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

Molecular, Histological, and Clinical Effects of Selective TYK2 Inhibition with Zasocitinib (TAK-279) in Patients with Moderate-to-Severe Plaque Psoriasis. (PubMed, J Invest Dermatol) - No abstract available

Journal • Dermatology • Immunology • Psoriasis • TYK2

P114 Efficacy and safety of oral Janus kinase, tyrosine kinase 2 and phosphodiesterase 4 inhibitors in the treatment of chronic plaque psoriasis: a network meta-analysis. (PubMed, Br J Dermatol) - "After 16-24 weeks of treatment, tofacitinib and deucravacitinib had the highest efficacy, followed by apremilast, orismilast, upadacitinib and brepocitinib. Zasocitinib, a new highly selective allosteric TYK2 inhibitor, has recently demonstrated promising efficacy in the treatment of psoriasis, with 33% of patients achieving PASI 100 (complete clearance of psoriasis lesions) after just 12 weeks of treatment. In conclusion, oral TYK2 inhibitors have shown efficacy in the treatment of chronic plaque psoriasis comparable with adalimumab, with newer agents demonstrating enhanced effectiveness and surpassing PDE-4 inhibitors in therapeutic outcomes. JAK inhibitors, particularly tofacitinib, exhibit comparable efficacy to some TYK2 and PDE-4 inhibitors."

Clinical • Journal • Retrospective data • Review • Dermatology • Immunology • Psoriasis • TYK2

Zasocitinib-induced modulation of tyrosine kinase 2 signaling biomarkers is associated with treatment response in patients with moderate-to-severe plaque psoriasis (ISDS 2025) - P2b | "Generally, modulation of both pathways together was associated with a greater % CfB in PASI. Overall, modulation of both IL-23 and type I IFN pathways was associated with zasocitinib treatment response."

Biomarker • Clinical • Dermatology • Immunology • Psoriasis • IL12A • IL23A • TYK2

TAK-279-3002: A Study About How Well TAK-279 Works and Its Safety in Participants With Moderate-to-severe Plaque Psoriasis During 60 Weeks of Treatment With a Withdrawal and Retreatment Period (clinicaltrials.gov) - P3 | N=1108 | Completed | Sponsor: Takeda | Active, not recruiting ➔ Completed

Trial completion • Dermatology • Immunology • Psoriasis

A Study of Zasocitinib in Adults With Hidradenitis Suppurativa (clinicaltrials.gov) - P2 | N=90 | Not yet recruiting | Sponsor: Takeda

New P2 trial • Dermatology • Hidradenitis Suppurativa • Immunology

A Long-Term Study of Zasocitinib in Children and Teenagers With Plaque Psoriasis (clinicaltrials.gov) - P3 | N=110 | Not yet recruiting | Sponsor: Takeda

New P3 trial • Dermatology • Immunology • Pediatrics • Psoriasis

A Study of Zasocitinib in Adults With Nonsegmental Vitiligo (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting

Enrollment open • Dermatology • Immunology • Vitiligo

Takeda Reports First Half FY2025 Results, with Business Fundamentals Tracking as Planned. Updates Full Year Outlook to Reflect FX Impact and Pipeline Impairment. On Track for Multiple Regulatory Filings This Fiscal Year (FinancialContent) - "First Half Revenue Declined 3.9% at Constant Exchange Rate (CER), -6.9% at Actual Exchange Rates (AER), Impacted by Generic Erosion of VYVANSE and FX Headwind...'We see FY2025 as a pivotal year for Takeda with regulatory filings for rusfertide and oveporexton expected in the second half of the year, as well as Phase 3 results for zasocitinib.'"

Commercial • Filing • P3 data • CNS Disorders • Polycythemia Vera • Psoriatic Arthritis

A Study About How Well TAK-279 Works and Its Safety in Participants With Moderate-to-severe Plaque Psoriasis During 52 Weeks of Treatment (clinicaltrials.gov) - P3 | N=693 | Completed | Sponsor: Takeda | Active, not recruiting ➔ Completed

Trial completion • Dermatology • Immunology • Psoriasis

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 (ACR Convergence 2025) - P2, P3 | "Zasocitinib modulates biomarkers of cartilage and bone turnover and articular tissue inflammation in patients with active PsA as early as Week 4, with changes linked to ACR20 clinical response. Zasocitinib 30 mg significantly reduced bone turnover biomarkers at Week 12 versus PBO. Ongoing phase 3 studies (NCT06671483 and NCT06671496) are examining TYK2 inhibition in PsA."

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

In Vitro Pharmacological Profile of GLPG3667 Suggests Differentiation from the TYK2 Inhibitors Deucravacitinib and Zasocitinib at Their Clinical Dose Regimens (ACR Convergence 2025) - "At concentrations corresponding to its highest anticipated clinical dose, GLPG3667 shows selective inhibition of TYK2-mediated signalling, with a level of inhibition similar to deucravacitinib clinical dose regimens. While GLPG3667 did not show any impact on IL-10-mediated signalling, inhibition of this anti-inflammatory pathway is expected for the allosteric TYK2 inhibitors at their clinical exposure levels."

Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • CD4 • IFNA1 • IL10 • IL12A • IL2 • IL23A • IL6 • JAK1 • TYK2

Modulation of Tyrosine Kinase 2- and Disease-Related Biomarkers by Zasocitinib (TAK-279), an Oral, Allosteric, Highly Selective and Potent Tyrosine Kinase 2 Inhibitor, Is Associated With Clinical Response in Patients with Active Psoriatic Arthritis (ACR Convergence 2025) - P2 | "In this phase 2b trial, zasocitinib 30 mg QD treatment led to modulation of key TYK2 pathway- and PsA activity-related biomarkers that mediate pathophysiology in patients with active PsA, particularly in ACR20 clinical responders. Baseline levels of key biomarkers may predict joint and skin responses to zasocitinib."

