InnoCare Pharma Announces Strong H1 2024 Results: Orelabrutinib Revenue Continues to Rise, Expands Comprehensive Pipeline in Autoimmune Diseases

On August 20, InnoCare (HKEX Stock Code: 09969; SSE Stock Code: 688428) released its 2024 interim results report and corporate updates for the six months ended June 30, 2024.

● Operating Revenue:Orelabrutinib revenue increased by 30.0% year-on-year in the first half of 2024, reaching RMB 420 million¹, with a year-on-year growth of 48.8% in the second quarter. This was primarily attributable to orelabrutinib becoming the first and only BTK inhibitor approved for marketing in China for the indication of marginal zone lymphoma (MZL). Following its inclusion in the National Reimbursement Drug List in 2023, this new indication achieved rapid sales volume growth in the first half of the year. Meanwhile, the company has continuously enhanced the capabilities of its commercialization team and accelerated execution efficiency.

● Loss:The net loss in the first half of 2024 narrowed by 37.6% year-on-year, decreasing to RMB 270 million.

● Company Cash and Other Financial Assets:As of June 30, 2024, it stood at RMB 7.99 billion. The robust cash flow helps accelerate global clinical trial development and invest in a competitive product pipeline.

● Gross Profit:Revenue rose by 19.3% year-on-year in the first half of 2024, reaching RMB 360 million; the gross profit margin for the same period reached 85.7%, an increase of 5.8 percentage points year-on-year, primarily driven by higher revenue from orelabrutinib and changes in the revenue mix.

● R&D Expenses:R&D expenses in the first half of 2024 increased by 17.5% year-on-year², reaching RMB 420 million. The increase in R&D expenses was primarily attributable to the establishment of a differentiated R&D platform and the advancement of more Phase III clinical trials.

In the first half of 2024, InnoCare achieved total revenues of RMB 420 million, primarily driven by sales of orelabrutinib. In 2024, the updated National Reimbursement Drug List (NRDL) came into effect, providing insurance coverage for three indications of orelabrutinib: adult patients with relapsed or refractory chronic lymphocytic leukemia (r/r CLL) or small lymphocytic lymphoma (r/r SLL) who have received at least one prior therapy; adult patients with relapsed or refractory mantle cell lymphoma (r/r MCL) who have received at least one prior therapy; and adult patients with relapsed or refractory marginal zone lymphoma (r/r MZL) who have received at least one prior therapy. Orelabrutinib is the first and only BTK inhibitor approved in China for the treatment of MZL, and it is listed as a Category I recommendation for second-line treatment of marginal zone lymphoma (MZL) in the "CSCO Guidelines for Diagnosis and Treatment of Lymphoma 2024" issued by the Chinese Society of Clinical Oncology (CSCO).

In terms of commercialization capability building, the Company has continuously strengthened its commercial team and capabilities, consistently improved execution and operational efficiency, and focused on strategic priorities to ensure effective implementation of its marketing plans, thereby achieving rapid market penetration. This underscores the Company’s commitment to continuously creating value in the commercialization domain and driving sustainable growth.

Entering a new era of rapid development in its 2.0 phase, InnoCare is strengthening its full-industry-chain platform and accelerating clinical trials and regulatory filings for its pipeline in the three major therapeutic areas of hematologic malignancies, solid tumors, and autoimmune diseases. Over the next three to five years, the company expects five to six innovative drugs to gain marketing approval, addressing unmet medical needs and leveraging China’s new quality productive forces to benefit patients worldwide.

Hematologic malignancies are highly lethal cancers, including lymphoma, leukemia, and myeloma. InnoCare is committed to developing therapies with diverse mechanisms of action (MoA) to achieve comprehensive coverage of hematologic oncology indications, striving to become a leader in the field of hematologic malignancies.

In addition to the approved indications,InnoCare is advancing the registration clinical trials and New Drug Application (NDA) for orelabrutinib in first-line indications. Tafasitamab (a CD19 monoclonal antibody) is expected to launch in the first half of next year, becoming another blockbuster product for the commercialization team to expand market reach. Meanwhile, the company is accelerating the development of ICP-248, a BCL-2 inhibitor, which demonstrates significant potential in combination with orelabrutinib. As BCL-2 inhibitors are the preferred treatment option following resistance to BTK inhibitors, this combination establishes an optimal sequential therapy regimen.With the addition of the molecular glue ICP-490, the monoclonal antibody ICP-B05, and the bispecific antibody ICP-B02, as well as by driving pipeline development through future potential internal R&D and external in-licensing, InnoCare is committed to becoming a leader in the field of hematologic malignancies in China and globally.

● The Phase II clinical trial of orelabrutinib in combination with the company’s self-developed BCL2 inhibitor ICP-248 as first-line treatment for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) was initiated in May this year.Patient enrollment was completed as of the report release date.；

● Accelerate the advancement of registrational clinical trials and new drug marketing applications for orelabrutinib in first-line indications, including CLL/SLL, MCL, and DLBCL;

● Orelabrutinib continues to garner attention at top international academic conferences. Five studies on orelabrutinib were selected for the 2024 European Society for Medical Oncology (ESMO) Annual Congress, including a prospective study of orelabrutinib in previously untreated marginal zone lymphoma, which was chosen for an oral presentation; additionally, ten studies on orelabrutinib were selected for the 2024 European Hematology Association (EHA) Annual Congress.

● New drug application for taletrectinib in combination with lenalidomide for the treatment of relapsed/refractory DLBCL submitted this JuneAccepted in China and included in the priority review program。Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL), accounting for 31%–34% of NHL cases globally. In China, DLBCL constitutes 45.8% of all NHL cases.³；

● Taletrectinib treatment regimen approved for market launch in Hong Kong, and approved for use in Boao, Hainan and the Guangdong-Hong Kong-Macao Greater Bay Area, with the first prescriptions issued at hospitals in the respective pilot zones.

● ICP-248 is a novel oral highly selective BCL-2 inhibitor currently being evaluated in combination with orelabrutinib as first-line therapy for CLL/SLL; Phase II patient enrollment has been completed.

● As of now, 47 patients have completed dosing. Among the 28 patients who completed the assessment, the overall response rate (ORR) in patients with mantle cell lymphoma (MCL) who had failed prior BTK inhibitor therapy reached 71.4%;

● The Investigational New Drug (IND) application for the clinical trial of ICP-248, a novel therapy for acute myeloid leukemia (AML), has been accepted in China.

● ICP-490 is an innovative drug independently developed by the company, derived from its molecular glue platform. As a monotherapy or in combination with other therapies, ICP-490 holds strong potential in the field of hematologic malignancies, aiming to treat conditions such as multiple myeloma (MM) and non-Hodgkin lymphoma (NHL).

● Currently conducting multiple myeloma (MM) andNon-Hodgkin Lymphoma (NHL) PatientsPhase I dose-escalation study demonstrated favorable safety and tolerability. The favorable safety profile supports further dose escalation.

● ICP-B02 is a CD20xCD3 bispecific antibody co-developed by InnoCare and Conmed. The intravenous (IV) and subcutaneous (SC) formulations of ICP-B02 have demonstrated favorable efficacy in patients with follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Among the 15 patients who received at least one dose exceeding 6 mg,ORR was 100%. All patients who achieved CR maintained remission as of the reporting date;

● Based on the encouraging results of ICP-B02 monotherapy, the company plans to conduct dose-expansion studies of ICP-B02 in combination with other immunochemotherapy regimens in patients with earlier-line non-Hodgkin lymphoma (NHL).ICP-B02 in combination with immunochemotherapy for the treatment of NHL patients was approved for clinical trials this June.

● ICP-B05 is a monoclonal antibody targeting chemokine receptor 8 (CCR8), a potential first-in-class drug co-developed by InnoCare and Keymed Biosciences, being developed as a monotherapy or in combination with other therapies for the treatment of highly prevalent advanced solid tumors and non-Hodgkin lymphoma (NHL);

● A Phase I trial is ongoing to evaluate the safety, tolerability, pharmacokinetic (PK) profile, and efficacy of ICP-B05 in patients with advanced solid tumors and relapsed or refractory NHL;

● Preliminary Efficacy of ICP-B05 Observed in NHL Patients. ICP-B05 demonstrated good tolerability, with no dose-limiting toxicity (DLT) observed.

Through targeted therapy and immuno-oncology approaches, InnoCare is committed to expanding the depth and breadth of its pipeline, covering the field of solid tumors. Zurletrectinib (ICP-723) helps the company establish a solid foundation in the treatment of solid tumors. To benefit a broader patient population, InnoCare’s early-stage pipeline, including the potential first-in-class therapies ICP-189 and ICP-B05, provides competitive treatment solutions for patients with solid tumors in China and globally.

● NTRK gene fusion mutations are oncogenic drivers in various cancers,including lung cancer, colorectal cancer, breast cancer, pancreatic cancer, and melanoma。Zurletrectinib is the company's self-developed second-generation TRK inhibitor, and its registration clinical trials in China are being accelerated.Entered the pre-NDA preparation stage；

● Zurletrectinib demonstrated favorable efficacy and safety. Zurletrectinib has been provenCan overcome resistance to first-generation TRK inhibitors, offering hope to patients who have developed resistance after receiving first-generation TRK inhibitors;

● Studies on zurletrectinib have included adult, adolescent (aged 12 to 18 years), and pediatric (aged 2 to 12 years) patients with NTRK gene fusion-positive tumors, and efficacy has been observed in both adolescent and pediatric patients.Dose-escalation trials in pediatric patients have been completed.

● ICP-189 is a novel allosteric inhibitor of the protein tyrosine phosphatase SHP2, independently developed by the company.A clinical trial of ICP-189 in combination with the third-generation EGFR inhibitor furmonertinib for the treatment of advanced or metastatic non-small cell lung cancer (NSCLC) is ongoing, with preliminary efficacy observed. Non-small cell lung cancer is the predominant subtype of lung cancer, accounting for approximately 85% of all cases.⁴；

● Preliminary efficacy observed with ICP-189 monotherapy. As a potential first-in-class innovative drug, SHP2 inhibitors are an ideal agent for combination therapy with various targeted drugs and immunotherapies in the treatment of solid tumors. ICP-189 in KRAS^G12CTumor models driven by mutations and EGFR overexpression exhibit significant antitumor effects,For patients with non-small cell lung cancer (NSCLC) who have developed resistance to third-generation EGFR inhibitors, SHP2 combination therapy offers a promising treatment option;

● As of the reporting period, dose escalation to the 120 mg once-daily cohort has been completed. No dose-limiting toxicities (DLTs) were observed, and favorable pharmacokinetics (PK) with a long half-life were demonstrated. Patient enrollment in the 160 mg once-daily cohort is ongoing.

InnoCare is also actively exploring preclinical development in the field of solid tumors, leveraging a differentiated platform to develop innovative small-molecule and large-molecule drugs, with a commitment to tackling solid tumors such as lung cancer and gastric cancer, thereby addressing significant unmet medical needs.

Autoimmune diseases can affect nearly every organ in the body and can occur at any stage of life. The global autoimmune disease market is projected to reach $185 billion by 2029.⁵InnoCare is further strengthening its drug discovery platform by developing global frontier targets in the field of autoimmune diseases through B-cell and T-cell pathways, building a differentiated autoimmune disease pipeline aimed at providing first-in-class or best-in-class therapies for a large number of unmet clinical needs. These innovative drugs have broad market potential globally.

● Orelabrutinib TreatmentPrimary Immune Thrombocytopenia(ITP has achieved proof of concept (PoC), and patient enrollment in the Phase III registration clinical trial is more than halfway complete.The annual incidence of adult ITP is approximately 2–10 cases per 100,000 people.⁶, only about 70% of patients respond to first-line therapy, with some patients experiencing treatment failure or relapse; orelabrutinib holds promise for providing a better therapeutic option⁷Orelabrutinib's expansion from hematologic malignancies into autoimmune diseases within the hematology field underscores its significant commercial potential.In April 2024, the Phase II study results of orelabrutinib in the treatment of ITP were published in the American Journal of Hematology. For details, please refer to:https://onlinelibrary.wiley.com/doi/10.1002/ajh.27303 

● Orelabrutinib TreatmentSystemic Lupus Erythematosus (SLE)The Phase IIa clinical trial yielded positive results, with the study demonstrating a dose-dependent improvement trend in the SLE Responder Index-4 (SRI-4) and a concurrent downward trend in urinary protein levels.Orelabrutinib is the first BTK inhibitor to demonstrate efficacy in Phase II clinical trials for systemic lupus erythematosus (SLE) worldwide.. The Phase IIb trial is currently ongoing,As of the reporting period, patient enrollment was nearly complete.。

Systemic lupus erythematosus (SLE) is a systemic disease that often leads to organ damage, particularly affecting the kidneys, nervous system, skin, hematologic system, and respiratory system; virtually all organ systems can be involved.According to Frost & Sullivan analysis, the global number of SLE patients is projected to reach 8.18 million in 2025. The “China Systemic Lupus Erythematosus Development Report 2020” indicates that China has approximately 1 million SLE patients, ranking first globally in total patient count and second in incidence rate.

● ICP-332 is a novel tyrosine kinase 2 (TYK2) inhibitor developed for the treatment of various T cell-mediated autoimmune diseases,Including atopic dermatitis (AD), vitiligo, and inflammatory bowel disease, with broad market prospects.；

● The latest Phase II clinical data on ICP-332 for the treatment of moderate-to-severe atopic dermatitis (AD) were presented as a late-breaking oral presentation at the 2024 American Academy of Dermatology Annual Meeting (2024 AAD Annual Meeting);

● The Phase II clinical study of ICP-332 for the treatment of moderate-to-severe atopic dermatitis (AD) conducted in China met multiple efficacy endpoints, demonstrating superior efficacy and safety. ICP-332 showed better efficacy compared with therapies of different classes/mechanisms of action (MoA) for AD patients (non-head-to-head comparison);

● Two treatment groups receiving 80 mg once daily and 120 mg once daily (four weeks of treatment）EASI  90(Eczema Area and Severity Index score improved by ≥90% from baseline) andNRS Itch Score Improved by ≥4 Points from Baseline(NRS≥4) response rates improved by 40% and 56%, respectively, compared with the placebo group, outperforming competing products;

● ICP-332 demonstrated a favorable safety and tolerability profile. The overall incidence of adverse events in both treatment groups was comparable to that in the placebo group;

● The Phase III clinical trial of ICP-332 for the treatment of AD is expected to be initiated in China in the fourth quarter of 2024, and an IND application for Phase II/III trials targeting the second indication, vitiligo, will be submitted;ICP-332 Has Initiated Clinical Trials in the United States。

● Data shows that 100 million people worldwide are affected by various forms of psoriasis⁸. ICP-488 is a potent, highly selective allosteric TYK2 inhibitor that blocks the signal transduction of inflammatory cytokines such as IL-23, IL-12, and type I interferons by binding to the JH2 domain of TYK2. The Phase II study of ICP-488 for the treatment of psoriasis was conducted in May this yearPatient enrollment completed; data readout expected by the end of this year.；

● A total of 129 patients were enrolled in the Phase II study and randomized in a 1:1:1 ratio to three treatment arms, including two active treatment groups and one placebo group, with continuous dosing for 12 weeks;

● ICP-488 demonstrated favorable safety and efficacy in the Phase I study in patients with psoriasis.

IL-17 is a pro-inflammatory cytokine that plays a crucial role in immune responses. Novel oral IL-17 inhibitors offer greater convenience for patients and can serve as alternatives to IL-17-targeting monoclonal antibodies. This novel oral small-molecule inhibitor effectively blocks the binding of IL-17AA and IL-17AF to the IL-17 receptor (IL-17R).

Co-founder, Chairman and CEO of InnoCareDr. Cui Jisong“He said, ‘In the first half of 2024, we exceeded our established commercial targets, achieving a substantial increase in revenue. We actively developed innovative drugs urgently needed by the market and submitted three new drug marketing applications during this period. We are also actively exploring source innovation to lay a solid foundation for future development. Looking ahead to the second half of the year, we will continue to strengthen our efforts in new drug R&D, clinical development, commercialization, and internationalization, focusing on key objectives to achieve high-quality development.’”

InnoCare (SSE Code: 688428; HKEX Code: 09969) is a commercial-stage, high-tech biopharmaceutical company focused on the development of first-in-class novel drugs for malignant tumors and autoimmune diseases. The company currently has multiple new drug products in various stages of commercialization, clinical development, and preclinical research. InnoCare maintains branches in Beijing, Nanjing, Shanghai, Guangzhou, Hong Kong, and the United States.