Alumis Inc. operates as a clinical stage biopharmaceutical company.
The company’s initial focus is on developing its two Tyrosine Kinase 2 (‘TYK2’) inhibitors: ESK-001, a second-generation inhibitor that the company is developing to maximize target inhibition and optimize tolerability, and A-005, a central nervous system (‘CNS’) penetrant molecule. ESK-001 has demonstrated significant therapeutic effect in its Phase 2 program in patients with PsO, which the company defines as moderate-to-severe...
Alumis Inc. operates as a clinical stage biopharmaceutical company.
The company’s initial focus is on developing its two Tyrosine Kinase 2 (‘TYK2’) inhibitors: ESK-001, a second-generation inhibitor that the company is developing to maximize target inhibition and optimize tolerability, and A-005, a central nervous system (‘CNS’) penetrant molecule. ESK-001 has demonstrated significant therapeutic effect in its Phase 2 program in patients with PsO, which the company defines as moderate-to-severe plaque psoriasis (‘PsO’), and is being evaluated in an additional Phase 2 clinical trial in patients with systemic lupus erythematosus (‘SLE’), for which the company expects to report results in 2026. With the favorable results in the company’s Phase 2 clinical trial in PsO, the company has initiated its Phase 3 ONWARD clinical program, which consists of two parallel Phase 3 clinical trials of ESK-001 in this indication, and for which the company expects to report topline results in the first quarter of 2026. These parallel Phase 3 clinical trials also include one long-term extension (‘LTE’) study, ONWARD3. In addition, the open-label extension (‘OLE’) of the company’s Phase 2 clinical trial in PsO remains ongoing. TYK2 genetic mutations are associated with a strong protective effect in multiple sclerosis (‘MS’), motivating the company to develop its second product candidate, A-005, as a CNS-penetrant, allosteric TYK2 inhibitor for neuroinflammatory and neurodegenerative diseases. In April 2024, the company initiated its Phase 1 program of A-005 in healthy volunteers and reported initial results in December 2024.
The company utilizes its proprietary precision data analytics platform, biological insights, and team of experienced research and development experts to deepen its understanding of disease pathologies, accelerate research and development, and increase the probability of clinical success. The company’s collective insights informed its selection of TYK2 as the target for its two lead programs. Beyond TYK2, the company’s proprietary precision data analytics platform and drug discovery expertise have led to the identification of additional preclinical programs that exemplify its precision approach.
The company recognizes that patients living with immune-mediated diseases need alternatives to currently available therapies.
The company is pioneering a precision approach that leverages insights derived from powerful data analytics to select the right target, right molecule, right indication, right patient, right endpoint, and right combination to dramatically improve patient outcomes.
Proposed Merger with ACELYRIN
On February 6, 2025, the company entered into an Agreement and Plan of Merger (the ‘Merger Agreement’) with ACELYRIN, Inc., a Delaware corporation (‘ACELYRIN’), and Arrow Merger Sub, Inc., a Delaware corporation and its direct wholly owned subsidiary (‘Merger Sub’). Under the terms of the Merger Agreement, Merger Sub will merge with and into ACELYRIN, with ACELYRIN continuing as its direct wholly owned subsidiary (the ‘Merger’). The Merger Agreement was approved by the disinterested directors on the company’s board of directors and the board of directors of ACELYRIN, and is subject to stockholder approval by the stockholders of each company, and satisfaction or waiver of other closing conditions.
Product Candidates and Pipeline
The company is building a pipeline of molecules with the potential to address a broad range of immune-mediated diseases as monotherapy or combination therapies. Within the company’s TYK2 franchise, it is developing its most advanced product candidate, ESK-001, an allosteric TYK2 inhibitor for the treatment of PsO and SLE. The company is developing its second TYK2 product candidate, A-005, as a CNS-penetrant allosteric TYK2 inhibitor, to offer the therapeutic benefit of TYK2 inhibition within the CNS for a broad range of neuroinflammatory and neurodegenerative diseases, and is pursuing MS as its initial indication.
Strategy
The company’s strategies are to maximize the opportunity presented by ESK-001’s differentiated pharmacological profile and breadth of potential indications; expand its TYK2 franchise with A-005, its allosteric TYK2 inhibitor selected to penetrate the CNS to treat neuroinflammation; discover and advance earlier-stage product candidates into clinical development; leverage its precision approach to increase speed of development, probability of success, and precision of therapy; and evaluate strategic collaborations to maximize the global impact of its product candidates.
TYK2 Franchise
ESK-001: The company’s Allosteric TYK2 Inhibitor
ESK-001 is a potent, highly selective, allosteric TYK2 inhibitor.
Development
ESK-001 is being evaluated in two parallel Phase 3 clinical trials in PsO, as well as in a Phase 2b clinical trial in SLE.
ESK-001 for the Treatment of Moderate-to-Severe Plaque Psoriasis (PsO)
ESK-001 has advanced to Phase 3 development in PsO. In March 2024, the company announced positive data from its randomized, double-blind, placebo-controlled Phase 2 clinical trial in patients with PsO (‘Phase 2 STRIDE trial’). The company’s Phase 2 STRIDE trial met its primary endpoint, the proportion of patients achieving a 75% improvement in the Psoriasis Area and Severity Index (‘PASI 75’) at week 12 compared to placebo, and key secondary efficacy endpoints at all clinically relevant doses tested. Clear dose-dependent responses were observed with maximal TYK2 inhibition achieved, and highest clinical response rates observed at the highest dose of 40 mg twice daily. ESK-001 was found to be generally well tolerated at all dose levels. Upon completion of the Phase 2 STRIDE trial, patients were eligible to be enrolled in an OLE study evaluating two ESK-001 doses (40 mg once daily and 40 mg twice daily), which the company designed to evaluate the safety and efficacy of long-term treatment with ESK-001 in patients with PsO. The OLE study remains ongoing and, at Week 40, all participants on the 40 mg once daily cohort transitioned to the 40 mg twice daily dose. In September 2024, the company announced positive 28-week data from the OLE, which showed dose-dependent sustained increases in Psoriasis Area and Severity Index (‘PASI’) endpoint responses observed over time, with the majority of patients achieving PASI 75, the primary endpoint, at the highest dose of 40 mg twice daily. ESK-001 was generally well tolerated in the OLE Week 28 data. In March 2025, the company announced positive 52-week data from the OLE, which demonstrated sustained PASI 90 and increased PASI 100 response rates in the 40 mg twice daily cohort. ESK-001 was generally well tolerated in the OLE Week 52 data.
With the favorable results in the company’s Phase 2 STRIDE trial in PsO, the company has initiated its Phase 3 ONWARD clinical program, which consists of two parallel global Phase 3, multi-center, randomized, double-blind placebo-controlled clinical trials, ONWARD1 and ONWARD2, designed to evaluate the efficacy and safety of ESK-001 in this indication. These parallel Phase 3 clinical trials also include one LTE study, ONWARD3.
ESK-001 for the Treatment of Systemic Lupus Erythematosus (SLE)
The company is conducting LUMUS, a Phase 2b, 48-week, global, placebo-controlled, double-blind, randomized, clinical trial evaluating ESK-001 in patients with moderate-to-severe active SLE, in the United States, Europe, the United Kingdom (‘UK’), Latin America, and Asia-Pacific (‘APAC’) countries. The primary endpoint in Part A of such trial is BILAG-Based Composite Lupus Assessment response (a validated composite measure of lupus disease activity) at Week 48. Eligible patients may enroll in Part B (an OLE) or participate in a four-week follow-up period.
Safety Profile of ESK-001
ESK-001 has been administered to more than 800 participants and, in some cases, administered for up to two years. ESK-001 has been generally well tolerated in the company’s Phase 2 STRIDE and OLE clinical trials to date, with the majority of AEs observed in such clinical trials having been graded mild-to-moderate in severity. As of December 31, 2024, the most common AEs reported by patients across active (ESK-001) trial arms were headaches, upper respiratory tract infections, and nasopharyngitis, and the most common AEs deemed related to study drug by the principal investigator included headaches, upper respiratory tract infections, nasopharyngitis, rash, and nausea. The safety profile of ESK-001 continues to be evaluated in the company’s ongoing Phase 2 OLE and Phase 3 trials.
ESK-001 is an allosteric inhibitor of TYK2. TYK2 is an intracellular tyrosine kinase protein shown to play an essential role in mediating cytokine receptor signaling pathways in both innate and adaptive immunity. Cytokines are a group of proteins in the body that play an important role in boosting the immune system. Other TYK2 inhibitors, such as deucravacitinib (marketed as Sotyktu, which is approved for the treatment of adults with PsO), have shown AEs, such as hypersensitivity reactions, infections, tuberculosis, malignancy, and rhabdomyolysis. The label for deucravacitinib includes a warning concerning the potential for JAK-related adverse events, such as cardiovascular and thrombotic events. The company has observed, and expects to continue to observe that additional AEs and SAEs, consistent with known side effects of TYK2 inhibition may emerge in its ongoing and future clinical trials of ESK-001, and the company has also observed and expects to continue to observe trial participant withdrawals or discontinuations due to AEs. As of December 31, 2024, four SAEs (one serious infection, one arthritis, and two malignancy cases) were reported in the STRIDE OLE trial and considered related to ESK-001 treatment by the principal investigator.
A-005: The company’s CNS-Penetrant Allosteric TYK2 Inhibitor
The second clinical product candidate in the company’s TYK2 franchise, A-005, is a highly differentiated, CNS-penetrant, allosteric TYK2 inhibitor that has potential applications in multiple sclerosis and other neurological diseases. A loss-of-function mutation in the TYK2 gene has been shown by the company’s proprietary genetic data set, as well as scientific literature, to reduce the risk of developing MS.
Development
A-005 for the Treatment of Multiple Sclerosis
In December 2024, the company announced positive data from a Phase 1 clinical trial evaluating the safety, tolerability, and PK of single- and multiple-ascending doses of A-005 in healthy participants. In the clinical trial, A-005 was well tolerated with no SAEs reported.
Discovery Programs
The company is building a pipeline of molecules with the potential to address a broad range of immune-mediated diseases. The company pursues drug targets that have been previously validated by strong human genetic evidence or human clinical data. The company’s drug discovery efforts for its selected targets take advantage of structure-guided approaches built from public or proprietary crystallographic structures to enable the use of advanced computational methods.
The company is actively engaged in lead generation activities to identify small molecules that can precisely bind and block IRF5 function. These efforts are aided by the company’s proprietary crystal structure of its compounds bound to IRF5, which enables computational approaches to optimize binders for either IRF5 inhibition or degradation. The company has developed several proprietary assays, including a biochemical dimerization assay that has been used in conjunction with high-throughput screening to identify leads.
Foresite Labs Services Agreement
Foresite Labs, LLC (‘Foresite Labs’) was an original stockholder in, and actively involved in the company’s incubation. The company and Foresite Labs have had an ongoing services agreement since its inception, with Foresite Labs originally providing incubation services, development assistance and oversight, and data analytics services; Foresite Labs provides data analytics services related to the company’s TYK2 franchise, its discovery programs, and to its business development activities. The original Services Agreement between the company and Foresite Labs was entered into in January 2021, was amended and restated in August 2021, was amended and restated for a second time in December 2023, and expires in December 2026, unless terminated earlier by the parties.
Intellectual Property
As of December 31, 2024, the company’s solely owned patent portfolio included four issued U.S. patents, over five pending U.S. provisional patent applications, over five pending non-provisional U.S. patent applications, over five granted foreign patents, which includes a granted European patent validated in over 35 countries, over 80 pending foreign patent applications, and five pending Patent Cooperation Treaty (‘PCT’) patent applications.
In regard to ESK-001 and A-005, the company owns one patent family with claims directed to composition of matter and methods of use that includes four issued U.S. patents, one pending U.S. patent application, over five granted foreign patents in Europe (validated in over 35 countries), and certain other countries, and over 10 foreign patent applications pending in various jurisdictions, such as Europe, Canada, China, Australia, Japan, and India. Not accounting for any patent term adjustment or extensions or terminal disclaimers, and assuming that all applicable annuity and/or maintenance fees are paid timely, the issued patents, and, if granted, the pending patent applications in this family, are expected to expire in 2039.
The company also owns three patent families with claims directed to crystalline and salt forms of ESK-001, which includes two pending PCT applications, one pending U.S. application, and over 20 foreign patent applications pending in various jurisdictions, such as Europe, Canada, China, Australia, and Japan. Not accounting for any patent term adjustment or extension, and assuming that all applicable annuity and/or maintenance fees are paid timely, the patent applications, if issued, and any patent applications claiming the benefit of these PCT applications, if issued, will be expected to expire in 2043.
The company owns one patent family with claims directed to methods of treating a TYK2-mediated disease using ESK-001, that includes a pending U.S. application and over 10 foreign applications pending in various jurisdictions, such as Europe, Brazil, Canada, China, Australia, and Japan. Not accounting for any patent term adjustment or extension, and assuming that all applicable annuity and/or maintenance fees are paid timely, any patent applications, if issued, will be expected to expire in 2043.
The company owns two pending PCT applications and one pending U.S. provisional patent application that disclose and/or contain claims directed to methods of treating various diseases with ESK-001. Not accounting for any patent term adjustment or extension, and assuming that all annuity and/or maintenance fees are paid timely, any patent applications claiming the benefit of the PCT applications, or patent applications claiming priority to the PCT applications or the provisional patent application, if issued, will be expected to expire between 2044 and 2045.
The company owns three pending U.S. provisional patent applications with claims directed to crystalline and salt forms of A-005, one pending U.S. provisional patent application with claims directed to processes for making ESK-001, and one pending U.S. provisional patent application with claims directed to formulations of ESK-001. Not accounting for any patent term adjustment or extension, and assuming that all applicable annuity and/or maintenance fees are paid timely, any patent applications claiming priority to the provisional applications, if issued, will be expected to expire in 2045.
Sales and Marketing
Given the company’s stage of development, it has not yet established a full commercial organization or distribution capabilities. The company has stage-appropriate commercial capabilities, and it intends to build a commercial infrastructure to support sales of any approved products. The company also intends to continue evaluating opportunities to work with partners that enhance its capabilities with respect to the development and commercialization of ESK-001 and A-005, if approved. In addition, the company intends to commercialize its product candidates, if approved, in key markets in the United States, the European Union (‘EU’), and APAC, either alone or with partners in order to maximize the worldwide commercial potential of its programs.
Research and Development
The company’s research and development expenses were $265.6 million for the year ended December 31, 2024.
History
The company was founded in 2021 as a Delaware corporation. The company was incorporated in 2021. The company was formerly known as Esker Therapeutics, Inc. and changed its name to Alumis Inc. in January 2022.