Biomarker • Clinical • IO biomarker • Dermatology • Immunology • Inflammation • Inflammatory Arthritis • Psoriasis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CCL8 • EREG • IL17A • IL17C • IL22 • IL6 • LAG3 • TYK2

Zasocitinib (TAK-279), an Investigational, Oral, Allosteric, Selective TYK2 Inhibitor, in Moderate-to-Severe Plaque Psoriasis: Efficacy Analysis by Baseline Characteristics from a Randomized Phase 2b Trial (ACR Convergence 2025) - P2b, P3 | "Treatment with zasocitinib 15 mg or 30 mg led to greater response rates at Week 12 versus PBO in patients with moderate-to-severe plaque psoriasis, for nearly all baseline characteristics assessed. 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

LONG-TERM SAFETY AND EFFICACY OF THE HIGHLY SELECTIVE TYROSINE KINASE 2 INHIBITOR ZASOCITINIB FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE: DESIGN OF A PHASE 2 OPEN-LABEL EXTENSION TRIAL (UEGW 2025) - P2 | "This open-label extension trial will provide data on the long-term safety of zasocitinib, as well as durability of treatment response among patients with CD or UC who experience treatment benefit in the phase 2 parent studies."

Clinical • P2 data • Crohn's disease • Fatigue • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • 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 (EADV 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

Treatment with zasocitinib (TAK-279), an investigational, oral, allosteric, highly selective and potent tyrosine kinase 2 inhibitor, is associated with improvements in Dermatology Life Quality Index in patients with moderate-to-severe plaque psoriasis (EADV 2025) - P2b, P3 | "Treatment with oral zasocitinib 30 mg QD resulted in greater improvements from baseline in DLQI total score and most individual DLQI domains vs placebo, particularly in the Symptoms and Feelings domain as early as Week 4. These results suggest that zasocitinib may provide early onset benefits to patients' health-related quality of life. Ongoing phase 3 trials (NCT06088043 and NCT06108544) are further investigating the efficacy and safety of zasocitinib in patients with moderate-to-severe plaque psoriasis."

Clinical • 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 (EADV 2025) - P2b, P3 | "Treatment with zasocitinib 15 mg or 30 mg resulted in greater response rates at Week 12 versus placebo in patients with moderate-to-severe plaque psoriasis, for nearly all baseline characteristics assessed. 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

Efficacy and safety of oral JAK, TYK2 and PDE4 inhibitors in the treatment of chronic plaque psoriasis - a network meta-analysis (EADV 2025) - "After 12-16 weeks of treatment, solcitinib (PASI75 odds ratio [OR] 37.92) had the highest efficacy compared to placebo , followed by zasocitinib (34.59), tofacitinib (22.01), ropsacitinib (16.79), brepocitinib (14.88) and deucravacitinib (14.17). Oral TYK2 inhibitors have shown efficacy in the treatment of chronic plaque psoriasis comparable to adalimumab, with newer agents demonstrating enhanced effectiveness and far surpassing PDE4 inhibitors in therapeutic outcomes. JAK inhibitors, particularly solcitinib and tofacitinib, exhibit comparable efficacy to TYK2 inhibitors. EADV Congress 2025 PARIS"

Retrospective data • Dermatology • Immunology • Psoriasis • TYK2

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 (EADV 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

Zasocitinib Shows Early DLQI Gains in Patients with Psoriasis (DermatologyTimes) - "DLQI Total Score: Patients receiving zasocitinib 30 mg had greater reductions in DLQI total scores versus placebo at weeks 4, 8, and 12, with improvements evident as early as week 4....DLQI 0/1 Achievement: A greater proportion of patients on zasocitinib achieved DLQI scores of 0 or 1, representing no or minimal impact of psoriasis on quality of life, compared with placebo."

P2b data • Psoriasis

Zasocitinib-induced modulation of tyrosine kinase 2 signalling biomarkers is associated with treatment response in patients with moderate-to-severe plaque psoriasis (ESDR 2025) - P2b | "Positive correlations were observed between the % CfB in PASI at W12 and modulation of IL-23 (ρ=0.68; p<0.001), T1 IFN (ρ=0.69; p<0.001) and IL-12 (ρ=0.41; p<0.01) pathway genes in all treatment arms. Most patients achieving PASI 90 had significant modulation of IL-23 and T1 IFN signalling pathways vs those achieving"

Biomarker • Clinical • Dermatology • Immunology • Psoriasis • IL12A • IL23A • TYK2

A Study of TAK-279 in Adult Participants With Generalized Pustular Psoriasis or Erythrodermic Psoriasis (clinicaltrials.gov) - P3 | N=18 | Active, not recruiting | Sponsor: Takeda | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2026 ➔ Jul 2026 | Trial primary completion date: Jun 2025 ➔ Oct 2025

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

A Study About How Well TAK-279 Works and Its Safety in Participants With Moderate-to-severe Plaque Psoriasis During 52 Weeks of Treatment (clinicaltrials.gov) - P3 | N=693 | Active, not recruiting | Sponsor: Takeda | Trial completion date: Apr 2026 ➔ Nov 2025 | Trial primary completion date: Aug 2025 ➔ Jan 2025

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

A Study of Zasocitinib in Adults With Nonsegmental Vitiligo (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: Takeda

New P2 trial • Dermatology • Immunology • Vitiligo

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

Enrollment open • Dermatology • Immunology • Psoriasis