Financial Data and Key Metrics Changes - The company recognized $1 million in revenue from licensing and supply agreements with its Japanese partner SKK for the second quarter [33] - Research and development expenses increased to $80.3 million in Q2 from $76.2 million in Q1, reflecting continued investment in clinical programs [33] - Selling, general and administrative expenses rose to $49.8 million in Q2 from $35.5 million in Q1, primarily due to investments in commercial capabilities [33] - The company ended the quarter with $1.2 billion in cash, cash equivalents, and investments [34] - The high end of the guidance for net cash used in operations in 2025 was lowered to $370 million from $380 million, reflecting greater precision on clinical timelines [35] Business Line Data and Key Metrics Changes - The company is preparing for the launch of Palsonify, its treatment for acromegaly, with a strong focus on building a commercial team and engaging with healthcare professionals [13][16] - Market research indicates that healthcare professionals view Palsonify as the preferred therapy among newly diagnosed patients due to its rapid reduction of IGF-1 levels [17] - There are approximately 500 newly diagnosed patients per year who are candidates for pharmaceutical therapy, and 11,000 currently diagnosed patients with high unmet needs [17] Market Data and Key Metrics Changes - The company is actively engaging with the patient community and healthcare professionals to shape its commercial strategy for Palsonify [8][20] - There is a significant opportunity to activate patients who have discontinued therapy or are dissatisfied with current treatment options, as nearly 80% of patients on injectable SRLs did not persist with treatment [19] - The company believes there are at least 17,000 undiagnosed patients who could benefit from treatment [20] Company Strategy and Development Direction - The company aims to transform the lives of patients with acromegaly through the anticipated launch of Palsonify and is focused on expanding the market by bringing in previously untreated patients [20] - The company is also advancing multiple pivotal programs, including trials for carcinoid syndrome and congenital adrenal hyperplasia [10][27] - The commercial strategy includes a disease state education campaign and patient support hub to increase awareness and empower patients [20][21] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the NDA review process for paltusotine, anticipating approval in September [6][25] - The company is optimistic about the potential of Palsonify to become the preferred treatment for the acromegaly community, supported by positive feedback from healthcare professionals [22] - Management acknowledged that patient engagement and education will be crucial for driving adoption post-launch [20][105] Other Important Information - The company is preparing for a potential launch in Europe in 2026 and is actively working with payers to ensure access pathways for Palsonify [23][22] - The company has made significant progress in its clinical pipeline, including ongoing studies for adamelin in congenital adrenal hyperplasia [29][30] Q&A Session Summary Question: How does the launch of Neurocrine's product affect enrollment for Phase III studies? - Management believes the launch raises awareness of the unmet need and positively impacts enrollment, particularly as most enrollment occurs outside the U.S. [40][42] Question: What is the timeline for IND submissions for TSH and SST3 agonists? - The company is targeting the end of the year for IND submissions for both molecules [46][47] Question: What is the comfort level with current consensus numbers for the paltusotine launch? - Management refrained from commenting on consensus numbers but expressed confidence in launch preparations [50][52] Question: What are the expectations around placebo response in the global CAH Phase III study? - Management does not expect a high placebo response rate and believes the trial is well-powered [55][56] Question: Will pricing for Palsonify be discussed at the time of approval? - Management indicated that pricing discussions will occur at the appropriate time post-approval, emphasizing the positive reception of the value proposition by payers [59][62] Question: How many patients are currently in the open-label extension for Palsonify? - Management noted that the open-label extension is ongoing in multiple countries, and decisions regarding patient transitions to commercial treatment will depend on regulatory outcomes [69][74] Question: What are the potential endpoints for Cushing's disease trials? - The primary endpoint will be normalization of 24-hour urine free cortisol excretion, with rapid normalization observed in initial trials [99][100] Question: How does the company plan to manage the progression towards NDA submission for atomelanit? - The company plans to treat each study as a distinct submission and will not hold one until the other is completed [121][123] Question: Is there a market for surgically naive patients for paltusotine? - While there is an unmet need, the company is not actively considering that segment at this time [127]

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]