Autologous human adipose tissue derived bone tissue therapy (Bonus BioGroup)

Bonus Biogroup (TASE: BONS) is pleased to announce that the U.S. Food and Drug Administration (FDA) has authorized the Company to proceed with a Phase III clinical trial in the United States to evaluate the efficacy and safety of MesenCure—a cell therapy drug developed by the Company, designed for the treatment of inflammation and tissue damage. Clearance was granted for the Investigational New Drug (IND) application submitted by the Company to the FDA for MesenCure with the intention to treat respiratory symptoms in hospitalized, severely ill patients ("respiratory distress") resulting from acute pneumonia associated with COVID-19. This approval is based, among other factors, on results from a Phase II clinical trial conducted by the Company, which demonstrated a reduction of approximately 68% in mortality, as well as a decrease of about 9.4 days in hospitalization duration among the most complicated patients treated with MesenCure, compared to the control group [1]. The Company is working to expand the indication for the Phase III clinical trial of MesenCure to include the treatment of respiratory distress from any cause, including Acute Respiratory Distress Syndrome (ARDS). Plans are underway to conduct a Phase III clinical trial in the U.S. for this broader indication. This decision is supported by clinical and preclinical findings, demonstrating MesenCure's ability to treat various respiratory and other conditions [2], highlighting its potential in treating ARDS, regardless of the underlying cause. ARDS is a critical and often fatal condition characterized by the inability of the lungs to provide sufficient oxygen to the body, leading to respiratory failure. The syndrome arises from acute lung injury, which may result from various causes, including viral, bacterial, or chemical pneumonia, as well as non-pulmonary factors such as sepsis or trauma. Respiratory distress episodes are marked by severe inflammation, lung injury, and pulmonary edema, which further accelerate disease progression. Despite advancements in respiratory support and other supportive treatments, which currently serve as the primary approach to managing the disease, ARDS remains associated with high mortality rates, ranging from 27% to 32% in mild to moderate cases and up to 45% in severe cases [3]. According to a market study published in November 2024, approximately 591,000 patients in the United States alone suffered from ARDS in 2023 [4]. Placing a significant burden on healthcare systems, ARDS accounts for 10% to 15% of intensive care unit (ICU) admissions [3]. The Company believes that the effectiveness of MesenCure may, in part, be attributable to the priming of the living cells that comprise this investigational drug product. This priming process is designed to enhance the natural ability of the cells in MesenCure to control inflammation and repair tissue damage, including acute lung injury, which can lead to life-threatening respiratory distress. MesenCure does not target the underlying cause of acute pneumonia, such as viruses, bacteria, or other pathogens, but is designed to reduce inflammation and repair the acute lung injury resulting from the disease. Because the drug focuses on treating inflammation rather than its triggers, the Company believes that various pathogens, including different species and strains of viruses, bacteria, or other disease-causing agents, are not expected to diminish its effectiveness. The immediate direct hospitalization costs for ARDS patients range from $108,000 to $158,000 per patient in the United States [5]. These significant expenses are primarily driven by prolonged and intensive hospital stays, which typically last between 17 to 47 days, including 10 to 39 days in the ICU, with mechanical ventilation required for 8 to 23 days in most cases [6]. Additionally, more than 75% of ARDS survivors experience a wide range of complications that significantly impact their quality of life [7]. These complications include impaired pulmonary and respiratory function, damage to the nervous, muscular, and cardiovascular systems, as well as cognitive and psychological impairments. ARDS survivors also face an increased risk of mortality within the first year following their acute illness. Many of these long-term effects result from prolonged hospitalization and the use of mechanical ventilation, as well as the administration of paralytic drugs and steroids. In many cases, these complications persist for years, contributing to a substantial rise in healthcare costs. In 2021, these additional expenses were estimated to range between $43,000 and $62,000 per patient in the United States during the first few years following the initial ARDS episode [8]. Dr. Shai Meretsky, CEO of Bonus Biogroup, said: " Receiving FDA approval for our IND application for a Phase III clinical trial in the U.S. marks a significant milestone in ARDS treatment research and an important achievement for the Company. This is our first approval of its kind for an advanced trial in the U.S., underscoring the depth of our research, the scientific innovation behind MesenCure, and