drug, Atumelnat, targeting congenital adrenal hyperplasia and Cushing's disease [3][4] - Crinetics has developed all its drugs in-house, with the exception of licensing paltusotine rights in Japan and a technology platform to Radionetics [4][6] Financial Position - The company is in a strong financial position with $1 billion in the bank, sufficient to last until 2029 without partnerships [6] Market Dynamics for Acromegaly - The acromegaly market has approximately 11,000 addressable patients, with segments for new therapies, switching from existing treatments, and re-engaging lost patients [13][15] - There is a significant unmet need, with 20% of patients requiring more frequent injections than the standard regimen [14] - Approximately 80% of patients discontinue treatment within three years, indicating a potential market for re-engagement [15][16] Sales and Marketing Strategy - The company is onboarding its sales team and engaging with key opinion leaders (KOLs) to improve patient care and drug delivery [9][10][18] - Crinetics aims to educate physicians on treatment guidelines and the importance of managing acromegaly effectively [25][26] Payer Engagement and Pricing Strategy - Crinetics has been actively engaging with payers, receiving positive feedback regarding the drug's efficacy and the cost savings associated with reducing wastage from current injectable therapies [32][33] - The company is still evaluating its pricing strategy based on value and market research [38] Future Outlook - The company anticipates a lag in revenue realization post-launch due to formulary updates and patient visits [40] - Crinetics is preparing for Phase III trials for Atumelnat, with a focus on rethinking treatment paradigms for congenital adrenal hyperplasia [42][44] Additional Important Content - The company emphasizes the importance of improving healthcare delivery for acromegaly patients, not just providing a new drug [10][12] - There is a focus on patient education and support services to enhance treatment adherence and outcomes [21][22] - The company has a diverse pipeline with multiple ongoing programs, indicating a long-term growth strategy [54]

Company Participation - Crinetics Pharmaceuticals will participate in the Jefferies Global Healthcare Conference from June 3-5, 2025 in New York, NY [1][2] Company Presentation Details - The company presentation is scheduled for Thursday, June 5, 2025, at 12:50 p.m. Eastern Time [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 an investigational once-daily, oral, selective somatostatin receptor type 2 (SST2) nonpeptide agonist, currently in clinical development for acromegaly and carcinoid syndrome associated with neuroendocrine tumors [3] - Atumelnant is in development for congenital adrenal hyperplasia and ACTH-dependent Cushing's syndrome [3] - All drug candidates are orally delivered, small molecule, new chemical entities resulting from in-house drug discovery efforts, targeting various endocrine conditions [3]

Core Insights - Crinetics Pharmaceuticals is presenting two abstracts at the AACE Annual Meeting 2025, highlighting the investigational candidate paltusotine's rapid and durable treatment effects in acromegaly patients and the significant symptom burden experienced by patients on standard treatments [1][2][3] Group 1: Paltusotine Development - Paltusotine is a once-daily oral medication that has shown promising results in controlling IGF-1 levels in surgically naïve acromegaly patients, with three out of four patients in one trial achieving IGF-1 normalization [4][10] - The company is preparing for a PDUFA action date of September 25 in the U.S., indicating potential regulatory approval for paltusotine [3][10] - Paltusotine is positioned as a viable first-line therapy for patients who cannot undergo surgery, with sustained IGF-1 control observed over 24 months in clinical trials [4][10] Group 2: Symptom Burden and Treatment Discontinuation - A study revealed that patients on long-acting injectable somatostatin analogs reported symptom exacerbations on 32% of days, leading to reduced quality of life and increased healthcare utilization [5][7] - A retrospective analysis indicated that 54% of acromegaly patients discontinued therapy, with only 20% remaining on their initial treatment, highlighting dissatisfaction with current injectable therapies [7] - The findings underscore the need for more effective treatments that provide consistent symptom control for acromegaly patients [5][7] Group 3: Atumelnant Development - Atumelnant, another investigational compound by Crinetics, is in development for ACTH-dependent Cushing's syndrome and has shown promising results in a Phase 2a study [11] - The compound is designed to selectively target the melanocortin type 2 receptor, potentially offering significant treatment benefits for patients with conditions related to excess ACTH [11]

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 [3] - The company's lead development candidate, paltusotine, is an investigational once-daily, oral, selective somatostatin receptor type 2 (SST2) nonpeptide agonist in clinical development for acromegaly and carcinoid syndrome associated with neuroendocrine tumors [3] - Crinetics is also developing atumelnant, a first-in-class oral ACTH antagonist for treating congenital adrenal hyperplasia and Cushing's disease [3] - All drug candidates are orally delivered, small molecules resulting from in-house drug discovery efforts, targeting various endocrine conditions [3] Recent Developments - On May 10, 2025, the Compensation Committee granted non-qualified stock option awards to purchase an aggregate of 152,475 shares and 101,800 restricted stock unit (RSU) awards to 35 new non-executive employees [1] - The stock options have an exercise price of $30.68 per share, equal to the closing price on May 9, 2025 [2] - The stock options and RSUs are granted under the 2021 Employment Inducement Incentive Award Plan, aimed at attracting new employees [1][2]

Company Performance - Crinetics Pharmaceuticals reported a quarterly loss of $1.04 per share, which was worse than the Zacks Consensus Estimate of a loss of $0.99, and compared to a loss of $0.93 per share a year ago, indicating a decline in performance [1] - The company posted revenues of $0.36 million for the quarter ended March 2025, surpassing the Zacks Consensus Estimate by 261%, but this was a decrease from year-ago revenues of $0.64 million [2] - Over the last four quarters, Crinetics has only surpassed consensus EPS estimates once, indicating inconsistent performance [2] Stock Movement and Outlook - Crinetics Pharmaceuticals shares have declined approximately 38.6% since the beginning of the year, significantly underperforming the S&P 500, which declined by only 4.3% [3] - The company's earnings outlook is uncertain, with current consensus EPS estimates for the upcoming quarter at -$1.10 on revenues of $2.6 million, and for the current fiscal year at -$4.33 on revenues of $5.63 million [7] Industry Context - The Medical - Drugs industry, to which Crinetics belongs, is currently ranked in the top 26% of over 250 Zacks industries, suggesting a relatively strong industry performance [8] - The performance of Crinetics may be influenced by the overall outlook for the industry, as empirical research indicates that the top 50% of Zacks-ranked industries outperform the bottom 50% by more than 2 to 1 [8]

Financial Data and Key Metrics Changes - The company recognized $400,000 in revenue during Q1 2025, down from $600,000 in Q1 2024, with revenue being non-cash based on amortization of payments from a licensing arrangement [40] - Research and development (R&D) expenses increased by 43% to $76.2 million in Q1 2025 compared to the same period in 2024, primarily due to additional personnel and higher manufacturing costs [40] - Selling, general, and administrative (SG&A) expenses rose by 71% to $35.5 million in Q1 2025, driven by growth to support ongoing programs and the planned commercial launch of paltusotine [41] - Cash used in operations for Q1 2025 was $88.5 million, compared to $52.9 million in Q1 2024, with expectations of cash used in operations for 2025 between $340 million and $380 million [42] - The company ended Q1 2025 with approximately $1.3 billion in cash, cash equivalents, and investments, expected to fund operations into 2029 [42] Business Line Data and Key Metrics Changes - The company is focused on the anticipated commercial launch of paltusotine, which is expected to significantly improve treatment for patients with acromegaly [8][10] - The pipeline includes two late-stage candidates and three additional candidates in preclinical studies, indicating a robust development strategy [8] Market Data and Key Metrics Changes - The company is preparing for the launch of paltusotine in the U.S. and has engaged with payers, receiving positive feedback regarding the product's value proposition [18][23] - The anticipated launch strategy includes educating healthcare professionals and patients, with a focus on addressing the unmet needs in acromegaly treatment [12][16] Company Strategy and Development Direction - The company aims to become a fully integrated global commercial organization, with a strong commitment to patient care and scientific innovation [8] - The strategic focus includes advancing a robust pipeline while preparing for the commercial launch of paltusotine, which is seen as a pivotal milestone [10][24] - The company is also exploring opportunities in the CAH (congenital adrenal hyperplasia) market with the development of adomelna [34] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the regulatory engagement with the FDA and the progress of clinical development activities [10][24] - The company remains optimistic about the potential uptake of paltusotine during the early launch phase, anticipating major interest from healthcare providers and patients [23] Other Important Information - The company has welcomed a new CFO, Toby Schulke, who brings extensive experience in transitioning R&D-focused companies into commercial organizations [9] - The company has launched the Kineticare patient support service platform to assist patients throughout their treatment journey [16][17] Q&A Session Summary Question: Can you discuss the powering of your primary endpoint and any data from cohort four? - Management indicated that the study is highly powered to detect significant differences between treatment and placebo groups, and cohort four is currently enrolling with no data available yet [46][48] Question: Is the CALM CAH study design approved by the FDA for registration? - The protocol was developed with input from the FDA, and the company expects to discuss the indication statement based on the data collected [51][54] Question: What is the rationale for testing the primary endpoint at a single time point? - Management explained that responder analyses are typically conducted at single points in time due to variability in biochemical markers, and they are confident in achieving the endpoint [57][58] Question: What is the rationale for morning versus evening dosing in cohort four? - The company aims to explore the convenience of morning dosing while considering the diurnal rhythm of CAH patients [61][62] Question: How is the launch strategy different in Europe compared to the U.S.? - The European markets are more concentrated in terms of patient populations, and the company is preparing for a launch in Germany while considering Brazil for expansion [64][68]