mesutoclax (ICP-248) / InnoCare - LARVOL DELTA

Mesutoclax (ICP-248) monotherapy or combined with orelabrutinib demonstrates encouraging activity and safety in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (ASH 2025) - P1, P2/3 | "Mesutoclax monotherapy or in combination with orelabrutinib demonstrated a tolerablesafety profile across all dose levels tested. Substantial efficacy and deep remission were observed in bothTN CLL/SLL patients receiving mesutoclax 125mg combined with orelabrutinib and R/R CLL/SLL treatedwith mesutoclax alone."

Clinical • Monotherapy • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma • TP53

Title: Mesutoclax monotherapy or combined with orelabrutinib demonstrates encouraging activity and safety in patients with CLL/SLL (Publication No.: 5677) (GlobeNewswire) - "Latest Data of InnoCare’s Novel BCL2 Inhibitor Presented at the 67th Annual Meeting of the American Society of Hematology (ASH)....Substantial efficacy and deep remission were observed in both treatment-naive (TN) CLL/SLL patients receiving mesutoclax 125mg combined with orelabrutinib and R/R CLL/SLL treated with mesutoclax alone. In both TN CLL/SLL and R/R CLL/SLL patients (including those who had previously failed BTK inhibitor), the ORR was 100% in the 125 mg mesutoclax dose group. At week 36, when combined with orelabrutinib, the peripheral blood (PB) uMRD rate was 65% at 125 mg."

Clinical data • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

Title: Safety, tolerability and efficacy of mesutoclax to treat patients with myeloid malignancies (Publication No.: 3417) (GlobeNewswire) - "Latest Data of InnoCare’s Novel BCL2 Inhibitor Presented at the 67th Annual Meeting of the American Society of Hematology (ASH)....The combination of mesutoclax and azacitidine (AZA) demonstrated encouraging antitumor activity. The composite CR (CR+CRi, cCR) rate was achieved in 92% of TN AML patients. 82.6% of the patients achieved uMR. Most CR+CRi in TN AML was achieved by the end of cycle 1. Notably, 44% of the treatment naive AML were classified as adverse risk group and median age is 68 years old."

P1 data • Acute Myelogenous Leukemia

Title: Efficacy and tolerability of mesutoclax monotherapy in Relapsed/Refractory MCL patients: High remission rates even in prior BTKi-refractory patients (Publication No.: 887) (GlobeNewswire) - "Latest Data of InnoCare’s Novel BCL2 Inhibitor Presented at the 67th Annual Meeting of the American Society of Hematology (ASH)....The clinical data from mesutoclax (ICP-248) monotherapy demonstrated potential best in class efficacy in MCL patients, particularly in heavily treated patients with BTK inhibitors refractory. The overall response rate (ORR) of MCL patients treated with 125 mg mesutoclax monotherapy was 87.5%, with a complete response rate (CRR) of 46.9%. Among MCL patients who were BTK inhibitor refractory, the ORR was 84.0% and the CRR was 36.0%."

P1 data • Mantle Cell Lymphoma

Preliminary Safety, Pharmacological and Efficacy Data from Patients with Relapsed or Refractory B-Cell Malignancies Treated with the ICP-248, a Next Generation BCL2 Inhibitor (ASH 2023) - P1 | "Venetoclax, the first and only approved BCL2 inhibitor, is associated with gastrointestinal toxicities and tumor lysis syndrome (TLS)...7 months); median of prior regimen numbers was 3 (range, 1-3; 2 out 3 patients failed on zanubrutinib or pirtobrutinib)... Preliminary results suggest that ICP-248 is safe and well tolerated in relapsed or refractory B-cell malignancies. The favorable clinical pharmacological and safety profiles support current dose ramp up strategy. Preliminary efficacy data demonstrated good response with deep remission."

Clinical • IO biomarker • Acute Myelogenous Leukemia • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

A Study to Evaluate the Efficacy and Safety of ICP-248 in Subjects With Relapsed or Refractory Mantle Cell Lymphoma (clinicaltrials.gov) - P2 | N=68 | Recruiting | Sponsor: Beijing InnoCare Pharma Tech Co., Ltd. | Not yet recruiting ➔ Recruiting | Trial primary completion date: Dec 2025 ➔ Dec 2027

Enrollment open • Trial primary completion date • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

InnoCare Announces First Patient Dosed in the Registrational Trial of BCL2 Inhibitor Mesutoclax for Treatment of BTKi-treated MCL Patients in China (GlobeNewswire) - "This registrational trial is designed to evaluate the safety and efficacy of mesutoclax in treating BTKi-treated MCL patients."

Trial status • Mantle Cell Lymphoma

A Study to Evaluate the Efficacy and Safety of ICP-248 in Subjects With Relapsed or Refractory Mantle Cell Lymphoma (clinicaltrials.gov) - P2 | N=68 | Not yet recruiting | Sponsor: Beijing InnoCare Pharma Tech Co., Ltd.

