First Quarter 2025 and Recent Highlights ● Updates related to merger agreement with ACELYRIN, Inc. (ACELYRIN), enabling enhanced value creation opportunities for each company's respective stockholders and positioning transaction for successful close in the second quarter of 2025 ● On May 13, 2025, Alumis stockholders voted to approve all proposals required to be approved in connection with the pending merger with ACELYRIN at its Special Meeting of Stockholders. ● In April 2025, Alumis and ACELYRIN agreed to ...

Core Insights - Alumis Inc. is experiencing strong momentum in its development programs, particularly with the ongoing clinical trials for its TYK2 inhibitor ESK-001, which is expected to yield pivotal Phase 3 data for moderate-to-severe plaque psoriasis in early 2026 [2][4] - The company is focused on the anticipated merger with ACELYRIN, which is expected to enhance its clinical pipeline and financial flexibility, creating value for both patients and stockholders [2][4] - Alumis reported a net loss of $99.0 million for Q1 2025, a significant increase from a loss of $49.8 million in Q1 2024, driven by higher research and development expenses [9][19] Recent Highlights - Alumis entered into a collaboration and licensing agreement with Kaken Pharmaceutical for ESK-001 in Japan, receiving an upfront license fee of $20 million and additional near-term co-development payments [4][9] - The merger agreement with ACELYRIN was approved by Alumis stockholders, with the combined company expected to have a pro forma cash position of approximately $737 million as of December 31, 2024, providing a runway for advancing its pipeline [4][9] - The company plans to initiate a Phase 2 clinical trial for A-005 in multiple sclerosis and finalize the clinical development plan for Lonigutamab following the merger [4][9] Financial Results - For the quarter ended March 31, 2025, Alumis reported total revenue of $17.4 million, primarily from license revenue related to the Kaken collaboration [9][19] - Research and development expenses increased to $96.6 million in Q1 2025 from $42.0 million in Q1 2024, reflecting higher costs associated with clinical trials and increased headcount [9][19] - General and administrative expenses rose to $22.3 million in Q1 2025 from $5.6 million in Q1 2024, mainly due to transaction costs related to the merger and personnel-related expenses [9][19] Anticipated Milestones - Key upcoming milestones include topline data for ESK-001 in psoriasis expected in Q1 2026 and Phase 2b data for systemic lupus erythematosus also expected in 2026 [4][9] - The merger with ACELYRIN is anticipated to close in the second quarter of 2025, which is expected to enhance value creation opportunities for stockholders [4][9]

Core Viewpoint - Alumis Inc. has received stockholder approval for its merger with ACELYRIN, INC., marking a significant step towards closing the transaction and enhancing its capabilities in developing therapies for immune-mediated diseases [1][2][3] Company Overview - Alumis Inc. is a clinical-stage biopharmaceutical company focused on developing oral therapies using a precision approach to improve clinical outcomes for patients with immune-mediated diseases [4] - The company utilizes a proprietary precision data analytics platform to build a pipeline of molecules targeting a wide range of immune-mediated diseases, both as monotherapy and combination therapies [4] - Alumis' leading product candidate, ESK-001, is an oral, selective small molecule inhibitor currently being evaluated for moderate-to-severe plaque psoriasis and systemic lupus erythematosus [4] Merger Details - The merger with ACELYRIN is anticipated to close in the second quarter of 2025, pending the fulfillment of customary closing conditions [3] - Martin Babler, President and CEO of Alumis, expressed gratitude to stockholders for their support and emphasized the goal of maximizing the value of their portfolio post-merger [2] Future Prospects - The merger is expected to provide Alumis with a strengthened financial foundation, enabling the advancement of breakthroughs in the treatment of immune-mediated diseases [2]

Core Points - ACELYRIN, INC. has adopted a limited-duration stockholder rights plan in response to Tang Capital Partners accumulating 8.8% of its outstanding common stock [1][3] - The rights plan aims to maximize stockholder value and is effective immediately, expiring on March 12, 2026 [2][4] Rights Plan Details - Each share of common stock will receive one right, which will become exercisable if any person acquires 10% or more of the company's outstanding common stock [3] - Holders of rights (excluding the acquiring person) can purchase additional shares at a price equal to twice the exercise price [3] - Current owners exceeding the Triggering Percentage can retain their shares but cannot acquire more without triggering the rights plan [3] Company Overview - ACELYRIN focuses on developing transformative medicines in immunology, with its lead program being lonigutamab, a monoclonal antibody for thyroid eye disease [5]

