rovadicitinib (TQ05105) / Sino Biopharm - LARVOL DELTA

A Study of TQ05105 in Patients With Chronic Graft Versus Host Disease (clinicaltrials.gov) - P1/2 | N=45 | Active, not recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Trial completion date: Dec 2024 ➔ Dec 2026

Trial completion date • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

Safety and efficacy of the JAK/rock inhibitor rovadicitinib in combination with the bromodomain and extra-terminal inhibitor TQB3617 in patients with myelofibrosis: A phase ib/II study (ASH 2025) - P1, P1/2, P2 | "Rovadicitinib in combination with TQB3617 was generally safe, well-tolerated, and showed clinical activityin pts with MF who were either JAKi-naïve or had a suboptimal response to JAKi treatment. This regimenmay represent a new treatment option for such patients with MF. A phase III study is currently beingplanned in pts with MF who had a suboptimal response to JAKi treatment."

Clinical • Combination therapy • P1/2 data • Hematological Disorders • Hematological Malignancies • Lymphoma • Myelofibrosis • CALR • HEY1 • JAK2

BCL-2 inhibitor TQB3909 combined with JAK inhibitors in patients with intermediate- or high-risk myelofibrosis: A two-cohort, open-label, Phase ib/II, multicenter study (ASH 2025) - P1/2 | "Previous studies of BCL-2 inhibitor plus ruxolitinib (RUX) have shown improved efficacycompared to JAKi monotherapy...Palpable splenomegaly (≥5 cm below LCM) or spleen volume ≥450 cm³ (MRI/CT) was required.Pts received either RUX or rovadicitinib (ROV) combined with TQB3909 based on investigator discretion.Dose escalation of TQB3909 (100 mg, 200 mg, 300 mg QD) was first explored in the RUX cohort, followedby a 3+3 dose-escalation design in the ROV cohort (10mg, 15 mg bid)... TQB3909 combined with JAKi demonstrated meaningful clinical activity in MF pts,particularly in combination with ROV, showing spleen reduction, symptom improvement, and potentialanemia benefit. However, TQB3909+ROV is associated with hematologic toxicities, and dose optimizationis ongoing to balance efficacy and tolerability. Acknowledgement: This research was funded by the Zhejiang Provincial Health High-level InnovativeTalent Project (2022-2026)."

Clinical • IO biomarker • P1/2 data • Infectious Disease • Myelofibrosis • Thrombocytopenia • BCL2L1 • MCL1

JAK/Rock Inhibitor Rovadicitinib for Glucocorticoid-Refractory or -Dependent Chronic Graft-Versus-Host Disease:Updated Results of Multicenter, Phase 1b/2a Trial (ASH 2024) - P1/2 | "The BOR was 83.3% in patients prior to ruxolitinib therapy. Conclusion : Rovadicitinib was well tolerated in patients with cGVHD, eliciting a high rate of clinical response, improved quality of life, and CS dose reduction. Rovadicitinib may be effective in patients with glucocorticoid-refractory or -dependent cGVHD, and a phase 3 randomized study for registration will be launched soon."

Clinical • P1/2 data • Anemia • Chronic Graft versus Host Disease • Epstein-Barr Virus Infections • Fibrosis • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Leukopenia • Neutropenia • Pneumonia • Respiratory Diseases • Thrombocytosis • JAK1 • JAK2

First-in-Class JAK/Rock Inhibitor Rovadicitinib in Myeloproliferative Neoplasms: A Single Arm, Multicenter, Open-Label, Phase I/Ib Study (ASH 2023) - P1, P2 | "Rovadicitinib was generally safe, well-tolerated and showed meaningful clinical activity in patients with MF, especially with palpable splenomegaly. Rovadicitinib may be a new treatment option for myelofibrosis patients. Furthermore, a randomized double-blind phase 2 study is ongoing, aiming to assess the efficacy and safety of rovadicitinib compared to hydroxyurea in patients with intermediate-2 or high-risk myelofibrosis in China (NCT05020652)."

