Tolebrutinib

BEIJING--(BUSINESS WIRE)-- Data of InnoCare's (HKEX: 09969; SSE: 688428) robust pipelines were presented at the European Hematology Association (EHA) 2024 Hybrid Congress. 1. Subcutaneous ICP-B02 (CM355), a Novel Bispecific CD20/CD3 Antibody Showed Promising Efficacy and Favorable Safety Pro Relapsed/Refractory B-cell Non-Hodgkin Lymphoma (Abstract No.: P2097) This study aimed to evaluate the safety, tolerability, efficacy, pharmacokinetics (PK)/ pharmacodynamics (PD) of ICP-B02 in relapsed/refractory (R/R) B-cell non-hodgkin lymphoma (NHL). At the doses evaluated, ICP-B02 subcutaneously (SC) demonstrated favorable safety pro promising efficacy in patients with R/R B-cell NHL. All Cytokine release syndrome (CRS) events were manageable with minimal intervention. Rapid and deep responses, as well as the convenience of SC formulation, support further clinical development for treatment of B cell NHL. Efficacy results showed that the overall response rate (ORR) was 100.0% with complete response rate (CRR) was 77.8%. 2. Preliminary Safety and Efficacy Data from Patients with Relapsed or Refractory B-Cell Malignancies Treated with ICP-248, a Novel BCL2 Inhibitor (Abstract No.: P1851) This study aimed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ICP-248 in patients with relapsed or refractory B-cell malignancies. Preliminary results of ICP-248 monotherapy suggest well tolerated safety pro promising efficacy with dose-dependent effect in relapsed or refractory B-cell malignancies. The ORR was 100% at 100 mg dose level, with three patients achieved complete response. Further assessment of safety and efficacy with additional dose levels and dosing strategies will be pursued in expanded patient population and in the combination with Orelabrutinib. 3. A Phase II, Single-Arm, Open-Label Study to Evaluate the Safety and Efficacy of Tafasitamab Combined with Lenalidomide in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (Abstract No.: P2091) Relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) remains a high unmet medical need, especially in patients who are ineligible for autologous stem cell transplant (ASCT). The study demonstrates that tafasitamab plus lenalidomide regimen is well tolerated in Chinese population with good efficacy, and the efficacy and safety data are consistent with the L-MIND study. As of the data by Jan. 29, 2024, the ORR assessed by IRC was 73.1%, with 32.7% of patients achieving CR and 40.4% of patients with partial response (PR). The ORR assessed by investigators was 69.2%, with 34.6% of patients reaching CR and 34.6% of patients achieved PR. 4. Orelabrutinib-Lenalidomide-Rituximab in Patients with Untreated Mantle Cell Lymphoma (MCL): Updated Results of the Multicenter, Phase II Polaris Study (Abstract No.: P1141) This study aimed to explore whether orelabrutinib combined with rituximab plus lenalidomide would exhibit synergistic antitumor activity in mantle cell lymphoma (MCL) and improve the depth and durability of response. The data confirmed the potent antitumor activity and manageable safety of the orelabrutinib-lenalidomide-rituximab regimen in patients with untreated MCL. Detection of peripheral blood (PB) ctDNA detection based on NGS could contribute to predicting prognosis. Of response-evaluable patients who had completed 6 cycles of induction therapy, 67.9% achieved CR and 17.9% achieved PR, with an ORR of 85.8%. Median duration of response (DOR) and median progress-free survival (PFS) were not reached. 5. Orient Study: Orelabrutinib Addition to R-Chop-Like Regimen Adapted to Response in Treatment-Naïve Non-GCB DLBCL (Abstract No.: P1167) This is a multicenter, open-label phase II study, aiming to assess efficacy and safety of orelabrutinib plus R-CHOP-like regimen for untreated non-GCB DLBCL patients who respond to induction therapy of orelabrutinib plus rituximab. Primary endpoint was complete remission rate (CRR) after 6-cycle orelabrutinib plus R-Chop-like regimen. All the patients who completed 6-cycle therapy attained CR at the end of cycle 6. Although preliminary, responders to orelabrutinib plus rituximab induction may further benefit from subsequent orelabrutinib plus R-Chop-like regimen, achieving high CRR and sustaining CR throughout post-therapy follow-up; no unexpected safety issue occurred. 6. The Primary Results of R-MTO Regimen (Rituximab, Methotrexate, Thiotepa, and Orelabrutinib) as the First-Line Induction Therapy in Newly Diagnosed Primary Central Nervous System Lymphoma (Abstract No.: P1193) This study aimed to investigate the efficacy and safety of rituximab, methotrexate, thiotepa, and orelabrutinib regimen followed by autologous hematopoietic stem cell transplantation (ASCT) in treatment of the patients with PCNSL. The rituximab, methotrexate, thiotepa, and orelabrutinib regimen induction treatment has demonstrated notable efficacy in achieving higher response rates among patients with newly diagnosed PCNSL, and a tolerable safety profile. 