Core Insights - Alumis Inc. is a clinical-stage biopharmaceutical company focused on developing oral therapies for immune-mediated diseases using a precision approach to enhance clinical outcomes and patient quality of life [3] Company Overview - Alumis is leveraging a proprietary precision data analytics platform to build a pipeline of molecules aimed at treating a variety of immune-mediated diseases, either as monotherapy or in combination therapies [3] - The company's lead product candidate, ESK-001, is an oral, highly selective small molecule that acts as an allosteric inhibitor of tyrosine kinase 2 (TYK2), currently under evaluation for moderate-to-severe plaque psoriasis and systemic lupus erythematosus [3] - Additionally, Alumis is developing A-005, a CNS-penetrant allosteric TYK2 inhibitor targeting neuroinflammatory and neurodegenerative diseases [3] - The company is incubated by Foresite Labs and is led by a team experienced in small-molecule drug development for immune-mediated diseases, aiming to pioneer a precision approach to drug development [3] Upcoming Events - Martin Babler, President and CEO of Alumis, will participate in a fireside chat at Leerink's 2025 Global Healthcare Conference on March 11, 2025, at 10:40 am ET [1]

Core Viewpoint - Alumis Inc. announced positive 52-week data from the open-label extension of its Phase 2 STRIDE clinical trial for ESK-001, indicating its potential as an effective oral therapy for moderate-to-severe plaque psoriasis [1][2][3] Group 1: Clinical Trial Results - Patients receiving 40 mg of ESK-001 twice daily showed sustained clinical responses at Week 52, with PASI 90 at 61.3% compared to 52.4% at Week 12, and PASI 100 at 38.8% compared to 26.8% [2] - At Week 52, 81.3% of patients reported improved control of itch (NRS≤4) and 61.3% reported enhanced quality of life (DLQI0/1) [2] - ESK-001 was well tolerated at Week 52, with safety profiles consistent with earlier data and no new safety findings reported [2][6] Group 2: Drug Profile and Mechanism - ESK-001 is a next-generation oral TYK2 inhibitor designed to correct immune dysregulation related to proinflammatory mediators such as IL-23, IL-17, and type 1 interferon [3][4] - The drug's selective targeting aims to maximize inhibition while minimizing off-target effects, positioning it as a potential best-in-class treatment for plaque psoriasis [4][6] Group 3: Ongoing and Future Studies - The Phase 3 ONWARD clinical program is currently underway, consisting of two parallel trials (ONWARD1 and ONWARD2) with approximately 840 patients each, comparing ESK-001 to placebo and apremilast [5][7] - Topline data from the ONWARD studies is expected in the first quarter of 2026, with ongoing patient enrollment for moderate-to-severe psoriasis [4][5] Group 4: Broader Development Strategy - Alumis is also developing a once-daily modified release formulation of ESK-001 and evaluating its application in systemic lupus erythematosus through the LUMUS Phase 2b trial [8] - The company leverages a precision data analytics platform to explore ESK-001's potential in other immune-mediated conditions, aiming to build a diverse pipeline of therapeutic options [9]

Core Viewpoint - The merger between Alumis Inc. and ACELYRIN, INC. aims to create a leading clinical-stage biopharma company focused on immune-mediated diseases, enhancing long-term value for shareholders through a diversified late-stage portfolio and strong financial position [1][2][5]. Company Overview - Alumis is a clinical-stage biopharmaceutical company developing oral therapies for immune-mediated diseases, utilizing a precision data analytics platform to optimize clinical outcomes [6]. - ACELYRIN focuses on providing transformative medicines and is currently developing lonigutamab for thyroid eye disease [7]. Merger Details - The all-stock transaction is expected to close in the second quarter of 2025, pending stockholder approval and customary closing conditions [3]. - The combined company will have a pro forma cash position of approximately $737 million as of December 31, 2024, allowing for the advancement of its pipeline and operational needs into 2027 [5]. Strategic Benefits - The merger will create a diversified portfolio of late-stage clinical assets targeting large, established markets, including therapies for plaque psoriasis, systemic lupus erythematosus, and multiple sclerosis [5]. - The combined company is expected to leverage increased financial flexibility and resources to develop life-changing medicines and enhance commercial capabilities [5]. Leadership and Governance - The executive leadership teams of both companies have a proven track record in public company management and value creation, positioning the combined entity for success [5]. - The ACELYRIN Board of Directors supports the merger, believing it maximizes long-term value for its stockholders [2]. Financial Advisors - Morgan Stanley & Co. LLC is serving as financial advisor to Alumis, while Guggenheim Securities, LLC is advising ACELYRIN [4].

