Gunagratinib

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