Orelabrutinib is a highly selective BTK inhibitor developed by InnoCare. As a novel BTK inhibitor, orelabrutinib has high selectivity due to its innovative compound structure, which results in exceptional target occupancy and good efficacy and safety profile. In 2020, orelabrutinib was approved for the treatment of patients with relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) in China. In 2021, orelabrutinib was included into National Reimbursement Drug list to better benefit lymphoma patients.

According to the latest data, the overall response rate (ORR) was 93.8%, with complete response (CR) of 30%.

More data can be found in the article published at American Journal Of Hematology.

CLL/SLL, one of the most common types of leukemia, is an indolent malignancy of B lymphocytes. Although CLL/SLL is indolent, some patients will progress over time. There are 191,000 newly diagnosed CLL cases and 61,000 deaths every year globally.

Orelabrutinib was included in the CSCO Guidelines and has been recommended as a Class I treatment for r/r CLL/SLL. It has also won multiple innovation awards.

Orelabrutinib is a highly selective BTK inhibitor developed by InnoCare. As a novel BTK inhibitor, orelabrutinib has high selectivity due to its innovative compound structure, which results in exceptional target occupancy and good efficacy and safety profile. Orelabrutinib was approved for the treatment of patients with r/r mantle cell lymphoma (MCL) in China in 2020, included into National Reimbursement Drug list to benefit more lymphoma patients in 2021, and approved for marketing in Singapore in 2022.

According to the latest data, the ORR was 83% with CR of 36.8%.

More data can be found in the article published at Blood Advances, part of leading hematology journal Blood.

MCL is a subtype of B-cell non-Hodgkin lymphoma that results from malignant transformation of B-lymphocytes in the mantle zone of lymph node follicles. Despite high response rates after first-line hemo-immunotherapy, the majority of patients relapse and require subsequent treatment. There is no standard therapy for relapsed/refractory MCL, and the therapies approved by the U.S. Food and Drug Administration for this patient population are still limited, with low rates of CR, short durations of remission, and unfavorable safety and tolerability for older patients.

Orelabrutinib was included in the CSCO Guidelines and has been recommended as a Class I treatment for r/r CLL/SLL. It has also won multiple innovation awards.

Orelabrutinib is a highly selective BTK inhibitor developed by InnoCare. As a novel BTK inhibitor, orelabrutinib has high selectivity due to its innovative compound structure, which results in exceptional target occupancy and good efficacy and safety profile. Orelabrutinib was approved for the treatment of patients with r/r marginal zone lymphoma (MZL) in China in April 2023, and included in the updated National Reimbursement Drug List (NRDL) 2023, thus becoming the first and only approved BTK inhibitor in mainland China. The Company is initiating a Phase III MZL confirmatory study with orelabrutinib.

According to latest data, the ORR assessed by an Independent Review Committee (IRC) was 58.9%, and tumor reduction was observed in 92.2% of patients.

More data can be found in the article published at American Journal Of Hematology.

Orelabrutinib was included in the CSCO Guidelines and has been recommended as a Class I treatment for second-line therapy of MZL.

Orelabrutinib is a highly selective BTK inhibitor developed by InnoCare. As a novel BTK inhibitor, orelabrutinib has high selectivity due to its innovative compound structure, which results in exceptional target occupancy and good efficacy and safety profile. Patient enrollment of the registrational trial of orelabrutinib for first-line treatment of CLL/SLL was completed in China. The Company expects to submit the NDA in 2024.

CLL/SLL, one of the most common types of leukemia, is an indolent malignancy of B lymphocytes. There are 191,000 newly diagnosed CLL cases and 61,000 deaths every year globally.

Orelabrutinib is a highly selective BTK inhibitor developed by InnoCare. As a novel BTK inhibitor, orelabrutinib has high selectivity due to its innovative compound structure, which results in exceptional target occupancy and good efficacy and safety profile. The Company is initiating a global Phase III trial of orelabrutinib for the first-line treatment of MCL.

MCL is a subtype of B-cell non-Hodgkin lymphoma that results from malignant transformation of B-lymphocytes in the mantle zone of lymph node follicles. MCL occurs most frequently in men at a median age of 60 years, and the majority of patients are in an advanced stage of disease when diagnosed.

