Patents Granted in Europe and the UK, Following Earlier Approvals in the US, Australia, and China, Position the Company at the Forefront of Engineered Organ Development and Commercialization

Bonus Biogroup is pleased to announce the approval of patents by the European and UK Patent Offices, covering 17 European countries and the UK [1]. These patents, valid until September 18, 2036, grant exclusive rights to Bonus Therapeutics, a wholly owned subsidiary of Bonus Biogroup, for using and commercializing a branched and hierarchical artificial blood vessel network (hereafter the "Vascular Network"). This Vascular Network is designed to support the development and commercialization of whole-organ engineering.

Globally, there is a critical shortage of live organs for transplantation, including livers, hearts, lungs, pancreas, kidneys, and more. In the United States alone, over 200,000 people annually require an organ transplant. Only about 43,000, or roughly one-fifth of those in need, receive a live organ transplant. The remaining 160,000+ individuals do not [2]. This issue is even more pronounced in other parts of the world.

This dire need has spurred the search for viable alternatives, leading to advancements in tissue engineering, including efforts to laboratory-engineer whole organs.

One of the paramount challenges [3], if not the key challenge [4], in transplanting engineered tissues or organs is ensuring adequate blood supply, nutrition, and waste removal. This challenge escalates with the complexity of a thick tissue or the entirety of an organ. In response, Bonus Biogroup offers a novel solution with its Vascular Network.

The Vascular Network, developed by Bonus Biogroup, includes branches leading to primary, secondary, and capillary vessels. It's engineered to transport blood, essential nutrients, and oxygen to nourish cells within lab-grown tissue or organ implants and to facilitate waste removal. Without such a vascular system, tissue may be rejected or necrotized due to insufficient nutrient and oxygen supply and inadequate waste removal.

Manufactured through electrospinning from various biodegradable biological materials, the Vascular Network's microscopic tubes feature controllable diameters. As natural blood vessels grow within the engineered tissue, the artificial network gradually degrades and is replaced. These tubes mimic the function of natural blood vessels, providing sustenance to body tissues. Additionally, tubes at the implant's ends can be connected to existing blood vessels at the transplantation site within the patient's body.

The company believes the Vascular Network could serve as a foundational infrastructure for developing and, potentially in the future, producing and commercializing whole organs for transplantation. This commercializing could be achieved independently or in collaboration with other entities, including through licensing for the R&D and production of tissues and organs based on the company's Vascular Network.

Potential applications of the Vascular Network include engineered tissues several centimeters thick for replacing parts of the heart damaged by myocardial infarction, regenerating a dysfunctional pancreas, or any other purpose.

The production cost of the Vascular Network via electrospinning is broadly comparable to that of bioprinting. Bonus Biogroup believes that the affordability of production could broaden research into engineered tissues or organs and eventually aid in commercializing the Vascular Network as infrastructure for transplantation.

The patents now approved in Europe and the UK—and previously in the US, Australia, and China [5]—secure Bonus Biogroup’s global exclusivity for the Vascular Network's use and commercialization in key markets.

Dr. Shai Meretzky, CEO of Bonus Biogroup, remarked, "At last month's premier international cell and gene therapy industry meeting in Miami, our company was honored with the Advanced Therapies Award in the prestigious Cell Therapy Biotech Innovation category [6]. This global acknowledgment of our leadership in biotech innovation and cell therapy and our development of effective patient treatments is founded on our remarkable clinical trial achievements for treatments targeting multi-billion-dollar markets and our pioneering work in other advanced therapy domains. Engineering an entire organ is an unfinished challenge. With worldwide protection now secured for the Vascular Network's exclusive use and commercialization through patents in major markets, we offer organ developers a transformative solution to enhance the acceptance of any engineered tissue or organ. This breakthrough could underpin collaborations with tissue or organ developers for transplantation, bolstering our stance in this sector. Our commitment is to continue advancing technologies and products that push the boundaries of future medicine."

By 2030, the transplantation market, excluding engineered tissues, is anticipated to reach $37 billion despite the ongoing scarcity of live organs for transplantation and the challenges associated with often absent tissue matching [7]. The necessity to prevent graft rejection forces most recipients to undergo lifelong immunosuppressive medication, leading to severe side effects and compromised immune defense.

The engineered tissue market, valued at approximately $12 billion in 2022, is predicted to grow by about 11% annually, reaching nearly $33 billion by 2032 [8]. Bonus Biogroup evaluates that this market has yet to achieve its full potential, partly due to challenges in ensuring consistent blood supply to engineered tissues. Addressing this issue through the company-developed artificial blood vessel network could unlock significant advancements in the field.

About Bonus Biogroup

Bonus Biogroup Ltd. is a clinical-stage biotechnology company dedicated to developing advanced therapies in tissue regeneration and biotech products using tissue engineering and cell therapy. The Company currently has two products 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-two approved patents and nine patent applications, spanning numerous countries worldwide.

About BonoFill™ – Living Human Bone Graft

Bonus Biogroup has announced results from twenty out of thirty bone grafts in Phase II clinical trial for treating facial bone deficiencies, following a six-month observation period after each transplantation. The Company has completed the recruitment of all participants and is conducting a multicenter Phase II clinical trial to treat critical-sized bone defects in limb, hand, or foot bones at five medical centers in Israel using BonoFill™.

Bone deficiencies can arise due to aging, infections, osteoarthritis, traumas, and tumors. To mitigate the risk of rejection, Bonus Biogroup developed a living human bone graft using cells sampled from the patient. This lab-grown bone ensures effective bone grafts are readily available for various medical needs, including oral and maxillofacial surgery, skull surgery, orthopedic surgery, and plastic surgery, where bone tissue is lacking.

About the drug MesenCure

Bonus Biogroup has completed a Phase II clinical trial for treating pneumonia and life-teetering respiratory distress in severe COVID-19 patients using the cell therapy drug 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 drug's effectiveness is attributed to the professionalization of the comprising cells, which enhances their natural ability to heal inflammation and tissue damage. The cells constituting MesenCure also affect inflammation and promote tissue regeneration through various mechanisms, potentially offering a broader and superior effect on diverse populations suffering from inflammation and tissue damage from multiple causes compared to drugs with 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) and Dr. Shai Meretzki (CEO and Director)

References

1. On December 20, 2023, patent EP3349816B1 was approved in the European Union, including the United Kingdom. On January 10, 2024, the patent was registered in the UK and on January 24, 2024, it was registered under a Unitary European patent program. This program includes the following seventeen countries: Austria, Belgium, Bulgaria, Denmark, Estonia, Finland, France, Germany, Italy, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Portugal, Slovenia and Sweden. All of these will become fully known to the Company on February 13, 2024.
2. https://www.sir.advancedleadership.harvard.edu/articles/engineering-high-tech-solutions-organ-shortage
3. https://doi.org/10.1002/jbm.b.34979
4. https://doi.org/10.1016/j.addr.2011.03.004
5. For more details on United States patent US10940238B2, Australian patent AU2016322971B2, and Chinese patent CN109414527B, see Immediate Report dated March 17, 2021 (reference: 2021-01-036792), which is included in this report by reference.
6. For more details, see Immediate Report dated January 21, 2024 (reference: 2024-01-008406), which is included in this report by reference.
7. https://www.researchandmarkets.com/reports/595578/organ_and_tissue_transplantation_global
8. https://www.precedenceresearch.com/tissue-engineering-market