Orelabrutinib

BEIJING--( BUSINESS WIRE )--InnoCare Pharma (HKEX: 09969; SSE: 688428), a leading biopharmaceutical company focusing on cancer and autoimmune diseases, today announced the 2024 interim results and corporate update as of 30 June 2024. Revenue of orelabrutinib increased by 30.0% year-on-year (YoY) to RMB417.0 million in the first half of 2024, with a YoY growth of 48.8% in the second quarter. This is attributed to the rapid growth of marginal zone lymphoma (MZL) as well as effective sales execution. The Loss decreased by 37.6% YoY to RMB268.0 million in the first half of 2024. Cash and Related Accounts Balance stood at about RMB7.99 billion as of 30 June 2024. This robust cash position provides the Company with flexibility to expedite clinical development and invest in a competitive pipeline. Gross Profit increased by 19.3% to RMB359.6 million in the first half of 2024. Gross profit margin was 85.7%, representing an increase of 5.8 percentage points, which was primarily due to the sales combination change of drugs and service. Research and Development Expenses increased by 17.5% 1 to RMB420.8 million in the first half of 2024 primarily due to mainly due to more resources to increased investment in advanced technology platform innovation and Phase III clinical trials aimed at accelerating the Group’s transformation. Total Revenue reached RMB419.7 million in the first half of 2024, which was primarily attributable to rapid ramp-up of orelabrutinib sales volume. All three approved indications of orelabrutinib, including relapsed and refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (r/r CLL/SLL), relapsed and refractory mantle cell lymphoma (r/r MCL) and relapsed and/or refractory marginal zone lymphoma (r/r MZL) have been covered under the updated National Reimbursement Drug List (NRDL) 2023. Orelabrutinib has been approved as the first and only BTK inhibitor for r/r MZL in China. Orelabrutinib was officially included as a class I recommended regimen for the treatment of r/r MZL patients in the 2024 Chinese Society of Clinical Oncology (CSCO) Guidelines. The Company’s commercial capabilities have undergone significant enhancements, including an optimized and upgraded commercial team, which has developed more executable strategies. The dedicated team has been optimized to operate with heightened efficiency and strategic focus, ensuring effective execution of market initiatives. This optimization has bolstered the team’s ability to penetrate markets swiftly and effectively. These advancements underscore InnoCare’s commitment to delivering value and driving sustainable growth in the Company’s commercial endeavors. Benefiting Patients Worldwide Entering InnoCare version 2.0, the Company is continuing to strengthen the entire value chain and rapidly advance the clinical trials of its pipeline. Over the next three to five years, five to six innovative drugs are expected to be approved for marketing, addressing unmet treatment needs and benefiting patients worldwide. Becoming a Leading Player in Hemato-Oncology Hemato-oncology, including lymphoma, leukemia, and myeloma, is known for its high mortality rates. InnoCare is dedicated to developing therapeutics with diverse mechanisms of action (MoA) to achieve comprehensive coverage of blood tumor indications, with the aspiration of becoming a leader in this field. Beyond the approved indications, InnoCare is advancing the first line registrational clinical trials and new drug application (NDA) for orelabrutinib. Tafasitamab (CD19 monoclonal antibody), another key product, is expected to be approved for marketing in the first half of next year, further strengthening the Company's market presence. InnoCare is also accelerating the development of BCL2 inhibitor ICP-248, which has significant combination synergy with orelabrutinib. Notably, BCL2 inhibitors are the preferred therapeutic option following resistance to BTK inhibitors, creating an optimal sequential treatment strategy. With these assets in the pipeline, along with the molecule glue ICP-490, monoclonal antibody ICP-B05 and bispecific antibody ICP-B02, and potential future developments from internal and external sources, the Company is aimed at becoming a leading player in hemato-oncology both in China and worldwide. Orelabrutinib The clinical trial of orelabrutinib in combination with ICP-248, a BCL2 inhibitor developed by InnoCare, for first-line treatment of CLL/SLL was initiated in May of this year, and patient enrollment of the Phase II trial has been completed as of this announcement . The Company is accelerating the registrational trials and NDA of the first line indications of orelabrutinib, including CLL/SLL, SCL and diffuse large B-cell lymphoma (DLBCL). Orelabrutinib continues to gain attention from top international academic conferences. Five studies of orelabrutnib were selected for the European Society for Medical Oncology (ESMO) Congress 2024, with a prospective study of orelabrutinib regimen in treatment-naive MZL as an oral presentation at the conference. 10 studies on orelabrutinib have been selected for the European Hematology Association (EHA) 2024 Hybrid Congress. Tafasitamab The biologics license application (BLA) for tafasitamab in combination with lenalidomide for adult patients with r/r DLBCL who are not eligible for Autologous Stem Cell Transplant (ASCT) was accepted and granted priority review in China in June 2024. DLBCL is the most common type of non-Hodgkin’s lymphoma (NHL), accounting for 31%~34% of NHL patients globally. In China, DLBCL accounts for 45.8% of all NHLs 2 . Tafasitamab regimen was approved by the Department of Health, the Hong Kong Special Administrative Region, China, and approved for use in Bo’ao and Greater Bay Area with first prescription issued respectively. ICP-248 ICP-248 is a novel, orally bioavailable BCL2 selective inhibitor. The clinical trial of ICP-248 in combination with orelabrutinib for first line (1L) CLL/SLL was initiated, and patient enrollment for the Phase II trial has been completed. So far, 47 patients have been dosed, and among 28 evaluable patients with BTK inhibitor failure r/r MCL, the overall response rate (ORR) was 71.4% . The investigational new drug (IND) filing for ICP-248 for Acute Myeloid Leukemia (AML) has been accepted by the CDE . ICP-490 Developed from InnoCare's molecular glue platform, ICP-490 shows strong potential to revolutionize the treatment of MM, NHL, and other hemato-oncology indications, whether as a monotherapy or in combination with other therapies. The Phase I dose escalation study is ongoing in China with multiple myeloma (MM) and NHL patients , demonstrating a good tolerability and safety profile. This safety profile has supported the decision to continue dose escalation to the next dosage level. ICP-B02 (CM355) ICP-B02 is a CD20xCD3 bispecific antibody co-developed with Keymed. Data from 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 15 patients who were treated with ICP-B02 at doses ≥6mg achieved response, resulting in an ORR of 100% . All patients who achieved CR maintained the remission as of the cutoff date. Based on the encouraging results of ICP-B02 as a single agent, the Company is planning for a dose expansion study of ICP-B02 in combination with other immunochemotherapies targeting earlier lines of treatment in NHL patients. The IND application for the combination therapies was approved in China in June 2024. ICP-B05 (CM369) ICP-B05 (CM369) is a potential first-in-class anti-CC chemokine receptor 8 (CCR8) monoclonal antibody, co-developed by InnoCare and Keymed as a monotherapy or in combination with other therapies for the treatment of various cancers. The Phase I trial is ongoing, aiming to evaluate the safety, tolerability, pharmacokinetic characteristics, and efficacy of ICP-B05 in subjects with advanced solid tumors and r/r NHL. Preliminary efficacy was observed in NHL patient . ICP-B05 was well tolerated with no dose-limiting toxicities (DLTs). Advancing Research and Development in Solid Tumors InnoCare strives to expand the breadth of its pipeline to cover solid tumor diseases areas through a combination of targeted therapy and immune-oncology approaches. The Company believes that potential best-in-class molecule, zurletrectinib (ICP-723), will enable InnoCare to establish a solid footprint in the field of solid tumor treatment. To benefit a broader range of patients, InnoCare’s rapidly maturing early-stage pipeline, including the cornerstone therapy ICP-189 and ICP-B05 immune-oncology treatment, aims to offer competitive treatment solutions for a large array of solid tumors, both in China and worldwide. Zurletrectinib (ICP-723) The fusion mutation of NTRK gene is a carcinogenic factor for many cancers, including lung cancer, colorectal cancer, breast cancer, pancreatic cancer and melanoma . Zurletrectinib is a second generation TRK inhibitor developed by InnoCare. The Company is accelerating the registrational trial of zurletrectinib in China, which has entered the pre-NDA stage . Zurletrectinib has demonstrated good efficacy and safety profile. It was shown to overcome acquired resistance to the first generation TRK inhibitors, bringing hope for patients who failed prior TRKi therapy. The clinical study with zurletrectinib has covered neurotrophic tyrosine receptor kinase (NTRK) gene fusion adult patients, adolescent patients (12 to 18 years old) and pediatric patients (2 to 12 years old). The efficacy has been observed in both adolescent and pediatric patients. The dose escalation trial for pediatric patients has been completed. ICP-189 The novel SHP2 allosteric inhibitor, ICP-189, is being developed for the treatment of solid tumors as a single agent and/or in combination with other antitumor agents. The clinical trial of the combination of InnoCare’s lCP-189 with ArriVent’s third generation EGFR inhibitor furmonertinib in patients with advanced non-small cell lung cancer (NSCLC) is ongoing, with the preliminary efficacy observed. NSCLC is the predominant subtype of lung cancer, accounting for approximately 85% of all cases 3 . Preliminary efficacy was observed in ICP-189 monotherapy. As a potential first-in-class SHP2 inhibitor, ICP-189 is an ideal partner for combination with multiple targeted and immune-oncology therapies in solid tumors. ICP-189 has demonstrated significant anti-tumor effect in tumor models driven by KRAS G12C mutation and Epidermal Growth Factor Receptor (EGFR) over-expression. The SHP2 combination therapy provides a promising treatment option for NSCLC patients who are resistant to the third generation EGFR inhibitors. As of this announcement, the study of the 120mg QD group has been completed, with no DLT observed, and it has shown a favorable PK profile with a long half-life. The patient enrollment at 160mg QD is ongoing. InnoCare is also actively exploring preclinical development in solid tumors, and developing small molecule and large molecule innovative drugs by building a differentiated platform for the treatment of solid tumors such as lung cancer and gastric cancer, so as to meet huge unmet medical needs. Comprehensive Coverage in Autoimmune Diseases Autoimmune diseases can affect almost every organ in the body and can occur at any age. The global market for autoimmune disease therapeutics anticipated to reach $185 billion by 2029 4 . The Company has fortified its powerful discovery engine focusing on global frontier targets for the development of differentiated autoimmune therapeutics through B-cell and T-cell pathways, aiming to offer first-in-class or best-in-class treatments to the massive unmet medical needs with promising market potential worldwide and/or regionally. Orelabrutinib ITP: The Company has achieved proof of concept (PoC) for orelabrutinib in the treatment of primary immune thrombocytopenia purpura (ITP), and has completed enrollment of over 50% of patients in the Phase III registrational trial. The annual incidence rate of adult ITP is about 2-10 per 100,000 people 5 . Only about 70% of patients respond to first-line treatment. Orelabrutinib has potential to provide a better treatment option for ITP patients 6 . From blood tumor to autoimmune diseases in the hematological field, orelabrutinib will demonstrate its huge commercial potential. The ITP Phase II result was published by the American Journal of Hematology in April 2024. For details, please refer to https://onlinelibrary-wiley-com.libproxy1.nus.edu.sg/doi/10.1002/ajh.27303 . SLE: The Phase IIa trial for systemic lupus erythematosus (SLE) demonstrated positive results, with remarkable SLE Responder Index (SRI)-4 response rates observed in a dose dependent manner, along with trends indicating a reduction in proteinuria levels. Orelabrutinib is global first and only BTK inhibitor ever shown efficacy in Phase II SLE trials. A Phase IIb trial is ongoing, and the patients enrollment has been nearly completed as of this announcement . 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. ICP-332 ICP-332 is a novel tyrosine kinase 2 (TYK2) inhibitor that is being developed for the treatment of various T-cell related autoimmune disorders, including atopic dermatitis (AD), vitiligo, inflammatory bowel disease, etc., with broad market prospects. The latest data of ICP-332 for the treatment of patients with moderate-to-severe AD has been released at the 2024 American Academy of Dermatology (AAD) Annual Meeting as a late-breaking oral presentation. ICP-332 achieved multiple efficacy endpoints in the China Phase II study for the treatment of patients with moderate-to-severe AD, demonstrating an outstanding efficacy and safety profile. ICP-332 showed better efficacy profile across different classes/MoAs of therapies for the treatment of AD patients (not a head-to-head comparison). In the ICP-332 80 mg once-daily (QD) and 120 mg QD groups for four weeks, the response rates of EASI 90 (improvement of at least 90% in EASI score from baseline) and NRS (Pruritus Numerical Rating Scale) score from baseline ≥4 points demonstrated a 40% and 56% improvement respectively compared with the placebo group, both of which were superior to competitors. ICP-332 was safe and well tolerated in AD patients. The overall incidence rates of adverse events (AEs) in the two treatment groups were comparable to that of the placebo group. The Company expects to start the patient enrollment of the Phase III trial for AD in China in the fourth quarter of 2024, and to submit IND for the Phase II/III trial for a second indication of vitiligo. The US trials have been initiated . ICP-488 Data shows that 100 million people worldwide are affected by various types of psoriasis 7 . ICP-488 is a potent and selective TYK2 allosteric inhibitor that binds to the pseudo kinase JH2 domain of TYK2 and blocks IL-23, IL12, type 1 IFN, and other cytokine receptors. The Phase II study of ICP-488 in psoriasis has completed patient enrollment in May 2024. The Company expects the data readout by the end of 2024 . A total of 129 patients were enrolled in this study. Patients were randomly assigned to two treatment groups and placebo group, for 12 consecutive weeks of treatment. ICP-488 demonstrated good efficacy and safety in the Phase I study of ICP-488 in psoriasis patients. Novel Small Molecule Inhibitor of IL-17 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. Dr. Jasmine Cui , the Co-founder, Chairwoman and CEO of InnoCare, said, "In the first half of 2024, our commercial team exceeded pre-set goals, with a significant increase in revenue. We have developed innovative drugs with huge unmet medical needs, with three NDAs submitted in the first half of this year. We have also been actively exploring preclinical innovation, laying a solid foundation for future development. Looking ahead to the second half of the year, we will continue to make concerted efforts in the fields of new drug R&D, clinical development, commercialization and globalization, focusing on key goals to achieve high-quality development.” To know more about the detailed financial data and business updates of InnoCare 2024 annual results, please log in to https://www.innocarepharma.com/en/investor/home . Conference Call Information InnoCare will host a conference call at 9:30 a.m. Beijing time on August 21 in Chinese and at 8:30 p.m. Beijing time in English on August 21, 2024. Participants must register in advance of the conference call. Details are as follows: For English conference call, please register through the below link: https://ubs-innocare-h124-earnings-call.open-exchange.net/ For Chinese conference call, please register through the below link: https://s.comein.cn/AHJAP Forward-looking Statement This report contains the disclosure of some forward-looking statements. Except for statements of facts, all other statements can be regarded as forward-looking statements, that is, about our or our management's intentions, plans, beliefs, or expectations that will or may occur in the future. Such statements are assumptions and estimates made by our management based on its experience and knowledge of historical trends, current conditions, expected future development and other related factors. This forward-looking statement does not guarantee future performance, and actual results, development and business decisions may not match the expectations of the forward-looking statement. Our forward-looking statements are also subject to a large number of risks and uncertainties, which may affect our short-term and long-term performance. About InnoCare InnoCare (HKEX: 09969; SSE: 688428) is a commercial stage biopharmaceutical company committed to discovering, developing, and commercializing first-in-class and/or best-in-class drugs for the treatment of cancer and autoimmune diseases with unmet medical needs in China and worldwide. InnoCare has branches in Beijing, Nanjing, Shanghai, Guangzhou, Hong Kong, and United States. ___________________________________ 1 Based on HKFRS (Hongkong Financial Reporting Standards) 2 Hematology Branch of Chinese Medical Association 3 Journal of Clinical Oncology，IF: 50.717 4 iHealthcareAnalyst, Inc., Oct. 3, 2023 5 Adult ITP Guidelines (2020 Edition) 6 Poster at the 63rd ASH Annual Meeting (Abstract Number: 3172) 7 Progress in Epidemiological Investigation of Psoriasis, Journal of Diagnostics Concepts & Practice. 2021.

BEIJING--( BUSINESS WIRE )--InnoCare Pharma (HKEX: 09969; SSE: 688428), a leading biopharmaceutical company focusing on the treatment of cancer and autoimmune diseases, today announced that the first subject has been dosed in clinical trial of the Company's novel TYK2 (Tyrosine Kinase 2) inhibitor ICP-332 in the United States. ICP-332 is a potent and selective TYK2 inhibitor. ICP-332 achieved multiple efficacy endpoints in the China Phase II study for the treatment of patients with moderate-to-severe atopic dermatitis (AD), demonstrating an outstanding efficacy and safety profile. ICP-332 showed better efficacy profile across different classes/MoAs of therapies for the treatment of AD patients (not a head-to-head comparison). The detailed data was presented at the 2024 American Academy of Dermatology (AAD) Annual Meeting as a late-breaking oral presentation. Currently, no TYK2 inhibitors have obtained marketing approval for the treatment of AD anywhere in the world. As a non-receptor tyrosine kinase, TYK2 is a member of the JAK kinase family, which is an important kinase on the JAK-STAT signaling pathway and plays an important role in the pathogenesis of inflammatory diseases. Dr. Jasmine Cui, Co-founder, Chairwoman and CEO of InnoCare, said, "We are committed to developing innovative drugs in the field of autoimmune diseases. In addition to ICP-332, we have developed robust pipeline of differentiated therapeutics for autoimmune disease with significant market potential worldwide, including orelabrutinib (BTK inhibitor), ICP-488 (TYK2-JH2 inhibitor) and ICP-923 (IL-17 small molecule inhibitor). Adhering to the core value of 'Science-driven innovation for the benefit of patients’, we are committed to accelerating clinical development and look forward to our innovative drugs benefiting patients with autoimmune diseases as early as possible." About InnoCare InnoCare is a commercial stage biopharmaceutical company committed to discovering, developing, and commercializing first-in-class and/or best-in-class drugs for the treatment of cancer and autoimmune diseases with unmet medical needs in China and worldwide. InnoCare has branches in Beijing, Nanjing, Shanghai, Guangzhou, Hong Kong, and United States.