Financial Data and Key Metrics Changes - In Q1 2025, total revenues reached $3.03 billion with non-GAAP diluted earnings per share at $8.22, reflecting strong financial performance [40]. Business Line Data and Key Metrics Changes - DUPIXENT's net product sales grew 20% globally on a constant currency basis compared to Q1 2024, with a 19% increase in the US, indicating strong demand across all approved indications [40][41]. - EYLEA faced challenges due to new competition, but enhancements are expected to strengthen its market position [41]. - Libtayo grew 21% in the US compared to the previous year, establishing itself as a cornerstone therapy in oncology [42]. Market Data and Key Metrics Changes - The branded anti-VEGF category contracted in Q1 2025, presenting challenges for EYLEA, while Libtayo is gaining market share in advanced non-small cell lung cancer [41][42]. Company Strategy and Development Direction - The company focuses on scientific innovation, investing over 30% of revenues into R&D, which is significantly above the industry average [31]. - Regeneron aims to expand its manufacturing capacity with a $3 billion investment in North Carolina and a $3.6 billion expansion in New York [48][49]. Management's Comments on Operating Environment and Future Outlook - The management acknowledges headwinds in the industry but emphasizes resilience and the importance of advocacy for fair pricing and patient access [33][34]. - The company is optimistic about its pipeline, with approximately 45 candidates in development, and believes in the potential of its existing products to drive future growth [39][43]. Other Important Information - Regeneron has secured regulatory approval for 14 homegrown medicines and has built a robust clinical pipeline [39]. - The company emphasizes the importance of protecting innovations through patents and ensuring that developed nations contribute fairly to the costs of innovative treatments [36][37]. Q&A Session Summary Question: What will happen with the drug last week that failed to meet its primary endpoint in the study? Will you conduct a new drug trial? - The drug candidate ipilimumab showed promising data initially, but efficacy waned during the trial. The company is analyzing the data and considering future steps based on findings [54][56][58]. - The management remains optimistic about the therapeutic candidate's potential and is in discussions with regulators regarding the next steps [59].

Industry Overview - The global cancer treatment market is rapidly transforming due to increasing demand for more effective and less toxic therapies, with the U.S. expected to see 2,041,910 new cancer cases and 618,120 cancer-related deaths in 2025 [2] - Advances in early detection and treatment have led to a decline in mortality rates for certain cancers, but the overall rise in cancer incidence is driving higher spending on oncology care globally [2][4] - Innovative treatment approaches such as immunotherapy, targeted therapies, and personalized cancer vaccines are reshaping the oncology landscape [3] Market Dynamics - The rise in cancer prevalence is attributed to aging populations, lifestyle factors, and improved diagnostics, positioning the market for novel oncology drugs and diagnostics for robust growth [4] - Major pharmaceutical companies like Novartis, AstraZeneca, Pfizer, AbbVie, Bristol Myers, and Eli Lilly are actively developing next-generation cancer therapies, including antibody-drug conjugates and immuno-oncology agents [5] - Smaller biotech firms are also making significant advancements in cancer research, leading to increased interest from larger drugmakers in acquiring these companies for their innovative therapies [5] Company Highlights - Pfizer's oncology revenues grew 7% on an operational basis in Q1 2025, driven by drugs like Xtandi, Lorbrena, and Padcev, and it has advanced its oncology clinical pipeline with several candidates entering late-stage development [8][9] - Novartis reported a 24% increase in oncology sales to $3.9 billion in Q1 2025, with significant contributions from drugs like Kisqali and Pluvicto, and is investing in research for both common and rare cancers [11] - Fate Therapeutics is focused on developing universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell platform, with ongoing clinical studies for its CAR T-cell product candidate [12][13][14]

Pipeline and Technology - Zymeworks has a differentiated pipeline of multifunctional therapeutics targeting solid tumor oncology and autoimmune & inflammatory diseases [8] - The company's ADC technologies combine antibodies with potent payloads for targeted delivery [7] - MSAT technology enhances therapy precision and efficacy, targeting complex disease mechanisms [7] - Zymeworks is advancing next-generation T cell engagers to overcome biological challenges [35] Zanidatamab and Partnerships - Zanidatamab has a potential peak sales of over $2 billion [22] - Zymeworks has a licensing agreement with Jazz Pharmaceuticals, eligible for up to $500 million in regulatory milestones and $862.5 million in commercial milestones [25] - Zymeworks has a licensing agreement with BeiGene, eligible for up to $164 million in development and commercial milestones [25] - Royalties from Jazz are tiered between 10-20%, and from BeiGene, from the high single digits to 19.5% [25] Financials and Milestones - Zymeworks has approximately $321.6 million in cash resources [7] - The company anticipates potential regulatory decisions in the EU and China for zanidatamab in 2L BTC in 2025 [167] - Zymeworks expects an IND submission for ZW251 (GPC3) by mid-2025 [167]

Industry Overview - The cancer market is experiencing significant growth due to rising demand for targeted and less toxic cancer medicines, with new cancer cases in the U.S. expected to exceed 2 million for the first time in 2024, leading to increased global spending on cancer treatments [1][3] - Innovative cancer treatments such as immunotherapy, targeted therapies, and personalized vaccines are emerging, utilizing the body's immune system and focusing on specific genetic mutations to provide more effective and less harmful alternatives to traditional chemotherapy [2][3] Company Developments - Major pharmaceutical companies like Novartis, AstraZeneca, Pfizer, AbbVie, and Eli Lilly are actively developing new cancer therapies, including antibody-drug conjugates and immune-oncology agents, while smaller biotech firms are also making significant advancements [4] - Verastem Oncology is seeking FDA approval for its combination regimen of avutometinib and defactinib for treating KRAS mutant recurrent low-grade serous ovarian cancer, with a decision expected by June 30, 2025 [6][7] - Relay Therapeutics has reported positive interim data for its RLY-2608 breast cancer program, leading to plans for a pivotal study in mid-2025 [9][10] - Pyxis Oncology is focused on developing next-generation therapeutics, with its lead candidate showing significant tumor regression in patients with recurrent and metastatic head and neck squamous cell carcinoma, and has received Fast Track Designation from the FDA [12][13][14]

Core Insights - Revolution Medicines, Inc. is a late-stage clinical oncology company focused on developing targeted therapies for RAS-addicted cancers [2] - The company is participating in two upcoming investor conferences, indicating active engagement with the investment community [1][3] Company Overview - Revolution Medicines specializes in RAS(ON) inhibitors aimed at suppressing various oncogenic variants of RAS proteins [2] - The current R&D pipeline includes daraxonrasib (RMC-6236), elironrasib (RMC-6291), and zoldonrasib (RMC-9805), all of which are in clinical development [2] - The company plans to advance RMC-5127, a RAS(ON) G12V-selective inhibitor, into clinical development next [2] - Additional pipeline opportunities include RMC-0708 (Q61H) and RMC-8839 (G13C), focusing on RAS(ON) mutant-selective inhibitors [2] Upcoming Events - The company will participate in the Needham 24 Annual Virtual Healthcare Conference on April 7 at 2:15 p.m. ET [3] - Additionally, Revolution Medicines will be part of the Stifel 2025 Virtual Targeted Oncology Forum on April 9 at 1:00 p.m. ET [3]

Summary of Perspective Therapeutics Conference Call Company Overview - **Company**: Perspective Therapeutics (CATX) - **Event**: Conference Call discussing VMT Alphanet clinical data at the 2025 ASCO GI Symposium - **Date**: January 24, 2025 Key Points Industry and Company Focus - Perspective Therapeutics is focused on developing next-generation targeted therapies, particularly in oncology, with a broad pipeline of radiopharmaceuticals aimed at treating various tumors [6][11] - The company emphasizes the potential of its platform technology to disrupt current treatment paradigms in oncology [6] Clinical Programs and Pipeline - The **VMT Alphanet program** has received fast track designation from the FDA based on strong preclinical results [15] - The program is currently in human clinical trials for neuroendocrine tumors, with ongoing dose-finding studies [15][19] - The **VMTA-one program** is in human clinical trials for melanoma, with both combination and monotherapy arms [10][11] - A **FAP targeted agent** is expected to initiate human clinical trials by mid-2025 [11] Clinical Data and Efficacy - Initial results from the VMT Alphanet program show promising safety profiles, with no dose-limiting toxicities observed in early cohorts [21][34] - Among the first nine patients, there were no serious adverse events, and renal function remained stable [21][23] - Tumor response data indicate significant reductions in tumor size, with one patient showing a 57% reduction [24][25] - The nature of neuroendocrine tumors may lead to delayed responses, with some patients showing continued tumor shrinkage after treatment [30][60] Safety and Tolerability - The safety profile of VMT Alphanet appears favorable compared to existing treatments, with no significant adverse events reported [34][80] - The company is exploring higher dose levels based on the encouraging safety data [33][34] Regulatory and Future Plans - The company plans to submit data to the FDA in 2024 and is considering expanding into other SSTR2 positive tumor types [33][35] - Ongoing discussions with regulators will shape the strategy for future cohorts and dosing regimens [40][46] Market Position and Competitive Landscape - Perspective Therapeutics aims to differentiate its therapies from existing agents like Lutathera by focusing on the unique properties of its radiopharmaceuticals, which may offer better safety and efficacy profiles [86] - The company is aware of other SSRT targeted programs and is positioning itself to compete effectively in the market [15] Additional Insights - The call highlighted the importance of long-term follow-up in assessing the efficacy of treatments for neuroendocrine tumors due to their slow growth rates [24][60] - The company is committed to generating high-quality data to support its clinical programs and regulatory submissions [45][68] Conclusion - Perspective Therapeutics is making significant strides in the development of targeted therapies for oncology, with promising early clinical data and a strong focus on safety and efficacy. The company is well-positioned to advance its clinical programs and explore new indications in the future.

TABLE OF CONTENTS As filed with the Securities and Exchange Commission on June 24, 2024. Registration No. 333-280068 UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 AMENDMENT NO. 2 TO FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Alumis Inc. (Exact name of registrant as specified in its charter) (State or other jurisdiction of incorporation or organization) (Primary Standard Industrial Classification Code Number) Delaware 2834 86-1771129 (I.R.S. Employer Identifica ...