girocitinib (TLL018) / Highlightll Pharma - LARVOL DELTA

Emerging and Investigational JAK Inhibitors for Rheumatoid Arthritis: Efficacy and Safety. (PubMed, Drug Des Devel Ther) - "Peficitinib has the most mature evidence base, including Phase 3 efficacy, radiographic protection, long-term extension data, and pooled safety analyses. Ivarmacitinib has phase 3 and exploratory MRI data, whereas the phase 3 trial of TLL-018 has reached primary completion, with sponsor-reported topline findings available but complete results not yet published. CPL409116/CPL'116 remains supported by limited Phase 2 evidence. Decernotinib represents an informative historical proof-of-concept programme. Overall, no emerging agent has yet demonstrated a reproducible advantage over established JAK inhibitors in sustained remission, structural preservation, difficult-to-treat disease, or overall benefit-risk balance. Future development should prioritise active comparators, prespecified structural outcomes, prolonged safety assessment, and prospectively validated treatment-specific biomarkers."

Journal • Review • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetic Profiles of TLL-018 in Patients With Moderate-to-Severe Atopic Dermatitis (clinicaltrials.gov) - P2/3 | N=390 | Not yet recruiting | Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd

New P2/3 trial • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

A Study of Efficacy and Safety of TLL-018 in CSU Participants With Inadequate Response to 2nd-generation H1-AHs (clinicaltrials.gov) - P2 | N=140 | Not yet recruiting | Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd

New P2 trial • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

TLL-018 in Patients With Moderate to Severe Active Rheumatoid Arthritis With Inadequate Response or Intolerance to csDMARDs (clinicaltrials.gov) - P2 | N=90 | Not yet recruiting | Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd

New P2 trial • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

A Phase Ib/IIa Randomized Study Assessing the Rapid Onset Characteristics of TLL-018 for Moderate-to-Severe CSU With Inadequate Response to Second-Generation H1 Antihistamines (clinicaltrials.gov) - P1/2 | N=36 | Not yet recruiting | Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd

New P1/2 trial • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

A Study of Efficacy and Safety of TLL-018 in CSU Participants (clinicaltrials.gov) - P3 | N=440 | Active, not recruiting | Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2027 ➔ Dec 2026 | Trial primary completion date: Mar 2026 ➔ Oct 2025

Enrollment closed • Trial completion date • Trial primary completion date • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

TARA: A Phase 3 Study Comparing TLL-018 to Tofacitinib in RA Subjects With Inadequate Response or Intolerance to bDMARDs (clinicaltrials.gov) - P3 | N=459 | Active, not recruiting | Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd | Trial completion date: Dec 2028 ➔ Dec 2026 | Trial primary completion date: Jul 2026 ➔ Jan 2026

Head-to-Head • Monotherapy • Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

TARA: A Phase 3 Study Comparing TLL-018 to Tofacitinib in RA Subjects With Inadequate Response or Intolerance to bDMARDs (clinicaltrials.gov) - P3 | N=459 | Active, not recruiting | Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2025 ➔ Dec 2028 | Trial primary completion date: Feb 2025 ➔ Jul 2026

Enrollment closed • Head-to-Head • Monotherapy • Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Safety and efficacy of the selective tyrosine kinase 2/Janus kinase 1 inhibitor TLL-018 in moderate to severe chronic spontaneous urticaria patients with inadequate response to H1 antihistamines: a phase Ib, randomized, double-blind, placebo-controlled pilot study. (PubMed, Br J Dermatol) - P1 | "TLL-018 was well-tolerated and effective in treating moderate-to-severe CSU in patients who had an inadequate response to antihistamines."

Clinical • Journal • Chronic Spontaneous Urticaria • Dermatology • Diabetes • Immunology • Urticaria • TYK2

Safety and efficacy of the selective TYK2/JAK1 inhibitor TLL-018 in moderate-to-severe plaque psoriasis: A phase 1b, randomized, double-blind, placebo-controlled study. (PubMed, Br J Dermatol) - P1 | "TLL-018 was well tolerated and showed promising efficacy at week 12 comparing placebo in patients with moderate-to-severe plaque psoriasis."

Clinical • Journal • P1 data • Dermatology • Immunology • Psoriasis • TYK2

An Open-label, Long-term Extension Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of TLL-018 in Patients With Rheumatoid Arthritis (clinicaltrials.gov) - P3 | N=350 | Recruiting | Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd

New P3 trial • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

A Study of Efficacy and Safety of TLL-018 in CSU Participants (clinicaltrials.gov) - P3 | N=436 | Recruiting | Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd | Not yet recruiting ➔ Recruiting | Initiation date: May 2024 ➔ Dec 2024

Enrollment open • Trial initiation date • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

The Efficacy and Safety of TLL018 in Moderate-to-severe Plaque Psoriasis (clinicaltrials.gov) - P2 | N=82 | Completed | Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd | Recruiting ➔ Completed | N=120 ➔ 82 | Trial completion date: May 2024 ➔ Dec 2024 | Trial primary completion date: Apr 2024 ➔ Dec 2024

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

Therapies for Chronic Spontaneous Urticaria: Present and Future Developments. (PubMed, Pharmaceuticals (Basel)) - "If symptoms persist despite this adjustment, the next step involves the use of omalizumab, a monoclonal anti-IgE antibody, which has shown efficacy in the majority of cases. However, a subset of patients remains refractory, necessitating alternative treatments such as immunosuppressive agents like cyclosporine or azathioprine...Among them, significant attention is being given to drugs that block Bruton's tyrosine kinase (BTK), such as remibrutinib, which reduces mast cell activation. Therapies like dupilumab, which target the interleukin-4 (IL-4) and IL-13 pathways, are also under investigation. Additionally, molecules targeting the Mas-related G protein-coupled receptor X2 (MRGPRX2), and those inhibiting the tyrosine kinase receptor Kit, such as barzolvolimab, show promise in clinical studies...Further research is essential to better elucidate the pathophysiology of CSU and optimize treatment protocols to achieve long-term benefits in managing this condition...."

Journal • Review • Cardiovascular • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria • BTK • IL13 • IL4

A Phase 3 Study of Efficacy and Safety of TLL-018 in CSU Participants With Inadequate Controll to Second Generation H1-antihistamines (clinicaltrials.gov) - P3 | N=436 | Not yet recruiting | Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd

New P3 trial • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

Safety and efficacy of selective TYK2/JAK1 inhibitor, TLL-018, in moderate-to-severe plaque psoriasis (AAD 2024) - P1 | "10 of 21 patients (47.6%) in the TLL-018 30 mg BID group achieved PASI 90. CONCLUSIONS TLL-018 was well tolerated and showed promising efficacy in patients with moderate-to-severe plaque psoriasis in this 12-week study."

Clinical • Dermatology • Immunology • Psoriasis • TYK2

Evaluation of TLL-018 Extended and Immediate Release Formulation for Bioequivalence Testing in Healthy Chinese Subjects (clinicaltrials.gov) - P1 | N=28 | Completed | Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd | Active, not recruiting ➔ Completed

Trial completion • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Safety and Efficacy of TLL018 in Patients With Chronic Spontaneous Urticaria. (clinicaltrials.gov) - P1 | N=41 | Completed | Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd | Active, not recruiting ➔ Completed

Trial completion • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

Efficacy and Safety of TLL-018 in Moderate to Severe Chronic Spontaneous Urticaria Patients with Inadequate Response to H1 Antihistamine: Results from a Phase Ⅰb Study (AAAAI 2024) - P1 | "TLL-018 was well tolerated and showed high efficacy in moderate-to-severe CSU patients with inadequate response to high doses or a combination of antihistamine treatment."

Clinical • Late-breaking abstract • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria • TYK2

Head-to-Head Comparison of TLL-018 and Tofacitinib in Patients with Active Rheumatoid Arthritis: Final Results from a Phase IIa Study (ACR Convergence 2023) - " 101 patients with moderate-to-severe active RA who had inadequate response or were intolerant to methotrexate were randomized (1:1:1:1 ratio) to receive twice-daily oral TLL-018 10mg, 20mg, 30mg or tofacitinib 5mg. TLL-018 20 and 30mg demonstrated superior efficacy over tofacitinib in RA patients, suggesting that inhibition of TYK2, in addition to JAK1, enhances efficacy. TLL-018 was well tolerated with most AEs being Grade 1 or 2 as expected from this class of compounds. No unexpected safety concerns were observed in the study."

Clinical • Head-to-Head • P2a data • Cardiovascular • Dyslipidemia • Herpes Zoster • Immunology • Infectious Disease • Inflammatory Arthritis • Oncology • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Varicella Zoster • Venous Thromboembolism • JAK1 • TYK2

TARA: A Phase 3 Study Comparing TLL-018 to Tofacitinib in RA Subjects With Inadequate Response or Intolerance to bDMARDs (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Head-to-Head • Monotherapy • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

Safety and Efficacy of TLL018 in Patients With Plaque Psoriasis (clinicaltrials.gov) - P1 | N=73 | Completed | Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd | Active, not recruiting ➔ Completed

Trial completion • Dermatology • Immunology • Psoriasis

The Efficacy and Safety of TLL018 in Moderate-to-severe Plaque Psoriasis (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd | Trial completion date: Sep 2023 ➔ May 2024 | Trial primary completion date: Aug 2023 ➔ Apr 2024

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

The Safety and Efficacy of TLL-018 in Active Rheumatoid Arthritis (clinicaltrials.gov) - P2a | N=101 | Completed | Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd | Active, not recruiting ➔ Completed

Trial completion • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

TARA: A Phase 3 Study Comparing TLL-018 to Tofacitinib in RA Subjects With Inadequate Response or Intolerance to bDMARDs (clinicaltrials.gov) - P3 | N=450 | Not yet recruiting | Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd

Head-to-Head • Monotherapy • New P3 trial • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP