zurletrectinib

BEIJING--(BUSINESS WIRE)-- InnoCare Pharma (HKEX: 09969; SSE: 688428), a leading biopharmaceutical company focusing on cancer and autoimmune diseases, today announced the 2023 annual results as of 31 December 2023. Financial Highlights Revenue increased by 18.1% to RMB738.5 million in 2023, including RMB670.7 million from orelabrutinib, an increase of 18.5%, mainly due to the continuous and rapid ramp-up of orelabrutinib sales. Gross Profit increased by 26.6% to RMB610.1 million in 2023, with a gross profit margin of 82.6%, representing an increase of 5.5%, mainly due to the increase of orelabrutinib sales and the reduction in the unit cost of sales. Research and Development Expenses increased by 17.5% to 751.2 million in 2023, primarily due to heightened spending on global clinical trials that have made significant progress and strategic investments in early-stage candidates poised to become key future assets. The Loss decreased by 27.8% to RMB645.6 million. Cash and Bank Balance stood at approximately RMB8.2 billion. With this robust cash position, the Company is well-positioned to expedite the clinical development of key projects and invest in a competitive pipeline. Accelerating Pipeline Development for the Benefit of Patients In 2023, InnoCare has continued to advance its robust pipeline across various clinical stages, continuously unleashing the power of innovation to meet unmet medical needs. Orelabrutinib has become the first and only BTK inhibitor approved for the treatment of relapsed or refractory Marginal Zone Lymphoma (r/r MZL) in China, an indication which has been included in the updated 2023 National Reimbursement Drug List (NRDL) without a price cut. The Company has continuously forged ahead on the road to improving public health. Additionally, the Phase II study results of our novel TYK2 inhibitor, ICP-332, met the primary endpoints in patients with moderate-to-severe atomic dermatitis. From research, clinical development, manufacturing, commercialization, to global collaboration, InnoCare not only established an integrated platform, but also formulated a clear growth strategy aimed at benefiting patients worldwide as we embark on the Company 2.0 phase. Building A Leading Franchise in Hemato-Oncology With orelabrutinib (BTK inhibitor) serving as the backbone therapy and a key component of InnoCare’s extensive pipeline in hemato-oncology – including tafasitamab (anti-CD19 antibody), ICP-248 (BCL2 inhibitor), ICP-B02 (CD20xCD3 bispecific antibody), ICP-490 (CRBN E3 Ligase modulator), and potential future developments from internal and external sources - InnoCare strives to become a leading player in hemato-oncology both in China and worldwide. Orelabrutinib's exceptional safety and efficacy profiles promise synergistic benefits when combined with other pipeline drugs, such as ICP-248 (BCL2 inhibitor). InnoCare intends to address various segments, such as non-Hodgkin lymphoma (NHL), multiple myeloma (MM), and leukemia, utilizing both single and combination therapies. Orelabrutinib Orelabrutinib was approved for the treatment of relapsed/refractory marginal zone lymphoma (r/r MZL) in April 2023 and included in the NRDL. Orelabrutinib has thus become the first and only BTK inhibitor for r/r MZL in China, which also marks orelabrutinib’s third indication approved in China. Patient enrollment of the Phase III registrational trial of orelabrutinib for the first-line treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) was completed in China in the first half of 2023. The Company expects to submit the NDA in the third quarter of 2024. In the U.S., patient enrollment of the Phase II registrational trial for relapsed/refractory mantle cell lymphoma (r/r MCL) was completed. The Company expects to submit the NDA to the U.S. Food and Drug Administration (US FDA) in the third quarter of 2024. The Company is initiating a global Phase III study of orelabrutinib for the first-line treatment of MCL. Orelabrutinib was approved by the Health Sciences Authority (HSA) of Singapore for the treatment of adult patients with r/r MCL, which marks InnoCare’s entrance onto international commercial markets. The Company expects to submit r/r MZL NDA in Singapore in 2024. The Company is initiating a Phase III MZL confirmatory study with orelabrutinib. The strategic combination of orelabrutinib with BCL2 inhibitor, ICP-248, for the first line treatment of CLL/SLL. A Phase III registrational study of orelabrutinib for the first-line treatment of MCD subtype diffuse large B-cell lymphoma (DLBCL) is ongoing in 45 sites in China. Tafasitamab 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 the second quarter of 2024 and anticipates BLA approval in the first half of 2025. Tafasitamab in combination with lenalidomide 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 The preliminary results demonstrated good safety pro achieved favorable pharmacokinetic (PK), demonstrating differentiation from other BCL2 inhibitors. So far, seventeen patients were dosed, and among six evaluated patients, the ORR was 100%, with three complete responses (CR) in which two achieved undetectable minimal residual disease (uMRD). The clinical trial approval of ICP-248 in combination with orelabrutinib as a first-line therapy for CLL/SLL in March 2024. In the U.S., the IND was cleared in January 2024. ICP-248 will become an important asset for the Company’s globalization. ICP-248 is a novel, orally bioavailable BCL2 selective inhibitor, developed as monotherapy or in combination with orelabrutinib for the treatment of CLL/SLL, MCL, AML, and other NHLs. ICP-B02 (CM355) 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 ORR of 100%. Among the nine patients who were evaluable in the SC