Bonus BioGroup (TASE: BONS) is a clinical-stage Israeli biotechnology company, engaged in research and development of biomedical tissue-engineered and cell therapy products.

Bonus Biogroup is pleased to announce that Jackson Laboratories, USA, in collaboration with University College London Hospital, hosted the Company in a webinar with about 1,000 registrants from around the world, including leaders in the pharmaceutical and biotechnology industry, academia, and medical centers. In the webinar, the Company presented preclinical results demonstrating that MesenCure reduced the life-threatening cytokine release syndrome (CRS) resulting from CAR-T immunotherapy products, which are intended for treating various cancers [1].

Established in 1929 in the United States, Jackson Laboratories (a non-profit organization) is one of the most respected research institutes in the world [2]. Today, it employs about three thousand researchers and employees across three continents: North America, Asia, and Europe. The seminar was recorded by Jackson Labs [3] and is available to stream on YouTube: https://youtu.be/6IN0zk5TYJM.

Companies developing CAR-T therapies activating the immune system against cancer have lost millions of dollars in value and capital investments in the past year alone due to serious safety events related to the side effects of their treatments in clinical trials, including CRS, the most common side effect, and even death [4-6]. This is compounded by expected losses of hundreds of millions of additional dollars for these companies, from lost investments in the initial stages of development of immunotherapy treatments, due to success rates of less than 50% for CAR-T in Phase I [7], which focuses on evaluating the safety and side effects of treatments.

The Company believes that combining MesenCure with CAR-T immunotherapy may reduce the incidence and severity of life-threatening CRS events, thereby expanding the development of new immunotherapies.

In addition, combining MesenCure with CAR-T may yield higher value for companies that develop or market CAR-T products, which is expected to exceed the ten-billion-dollar mark by 2027 [8]. This is because some reimbursement models for immunotherapy treatments are based on the results achieved in each patient (outcomes-based reimbursement) [9, 10], including the safety of the treatments and the management of side effects, such as CRS [11]. Outcome-based reimbursement mechanisms have been developed, among other things, due to the high cost of immunotherapies, which may rise to half a million dollars per patient [12].

The seminar began with a lecture by a representative of University College London Hospital, one of the most respected universities in the world, who described the clinical challenge involved in treating CRS that occurred as a result of CAR-T immunotherapy. This syndrome, characterized by excessive secretion of pro-inflammatory cytokines, develops in about 41% to 78% of cancer patients treated with drugs that harness the immune system against cancer (immunotherapy treatments). About 13% to 27% of patients with CRS might develop multi-system failure and reach a severe or life-threatening condition.

Next, a representative of Jackson Labs reviewed preclinical models that enable reliable prediction of the severity of CRS due to CAR-T immunotherapy and the efficacy of possible treatments to reduce CRS.

Later in the seminar, the Company presented a demonstration of MesenCure efficacy in treating CRS, obtained from an experiment at Jackson Labs in model animals carrying human immune systems bearing blood cancer of human origin. Similar to patients, these model animals develop CRS after treatment with CAR-T immunotherapy against cancer [13]. The human components of this model make it highly predictive of the expected effect of MesenCure treatment on people suffering from CRS.

Following treatment of CRS using the MesenCure, the level of a variety of cytokines in each of the individuals in the experimental group decreased to below the median level measured in the control group, indicating a positive response to treatment at a high rate of at least 50%. The cytokine levels in the experimental group were significantly reduced (p<0.05) compared to those in the control group. It was also found that treating CRS using MesenCure, maintained the effectiveness of the immunotherapy against the tumor. In addition, the safety of MesenCure in treating CRS was demonstrated.

Dr. Tomer Bronshtein, a biotechnology researcher and inventor who serves as Bonus Biogroup's BD Manager, described to the seminar participants the opportunity for immunotherapy developers based on their expected losses due to safety events associated with CRS. In conclusion, Dr. Bronshtein suggested that the Company may consider collaborations with companies that develop CAR-T therapies and with medical centers that implement these therapies to improve their safety and efficacy in cancer patients.

Dr. Shai Meretzki, CEO of Bonus Biogroup, said: "In light of the reality that immunotherapy is becoming a crucial tool in treating cancer, we are proud to offer the possibility of a solution that may further expand the range of applications of these treatments. The impact of Bonus Biogroup on immunotherapy may be realized by combining MesenCure with existing immunotherapies to reduce CRS incidence and severity or by integrating it in the development of new, more effective, and safer immunotherapies. The joint seminar may help bring the Biogroup Bonus message to the most important decision-makers in developing and applying advanced immunotherapies. We thank University College London Hospital for participating in the seminar and Jackson Labs for hosting and marketing it and for their support and trust in Bonus Biogroup."