the substantial investment and extensive efforts that have brought us to this stage. Based on the findings of the Phase II trial and additional studies, we believe that MesenCure has the potential to provide a breakthrough solution for this critical medical challenge, which, until now, has been addressed only through supportive treatments without a true curative option. The clinical findings, demonstrating not only a significant reduction in mortality rates among patients treated with MesenCure but also a 57% decrease in the need for invasive ventilation and a 38% reduction in hospitalization duration for the most severely ill patients in the Phase II trial, reinforce our confidence that MesenCure may not only save lives but also significantly alleviate the burden on hospitals and intensive care units, while leading to substantial cost savings in the treatment of ARDS patients. We remain committed to advancing the Phase III clinical trial with full dedication and making MesenCure accessible as a pioneering medical solution for patients suffering from acute respiratory distress." The Company estimates that the market potential of MesenCure for the treatment of ARDS in the United States alone could reach approximately $9.6 billion per year by 2030. This estimate is based on the projected savings in immediate direct hospitalization costs for patients treated with MesenCure, which is estimated at $41,000 per patient on average—a 38% reduction compared to the current minimum direct hospitalization cost of $108,000 per patient. Additionally, the estimate considers a minimum ARDS incidence rate of 66 cases per 100,000 people per year [9]. About Bonus Biogroup Bonus Biogroup Ltd. is a biotechnology company conducting advanced clinical trials, focused on developing next-generation therapies in regenerative medicine for cell and tissue regeneration. The company is dedicated to creating effective and safe tissue engineering and cell therapy products to treat common and severe conditions with limited treatment options while ensuring broad accessibility through cost-effective solutions. Bonus Biogroup develops proprietary technologies to enhance the regenerative capabilities of mesenchymal cells—whether autologous (patient-derived) or allogeneic (donor-derived)—to promote tissue regeneration, reduce inflammation, and improve cell production methodologies. Leveraging these technologies, the Company currently has two investigational product candidates in clinical development: BonoFill™, a live tissue-engineered human bone graft intended for bone tissue regeneration and rehabilitation, and MesenCure™, a cell therapy designed to treat inflammation and tissue damage, including pneumonia and respiratory distress. Bonus Biogroup also maintains a variety of technologies and products in the preclinical development phase. The development of these products involves the application of unique technologies and knowledge proprietary to Bonus Biogroup. The Company's robust intellectual property portfolio includes six families of patents and patent applications, comprised of thirty-nine approved patents and ten patent applications, spanning numerous countries worldwide. About BonoFill™ – A Live Human Bone Graft Bone deficiencies can result from a wide variety of causes, including aging, infections, arthritis accompanied by bone loss, various types of trauma (accidents or falls), and cancerous tumors. Bonus Biogroup develops live grafts of injectable human bone based on cells sampled from the patient to reduce the risk of rejection. The cells sampled from adipose tissue are grown in a bioreactor on three-dimensional scaffolds for 2-3 weeks. This process yields a large amount of bone tissue to create a live human bone graft that matches the patient's existing bone deficiency. Growing bone grafts outside the patient's body allows bone grafts to be made upon request. These grafts can be effectively used for various medical needs, including oral and maxillofacial surgery, skull surgery, orthopedic surgery, and plastic surgery in cases lacking bone tissue. The Company has completed a Phase II clinical trial to treat bone deficiencies in the upper or lower jaw bones using BonoFill™. The results indicate that BonoFill™ achieved complete success in bone reconstruction in 90% of the transplants conducted, with a reduction of approximately half to two-thirds of the healing period, enabling patients to return to their regular routine within a relatively short time. In addition to the Phase II clinical trial for treating facial bone deficiencies, the Company is conducting a Phase II multicenter clinical trial to treat limb bone defects in the hand or leg at six medical centers in Israel. The existing alternative solutions to using a live human bone graft manufactured by Bonus Biogroup are autologous (self) bone transplantation—surgery to harvest bone from another part of the patient's body, sometimes together with its peripheral blood vessels, and implant it in the deficient area—or using a bone graft substitute, which in most cases does not lead to healing and does not allow the patient to return to normal functioning due to the lack of a natural