group, seven achieved a complete response (CR), including two with DLBCL. Based on the encouraging results of ICP-B02 single agent, the Company is planning for dose expansion study of ICP-B02 in combination with other immunochemotherapies for earlier lines of treatment in NHL patients. An IND for the combination therapies has been submitted. ICP-B02 is a CD20xCD3 bispecific antibody co-developed with Keymed. ICP-490 The Phase I dose escalation study is ongoing in China with multiple myeloma (MM) patients, demonstrating a good tolerability and safety profile. Pharmacodynamic (PD) analysis showed deeper degradation of primary pharmacological targets Aiolos (IKZF3) and Ikaro (IKZF1). In September 2023, 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. ICP-490 was developed from InnoCare’s molecular glue platform for the treatment of MM and other hematological malignancies. ICP-B05 (CM369) The Phase I trial is ongoing, showing good tolerability with no DLT observed. The preliminary results demonstrate favorable PK pro PD biomarker, Treg depletion, was observed. Dose escalation in solid tumors has been escalated up to 150 mg, which is also the initial dose designated for NHL. Preliminary efficacy was observed in NHL. ICP-B05 is an anti-CC chemokine receptor 8 (CCR8) monoclonal antibody, a potential first-in-class drug co-developed with KeyMed as a monotherapy or in combination with other therapies for the treatment of various cancers. Developing B-cell and T-cell Pathways 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 20291. 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) of orelabrutinib for the treatment of primary immune thrombocytopenia purpura (ITP), with a Phase III registrational trial underway in China. The last patient is expected to be enrolled by the end of 2024. In June 2023, the ITP Phase II result was orally presented at the European Hematology Association (EHA) 2023 Hybrid Congress. The results showed that 40% of patients met primary endpoint at 50mg. 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. 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. A Phase IIb trial is ongoing, and the Company expects to complete patient enrollment by mid-2024. MS: The 24-week data of orelabrutinib from the multiple sclerosis (MS) global Phase II trial is consistent with the previous reported 12-week data in terms of both efficacy and safety. The primary endpoint was achieved dose-dependently (Cmax driven) in all three active orelabrutinib treatment groups. Notably, a 92.3% relative reduction was achieved in cumulative number of new gadolinium (Gd) + T1 lesions at week 24 at 80mg QD compared to placebo arm (which switched to orelabrutinib 50mg QD after Week 12). This reduction stands out as a leading indicator of efficacy when compared to other MS therapies that are approved or in developmental stages. All orelabrutinib groups achieved T1 new lesion control after 4 weeks of treatment, with effects sustained through 24 weeks. The 80 mg QD cohort showed the highest reduction rate of cumulative number of new lesions Gd+T1 lesions and the best for lesion control throughout 24 weeks, with the best safety profile, indicating orelabrutinib’s potential as a leading MS treatment. NMOSD: The Phase II clinical trial for the treatment of neuromyelitis optica spectrum disorder (NMOSD) is ongoing in China. ICP-332 The latest data of ICP-332 for the treatment of patients with moderate-to-severe atopic dermatitis (AD) has been released at the 2024 American Academy of Dermatology (AAD) Annual Meeting as a late-breaking oral presentation. ICP-332 demonstrated an outstanding efficacy and safety profile. ICP-332 achieved multiple efficacy endpoints in the 80 mg QD and 120 mg QD dosing groups respectively, including the percentage change in Eczema Area and Severity Index (EASI) score from baseline, EASI 50, EASI 75, EASI 90 (improvement of at least 50%, 75% and 90% in EASI score from baseline), Investigator’s Global Assessment (IGA) 0/1 (score of 0 ‘clear’ or 1 ‘almost clear’) with >= 2 points improvement, and Pruritus Numerical Rating Scale (NRS) score from baseline, etc. The mean percentage change from baseline of the EASI score reached 78.2% and 72.5% at the 80 mg QD and 120 mg QD groups respectively, both with a highly significant P value (p<0.0001), compared to 16.7% for the patients receiving placebo. 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%), which are better than the reported efficacies of multiple approved innovative drugs treated for 12 weeks or 16 weeks (not a head-to-head comparison). In the ICP-332 80 mg QD group, the response rates of EASI 90 and IGA 0/1 with >=2 points from baseline demonstrated a 40.0% (P=0.0009) and 32.0% (P=0.0047) improvement respectively compared with the placebo group. ICP-332 was safe and well tolerated in AD patients. The overall incidence rates of adverse events (AEs) and AEs related to infections and infestations 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, initiate US trials, and initiate a Phase II trial for a second indication of vitiligo in 2024. ICP-332 is a novel tyrosine kinase 2 (TYK2) inhibitor that is being developed for the treatment of various T-cell related autoimmune disorders. ICP-488 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. Following single ascending doses (1mg to 36mg) and multiple ascending doses (3mg -12mg) once daily, ICP-488 plasma exposures were dose proportional. No significant food effect was observed following co-administration with standard high-fat, high-calorie meals. ICP-488 demonstrated good tolerability and safety. The TRAE rate was the same between the ICP-488 arm and placebo arm. The Phase II study of psoriasis is ongoing, InnoCare targets to finish the patient enrollment in the first half of 2024. 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. ICP-B02 (CM355) ICP-B02 (SC & IV) induced a profound and sustained depletion of peripheral B- cells after first infusion in Phase I/II clinical trial in r/r NHL patients. Given the critical role of B-cells in a variety of severe autoimmune diseases, ICP-B02 may have wider applications in severe autoimmune diseases. ICP-923 (New Target) 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. Building Innovative Solid Tumor Assets 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-192, 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) InnoCare is accelerating the registrational trial of zurletrectinib in China. The NDA is expected to be submitted by the end of 2024. An outstanding efficacy of 80-90% ORR was observed in adult patients with various cancers carrying NTRK gene fusion who received ≥8 mg dosages. Zurletrectinib 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 a clinical trial of zurletrectinib for pediatric (2 to 12 years old) and adolescent patients (12 to 18 years old). Patient enrollment of pediatric patients is ongoing, with PR observed. ICP-189 InnoCare and ArriVent reached a clinical development collaboration to evaluate the anti-tumor activity and safety of the combination of InnoCare’s novel SHP2 allosteric inhibitor, ICP-189, with ArriVent’s third generation EGFR inhibitor furmonertinib in patients with advanced non-small cell lung cancer (NSCLC). Currently, the combo study is underway. NSCLC is the predominant subtype of lung cancer, accounting for approximately 85% of all cases2. 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. Preliminary efficacy was observed in ICP-189 monotherapy. As of this announcement, the dosage has been escalated up to 120 mg with no DLT observed, and it has shown a favorable PK pro a long half-life. The patient enrollment at 160mg QD is ongoing. 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 KRASG12C mutation and EGFR over-expression. Gunagratinib (ICP-192) The latest data of gunagratinib in patients with cholangiocarcinoma (CCA) was presented at 2023 ASCO-GI3. Gunagratinib showed good efficacy and safety in previously treated patients with locally advanced or metastatic CCA harboring FGR2 gene fusions or rearrangements. Other Corporate Development InnoCare appointed Xin Fu and Jeff Chen as Chief Financial Officer and Chief Commercial Officer respectively. InnoCare was approved by the Hong Kong Stock Exchange to remove "B" from the stock code from May 12, 2023. This is another important milestone in the Company's development. Following the approval for commercial production, InnoCare Guangzhou quickly launched the manufacturing of orelabrutinib, which is now available to patients in China. This achievement allows InnoCare to cover the entire industry chain from in-house research and development to production. Dr. Jasmine Cui, the Co-founder, Chairwoman and CEO of InnoCare, said, "We must maintain the entrepreneurial spirit and persist in continuous innovation, focusing on key objectives with high quality growth, so as to make our contributions to patients, partners, and the broader biopharmaceutical industry. We’re committed to deepening our focus on original innovation, pushing forward multiple innovative molecules to further strengthen our pipeline; we will accelerate the registrational trials both in China and worldwide, aiming to submit multiple NDAs; we will increase market penetration to achieve our long-term strategy and realize significant sales increases; we will amplify our global presence and push more projects to reach international markets.” To know more about the detailed financial data and business updates of InnoCare 2023 annual results, please log in to . Conference Call Information InnoCare will host a conference call at 8:30 p.m. Beijing time on March 28 in English and at 9:30 p.m. Beijing time in Chinese on March 29, 2024. Participants must register in advance of the conference call. Details are as follows: For English conference call, please register through the below link: For Chinese conference call, please register through the below link: 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 iHealthcareAnalyst, Inc., Oct. 3, 2023 2 Cancer-free 3 2023 ASCO GI Abstract

2024年3月28日，中国北京——诺诚健华（香港联交所代码：09969；上交所代码：688428）今日发布截至2023年12月31日的2023年业绩报告和公司进展。 主要财务业绩摘要营业收入：2023收入同比上涨18.1%，达到7.4亿元[1] ，主要是奥布替尼收入同比增长18.5%，达到6.7亿元。毛利：2023年毛利同比上涨26.6%，达到6.1亿元；2023年毛利率达到82.6%，比去年上涨5.5%，主要是奥布替尼收入的上涨以及单位销售成本的下降。研发费用：2023年研发费用同比增加17.5%，达到7.5亿元，研发费用的增加主要是持续推进重要管线的全球临床试验和加大早研产品投资，为未来打好坚实基础。亏损：2023年亏损同比缩窄27.8%，减少至6.5亿元。公司现金和银行结余：截至2023年12月31日为82.2亿元。强劲的现金流有助于加速全球临床试验开发，并投资于有竞争力的产品管线。 高质量创新药赋能新质生产力发展 加速管线开发造福全球患者生物医药是新质生产力的重要力量。作为生物医药高科技公司，诺诚健华始终坚持高质量发展，为解决患者未满足的医疗需求而不懈努力。公司持续推进核心管线的全球开发，不断释放创新的价值。奥布替尼获批新适应症并维持原价续约国家医保，成为中国首个且唯一获批针对边缘区淋巴瘤的BTK抑制剂；公司加速临床开发，新型TYK2抑制剂ICP-332 治疗中重度特应性皮炎的II期研究达到主要终点……从源头创新、临床开发、商业化、生产到全球合作，公司全力以赴，不仅搭建了全产业链平台，同时制定明确的增长战略，加速推进公司2.0发展，造福全球患者。 持续深耕血液瘤管线 为患者带来更大获益以奥布替尼（BTK抑制剂）作为核心疗法，以及坦昔妥单抗（tafasitamab，CD19 单抗）、ICP-248（BCL2抑制剂）、ICP-490（CRBN E3 连接酶调节剂）、ICP-B02（CD20xCD3双特异性抗体）、ICP-B05（CCR8单抗）等血液瘤领域丰富的管线，以及通过未来潜在的内部开发和外部引进的管线开发，诺诚健华致力于发展成为中国和全球的血液瘤领域领导者。鉴于奥布替尼卓越的有效性和安全性，这些管线也将发挥巨大的协同效应，比如BTK和BCL2抑制剂的联用有潜力为血液瘤患者带来更大获益。公司通过单一或联合疗法覆盖非霍奇金淋巴瘤（NHL）、多发性骨髓瘤（MM）和白血病。奥布替尼奥布替尼2023年4月获批用于既往至少接受过一次治疗的边缘区淋巴瘤（MZL）患者，成为奥布替尼获批的第三个适应症，也成为中国首个且唯一获批针对MZL适应症的BTK抑制剂，填补国内空白。奥布替尼一线治疗慢性淋巴细胞白血病（CLL）/小淋巴细胞淋巴瘤（SLL）III 期注册临床试验2023年上半年完成患者入组，预计2024年第三季度递交新药上市申请（NDA）。 在美国，奥布替尼用于既往至少接受过一次治疗的套细胞淋巴瘤（MCL）患者的 II 期注册临床试验2023年上半年完成患者入组，预计2024年第三季度向美国FDA递交NDA上市申请。公司正启动奥布替尼一线治疗MCL的全球III期临床试验。奥布替尼在新加坡获批用于既往至少接受过一次治疗的MCL患者，标志着诺诚健华商业化走向国际。预计2024年将在新加坡提交既往至少接受过一次治疗的MZL的NDA上市申请。公司正启动奥布替尼针对MZL的三期确证性临床试验。联合BCL2抑制剂ICP-248一线治疗CLL/SLL。奥布替尼一线治疗弥漫大B细胞淋巴瘤（DLBCL）MCD 亚型III期注册研究目前在中国45个中心开展。坦昔妥单抗（Tafasitamab）坦昔妥单抗联合来那度胺治疗复发/难治性DLBCL注册临床试验在中国完成患者入组，预计2024年第二季度递交BLA上市申请，预计2025年上半年获批上市。坦昔妥单抗治疗方案在香港获批上市，并在海南博鳌和粤港澳大湾区获批使用并分别在两地先行区的医院开出首方。ICP-248ICP-248的初步研究结果展示了良好的安全性和药代动力学（PK），展示了和其他BCL2抑制剂的差异化。截至目前，17名患者完成给药，在完成评估的六名患者中，总缓解率（ORR）达到100%，三名患者达到完全缓解（CR），其中两名患者的微小残留病灶已检测不到（uMRD）。ICP-248成为公司重要的全球化管线。2024年1月，ICP-248获美国FDA批准开展临床研究。2024年3月，ICP-248联合奥布替尼一线治疗CLL/SLL在中国获批临床。ICP-248是一款新型口服高选择性BCL2抑制剂，旨在单药或与BTK抑制剂等其他药物联合治疗CLL/SLL、MCL、急性髓性白血病（AML）和其他NHL患者。ICP-B02（CM355）初步数据显示，ICP-B02的静脉输注（IV）制剂和皮下注射（SC）制剂在滤泡性淋巴瘤（FL）和 DLBCL 患者中都展示了良好的疗效。 在接受至少一剂6毫克以上剂量的13名患者中，ORR为100%。 9名可评估的皮下注射患者中，7名患者完全缓解（CR），其中2名DLBCL患者完全缓解。 基于ICP-B02单药令人鼓舞的结果，公司计划在更早线NHL患者中开展ICP-B02联合其他免疫化疗的剂量扩展研究。 目前，公司已提交联合疗法的新药研究申请（IND）。ICP-B02 是诺诚健华和康诺亚合作开发的CD20xCD3双特异性抗体。ICP-490公司正在进行多发性骨髓瘤（MM）患者 I 期剂量递增研究，展示了良好的安全性和耐受性。药效学（PD）分析显示主要药理靶点 Aiolos (IKZF3) 和 Ikaro (IKZF1) 的降解更深。2023年9月，ICP-490联合地塞米松在中国获批临床。作为单一疗法或与其他疗法联用，ICP-490有望在血液肿瘤领域展现强劲的潜力。ICP-490是公司自主研发的创新药，源自分子胶平台，旨在治疗MM等血液肿瘤。ICP-B05（CM369）正在进行I 期试验，ICP-B05 展示良好的耐受性，未观察到剂量限制毒性（DLT）。初步结果展现了良好的PK，同时观察到作为药效学（PD）生物标志物的Treg被清除。 实体瘤研究中的剂量递增已升至 150毫克，这也是针对 NHL 患者的初始剂量。ICP-B05在 NHL 患者中观察到初步疗效。ICP-B05是一款抗趋化因子受体8（CCR8）单克隆抗体，是诺诚健华和康诺亚共同开发的潜在first-in-class药物，开发作为单一疗法或与其他疗法联合治疗高发的晚期实体瘤和NHL。 继续夯实自身免疫性疾病管线 自身免疫性疾病几乎可以影响身体的每个器官，且在生命的任何阶段都会发生。全球自身免疫性疾病市场到2029年预计将达 1850 亿美元[2]。诺诚健华正进一步加强药物发现平台，通过B细胞和T细胞通路开发自身免疫性疾病领域的全球前沿靶点，打造差异化的自身免疫性疾病管线，旨在为大量未满足的临床需求提供first-in-class或者best-in-class疗法。这些创新药在全球都具有广阔市场潜力。奥布替尼奥布替尼治疗原发免疫性血小板减少症（ITP）已获得概念验证（PoC），并启动III期注册临床，预计2024年年底完成患者入组。2023年6月，奥布替尼治疗ITP的II期研究成果在第28届欧洲血液学协会（EHA）年会上进行口头报告。最新数据显示，50毫克组别中，40%的患者达到主要终点。在达到主要终点的患者中，83.3%的患者获得持久缓解。在对糖皮质激素（GC）或静脉注射免疫球蛋白（IVIG）敏感的患者中，50毫克剂量组中，75.0%的患者达到主要终点。奥布替尼治疗系统性红斑狼疮（SLE）IIa 期临床试验取得积极效果 ，研究显示SLE反应指数-4（SRI-4）呈剂量依赖性的改善趋势，同时观察到尿蛋白呈下降趋势。IIb 期试验持续推进中，预计2024年年中完成患者入组。奥布替尼治疗多发性硬化（MS）全球 II 期试验的 24 周数据与之前报告的 12 周的数据在有效性和安全性方面趋势均一致。奥布替尼治疗MS 三个剂量组的24 周数据都达到主要终点，奥布替尼显著降低了多发性硬化（MS）患者的疾病活动，呈现剂量依赖性（Cmax driven）的改善趋势。与安慰剂组（第 12 周后每天一次50毫克奥布替尼）相比，每天一次80毫克剂量组在第 24 周时钆增强T1 脑部累计新发病灶（Gd+ T1）减少了 92.3%。与其他已批准或处于开发阶段的MS药物相比，这种减少最为显著。所有奥布替尼剂量组在治疗4周后均达到T1新病灶控制，且效果可持续长达24周。每天一次80毫克剂量组显示了最优的有效性，并且在整个 24 周内病灶控制效果最佳，安全性也最好，这表明每天一次80毫克有潜力成为治疗 MS的最佳剂量。奥布替尼治疗视神经脊髓炎谱系疾病（NMOSD）的II期临床试验正在中国进行。ICP-332ICP-332治疗中重度特应性皮炎（AD）II期临床的最新数据在2024年美国皮肤病学会年会（2024 AAD Annual Meeting）以重磅口头报告（late-breaking oral presentation）形式发布。ICP-332展示了卓越的疗效和安全性，达到多个有效性终点，包括EASI（湿疹面积和严重程度指数）较基线变化百分比、EASI 50、EASI 75、EASI 90（EASI评分较基线改善≥50%，75%，90%）、研究者整体评估（IGA）0/1（即皮损完全清除或基本清除）且较基线改善≥2分、以及瘙痒NRS评分较基线变化等。80毫克和120毫克两个治疗组EASI 评分较基线改善的百分比变化分别为 78.2% 和 72.5%，与安慰剂组的 16.7%相比，具备显著的统计学差异；两个治疗组EASI 75应答率均为64.0%，较安慰剂组（8.0%）改善了56.0%，优于多种获批创新药物单药治疗12周或16周的疗效（非头对头比较）。ICP-332 80毫克组EASI 90和IGA 0/1且较基线改善≥2分的应答率较安慰剂组分别改善40.0%和32.0%，具有统计学意义。ICP-332展示了良好的安全性和耐受性。两个治疗组的总体不良事件发生率、感染及侵染类疾病的不良事件发生率均与安慰剂组相当。预计2024年在中国启动ICP-332治疗AD的 III 期临床试验，在美国启动临床试验，以及针对第二个适应症白癜风的 II 期试验。ICP-332 是一种新型酪氨酸激酶 2 (TYK2) 抑制剂，开发用于治疗各种 T 细胞相关的自身免疫性疾病。ICP-488已完成ICP-488治疗银屑病患者的 I 期研究，在接受治疗4周的患者中，ICP-488展示了有效性。在每日一次6毫克剂量组中，银屑病面积和严重程度指数（PASI）评分较基线变化百分比的最小二乘均值改善38%，而安慰剂组为14%，具有统计学意义。6毫克组PASI 50 的应答率为42%。 已完成单剂量爬坡（1毫克到36毫克）和多剂量爬坡（2毫克到12毫克）研究，观察到ICP-488 血浆暴露与剂量成比例。给药期同时服用标准高脂肪、高热量膳食，没有观察到明显的食物效应。ICP-488 展示了良好的安全性和耐受性，治疗组与安慰剂组的不良事件相当。ICP-488治疗银屑病的 II 期研究预计 2024 年上半年完成患者入组。ICP-488是一款强效的高选择性TYK2变构抑制剂，通过结合TYK2 JH2结构域，阻断IL-23、IL-12和I型干扰素等炎性细胞因子的信号转导。ICP-B02（CM355）在 I/II 期临床试验中，ICP-B02在复发难治性 NHL患者中首次输注（SC 和 IV）后，诱导外周 B 细胞的深度且持续清除。鉴于 B 细胞在多种严重自身免疫性疾病中发挥的关键作用，ICP-B02 有潜力在严重的自身免疫性疾病中具有更广泛的应用。ICP-923（新靶点）IL-17 是一种促炎细胞因子，在免疫应答中发挥重要作用。靶向 IL-17的口服小分子对患者而言更便利，可替代 IL-17 靶向单克隆抗体。这款新型口服小分子可有效阻断 IL-17AA 和 IL-17AF 与 IL-17R 的结合。 创新的实体瘤管线通过靶向治疗和免疫肿瘤学方法，诺诚健华致力于拓展管线的深度和广度，涵盖实体瘤疾病领域。Zurletrectinib（ICP-723）有助于公司在实体瘤治疗领域建立坚实的基础。为了使更广泛的患者受益，诺诚健华开发的早期管线，包括基石疗法ICP-192、ICP-189和ICP-B05，能够为中国和全球的实体瘤患者提供有竞争力的治疗解决方案。Zurletrectinib（ICP-723）诺诚健华正加速推进zurletrectinib在中国的注册临床试验，预计2024年年底递交NDA。截至报告期，zurletrectinib展示了良好的有效性和安全性，ORR为80-90%。Zurletrectinib 被证明可以克服第一代 TRK 抑制剂的耐药性，为接受第一代TRK抑制剂后耐药的患者带来希望。除成年患者之外，zurletrectinib在青少年（12周岁到18周岁）患者和儿童患者（2周岁到12周岁）中开展临床研究，已覆盖所有年龄的NTRK基因融合阳性患者。儿童患者入组正进行中，已观察到部分缓解。ICP-189诺诚健华与ArriVent达成临床合作协议，ICP-189联合第三代EGFR抑制剂伏美替尼治疗晚期或转移性非小细胞肺癌（NSCLC）患者的疗效和安全性。这一联合用药临床研究正推进中。非小细胞肺癌是肺癌的主要亚型，约占所有病例的 85%[3]。ICP-189是公司自主研发的新型蛋白酪氨酸磷酸酶SHP2变构抑制剂，可用作单药疗法及/或和其他抗肿瘤药的联合疗法，旨在为肺癌、头颈癌及消化道肿瘤等实体瘤提供新的临床治疗方法。ICP-189 单药治疗观察到初步疗效。截至报告期，剂量已增至120 毫克，未观察到DLT，并显示出良好的 PK 和长半衰期。160毫克剂量组的患者入组正在进行中。作为潜在first-in-class创新药，SHP2抑制剂是和多种靶向药和免疫疗法联合治疗实体瘤的理想药物。ICP-189在KRASG12C 突变和 EGFR 过表达驱动的肿瘤模型具有显著的抗肿瘤作用。Gunagratinib（ICP-192）2023 ASCO-GI 会议公布gunagratinib 治疗胆管癌 (CCA) 患者的最新临床数据[4]。在既往接受过治疗的局部晚期或转移性的FGFR2基因融合/重排的胆管癌患者中，gunagratinib显示出良好的安全性和有效性。其他业务进展诺诚健华任命傅欣和陈少峰分别担任公司首席财务官和首席商务官。诺诚健华获得香港联交所批准，2023年5月12日起正式将“B”标记从股票代码中移除，这是公司发展历程中取得的又一重要里程碑，标志着公司从Biotech持续向Biopharma迈进。广州诺诚健华获批商业化生产后快速实现奥布替尼生产下线，向中国患者提供这款创新药，标志着诺诚健华完全实现从自主研发、自主生产到自主销售的研产销一体化的全产业链平台。 诺诚健华联合创始人、董事长兼首席执行官崔霁松博士说：“我们将继续保持敏锐的洞察力和不断创新的精神，聚焦重点目标实现高质量发展，致力于为患者、合作者、投资者和生物医药行业做出我们的贡献。我们将深耕源头创新，推动多个新分子进入临床阶段，进一步夯实产品管线；加速临床开发：在中国及全球加速注册临床研究，提交多个新药上市申请；加强市场拓展：建立长期成功的商业化策略，快速推动商业化进程；推进业务国际化，进一步提升公司全球化水平，争取更多创新项目走向国际。” 想要了解诺诚健华2023年业绩报告财务数据，敬请登录https://www.innocarepharma.com/investor/home进行查询。电话会议信息诺诚健华将在北京时间3月28日晚上8:30举行英文电话会议，并于3月29日早上9点半召开中文电话会议。如要参加电话会议，需提前注册。详情如下： 英文场注册链接：https://goldmansachs.zoom.us/webinar/register/WN_DYQFyxtGQiC_WaqnlGAMvw#/registration 中文场注册链接：https://net.comein.cn/roadshow/home/199181?institute=zjgs前瞻性声明本报道含有一些前瞻性声明的披露。除对事实的陈述以外，所有其他声明可被看作是前瞻性声明，即关于我们或者我们的管理部门打算、期望、计划、相信或者预期将会或者可能会在未来发生的行为、事件或者发展所做出的声明。此类声明是我们的管理部门根据其经验和对历史趋势、当前条件、预期未来发展和其他相关因素的认知，做出的假设与估计。该前瞻性声明并不能保证未来的业绩，实际的结果，发展和业务决策可能与该前瞻性声明的设想不符。我们的前瞻性声明同样受到大量的风险和不确定性因素的制约，这可能会影响我们的近期以及长期的业绩表现。  关于诺诚健华诺诚健华（上交所代码：688428；香港联交所代码：09969）是一家商业化阶段的生物医药高科技公司，专注于恶性肿瘤及自身免疫性疾病领域的一类新药研制。公司现有多个新药产品处于商业化、临床及临床前研发阶段。公司在北京、南京、上海、广州、香港以及美国设有分支机构。[1] 财务业绩摘要中的货币均为人民币[2] iHealthcareAnalyst, Inc., 2023年10月3日[3] 癌度[4] 2023 ASCO GI摘要