7. Orelabrutinib in Patients with Indolent Non-Hodgkin Lymphoma (INHL) Intolerant to Prior Bruton Tyrosine Kinase Inhibitors (BTKI): Preliminary Results from a Phase 2 Study (Abstract No.: P2074) This study aimed to assess the safety and activity of orelabrutinib in prior BTKi-intolerant iNHL. Orelabrutinib improved outcomes of prior BTKi-intolerant AEs, particularly the off-target toxicities (cardiac/infectious AEs). The preliminary result of this study showed promising efficacy and safety data of orelabrutinib in prior BTKi-intolerant iNHL patients. 8. Orelabrutinib, Fludarabine, Cyclophosphamide, and Obinutuzumab (OFCG) for First-Line Treatment of Chronic Lymphocytic Leukemia: A Multicenter, Investigator-Initiated Study (CWCLL-001 Study) (Abstract No.: P680) This study was initiated to evaluate the efficacy and safety of orelabrutinib plus fludarabine, cyclophosphamide and obinutuzumab in younger, fit patients with previously untreated CLL/SLL without restriction by del(17p)/TP53 aberrations and/or IGHV mutation status. The regimen leads to a rapid and deep molecular remission with a manageable safety pro previously untreated CLL patients including those with unfavorable characteristics. 9. Different Subtype of DLBCL Patients Treated with R-Chop (Like) Plus Orelabrutinib Regimen: A Real-World Study (Abstract No.: PB3034) This retrospective study aimed to compare the efficacy and safety of R-CHOP-like regimen combined with orelabrutinib in patients with different subtypes of DLBCL. The study demonstrated that patients with double-expression and extranodal involvement benefit from orelabrutinib and that earlier addition of orelabrutinib results in a higher proportion of complete remissions, and more detailed analyses comparing the benefits in different types of patients are underway. 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. InnoCare Forward-looking Statements 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. View source version on businesswire.com: Contacts Media Chunhua Lu 86-10-66609879 chunhua.lu@innocarepharma.com Investors 86-10-66609999 ir@innocarepharma.com Source: InnoCare Pharma View this news release online at:

SUZHOU, China, and ROCKVILLE, Md., June 4, 2024 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, announced today that it has released updated results from a global, multicenter Phase Ib/II study of the Bcl-2 inhibitor lisaftoclax (APG-2575) alone or in combinations for the treatment of patients with Waldenström macroglobulinemia (WM), in a poster presentation at the 60th American Society of Clinical Oncology (ASCO) Annual Meeting taking place in Chicago, IL. This is the second consecutive year in which this study of lisaftoclax, a key drug candidate in the company's apoptosis-targeted pipeline, was selected for presentations at the ASCO Annual Meeting. The ASCO Annual Meeting showcases the most cutting-edge research in clinical oncology and state-of-the-art advanced cancer therapies and is the world's most influential and prominent scientific gathering of the clinical oncology community. Presenting clinical development progress at the ASCO Annual Meeting for the seventh consecutive year, Ascentage had four clinical studies of three of the company's proprietary drug candidates selected for presentations, including an oral report, at ASCO 2024. The latest results from this clinical study validated the favorable safety and efficacy of lisaftoclax monotherapy and in combinations in WM. According to the data, lisaftoclax combined with ibrutinib showed an objective response rate (ORR) of 90.9% in treatment-naïve patients with WM (responses that were unaffected by the CXCR4 mutation), manageable adverse events (AEs), and a low risk of tumor lysis syndrome (TLS). In addition, no potential drug-drug interactions (DDIs) with ibrutinib were observed in the study. "Lisaftoclax is a novel Bcl-2 selective inhibitor developed to treat malignancies by selectively blocking the antiapoptotic protein Bcl-2 and hence restoring the normal apoptosis process in cancer cells," said Dr. Sikander Ailawadhi, the Principal Investigator of the Study from Mayo Clinic. "In this global Phase Ib/II study in patients with relapsed/refractory (R/R) WM, lisaftoclax both as a monotherapy and in combination with ibrutinib or rituximab has shown favorable efficacy that was not negatively affected by the presence of the CXCR4 mutation. In addition, lisaftoclax showed a manageable safety profile with low risk of TLS during daily dose ramp-up. We look forward to seeing more data from this trial." "Lisaftoclax is the first pivotal-stage Bcl-2 inhibitor in China and the second globally that has demonstrated promising efficacy," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "The updated clinical data of lisaftoclax in WM presented at this year's ASCO Annual Meeting underscore the drug's strong therapeutic potential, both as a monotherapy and in combinations, for the treatment of hematologic malignancies. We will continue to advance the clinical development of lisaftoclax with the hope to allow more patients to benefit from the drug as soon as possible." Highlights of these data presented at ASCO 2024 are as follows: Updated efficacy and safety results of BCL-2 inhibitor lisaftoclax (APG-2575) alone or combined with ibrutinib or rituximab in patients (pts) with Waldenström macroglobulinemia (WM) Abstract#: 7078 Session Title: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia Date and Time: June 3, 2024, Monday, 9:00 AM– 12:00 PM (Central Time) First Author: Masa Lasica, MBBS, FRACP, FRCPA, St Vincent's Hospital, Melbourne, Victoria, Australia. Highlights: Background: Lisaftoclax is a novel, oral, highly selective, potent Bcl-2 inhibitor. In an ibrutinib-resistant patient-derived WM xenograft/preclinical model, lisaftoclax combined with ibrutinib has a strong synergistic effect. Introduction: This was an open-label, multicenter, global Phase Ib/II study designed to evaluate the efficacy, safety, tolerability, and pharmacokinetics (PK) of lisaftoclax monotherapy or in combinations with agents such as ibrutinib/rituximab in patients with WM. Patient enrollment and methods: In this study, patients with WM were enrolled in 3 arms, including Arm A: lisaftoclax monotherapy in patients resistant to or intolerant of prior treatment with Bruton's tyrosine kinase inhibitors (BTKis); Arm B: lisaftoclax combined with ibrutinib in treatment-naïve patients with WM; and Arm C: lisaftoclax combined with rituximab in BTKi-naïve patients with relapsed/refractory WM. Lisaftoclax was orally administered once daily in 28-day cycles. Lisaftoclax was gradually escalated from the starting dose of 400 mg to 1,200 mg. As of January 25, 2024, a total of 46 patients were enrolled in the study (Arm A [n=14] at doses of up to 1,000 mg; Arm B [n=24] at doses of up to 1,200 mg; Arm C [n=8] at doses of up to 800 mg). Efficacy results: The median (range) durations of treatment were 11 (1-28), 23.5 (1-34), and 11.5 (5-33) months for Arms A, B, and C, respectively. The ORRs (PR, very good partial response [VGPR], CR) were 41.7%, 90.9%, and 37.5% for Arms A, B, and C, respectively. In Arm A, patients with wild-type CXCR4 (n =7) had better overall responses to lisaftoclax than the CXCR4 mutation group (n = 3). In Arms B and C, no significant differences between patients with/without CXCR4 mutation were observed. Safety results: In Arm B, 1 dose-limiting toxicity (DLT, grade 3 clinical TLS), in the setting of anticipated renal impairment, occurred at 1,200 mg; and 1 grade 3 laboratory TLS, primarily attributed to dehydration and concomitant symptomatic therapies, occurred at 1,000 mg. Abnormal electrolytes was resolved without recurrence after 1 day of drug interruption. Grade ≥ 3 lisaftoclax-related AEs included neutropenia (15.2%), thrombocytopenia (4.3%), decreased leukocytes (4.3%), TLS (4.3%), anemia (2.2%), weight loss (2.2%), and septic shock (2.2% in the setting of neutropenia). Ventricular arrhythmia was not observed. One patient required dose reduction because of neutropenia. The maximum-tolerated dose (MTD) was not reached. Lisaftoclax combined with ibrutinib showed a PK exposure comparable to lisaftoclax or ibrutinib alone, indicating no potential DDIs. Conclusions: Lisaftoclax alone or combined with ibrutinib or rituximab was well tolerated and demonstrated measurable effects in patients with treatment-naïve or BTKi-treatment-failed WM. *Lisaftoclax is an investigational drug that has not been approved in any country and region. Appendix: The four clinical studies of Ascentage Pharma's three drug candidates, including lisaftoclax, presented at this year's ASCO Annual Meeting. About Ascentage Pharma Ascentage Pharma (6855.HK) is a globally focused biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B, and age-related diseases. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK. Ascentage Pharma focuses on developing therapeutics that inhibit protein-protein interactions to restore apoptosis, or programmed cell death. The company has built a pipeline of 9 clinical drug candidates, including novel, highly potent Bcl-2, and dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation tyrosine kinase inhibitors (TKIs). Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company is conducting more than 40 Phase I/II clinical trials, including 5 global registrational phase III studies, in the US, Australia, Europe, and China. Ascentage Pharma has been designated for multiple Major National R&D Projects, including five Major New Drug Projects, one New Drug Incubator status, four Innovative Drug Programs, and one Major Project for the Prevention and Treatment of Infectious Diseases. Olverembatinib, the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company's first approved product in China, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China 2022 National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU. To date, Ascentage Pharma has obtained a total of 16 ODDs from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company's investigational drug candidates. Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships with numerous renowned biotechnology and pharmaceutical companies and research institutes such as UNITY Biotechnology, MD Anderson Cancer Center, Mayo Clinic, Dana-Farber Cancer Institute, MSD, and AstraZeneca. The company has built a talented team with global experience in the discovery and development of innovative drugs and is setting up its world-class commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients. Forward-Looking Statements The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, Ascentage Pharma undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development. SOURCE Ascentage Pharma