Mitoxantrone liposomal(CSPC Pharmaceutical Group Ltd.)

The data, published in the International Journal of Molecular Sciences, demonstrate that opaganib significantly improved long-term survival in an in vivo model of lung damage following exposure to ionizing radiation Opaganib is the first selective sphingosine kinase-2 (SPHK2) inhibitor investigational drug targeting sphingolipid metabolism for the treatment of radiation-induced inflammation Opaganib, a novel oral, small molecule pill with a five-year shelf-life, is easy to administer and distribute, supporting potential central government stockpiling for use as radioprotection therapy in mass casualty radiological or nuclear incidents, if approved by the FDA Opaganib is being tested as a potential treatment for Acute Radiation Syndrome (ARS) following selection by the U.S government National Institutes of Health's (NIH) Radiation and Nuclear Countermeasures Program (RNCP) for its radiation medical countermeasures Product Development Program Opaganib is being developed for multiple additional indications, including COVID-19, acute respiratory distress syndrome (ARDS), filoviruses (including Ebola) and oncology TEL AVIV, Israel and RALEIGH, N.C., Feb. 20, 2024 /PRNewswire/ -- RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, today announced a new publication of data from multiple experiments in the International Journal of Molecular Sciences1. The published data shows that opaganib2 protects against radiation-induced lung inflammation and fibrosis in an in vivo mouse model of lung damage following exposure to ionizing radiation, demonstrating its potential use as a medical countermeasure against nuclear irradiation and in cancer radiotherapy. Radiation-induced inflammation is known to occur in two phases – in an initial inflammatory response immediately after irradiation and in a delayed response that can occur weeks later. As such, one of the experiments looked specifically at longer-term survival with two treatment windows: 1-3 days post-radiation and 31-45 days post-radiation. The opaganib group treated both during the initial and delayed phases of inflammation demonstrated a highly statistically significant improvement in survival at Day 180 (60% survival compared with 10% for controls, p=0.008). Thus, treating with opaganib during both initial and delayed phases of inflammation provided the greatest improvement in survival. "The data, when looked at collectively across multiple experiments, demonstrate that opaganib significantly improved long-term survival associated with reduced lung fibrosis, suppression of granulocyte infiltration, and reduced expression of IL-6 and TNFα in an in vivo model of lung damage following exposure to ionizing radiation," said Dr. Lynn W. Maines, lead author of the publication and VP of Research at Apogee Biotechnology Corporation, RedHill's development partner for opaganib. "These data further demonstrate that sphingolipid metabolism is a critical regulator of fibrogenesis, and specifically show that opaganib suppresses radiation-induced pulmonary inflammation and fibrosis." Opaganib is being tested as a potential treatment for Acute Radiation Syndrome (ARS), following selection by the U.S government National Institutes of Health's (NIH) Radiation and Nuclear Countermeasures Program (RNCP) for its radiation medical countermeasures Product Development Program. Opaganib was also recently selected for inclusion into the BARDA/NIH Chemical Countermeasures screening program for Sulfur Mustard exposure. Opaganib, a novel, oral, small molecule pill with a five-year shelf-life, is easy to administer and distribute, supporting potential central government stockpiling for use as a medical countermeasure in the event of mass casualty nuclear radiation incidents or Sulfur Mustard attack, if approved by the U.S. Food and Drug Administration (FDA). About Lung Inflammation, Fibrosis and Acute Radiation Syndrome (ARS) ARS, sometimes known as radiation toxicity or radiation sickness, is generally rare; however, public health emergencies, such as a nuclear power plant accident or detonation of a nuclear device, could affect large numbers of people. ARS is an acute illness caused by irradiation of the body by a high dose of penetrating radiation in a short period of time. Much of the damage caused by ARS is caused by inflammation secondary to the direct effects of ionizing radiation itself. The inflammation can occur throughout the body, but specifically, inflammation in the lungs can cause the tissue around the air sacs of the lungs (alveoli) to become damaged, thickened, and scarred – this is known as pulmonary fibrosis. As the lungs