Core Insights - Alumis Inc. is advancing its pipeline with key milestones expected in early 2026, including topline Phase 3 ONWARD data for envudeucitinib in moderate-to-severe plaque psoriasis and Phase 2b LUMUS data in systemic lupus erythematosus [2][4] Financial Results - For the quarter ended September 30, 2025, Alumis reported total revenue of $2.1 million, primarily from collaboration revenue, compared to no revenue in the same quarter of 2024 [10][12] - Research and development expenses increased to $97.8 million from $87.8 million year-over-year, driven by higher clinical trial costs and severance expenses related to the merger with ACELYRIN [10][12] - General and administrative expenses rose to $19.5 million from $10.6 million year-over-year, attributed to severance costs and increased personnel-related expenses [10][12] - The net loss for the quarter was $110.8 million, compared to a net loss of $93.1 million in the same quarter of 2024 [10][12] Cash Position - As of September 30, 2025, Alumis had cash, cash equivalents, and marketable securities totaling $377.7 million, which is expected to support its pipeline advancement through 2027 [7][10] Pipeline Developments - Envudeucitinib is a next-generation oral TYK2 inhibitor showing promise in treating immune-mediated diseases, with positive results from Phase 2 trials published in the Journal of the American Academy of Dermatology [5][8] - A-005, another TYK2 inhibitor, is set to enter a Phase 2 clinical trial for multiple sclerosis in the first half of 2026 [5][4] - Lonigutamab, an anti-IGF-1R therapy for thyroid eye disease, is also progressing with positive early results [5][4]

Summary of Alumis Conference Call Company Overview - **Company**: Alumis (NasdaqGS:ALMS) - **Focus**: Development of TYK2 inhibitors for autoimmune diseases, specifically psoriasis and lupus [2][4] Key Points Product Pipeline - **Envudeucitinib**: - Phase 3 trial for psoriasis nearing completion, with data readout expected in Q1 2026 [4] - Phase 2b trial for systemic lupus erythematosus (SLE) planned for Q3 2026 [4] - **Second TYK2 Inhibitor**: - A brain-penetrant TYK2 inhibitor entering Phase 2 for multiple sclerosis (MS) in H1 2026 [3] - **Lonigutamab**: - Acquired through merger with Acelyrin, currently in Phase 2 [3] Market Opportunity - **Psoriasis**: - Significant unmet need for high-efficacy oral drugs; over 75% of patients prefer oral medications over injectables [5][6] - Current leading drugs are Otesla and methotrexate, indicating a gap for better-tolerated options [6] - **Lupus**: - No approved oral therapies currently available; potential for Envudeucitinib to fill this gap [14] - Anifrolumab, a competitor, is projected to reach $1 billion in sales, highlighting market potential [14] Clinical Data and Efficacy - **Psoriasis Data**: - Phase 2 results show PASI 75 efficacy between 80-90%, PASI 90 between 60-70%, and PASI 100 between 35-45% [11] - Strong impact on itch reduction, with over 70% of patients experiencing significant improvement [12] - **Safety Profile**: - Data from over 2,000 patients shows no significant safety signals, critical for market acceptance [7] Competitive Landscape - **TYK2 Inhibitors**: - Conviction that TYK2 can be effective across various immune indications based on early data [4][20] - Comparison with other TYK2 inhibitors indicates a more favorable PK/PD profile for Envudeucitinib [21][23] - **Market Positioning**: - Emphasis on the simplicity of oral administration as a competitive advantage [9][30] Strategic Considerations - **Partnership Strategy**: - Plans to partner Envudeucitinib to maximize asset value, with flexibility to wait for additional data before finalizing partnerships [32][33] - **Cash Position**: - Over $480 million in cash, providing runway into 2027 to support ongoing trials [37] Future Outlook - **2026 Expectations**: - Anticipation of multiple transformational events, including data readouts for psoriasis and lupus [4][18] - **Long-term Vision**: - Continued development of A-005 and Lonigutamab as part of Alumis's future pipeline [34] Additional Insights - **Genomic Data**: - Strong correlation between TYK2 inhibition and autoimmune disease prevention, suggesting a robust scientific foundation for the drug's efficacy [10][20] - **Enrollment Success**: - Rapid enrollment in lupus trials, indicating strong investigator interest and confidence in the drug's profile [30][31]

