zasocitinib (TAK-279) / Takeda, Schrodinger - LARVOL DELTA

ASSESSMENT OF LABORATORY PARAMETER CHANGES IN A PHASE 2b TRIAL OF ZASOCITINIB (TAK-279), AN ORAL, HIGHLY SELECTIVE TYK2 INHIBITOR, IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS (EULAR 2025) - P2, P3 | "Overall, 62.4% of patients were receiving conventional disease modifying anti-rheumatic drugs at baseline (57.6% on methotrexate). Treatment with zasocitinib did not appear to result in laboratory parameter changes reported in studies of JAK1/2/3 inhibitors. Further larger phase 3 studies in patients with active PsA are planned to confirm these observations (NCT06671483, NCT06671496)."

Clinical • P2b data • Hematological Disorders • Immunology • Inflammatory Arthritis • Neutropenia • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Thrombocytopenia • JAK1 • JAK2 • TYK2

ZASOCITINIB (TAK-279), AN ORAL, ALLOSTERIC, SELECTIVE TYK2 INHIBITOR, IN MODERATE-TO-SEVERE PLAQUE PSORIASIS: EFFICACY ANALYSIS BY BASELINE CHARACTERISTICS FROM A RANDOMISED PHASE 2B TRIAL (EULAR 2025) - P2b, P3 | "Treatment with zasocitinib 15 mg or 30 mg demonstrated consistent improvements in PASI 75, PASI 90, PASI 100, PGA 0/1 and DLQI at Week 12 versus placebo in patients with moderate-to-severe plaque psoriasis, regardless of baseline weight, sex, age, disease duration, prior biologic use and PASI. Phase 3 trials (NCT06088043 and NCT06108544) are ongoing to investigate the efficacy and safety of zasocitinib in larger patient groups."

Clinical • P2b data • Dermatology • Immunology • Psoriasis • TYK2

Modulation of soluble biomarkers of cartilage and bone turnover and inflammation by zasocitinib (TAK-279), an oral, allosteric, highly selective and potent TYK2 inhibitor, is associated with clinical response in patients with active psoriatic arthritis (EULAR 2025) - P2, P3 | "Zasocitinib modulates biomarkers associated with cartilage and bone turnover and articular tissue inflammation in patients with active PsA. These changes occur as early as Week 4 and are associated with clinical response. The highest dose of zasocitinib (30 mg) was required to significantly reduce bone turnover biomarkers versus placebo at Week 12."

Biomarker • Clinical • Immunology • Inflammation • Inflammatory Arthritis • Oncology • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CCL8 • CSF1 • IL6 • MMP3 • TNFSF12 • TYK2

Zasocitinib (TAK-279), a highly selective oral tyrosine kinase 2 (TYK2) inhibitor, elicits minimal disease activity and early skin responses in patients with active psoriatic arthritis: results from a randomised phase 2b study (EULAR 2025) - P2 | "At Week 12, treatment with zasocitinib 30 mg led to substantially higher responses versus placebo across all outcomes assessed, with exception to PASI 100. Higher doses of zasocitinib (15 and 30 mg) achieved higher rates of MDA and robust efficacy across all skin endpoints compared with placebo by Week 12, indicating meaningful improvement in core PsA domains. Skin responses were evident from Week 2 onwards, and more patients treated with zasocitinib 30 mg achieved total or near-total clearance of PsO lesions at Week 12 versus placebo."

Clinical • P2b data • Dermatology • Immunology • Inflammatory Arthritis • Psoriasis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • TYK2

Zasocitinib (TAK-279) exhibits high levels of TYK2 inhibition and no inhibition of JAK 1/3 when compared with licensed TYK2 and JAK inhibitors (EULAR 2025) - "Simulated plasma concentrations were above TYK2 IC 50 for 24 hours for zasocitinib 30 mg once daily (QD) versus 3 hours for deucravacitinib 6 mg QD, and 0 hours for baricitinib 4 mg QD, upadacitinib 30 mg QD and tofacitinib 10 mg twice daily (Figure 1). Selective TYK2 inhibition offers a distinct cytokine receptor associated proximal signal kinase inhibition profile. Zasocitinib showed greater and longer selective inhibition of TYK2-mediated signalling versus deucravacitinib at modelled comparative clinical dose, without affecting JAK1/3-mediated signalling."

Dermatology • Immunology • Psoriasis • IFNG • IL12A • IL2 • JAK1 • TYK2

A Continuation Study of TAK-279 in Adults With Ulcerative Colitis (UC) and Crohn's Disease (CD) (clinicaltrials.gov) - P2 | N=183 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting

Enrollment open • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Pharmacological Characterization of Zasocitinib (TAK-279): An Oral, Highly Selective and Potent Allosteric TYK2 Inhibitor. (PubMed, J Invest Dermatol) - "Simulated clinical concentrations of zasocitinib 30 mg once daily exceeded the TYK2 IC50 for 24 hours, maintaining >90% daily inhibition, with no JAK1/2/3 inhibition. The distinct potent and selective inhibition profile of zasocitinib defines it as a next-generation TYK2 inhibitor."

Journal • Inflammation • IL12A • IL2 • IL23A • JAK1 • TYK2

A Study Comparing Zasocitinib (TAK-279) With Deucravacitinib in Adults With Plaque Psoriasis (clinicaltrials.gov) - P3 | N=600 | Not yet recruiting | Sponsor: Takeda

New P3 trial • Dermatology • Immunology • Psoriasis

Takeda TYK2 inhibitor 'zasocitinib' targets Crohn's disease [Google translation] (Chosun Ilbo) - "On the 23rd, Takeda received approval for the Phase 3 clinical trial plan (IND) for 'zasocitinib' from the Ministry of Food and Drug Safety. The trial is to evaluate the efficacy and safety of 'zasocitinib' in patients with active psoriatic arthritis who have not been administered biological disease-modifying antirheumatic drugs."

New P3 trial • Crohn's disease

A Study of Interaction of Zasocitinib (TAK-279) With Other Medicines in Healthy Adults (clinicaltrials.gov) - P1 | N=78 | Completed | Sponsor: Takeda | Active, not recruiting ➔ Completed

Trial completion

Pharmacological Management of Psoriasis: Current Landscape and Future Perspectives. (PubMed, Recent Adv Inflamm Allergy Drug Discov) - "Numerous novel synthetic agents, such as JAK/STAT inhibitors [ruxolitinib, peficitinib], TYK2 inhibitors [zasocitinib, ropsacitinib], RORꝩT inhibitors [cedirogant], A3AR agonists [piclodenoson], and CXCR2 antagonists [vimnerixin] are undergoing extensive clinical trials and have demonstrated beneficial outcomes in multiple phases of these trials. Deucravacitinib, an orally administered TYK2 inhibitor, has recently received FDA approval for the treatment of moderate to severe plaque psoriasis...Moreover, these pathways can be exploited to personalize anti-psoriatic therapy, minimize side effects, and maximize therapeutic outcomes. Altogether, the integration of biological agents and synthetic agents can overcome the challenges associated with the management of the repertoire of psoriatic pathophysiology and symptoms."

Journal • Dermatology • Immunology • Inflammation • Psoriasis • CXCR2 • IL23A • TYK2

A Study of Interaction of Zasocitinib (TAK-279) With Other Medicines in Healthy Adults (clinicaltrials.gov) - P1 | N=78 | Active, not recruiting | Sponsor: Takeda | Recruiting ➔ Active, not recruiting

Enrollment closed

LATITUDE-PsA-3002: A Study of Zasocitinib in Adults With Psoriatic Arthritis Who Have or Have Not Been Treated With Biologic Medicines (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies

Zasocitinib (TAK-279), an oral, allosteric, highly selective TYK2 inhibitor, reduced PASI body region and individual component scores in a phase 2b trial in moderate-to-severe plaque psoriasis (AAD 2025) - P2b | "Zasocitinib led to consistent improvements across all body regions and components versus placebo, with similar effects in each body region and component observed."

Clinical • P2b data • Dermatology • Immunology • Psoriasis • TYK2

Efficacy of zasocitinib (TAK-279), an oral, allosteric, potent and selective TYK2 inhibitor, evaluated by Physician's Global Assessment×Body surface area (PGA×BSA), in a randomized phase 2b trial in moderate-to-severe plaque psoriasis (AAD 2025) - P2b | "Zasocitinib improved PGA×BSA versus placebo. Strong correlations between PGA×BSA and PASI were observed, validating use of PGA×BSA in routine clinical practice."

Clinical • P2b data • Dermatology • Immunology • Psoriasis • TYK2

Zasocitinib (TAK-279), an oral, allosteric, selective TYK2 inhibitor, in moderate-to-severe plaque psoriasis: efficacy analysis by baseline characteristics from a randomized phase 2b trial (AAD 2025) - "Zasocitinib improved PASI-75/90/100, PGA 0/1 and DLQI at week 12 versus placebo for nearly all baseline characteristics assessed."

Clinical • P2b data • Dermatology • Immunology • Psoriasis • TYK2

LATITUDE-PsA-3001: A Study of Zasocitinib in Adults With Psoriatic Arthritis Who Have Not Taken Biologic Medicines (clinicaltrials.gov) - P3 | N=1088 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CRP

Takeda Delivers Strong Third-Quarter FY2024 Results; Raises Full Year Outlook, Forecasting Revenue and Core Operating Profit Margin Growth (Businesswire) - "Among the multiple late-stage programs presented, the company expects...Phase 3 data readouts in the calendar year 2025 with filings anticipated in FY2025-FY2026 for the following programs and indications: oveporexton (TAK-861) for the treatment of narcolepsy type 1; zasocitinib for the treatment of psoriasis...Moreover, five additional indication filings for late-stage programs are on pace for FY2027-FY2029. zasocitinib for the treatment of psoriatic arthritis; mezagitamab for treatments of immune thrombocytopenia (ITP), a rare immune-mediated bleeding disorder, and immunoglobulin A nephropathy (IgAN), a chronic progressive autoimmune mediated kidney disease; fazirsiran for the treatment of alpha-1 antitrypsin deficiency-associated liver disease, and elritercept for the treatment of anemia associated with myelodysplastic syndrome."

Filing • P3 data • Alpha-1 Antitrypsin Deficiency • Anemia • IgA Nephropathy • Immune Thrombocytopenic Purpura • Narcolepsy • Psoriasis • Psoriatic Arthritis

Zasocitinib: Data readout from P2b trial (NCT06233461) for moderate to severe active Crohn's disease in FY 2026 (Takeda) - Q3 FY2024 Results: Data readout from P2 trial (NCT06254950) for moderate to severe active ulcerative colitis in FY 2026

P2 data • P2b data • Crohn's disease • Inflammatory Bowel Disease • Ulcerative Colitis

A Study of Interaction of Zasocitinib (TAK-279) With Other Medicines in Healthy Adults (clinicaltrials.gov) - P1 | N=78 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting

Enrollment open

A Study of Interaction of Zasocitinib (TAK-279) With Other Medicines in Healthy Adults (clinicaltrials.gov) - P1 | N=78 | Not yet recruiting | Sponsor: Takeda

New P1 trial

A Continuation Study of TAK-279 in Adults With Ulcerative Colitis (UC) and Crohn's Disease (CD) (clinicaltrials.gov) - P2 | N=183 | Not yet recruiting | Sponsor: Takeda

New P2 trial • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Zasocitinib (TAK-279) exhibits high levels of TYK2 inhibition and no inhibition of JAK 1/3 when compared with licensed TYK2 and JAK inhibitors (PsoriasisG2C 2024) - "Simulated plasma concentrations were above TYK2 IC50 for 24 h for zasocitinib 30 mg once daily (QD) vs. 3 h for deucravacitinib 6 mg QD, and 0 h for baricitinib 4 mg QD, tofacitinib 10 mg twice daily and upadacitinib 30 mg QD. Selective TYK2 inhibition offers a distinct cytokine receptor inhibition profile. Zasocitinib showed greater and longer selective inhibition of TYK2-mediated signalling vs. deucravacitinib at its clinical dosage, without affecting JAK1/3- mediated signalling."

Dermatology • Immunology • Inflammation • Psoriasis • IFNG • IL12A • IL2 • JAK1 • TYK2

Zasocitinib (TAK-279), an oral, allosteric, highly selective TYK2 inhibitor, modulates disease-central cytokine pathways that define clinical response in patients with moderate-to-severe plaque psoriasis (PsoriasisG2C 2024) - P2b | "Zasocitinib treatment did not result in clinically meaningful longitudinal changes in laboratory parameters associated with Janus kinase inhibition. Zasocitinib modulated psoriasis/TYK2 biomarkers were associated with clinical and histological response in patients with moderate-to-severe plaque psoriasis."

Clinical • Dermatology • Immunology • Psoriasis • IL12A • IL17A • IL17C • IL23A • ITGAX • KRT16 • TYK2

Takeda Spotlights High-Value, Late-Stage Pipeline Accelerating the Development of Potential Transformative Treatments for Patients in Multiple Therapeutic Areas (Businesswire) - "Data from...Phase 3 programs is expected to read out in 2025...zasocitinib, an investigational next-generation, highly selective and potent oral allosteric tyrosine kinase 2 (TYK2) inhibitor will deliver Phase 3 results in psoriasis...Filings for these...indications are expected in fiscal years 2025 and 2026. Five additional indication filings for late-stage programs are on pace for fiscal years 2027 through 2029: zasocitinib in psoriatic arthritis; mezagitamab, an investigational anti-CD38 antibody providing rapid, selective and sustained depletion of disease-causing immune cells that could set a new standard for the treatment of immune thrombocytopenia (ITP) and immunoglobulin A neuropathy (IgAN)."

Filing • P3 data • Immune Thrombocytopenic Purpura • Psoriasis • Psoriatic Arthritis