New P2 trial • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

InnoCare Announces FDA Approval of Clinical Trial for BCL2 Inhibitor Mesutoclax in AML and MDS (InnoCare Pharma Press Release) - "InnoCare Pharma...announced today that the U.S. Food & Drug Administration has approved the Investigational New Drug (IND) application to conduct the clinical trial of B-cell lymphoma-2 (BCL2) inhibitor mesutoclax (ICP-248) in combination with azacitidine for the treatment of myeloid malignancies, such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS)."

IND • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

ICP-CL-01205: ICP-248 in Combination With Azacitidine for the Treatment in Patients With Myeloid Malignancies (clinicaltrials.gov) - P1 | N=206 | Recruiting | Sponsor: Beijing InnoCare Pharma Tech Co., Ltd. | N=102 ➔ 206

Enrollment change • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ICP-248 as Monotherapy or in Combination With Anti-CD20 Monoclonal Antibody in Mature B-cell Malignancies (clinicaltrials.gov) - P1 | N=78 | Recruiting | Sponsor: InnoCare Pharma Inc. | Not yet recruiting ➔ Recruiting | N=40 ➔ 78

Enrollment change • Enrollment open • Monotherapy • Chronic Lymphocytic Leukemia • Hematological Malignancies • Oncology

MRD GUIDED MESUTOCLAX PLUS ORELABRUTINIB FOR CLL/SLL DEMONSTRATES HIGH RESPONSE AND EARLY MRD CLEARANCE WITH GOOD TOLERABILITY: PRELIMINARY ANALYSIS FROM AN ONGOING PHASE II DOSE OPTIMIZATION STUDY (EHA 2025) - P2/3 | "Background: The combination of venetoclax with BTK inhibitor is effective in CLL/SLL, but their clinical use can be limited by toxicity or suboptimal MRD clearance. Mesutoclax (ICP-248) is highly selective and potent BCL2 inhibitor with low drug-drug interaction and food effect... Mesutoclax (100 and 125 mg) in combination with orelabrutinib was safe and well tolerated in patients with TN CLL/SLL. Substantial efficacy was observed, with a 100% ORR and early high uMRD rate at 12 weeks of target therapy in patients of the 125mg cohort. The preliminary result of this study support further clinical development and a registrational phase 3 study has been initiated to evaluate the efficacy and safety of the combination of orelabrutinib and mesutoclax of 125mg QD."

IO biomarker • P2 data • Chronic Lymphocytic Leukemia • Infectious Disease • Oncology • Respiratory Diseases • Small Lymphocytic Lymphoma • IGH • TP53

Preliminary safety and efficacy data of ICP-248, a novel BCL2 inhibitor, in patients with relapsed or refractory B-cell malignancies. (ASCO 2025) - P1 | "The only approved BCL2 inhibitor, Venetoclax, has been approved for the treatment of chronic lymphocytic leukemia/small cell lymphoma (CLL/SLL) or acute myeloid leukemia (AML). The preliminary results of ICP-248 monotherapy suggests a well-tolerated safety profile and an exciting efficacy with dose-dependent effect in BTK failed, heavily treated, relapsed or refractory B-cell malignancies."

Clinical • Acute Myelogenous Leukemia • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Leukopenia • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Thrombocytopenia

Title: Preliminary safety and efficacy data of ICP-248, a novel BCL2 inhibitor, in patients with relapsed or refractory B-cell malignancies (Abstract No.: 7038) (Businesswire) - P1 | N=191 | NCT05728658 | Sponsor: Beijing InnoCare Pharma Tech Co., Ltd. | "Latest data of InnoCare’s robust oncology pipelines presented at the 2025 ASCO Annual Meeting....As of April 15, 2025, a total of 68 patients were enrolled in the dose escalation and dose expansion study....17 CLL/SLL and 26 MCL patients had at least one response assessment. Among the BTK naïve patients, the ORR for R/R CLL/SLL and R/R MCL patients were both 100%, and the CRR was 14.3% and 71.4% respectively, of which 43% of MCL patients reported undetectable minimal residual disease (uMRD). Among the BTK treated patients, the ORR for R/R CLL/SLL and R/R MCL patients were 100% and 78.9% respectively, and the CRR were 30.0% and 26.3% respectively, of which uMRD was reported in 20% of CLL/SLL and 16% of MCL patients. The median PFS of R/R MCL patients who had received treatment of BTK inhibitors before was 8.3 months."

P1 data • Chronic Lymphocytic Leukemia • Mantle Cell Lymphoma • Small Lymphocytic Lymphoma

InnoCare Announces Approval of Clinical Trial of BCL2 Inhibitor Mesutoclax for Myelodysplastic Syndromes in China (Businesswire) - "InnoCare Pharma...announced today the approval of the Investigational New Drug (IND) by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) to conduct the clinical trial of B-cell lymphoma-2 (BCL2) inhibitor mesutoclax (ICP-248) in combination with azacitidine for the treatment of myeloid malignancies, including but not limited to myelodysplastic syndromes (MDS)."