Clinical • P1 data • Anemia • Myelofibrosis • Myeloproliferative Neoplasm • CALR • JAK2

Rovadicitinib in Patients with Hemophagocytic Lymphohistiocytosis: A Single Arm, Open-Label, Phase I Study (ASH 2024) - P1, P2 | "Rovadicitinib combined with glucocorticoid may be a new treatment option for patients with HLH unresponsive to glucocorticoid therapy. Meanwhile, a phase Ib/II study is ongoing, aiming to assess the efficacy and safety of rovadicitinib in patients with MAS unresponsive to glucocorticoid therapy."

Clinical • P1 data • Anemia • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Lymphoma • Myelofibrosis • Oncology • Rare Diseases • IL2RA

Rovadicitinib in Patients with Myelofibrosis Who Were Refractory or Relapsed or Intolerant to Ruxolitinib: A Single Arm, Multicenter, Open-Label, Phase Ib Study (ASH 2024) - P1, P1/2, P2 | "Rovadicitinib may be a new treatment option for those patients who failed ruxolitinib. Meanwhile, a phase Ib/II study is ongoing, aiming to assess the efficacy and safety of Rovadicitinib combined with TQB3617 (a novel oral BET inhibitor) in patients with myelofibrosis (NCT06122831)."

Clinical • P1 data • Anemia • Hematological Disorders • Infectious Disease • Myelofibrosis • Respiratory Diseases • CALR • JAK2

New molecules in the therapy of chronic graft-versus-host disease. (PubMed, Curr Opin Hematol) - "Expanding therapeutic options in cGvHD require decision-making based on organ involvement, prior therapy, and tolerability. Emerging compounds offer the potential to modulate chronic inflammation and fibrosis more precisely, supporting a move toward personalized and combinatorial approaches in advanced-line settings."

Journal • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Immunology • Inflammation • Transplantation

TQ05105 Tablet for Myelofibrosis Treatment in Ruxolitinib-Resistant or Intolerant Patients (clinicaltrials.gov) - P1 | N=9 | Terminated | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Trial completion date: Dec 2024 ➔ Aug 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2024 ➔ Aug 2025; This study was closed due to business reasons. Closure was not prompted by any safety or efficacy concerns.

Trial completion date • Trial primary completion date • Trial termination • Myelofibrosis

To Evaluate the Pharmacokinetics and Safety of TQ05105 Tablet in Renal Impairment Subjects (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Not yet recruiting ➔ Completed | Trial primary completion date: Jul 2025 ➔ Mar 2025

Trial completion • Trial primary completion date • Myelofibrosis • Renal Disease

ROVADICITINIB TABLET “JAK/ROCK INHIBITOR” INCLUDED IN THE BREAKTHROUGH THERAPEUTIC DESIGNATION PROCESS (HKEXnews) - "The board of directors (the 'Board') of Sino Biopharmaceutical Limited (the 'Company', together with its subsidiaries, the 'Group') announces that Rovadicitinib Tablet 'TQ05105 (JAK/ROCK inhibitor)' independently developed by the Group has been included in the Breakthrough Therapeutic Designation (BTD) process by the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China for the treatment of chronic graft-versus-host disease (cGVHD)....Currently, the Phase III clinical trial of rovadicitinib for the treatment of moderate to severe cGVHD is in the process of subject recruitment. The Group will accelerate the R&D of rovadicitinib globally to bring a better treatment solution to patients worldwide as soon as possible."

Breakthrough therapy • Trial status • Chronic Graft versus Host Disease

A First-in-Class JAK/ROCK Inhibitor, Rovadicitinib in Patients with Myelofibrosis who were Refractory or Relapsed or Intolerant to Ruxolitinib: A Single-Arm, Multicenter, Open-Label, Phase Ib Study. (PubMed, Eur J Pharmacol) - P1 | "This study suggests that patients with MF who are intolerant or resistant to Ruxolitinib or other JAK inhibitors might achieve significant clinical benefit after treatment with Rovadicitinib. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT06388759."

Journal • P1 data • Hematological Disorders • Myelofibrosis • Thrombocytopenia

PRECLINICAL…DATA ON ROVADICITINIB PRESENTED AT EHA 2025 (HKEXnews) - "The board of directors (the 'Board') of Sino Biopharmaceutical Limited...announces that the Group presented orally the results of preclinical...study of rovadicitinib for the treatment of acute graft-versus-host disease (aGVHD) at the 2025 European Hematology Association (EHA) Congress....Immunomodulatory mechanism of rovadicitinib: (i) Regulation of T cell subsets: It reduced the infiltration of pro-inflammatory Th1 and Tc1 cells in the small intestine of aGVHD mouse models while increasing the number of anti-inflammatory Treg cells, thereby improving the intestinal immune microenvironment; (ii) Inhibition of dendritic cell (DC) function: It downregulated the secretion of co-stimulatory molecules (CD80, CD86, CD40), chemokines (Cxcl9, Cxcl10), and IL-12, thereby weakening DC mediated T cell activation and differentiation."

Preclinical • Acute Graft versus Host Disease

EHA 2025 | Rovaxin Phase Ib data is amazing, which may rewrite the treatment pattern of hormone-resistant aGVHD [Google translation] (Sino Biopharm Press Release) - P1b | N=13 | NCT04941404 | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | "Recently, at the 30th European Hematology (EHA 2025) Congress, Sino Biopharmaceutical...announced the results of a Phase Ib clinical study of rovacitinib (JAK/ROCK dual pathway inhibitor, TQ05105) for acute graft-versus-host disease (aGVHD) in the form of an oral presentation....The single-arm, open, multicenter Phase Ib clinical trial of rovacitinib for the treatment of glucocorticoid-resistant aGVHD showed that for patients with hormone-resistant aGVHD, the overall remission rate reached 84% within 28 days, and the intestinal remission rate was as high as 80%, showing the characteristics of high response rate, rapid onset of action, and lasting remission. 38.5% of aGVHD patients completely stopped using glucocorticoids within 56 days , greatly reducing the side effects of long-term immunosuppression, and the 1-year survival rate was as high as 92.3%."

P1 data • Acute Graft versus Host Disease

JAK/ROCK INHIBITION WITH ROVADICITINIB SUPPRESSES MURINE AND HUMAN ACUTE GRAFT-VERSUS-HOST DISEASE: THE RESULTS OF PRECLINICAL AND PHASE 1B STUDY (EHA 2025) - P1/2 | "These data provide further evidence that rovadicitinib represents a new and potentially clinically approach to aGVHD in mice and humans."

P1 data • Preclinical • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Immunology • Oncology • Pneumonia • Thrombocytopenia • CD80 • CD86 • IFNG • JAK1 • TNFA

Role of ROCK2 inhibitors in the Treatment of Chronic Graft-versus-Host disease. (PubMed, Expert Opin Investig Drugs) - "This includes a review of the current and ongoing clinical data with belumosudil, and an overview of current ROCK2 inhibitors in development for cGVHD including rovadicitinib, zelasudil and GV-101. Many of the recent novel agents with unique mechanisms such as ROCK2 inhibitors (i.e. belumosudil) provide high response rates but rarely yield complete responses in cGVHD. The future of management of cGVHD will rely on investigating combination therapy upfront that may achieve deeper complete responses, developing newer preventative therapies, and advancements in biomarker detection/risk stratification for cGVHD."

Journal • Review • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Immunology • Transplantation

RESULTS FROM PHASE IB/IIA CLINICAL STUDY OF FIRST-IN-CLASS JAK/ROCK INHIBITOR “ROVADICITINIB” PUBLISHED IN BLOOD (HKEXnews) - P1b/2 | N=45 | NCT04944043 | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | "A total of 44 subjects were enrolled in the study, with 29 in a 10 mg twice-daily group and 15 in a 15 mg twice-daily group. The results showed that rovadicitinib was well tolerated, with no dose-limiting toxicity at both dosages and no rovadicitinib-related adverse events leading to discontinuation....The best overall response (BOR) for the overall study population was 86.4% (95% confidence interval (CI), 72.6-94.8), with no difference between the two dosage groups. Besides, BOR achieved 72.7% (8/11) in the glucocorticoid-refractory cohort and 90.9% (30/33) in the glucocorticoid-dependent cohort. All affected organs exhibited responses regardless of any prior therapy. The failure-free survival rate for 12 months was 85.2% (95% CI, 64.5-94.3)."

P1/2 data • Chronic Graft versus Host Disease

A First-in-Class JAK/ROCK Inhibitor, Rovadicitinib, for Glucocorticoid-Refractory or -Dependent Chronic GVHD. (PubMed, Blood) - P1/2 | "cGVHD-related symptoms were improved in 59.1% of patients. Rovadicitinib has favorable tolerability and notable clinical response rates, ameliorating the quality of life and reducing corticosteroid dose requirements in patients with glucocorticoid-refractory or -dependent cGVHD."

Journal • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Hematological Disorders • Immunology • JAK1 • JAK2

A Clinical Trial of TQ05105 Tablets in the Treatment of Chronic Graft-versus-host Disease (clinicaltrials.gov) - P2 | N=52 | Recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | N=40 ➔ 52

Enrollment change • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

Food effect trial of the pharmacokinetics and safety of TQ05105 in healthy Chinese subjects. (PubMed, Cancer Chemother Pharmacol) - P1 | "The findings demonstrate that food intake significantly alters the pharmacokinetic parameters of TQ05105 and its metabolite TQ12550, with a notable decrease in Cmax and AUC, and an increase in Tmax and t1/2. The single dose of the drug was well tolerated."

Journal • PK/PD data

Rovadicitinib Shows Safety, Clinical Activity After Ruxolitinib Intolerance in Myelofibrosis (OncLive) - "The novel, oral, small molecule JAK/ROCK inhibitor rovadicitinib (TQ05105) was generally well-tolerated and demonstrated clinical activity, including splenic and symptom responses, in patients with myelofibrosis who were relapsed/refractory or intolerant to ruxolitinib (Jakafi), according to primary results from a phase 1b study (NCT06388759) presented during the 2024 ASH Annual Meeting. All patients treated with rovadicitinib for longer than 24 weeks (n = 8) experienced a decrease in spleen volume compared with baselines. Throughout the study period, 6 patients (75%) achieved a spleen volume reduction of at least 35% (SVR35). Of these patients, 3 achieved SVR35 by their 12-week assessment. At week 24, 2 patients (25%) achieved SVR35, and 5 patients (62.5%) experienced a spleen volume reduction of at least 20% (SVR20)."

P1 data • Myelofibrosis

TQ05105-III-01: Evaluation of Rovadicitinib Compared to the Protocol Selected by Researchers in Third Line and Subsequent Studies of Moderate to Severe Chronic Graft-versus-host Disease (clinicaltrials.gov) - P3 | N=182 | Recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

Evaluation of Rovadicitinib Compared to the Protocol Selected by Researchers in Third Line and Subsequent Studies of Moderate to Severe Chronic Graft-versus-host Disease (clinicaltrials.gov) - P3 | N=182 | Not yet recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

New P3 trial • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

China Biopharmaceuticals’ new drug application has been accepted, bringing more clinical options to patients [Google translation] (Sohu.com) - "Recently, the official website of the Center for Drug Evaluation (CDE) of the National Medical Products Administration announced that the application for the listing of Rovadicitinib Tablets (TQ05105), a Class 1 new drug of Sino Biopharmaceutical (1177.HK) subsidiary Chia Tai Tianqing, has been accepted for the treatment of intermediate- and high-risk myelofibrosis (MF)."

China filing • Hematological Malignancies • Myelofibrosis • Oncology

To Evaluate the Pharmacokinetics and Safety of TQ05105 Tablet in Renal Impairment Subjects (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

New P1 trial • Myelofibrosis • Renal Disease