Bonus Biogroup is pleased to announce that on May 31, 2024, it presented at a special session [1] at the annual meeting of the International Society for Cell & Gene Therapy (ISCT) in Vancouver, Canada, the results of a Phase II clinical trial for treating facial bone deficiencies in the upper or lower jaw bones using BonoFill™ – a live human bone graft manufactured by the Company (hereinafter: "the Clinical Trial to Treat Facial Bone Deficiencies"):

• Complete success in bone reconstruction using BonoFill™ was achieved in 90% of the thirty transplants conducted in the clinical trial to treat facial bone deficiencies. Success is defined as achieving a natural and complete jawbone six months after BonoFill™ transplantation, enabling rehabilitation procedures such as installing dental implants, which were successfully installed in all patients who opted for them. Additionally, BonoFill™ demonstrated a perfect safety profile, with no serious side effects reported.
• Remarkably, three months after BonoFill™ transplantation, complete and rapid healing was achieved in 87% of the transplants, along with bone regeneration to its maximum height. This finding reflected a growth of three times, on average, from the height of the residual bone before transplantation (p<0.0001) [2]. In contrast, today's standard treatment requires two to three times longer healing to achieve similar bone growth [3]. The significant reduction in the healing period allows patients to return to routine within a relatively short period, including the ability to eat.
• The success of the treatment using BonoFill™ does not depend on patient characteristics such as weight, age, gender, or bone condition before transplantation. This finding underscores the effectiveness of BonoFill™ therapy and its potential applicability for a wide range of patients.

The Company estimates that by 2025, approximately 3.4 million facial bone graft procedures could be performed in the United States alone, representing a market valued at $7.7 billion annually in this territory and potentially double that amount worldwide [4]. Bonus Biogroup is developing a unique solution for this market and is the first company to successfully complete an advanced phase clinical trial for treating facial bone deficiencies using engineered bone tissue [5].

Treating bone deficiencies with BonoFill™, a live human bone graft, is not a complex surgical process. Furthermore, for treating jawbone deficiencies, BonoFill™ therapy does not require an operating room and can be performed in a dental clinic. These characteristics may expand the application and availability of BonoFill™ to many patients, improving their chances of recovery while reducing additional risks and costs associated with surgery and recovery.

In the clinical trial to treat facial bone deficiencies, 30 BonoFill™ transplants were conducted, with 17 in women and 13 in men. The mean age of patients was 56 years (age range 32 to 71 years).

Dr. Shai Meretzki, CEO of Bonus Biogroup, stated, "The publication of the Phase II results of the clinical trial to treat facial bone deficiencies is a milestone of global achievement for us. As a company dedicated to turning the promise of tissue engineering into practical bone restoration, we have taken a significant step towards making BonoFill™ a unique solution for millions of patients. Along with achieving successful final results in Phase II clinical trials for treating inflammation and tissue damage using MesenCure™, a drug composed of living cells also manufactured by the Company, we are entering a crucial phase: entry into pivotal clinical trials of two of the most advanced cellular medicine products in the world, BonoFill™ and MesenCure™. This is in parallel with the continuation of Phase II of a clinical trial for treating limb bone defects—hand or leg—conducted by the Company in six medical centers in Israel, demonstrating success in BonoFill™ therapy where other treatments have failed or are not applicable. These achievements establish the Company's position as a world leader in its field and may help us realize our vision of helping millions of patients live healthier and longer lives."

Dr. Ephraim Tzur, former head of the Oral Maxillofacial Unit at Shamir Medical Center (Assaf Harofeh) and an expert in oral and maxillofacial surgery who led the clinical trial to treat facial bone deficiencies, added, "The results of Phase II of the clinical trial indicate a significant, potential breakthrough in the treatment of facial bone deficiencies. The patients in the clinical trial experienced rapid healing of large and complex deficiencies without significant complications that frequently arise with standard treatment. The bone built using BonoFill™ is stronger and is expected to support better rehabilitative procedures, including installing, establishing, and preserving dental implants. I thank ISCT for recognizing this breakthrough, which is reflected in the invitation to present the successful final results of the clinical trial to attendees of the annual conference."

The leading causes of facial bone deficiencies that require bone grafting include bone resorption due to inflammatory diseases, bone loss due to aging, trauma, or the removal of tumors and cysts, and congenital and developmental defects. Additionally, bone grafting is often required where there is insufficient jawbone to install dental implants.

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-three approved patents and eight 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, sufficient 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 normal routine within a relatively short period of 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. In these two clinical trials, bone deficiencies were treated using BonoFill™.

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

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. Mesenchymal Stem/Stromal Cells Oral Abstracts | Friday, May 31, 2024
2. According to one-way ANOVA with Holm-Šídák's multiple comparisons test.
3. Karagah et al. Effect of Sinus Floor Augmentation with Platelet-Rich Fibrin Versus Allogeneic Bone Graft on Stability of One-Stage Dental Implants: A Split-Mouth Randomized Clinical Trial. Int J Environ Res Public Health. 2022 Aug 4;19(15):9569. doi: 10.3390/ijerph19159569. PMID: 35954926; PMCID: PMC9367838.
4. For more details, see Section 7.3.2 and Section 15 of Part A of the Company Annual Report for 2023, dated March 29, 2024 (reference 2024-01-034929), which is included in this report by reference.
5. https://doi.org/10.3390%2Fgels9050389; https://doi.org/10.3390%2Fcells10102687