Hormone refractory breast cancer

Evexta Bio Reports Progress towards Clinical Development of Rupitasertib in Advanced Breast Cancer Feedback from FDA following Type B meeting enables Evexta Bio to move forward in clinical development of rupitasertib in advanced breast cancer (ABC) Phase 2 clinical trial on track to start in Q4 2024 New preclinical efficacy data strengthen rationale to develop rupitasertib, in combination with elacestrant, in ESR1mt ER+ HER2- ABC Evexta Bio to present at 10th LSX World Congress taking place in London, April 29-30, 2024 Paris, France, April 22, 2024 - Evexta Bio SA, a clinical-stage biotechnology company focused on developing first-in-class therapies in oncology, today provided an update on the clinical development of its lead asset, rupitasertib, a selective oral inhibitor of S6K and AKT1/AKT3. Following a Type B meeting held on March 13, 2024, the U.S. Food and Drug Administration (FDA) provided Evexta Bio with valuable input on various aspects of rupitasertib development, including CMC, preclinical and clinical topics, enabling the company to proceed with the Phase 2 study in advanced breast cancer. The Phase 2 trial is expected to start enrolling patients in Q4/2024. This Phase 2, open label study will evaluate the safety and efficacy of rupitasertib + elacestrant (ORSERDU®) in patients with ER+1 HER2-2 advanced breast cancer with detectable mutation/s of the estrogen receptor 1 gene (ESR1mt). Rupitasertib is a selective oral inhibitor of S6K and AKT1/AKT3 designed to efficiently block the PI3K/AKT/mTOR (PAM) pathway while controlling the compensatory AKT feedback loop. In a Phase 1 trial (Tsimberidou et al 2021) involving heavily pretreated patients with various solid tumors, including those with ESR1mt, rupitasertib was shown to have a favorable safety pro with preliminary signs of efficacy. Recent preclinical studies in ESR1mt breast cancer models have shown compelling synergistic effects of rupitasertib administered in combination with elacestrant. These data support the preliminary clinical efficacy observed in the Phase 1 study and warrant the development of rupitasertib in ESR1mt ER+ HER2- advanced breast cancer patients. Scott Filosi, CEO of Evexta Bio,said: "The feedback we have received from the FDA on the clinical development plan for rupitasertib, along with the new preclinical efficacy data generated in estrogen-resistant breast cancer models, is enabling us to move forward with strong confidence to initiate our Phase 2 study. Advanced breast cancer patients with ESR1 mutations who progressed on or after a CDK4/6 inhibitor have limited treatment options, and our goal is to provide them with an effective and well-tolerated therapy choice.” Dominique Bridon, CSO of Evexta Bio,added: “Patients with ER+ HER2- breast cancer often develop resistance to first-line treatment with the acquisition of ESR1 mutations, and the prognosis for these patients is poor. In addition, S6K has been shown to be closely associated with the emergence of cancer resistance, particularly in breast cancer, through ER modulation. Rupitasertib, which inhibits S6K while controlling the AKT compensatory feedback loop, could be a major advance to better treat these patients who are in need of alternative therapies.” Upcoming meeting Evexta Bio will present at the LSX World Congress in London, April 29-30, 2024. ***** About Evexta Bio ( ) EvextaBio is a clinical-stage biopharmaceutical company exploring the new frontiers of oncology in search of daring novel therapeutic approaches with the potential to save lives. The company is currently developing two proprietary therapeutic assets with novel mechanisms of action across several indications: Rupitasertib, an optimized S6K inhibitor with efficient AKT1/AKT3 control of the compensatory AKT feedback loop. The oral anti-tumor agent is expected to enter a Phase 2 clinical trial in ESR1mt ER+ HER2- advanced breast cancer later in 2024. EVX020, a sole-in-class KIF20A kinesin inhibitor that has shown potent preclinical efficacy in hematological and solid tumor models. Two strategies are under assessment - development of EVX020 as a prodrug and as an antibody-drug conjugate (ADC) payload. Founded by Truffle Capital and supported by Merck KGaA (Darmstadt, Germany) as a shareholder, Evexta Bio has forged alliances with leaders in academia and industry, including CNRS, Paoli-Calmettes Institute (Marseille, France) and Merck KGaA. The company is supported by a seasoned management team, board of directors and medical advisory board. Contact ATCG PARTNERS Marie Puvieux +33 (0)6 10 54 36 72 presse@atcg-partners.com 1 Estrogen Receptor-positive. 2 Human Epidermal growth factor Receptor 2 negative. Attachment PR in English

Researchers have revealed a reason why endocrine resistance develops in breast cancers and how to potentially treat it in patients. Endocrine resistance -- a major cause of breast cancer deaths -- can be underpinned by an epigenetic change called DNA methylation, researchers at the Garvan Institute of Medical Research have discovered. The team successfully reversed this methylation to reduce cancer growth in patient-derived animal models. Using a low dose of the epigenetic therapy drug decitabine, which is currently used to treat some blood cancers, the researchers significantly suppressed the growth of endocrine-resistant breast tumours in mice and increased survival time by 90%. The finding, which will be tested in a future Phase I clinical trial, is a potential gamechanger for the more than 4,000 people who are diagnosed with endocrine-resistant breast cancer each year in Australia alone. "This research has uncovered a completely new approach to treating endocrine-resistant breast cancer. In our study, we have not only pinpointed a new molecular mechanism that explains how endocrine resistance might develop -- we have identified a treatment currently used in the clinic that can target this mechanism precisely," says Professor Susan Clark, Head of the Cancer Epigenetics Laboratory at Garvan and senior author of the paper published in Nature Structural & Molecular Biology. Epigenetic change drives breast cancer treatment resistance An estimated 70% of all diagnosed breast cancers are oestrogen receptor positive (ER+), which means their growth is activated by oestrogen -- a hormone that plays a key role in sexual and reproductive health in women. While endocrine therapy that suppresses oestrogen in the body can slow or stop the growth of these tumours, more than 30% of patients develop resistance, with their tumours no longer requiring oestrogen to grow. In a 2020 study, the Garvan team investigated the endocrine-resistant cancer's epigenome, the layer of instructions that organises and regulates DNA's activity, and revealed that endocrine resistance is linked to methyl groups attaching to regulatory regions of DNA and changing the 3D structure of DNA inside cancer cells. New approach to breast cancer therapy "In this current study, we set out to reverse the abnormal methylation patterns and restore the 3D DNA structure in the endocrine-resistant ER+ breast cancers using epigenetic therapy," says first author Dr Joanna Achinger-Kawecka, Head of the 3D Epigenome in Cancer Group at Garvan. "We found that decitabine removed methyl groups at specific DNA regulatory regions, rewiring the 3D structure of DNA to not only reactivate the production of oestrogen receptors, but also activate tumour suppressor genes that can reduce cancer growth." "After treating patient-derived endocrine resistant breast cancer tumours with decitabine alone, we were surprised to see cancer growth significantly reduced in mice," says co-first author Associate Professor Clare Stirzaker, Head of the Epigenetic Biomarker Group. "This highlights the importance of studying fundamental molecular mechanisms to best guide targeted treatments." Decitabine is an FDA- and TGA-approved epigenetic therapy currently used to successfully treat certain blood cell cancers, including myelodysplastic syndromes, but there are limited studies in other cancers. While the current study focused on ER+ breast cancer, the researchers say the drug may also have potential for other endocrine-resistant cancers driven by epigenetic changes. "The next stage of our research will be to test decitabine together with endocrine therapy, which could be even more effectively target this difficult-to-treat cancer," says Professor Clark. "We hope that such a combination approach is a turning point that enables significantly better clinical outcomes." This research was supported by Australia's National Health and Medical Research Council (Project Grant #1128916), the National Breast Cancer Foundation (IIRS-21-047), Cancer Council NSW (RG20-04 and RG16-02) and the Van Andel Institute Stand Up To Cancer Epigenetics Dream Team. Professor Susan Clark is a Conjoint Professor, Dr Joanna Achinger-Kawecka is a Conjoint Lecturer and Associate Professor Clare Stirzaker is a Conjoint Associate Professor at St Vincent's Clinical School, Faculty of Medicine and Health, UNSW Sydney.

Dr. Adam M. Brufsky of University of Pittsburgh School of Medicine and Dr. Saranya Chumsri of Mayo Clinic will discuss the current treatment landscape for patients with advanced metastatic breast cancer and the latest clinical data of the Bria-IMT™ regimenBriaCell recently reported benchmark-beating patient survival and clinical benefit with median overall survival of 13.5 months in BriaCell’s advanced metastatic breast cancer patients (vs. 6.7-9.8 months for similar patients reported in the literature)Bria-IMT™ has been awarded Fast Track status by the U.S Food and Drug Administration for the treatment of advanced metastatic breast cancer and initiated a phase 3 pivotal registration study. PHILADELPHIA and VANCOUVER, British Columbia, Oct. 11, 2023 (GLOBE NEWSWIRE) -- BriaCell Therapeutics Corp. (Nasdaq: BCTX, BCTXW) (TSX: BCT) (“BriaCell” or the “Company”), a clinical-stage biotechnology company that develops novel immunotherapies to transform cancer care, today announces that it will host a virtual KOL event on Bria-IMT™ potential in advanced metastatic breast cancer on Thursday, October 26, 2023 at 10:00am ET. To register for the event, please click here. The event will feature KOLs Adam M. Brufsky, MD, PhD, FACP (University of Pittsburgh School of Medicine) and Saranya Chumsri, MD (Mayo Clinic) who will discuss the unmet medical need and current treatment landscape for patients suffering from advanced metastatic breast cancer, along with the combination study of Bria-IMT™ with immune check point inhibitor. Dr. William V. Williams, BriaCell’s President & CEO, and Dr. Giuseppe Del Priore, BriaCell’s Chief Medical Officer, will provide a pipeline overview and highlight the next steps for the Phase 3 study, and will be available to answer questions. The event’s agenda is summarized below: BriaCell Virtual KOL Event Agenda – October 26, 2023 Dr. William Williams (CEO) – Introduction and opening remarksDr. Giuseppe Del Priore (CMO) – Event agenda and KOL introductionsDr. Adam Brufsky (KOL) – Review all metastatic breast cancer and current treatment landscapeDr. Saranya Chumsri (KOL) – Bria-IMT™ Clinical data to date & Phase 3 clinical study details Q&A Drs. Del Priore and Williams – Summary and next steps About Adam M. Brufsky, MD, PhDDr. Brufsky is Professor of Medicine at the University of Pittsburgh School of Medicine. He serves as Co-Director, Comprehensive Breast Cancer Center and Medical Director, Women’s Cancer Center at the UPMC Magee Women’s Hospital, Pittsburgh, PA. Dr. Brufsky received an AB in Chemistry (Cum Laude) from Dartmouth College in Hanover, New Hampshire. He earned his MD and his PhD in Developmental Biology at the University of Connecticut School of Medicine in Farmington, CT. He was an Intern and Resident in Internal Medicine at Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. He then completed a Fellowship in Medical Oncology and Bone Marrow Transplantation and the Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, where his appointments included Associate Physician and Instructor in Medicine at Dana Farber Cancer Institute and Harvard Medical School in Boston, MA. Dr. Brufsky is board certified in Internal Medicine and Medical Oncology by the American Board of Internal Medicine. He is an active member of the American Society of Clinical Oncology and the American Association for Cancer Research. He has authored or co-authored more than 300 abstracts and research articles in leading journals, including the New England Journal of Medicine, Journal of Clinical Investigation, Journal of Clinical Oncology, and Lancet Oncology. Dr. Brufsky is a Principal Investigator on a number of research grants funded by the National Institutes of Health, Susan G. Komen Foundation, and US Army Breast Cancer Research Program. About Saranya Chumsri, MDDr. Chumsri is a breast cancer oncologist and Professor of Oncology at Mayo Clinic, FL. Through clinical trials, she has developed expertise in immunotherapy, cancer vaccines, triple-negative breast cancer, endocrine-resistant breast cancer, and related combinational studies. She currently serves as the Mayo Clinic enterprise research chair for the Breast Disease Group. Moreover, Dr. Chumsri also serves on multiple international steering committees, including (Neo) ALTTO steering committee, ACCRU Consortium Breast Cancer Committee, and the Alliance for Clinical Trials in Oncology Immuno-Oncology Committee. She is clinician-scientist reviewer for the Breast Cancer Research Program (BCRP) for the Department of Defense Congressionally Directed Medical Research Programs (CDMRP), and leads the Experimental Trials for Precision Medicine at the Jacoby Center for Breast Health committee at Mayo Clinic, FL. Dr. Chumsri has received funding awards from the Department of Defense, National Cancer Institute, Foundations, and pharmaceutical companies to conduct novel clinical trials in immuno-oncology and cancer vaccines for both the treatment and prevention of breast cancer. She received the prestigious Career Catalyst Research Grant from Susan G. Komen for the Cure and the Outstanding Research Award from the Department of Medicine at Mayo Clinic, FL. Dr. Chumsri completed her medical degree at Chulalongkorn University in Bangkok, Thailand, and her residencies in internal medicine at the Albert Einstein Medical Center and in Hematology and Oncology at the University of Maryland. She has authored over 63 publications. About BriaCell Therapeutics Corp. BriaCell is a clinical-stage biotechnology company that develops novel immunotherapies to transform cancer care. More information is available at https://briacell.com/. Safe Harbor This press release contains “forward-looking statements” that are subject to substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as “anticipate,” “believe,” “contemplate,” “could,” “estimate,” “expect,” “intend,” “seek,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “target,” “aim,” “should,” “will,” “would,” or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements, including those relating to the Company hosting the virtual KOL event described herein and the potential topics discussed at such event, are based on BriaCell’s current expectations and are subject to inherent uncertainties, risks, and assumptions that are difficult to predict. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. These and other risks and uncertainties are described more fully under the heading “Risks and Uncertainties” in the Company's most recent Management’s Discussion and Analysis, under the heading "Risk Factors" in the Company's most recent Annual Information Form, and under “Risks and Uncertainties” in the Company's other filings with the Canadian securities regulatory authorities and the U.S. Securities and Exchange Commission, all of which are available under the Company's profiles on SEDAR at www.sedar.com and on EDGAR at www.sec.gov. Forward-looking statements contained in this announcement are made as of this date, and BriaCell Therapeutics Corp. undertakes no duty to update such information except as required under applicable law. Neither the Toronto Stock Exchange nor its Regulation Services Provider (as that term is defined in the policies of the Toronto Stock Exchange) accepts responsibility for the adequacy or accuracy of this release. Contact Information Company Contact:William V. Williams, MDPresident & CEO1-888-485-6340info@briacell.com Media Relations:Jules AbrahamDirector of Public RelationsCORE IR917-885-7378julesa@coreir.com Investor Relations Contact:CORE IRinvestors@briacell.com