Bcl-xl

SOUTH SAN FRANCISCO, Calif., Feb. 06, 2024 (GLOBE NEWSWIRE) -- UNITY Biotechnology, Inc. (“UNITY”) [NASDAQ: UBX], a biotechnology company developing therapeutics to slow, halt or reverse diseases of aging, today announced new research published in the peer-reviewed journal Nature Medicine that supports the clearance of senescent cells in the retina as a therapeutic approach that can lead to long-term improvements in vision in patients with diabetic macular edema (DME). Sustained hyperglycemia from diabetes induces cellular senescence which damages the retina, including the delicate vasculature in the eye. This can lead to fluid accumulation and retinal thickening – a key feature of DME. The study shows that the therapeutic clearance of senescent cells can potentially remove an underlying source of pathogenesis and thus allow healthy cells to regenerate and remodel retinal vasculature, ultimately leading to long-term disease modification. Multiple studies have demonstrated that cells enter a state of senescence, in which they remain viable and metabolically active in the body, yet generate various inflammatory factors and metalloproteases. These senescent cells can modify the surrounding environment and contribute to different cellular dysfunction and tissue degeneration. A team of scientists at University of Montreal and UNITY Biotechnology revealed that cellular senescent pathways are triggered in the diabetic retina and are specifically activated in endothelial cells. They demonstrated that these senescent cells contribute to loss of barrier function, which can cause leaky blood vessels. Researchers showed that senolysis through BCL-xL inhibition improved retinal barrier function in diabetic mice, modifying the retinal microenvironment and reestablishing tissue homeostasis. In addition, in clinical trials BCL-xL inhibition led to improvements in visual acuity and retinal structure stabilization in patients with advanced disease. “This research provides compelling mechanistic evidence of the therapeutic approach of eliminating senescent cells to reduce diabetes-induced retinal vascular leakage and preserve retinal function,” Anirvan Ghosh, Ph.D., chief executive officer of UNITY and an author of the paper. “As senescent cell burden is observed in many other diseases, this study highlights the potential benefit of senolytic drugs for various age-related and metabolic diseases.” The BCL-xL inhibitor UBX1325 has been evaluated in a Phase 2 study as well, as previously announced, which demonstrated that a single injection led to statistically significant and clinically meaningful improvements in visual acuity through 48 weeks in patients with DME, while reducing anti-VEGF treatment burden. UNITY is actively enrolling patients for a Phase 2b clinical trial where UBX1325 is being evaluated head-to-head versus aflibercept, with 16-week results expected in Q4 2024. “Most therapeutic options available and in development for DME target the VEGF pathway. As a BCL-xL inhibitor, the senolytic UBX1325 targets an alternative mechanism and holds the potential to not only address the limitations of but also compliment anti-VEGF agents,” said Przemyslaw (Mike) Sapieha, Ph.D., chief scientist at UNITY and the lead author of the paper. “A new long-lasting and disease-modifying therapy for DME would be transformative for patients. This research further supports the potential for senolytic medicines to address the significant unmet need with current standard of care.” About UBX1325UBX1325 is an investigational compound being studied in retinal diseases, including DME and wet AMD, and is not approved for any use in any country. UBX1325 is a potent small molecule inhibitor of BCL-xL, a member of the BCL-2 family of apoptosis regulating proteins. UBX1325 is designed to inhibit the function of proteins that senescent cells rely on for survival. The Phase 2 BEHOLD study in patients with DME demonstrated that a single injection of UBX1325 resulted in a statistically significant and clinically meaningful improvement in mean Best Corrected Visual Acuity (BCVA) through 48 weeks compared to sham treatment. In preclinical studies, UNITY has demonstrated that targeting Bcl-xL with UBX1325 preferentially eliminated senescent cells from diseased tissue while sparing cells in healthy tissue. UNITY’s goal with UBX1325 is to transformationally improve real-world outcomes for patients with retinal disease. About UNITYUNITY is developing a new class of therapeutics to slow, halt, or reverse diseases of aging. UNITY’s current focus is on creating medicines to selectively eliminate or modulate senescent cells and thereby provide transformative benefit in age-related ophthalmologic and neurologic diseases. More information is available at www.unitybiotechnology.com or follow us on X (Formerly Twitter) and LinkedIn. Forward-Looking StatementsThis press release contains forward-looking statements including statements related to UNITY’s understanding of cellular senescence and the role it plays in diseases of aging, the potential for UNITY to develop therapeutics to slow, halt, or reverse diseases of aging, including for ophthalmologic and neurologic diseases, the potential for UNITY to successfully commence and complete clinical studies of UBX1325 for DME, AMD, and other ophthalmologic diseases, the expected timing of enrollment and results of the clinical trials in UBX1325, and UNITY’s expectations regarding the sufficiency of its cash runway. These statements involve substantial known and unknown risks, uncertainties, and other factors that may cause our actual results, levels of activity, performance, or achievements to be materially different from the information expressed or implied by these forward-looking statements, including the risk that the COVID-19 worldwide pandemic may continue to negatively impact the development of preclinical and clinical drug candidates, including delaying or disrupting the enrollment of patients in clinical trials, risks relating to the uncertainties inherent in the drug development process, and risks relating to UNITY’s understanding of senescence biology. We may not actually achieve the plans, intentions, or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. The forward-looking statements in this press release represent our views as of the date of this release. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we have no current intention of doing so except to the extent required by applicable law. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this release. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the Company in general, see UNITY’s most recent Quarterly Report on Form 10-Q for the quarter ended September 30, 2023, filed with the Securities and Exchange Commission on November 13, 2023, as well as other documents that may be filed by UNITY from time to time with the Securities and Exchange Commission. Media ContactInizio Evoke CommsKatherine SmithKatherine.Smith@inizioevoke.com Investor ContactLifeSci Advisors, LLCJoyce Allairejallaire@lifesciadvisors.com

SUZHOU, China and ROCKVILLE, Md., Dec. 14, 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 Prof. Xiaoyuan Gong of the Institute of Hematology and Blood Diseases Hospital, the Chinese Academy of Medical Sciences, has presented the preliminary results from a Phase II study of Ascentage Pharma's novel drug candidate, olverembatinib, combined with reduced-intensity chemotherapy in treatment-naïve patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), in an Oral Report at the 65th American Society of Hematology (ASH) Annual Meeting, taking place in San Diego, CA, the United States. The ASH Annual Meeting is one of the largest gatherings of the international hematology community, bringing together the most cutting-edge scientific research and latest data of investigational therapies that represent leading scientific and clinical advances in the global hematology field. Garnering growing interest from the global research community, multiple studies of Ascentage Pharma's key drug candidates (olverembatinib and lisaftoclax) have been selected for presentations at this year's ASH Annual Meeting, including two Oral Presentations on olverembatinib. This is the sixth consecutive year in which the clinical results of olverembatinib have been selected for Oral Presentations at the ASH Annual Meeting. Following the introduction of tyrosine kinase inhibitors (TKIs), the combination of TKIs and intensive chemotherapy has become a widely adopted treatment for patients with Ph+ ALL because it can offer significantly improved prognosis. However, a large number of patients are ineligible for the treatment because of intolerance to intensive chemotherapy. Clinical results featured in this Oral Presentation demonstrated encouraging clinical benefit and favorable tolerability of olverembatinib, a third-generation TKI, when combined with reduced-intensity chemotherapy in patients with Ph+ ALL, with data showing a complete remission/incomplete hematologic recovery (CR/CRi) rate of 100% in patients treated with the olverembatinib combination regimen; a complete molecular response (CMR) rate of 62.2% in patients who received three cycles of the treatment that was free of intensive chemotherapy or immunotherapy; and a favorable tolerability profile. Compared to the existing data on TKI plus intensive chemotherapy combinations, patients on this combination regimen have a lower need for transfusion and a reduced incidence of infections. Olverembatinib is a global best-in-class novel drug developed by Ascentage Pharma. As the first and only approved third-generation BCR-ABL inhibitor in China, olverembatinib has been approved for the treatment of adult patients with TKI-resistant chronic-phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation and adult patients with CML-CP resistant and/or intolerant to first- and second-generation TKIs. Olverembatinib is being jointly commercialized in China by Ascentage Pharma and Innovent Biologics. Prof. Xiaoyuan Gong, commented, "The introduction of high-potency TKIs has made it a real possibility to treat patients with Ph+ ALL with reduced-intensity chemotherapy, or even without chemotherapy, while achieving improved efficacy and safety. As a third-generation TKI, olverembatinib has shown impressive therapeutic potential for the treatment of Ph+ ALL and for its role as a key part of chemotherapy-free regimens." "In this study, olverembatinib combined with reduced-intensity chemotherapy continued to demonstrate promising clinical benefit in patients with Ph+ ALL, once again indicating the potential superiority of this third-generation TKI over other TKIs and that an era of chemotherapy-free treatment for patients with Ph+ ALL might be on the horizon," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "Remaining committed to the mission of addressing unmet clinical needs in China and around the world, we will expedite our clinical development programs to bring safe and effective therapies to patients in need." Highlights of the study presented at ASH 2023: 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 TKI, with venetoclax generated high response rates in patients with relapsed/refractory (R/R) 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 ≥ 14 years (yrs) of age with newly diagnosed Ph+ ALL. In cycle 1, patients were treated with a combination of venetoclax (100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28), olverembatinib (40 mg once every continuously other day [QOD], from day 1-28), 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 2-3, oral treatment with venetoclax (400 mg × 7 days), olverembatinib once every other day continuously, and injectable prednisone (60 mg/m2 × 7 days) were administered. Cycles were repeated every 28 days. During cycle 1, the dose of olverembatinib for patients who reached CMR was reduced from 40 mg QOD to 30 mg QOD. The primary endpoint of this study was the rate of CMR at 3 months. CMR was defined as undetectable BCR-ABL1 transcripts by using the RT-PCR method with a sensitivity of 0.001%. Major molecular response (MMR) was defined as more than 3-log reduction of BCR::ABL1 transcripts. Patients: From August 2022 to July 2023, a total of 45 patients were enrolled. The median age was 42 years (range, 19-74) and males accounted for 48.9%. 31 patients (68.9%) expressed the p190 transcript, and 14 patients (31.1%) expressed the p210 transcript. The median expression level of BCR::ABL1 was 90.3% (range, 25.9%-175.4%). Efficacy results: All patients have reached CR/CRi. At the end of cycle 1, 53.3% of patients achieved CMR and 28.9% MMR; at the end of cycle 2, 60.0% achieved CMR and 35.6% MMR; at the end of cycle 3, 62.2% achieved CMR and 31.1% MMR. As of October 30, 2023, 16 of the 45 patients received autologous hematopoietic stem cell transplantation (Auto-SCT, 1 death), 8 patients received allogeneic hematopoietic stem cell transplantation (Allo-SCT), 5 patients received olverembatinib combined with blinatumomab, and 16 received olverembatinib combined with chemotherapy. 88.9% (40) of patients achieved CMR during treatment. The median (range) duration of follow-up was 8 (3-14) months, and no patient relapsed during follow-up. Safety results: The combination regimen was well tolerated and safe. Most adverse events were grade 1-2. The demand for transfusion and the incidence of infections significantly decreased compared to the existing data on intensive chemotherapy plus TKI combinations. No patient discontinued olverembatinib or venetoclax because of 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. *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. 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

SAN DIEGO, Dec. 13, 2023 /PRNewswire/ -- ChemDiv Inc., dedicated to partnering in discovery and development of breakthrough therapies based on its unique chem-bio platforms, announces the presentation of non-clinical summary data for the best-in-class selective BCL2 inhibitor clinical candidate at the 65th ASH Annual Meeting and Exposition in San Diego, CA. "A Novel Selective BCL2 Inhibitor with Limited Immune Suppression and Improved Safety Compared to Venetoclax" was presented by collaborators from University of Cincinnati (Ohio), Molsoft LLC, Expert Systems Inc of San Diego California, and Eilean Therapeutics LLC of Dover, Delaware. The presentation highlighted best-in-class potency and selectivity against BCL2, a key pro-survival protein that is overexpressed in many cancers. This clinical candidate demonstrated an equivalent in vivo anti-tumor efficacy as venetoclax in both B cell and myeloid malignancy cell lines and in vivo models. Compared to venetoclax, the candidate exhibits significantly less suppression of non-malignant immune cell populations, a result that signals superior selectivity and improved safety profile. In collaboration with rational design groups of Molsoft and Expert Systems, John Byrd's lab at University of Cincinnati, ChemDiv deployed a fragment-based approach to completely redesign a binding interface comparing to venetoclax and venetoclax-like molecules to achieve differentiated pharmacology according to the target product profile. The 4600-fold selectivity for BCL2 over BCL-xl; high oral bioavailability, short half-life and low interaction with CYP3A of the resulting clinical candidate translated in best-in-class safety, tolerability and developable pharmacology advantages delivered to partners at Eilean Therapeutics LLC. About ChemDiv Inc. ChemDiv is dedicated to partnering in discovery and development of breakthrough therapies based on its unique chem-bio platforms: molecular glues, stabilizers and degraders; covalent and non-covalent binders; bifunctional molecules for synergistic effect and synthetic lethality. Over the past 32 years ChemDiv has successfully completed hundreds of lead, candidate and new drug programs to treat cancer, neurological, infectious, cardiometabolic and immune diseases with pharma, biotech and academic partners around the globe. Learn more at About Expert Systems Expert Systems is a global target to clinic accelerator. It deploys a comprehensive hybrid AI/ML based platform, covering all aspects of preclinical drug discovery and early development, from target identification and virtual screening, to non-clinical and clinical pharmacology, including chemical liability assessment and toxicology. Expert Systems uses proprietary and public databases and software tools to evaluate the intellectual property landscape and provide competitive intelligence to de-risk candidate selection for fast transition from in silico to first-time-in-man. Expert Systems sets up seed & series A companies, organizes and manages R&D programs for financial investors and strategic partners in North America, Europe and Australia. Learn more at About Eilean Therapeutics Eilean Therapeutics is a small molecule oncology company that is committed to defeating cancer and improving lives of cancer patients. Eilean develops differentiated best-in-class molecules that target fundamental biological pathways with resistant mutations and escape mechanisms in hematologic malignancies. Learn more at Media contact: Ronald Demuth CEO of ChemDiv, [email protected] SOURCE ChemDiv