envudeucitinib (ESK-001) / Alumis - LARVOL DELTA

Shifting Role of Oral Therapies in Psoriasis: Unmet Needs and Perspectives on Current and Emerging Therapies, and Evolving Treatment Sequencing Among Dermatologists. (AAD 2026) - " Deucravacitinib gained first-line traction, with dermatologists increasingly delaying biologic initiation...Pipeline interest shifted year-over-year: oral IL-17 and aIL-23R mechanisms remained most valued (>83%), but icotrokinra (oral aIL-23R) emerged as the leading candidate, with aIL-23R awareness surpassing IL-17 agents and >60% of dermatologists favoring icotrokinra for first-line use, while TYK2 inhibitors (envudeucitinib, zasocitinib) were increasingly viewed as later-line options... Dermatologists report an expanding role for oral therapies in PsO. Broader availability of effective oral agents is expected to further delay biologic initiation, representing a paradigm shift in PsO management."

Dermatology • Immunology • Psoriasis • TYK2

Envudeucitinib (ESK-001) in moderate-to-severe plaque psoriasis: 24-week results from the randomized, double-blind, active comparator- and placebo-controlled, Phase 3 ONWARD 1 and 2 studies (AAD 2026) - No abstract available

Clinical • Late-breaking abstract • P3 data • Dermatology • Immunology • Psoriasis

Envudeucitinib Attenuates Inflammatory Biomarkers in Plaque Psoriasis at Both a Proteomic and Transcriptomic Level: A Subgroup Analysis of Tape Strip Biomarkers from the STRIDE Phase 2 Clinical Trial (AAD 2026) - "Conclusion In moderate-to-severe psoriasis, envudeucitinib achieved robust suppression of pathogenic IL-23 and interferon-related pathways at transcriptomic and proteomic levels, underscoring its potential as an effective therapeutic strategy. Non-invasive tape-strip biomarker collection demonstrated concordance with biopsies, supporting its use for monitoring in clinical settings."

Biomarker • Clinical • P2 data • Dermatology • Immunology • Psoriasis • IL17A • IL23A • TYK2

Alumis Announces Late-Breaker Oral Presentation of Phase 3 Data for Envudeucitinib in Moderate-to-Severe Plaque Psoriasis at 2026 American Academy of Dermatology Annual Meeting (GlobeNewswire) - "Phase 3 data presentation highlighting results from the ONWARD1 and ONWARD2 clinical trials of envudeucitinib. Phase 2 STRIDE e-poster presentation to describe disease biomarker activity of envudeucitinib."

Biomarker • Clinical data • Late-breaking abstract • Psoriasis

Key Baseline Demographics from ONWARD 1 & 2 Phase 3 Studies of Envudeucitinib in Moderate-to-Severe Psoriasis (AAD 2026) - "Mean (SD) duration of disease among 1667 patients was 19.1 years (13.5) with 46.3% having previously used systemic therapies, including biologic use in 27% and apremilast in 5.4%. The ONWARD 1 & 2 populations were predominantly comprised of long-standing, treatment-experienced patients – about a quarter with prior biologic exposure – and exhibited high disease burden. These characteristics underscore the real-world relevance of these studies and provide important context for interpreting forthcoming efficacy and safety outcomes."

P3 data • Dermatology • Immunology • Psoriasis • TYK2

Psoriasis phase III: top-line efficacy and upcoming AAD details (MarketBeat) - "Babler also said Alumis has quality-of-life and itch data from the studies that have not yet been disclosed and are expected to be presented at the American Academy of Dermatology (AAD) meeting. He noted that AAD’s website lists a late-breaking presentation involving envudeucitinib."

P3 data • Psoriasis

ONWARD3: Long-term Safety and Efficacy of ESK-001 in Moderate to Severe Plaque Psoriasis (clinicaltrials.gov) - P3 | N=1680 | Active, not recruiting | Sponsor: Alumis Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Dermatology • Immunology • Psoriasis

Alumis expects results in the third quarter of this year from its Phase IIb lupus study, which Babler described as designed as a pivotal trial. (Yahoo Finance)

P2b data • Systemic Lupus Erythematosus

An Investigational Study to Evaluate the Cardiac Safety Assessment (TQTc Study) of ESK-001 (clinicaltrials.gov) - P1 | N=52 | Completed | Sponsor: Alumis Inc

New P1 trial

Alumis Inc announced positive topline results from ONWARD1 and ONWARD2, 2 parallel, global, randomized, double-blind phase 3 trials designed to assess the efficacy and safety of envudeucitinib over 24 weeks. (DermatologyTimes) - "According to the topline results, envudeucitinib met all primary and secondary endpoints in both trials with high statistical significance compared with placebo (p < 0.0001)...Across ONWARD1 and ONWARD2, an average of 74% of patients treated with envudeucitinib achieved PASI 75 at week 16, and 59% achieved sPGA 0/1. The placebo-adjusted response rates for both co-primary endpoints were reported to be consistent between the 2 studies, supporting reproducibility of the findings...Based on the phase 3 results, Alumis plans to submit a New Drug Application to the US FDA in the second half of this year and to present more detailed trial data at an upcoming medical meeting."