Orelabrutinib is a highly selective BTK inhibitor developed by InnoCare. As a novel BTK inhibitor, orelabrutinib has high selectivity due to its innovative compound structure, which results in exceptional target occupancy and good efficacy and safety profile. A registrational trial of orelabrutinib for the first-line treatment of MCD subtype diffuse large B-cell lymphoma (MCD DLBCL) is ongoing in China. The Company has designed a comprehensive combination therapy toolkit aimed at providing effective solutions for DLBCL.

DLBCL is the most common type of non-Hodgkin lymphoma (NHL), accounting for 31%~34% of NHL patients globally. In China, DLBCL accounts for 45.8% of all NHLs.

Orelabrutinib was included in the CSCO Guidelines.

Orelabrutinib is a highly selective BTK inhibitor developed by InnoCare. As a novel BTK inhibitor, orelabrutinib has high selectivity due to its innovative compound structure, which results in exceptional target occupancy and good efficacy and safety profile. Patient enrollment of a registrational trial of orelabrutinib for the treatment of r/r MCL was completed in the U.S. The Company expects to submit the NDA to the U.S. FDA in 2024.

MCL is a subtype of B-cell non-Hodgkin lymphoma (NHL) that results from malignant transformation of B-lymphocytes in the mantle zone of lymph node follicles. There is no standard therapy for r/r MCL, and the therapies approved by the FDA for this patient population are still limited, with low rates of CR, short durations of remission, and unfavorable safety and tolerability for older patients. Orelabrutinib was granted as Breakthrough Therapy Designation for the treatment of r/r MCL by U.S. FDA.

Tafasitamab is a humanized Fc-modified CD19 targeting immunotherapy, mediating B-cell lysis through apoptosis and immune effector mechanism. The tafasitamab regimen has been approved for marking in Hong Kong and approved for use in Bo’ao and Greater Bay Area. Patient enrollment of the registrational trial of tafasitamab in combination with lenalidomide for the treatment of r/r DLBCL was completed in China. The Company expects to submit the biologics license application (BLA) in 2024. The Company has designed a comprehensive combination therapy toolkit aimed at providing effective solutions for DLBCL.

Final five-year results showed that tafasitamab plus lenalidomide followed by tafasitamab monotherapy provided prolonged, durable responses in adult patients with r/r DLBCL. The ORR was 57.5% (primary endpoint).

DLBCL is the most common type of NHL, accounting for 31%~34% of NHL patients globally. In China, DLBCL accounts for 45.8% of all NHLs.

Tafasitamab in combination with lenalidomide was included in the CSCO Guidelines.

ICP-B02 (CM355) is a CD20xCD3 bispecific antibody co-developed by InnoCare and Keymed. ICP-B02 binds to CD20 on the tumor cells and CD3 on the T cells, redirects and activates T cells to eradicate tumor cells through T-cell Directed Cellular Cytotoxicity (TDCC) in the treatment of CD20+ B-cell malignancies.

The preliminary data of both the intravenous infusion (IV) and the subcutaneous (SC) formulations have shown good efficacy of ICP-B02 in patients with follicular lymphoma (FL) and DLBCL. All 13 patients who were treated with ICP-B02 at doses ≥6mg achieved response, resulting in an overall response rate (ORR) of 100%.

NHLs are the main type of CD20+ B-cell malignancies, accounting for 80%-90%, which include DLBCL, follicular lymphoma (FL), MCL, and CLL/SLL.

ICP-248 is a novel, orally bioavailable BCL2 selective inhibitor developed by InnoCare. BCL2 is an important part of apoptotic pathway and is overexpressed in a variety of hematologic malignancies. ICP-248 has an anti-tumor effect by selectively inhibiting BCL2 and restoring the mechanism of programmed cell death. The first patient has been dosed in a clinical trial of ICP-248 in combination with orelabrutinib as a first-line therapy for chronic lymphocytic leukemia /small lymphocytic lymphoma (CLL/SLL) in China.

ICP-248 demonstrated good safety and efficacy in Phase I study. At a dose of 100 mg QD, all patients achieved objective response, with a complete response rate (CR) of 50%.

ICP-248 will be developed as mono-therapy or in combination with other therapies in the treatment of hematological malignancies, with significant synergy with orelabrutinib.

