Rambam Health Care Campus

REHOVOT, Israel, Aug. 15, 2023 /PRNewswire/ -- Biomica Ltd., a clinical-stage biopharmaceutical company developing innovative microbiome-based therapeutics and a subsidiary of Evogene Ltd. (Nasdaq: EVGN) (TASE: EVGN), has announced the opening of a second site at The Davidoff Cancer Center for its ongoing Phase I clinical trial of its immuno-oncology drug candidate, BMC128. The trial aims to assess the safety and tolerability of BMC128 in combination with immune checkpoint inhibitor (ICI) immunotherapy, Bristol Myers Squibb's Opdivo®, for the treatment of refractory patients with non-small cell lung cancer (NSCLC), melanoma, or renal cell carcinoma (RCC). The Davidoff Center for the Treatment and Research of Cancer, situated at Beilinson Hospital, Rabin Medical Center (RMC), holds a preeminent position as Israel's first and foremost comprehensive cancer center, known for its international leadership in cancer care. This state-of-the-art and patient-centric facility diligently serves over 200,000 patients annually, both from Israel and around the globe. This new site at The Davidoff Center represents another milestone in Biomica's commitment to advancing cutting-edge clinical research in immuno-oncology. The company established its first site at the Rambam Health Care Campus, where the first patient was dosed in July 2022 in the Phase I study of its Microbiome-Based immuno-oncology drug. Prof. Gal Markel, Director of Davidoff Cancer Center and Biomica's Scientific Advisory Board member, said: "I am excited about Biomica's significant progress in their Phase I clinical trial at The Davidoff Cancer Center. As a Biomica Scientific Advisory Board member, I am proud to contribute my expertise to this important research endeavor. The exploration of microbiome-based immuno-oncology therapies represents a promising frontier in cancer treatment. I look forward to witnessing the potential impact of this approach on refractory patients with NSCLC, melanoma, or RCC." Dr. Elran Haber, CEO of Biomica, expressed his pride: "The opening of this new site at The Davidoff Center, a world-renowned cancer institution, marks an important milestone for Biomica's BMC128 clinical program. Collaborating with esteemed Prof. Gal Markel further strengthens our commitment to advancing clinical research and expediting patient recruitment. We are resolute in our pursuit of accelerating progress and bringing hope to patients through innovative therapies." About Biomica Ltd.: Biomica is a clinical stage biopharmaceutical company developing innovative microbiome-based therapeutics utilizing PRISM system, a proprietary computational platform powered by Evogene's MicroBoost AI tech-engine. licensed from Evogene. Biomica aims to identify and characterize disease-related microbiome entities and to develop novel therapeutics based on these understandings. The company is focused on the development of therapies for antibiotic resistant bacteria, immuno-oncology, and microbiome-related gastrointestinal (GI) disorders. Biomica is a subsidiary of Evogene Ltd. (Nasdaq: EVGN, TASE: EVGN). For more information, please visit About Evogene Ltd.: Evogene (Nasdaq: EVGN, TASE: EVGN) is a computational biology company aiming to revolutionize the development of life-science-based products by utilizing cutting-edge technologies to increase the probability of success while reducing development time and cost. Evogene established three unique tech-engines - MicroBoost AI, ChemPass AI, and GeneRator AI – leveraging Big Data and Artificial Intelligence and incorporating deep multidisciplinary understanding in life sciences. Each tech-engine is focused on the discovery and development of products based on one of the following core components: microbes (MicroBoost AI), small molecules (ChemPass AI), and genetic elements (GeneRator AI). Evogene uses its tech-engines to develop products through subsidiaries and strategic partnerships. Evogene's subsidiaries currently utilize the tech-engines to develop human microbiome-based therapeutics by Biomica, ag-biologicals by Lavie Bio, ag-chemicals by AgPlenus, medical cannabis products by Canonic and castor varieties, for the biofuel and other industries, by Casterra. For more information, please visit . Forward-Looking Statements: This press release contains "forward-looking statements" relating to future events. These statements may be identified by words such as "will", "may", "could", "expects", "intends", "anticipates", "plans", "believes", "scheduled", "estimates", "demonstrates", or words of similar meaning. For example, Evogene and Biomica are using forward-looking statements in this press release when they discuss the safety and tolerability of BMC128 and the success of microbiome-based immuno-oncology therapies in cancer treatment. Such statements are based on current expectations, estimates, projections and assumptions, describe opinions about future events, and involve certain risks and uncertainties which are difficult to predict and are not guarantees of future performance. Therefore, actual future results, performance or achievements of Evogene and its subsidiaries may differ materially from what is expressed or implied by such forward-looking statements due to a variety of factors, many of which are beyond the control of Evogene and its subsidiaries, including, without limitation, those risk factors contained in Evogene's reports filed with applicable securities authorities. Evogene and its subsidiaries disclaim any obligation or commitment to update these forward-looking statements to reflect future events or developments or changes in expectations, estimates, projections, and assumptions. Contacts Rachel Pomerantz Gerber Head of Investor Relations at Evogene rachel.pomerantz@evogene.com Tel: +972-8-9311901 Logo - Logo - Company Codes: NASDAQ-NMS:EVGN, TelAviv:EVGN

Researchers found that alterations in the gut microbiome that are linked to graft-versus-host disease severity are connected to an increase in oxygen levels in the intestine that follows immune-mediated intestinal damage. Pharmacologically reducing intestinal oxygen levels alleviated the microbial imbalance and reduced the severity of the condition in animal models. The severity of immune-mediated intestinal diseases such as graft-versus-host disease (GVHD) or inflammatory bowel diseases is known to be associated with alterations in the gut microbiome, but what leads to such disruption in the microbial community has remained a mystery. Researchers at Baylor College of Medicine, the University of Michigan and collaborating institutions working with animal models of GVHD report today in the journal Immunity that alterations in the gut microbiome are connected to an increase in oxygen levels in the intestine that follows immune-mediated intestinal damage. Pharmacologically reducing intestinal oxygen levels alleviated the microbial imbalance and reduced the severity of the intestinal disease. "There is a lot of data showing that microbes change in many diseases, but we do not understand how that happens," said leading author Dr. Pavan Reddy, professor and director of Baylor's Dan L Duncan Comprehensive Cancer Center, who was at the University of Michigan during the development of this project. "This study is one of the first to provide an explanation and a potential solution for the imbalance in the gut microbiome that exacerbates GVHD and possibly other inflammatory intestinal conditions." GVHD is a potentially life-threatening complication of bone marrow transplantation. "It is the complication that can prevent us from using this therapy that has proven to be effective to treat many blood cancers and inherited blood diseases," Reddy said. "The idea is to understand what makes GVHD worse so we can effectively control it. The study also is relevant to more common inflammatory bowel diseases, including Crohn's disease and ulcerative colitis." Reddy and his colleagues discovered that the damage immune cells cause to intestinal cells prevents these cells from fully using oxygen to conduct their normal functions. Consequently, all the oxygen that is not being used by intestinal cells oozes into the intestine, changing the environment for the resident microbes. "Most of the 'good microbes' we have in the intestine grow in oxygen-poor environments -- oxygen is toxic to them. They are called anaerobic (without oxygen) bacteria," Reddy said. "When oxygen levels in the intestine increase, these microbes tend to disappear, and oxygen-loving microbes tend to grow. An increase in oxygen level provides an explanation for the microbiome changes in the context of these inflammatory diseases." The findings suggested that restoring the normal environment by reducing the oxygen level in the intestine could help reestablish the balance of the microbial community and lead to attenuation of GVHD. "Indeed, we discovered that reducing the intestinal oxygen level actually made a difference in the progression of GVHD in the animal models," Reddy said. "We found that a commonly used drug to reduce iron overload, an iron chelator, mitigated the microbial imbalance and reduced the severity of GVHD." Iron chelators have been used for many years to treat conditions in which excess iron causes tissue damage, such as hemochromatosis. Iron chelators are compounds that bind to iron, pulling it out and removing it from the body. "We discovered that iron chelators also can act as oxygen sinks," Reddy said. "In our animal models, iron chelators removed iron from the intestine and that facilitated the restoration of an oxygen-poor environment that gave anaerobic bacteria an opportunity to bloom. Importantly, this reduced the severity of GVHD." The researchers' next steps include conducting studies to determine whether iron chelation can help control the severity of GVHD in patients who have received a bone marrow transplant. Another advantage of iron chelation would be that it may reduce or avoid the use of immune suppressor medications that are usually used to control GVHD. Suppressing the immune system may control GVHD, but also favors infections, which can be life-threatening. "If iron chelation helps control the condition in patients, it would be a novel non-immunosuppressive approach to treat GVHD with seemingly little side effects," Reddy said. Other contributors to this work include Keisuke Seike, Anders Kiledal, Hideaki Fujiwara, Israel Henig, Marina Burgos da Silva, Marcel R.M. van den Brink, Robert Hein, Matthew Hoostal, Chen Liu, Katherine Oravecz-Wilson, Emma Lauder, Lu Li, Yaping Sun, Thomas M. Schmidt, Yatrik M. Shah, Robert R. Jenq and Gregory Dick. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, University of Michigan, Okayama University Hospital, Rambam Health Care Campus-Israel, Memorial Sloan Kettering Cancer Center, Yale University School of Medicine and MD Anderson Cancer Center. This work was supported by the US National Institutes of Health grants P01HL149633, HL152605, CA217156, R01CA148828, 4 R01CA245546 and R01DK095201. Further support was provided by National Cancer Institute award numbers R01-CA228358, R01-CA228308, P30 CA008748 MSK Cancer Center Support Grant/Core Grant and P01-CA023766; National Heart, Lung, Blood Institute award number R01-HL123340 and R01- 8 HL147584; Tri-Institutional Stem Cell Initiative and NIH grant CA46592.

JERUSALEM, July 26, 2022 (GLOBE NEWSWIRE) -- Entera Bio Ltd. (NASDAQ: ENTX), (“Entera” or the “Company”) a leader in the development of orally delivered peptides and therapeutic proteins, today announced the formation of its Clinical and Scientific Advisory Board (CSAB), consisting of world class experts in bone diseases, endocrinology, and metabolic disorders. In addition, the Company announced today that it will be presenting new data from its 6-month Oral PTH (EB613) Phase 2 Study in postmenopausal women with low bone mass, or osteoporosis at the 2022 Annual Meeting of the American Society for Bone and Mineral Research (ASBMR), which will take place in Austin, Texas from September 9-12, 2022. The inaugural members of Entera’s CSAB include: Professor John P. Bilezikian: Vice-Chair, Department of Medicine for International Research and Education; Chief, Emeritus, of the Division of Endocrinology; Director, Emeritus, of the Metabolic Bone Diseases Program at Columbia University Medical Center Professor Maria Luisa Brandi: Professor of Endocrinology, FIRMO Foundation, Florence, Italy Professor Bart Clarke: Professor of Medicine and Consultant, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic Professor Felicia Cosman: Professor of Medicine, Emerita, Columbia University College of Physicians and Surgeons, Division of Endocrinology; Co-Editor in Chief of the journal Osteoporosis International Professor William Fraser: Professor of Medicine and Deputy Head of Norwich Medical School at the University of East Anglia and Consultant in Metabolic Medicine at the Norfolk and Norwich University Hospital, UK Dr. Roger Garceau: Former Chief Medical Officer and EVP at NPS Pharmaceuticals and Shire plc (Natpara®); with previous senior management roles at Sanofi Aventis and Pharmacia Professor Sophia Ish-Shalom: Vice President of the Israeli Foundation for Osteoporosis and Bone Diseases (IFOB), Endocrine Clinic Elisha Hospital; prior Head of Bone and Mineral Metabolism Unit, Rambam Health Care Campus , Haifa Israel Professor Socrates Papapoulos: Emeritus Professor in Diseases of Bone & Mineral Metabolism, Advisor Center for Bone Quality, Leiden University Medical Center, The Netherlands “We are honored to be working with this distinguished group of thought leaders and appreciate their support and guidance of our clinical development strategy,” said Miranda Toledano, Entera’s Chief Executive Officer. “Their extensive clinical and scientific experience in late-stage clinical trials have been invaluable to the advancement of our core osteoporosis and hypoparathyroidism programs.” Arthur Santora, M.D., Ph.D., Chief Medical Officer of Entera said, “We have been working collaboratively to advance Entera’s proprietary oral pipeline and the support of our CSAB provides phenomenal validation to our efforts. We look forward to benefitting from their collective expertise as we continue to move toward our mission of delivering oral therapeutic options to patients high unmet medical needs.” The title of the abstract accepted for presentation at the ASBMR 2022 National Meeting and current schedule for presentation follows: Abstract Title: A Six-month Phase 2 Study or Oral PTH (EBP05) in Postmenopausal Women with Low Bone Mass – Dose Proportional Absorption and Effect on Lumbar Spine BMD Presentation Type: Poster Presentation Session: Poster Session II & Poster Tours Session Date/Time: Sunday, September 11, 2022 from 1:00 pm – 3:00 pm Presentation Time: 1:00 pm – 3:00 pm Location: ASBMR Discovery Hall About EB613 (a.k.a. EBP05) Parathyroid hormone (PTH) is an 84-amino acid hormone and the primary regulator of calcium and phosphate metabolism in bone and kidney. EB613 is an oral formulation of synthetic hPTH (1-34), (teriparatide), a peptide consisting of the first 34 amino acids of PTH which represent the functional region. Subcutaneous Forteo® (teriparatide injection) has been the leading anabolic treatment of osteoporosis since 2002. EB613 utilizes Entera’s oral drug delivery platform which promotes enteric absorption and stabilizes teriparatide in the gastrointestinal tract. Entera’s Oral PTH formulations have been administered collectively to a total of 225 subjects in two Phase 1 studies and 3 phase 2 studies (including 35 in 2 phase 2 hypoparathyroidism studies). The most recent study was a dose ranging Phase 2 study in postmenopausal women with low bone mass. This study met primary and key secondary endpoints and was presented in a late-breaker oral presentation at the ASBMR 2021 conference. For the primary efficacy endpoint: a statistically significant increase in P1NP (a bone formation marker) at 3 months was achieved. A significant dose response was observed for 0.5, 1.0, 1.5 and 2.5 mg oral PTH doses on P1NP, Osteocalcin and bone mineral density (BMD). Subjects receiving the 2.5 mg dose of EB613 showed significant increases in dose-related BMD at the lumbar spine, total hip, and femoral neck at 6 months. Subjects receiving the 2.5 mg dose of EB613 daily for 6 months had a significant placebo adjusted increase of 3.78% in lumbar spine BMD (p<0.008) which is similar to the 3.9% increase in lumbar spine BMD seen with Forteo® in clinical studies reported in the literature1. Increases in total hip and femoral neck BMD were greater than those previously reported with Forteo®. EB613 exhibited an excellent safety profile, with no drug related serious adverse events. The most common adverse events included mild nausea, moderate back pain, moderate headache, and moderate upper abdominal pain. About Entera Bio Entera is a leader in the development of orally delivered macromolecules therapeutics including peptides and other therapeutic proteins, for use in areas with significant unmet medical need where adoption of injectable therapies is limited due to cost, convenience and compliance challenges for patients. The Company’s proprietary, oral drug delivery technology is designed to address the technical challenges of poor absorption, high variability, and the inability to deliver large molecules to the targeted location in the body through the use of a synthetic absorption enhancer to facilitate the absorption of large molecules, and protease inhibitors to prevent enzymatic degradation and support delivery to targeted tissues. The Company’s most advanced product candidates, EB613 for the treatment of osteoporosis and EB612 for the treatment of hypoparathyroidism are in clinical development. The Company recently completed the phase 2 study for EB613 and has a Type C meeting scheduled with FDA with respect to its Phase 3 program in H2 2022. Entera also licenses its technology to biopharmaceutical companies for use with their proprietary compounds and, to date, has established a collaboration with Amgen Inc. For more information on Entera Bio, visit . Cautionary Statement Regarding Forward Looking Statements Various statements in this press release are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements (other than statements of historical facts) in this press release regarding our prospects, plans, financial position, business strategy and expected financial and operational results may constitute forward-looking statements. Words such as, but not limited to, “anticipate,” “believe,” “can,” “could,” “expect,” “estimate,” “design,” “goal,” “intend,” “may,” “might,” “objective,” “plan,” “predict,” “project,” “target,” “likely,” “should,” “will,” and “would,” or the negative of these terms and similar expressions or words, identify forward-looking statements. Forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. Forward-looking statements should not be read as a guarantee of future performance or results and may not be accurate indications of when such performance or results will be achieved. Important factors that could cause actual results to differ materially from those reflected in Entera’s forward-looking statements include, among others: changes in the interpretation of clinical data; results of our clinical trials; the FDA’s interpretation and review of our results from and analysis of our clinical trials; unexpected changes in our ongoing and planned preclinical development and clinical trials, the timing of and our ability to make regulatory filings and obtain and maintain regulatory approvals for our product candidates; the potential disruption and delay of manufacturing supply chains; loss of available workforce resources, either by Entera or its collaboration and laboratory partners; impacts to research and development or clinical activities that Entera is contractually obligated to provide, such as those pursuant to Entera’s agreement with Amgen; overall regulatory timelines; the size and growth of the potential markets for our product candidates; the scope, progress and costs of developing Entera’s product candidates; Entera’s reliance on third parties to conduct its clinical trials; Entera’s expectations regarding licensing, business transactions and strategic collaborations; Entera’s operation as a development stage company with limited operating history; Entera’s ability to continue as a going concern absent access to sources of liquidity; Entera’s ability to obtain and maintain regulatory approval for any of its product candidates; Entera’s ability to comply with Nasdaq’s minimum listing standards and other matters related to compliance with the requirements of being a public company in the United States; Entera’s intellectual property position and its ability to protect its intellectual property; and other factors that are described in the “Cautionary Statements Regarding Forward-Looking Statements,” “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections of Entera’s most recent Annual Report on Form 10-K filed with the SEC, as well as the company’s subsequently filed Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. There can be no assurance that the actual results or developments anticipated by Entera will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, Entera. Therefore, no assurance can be given that the outcomes stated or implied in such forward-looking statements and estimates will be achieved. Entera cautions investors not to rely on the forward-looking statements Entera makes in this press release. The information in this press release is provided only as of the date of this press release, and Entera undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, except to the extent required by law. _______________________ 1Leder BZ et.al. JCEM 2015 Contact: Entera Bio: Ms. Miranda Toledano Chief Executive Officer Entera Bio Email: miranda@enterabio.com Phone: +972-58-55-88-470 IR: Mr. Christopher M. Calabrese Managing Director LifeSci Advisors LLC Email: ccalabrese@lifesciadvisors.com Phone: (917) 680-5608