FDA filing • P3 data: top line • Psoriasis

An Investigational Study of ESK-001 in Participants With Normal Renal Function and Participants With Mild, Moderate, and Severe Impaired Renal Function (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Alumis Inc | Recruiting ➔ Completed | N=48 ➔ 16 | Trial completion date: Dec 2025 ➔ Aug 2025 | Trial primary completion date: Dec 2025 ➔ Aug 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Renal Disease

Transcriptomic and Proteomic Modulation in Psoriatic Skin Following Envudeucitinib Treatment: Subgroup Analysis of a Phase 2 Randomized Trial (ISDS 2025) - P2 | "In moderate-to-severe psoriasis, envudeucitinib at 40mg QD and 40mg BID produced robust suppression of pathogenic Th1, Th17, and interferon-related pathways at transcriptomic and proteomic levels. These findings present further evidence of TYK2 inhibition as an effective treatment for moderate-to-severe plaque psoriasis."

Clinical • P2 data • Dermatology • Immune Modulation • Immunology • Pruritus • Psoriasis • AXL • CCL20 • CCL3 • CXCL11 • CXCL8 • CXCL9 • IFIT2 • IFNG • IL12B • IL17A • IL22 • IL6R • ITGB2 • MX1 • OASL • TNFRSF1A • TYK2 • XCL2

Anticipated Milestones (GlobeNewswire) - "Envu: topline data from ONWARD1 and ONWARD2 in moderate-to-severe plaque psoriasis are expected early in the first quarter of 2026; Envu: topline data from LUMUS in SLE are expected in the third quarter of 2026; Envu: Alumis expects to establish a once-daily formulation in 2025. A-005: initiation of a Phase 2 clinical trial in multiple sclerosis is anticipated in the first half of 2026; Lonigutamab: the lonigutamab development program continues to be evaluated; Third internally-developed program: Phase 1 clinical data is anticipated in the second half of 2026."

Clinical data • New P2 trial • Multiple Sclerosis • Psoriasis • Systemic Lupus Erythematosus • Thyroid Eye Disease

Response to Papp et al., "Efficacy and safety of ESK-001, a highly selective, oral allosteric TYK2 inhibitor, in patients with moderate-to-severe plaque psoriasis: 52-week results from the long-term Phase 2 study in patients who participated in the Phase 2 STRIDE study". (PubMed, J Am Acad Dermatol) - No abstract available

Journal • P2 data • Dermatology • Immunology • Psoriasis • TYK2

Safety and Efficacy of envudeucitinib, a highly selective, oral allosteric TYK2 inhibitor, in patients with moderate-to-severe plaque psoriasis: Results from the 52-week open-label extension period of the Phase 2 STRIDE study. (PubMed, J Am Acad Dermatol) - P2 | "Envudeucitinib 40 mg BID in adults with moderate-to-severe plaque psoriasis demonstrated increasing and durable improvements in skin clearance and pruritus and was well-tolerated throughout 52 weeks of treatment."

Journal • P2 data • Dermatology • Immunology • Pruritus • Psoriasis • TYK2

Treat-to-Target Outcomes With ESK-001 in Moderate-to-Severe Plaque Psoriasis: Results From the Phase 2 STRIDE & Open-Label Extension Studies (ESDR 2025) - "Treatment with ESK-001 resulted in meaningful clinical improvements in patients with moderate-to-severe plaque psoriasis. Patients achieved stringent absolute thresholds in STRIDE, with continued PASI and BSA improvements and DLQI maintenance through 52 weeks of treatment in OLE."

Clinical • P2 data • Dermatology • Immunology • Psoriasis • TYK2

Envudeucitinib designated generic name for ESK-001 (GlobeNewswire)

Commercial • Immunology • Psoriasis • Systemic Lupus Erythematosus

Alumis Completes Patient Enrollment in the Global LUMUS Phase 2b Trial of ESK-001, a Next-Generation Oral TYK2 Inhibitor for the Treatment of Systemic Lupus Erythematosus (GlobeNewswire) - "Alumis...announced the completion of patient enrollment in its global LUMUS Phase 2b trial of ESK-001, a highly selective, next-generation oral tyrosine kinase 2 (TYK2) inhibitor, for the treatment of systemic lupus erythematosus (SLE), the most common form of lupus....The global LUMUS Phase 2b trial is a randomized, double-blind, placebo-controlled study evaluating multiple doses of ESK-001 in adults with moderately-to-severely active, autoantibody-positive SLE. The trial enrolled 408 patients who are receiving ESK-001 or placebo for 48 weeks....Topline readout expected in Q3 2026."

