Bonus Biogroup is delighted to announce the successful preclinical demonstration [1] of MesenCure's effectiveness in treating lethal toxicity induced by chemotherapy drugs, such as Cisplatin and Bleomycin, routinely used in cancer treatment.

Common chemotherapy drugs are designed to eliminate cancer cells, ostensibly without harming healthy body cells. In actuality, these drugs also have toxic effects on healthy cells, leading to damage across various tissues and organs and causing severe side effects in approximately half of the patients [2].

MesenCure's effectiveness, as showcased by the trial results in combating lethal toxicity due to chemotherapy drugs, includes:

• Treating with MesenCure increased overall survival rates after exposure to a lethal dose of cisplatin by 2.6 times, from a 21% survival rate in the untreated control group to 55% in the treated test group, and significantly extended survival duration (p<0.01). Cisplatin and similar platinum-based drugs, such as carboplatin and oxaliplatin, are the most frequently used chemotherapy drugs, treating approximately 63% of solid tumor patients [5].
• Treatment with MesenCure significantly extended survival (p<0.001) [6] and doubled the survival rate after exposure to a lethal dose of bleomycin. This was evidenced by the fact that the treated group took twice as long to reach 50% mortality compared to the untreated control group. Bleomycin and another topo-isomerase II inhibitor, etoposide, are highly toxic and cause severe side effects in about 69% of solid tumor patients [2].

The successful use of MesenCure in treating toxic damage, including inflammation and tissue damage, and preventing death from a broad array of chemical, biological, and cellular hazards, is reflected in the Company's consistent accomplishments in developing potential MesenCure applications. These include doubling survival rates after exposure to the lethal toxicity of chemotherapy drugs, mitigating the toxicity of cellular CAR-T immunotherapy for cancer [7], and our collaborative study with the Israel Institute for Biological Research, which focused on examining MesenCure's effectiveness in treating acute respiratory distress syndrome and rehabilitating lung tissue damage caused by various biological agents [8]

These successes offer substantial additional opportunities for the Company to use MesenCure in treating various toxicities, including those resulting from the considerable toxicity of chemotherapy drugs, which can cause severe, life-threatening side effects and limit drug dosages, potentially reducing their efficacy. Drugs like cisplatin and similar platinum-based drugs are used to treat numerous cancers, such as ovarian, testicular, bladder, cervical, lung, and head and neck cancers, among others, which together constitute a market of approximately 500,000 patients per year in the U.S. alone [9]. More than 50% of these patients suffer from severe side effects from these drugs [10].

On June 16, 2023, Bonus Biogroup presented these trial results for treating lethal chemotherapy drug toxicity to cellular drug development experts, both from academia and industry, at the invitation of Jackson Laboratory. This was part of their seminar on Advances and Applications of Humanized In Vivo Models in Preclinical Drug Development, held in Paris, Munich, Zurich, and London from June 12-19, 2023 [11].

Jackson Laboratory, a respected non-profit organization founded in 1929 [12], stands as one of the world's leading research institutes. It employs roughly three thousand researchers and staff across three continents: the Americas, Asia, and Europe.

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 twenty-eight approved patents and fifteen 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 in this trial. In parallel, Bonus Biogroup 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, injectable human bone graft using cells sampled from the patient. The patient's cells are cultured in a bioreactor on three-dimensional scaffold particles. Within a span of two to three weeks, this innovative growth system can generate a substantial volume of cells, sufficient to create a personalized, living bone graft suited to the patient's bone defect. 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.

Existing alternatives to Bonus Biogroup's living, injectable human bone graft include autologous bone transplantation, necessitating surgical extraction of bone from a different part of the patient's body for implantation in the bone-deficient area. Other alternatives involve using human bone substitutes, which generally fail to achieve complete healing and functional restoration due to their lack of a natural connection with the human body.

Unlike autologous bone transfer, the Bonus Biogroup's bone graft is created in a laboratory rather than harvested through invasive and potentially risky surgical procedures. This innovative approach allows the graft to be produced in the precise volume needed to fill the patient's bone defect, offering a rapid, safe, and accessible solution for patients and healthcare providers. Moreover, living, injectable human bone grafting does not necessitate a complex surgical procedure, potentially accelerating the patient's recovery process.

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.

Following the successful demonstration of MesenCure's effectiveness in treating respiratory distress in severe COVID-19 patients, the Company has expanded its research initiatives to explore the drug and its derivatives potential efficacy in treating other conditions. These include cytokine release syndrome resulting from immunotherapies designed to activate the immune response against cancer, hematopoietic stem cell transplantation, and the lethal toxicity induced by chemotherapy drugs utilized in cancer treatment. Furthermore, the Company is exploring MesenCure's utility in tissue rehabilitation and healing processes.

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. The poisoning was carried out in C57BL-type mice via intraperitoneal or intranasal injection to enhance the damage to organs most sensitive to cisplatin or bleomycin, respectively.
2. https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.14159
3. Statistical significance was calculated based on the Log-rank (Mantel-Cox) test.
4. In this experiment, the efficacy of MesenCure is calculated based on the comparison of survival rates at the end of the follow-up period after exposure to lethal toxicity since, in the MesenCure treatment group, the mortality rate did not reach 50% at the end of the follow-up period.
5. https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.14159
6. Statistical significance was calculated based on the Log-rank (Mantel-Cox) test. Median survival time stood at two days and four days after poisoning in the control and treatment groups, respectively.
7. For more information, see the Immediate Report Dated April 10, 2023 (REF: 2023-01-039753), included herein as a reference.
8. For more information, see the Immediate Report Dated May 22, 2023 (REF: 2023-01-054261), included herein as a reference.
9. https://cancerletter.com/issues/20230526/
10. https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.14159
11. Advances and Applications of Humanized In Vivo Models in Preclinical Drug Development. https://insight.jax.org/jmcrs/jax-eu-2023/index.html?utm_source=jax_web&utm_medium=event_module&utm_campaign=2023_EURS
12. https://www.jax.org/about-us/fast-facts