Summary of Conference Call on Alumis and Accelerant Merger Industry and Companies Involved - **Industry**: Biotechnology, specifically focusing on immunology and drug development - **Companies**: Alumis and Accelerant Key Points and Arguments 1. **Merger Announcement**: Alumis is merging with Accelerant, creating a differentiated late-stage portfolio with significant financial strengths [3][5] 2. **Transaction Terms**: Accelerant stockholders will receive 0.4274 shares of Alumis stock for each share they own, resulting in approximately 55% ownership for Alumis stockholders and 45% for Accelerant stockholders [4] 3. **Leadership Structure**: The current leadership team of Alumis will remain in place post-merger, and the combined company will operate under the Alumis name [4] 4. **Financial Position**: The pro forma cash position at the end of 2024 is projected to be $737 million, providing a cash runway into 2027 [17] 5. **Pipeline Overview**: Alumis focuses on precision immunology, with two clinical-stage TIK2 inhibitors, ESSCAR001 and A5, targeting immune-mediated diseases like psoriasis and lupus [6][8] 6. **Upcoming Milestones**: Top-line data readouts for ESSCAR001 in psoriasis are expected in the first half of 2026, and for the Phase IIb LUMUS trial in lupus in 2026 [7] 7. **Lonigutumab Development**: The merger adds lonigutumab, an anti-IGF-1R therapy for thyroid eye disease, to the portfolio, which has shown promising data [9][10] 8. **Market Potential**: There is significant unmet need in the thyroid eye disease market, and lonigutumab is expected to have a differentiated safety profile compared to existing therapies [58] 9. **Capital Efficiency**: Both companies emphasize a commitment to capital efficiency in their operations and development strategies [16][11] 10. **Enrollment Strategies**: Efforts are ongoing to accelerate enrollment in clinical trials, particularly for psoriasis, leveraging the combined resources of both companies [54] Other Important but Overlooked Content 1. **Forward-Looking Statements**: The call included caution regarding reliance on forward-looking statements, highlighting potential risks and uncertainties [2][3] 2. **Operational Discipline**: Alumis has a history of managing costs prudently to ensure maximum return on investment, which will continue post-merger [17] 3. **Synergies from Merger**: While immediate development synergies may not be evident, the merger is expected to reduce operational redundancies and enhance financial stability [62] 4. **Focus on Execution**: The primary focus remains on executing existing programs and understanding how to advance the development of lonigutumab efficiently [46] This summary encapsulates the critical aspects of the conference call regarding the merger between Alumis and Accelerant, highlighting the strategic, financial, and operational implications for both companies in the biotechnology sector.

Core Insights - Alumis Inc. is advancing its clinical programs, particularly focusing on ESK-001 and A-005, which target immune-mediated diseases through maximal TYK2 inhibition [1][2][4] Clinical Programs - The company is conducting three clinical programs: a global Phase 3 ONWARD trial for ESK-001 in moderate-to-severe plaque psoriasis, a Phase 2b trial for ESK-001 in systemic lupus erythematosus (SLE), and a Phase 1 study for A-005 aimed at neuroinflammatory and neurodegenerative diseases [1][4][5] - ESK-001 has shown promising results in a Phase 2 study, with 93% of patients achieving the primary endpoint of PASI 75 at the highest dose of 40 mg twice daily [4] - A-005 is designed to be a first-in-class CNS inhibitor, with Phase 1 data expected by the end of 2024 [2][5] Financial Performance - As of September 30, 2024, Alumis reported cash and cash equivalents of $361.9 million, sufficient to fund operations into 2026 [5] - Research and development expenses increased to $87.8 million for Q3 2024, up from $37.8 million in Q3 2023, primarily due to clinical milestone payments and increased trial costs [5][10] - The net loss for Q3 2024 was $93.1 million, compared to $43.4 million for the same period in 2023 [5][10] Upcoming Milestones - Key upcoming milestones include the expected Phase 1 data for A-005 by year-end 2024 and the 52-week Phase 2 OLE study data for ESK-001 anticipated in Q1 2025 [2][5] - Topline results for the Phase 3 ONWARD program in psoriasis are expected in the first half of 2026, along with topline data for the SLE Phase 2b trial [5][6] Company Overview - Alumis is a clinical-stage biopharmaceutical company focused on developing oral therapies for immune-mediated diseases using a precision approach [7] - The company's lead product candidate, ESK-001, is a selective TYK2 inhibitor, while A-005 is being developed for neuroinflammatory and neurodegenerative conditions [7]

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 ...