Summary of Alumis Conference Call Company Overview - **Company**: Alumis - **Lead Asset**: Envutuzitinib, a TYK2 inhibitor - **Age**: Approximately 4.5 years old, approaching 5 years Key Points and Arguments Product Development and Pipeline - **Envutuzitinib** is the lead molecule targeting autoimmune diseases, particularly psoriasis and lupus [2][3] - The company has three clinical assets, all beyond phase one, with the lead indication being psoriasis [3] - **Psoriasis Program**: Expected data readout in early Q1 next year, with confidence in competitive positioning based on preclinical and phase two data [3][4] - **Lupus Program**: Phase 2b trial designed as a pivotal trial, with data expected in Q3 next year [4] Competitive Landscape - Anticipation of multiple readouts in the TYK2 space from competitors next year [6] - The company plans to partner Envutuzitinib, which could influence overall business strategy [6] Clinical Trial Insights - **Phase Two Data**: Envutuzitinib showed a clear dose response, with the ability to dose-increase without reduction, distinguishing it from competitors [9][10] - **Enrollment Success**: Rapid enrollment attributed to the simplicity and safety of the drug, leading to over-enrollment in trials [12][13] - **Demographics**: Phase two primarily involved U.S. and Canadian patients, with expectations for more diverse demographics in phase three [15][16] Market Expectations - Aiming for PASI 90 response rates between 60-70% in phase three, which would position the product competitively [23][24] - Potential NDA filing could occur next year, pending data collection on durability and maintenance [25] Lupus Opportunity - The LUMA study involves over 400 patients, with data expected in Q3 next year [29] - The primary endpoint is BICLA, with secondary endpoints including SRI-4 [31] Future Indications - If lupus trial is successful, it may open opportunities in other interferon-driven diseases [35] - Interest in exploring indications for inflammatory bowel disease (IBD) based on competitor trials [35] Other Assets - **A-005**: A brain-penetrant molecule, with phase one completed and plans to start phase two in MS in the first half of next year [36][37] - **Lonigutamab**: Under evaluation for potential development, with ongoing assessments of competitive landscape [40] Financial Health - The company reported a strong balance sheet with over $480 million at the end of Q2, providing a cash runway into 2027 [41]

Core Insights - Alumis Inc. is a late-stage biopharma company focused on developing next-generation targeted therapies for immune-mediated diseases [2] - The company is leveraging a proprietary data analytics platform to create a pipeline of oral tyrosine kinase 2 inhibitors and other therapies [2] Company Overview - Alumis is developing envudeucitinib (formerly ESK-001) for systemic immune-mediated disorders, including moderate-to-severe plaque psoriasis and systemic lupus erythematosus [2] - The pipeline also includes A-005 for neuroinflammatory and neurodegenerative diseases, and lonigutamab for thyroid eye disease [2] - Several preclinical programs are being identified through a precision approach [2] Upcoming Events - Alumis will participate in the Guggenheim's 2nd Annual Healthcare Innovation Conference from November 10-12, 2025, with a fireside chat scheduled for November 11, 2025, at 1:30 pm ET [4] - The company will also present at the Stifel 2025 Healthcare Conference from November 11-13, 2025, on November 12, 2025, at 2:00 pm ET [4]

Market Overview - U.S. stock futures are higher, with Dow futures gaining approximately 0.2% on Monday [1] Company-Specific Movements - Olema Pharmaceuticals Inc (NASDAQ:OLMA) shares fell 18.3% to $7.64 in pre-market trading following the announcement of new data from the Phase 1b/2 trial of palazestrant plus ribociclib in ER+/HER2- metastatic breast cancer at ESMO 2025 [1] - Concord Medical Services Hldgs Ltd (NYSE:CCM) experienced a decline of 24.4% to $4.15 in pre-market trading after a 6% drop on Friday [3] - Addex Therapeutics Ltd – ADR (NASDAQ:ADXN) dipped 15.6% to $9.23 in pre-market trading after a significant gain of 28% on Friday [3] - Exelixis Inc (NASDAQ:EXEL) shares fell 8.3% to $36.00 after announcing detailed results from the Phase 3 STELLAR-303 pivotal trial evaluating zanzalintinib in combination with an immune checkpoint inhibitor in metastatic colorectal cancer, presented at ESMO 2025 and published in The Lancet [3] - Cellectis SA (NASDAQ:CLLS) shares declined 7.3% to $3.69 in pre-market trading [3] - Alumis Inc (NASDAQ:ALMS) saw a decline of 6.7% to $4.19 in pre-market trading [3] - Nanobiotix SA – ADR (NASDAQ:NBTX) fell 6.3% to $23.98 in pre-market trading after a 4% decline on Friday [3] - Genmab A/S – ADR (NASDAQ:GMAB) declined 4.1% to $31.81 in pre-market trading, with Rinatabart Sesutecan achieving a 50% objective response rate and two complete responses in advanced endometrial cancer [3] - Taysha Gene Therapies Inc (NASDAQ:TSHA) fell 4% to $4.53 in pre-market trading [3]