Enrollment closed • P2b data • Systemic Lupus Erythematosus

LUMUS: Phase 2 Placebo-Controlled Study to Assess the Safety and Efficacy of ESK-001 in Active Systemic Lupus Erythematosus (clinicaltrials.gov) - P2 | N=408 | Active, not recruiting | Sponsor: Alumis Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Highly selective, allosteric inhibition of TYK2 with oral ESK-001 in patients with moderate-to-severe plaque psoriasis: Results from STRIDE, a 12-week, randomized, double-blinded, placebo-controlled, dose-ranging Phase 2 study. (PubMed, J Am Acad Dermatol) - P2 | "ESK-001 demonstrated significant dose-dependent improvement in signs and symptoms of psoriasis while achieving continuous target inhibition at the highest dose in patients with psoriasis and was well-tolerated."

Clinical • Journal • P2 data • Dermatology • Immunology • Psoriasis • TYK2

...Anticipated Milestones (GlobeNewswire) - "Topline data from ONWARD1 and ONWARD2 are expected early in the first quarter of 2026...A-005 is anticipated to enter a Phase 2 clinical trial in multiple sclerosis in the first half of 2026...Alumis anticipates Phase 1 clinical data from the next program in the second half of 2026."

Clinical data • New P2 trial • Multiple Sclerosis • Psoriasis

ONWARD2: A Study in Patients With Moderate to Severe Plaque Psoriasis to Evaluate the Efficacy and Safety of ESK-001 (clinicaltrials.gov) - P3 | N=840 | Active, not recruiting | Sponsor: Alumis Inc | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2026 ➔ Dec 2025 | Trial primary completion date: May 2026 ➔ Sep 2025

Enrollment closed • Trial completion date • Trial primary completion date • Dermatology • Immunology • Psoriasis

ONWARD1: A Study to Evaluate the Efficacy and Safety of ESK-001 in Patients With Moderate to Severe Plaque Psoriasis (clinicaltrials.gov) - P3 | N=840 | Active, not recruiting | Sponsor: Alumis Inc | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2026 ➔ Dec 2025 | Trial primary completion date: May 2026 ➔ Sep 2025

Enrollment closed • Trial completion date • Trial primary completion date • Dermatology • Immunology • Psoriasis

Alumis Completes Enrollment of Pivotal Phase 3 ONWARD Clinical Program of Lead Candidate ESK-001, a Highly Selective, Next-Generation Oral TYK2 Inhibitor for the Treatment of Moderate-to-Severe Plaque Psoriasis (GlobeNewswire) - "Alumis Inc...announced the completion of patient enrollment in its pivotal Phase 3 ONWARD clinical program of ESK-001 for the treatment of moderate-to-severe plaque psoriasis...'With over 1,700 patients enrolled across the two trials, this milestone reflects the dedication of our patients, investigators, and the Alumis team'....The Phase 3 ONWARD clinical program consists of two parallel global Phase 3, multi-center, randomized, double-blind placebo-controlled 24-week clinical trials, ONWARD1 and ONWARD2, designed to evaluate the efficacy and safety of ESK-001 in adult patients with moderate-to-severe plaque psoriasis."

Enrollment closed • Psoriasis

Alumis Completes Enrollment of Pivotal Phase 3 ONWARD Clinical Program of Lead Candidate ESK-001, a Highly Selective, Next-Generation Oral TYK2 Inhibitor for the Treatment of Moderate-to-Severe Plaque Psoriasis (Firstwordpharma Press Release) - "Alumis Inc...announced the completion of patient enrollment in its pivotal Phase 3 ONWARD clinical program of ESK-001 for the treatment of moderate-to-severe plaque psoriasis...'With over 1,700 patients enrolled across the two trials, this milestone reflects the dedication of our patients, investigators, and the Alumis team, whose efforts have made it possible. We remain on track to report topline results in early Q1 2026, bringing us closer to delivering transformative treatment solutions for patients in need.'....The Phase 3 ONWARD clinical program consists of two parallel global Phase 3, multi-center, randomized, double-blind placebo-controlled 24-week clinical trials, ONWARD1 and ONWARD2, designed to evaluate the efficacy and safety of ESK-001 in adult patients with moderate-to-severe plaque psoriasis."

Enrollment closed • P3 data: top line • Psoriasis