scar and stiffen, breathing becomes more difficult, and the amount of oxygen entering the blood system becomes reduced. Current treatments for ARS are supportive care, including blood transfusions, antibiotics, etc., as well as the availability of four approved products (three growth factors to address neutropenia and one to mitigate thrombocytopenia*). However, other radiation-induced clinical manifestations that have been observed in natural history studies and remain unaddressed with the current treatments include GI-ARS, cutaneous injury, and late effects in the lung, heart, and kidneys. Opaganib, an SPHK2 inhibitor, may offer a new therapeutic approach to mitigate both hematopoietic-ARS and GI-ARS. It has also been reported in the literature that inhibition of SPHK2 promotes the viability and robustness of hematopoietic stem cells, even in the face of radiation damage, supporting increased survival. * The agents are filgrastim, PEGylated filgrastim and romiplostim (Neupogen®, Neulasta® and Nplate®, all Amgen Inc., NasdaqGS: AMGN), sargramostim (Leukine®, Partner Therapeutics Inc.). About Opaganib (ABC294640) Opaganib, a proprietary investigational host-directed and potentially broad-acting drug, is a first-in-class, orally administered sphingosine kinase-2 (SPHK2) selective inhibitor with anticancer, anti-inflammatory and antiviral activity, targeting multiple potential diseases, including gastrointestinal acute radiation syndrome (GI-ARS), COVID-19, other viruses as part of pandemic preparedness, and cholangiocarcinoma (bile duct cancer). Opaganib's host-directed action is thought to work through the inhibition of multiple pathways, the induction of autophagy and apoptosis, and disruption of viral replication, through simultaneous inhibition of three sphingolipid-metabolizing enzymes in human cells (SPHK2, DES1 and GCS). Opaganib was selected by the U.S. government's Radiation and Nuclear Countermeasures Program (RNCP), led by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, for the nuclear medical countermeasures product development pipeline as a potential treatment for Acute Radiation Syndrome (ARS). Opaganib has demonstrated antiviral activity against SARS-CoV-2, multiple variants, and several other viruses, such as Influenza A. Opaganib also recently demonstrated a distinct synergistic effect when combined individually with remdesivir (Veklury®, Gilead Sciences Inc., Nasdaq: GILD), significantly improving potency while maintaining cell viability, in a U.S. Army-funded and conducted in vitro Ebola virus study. Being host-targeted, and based on data accumulated to date, opaganib is expected to maintain effect against emerging viral variants. In prespecified analyses of Phase 2/3 clinical data in hospitalized patients with moderate to severe COVID-19, oral opaganib demonstrated improved viral RNA clearance, faster time to recovery and significant mortality reduction in key patient subpopulations versus placebo on top of standard of care. Opaganib has demonstrated its safety and tolerability profile in more than 470 people in multiple clinical studies and expanded access use. Data from the opaganib global Phase 2/3 study was published in medRxiv. Opaganib has received Orphan Drug designation from the FDA for the treatment of cholangiocarcinoma and has undergone studies in advanced cholangiocarcinoma (Phase 2a) and prostate cancer. Opaganib also has a Phase 1 chemoradiotherapy study protocol ready for FDA-IND submission. Opaganib has also shown positive preclinical results in renal fibrosis, and has the potential to target multiple oncology, radioprotection, viral, inflammatory, and gastrointestinal indications. About RedHill Biopharma RedHill Biopharma Ltd. (Nasdaq: RDHL) is a specialty biopharmaceutical company primarily focused on gastrointestinal and infectious diseases. RedHill promotes the gastrointestinal drugs Talicia®, for the treatment of Helicobacter pylori (H. pylori) infection in adults[3], and Aemcolo®, for the treatment of travelers' diarrhea in adults[4]. RedHill's key clinical late-stage development programs include: (i) opaganib (ABC294640), a first -in -class oral broad-acting, host-directed SPHK2 selective inhibitor with potential for pandemic preparedness, targeting multiple indications with a U.S. government collaboration for development for Acute Radiation Syndrome (ARS), a Phase 2/3 program for hospitalized COVID-19, and a Phase 2 program in oncology; (ii) RHB-107 ( upamostat), an oral broad-acting, host-directed, serine protease inhibitor with potential for pandemic preparedness is in late-stage development as a treatment for non-hospitalized symptomatic COVID-19, with non-dilutive external funding covering the entirety of the RHB-107 arm of the 300-patient Phase 2 adaptive platform trial, and is also targeting multiple other cancer and inflammatory gastrointestinal diseases; (iii) RHB-102, with potential UK submission for chemotherapy and radiotherapy induced nausea and vomiting, positive results from a Phase 3 study for acute gastroenteritis and gastritis and positive results from a Phase 2 study for IBS-D; (iv) RHB-104, with positive results from a first Phase 3 study for Crohn's disease; and (v) RHB-204, a Phase 3-stage program for pulmonary nontuberculous mycobacteria (NTM) disease. RedHill is open to opportunities to acquire revenue generating assets in various indications, aligned to our strategic direction. Trading in RedHill's shares, ADSs and Warrants is regulated by the Securities and Exchange Commission (SEC), and the Company is committed to work in compliance with all relevant SEC and FDA regulations and requirements. More information about the Company is available at / twitter.com/RedHillBio. Forward Looking Statements This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 and may discuss investment opportunities, stock analysis, financial performance, investor relations, and market trends. Such statements, including, but not limited to, statements regarding the intended use of net proceeds from the offering, may be preceded by the words "intends," "may," "will," "plans," "expects," "anticipates," "projects," "predicts," "estimates," "aims," "believes," "hopes," "potential" or similar words and include statements regarding the risk that the Company will not comply with the listing requirements of the Nasdaq Capital Market ("Nasdaq") to remain listed for trading on Nasdaq, the addition of new revenue generating products, out-licensing of the Company's development pipeline assets, timing of opaganib's development for Acute Radiation Syndrome, non-dilutive development funding from RHB-107 and its inclusion in a key platform study. Forward-looking statements are based on certain assumptions and are subject to various known and unknown risks and uncertainties, many of which are beyond the Company's control and cannot be predicted or quantified, and consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, market and other conditions, the risk that the addition of new revenue generating products or out-licensing transactions will not occur; the risk that acceptance onto the RNCP Product Development Pipeline will not guarantee ongoing development or that any such development will not be completed or successful; the risk that the FDA does not agree with the Company's proposed development plans for opaganib for any indication, the risk that observations from preclinical studies are not indicative or predictive of results in clinical trials; the risk that the FDA pre-study requirements will not be met and/or that the Phase 3 study of RHB-107 in COVID-19 outpatients will not be approved to commence or if approved, will not be completed or, should that be the case, that we will not be successful in obtaining alternative non-dilutive development funding for RHB-107, the risk that HB-107's late-stage development for non-hospitalized COVID-19 will not benefit from the resources redirected from the terminated RHB-204 Phase 3 study, that the Phase 2/3 COVID-19 study for RHB-107 may not be successful and, even if successful, such studies and results may not be sufficient for regulatory applications, including emergency use or marketing applications, and that additional COVID-19 studies for opaganib and RHB-107 are likely to be required, as well as risks and uncertainties associated with the risk that the Company will not successfully commercialize its products; as well as risks and uncertainties associated with (i) the initiation, timing, progress and results of the Company's research, manufacturing, pre-clinical studies, clinical trials, and other therapeutic candidate development efforts, and the timing of the commercial launch of its commercial products and ones it may acquire or develop in the future; (ii) the Company's ability to advance its therapeutic candidates into clinical trials or to successfully complete its pre-clinical studies or clinical trials or the development of a commercial companion diagnostic for the detection of MAP; (iii) the extent and number and type of additional studies that the Company may be required to conduct and the Company's receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings, approvals and feedback; (iv) the manufacturing, clinical development, commercialization, and market acceptance of the Company's therapeutic candidates and Talicia®; (v) the Company's ability to successfully commercialize and promote Talicia® and Aemcolo®; (vi) the Company's ability to establish and maintain corporate collaborations; (vii) the Company's ability to acquire products approved for marketing in the U.S. that achieve commercial success and build its own marketing and commercialization capabilities; (viii) the interpretation of the properties and characteristics of the Company's therapeutic candidates and the results obtained with its therapeutic candidates in research, pre-clinical studies or clinical trials; (ix) the implementation of the Company's business model, strategic plans for its business and therapeutic candidates; (x) the scope of protection the Company is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; (xi) parties from whom the Company licenses its intellectual property defaulting in their obligations to the Company; (xii) estimates of the Company's expenses, future revenues, capital requirements and needs for additional financing; (xiii) the effect of patients suffering adverse experiences using investigative drugs under the Company's Expanded Access Program; (xiv) competition from other companies and technologies within the Company's industry; and (xv) the hiring and employment commencement date of executive managers. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's filings with the Securities and Exchange Commission (SEC), including the Company's Annual Report on Form 20-F filed with the SEC on April 28, 2023. All forward-looking statements included in this press release are made only as of the date of this press release. The Company assumes no obligation to update any written or oral forward-looking statement, whether as a result of new information, future events or otherwise unless required by law. Company contact: Adi Frish Chief Corporate & Business Development Officer RedHill Biopharma +972-54-6543-112 [email protected] Category: Financials [1] Maines LW, Keller SN, Smith RA, Green CL, Smith CD. The Sphingolipid-Modulating Drug Opaganib Protects against Radiation-Induced Lung Inflammation and Fibrosis: Potential Uses as a Medical Countermeasure and in Cancer Radiotherapy. International Journal of Molecular Sciences. 2024; 25(4):2322. [2] Opaganib is an investigational new drug, not available for commercial distribution. [3] Talicia® (omeprazole magnesium, amoxicillin and rifabutin) is indicated for the treatment of H. pylori infection in adults. For full prescribing information see: . [4] Aemcolo® (rifamycin) is indicated for the treatment of travelers' diarrhea caused by noninvasive strains of Escherichia coli in adults. For full prescribing information see: . SOURCE RedHill Biopharma Ltd.

SUZHOU, China, and ROCKVILLE, Md., Nov. 2, 2023 /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 results from multiple clinical studies of the company's novel drug candidate, olverembatinib, have been selected for presentations, including two Oral Reports, at the 65th American Society of Hematology (ASH) Annual Meeting. Being selected for Oral Reports at the ASH Annual Meeting for the sixth consecutive year underscores the significant interest in the drug by the global hematology community. This year, results from multiple clinical studies on two of Ascentage Pharma's lead drug candidates (olverembatinib and lisaftoclax) have been selected for presentations at the ASH Annual Meeting. As a potential best-in-class drug, olverembatinib has broad therapeutic potential for the treatment of multiple solid tumors and hematologic malignancies. Currently, olverembatinib is being jointly commercialized by Ascentage Pharma and Innovent Biologics. Through an Oral Report at this year's ASH Annual Meeting, Ascentage Pharma will present the latest results from a randomized, controlled registrational Phase II study in patients with first- and second-generation tyrosine kinase inhibitor (TKI)-resistant chronic myeloid leukemia in the chronic-phase (CML-CP), led by Prof. Xiaojun Huang and Prof. Qian Jiang, from the Institute of Hematology of the Peking University People's Hospital. These data show that, in patients with CML-CP who were resistant/intolerant to TKIs, olverembatinib demonstrated statistically significant and clinically meaningful improvement in event-free survival (EFS), compared with the best available therapy (BAT), meeting the primary endpoint of the study. The other Oral Report featuring early results from a Phase II study of olverembatinib combined with venetoclax and reduced-intensity chemotherapy in treatment-naïve patients with Ph+ ALL, led by Prof. Xiaoyuan Gong of the Institute of Hematology and Blood Diseases Hospital, the Chinese Academy of Medical Sciences Also at this year's ASH Annual Meeting, Ascentage Pharma will release updated results from a US study of olverembatinib in a Poster Presentation. These data demonstrate the favorable potential clinical benefit of olverembatinib monotherapy and combination regimens in patients with heavily pretreated CML or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and show the drug's therapeutic effect in patients who had failed prior treatment with ponatinib or asciminib, further demonstrating the drug's potential as a new treatment option to patients with CML or Ph+ ALL worldwide. In addition, multiple studies of olverembatinib were also selected for Poster Presentations, including one featuring a case series study of liposome mitoxantrone combined with venetoclax, homoharringtonine, and olverembatinib (the MVHO regimen) in pediatric patients with refractory or recurrent acute myeloid leukemia (AML), carried out by a team of investigators including Wenting Hu and Prof. Shuhong Shen of the Department of Hematology & Oncology, Shanghai Children's Medical Center of Shanghai Jiao Tong University School of Medicine (see the table below for details). The ASH Annual Meeting is one of the largest gatherings of the international hematology community, bringing together the latest and most cutting-edge scientific research in the pathogenesis and clinical treatment of hematologic diseases. The 65th ASH Annual Meeting will take place on December 9-12, 2023, local time, both online and in-person in San Diego, CA (United States). "This is the sixth consecutive year for the updated clinical data of olverembatinib to be accepted for presentation at the ASH Annual Meeting, a new record for the drug," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "This year, results from multiple studies of olverembatinib have been selected for presentations, including two Oral Reports, at the meeting. This indicates the global hematology community's strong recognition of olverembatinib, a global best-in-class drug. The large body of clinical data we are bringing to this year's ASH Annual Meeting underscores our broad progress in new drug discovery and clinical development. Moving forward, we will continue to expeditiously advance our clinical development programs globally for the benefit of patients in China and around the world." Studies of Ascentage Pharma's Drug Candidates to be presented at ASH 2023 Abtracts on olverembatinib presented at the 2023 ASH Annual Meeting are as follows (for details on the abstracts featuring lisaftoclax, please refer to a separate press release published at the same time): Olverembatinib (HQP1351) Demonstrates Efficacy Vs. Best Available Therapy (BAT) in Patients (Pts) with Tyrosine Kinase Inhibitor (TKI)-Resistant Chronic Myeloid Leukemia Chronic-Phase (CML-CP) in a Registrational Randomized Phase 2 Study Format: Oral Report Abstract: #869 Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Novel Therapeutic Approaches Time: December 11, 2023, Monday, 3:45 PM (Pacific Time) / December 12, 2023, Tuesday, 7:45 AM (Beijing Time) Highlights: This is a multicenter, randomized, registrational Phase II study designed to assess the efficacy and safety of olverembatinib compared with the BAT in patients with CML-CP. As of April 30, 2023, a total of 144 patients were enrolled, of whom 69.4% were male and 30.6% were female. The median (range) age of these patients was 49.0 (18-77) years. A total of 96 patients were treated with olverembatinib, and 48 patients were treated with BAT. The median (range) duration of follow-up for the olverembatinib and BAT arms were 12.67 (0.0-40.9) months and 2.94 (0.0-40.4) months, respectively. 66 (45.8%) patients had ≥1 BCR::ABL1 mutations, and 39 (27.1%) had the "gatekeeper" BCR::ABL1T315I mutation, which confers resistance against all first- and second-generation tyrosine kinase inhibitors (TKIs). A total of 97 patients discontinued therapies (56 [58.3%] from the olverembatinib arm, 41 [85.4%] from the BAT arm) due to disease progression, treatment failure, adverse events (AEs), consent withdrawal, poor compliance, or death. Safety results: 82/96 (85.4%) patients receiving olverembatinib and 31/46 (67.4%) patients receiving BAT experienced grade≥3 AEs. AEs with an incidence >20% included thrombocytopenia; leukopenia; anemia; neutropenia; elevated creatine phosphokinase (CPK), alanine aminotransferase (ALT), and aspartate aminotransferase (AST); and hypertriglyceridemia. Serious AEs (SAEs) with an incidence >5% included thrombocytopenia. Common AEs (≥10%) that led to discontinuation, dose reduction, or treatment withdrawal were thrombocytopenia, neutropenia, and leukopenia. Efficacy results: Data showed that, in patients with CML-CP resistant/intolerant to prior treatment with TKIs, the olverembatinib arm, compared with the BAT arm, achieved statistically significant improvement in event-free survival (EFS), therefore meeting the primary endpoint of the study. The median (range) EFS was 21.22 (95% CI: 10.15 to not reached) months in the olverembatinib arm compared to 2.86 (95% CI 2.53-4.73) months in the BAT arm. Compared with the BAT control arm, olverembatinib reduced the risk of events by 65%. In the olverembatinib arm, the estimated EFS at 6, 12, and 24 months was 73% (95% CI, 62.5-81.0), 58.7% (95% CI, 47.5-68.2), and 46.9% (95% CI, 35.9-57.2), respectively. In the BAT group, it was 32.6% (95% CI,19.7-46.2), 26.1% (95% CI, 14.5-39.3), and 16.9% (95% CI, 7.7-29.2) at 6, 12 and 24 months, respectively. Neither the olverembatinib nor the BAT arm reached the median overall survival (OS). As of the data cutoff date, 34 (71%) patients in the BAT control arm were crossed-over to be treated with olverembatinib after reaching the EFS endpoint. The olverembatinib arm showed significantly better efficacy and higher response rates than the BAT control arm. Conclusions: Olverembatinib was observed to be better tolerated and more effective than BAT in patients with CML-CP resistant or intolerant to first- and second-generation TKIs. Update of Olverembatinib (HQP1351) Overcoming Ponatinib and/or Asciminib Resistance in Patients (Pts) with Heavily Pretreated/Refractory Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) Format: Poster Presentation Abstract: #1798 Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster I Time: December 9, 2023, Saturday, 5:30 PM - 7:30 PM (Pacific Time) / December 10, 2023, Sunday, 9:30 AM – 11:30 AM (Beijing Time) Highlights Olverembatinib, a novel, potent BCR::ABL1 tyrosine kinase inhibitor (TKI), has shown strong antitumor activity in patients with CML and Ph+ ALL. This abstract reports on the safety, efficacy, and pharmacokinetics (PK) of olverembatinib in patients with CML and Ph+ ALL outside China, particularly in patients previously treated with third-generation TKI ponatinib and/or allosteric STAMP inhibitor asciminib. Methods: Olverembatinib was administered orally once every other day (QOD) in 28-day cycles. In the monotherapy cohort, patients were enrolled after treatment failures on at least 2 prior TKIs and randomized to receive olverembatinib QOD at 30, 40, or 50 mg. In the combination cohort, patients with Ph+ B-cell precursor ALL (BCP ALL) or lymphoid CML-BP (CML-LBP) resistant to at least 1 TKI were enrolled and administered olverembatinib (30 or 40 mg) QOD in combination with blinatumomab. As of June 30, 2023, 76 patients were enrolled, including 57 with CML-CP and 19 with advanced Ph+ leukemia. The median (range) age was 54.5 (21-80) years and 56.6% of patients were male.11 (14.5%), 23 (30.3%) and 39 (51.3%) patients had received 2, 3, and ≥4 TKIs, respectively. A total of 52.6% of patients were previously treated with ponatinib, of whom 67.5% were resistant and 25.0% were intolerant to the drug, and 7.5% of patients failed for other reasons. A total of 27.6% of patients were previously treated with asciminib, of whom 71.4% were resistant and 19.1% were intolerant to the agent, and 9.5% failed for other reasons. At baseline, 32% of patients had T315I mutations, 38% had hypertension, and 17.1% had other cardiovascular comorbidities. The median (range) duration of treatment was 24.1 (0-134) weeks. PK analysis showed that western patients had a PK profile similar to historical data on Chinese patients. Safety results: 12 patients with CML-CP and 7 with advanced Ph+ leukemia discontinued treatment for reasons including AEs (n=4), disease progression (n=7), and other reasons (n=8). A total of 54 (83.1%) patients experienced treatment-related AEs (TRAEs) of any grade after receiving olverembatinib. Grade ≥3 AEs occurring in ≥3 patients (≥ 4.6% incidence) included thrombocytopenia (17%), neutropenia (13.8%), elevated blood creatine phosphokinase (13.8%), leukopenia (7.7%), anemia (4.6%), and elevated lipase (4.6%). 10 (15.4%) patients experienced olverembatinib treatment-related serious AEs (SAEs). 2 (3.1%) patients discontinued the study due to TRAEs, and no TRAE-related deaths were reported. Efficacy results: Among 50 efficacy-evaluable patients with CML-CP, 57% (25/44) achieved a complete cytogenetic response (CCyR), 43% (21/49) achieved a major molecular response (MMR), and efficacy continued to improve over time. The rate of MMR in patients with CML-CP treated for 6 months and 12 months was 66% and 88%, respectively. At 24 months, the rate of progression-free survival (PFS) was 75% (95% CI: 56.1-86.7) and the OS was 97.6% (95% CI: 90.8-99.4). Among patients whose disease failed ≥4 prior TKIs, CCyR and MMR rates were 57% (13/23) and 42% (11/26), respectively; In patients with CML-CP harboring the T315I mutation, CCyR and MMR rates were 60% (9/15) and 44% (7/16), respectively; In patients without the T315I mutation, CCyR and MMR rates were 55% (16/29) and 42% (14/33), respectively; In patients who had failed treatment with ponatinib, CCyR and MMR rates were 53% (8/15) and 38% (6/16), respectively; In patients who had failed treatment with asciminib, CCyR and MMR rates were 43% (3/7) and 38% (3/8), respectively. Among the 8 patients who were resistant/intolerant to both ponatinib and asciminib, 2 achieved MMR. Among the 13 efficacy-evaluable patients with advanced Ph+ leukemia, 3 (23%) achieved MMR, of whom 1 patient harbored the T315I mutation and 2 were T315I mutation negative and resistant to ponatinib. In the combination cohort, 2 patients with Ph+ BCP ALL received olverembatinib 30 mg QOD in combination with blinatumomab. Both patients achieved CCyR and 1 achieved negative minimal residual disease (MRD) status after 1 treatment cycle. Conclusions: Olverembatinib alone or combined with blinatumomab was efficacious and well tolerated in heavily pretreated patients with CML or Ph+ ALL. The efficacy of olverembatinib was not affected by prior exposure to ponatinib or asciminib, and the status of the T315I mutation. Olverembatinib may provide an effective treatment option for patients with CML or Ph+ ALL who have failed 2 or more TKIs. Olverembatinib Combined with Venetoclax and Reduced-Intensity Chemotherapy for Patients with Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Early results from a phase II study Format: Oral Report Abstract: #827 Session: 614. Acute Lymphoblastic Leukemia: Therapies, Excluding Transplantation and Cellular Immunotherapies: Optimal Frontline Treatment for ALL Time: December 11, 2023, Monday; 3:45 PM (Pacific Time) / December 12, 2023, Tuesday; 7:45 AM (Beijing Time) Highlights : Background: The combination of olverembatinib (HQP1351), a novel third-generation tyrosine kinase inhibitors (TKIs), with venetoclax generated high response rates in patients with relapsed/refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL). However, the efficacy and safety of these two agents-based regimens as frontline treatment remains unknown. Methods: This is a single-arm phase II study (NCT05594784) that enrolled patients (pts) ≥ 14 years (yrs) of age with newly diagnosed Ph+ ALL. Pts were treated with a combination of venetoclax (100 mg d1, 200 mg d2, 400 mg d3-28), olverembatinib 40 mg once every continuously other day, vincristine 1.4 mg/m2 (maximum dose 2 mg) on day 1, 8, 15, 22, and prednisone 60 mg/m2 on day 1-14; 40 mg/m2 on day 15-28 in cycle 1. In cycle 2-3, oral treatment with venetoclax 400 mg × 7 days, olverembatinib once every other day continuously and prednisone 60 mg/m × 7 days were administrated. Cycles were repeated every 28 days. During cycle 1, The dose of olverembatinib was reduced to 30 mg once every other day for pts achieving a complete molecular response (CMR). The primary endpoint of this study was the CMR rate at 3 months. CMR was defined as undetectable BCR:ABL1 transcripts by using the RT-PCR method with sensitivity of 0.001%. MMR was defined as more than 3-log reduction of BCR:ABL1 transcripts. From August 2022 to April 2023, a total of 31 pts were enrolled. All pts completed 3 cycles of treatment and could be assessed for the primary endpoint. The data cutoff date was July 25, 2023 with a median follow-up time of 5.8 months. The median age was 40 years (range, 20-66 years) and males accounted for 58.1%. Twenty-three pts (74.2%) expressed the p190 transcript and 8 pts (25.8%) expressed the p210 transcript. The median expression level of BCR:ABL1 was 96.33% (range, 70.79%-175.39%). Efficacy results: All patients achieved CR at the end of cycle 1 and no TLS or treatment-related deaths occurred. Molecular response at the end of cycle 1 was CMR in 17 patients (54.8%), and MMR in 8 (25.8%). Molecular response at 3 months was CMR in 19 patients (61.3%) and MMR in 10 (32.3%). No patients developed relapses or deaths at the last follow-up. Safety results: The regimen was well-tolerated and safe. Most side effects were grade 1-2. The demand for transfusion and the incidence of infections significantly decreased compared to our historic data. No patient discontinued olverembatinib or venetoclax due to toxicity. Conclusions: The combination of olverembatinib and venetoclax with reduced-intensity chemotherapy is a safe and effective regimen in patients with newly diagnosed Ph ALL. The regimen results in high rates of CMR in the absence of intensive chemotherapy or immunotherapy. Combination of Liposome Mitoxantrone, Venetoclax, Homoharringtonine, and Olverembatinib (HQP1351) (MVHO) in Pediatric Patients with Refractory or Recurrent Acute Myeloid Leukemia (AML): Case Series Format: Poster Presentation Abstract: #2840 Session: 613. Acute Myeloid Leukemias: Clinical and Epidemiological: Poster II Time: December 10, 2023, Sunday, 6:00 PM - 8:00 PM (Pacific Time) / December 11, 2023, Monday, 10:00 AM – 12:00 PM (Beijing Time) Highlights: Background: AML accounts for up to 25% of all pediatric acute leukemia cases. Although the OS in pediatric AML has increased to approximately 70% in recent years because of enhanced risk stratification and therapeutics, approximately 30% of patients experience relapse, and 5% to 10% die because of disease complications or untoward medication effects. Hence, pediatric AML continues to represent an unmet medical need. This study investigated the safety and efficacy of the MVHO therapy in pediatric patients with refractory or relapsed AML. Methods: The study enrolled patients with recurrent or newly diagnosed AML with poor prognosis secondary to related molecular abnormalities, including NUP98 rearrangements, FUS-ERG, CBFA2T3-GLIS2, and del(7/7q), who did not achieve complete remission (CR) after first-line induction therapy (i.e., DA, DAE, DAH, MAG, and CLAG). Patients were administered the MVHO regimen, which included 1 dose of liposome mitoxantrone at 8 mg/m2; venetoclax at 300 to 350 mg/m2 once daily on days (D) 1 through 7 (with dose escalation if high tumor burden); homoharringtonine at 2 mg/m2 once daily on D1 through 7; and olverembatinib at 20-30 mg/m2 every other day on D1, 3, 5, and 7. The remission rate after 1 cycle (28-35 days, depending on hematopoietic recovery), overall response rate, recurrence rate, EFS, hematologic toxicity, and infection rate of the MVHO protocol were evaluated. A total of 18 patients were enrolled (9 boys and 9 girls), with a median (range) age of 7.3 (4 months-13 years) years, and underwent a total of 27 cycles of the MVHO therapy. Half of the patients underwent 1 cycle and the other half underwent 2 cycles. Per French-American-British (FAB) classification criteria, patients had myelodysplastic syndrome (n = 2); mixed-phenotype acute leukemia (n = 2); and AML subtypes M7 (n = 4), M2 (n = 4), M5 (n = 4), M4 (n = 1), and M0 (n = 1). Efficacy results: The median (range) follow-up time was 131 (26-256) days. The objective response rate (CR + complete remission with incomplete hematological recovery [Cri] + partial response) was 83.3%, and the remission rate (CR + Cri) after 1 cycle was 72.2%. A total of 8 patients were minimum residual disease negative. For the 6 patients with relapsed AML, the remission rate after 1 cycle was 66.7%. A total of 3 patients discontinued because of no response or disease progression, and 12 patients underwent hematopoietic stem cell transplantation, after which 1 patient relapsed. The rate of recurrence was 6.7% (1/15). The 8-month mean (± SD) EFS was 60.1% (± 19%) and the OS was 100%. Safety results: Among the 26 cycles of treatment evaluated for toxicity, there were no associated fatal infections or bleeding events. Prophylactic levofloxacin and posaconazole were administered orally (or intravenously administered anti-infection treatment in the case of infection) during myelosuppression in each cycle. No breakthrough infection was observed in 5 of 26 cycles of MVHO. There was 1 case of septic shock, and the incidence of grade ≥ 3 infection was 80.7%, which included pneumonia and bloodstream infections. Common grade 4 TRAEs were neutropenia, which was experienced by 100% of patients, and grade 4 thrombocytopenia, which was experienced by 46.1% of patients. Platelets did not decrease to below 100,000/μL after 5 of 26 cycles of MVHO treatment. Conclusions: MVHO therapy was effective and reasonably well tolerated in pediatric patients with refractory or recurrent AML, suggesting that it may comprise a suitable first-line treatment option for pediatric patients with AML. * Olverembatinib is an investigational drug that has not been approved for any indication outside the Chinese mainland 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 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, 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, 2 FTDs, and 2 Rare Pediatric Disease (RPD) Designations 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. 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