Neoplasms by Histologic Type

ROCKVILLE, Md. and SUZHOU, China, April 7, 2024 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, age-related diseases, and chronic hepatitis B (CHB), announced today that it releases the latest results from three preclinical studies of its novel drug candidates olverembatinib, MDM2-p53 inhibitor alrizomadlin (R&D Code: APG-115), FAK/ALK/ROS1 tyrosine kinase inhibitor APG-2449, and embryonic ectoderm development (EED) inhibitor APG-5918, at the 2024 American Association of Cancer Research Annual Meeting (AACR 2024). This year's AACR annual meeting will be held from April 5-10 2024, in San Diego, California, USA. "We are pleased to present the preclinical research data of four assets in our pipeline at the AACR 2024. The results provided essential support for the potential clinical development and therapeutic combinations of these compounds in SDH-deficient neoplasms, prostate cancer, and ovarian cancer," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "Moving forward, we will continue to advance these programs toward the clinical stage in order to bring more treatment options to patients in need." The details of these three preclinical studies are as follows: Olverembatinib, a novel multikinase inhibitor, demonstrates superior antitumor activity in succinate dehydrogenase (SDH)-deficient neoplasms Abstract#: 1971 Time: Monday April 8, 2024, 9:00 AM - 12:30 PM (Pacific Time) Introduction: Succinate dehydrogenase (SDH) – deficient (dSDH) neoplasms are identified by the loss of immunohistochemical expression of SDHB due to the bi-allelic inactivation of any of the four components of mitochondrial SDH complex (SDH A-D). Succinate accumulation, due to SDH deficiency, is involved in tumorigenesis of different types of cancers including gastrointestinal stromal tumor (GIST), paraganglioma, pheochromocytoma, renal cell carcinoma, pituitary adenomas, and pancreatic neuroendocrine tumors. The prognosis of patients with dSDH neoplasia, especially GIST, is poor and approved tyrosine kinase inhibitors (TKIs) have limited efficacy. There is a high unmet medical need for these patients. Olverembatinib, a novel multi-kinase inhibitor, targets a broad spectrum of kinases and has demonstrated promising efficacy in dSDH GIST patients in an ongoing phase I clinical trial. In this study, we assessed antitumor effects of olverembatinib in preclinical models of dSDH cancers and dSDH GIST primary tumor cells, and explored potential mechanisms of action. Conclusions: Olverembatinib showed superior anti-tumor activity in dSDH cell lines in vitro and human dSDH GIST primary tumor cells ex vivo. Olverembatinib, as a multi-target kinase inhibitor, exerted antitumor effects by modulating multiple signaling pathways including hypoxia, angiogenesis, apoptosis, proliferation, and survival, which are involved in tumorigenesis of dSDH cancers. Olverembatinib demonstrated more potent in vivo antitumor activity in mice bearing PC12#5F7 (SDHB KD) xenograft tumors than other TKIs. Western blot analysis in tumor tissues collected from mice further confirmed the modulation of the signal pathways by olverembatinib observed in cell lines. In summary, the results provide a rationale for future clinical development of olverembatinib in dSDH cancers. Embryonic ectoderm development (EED) inhibitor APG-5918 (EEDi-5273) and MDM2 inhibitor alrizomadlin (APG-115) synergistically inhibit tumor growth in preclinical models of prostate cancer (PCa) Abstract#: 3223 Time: Monday April 8, 2024, 1:30 PM - 5:00 PM (Pacific Time) Introduction: Prostate cancer (PCa) is one of the most frequently diagnosed malignancies among elderly males. Androgen deprivation therapy (ADT) with or without androgen receptor (AR) inhibitors is widely used as initial treatment for advanced PCa. However, most ADT-treated patients eventually develop castration-resistant prostate cancer (CRPC), which is in urgent need of novel therapies. Polycomb repressive complexes 2 (PRC2) dysregulation is common in PCa and correlates with poor prognosis. PRC2 mediates histone H3 lysine 27 tri-methylation (H3K27me3), a repressive epigenetic marker for gene transcription. embryonic ectoderm development (EED), a PRC2 core component, is crucial for histone methyltransferase activity through direct binding to H3K27me3. MDM2, a negative regulator of the tumor suppressor p53, is frequently amplified or overexpressed in PCa, and associated with poor clinical outcomes and metastasis. The aim of this study was to evaluate antitumor activity and molecular mechanisms of the investigational, clinical-stage EED inhibitor APG-5918/EEDi-5273 and MDM2 selective inhibitor alrizomadlin (APG-115) in PCa preclinical models Conclusions: In PCa preclinical models, the combination of APG-5918 and alrizomadlin synergistically inhibited cellular proliferation and induced cellular apoptosis. APG-5918 in combination with alrizomadlin synergistically enhanced antitumor activity in PCa xenograft models in vivo. Mechanistically, PD analysis revealed that APG-5918 downregulated the oncogenic DNA methylation factors (UHRF1, DNMT1) and histone methylation marker H3K27me3. Alrizomadlin markedly downregulated UHRF1 and DNMT1, and upregulated p53 and p21 expression. Combined treatment further enhanced downregulation of DNMT1, UHRF1, cell cycle pathway proteins (pRb, CDK6), antiapoptotic protein MCL-1, and synergistically increased cleavage of PARP-1, a marker of apoptosis. Therefore, the findings provide a scientific rationale for future clinical development of APG-5918 and alrizomadlin to treat patients with PCa. APG-2449, a novel focal adhesion kinase (FAK) inhibitor, inhibits metastasis and enhances the antitumor efficacy of PEGylated liposome doxorubicin (PLD) in epithelial ovarian cancer (EOC) Abstract#: 4569 Time: Tuesday April 9, 2024, 9:00 AM - 12:30 PM (Pacific Time) Introduction: Ovarian cancer is among the leading causes of cancer-related death in women, and most cases are diagnosed at later stages with distant metastasis. FAK overexpression or activation occurs in a substantial proportion of epithelial ovarian cancers (EOCs) and is predictive of poor clinical outcomes. FAK plays an important role in cell migration and chemoresistance, rendering FAK inhibition a promising treatment approach to reduce metastasis of tumor cells and sensitize them to chemotherapy. FAK is therefore emerging as a potential treatment target. The aim of this study was to evaluate the antitumor efficacy of investigational APG-2449, a novel FAK inhibitor, combined with PLD, a commonly used chemotherapy, in relapsed or refractory ovarian cancer. Conclusions: APG-2449 combined with doxorubicin showed synergistic antiproliferative effects in both platinum-resistant and platinum-sensitive ovarian cancer cell lines. FAK inhibition via APG-2449 alone attenuated migration of ovarian cancer cells in a dose-dependent manner. APG-2449 in combination with PLD showed enhanced antitumor activity in platinum-resistant OVCAR-3 ovarian cancer CDX model. The combination regimen prolonged ascites-free and survival times in the ID8-Luc peritoneal syngeneic model. These promising results support the future clinical development of this combination treatment for ovarian cancer. 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 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

Real-world data demonstrate non-classical mutations are present in 20-30% of all patients with EGFRm NSCLC Emerging data show non-classical EGFR mutations can be co-expressed with the classical L858R mutation, a setting characterized by shorter duration of response to osimertinib BDTX-1535 profile differentiated as the most advanced fourth-generation oral TKI in clinical development addressing the full spectrum of classical, non-classical, and C797S resistance EGFR mutations CAMBRIDGE, Mass., April 07, 2024 (GLOBE NEWSWIRE) -- Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with cancer, presented real-world evidence of the evolving epidermal growth factor receptor (EGFR) mutation landscape in non-small cell lung cancer (NSCLC), and the potential of BDTX-1535 to address a broader range of mutations compared to existing therapies. The results were disclosed in an oral presentation on April 7, 2024, at the 2024 American Association of Cancer Research (AACR) Annual Meeting held in San Diego, California. The oral presentation, titled “BDTX-1535 – A MasterKey EGFR Inhibitor Targeting Classical, Non-Classical and the C797S Resistance Mutation to Address the Evolved Landscape of EGFR Mutant NSCLC,” evaluated more than 235,000 sequenced cases of NSCLC sourced from Guardant Health (GuardantINFORM™) and Foundation Medicine (FoundationInsights™). The analyses reveal a broad spectrum of non-classical mutations, as well as an increased prevalence of the acquired resistance mutation, C797S. Over 100 unique non-classical EGFR oncogenic driver mutations were identified in newly diagnosed patients with NSCLC, and these non-classical EGFR mutations were present in 20-30% of patients across all lines of treatment. “The landscape of EGFR mutations in NSCLC continues to evolve, revealing classical and non-classical driver mutations,” said John Heymach, M.D., Ph.D., Chair of Thoracic/Head and Neck Medical Oncology at MD Anderson Cancer Center. “Non-classical mutations fall into categories including kinase domain PACC mutations and ectodomain mutations; therefore, next generation EGFR targeted therapies must effectively cover multiple subgroups of mutations.” “Novel targeted therapies are still needed to continue to improve clinical outcomes for patients with EGFR-mutant lung cancers,” added Xiuning Le, M.D., Ph.D., Associate Professor, Thoracic/Head and Neck Medical Oncology at MD Anderson Cancer Center. “To extend survival for our patients, newer drugs need to have good mutational coverage, good tolerability, and good brain penetrance.” Preclinical data demonstrated that BDTX-1535 potently inhibits more than 50 clinically relevant, non-classical EGFR mutations (as well as the classical L858R and exon19-del mutations) while sparing wild-type EGFR. The compound also potently inhibits the drug resistance C797S mutation, which emerges following treatment with