Company Overview - Alumis is a precision immunology company that has been operational for approximately four years, focusing on a lead asset, a TYK2 inhibitor [2] - The lead asset, envudeucitinib, is being studied for psoriasis and lupus, with three clinical molecules and a research pipeline in development [2] Clinical Trials - The readout for psoriasis is expected in early Q1 of next year, with results from two Phase III trials, each involving around 850 patients [3] - The trials will assess both a 16-week endpoint against placebo and active drug, and a 24-week endpoint against active drug, positioning the company competitively in the market [3] - The readout for lupus is scheduled for the third quarter of next year, with the company currently in a Phase IIb trial for this indication [4]

Summary of Alumis Conference Call - September 16, 2025 Company Overview - Alumis is a precision immunology company focused on developing TYK2 inhibitors, with its lead asset being ESK-001, aimed at treating psoriasis and lupus [2][4] Key Clinical Developments - ESK-001 is currently in phase 3 trials for psoriasis, with readouts expected in early Q1 next year, involving approximately 850 patients per trial [2][3] - A pivotal phase 2b trial for lupus is ongoing, with results anticipated in Q3 next year [3] - A-005, another TYK2 inhibitor, is set to enter phase 2 trials for multiple sclerosis (MS) [3] - The merger with Acceleron has provided sufficient cash to support clinical trials through 2027 [4] Mechanism and Market Potential - The TYK2 class is considered a potential multi-blockbuster class, akin to the JAK class, with evidence suggesting strong therapeutic effects against autoimmune diseases [5][6] - Genetic studies indicate that effective inhibition of TYK2 is crucial for therapeutic success, with specific mutations showing protective effects against autoimmune diseases [6][7] - The initial negative perceptions of the TYK2 class stem from early molecules that did not meet efficacy expectations, but recent data from multiple molecules, including ESK-001, show promising results [9][10] Competitive Landscape - ESK-001 is differentiated from other next-generation TYK2 inhibitors due to its favorable safety profile, allowing for higher dosing without the need for dose reductions [11][12] - The upcoming phase 3 data from Takeda's NIMUS molecule will be critical for Alumis, as it may set a new standard for efficacy and safety in psoriasis treatments [13][14] - The IL-23 receptor antagonist ixekizumab is viewed as a competitive molecule, but concerns about patient compliance with its administration may impact its market performance [15][17] Phase 3 Trial Design - The phase 3 trial design includes a 16-week primary endpoint against placebo and active control, with long-term extension for durability data [19][20] - Competitive efficacy benchmarks are set at 50%-60% at 16 weeks and 80% for PASI 75 at 24 weeks [19] Market Strategy - Alumis is considering its options for launching ESK-001, with a preference for partnership but also preparing for a potential independent launch [21][23] - The company is actively preparing for the launch, regardless of whether a partner is secured [23] Future Opportunities - The focus on systemic lupus erythematosus (SLE) is driven by the strong role of the interferon pathway, with existing data supporting TYK2's efficacy in this area [24][25] - There is potential for exploring indications in inflammatory bowel disease (IBD) and other interferon-driven diseases, although the exact dosing requirements remain a question [26][27][28] Lonigutamab and Other Programs - Lonigutamab, a new asset for thyroid eye disease, is being evaluated for its unique mechanism and market potential, although its development path is still under consideration [31][32] - The IRF5 program is in early stages, with further details to be disclosed in the future [36][37] Financial Position - The merger with Acceleron has extended Alumis's cash runway into 2027, allowing for continued investment in clinical trials and development programs [4][31]

Summary of Alumis FY Conference Call - September 08, 2025 Company Overview - Alumis is a precision immunology company based in the Bay Area, established four years ago, with a focus on TIK2 inhibitors [3][4] - The lead asset, Envuducitinib (ESK-021), is in Phase 3 for psoriasis and Phase 2 for lupus, with readouts expected in early Q1 2026 and Q3 2026, respectively [3][4][16] Pipeline and Strategic Priorities - The company has four key assets, including a second TIK2 inhibitor that is brain-penetrant and shows a 1:1 ratio between blood and brain [3][4] - A preclinical asset, lenaludomab, is expected to enter the clinic soon, with Phase 1 data anticipated next year [4][5] - The company emphasizes genomic analysis and has identified biomarkers related to TIK2, which may help predict responses in lupus and CNS indications [4][5] TIK2 Inhibition and Clinical Insights - TIK2 is considered a promising target due to its genomic richness and specific mutations that may downregulate its kinase function, potentially leading to safer drugs [7][8] - The protective effect of the P1104A mutation against autoimmune diseases is highlighted, with a 50% average protective rate in lupus and psoriasis [8][9] - The company aims to achieve maximum inhibition of TIK2 without significant side effects, which has been a differentiating factor in their clinical trials [10][24] Competitive Landscape - The oral drug market for psoriasis is growing, with oral drugs currently holding a higher patient share than injectables, despite the latter's higher dollar share [14][15] - Alumis aims to develop a high-efficacy oral drug, with Phase 2 data showing promising results that could change treatment paradigms [15][16] - The company is aware of competitors like Sotyktu and Johnson & Johnson's oral IL-23, and believes that their drug's efficacy and safety profile will differentiate it in the market [27][28] Upcoming Trials and Data Expectations - The Phase 3 trial for psoriasis (Onward) is designed with a placebo-controlled portion and an active control section, with data expected in early Q1 2026 [17][18] - The primary endpoint for the trial is PASI 75, with expectations to exceed 50-60% efficacy at week 16 [20][21] - The company is also preparing for a Phase 2 trial for their CNS-penetrant TIK2 inhibitor, which has been delayed to the first half of 2026 due to resource allocation [56][58] Financial Position and Strategic Partnerships - Alumis ended Q2 2025 with $486 million in cash, projecting a runway into 2027, allowing them to navigate key inflection points [53][55] - The company is considering strategic partnerships for global launches, with a focus on maximizing asset value [37][38] Future Opportunities - High conviction in lupus treatment due to successful trials with interferon inhibition, and ongoing analysis to minimize placebo effects in trials [49][50] - Interest in IBD as a potential indication for TIK2, with ongoing research into the genomic data supporting this [52] - Plans to introduce a new molecule targeting a different mechanism, with Phase 1 expected next year [61][62] Conclusion - Alumis is positioned to make significant advancements in the immunology space with its TIK2 inhibitors, focusing on both efficacy and safety, while navigating a competitive landscape and preparing for upcoming clinical data releases. The strategic financial position allows for flexibility in partnerships and future developments.

Financial Data and Key Metrics Changes - The company ended the second quarter with $486 million in cash and cash equivalents, providing a runway into 2027 [53] Business Line Data and Key Metrics Changes - The company is focused on Tyk2 inhibitors, with two lead molecules in development: a Phase 3 readout in psoriasis expected in early Q1 next year and a Phase 2b readout in systemic lupus erythematosus (SLE) anticipated in Q3 next year [4][5] Market Data and Key Metrics Changes - The company aims to position its oral Tyk2 inhibitors as a first-line treatment for lupus, targeting patients who currently receive methotrexate or steroids [34] Company Strategy and Development Direction - The company is preparing for commercialization but is considering partnerships for global commercialization due to the potential of the molecule [17] - The strategy includes a robust trial design for lupus, potentially allowing the Phase 2b trial to serve as a pivotal trial, which could streamline the path to registration [27][29] Management's Comments on Operating Environment and Future Outlook - Management believes that the Tyk2 target has significant potential, despite previous disappointments with other molecules in the space, emphasizing the need for maximum target inhibition to achieve efficacy [54][55] - The unmet need in lupus is significant, and the company is optimistic about the potential of its oral therapies to provide safe and effective treatment options [20][26] Other Important Information - The company has a research organization in place to support its pipeline development, including the recently acquired lonigutamab, which is being evaluated for its safety profile [48] - The company is also exploring the potential of its Tyk2 inhibitors in other interferon-driven diseases, which could expand its market opportunities [36] Q&A Session Summary Question: What are the next steps for commercialization? - The company is preparing for commercialization but is unlikely to do so independently on a global scale, considering partnerships based on the data from psoriasis and lupus trials [17] Question: What are the expectations for the lupus trial? - Management believes that achieving a placebo-adjusted benefit of 8% to 15% would position the oral therapy favorably in the market [25] Question: How does the company view the competitive landscape? - The company believes its oral Tyk2 inhibitor has advantages in safety and convenience compared to other therapies, which could make it competitive in the market [16] Question: What is the market opportunity for Tyk2 in lupus? - The company sees the Tyk2 inhibitor as likely being used as a first-line treatment due to its favorable safety profile and ease of administration [34] Question: How does the company plan to address the challenges in lupus trials? - The company has implemented measures to ensure that only patients with active disease are enrolled and has controlled for co-medications to minimize placebo effects [22][24] Question: What is the funding strategy moving forward? - The company aims to maintain sufficient cash reserves to support strategic decisions based on the outcomes of the psoriasis and lupus trials [52]

Summary of Alumis Inc. Conference Call Company Overview - **Company**: Alumis Inc. (Ticker: ALMS) - **Industry**: Precision Immunology - **Key Products**: Focus on TIK2 inhibitors for autoimmune diseases, specifically psoriasis and lupus Core Points and Arguments 1. **Clinical Assets**: Alumis has three clinical assets, with a strong research organization. Currently in Phase 3 for psoriasis and Phase 2b for lupus, with read-outs expected in early Q1 and Q3 of next year respectively [2][3] 2. **TIK2 Target**: TIK2 was selected as a target due to its significant role in autoimmune diseases, with 5% of the population having mutations that provide protection against such diseases [4][5] 3. **Efficacy of Envu**: The company's TIK2 inhibitor, now called Envutucitinib (Envu), has shown a clean safety profile and high efficacy, with PASI-75 scores being the highest seen with an oral drug [8][10] 4. **Market Positioning**: The company believes that the oral drug market is underutilized, with less than 10% of diagnosed psoriasis patients on biologics. There is a strong preference for oral treatments among patients [18][19] 5. **Phase 3 Data Benchmarking**: The company is focused on long-term efficacy data (24-week and 52-week) rather than short-term results, which are more relevant for dermatologists [10][11] 6. **Lupus Opportunity**: The Phase 2b trial for lupus is pivotal, with the potential for only one Phase 3 trial if successful. The genetic evidence supports TIK2's role in lupus treatment [30][32] 7. **Trial Design**: The lupus trial includes 408 patients with strict entry criteria to minimize placebo effects, focusing on active SLE patients [35][36] 8. **Market Expansion**: There is potential to expand the systemic treatment market with better-tolerated oral drugs, targeting patients who may currently be on topical therapies [21][22] 9. **Launch Strategy**: Alumis plans to learn from competitors' launches, focusing on drug positioning, pricing, and effective communication of benefits [22][23] 10. **Cash Position**: As of the end of Q2, Alumis had $486 million in cash, expected to last into 2027, with anticipated spikes in R&D spending due to Phase 3 trial enrollment [46] Additional Important Content - **BMI Considerations**: The company acknowledges that BMI can influence drug efficacy and is a factor in cross-trial comparisons [15][16] - **Formulation Development**: Multiple formulations of Envu are being developed, with plans for a once-daily dosing regimen [28] - **Collaboration Potential**: Alumis is unlikely to launch Envu globally on its own and is considering partnerships for market entry [26][27] - **Future Indications**: The company is exploring the potential of TIK2 inhibitors in other diseases driven by interferon pathways, such as Sjogren's syndrome [33] This summary encapsulates the key points discussed during the conference call, highlighting Alumis Inc.'s strategic focus, clinical developments, and market opportunities in the precision immunology sector.