RAD51

TAIPEI and SAN DIEGO, Oct. 14, 2024 /PRNewswire/ -- Senhwa Biosciences, Inc. (TPEx: 6492), a drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and infectious diseases, today announced that FDA issues Study May Proceed letter for its developing drug Pidnarulex (CX-5461) in trial entitled "Pilot Study of Pidnarulex Pharmacodynamics in Patients with Advanced Solid Tumors" sponsored by the US National Cancer Institute (NCI). The study will assess whether Pidnarulex (CX-5461) induces a Rad51 response, in patients with and without homologous repair deficiency (HRD) genetic mutations. This pilot study also aims to explore potential biomarkers beyond BRCA1/2 and PALB2 that may demonstrate synthetic lethality with Pidnarulex (CX-5461). The findings from this study may identify patients who are more responsive to Pidnarulex (CX-5461) treatment, potentially expanding its therapeutic applications, and may accelerate its path to market approval. In addition to this monotherapy trial, the NCI is considering future clinical trials involving Pidnarulex (CX-5461) in combination with other therapies, such as immunotherapies and antibody-drug conjugates (ADCs). Should these trials proceed as planned, they will be led by the NCI, utilizing its vast medical expertise, scientific resources, and regulatory experience—support that could significantly accelerate the development of Pidnarulex. Pidnarulex (CX-5461), developed by Senhwa, is a first-in-class small-molecule designed to stabilize G-quadruplex (G4) structures, which are frequently observed in promoters of oncogenes. By stalling replication fork progression, Pidnarulex induces DNA damage and promotes cancer cell death. Through this mechanism, Pidnarulex holds great potential as a therapeutic agent for various cancers. In recent years, immunotherapy has been the fastest-growing category in the cancer drug market. According to the 2023 global best-selling drug market analysis, the first PD-1 inhibitor Keytruda(Pembrolizumab), developed by Merck, topped the sales charts with $25.11 billion. Immunotherapy and cancer drugs account for nearly half of the market sales. International clinical research indicates that combined immunotherapy can enhance tumor response rates, reduce mortality, and prolong patient survival. Given that only 20% to 25% of patients benefit from effective immunotherapy, Senhwa expects that in future immuno-combination therapy trials, CX-5461 will change the tumor microenvironment with its innovative mechanism, thereby enhancing the efficacy of immunotherapy, realizing the corporate mission of bringing hope to life. SOURCE Senhwa Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

– New data show istisociclib (KB-0742) triggered cell death in preclinical ovarian cancer models of platinum and PARP-inhibitor (PARPi) resistance – – New PK/PD results demonstrate that istisociclib given at 80mg on a 4 days on/3 days off schedule resulted in sustained downregulation of CDK9-dependent genes in peripheral blood mononuclear cells (PBMCs) – SAN MATEO, Calif. and CAMBRIDGE, Mass., Sept. 23, 2024 (GLOBE NEWSWIRE) -- Kronos Bio, Inc. (Nasdaq: KRON), a company dedicated to developing small molecule therapeutics that address cancers and other diseases driven by deregulated transcription, today highlighted new preclinical data from a study of istisociclib (KB-0742). The poster presentation took place over the weekend at the American Association for Cancer Research (AACR) 15th Biennial Ovarian Cancer Research Symposium. Kronos Bio is currently evaluating istisociclib, a CDK9 inhibitor, in an expansion cohort of a Phase 1/2 clinical trial to explore single agent activity in platinum-resistant high-grade serous ovarian cancer (HGSOC). "We’ve demonstrated preclinical evidence that istisociclib induced DNA damage and subsequent cell death, which further supports our clinical program focused on platinum-resistant high-grade serous ovarian cancer," said Luis A. Carvajal, Ph.D., Director of Translational Development at Kronos Bio, the lead author on the poster. "Importantly, platinum or PARPi insensitive cell lines showed greater sensitivity to istisociclib in cell viability assays. Moreover, ovarian cancer cells with PARPi resistance were sensitized to PARP inhibition in the presence of istisociclib.” Dr. Carvajal added, “Based on new PK data from our ongoing clinical trial, we conclude that plasma levels were consistent with efficacious exposures observed in preclinical models of ovarian cancer, and we are excited to be enrolling patients into an expansion cohort of patients with platinum-resistant high-grade serous ovarian cancer.” From the presentation, “Preclinical and clinical data support clinical expansion of istisociclib (KB-0742), an oral CDK9 inhibitor, into platinum-resistant ovarian cancer,” a summary of results is outlined below. In vitro data demonstrate that istisociclib induced apoptosis/cell deathIstisociclib resulted in the accumulation of γH2AX, a sensitive molecular marker of DNA damageIstisociclib disrupted homologous recombination (HR) DNA damage repair by downregulating BRCA1 and RAD51 creating a “BRCAness” phenotype in platinum and PARP resistant HR-proficient ovarian cancer cells From the dose escalation portion of the Company's ongoing Phase 1/2 trial of istisociclib in relapsed or refractory transcriptionally addicted advanced solid tumors, new pharmacokinetic/pharmacodynamic (PK/PD) results were presented. From the dose and schedule optimization portion of the trial evaluating 60mg and 80mg of istisociclib administered once daily on a 4 days on/3 days off schedule: Clinical exposures resulted in a long half-life of approximately 24 hours, and increased and prolonged weekly exposures consistent with efficacious levels observed in preclinical modelsConcurrent with increased and prolonged istisociclib exposure, deeper and more sustained downregulation of CDK9-dependent genes was observed in peripheral blood mononuclear cells (PBMCs) The poster from the presentation is available under the Science & Pipeline section of the Kronos Bio website. About Kronos BioKronos Bio, Inc. (Nasdaq: KRON) is a clinical-stage company dedicated to developing small molecule therapeutics that address deregulated transcription, a hallmark of cancer and other diseases. Our proprietary discovery engine decodes complex transcription factor regulatory networks to identify druggable cofactors. We screen for and optimize small molecules that target these cofactors in a tumor-specific context. These efforts have yielded a preclinical pipeline along with two internally developed drug candidates. Istisociclib (KB-0742) targets CDK9 to address MYC deregulation in solid tumors and KB-9558 targets p300 to address IRF4 dependence in multiple myeloma. Kronos Bio is based in San Mateo, Calif., and has a research facility in Cambridge, Mass.For more information, visit https://www.kronosbio.com or follow the Company on LinkedIn.

TORONTO--( BUSINESS WIRE )--Today, Breast Cancer Canada , a national charity dedicated to saving lives through breast cancer research, is proud to announce a series of initiatives to support the progress of breast cancer research. The announcements include the introduction of a $1 million Canadian fellowship, as well as three diverse investments into breast cancer research. The grants are generously funded by AstraZeneca Canada and Breast Cancer Canada’s annual Precision Oncology Research Grants. “ As the breast cancer landscape evolves and we continue to push the boundaries of what’s possible, it’s important that we diversify our funding to ensure we keep up with research needs right here in Canada. Right now, that looks like investing in the next generation of Canadian breast cancer specialists, partnering with industry stakeholders to co-fund research grants, and continuing financial support for research in precision oncology,” said Kimberly Carson, CEO of Breast Cancer Canada. “ Through strategic partnerships and targeted funding, we are driving innovation and improving health outcomes for the breast cancer patients of tomorrow.” Canadian Breast Cancer Clinical Scientist Fellowship Program With early-age incidence of breast cancer on the rise 1 and the demand for specialized oncology expertise increasing 2 , the development of top-tier Canadian specialists is critical, including a focus on research learning. Breast Cancer Canada is proud to introduce the Canadian Breast Cancer Clinical Scientist Fellowship Program to support and attract the next generation of breast cancer specialists. This funding initiative will provide a significant investment of $1 million into advancing the future of breast cancer training, development, research, and care in Canada. More details on the Fellowship program process and competitive candidate application process will be released in the fall by Breast Cancer Canada at breastcancerprogress.ca . NeoAdjuvant Equity and Outcomes Research Matching Grants In partnership with AstraZeneca Canada, a global, science-led biopharmaceutical company, Breast Cancer Canada is also launching a $200,000 call for grants in solutions to equitable access for pre-surgery chemotherapy (neoadjuvant chemotherapy) and outcomes including the patient lived experience. In a co-sponsored grant of $100,000 each from Breast Cancer Canada and AstraZeneca Canada, two research grants will be awarded. As breast cancer care needs continue to evolve for stage II and III patients, Breast Cancer Canada is proud to partner with industry stakeholders to support progress through research programs that will expand knowledge on pre-surgery therapy planning and uses in Canada. “ There have been tremendous advances in breast cancer care, and we’re proud of the role that AstraZeneca continues to play in delivering these innovations to change the way breast cancer is treated and pursue our goal of eliminating breast cancer as a cause of death,” says Brian Seguin, AstraZeneca Canada, Head – Breast Cancer. “ This transformative work can’t be done alone, which is why we’re excited to build on our partnership with BCC and work collaboratively to support leading-edge Canadian health outcomes research that will not only help to enable access to neo-adjuvant treatment options earlier, but also contribute to greater health equity and health system sustainability over the patient’s lifetime.” The contributions from AstraZeneca Canada are unrestricted, which enables Breast Cancer Canada to allocate funds strategically and under the comprehensive review of a Scientific Advisory Committee. Applications are being accepted for the NeoAdjuvant Equity and Outcomes Research Matching Grants from now until August 2, 2024. For application details please visit: https://breastcancerprogress.ca/apply-for-grant-funding/ . Precision Oncology Research Grants The Fellowship funding initiative and AstraZeneca Canada research partnership come on the heels of Breast Cancer Canada’s third annual Precision Oncology Research Grants program. Breast cancer researchers from across Canada were invited to submit projects in December 2024 for funding consideration. Breast Cancer Canada’s Scientific Advisory Committee awards funding across the spectrum of breast cancer research – from basic discovery studies to accelerating the translation of results into clinical practice. The selected projects undergo a rigorous peer review process and focus on the four divisions of precision oncology research pillars: basic science, screening and detection, personalized treatment, and patient-reported outcomes. The following are the selected grant recipient researchers for Breast Cancer Canada research funding: $75,000 Dr. David Lim, Women's College Hospital Identifying a prognostic gene signature for invasive lobular breast carcinoma. $50,000 Dr. Saima Hassan Centre de Recherche de Centre Hospitalier de l’Université de Montréal Researching dissecting tumor and microenvironment influences in PARPi response in BRCA-mutant and BRCA-wild type breast cancer patients $75,000 Dr. Lisa Porter WE-SPARK Health Institute, University of Windsor Establishing a Biomarker Platform for Postpartum Breast Cancer $50,000 Dr. Ives Levesque McGill University Exploring the validation of FxMammo, AI Assistant for Breast Cancer Screening, in the Canadian Population $75,000 Dr. Rodney Ouelette Centre de Médecine de Précision du Nouveau Brunswick Exploring extracellular-vesicle-based liquid biopsy profiles in early-stage triple-negative breast (TNBC) cancer and their response to neoadjuvant chemotherapy $50,000 Dr. Mark Vincent London Health Sciences Evaluating small molecule RAD51 inhibitors $75,000 Dr. Caroline Hamm We-SPARK Health Institute Windsor Regional Hospital Assessing the effectiveness and implementation of the CTN program, using a navigator-assisted clinical trial enrollment platform $50,000 Dr. Edward Chow Sunnybrook Research Institute Preventing Radiation Dermatitis in Large-Breasted Patients: A Randomized Phase III Trial Breast Cancer Canada remains dedicated to progress through breast cancer research, advocacy for access to the best care, and elevating the patient voice to improve the lives of Canadians affected by breast cancer. Through strategic investments and collaborative partnerships, we continue to drive progress so that the more we know, the sooner we can end breast cancer. To know more about how Breast Cancer Canada powers progress through research, visit: breastcancerprogress.ca/progress-and-research/ . About Breast Cancer Canada Breast Cancer Canada is a national charity dedicated to saving lives through breast cancer research. With a focus on precision oncology (personalized care), it is the only national breast cancer organization in Canada that has a clear mandate to raise money for research and advocate and educate on the progress of new research evidence. The organization receives no government funding, meaning all research is funded through the generosity of donors. For more information visit, breastcancerprogress.ca. About AstraZeneca Canada AstraZeneca is a global, science-led biopharmaceutical business whose innovative medicines are used by millions of patients worldwide. The company’s core areas of scientific focus are Oncology; Cardiovascular, Renal and Metabolic (CVRM); Rare Disease; Respiratory & Immunology; and Vaccine & Immune Therapies. In Canada, the company employs approximately 1,800 people and recently announced a major expansion of its research footprint in Mississauga – including the expansion of its AstraZeneca R&D Hub and the creation of a new Alexion Development Hub for Rare Diseases. AstraZeneca was recently recognized as one of Canada’s Top 100 Employers, one of Canada’s Most Admired Corporate Cultures, and a Greater Toronto Top Employer. AstraZeneca is committed to contributing to a more sustainable future for people, society and planet taking important steps to help tackle some of the most pressing sustainability challenges globally – from climate and biodiversity loss, to health equity and health system resilience. AstraZeneca was one of the first seven companies globally to have its net zero targets verified by the Science-Based Targets initiative (SBTi) Corporate Net-Zero Standard. For more information, please visit the company’s website at www.astrazeneca.ca . ______________________________________ 1 https://www.uottawa.ca/about-us/media/news-all/breast-cancer-rates-rising-among-canadian-women-their-20s-30s-40s#:~:text=For%20women%20in%20their%20Thirties,2019%20for%20a%2012.5%25%20increase . 2 https://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/pmc/articles/PMC10742250/