Bonus Biogroup – the Company

Since its inception, Bonus BioGroup has been involved in cellular medicine and tissue engineering. To date, the Company has two products in clinical development: BonoFill - a viable human bone graft for the regeneration and reconstruction of bone tissue, and MesenCure - a cell therapy for acute inflammation, including acute respiratory distress in severe COVID patients. In addition, the Company has a variety of other technologies and products in preclinical development.

The main building block utilized to produce BonoFill bone graft is mesenchymal cells extracted from the patient's adipose tissue. Alongside the development of BonoFill, the Company developed a cell therapy based on mesenchymal cells isolated from adipose tissue of healthy donors that are professionalized to enhance their ability to counteract acute inflammation, including cytokine storms prevalent in COVID patients and other diseases. These efforts led to the development of the professionalized cell therapy product MesenCure.

In light of the Company's demonstration of the efficacy of MesenCure in treating severe COVID patients, the Company has expanded its efforts to examine the potential of MesenCure to treat other conditions involving systemic inflammations and multi-organ injuries. Such conditions include CRS caused by biological therapies or hematopoietic stem cell transplantation. In developing its drug products, Bonus BioGroup uses unique technologies and knowledge developed in-house. The Company's rich intellectual property, including seven families of patents and patent applications, encompasses thirty-eight (38) approved patents and seventeen (17) patent applications in many countries worldwide.

BonoFill – a viable human bone graft

Bone deficiencies can result from various causes, including aging, infections, arthritis accompanied by bone loss, trauma (accident or fall), and tumors. Bonus Biogroup develops viable human bone grafts based on cells sampled from the patient (autologous tissue). Growing bone grafts outside the patient's body allow their on-demand manufacturing to provide effective bone grafts for various medical conditions involving bone loss, including oral and maxillofacial surgery, cranial surgery, orthopedic surgery, and plastic surgery.

MesenCure cell therapy

The cell therapy MesenCure consists of professionalized mesenchymal cells. MesenCure is designed to treat acute inflammations and subsequent conditions. These conditions may include life-threatening pneumonia and respiratory distress, whether caused by the coronavirus, any other virus or bacterial infection, or whether caused by other conditions underlined by a hyperactive immune system. The efficacy of MesenCure, as demonstrated in the clinical trial for treating severe COVID patients, is presumably attributed to the professionalization of the mesenchymal cells comprising MesenCure. This professionalization enhances the cells' natural ability to attenuate the inflammation and cytokine storm, which, without MesenCure, could lead to life-threatening multi-organ damage. Furthermore, the cells comprising the drug product MesenCure affect inflammation and cytokine storm through various mechanisms. Therefore, MesenCure may have a broader and more robust effect on diverse populations of patients than drugs acting via a single mechanism.

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)

[1] For details, see the Immediate Report dated April 27, 2022 (2022-01-042405), included herein as a reference. https://www.jax.org/about-us/fast-facts

[2] The webinar recording was sent to the company, which completed its review by April 9, 2023.

[3] Bellicum's GoCAR-Ts crash out of clinic over safety signal, sparking search for strategic alternatives, https://www.fiercebiotech.com/biotech/bellicums-gocar-ts-crash-out-clinic-over-safety-signal-sparking-search-strategic

[4] Astellas, Tmunity, Underscore Rocky Terrain of CAR-T and Gene Therapies,

[5] https://www.biospace.com/article/the-rocky-history-of-car-t-and-gene-therapies/

[6] Bayer pulls plug on $670M CAR-T cell therapy pact with Atara in wake of patient death, https://www.fiercebiotech.com/biotech/bayer-pulls-plug-670m-car-t-cell-therapy-pact-atara-wake-patient-death

[7] Clinical Development Success Rates and Contributing Factors 2011–2020. BIO | QLS Advisors | Informa UK Ltd 2021 https://go.bio.org/rs/490-EHZ-999/images/ClinicalDevelopmentSuccessRates2011_2020.pdf

[8] https://www.marketresearchfuture.com/reports/car-t-cell-therapy-market-8102

[9] The use of innovative payment mechanisms for gene therapies in Europe and the USA, https://doi.org/10.2217/rme-2020-0169

[10] Novartis’ CAR T Reimbursement Strategy Finds Sweet Spot Between Value and Price, https://www.biospace.com/article/novartis-car-t-reimbursement-strategy-finds-sweet-spot-between-value-and-price/

[11] Outcomes-based reimbursement for gene therapies in practice: the experience of recently launched CAR-T cell therapies in major European countries, https://doi.org/10.1080%2F20016689.2020.1715536

[12] Concern Rises Over $475,000 Price Tag for Breakthrough Cancer Treatment, https://www.healthline.com/health-news/concern-rises-over-price-tag-for-breakthrough-cancer-treatment#Kymriahs-breakthrough

[13] https://www.jax.org/jax-mice-and-services/in-vivo-pharmacology/safety-and-efficacy-assessment