ICP-490 is a novel targeted protein degrader developed from InnoCare’s molecular glue platform. It can overcome acquired resistance against earlier-generation of CRBN modulators. A clinical trial of ICP-490 for the treatment of multiple myeloma (MM) is ongoing in China. The IND was approved to conduct a clinical trial of ICP-490 in combination with dexamethasone. ICP-490 shows strong potential in hemato-oncology therapeutics as a monotherapy or in combination with others.

In the dose escalation study, ICP-490 demonstrated a good tolerability and safety profile. Pharmacodynamic (PD) analysis showed deeper degradation of primary pharmacological targets Aiolos (IKZF3) and Ikaro (IKZF1).

MM accounts for about 10% of blood tumors. NHL is the most common hematological malignancy in the world, ranking among the top 10 common malignant tumors in China.

ICP-B05 (CM369) is an anti-CC chemokine receptor 8 (CCR8) monoclonal antibody, developed by a joint venture between InnoCare and Keymed called Tiannuojiancheng Pharma in China. There are no CCR8-targeted drugs approved for marketing in the world.  ICP-B05 selectively depletes Tregs in the tumor microenvironment, which is more specific than other immunotherapies.

Preliminary efficacy was observed in NHL, demonstrating good tolerability and favorable PK profile with no DLT observed. PD biomarker, Treg depletion, was observed.

Orelabrutinib, a novel BTK inhibitor developed by InnoCare, has high target selectivity, 100% BTK target occupancy rate and favorable PK profile, which make it suitable for the development and treatment of various autoimmune diseases. The Company has achieved proof of concept (PoC) of orelabrutinib for the treatment of systemic lupus erythematosus (SLE) and the Phase IIb trial is ongoing in China. The Company expects to complete patient enrollment in 2024. Orelabrutinib is expected to become a potential first-in class BTK inhibitor for the treatment of SLE.

The Phase IIa trial for SLE demonstrated positive results, showing that orelabrutinib was safe and well tolerated with a dose dependent efficacy, along with trends indicating a reduction in proteinuria levels. More data can be found in the late-breaking oral presentation at EULAR 2022 (abstract number: LB0005).

SLE is a systemic disease that often leads to damage to organs, especially the kidneys and nervous system, skin, blood system, respiratory system, and almost all systems may be affected. According to Frost Sullivan analysis, it is expected that there will be 8.18 million SLE patients worldwide by 2025. The Chinese Systemic Lupus Erythematosus Development Report 2020 points out that there are about one million SLE patients in China, ranking first in the world in number of patients and second in incidence rate.

Orelabrutinib, a novel BTK inhibitor developed by InnoCare, has high target selectivity, 100% BTK target occupancy rate and favorable PK profile, which make it suitable for the development and treatment of various autoimmune diseases. Due to its excellent blood-brain barrier penetration, orelabrutinib has the potential to treat neurological diseases such as multiple sclerosis (MS). There are no BTK inhibitors for the treatment of MS approved for marketing in the world.

The global multicenter Phase II trial of orelabrutinib for the treatment of MS showed that the primary endpoint was achieved in all three treatment groups at week 24, and orelabrutinib significantly reduced disease activity in MS patients.

MS is an autoimmune, inflammatory disease of the central nervous system. If not diagnosed and treated in a timely manner, patients may experience paralysis, blindness, etc., and their quality of life is severely affected. According to Frost Sullivan analysis, it is estimated that the total number of MS patients worldwide will be 3.2447 million in 2025^[1].

[1] https://www.chinabaogao.com/market/202112/562541.html

Orelabrutinib, a novel BTK inhibitor developed by InnoCare, has high target selectivity, 100% BTK target occupancy rate and favorable PK profile, which make it suitable for the development and treatment of various autoimmune diseases. There are no BTK inhibitors for the treatment of primary immune thrombocytopenia (ITP) approved for marketing in the world. The last patient of the Phase III registrational trial is expected to be enrolled in China by the end of 2024.

According to Phase II study results, both 50mg QD and 30mg QD of orelabrutinib were safe in the treatment of patients with ITP. 40% at the 50mg arm reached primary endpoint. 83.3% achieved durable response among patients met the primary endpoint. A subgroup analysis of patients who previously responded to glucocorticoids (GC) or intravenous immunoglobulin (IVIG) showed that 75.0% of patients at the 50mg dose achieved the primary endpoint. More data can be found in the oral presentation at the European Hematology Association (EHA) 2023 Hybrid Congress (abstract number: S299) and the article published at American Journal of Hematology.

ITP is an acquired immune mediated disorder characterized by a decrease in peripheral blood platelet counts, resulting in an increased risk of bruising and bleeding. The annual incidence rate of adult ITP is about 2-10 per 100,000 people. Only about 70% of patients respond to first-line treatment, which is still ineffective for some patients or relapse. Therefore, it is necessary to explore new therapeutic targets. Inhibiting BTK can inhibit B cell activation and autoantibody production, thereby reducing damage to platelets.

Orelabrutinib, a novel BTK inhibitor developed by InnoCare, has high target selectivity, 100% BTK target occupancy rate and favorable PK profile, which make it suitable for the development and treatment of various autoimmune diseases. There are no BTK inhibitors for the treatment of neuromyelitis optica spectrum disorder (NMOSD) approved for marketing in the world. A Phase II clinical trial of orelabrutinib for the treatment of NMOSD is ongoing in China.

NMOSD is a chronic inflammatory demyelinating autoimmune disease of the central nervous system mainly involving the optic nerve and spinal cord, which are mediated by antigen-antibodies related to humoral immunity. NMOSD is a highly recurrent and disabling disease, with over 90% of patients having a recurrent course. Most patients have severe visual impairment (blindness), limb dysfunction (paraplegia), and urinary and fecal disorders.

ICP-332 is an oral TYK2 JH1 inhibitor developed by InnoCare. There are no TYK2 inhibitors for the treatment of atopic dermatitis (AD) approved for marketing in the world. ICP-332 was designed to be a potent and selective TYK2 inhibitor with 400 folds of selectivity against JAK2 to avoid the adverse events associated with nonselective JAK inhibitors.

ICP-332 achieved multiple efficacy endpoints in the Phase II study for the treatment of patients with moderate-to-severe atopic dermatitis (AD). The percentages of patients achieving at least 75% improvement in EASI 75 were significantly higher in the ICP-332 80 mg QD (64.0%, p<0.0001) and 120 mg QD (64.0%, p<0.0001) groups than that of placebo (8.0%). The overall incidence rates of adverse events (AEs) in the two treatment groups were comparable to that of the placebo group. ICP-332 showed top efficacy profile across different classes/MoAs of therapies for the treatment of AD patients (not a head-to-head comparison). More data can be found in the late-breaking oral presentation at 2024 American Academy of Dermatology (AAD) Annual Meeting (abstract number: 56157).

The Company expects to start the patient enrollment of the Phase III trial for AD in China, initiate US trials, and initiate a Phase II trial for a second indication of vitiligo in 2024.

According to the source of Pharma Intelligence, AD has become a major autoimmune disease with a global market potential of US$10 billion by 2030.

ICP-488 is a potent and selective TYK2 (tyrosine kinase 2) JH2 allosteric inhibitor developed by InnoCare. By binding the JH2 domain, ICP-488 blocks the signal transduction of IL-23, IL-12, type 1 IFN and other inflammatory cytokine, thereby inhibiting the pathological process of autoimmune and inflammatory diseases. The Company has completed the patient enrollment of the Phase II study of ICP-488 with psoriasis patients.

The Phase I trial has been completed, with preliminary efficacy assessed in psoriasis patients. The least-squares mean percentage change from baseline in the Psoriasis Area and Severity Index (PASI) score indicated preliminary significantly difference between the ICP-488 6 mg once-daily dosing group and placebo group at week 4 (38% vs 14%, p=0.0870). PASI 50 assessments demonstrated a 42% improvement with treatment of ICP-488 at 6 mg QD. The TRAE rate was the same between the ICP-488 arm and placebo arm.

Autoimmune diseases have become the third largest chronic disease after cardiovascular diseases and cancer. Data shows that 100 million people worldwide are affected by various types of psoriasis^[1].

[1] Progress in Epidemiological Investigation of Psoriasis, Journal of Diagnostics Concepts & Practice. 2021.

ICP-923 is an oral IL-17A blocker developed by InnoCare. IL-17 is a pro-inflammatory cytokine that plays an important role in immune functional responses. Orally administered small molecules targeting IL-17 may represent a convenient alternative to IL-17-targeting monoclonal antibodies for patients. This novel orally available small molecule can potently block the binding of both IL-17AA and IL-17AF to IL-17R.

Zurletrectinib, a pan-TRK inhibitor developed by InnoCare, markedly inhibits the activity of the wild type TRKA, TRKB and TRKC, as well as mutant TRKA with resistant mutation G595R or G667C. Zurletrectinib could overcome acquired resistance to the first generation TRK inhibitors.

InnoCare is accelerating the registrational trial of zurletrectinib in China and expecting to submit NDA by end of 2024. Zurletrectinib has demonstrated good efficacy and safety profile with an overall response rate (ORR) of 80-90%, and was shown to overcome acquired resistance to the first generation TRK inhibitors, bringing hope for patients who failed prior TRKi therapy.

The Company is conducting clinical trial of zurletrectinib to treat pediatric patients (2 to 12 years old), adolescent patients (12 to 18 years old) and adult patients.

In some rare tumor types, such as congenital infantile fibrosarcoma, the incidence of NTRK gene fusion is as high as 90%. NTRK gene fusion is associated with at least 19 tumor types in adults and children, including lung cancer, colorectal cancer, breast cancer, pancreatic cancer and melanoma.

Gunagratinib is a highly selective pan-FGFR inhibitor developed by InnoCare, which has the potential to treat various solid tumors. Compared with approved FGFR inhibitors, gunagratinib has higher target selectivity and can overcome the acquired resistance of the first generation FGFR inhibitors. The registrational trial of gunagratinib for the treatment of cholangiocarcinoma is ongoing in China, with the potential to be best-in-class.

The latest clinical study shows that gunagratinib is safe and well-tolerated with high response rate (52.9%) compared to other approved FGFR inhibitors in previously treated patients with locally advanced or metastatic CCA harboring FGR2 gene fusions or rearrangements. More data can be found in the poster at 2023 American Society of Clinical Oncology Gastrointestinal (ASCO GI) Cancers Symposium (abstract number: 572).

According to Frost Sullivan analysis, FGFR gene abnormalities occur in approximately 7.1% of solid tumor patients, with approximately 25% of them are cholangiocarcinoma patients. In China, it is expected that the number of new solid tumor patients carrying FGFR gene abnormalities will reach 454,000 by 2025, and the market size of pan-FGFR inhibitors is expected to reach 100 million US dollars by 2025.

ICP-189 is a novel SHP2 (Src Homology 2 domain containing protein tyrosine phosphatase) allosteric inhibitor developed by InnoCare. There are no SHP2 inhibitors approved for marketing in the world. ICP-189 is a potent oral allosteric inhibitor of SHP2 with reliable selectivity over other phosphatases. It demonstrated significant anti-tumor effects in various xenograft models as monotherapy.

InnoCare is collaborating with ArriVent to accelerate the clinical trial of ICP-189 in combination with furmonertinib, a highly brain-penetrant, broadly active mutation-selective EGFR (epidermal growth factor receptor) inhibitor, in China.

Preliminary efficacy was observed in ICP-189 monotherapy. As of the end of 2023, the dosage has been escalated up to 120 mg with no DLT observed, and it has shown a favorable PK profile with a long half-life. ICP-189 has demonstrated significant anti-tumor effect in tumor models driven by KRAS^G12C mutation and EGFR over-expression.

ICP-B05 (CM369) is an anti-CC chemokine receptor 8 (CCR8) monoclonal antibody, developed by a joint venture between InnoCare and Keymed called Tiannuojiancheng Pharma in China. There are no CCR8-targeted drugs approved for marketing in the world.  ICP-B05 selectively depletes Tregs in the tumor microenvironment, which is more specific than other immunotherapies. A Phase I trial of ICP-B05 in the treatment of solid tumors is ongoing in China.

ICP-033 is a multi-kinase inhibitor mainly targeting discoid in domain receptor 1 (DDR1) and vascular endothelial growth factor receptor (VEGFR) that inhibits angiogenesis and tumor cell invasion, normalizes abnormal blood vessels, and reverses the immunosuppressive state of the tumor microenvironment. Preclinical studies have shown that ICP-033 exhibits strong anti-tumor effects both in vivo and in vitro. A Phase I trial of ICP-033 for the treatment of solid tumors is ongoing in China.