third-generation EGFR inhibitors, including osimertinib. Real-world data indicate non-classical EGFR mutations can be co-expressed with classical mutation L858R, a setting that has been characterized by shorter duration of response to osimertinib first-line therapy. Preclinical data show that BDTX-1535 potently inhibits these co-expressed non-classical mutations. “BDTX-1535 was designed to address a broad spectrum of more than 50 non-classical oncogenic EGFR mutations, as well as the C797S resistance mutation,” said Elizabeth Buck, Ph.D., Chief Scientific Officer and co-founder of Black Diamond Therapeutics. “We believe that the potency of BDTX-1535 against the full spectrum of classical, non-classical, and C797S mutations positions the compound as the first and best-in-class fourth-generation EGFR inhibitor potentially offering NSCLC patients a well-tolerated, brain-penetrant, oral therapy across various lines of treatment.” Phase 1 proof-of-concept data demonstrating durable responses in recurrent NSCLC patients with both non-classical and acquired resistance C797S mutations were presented in October 2023. Black Diamond is currently advancing BDTX-1535 in a Phase 2 trial for patients with EGFRm NSCLC across multiple lines of therapy. Patients are being enrolled both in a first-line (1L) setting (for those expressing EGFR non-classical mutations) and in second- and third-line (2L/3L) settings following prior treatment with an EGFR inhibitor. Initial results from 2L/3L patients are anticipated in the third quarter of 2024. About BDTX-1535BDTX-1535 is an oral, brain-penetrant MasterKey inhibitor of oncogenic epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC), including classical driver mutations, non-classical driver mutations, and the acquired resistance C797S mutation. BDTX-1535 is a fourth-generation tyrosine kinase inhibitor (TKI) that potently inhibits, based on preclinical data, more than 50 oncogenic EGFR mutations expressed across a diverse group of patients with NSCLC in multiple lines of therapy. Based on preclinical data, BDTX-1535 also inhibits EGFR extracellular domain mutations and alterations commonly expressed in glioblastoma (GBM) and avoids paradoxical activation observed with earlier generation reversible TKIs. A “window of opportunity” trial of BDTX-1535 in patients with GBM is ongoing (NCT06072586) and a Phase 2 trial is ongoing in patients with NSCLC (NCT05256290). About Black Diamond TherapeuticsBlack Diamond Therapeutics is a clinical-stage oncology company focused on the development of MasterKey therapies that address families of oncogenic mutations in clinically validated targets. The Company’s MasterKey therapies are designed to address broad genetically defined patient populations, overcome resistance, minimize wild-type mediated toxicities, and be brain penetrant to treat CNS disease. The Company is advancing two clinical-stage programs: BDTX-1535, a brain-penetrant fourth-generation EGFR MasterKey inhibitor targeting EGFR mutant NSCLC and GBM, and BDTX-4933, a brain-penetrant RAF MasterKey inhibitor targeting KRAS, NRAS and BRAF alterations in solid tumors. For more information, please visit www.blackdiamondtherapeutics.com. Forward-Looking StatementsStatements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding: the potential of BDTX-1535 to address a broader range of mutations compared to existing therapies, the position of BDTX-1535 as compared to other fourth-generation EGFR inhibitors, the timing of clinical updates for BDTX-1535 in patients with NSCLC and in patients with recurrent GBM, and the potential of BDTX-1535 to benefit patients with NSCLC. Any forward-looking statements in this statement are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include those risks and uncertainties set forth in its Annual Report on Form 10-K for the year ended December 31, 2023, filed with the United States Securities and Exchange Commission and in its subsequent filings filed with the United States Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. ContactsFor Investors:Mario Corso, Head of Investor Relations, Black Diamond Therapeuticsmcorso@bdtx.com For Media:media@bdtx.com

RP1 monotherapy showed clear anti-tumor activity with an overall response rate of nearly 35 percent and complete response rate of nearly 22 percent in evaluable patientsSAN DIEGO, April 07, 2024 (GLOBE NEWSWIRE) -- Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of a novel portfolio of oncolytic immunotherapies, today announced the presentation of interim results from ARTACUS, a Phase 1/2 clinical trial evaluating RP1 monotherapy for the treatment of skin cancers in patients who have had solid organ or hematopoietic cell transplants, by Michael R. Midgen, M.D., of the University of Texas MD Anderson Cancer Center during an oral session at the AACR 2024 Annual Meeting in San Diego. The results were initially presented late last year at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC). In the study, treatment with RP1 as monotherapy, for up to 25 doses, resulted in an overall response rate (ORR) of 34.8 percent (8 of 23 evaluable patients, including 5 complete responses and 3 partial responses) with most responses ongoing as of the data cutoff date of September 18, 2023. In the evaluable patient population (n=23), 20 had cutaneous squamous cell carcinoma (CSCC) and three had merkel cell carcinoma. Of note, a patient treated with RP1 for CSCC also had a complete response of a new primary basal cell carcinoma which appeared post baseline. There was no evidence of allograft rejection including of hepatic and lung allografts. RP1 monotherapy was well tolerated, and the safety profile was similar to the profile in non-immunocompromised patients with advanced skin cancers. Additional biomarker data collected showed an increase in CD+8 T, a type of immune cell, and an increase in the expression of PD-L1, after treatment suggesting immune activation. The slides are available on the Replimune website under presentations. “Organ transplant recipients are at a higher risk for skin cancer when compared to the broader population and have access to a limited number of treatment options given that systemic immunotherapy is typically contra-indicated,” said Sushil Patel, Ph.D., CEO of Replimune. “These data show RP1 as monotherapy has clear anti-tumor activity and may be a safe and effective treatment option for these patients with an overall response rate of nearly 35 percent with good durability of benefit to date.” About ARTACUSARTACUS is a multicenter, open-label, two-part Phase 1b/2 study evaluating RP1 as monotherapy for the treatment of locally advanced or metastatic cutaneous malignancies in patients who underwent a kidney, liver, heart, lung, or other solid organ transplant, or hematopoietic cell transplantation, who are on chronic immunosuppressive treatment, in whom systemic immunotherapy is typically contra-indicated. Researchers will assess the safety of RP1 and also evaluate its ability to shrink tumors. ARTACUS is currently recruiting patients. To learn more, contact clinicaltrials@replimune.com or +1-781-222-9570. About RP1RP1 is Replimune’s lead product candidate and is based on a proprietary new strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response. About Replimune Replimune Group, Inc., headquartered in Woburn, MA, was founded in 2015 with the mission to transform cancer treatment by pioneering the development of a novel portfolio of oncolytic immunotherapies. Replimune’s proprietary RPx platform is based on a potent HSV-1 backbone intended to maximize immunogenic cell death and the induction of a systemic anti-tumor immune response. The RPx platform is designed to have a unique dual local and systemic activity consisting of direct selective virus-mediated killing of the tumor resulting in the release of tumor derived antigens and altering of the tumor microenvironment to ignite a strong and durable systemic response. The RPx product candidates are expected to be synergistic with most established and experimental cancer treatment modalities, leading to the versatility to be developed alone or combined with a variety of other treatment options. For more information, please visit www.replimune.com. Forward-Looking StatementsThis press release contains forward looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including statements regarding the design and advancement of our clinical trials, the timing and sufficiency of our clinical trial outcomes to support potential approval of any of our product candidates, our goals to develop and commercialize our product candidates, patient enrollments in our existing and planned clinical trials and the timing thereof, and other statements identified by words such as “could,” “expects,” “intends,” “may,” “plans,” “potential,” “should,” “will,” “would,” or similar expressions and the negatives of those terms. Forward-looking statements are not promises or guarantees of future performance and are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in such forward-looking statements. These factors include risks related to our limited operating history, our ability to generate positive clinical trial results for our product candidates, the costs and timing of operating our in-house manufacturing facility, the timing and scope of regulatory approvals, changes in laws and regulations to which we are subject, competitive pressures, our ability to identify additional product candidates, political and global macro factors including the impact of the coronavirus as a global pandemic and related public health issues, and other risks as may be detailed from time to time in our Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q and other reports we file with the Securities and Exchange Commission. Our actual results could differ materially from the results described in or implied by such forward-looking statements. Forward-looking statements speak only as of the date hereof, and, except as required by law, we undertake no obligation to update or revise these forward-looking statements. Investor InquiriesChris BrinzeyICR Westwicke339.970.2843chris.brinzey@westwicke.com Media InquiriesArleen GoldenbergReplimune917.548.1582media@replimune.com