rovadicitinib (TQ05105) / Sino Biopharm - LARVOL DELTA

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

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

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

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 • Bone Marrow Transplantation • 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

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

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

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

Rovadicitinib Bests Hydroxyurea in Myelofibrosis (Cancer Therapy Advisor) - P2 | N=105 | NCT05020652 | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | "At week 24, the SVR35 rate was 58.33% in the rovadicitinib arm and 22.86% in the hydroxyurea arm (P =.0006). The best spleen response rate during the study period was 63.89% with rovadicitinib and 31.43% with hydroxyurea (P =.0017). The proportion of patients who achieved a 50% or greater reduction in total symptom score at week 24 was 61.11% with rovadicitinib and 45.71% with hydroxyurea (P =.136). The best symptom response rate during the study period was 77.78% with rovadicitinib and 54.29% with hydroxyurea (P =.0136)."

P2 data • Hematological Malignancies • Myelofibrosis • Oncology

The primary results from a randomized double-blind phase II study of rovadicitinib versus hydroxyurea in patients with myelofibrosis (ESMO 2024) - P1, P2 | "Rovadicitinib demonstrated significant clinical benefits compared to hydroxyurea in MF pts for spleen response or improved symptom response. Rovadicitinib may be a new treatment option for myelofibrosis pts."

Clinical • P2 data • Myelofibrosis • Oncology • JAK2

A Study of TQ05105 Tablets in Subjects With Glucocorticoid-Refractory Acute Graft-Versus-Host Disease (aGVHD) (clinicaltrials.gov) - P1/2 | N=13 | Active, not recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Trial completion date: Dec 2023 ➔ Dec 2024

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

A Clinical Trial of TQ05105 Tablets in the Treatment of Chronic Graft-versus-host Disease (clinicaltrials.gov) - P2 | N=40 | 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

First-in-human study of TQB3617, a BET inhibitor in patients with relapsed/refractory hematologic malignancies. (ASCO 2024) - P1, P1/2 | "TQB3617 was generally safe, well-tolerated and demonstrated encouraging efficacy in pts/w lymphoma or MF. Meanwhile, a phase Ib/II study is ongoing, aiming to assess the efficacy and safety of rovadicitinib combined with TQB3617 in pts/w MF (NCT06122831). More studies are planned."

Clinical • P1 data • Anemia • Diabetes • Dyslipidemia • Hematological Disorders • Hematological Malignancies • Herpes Zoster • Hypertriglyceridemia • Lymphoma • Myelofibrosis • Oncology • Solid Tumor • Varicella Zoster

A Clinical Trial of TQ05105 Tablets Combined With TQB3909 Tablets in the Treatment of Myelofibrosis (MF) (clinicaltrials.gov) - P1/2 | N=93 | Recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Not yet recruiting ➔ Recruiting | Initiation date: Feb 2024 ➔ May 2024

Enrollment open • Trial initiation date • Myelofibrosis

TQ05105 Tablet for Myelofibrosis Treatment in Ruxolitinib-Resistant or Intolerant Patients (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

New P1 trial • Myelofibrosis

A Clinical Trial of TQ05105 Tablets in the Treatment of Chronic Graft-versus-host Disease (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

New P2 trial • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

A Clinical Trial of TQ05105 Tablets Combined With TQB3909 Tablets in the Treatment of Myelofibrosis (MF) (clinicaltrials.gov) - P1/2 | N=93 | Not yet recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

New P1/2 trial • Myelofibrosis

A Clinical Trial of TQ05105 Tablets Combined With TQB3617 Capsules in the Treatment of Myelofibrosis (MF) (clinicaltrials.gov) - P1/2 | N=78 | Recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Myelofibrosis

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