New trial • Myelodysplastic Syndrome

InnoCare’s Mesutoclax Receives Breakthrough Therapy Designation from China’s NMPA (Businesswire) - "InnoCare Pharma...announced today that its B-cell lymphoma-2 (BCL2) inhibitor, Mesutoclax (ICP-248), has been granted Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) for the treatment of BTKi-treated relapsed or refractory mantle cell lymphoma (R/R MCL). This marks the first BCL2 inhibitor to receive BTD recognition in China."

Breakthrough therapy • Mantle Cell Lymphoma

InnoCare Announces First Patient Dosed in the Phase III Registrational Trial of BCL2 Inhibitor ICP-248 in Combination with Orelabrutinib as First-Line Therapy for Treatment of CLL/SLL Patients in China (Businesswire) - "InnoCare Pharma...announced today that the first patient has been dosed in the Phase III registrational trial of B-cell lymphoma-2 (BCL2) inhibitor ICP-248 (Mesutoclax) in combination with BTK inhibitor orelabrutinib as a first-line therapy for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in China."

Trial status • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

ICP-CL-01201: The Study of ICP-248 in Patients with Mature B-cell Malignancies (clinicaltrials.gov) - P1 | N=191 | Recruiting | Sponsor: Beijing InnoCare Pharma Tech Co., Ltd. | N=105 ➔ 191 | Trial primary completion date: Aug 2024 ➔ Aug 2025

Enrollment change • Monotherapy • Trial primary completion date • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Oncology

InnoCare Announces the Approval of Registrational Phase III Study of BCL2 Inhibitor ICP-248 in Combination with Orelabrutinib as First-Line Therapy for Treatment of CLL/SLL Patients in China (Businesswire) - "InnoCare Pharma...announced today that the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) has approved the registrational Phase III clinical trial of B-cell lymphoma-2 (BCL2) inhibitor ICP-248 (Mesutoclax) in combination with BTK inhibitor orelabrutinib as a first-line therapy for the treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients in China."

New P3 trial • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

ICP-CL-01205: ICP-248 in Combination with Azacitidine in Treatment-Naïve Subjects with Acute Myelogenous Leukemia(AML) or Previously Treated Relapsed/Refractory Subjects with Acute Myelogenous Leukemia(R/R AML). (clinicaltrials.gov) - P1 | N=102 | Recruiting | Sponsor: Beijing InnoCare Pharma Tech Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

ICP-248 in Combination with Azacitidine in Treatment-Naïve Subjects with Acute Myelogenous Leukemia(AML) or Previously Treated Relapsed/Refractory Subjects with Acute Myelogenous Leukemia(R/R AML). (clinicaltrials.gov) - P1 | N=90 | Not yet recruiting | Sponsor: Beijing InnoCare Pharma Tech Co., Ltd.

New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

InnoCare Releases 2024 Interim Results and Business Highlights (Businesswire) - P2/3 | N=226 | NCT06378138 | Sponsor: Beijing InnoCare Pharma Tech Co., Ltd. | "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."

Enrollment closed • New trial • P2 data • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Mantle Cell Lymphoma • Small Lymphocytic Lymphoma

InnoCare Announces Approval of Clinical Trial of BCL2 Inhibitor ICP-248 for Acute Myeloid Leukemia in China (Businesswire) - "InnoCare Pharma...announced today the approval of the Investigational New Drug (IND) to conduct the clinical trial of B-cell lymphoma-2 (BCL2) inhibitor ICP-248 in combination with azacitidine for acute myeloid leukemia (AML) in China....ICP-248 is a novel, orally bioavailable BCL2-selective inhibitor."

New trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

ICP-CL-01203: ICP-248 in Combination With Orelabrutinib in Treatment-naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (clinicaltrials.gov) - P2/3 | N=226 | Recruiting | Sponsor: Beijing InnoCare Pharma Tech Co., Ltd. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

PRELIMINARY SAFETY AND EFFICACY DATA FROM PATIENTS WITH RELAPSED OR REFRACTORY B-CELL MALIGNANCIES TREATED WITH ICP-248, A NOVEL BCL2 INHIBITOR. (EHA 2024) - P1 | "Venetoclax, the only approved BCL2 inhibitor, is authorized for treating patients with chroniclymphocytic leukemia/small cell lymphoma (CLL/SLL) or acute myeloid leukemia (AML), althoughgastrointestinal toxicities and tumor lysis syndrome (TLS) remain challenging in clinical practice. Preliminary results of ICP-248 monotherapy suggest well tolerated safety profile andpromising efficacy with dose-dependent effect in relapsed or refractory B-cell malignancies. Further assessmentof safety and efficacy with additional dose levels and dosing strategies will be pursued in expanded patientpopulation and in the combination with Orelabrutinib."

Clinical • Acute Myelogenous Leukemia • Cardiovascular • Chronic Lymphocytic Leukemia • Endocrine Disorders • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma