Byondis BV

-Collaboration with NKI and Funding Support for New Colorectal Cancer Clinical Trial by Major Pharma Company- -Distinguished Oncologist Jan Schellens Joins LIXTE as Chief Medical Officer- -Preclinical Data Published in Journal EMBO Reports Shows LB-100 as Potentially Enhancing the Benefit of Immunotherapy- -LIXTE to Present at Two Upcoming Investor Conferences- PASADENA, CA, Aug. 19, 2024 (GLOBE NEWSWIRE) -- LIXTE Biotechnology Holdings, Inc. (“LIXTE” or the “Company”) (Nasdaq: LIXT and LIXTW), a clinical-stage pharmaceutical company developing a new class of cancer therapy to enhance chemotherapy and immunotherapy, today provided an update on the Company’s recent activities. “We are encouraged by the growing interest shown by major pharmaceutical companies in our proprietary compound, LB-100, as demonstrated by their support in clinical trial collaborations,” said Bas van der Baan, LIXTE’s President and Chief Executive Officer. “Highlighting the Company’s recent progress is our new agreement with The Netherlands Cancer Institute, supported by F. Hoffmann- La Roche Ltd. (“Roche”), which is funding the clinical trial in metastatic colorectal cancer and providing atezolizumab (Tecentriq®, a PD-L1 inhibitor) through the imCORE network, an academic industry collaboration that aims at accelerating cancer immunotherapy research through institution sponsored studies. Already underway is a proof-of-concept trial, funded by GSK, of LB-100 plus GSK’s dostarlimab-gxly in ovarian clear cell cancer. “We are seeing encouraging results in the first phase of our clinical trial to determine appropriate dosing and toxicity for treating advanced soft tissue sarcomas with a combination of LB-100 and standard-of-care chemotherapy and expect to see the data from this first phase early in 2025. We are exploring alternative sites, including international locations, for our small cell lung cancer trial, following termination of that clinical trial at City of Hope due to limited patient accrual,” Mr. van der Baan added. Recent Company Highlights: Collaboration with the Netherlands Cancer Institute, supported by Roche, to conduct a new clinical trial (NCT06012734 in clinicaltrials.gov) in immune therapy for unresponsive (MSI Low) metastatic colorectal cancer. LIXTE is providing its lead compound, LB-100, and Roche will provide atezolizumab (Tecentriq®,a PD-L1 inhibitor). The clinical trial will test recent findings that indicate that LB-100 increases recognition of colorectal cancer cells by the immune system.Jan Schellens, M.D., Ph.D., joined LIXTE as Chief Medical Officer effective August 1, 2024. Dr. Schellens brings to the Company more than 25 years of clinical experience as a medical oncologist, pharmacologist and clinical pharmacologist, including more than two decades developing and bringing new drugs to market. Co-author of more 900 publications in peer-reviewed scientific journals, Dr. Schellens has held leadership positions at the Netherlands Cancer Institute in Amsterdam and the Dr. Daniel den Hoed Clinic-Erasmus University in Rotterdam. He was professor of clinical pharmacology at Utrecht University in the Netherlands, where he earned his M.D. degree, and he served as a board member and Chief Medical Officer of Byondis B.V. in Nijmegen, Netherlands. Dr. Schellens also earned a Ph.D. degree in Pharmaceutical Sciences from Leiden University in Leiden, Netherlands.New pre-clinical data in the journal EMBO Reports shows that LIXTE’s lead compound, LB-100, can turn immunologically “cold” tumors “hot,” potentially enhancing the benefit of immunotherapy. In a paper titled, “The Phosphatase Inhibitor LB-100 Creates Neoantigens in Colon Cancer Cells through Perturbation of mRNA Splicing,” the article reported that LIXTE’s collaborators from the Netherlands Cancer Institute have demonstrated that treatment of cancer cells with LB-100 disrupts the normal processing of the mRNA that encodes proteins, thereby generating neo-antigens that are presented to the host immune system. This new mechanism adds to several previous discoveries showing that LB-100 sensitizes cancer cells to immune checkpoint blockade.LIXTE will present at two upcoming investor conferences: the 2004 Summit Summer 2024 Virtual Conference, August 20, 2024, and the H.C. Wainwright 26th Annual Global Investor Conference, September 9-11, 2024. Both conferences will be virtual presentations. About LIXTE Biotechnology Holdings, Inc. LIXTE Biotechnology Holdings, Inc. is a clinical-stage pharmaceutical company focused on new targets for cancer drug development and developing and commercializing cancer therapies. LIXTE has demonstrated that its first-in-class lead clinical PP2A inhibitor, LB-100, is well-tolerated in cancer patients at doses associated with anti-cancer activity. Based on extensive published preclinical data (see www.lixte.com), LB-100 has the potential to significantly enhance chemotherapies and immunotherapies and improve outcomes for patients with cancer. LIXTE’s lead compound, LB-100, is part of a pioneering effort in an entirely new field of cancer biology – activation lethality – that is advancing a new treatment paradigm. LIXTE's new approach is covered by a comprehensive patent portfolio. Proof-of-concept clinical trials are currently in progress for colorectal, ovarian and sarcoma cancers. Additional information about LIXTE can be found at www.lixte.com. Forward-Looking Statement Disclaimer This announcement contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, and Section 21E of the Securities Exchange Act of 1934. For example, statements regarding the Company's financial position, business strategy and other plans and objectives for future operations, and assumptions and predictions about future activities, including the continuing development of proprietary compounds, the planning, funding, coordination and potential results of clinical trials, the patent and legal costs to protect and maintain the Company's intellectual property worldwide, and the Company’s ability to obtain and maintain compliance with Nasdaq’s continued listing requirements, are all forward-looking statements. These statements are generally accompanied by words such as "intend," anticipate," "believe," "estimate," "potential(ly)," "continue," "forecast," "predict," "plan," "may," "will," "could," "would," "should," "expect" or the negative of such terms or other comparable terminology. The Company believes that the assumptions and expectations reflected in such forward-looking statements are reasonable, based on information available to it on the date hereof, but the Company cannot provide assurances that these assumptions and expectations will prove to have been correct or that the Company will take any action that the Company may presently be planning. However, these forward-looking statements are inherently subject to known and unknown risks and uncertainties. Actual results or experience may differ materially from those expected or anticipated in the forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, regulatory policies, available cash resources, research results, competition from other similar businesses, and market and general economic factors. Readers are urged to read the risk factors set forth in the Company’s filings with the United States Securities and Exchange Commission at https://www.sec.gov. The Company disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. For more information about LIXTE, Contact: info@lixte.com General Phone: (631) 830-7092; Investor Phone: (888) 289-5533 Or PondelWilkinson Inc. Investor Relations pwinvestor@pondel.comRoger Pondel: (310) 279-5965; Laurie Berman: (310) 279-5962

Experienced industry executive Marco Timmers takes helm as CEO, bringing over two decades of drug development experience Corporate venture veteran Jeanne Bolger moves from member to Chair of Sapreme’s Board of Directors Company establishes SAB to support next stage of preclinical pipeline towards clinical proof-of-concept with Prof. Steven Dowdy, Prof. Annemieke Aartsma-Rus, Prof. Philip Van Damme, and Prof. Hendrik Fuchs BILTHOVEN, The Netherlands--(BUSINESS WIRE)-- Sapreme, a biotechnology company focused on developing next-generation RNA therapeutics for patients with genetically driven diseases, today announced the appointment of Marco Timmers, PhD, as Chief Executive Officer and Jeanne Bolger, MD, to Chair of the Sapreme Board of Directors (BoD). Additionally, the company has established its Scientific Advisory Board (SAB), comprised of experts in diseases with high unmet medical need, as well as the rapidly expanding field of RNA delivery. Marco Timmers has cultivated a career spanning over 25 years in pharmaceutical R&D and has held various leadership positions at international biotechnology and pharmaceutical corporations. Before joining Sapreme, he was CEO of Byondis (formerly Synthon Biopharmaceuticals), a clinical-stage biopharmaceutical company developing Antibody-Drug Conjugates (ADCs) targeting intractable cancers and auto-immune diseases. During his time at Byondis, Dr. Timmers also served as Chief Scientific Officer, guiding the company’s clinical strategies and growth. Before that, he held various positions of increasing responsibility at Organon, Schering-Plough and MSD, including Head of Medicinal Chemistry, Proof-of-Concept Team Leader and Site Lead Women’s Health and Endocrinology. He holds a MSc and a PhD in bio-organic chemistry from Leiden University in The Netherlands. “Sapreme’s endosomal escape technology holds great potential in enabling much-needed improved intracellular delivery for next-generation large molecule drugs. I look forward to working with the team at Sapreme to further advance this innovative platform and accelerate our pipeline of RNA therapeutic candidates addressing a range of genetically driven diseases,” said Marco Timmers, Chief Executive Officer of Sapreme. Jeanne Bolger is an experienced biopharma senior executive with extensive business development and investment expertise over her 35 years in the pharmaceutical sector. She served on the board of over a dozen life sciences companies during her 10 years as Vice President of Venture Investing at Johnson & Johnson Innovation-JJDC. Dr. Bolger’s drug development and commercial expertise spans numerous therapeutic fields, including oncology, neurology, psychiatry, respiratory, immunology, infectious disease and vaccines, and cell and gene therapy. She is a Non-Executive Board Director of Life Healthcare. She is also the Chair of the Board at ExeVir and at Astrivax. Dr. Bolger holds an MB BCh in Medicine from University College Dublin. She has been a member of the Sapreme Board of Directors since July 2023. “Marco’s deep R&D and leadership expertise, coupled with the newly formed SAB places Sapreme in an optimal position to deliver on its upcoming corporate and clinical goals,” commented Jeanne Bolger, Chair of the Board of Directors of Sapreme. “It is a great pleasure to support this dynamic team on its path to overcoming significant hurdles in next-generation therapeutics.” Scientific Advisory Board Appointments |Sapreme has established a SAB to guide the company as it advances its preclinical candidates toward clinical proof-of-concept. The new members of the Sapreme SAB include: Steven Dowdy, PhD Steven Dowdy is professor of cellular and molecular medicine at the University of California San Diego School of Medicine and is a leading expert in the field of endosomal escape. Dr. Dowdy has been advising biotech and pharmaceutical companies for 35 years, and he is currently a member of five biotech SABs. His research over the last 30 years has primarily focused on the delivery of macromolecular therapeutics, including siRNAs, ASOs, peptides, and proteins, and developing new chemistries to tackle the issue of rate-limiting endosomal escape. He received his PhD in molecular genetics from the University of California Irvine and was a postdoctoral fellow at the Whitehead Institute, MIT. Annemieke Aartsma-Rus, PhD Annemieke Aartsma-Rus is professor of translational genetics in the Department of Human Genetics at the Leiden University Medical Center (LUMC), and one of the most influential researchers in the field of Duchenne Muscular Dystrophy (DMD). Her research focuses on advancing therapeutic exon skipping for DMD into the clinic. Dr. Aartsma-Rus also serves as a scientific advisor for various DMD organizations. As a foremost expert in the field, Dr. Aartsma-Rus received the Duchenne Award from the Duchenne Parent Project for her dedication and research in DMD in 2011 and the Black Pearl Science Award from Eurordis in 2021. She received her PhD from Leiden University and was a postdoctoral fellow at the LUMC. Philip Van Damme, MD Philip Van Damme is professor of neurology at the University Hospitals in Leuven (Belgium), where he leads the Neuromuscular Reference Center. His current research focuses on genetic modifiers of amyotrophic lateral sclerosis (ALS) and disease pathways in pluripotent stem cell models derived from ALS patients. As a prominent medical expert in neurology, Dr. Van Damme has published over 200 papers in international peer-reviewed journals on ALS and related neuromuscular disorders, and he is the chair of the European Academy of Neurology (EAN) guideline panel on ALS. He holds an MD from KU Leuven University. Hendrik Fuchs, PhD Hendrik Fuchs is professor at the Institute for Laboratory Medicine, Clinical Chemistry, and Pathobiochemistry at the Charité – Universitätsmedizin Berlin in Germany. Dr. Fuchs has spent more than 20 years researching the development of protein-based targeted anti-tumor therapeutics and is widely recognized as a pioneer in the use of saponins for endosomal escape. He was the coordinator of a large European project on targeted gene delivery and has published over 100 peer-reviewed articles. He holds a PhD from Free University of Berlin. About Sapreme Sapreme is developing next-generation RNA therapeutics for patients with genetically driven diseases. Our proprietary endosomal escape technology enables targeted delivery of large molecules such as PMOs, ASOs and siRNAs to intracellular targets in extrahepatic tissues as well as the liver. We have successfully translated the technology to non-human primates and have obtained in vivo PoCs in muscle, heart, kidney and tumor tissue. Sapreme is now building a broader pipeline to address high unmet needs in neuromuscular, renal, cardiometabolic diseases and beyond. Our lead candidate is designed as best-in-class in Duchenne Muscular Dystrophy and we are pursuing strategic partnerships to co-develop product candidates with selected pharma/biotech companies based on our endosomal escape platform. View source version on businesswire.com: Contacts For further inquiries, please contact: Marco Timmers, CEO +31 30 760 09 76 info@sapreme-technologies.com For media inquiries, please contact: Trophic Communications Desmond James or Valeria Fisher +49 151 67859086 or +49 175 8041816 sapreme@trophic.eu Source: Sapreme View this news release online at:

Dutch biopharma Byondis that the U.S. FDA issued a complete response letter for the company's lead asset, an anti-HER2 antibody-drug conjugate (ADC) for breast cancer treatment. With its BLA, Byondis sought approval for SYD985 in HER2-positive unresectable locally advanced or metastatic breast cancer — a disease with a high unmet medical need. According to Byondis, the agency requested additional information that "requires time and resources that extend beyond the current evaluation period." Byondis submitted its to the FDA back in July of last year, along with aMarketing Authorization Application to the . The EMA's decision is still pending, and is between April 2023 and October 2023. The BLA and MAA were supported by data from the phase 2 TULIP trial comparing SYD985 to physician’s choice (PC) treatment in patients with pre-treated HER2-positive unresectable breast cancer. The study met its primary endpoint of progression-free survival, demonstrating a statistically significant improvement of 2.1 months over PC. The trial also demonstrated supportive overall survival. Despite the CRL, Byondis remains optimistic about SYD985’s potential and is working with the FDA on next steps. “We continue to believe that SYD985 can present a meaningful treatment option for patients living with HER2-positive metastatic breast cancer,” said Byondis CEO Marco Timmers. HER2has become an increasingly popular target for drugmakers in the cancer space. Back in BioNTech signed a $1.5 billiondeal with China-based biotech DualityBio to co-develop and commercialize two cancer ADCs candidates, including DualityBio’s lead candidate, DB-1303, which is a topoisomerase-1 inhibitor-based ADC directed against HER2. Eisai and China-based Bliss Biopharmaceutical just a clinical trial collaboration agreement — with the option to license — for BlissBio's ADC candidate directed against HER2 for the treatment of cancers. SYD985 is also in for uterine cancer and solid tumors.