connection between the artificial bone replacement and the human body. Unlike autologous bone transplantation, which is the standard treatment today, the bone graft produced by Bonus Biogroup is not taken from the patient's body, avoiding an invasive, dangerous, and complex procedure. Instead, it is grown in the laboratory in the required volume to fully address the bone deficiency in the patient's body, based on a sample of the patient's cells, in a fast, safe, and patient- and health-system-friendly procedure. Additionally, the live implantation of human bone is done by injection, does not require a complex surgical procedure, and may expedite the patient's rehabilitation. About the drug MesenCure™ MesenCure is an investigation cell therapy drug composed of primed, adipose-derived allogeneic mesenchymal cells designed to treat inflammation and tissue damage, including pneumonia and life-threatening respiratory distress. Bonus Biogroup has completed a Phase II clinical trial for treating pneumonia and life-teetering respiratory distress in severe COVID-19 patients using MesenCure™. Clinical trial results indicate that MesenCure reduced the mortality rate of severe COVID-19 patients by 68% compared to the control group, with the survival rate standing at 94% for the 50 severe patients treated with the drug. MesenCure, comprised of professionalized mesenchymal cells, aims to treat inflammation and tissue damage, including pneumonia and respiratory distress caused by the coronavirus or other viruses, bacterial infections, or other sources of immune overactivity, inflammation, or tissue damage. The effectiveness of MesenCure is believed to stem, in part, from the priming of its cellular components, which enhances their natural ability to heal inflammation and repair tissue damage. Unlike treatments that target the underlying cause of the disease, MesenCure is designed to control inflammation and restore damaged tissue, regardless of the cause. As a result, the Company estimates that various pathogens, including different species and strains of viruses, bacteria, or other disease-causing agents, are unlikely to reduce the drug's effectiveness in treating pneumonia, respiratory distress, or other conditions caused by such factors. Additionally, the cells within MesenCure are believed to exert their therapeutic effects through multiple mechanisms, potentially offering a broader and more effective treatment for a diverse range of patients suffering from inflammation and tissue damage of various origins, compared to drugs that operate through a single mechanism of action. Given the successful demonstration of MesenCure's effectiveness in treating acute respiratory distress in severe COVID-19 patients, the Company has broadened its efforts to investigate the potential efficacy of the drug and its derivatives in treating other indications such as cytokine release syndrome resulting from immunotherapy treatments to activate the immune system against cancer or from hematopoietic stem cell transplantation, as well as in tissue rehabilitation and healing. Company Estimations Regarding Forward-Looking Statements Bonus Biogroup's assessments regarding the medical effect and/or commercial potential of its products and/or the resulting economic opportunities, and the Company's ability to continue the process of their development, including conducting studies and arriving at a product that can be medically applied in humans, for the duration and expected dates to perform any stage in any experiment and publish its results and obtain regulatory approvals for marketing the product, are forward-looking statements, as defined by the Securities Law of 1968, which are based on the Company's estimates and on the information in its possession at the time of reporting. There is no certainty that these estimates will materialize, in whole or in part, among others, due to dependence on the actions of third parties, which are not under the Company's control, on the development of future cancer therapies, on future studies results, if any, due to the possibility of delay in obtaining approval from relevant authorities and/or change in the relevant conditions and/or feasibility tests that the Company may conduct and/or delay in performing studies and/or need to perform further experiments and/or failure of experiments and/or technological changes and/or the development and/or marketing of similar and/or more efficient competing products and/or the lack of resources and/or the realization of any of the risk factors associated with the research and/or studies and/or its results. Sincerely, Bonus Biogroup Ltd. By: Yossi Rauch (Chairman of the Board) & Dr. Shai Meretzki (CEO and Director) This document is a convenience translation of the Company's Immediate Report on the matter dated February 18, 2025 (Reference 2025-01-011266). The original Hebrew version of the Immediate Report is incorporated herein by reference and can be accessed at the following link: https://mayafiles.tase.co.il/rpdf/1646001-1647000/P1646673-00.pdf. In the event of any discrepancies between this translation and the original Hebrew version, the Hebrew version shall prevail. References: