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Amsterdam, Netherlands – November 7, 2018
Esperite biotechnology company (Euronext: ESP), The Cell Factory, has been granted the patent for the use of extracellular vesicles (EVs) in the treatment of acute and chronic inflammatory and autoimmune diseases in Canada. The Cell Factory has already protected the intellectual property of the use of immunotherapeutic drugs for electric vehicles in Europe and China. The patent family EV covers both first-generation drugs and second-generation anti-inflammatories and immunosuppressants. Currently, The Cell Factory is developing four drug candidates for electric vehicles: the CF-MEV-107 for the treatment of Crohn's disease, the CF-MEV-117 for the treatment of drug-resistant epilepsy, CF -MEV-126 for the treatment of stroke and MEV-132 for the treatment of bronchopulmonary dysplasia.
The Cell Factory, an Esperite Group Company, holds the full rights of a broad family of international patents allowing the use of MSC-derived extracellular vesicles (ESVs) in the treatment of autoimmune, chronic and acute inflammatory diseases . Patents have already been granted in Europe, China and recently in Canada. The Cell Factory develops biological drugs for electric vehicles for multiple indications in immunology, neurology, gastroenterology and respiratory diseases. The main products are CF-MEV-107 for the treatment of Crohn's disease (pharmaco-resistant peribad fistulas), CF-MEV-117 for the treatment of drug-resistant epilepsy in children , CF-MEV-126 for the treatment of acute stroke-induced inflammation and CF-MEV-132 for the treatment of bronchopulmonary dysplasia in prematurely born infants.
Cell Factory has developed an exclusive technology for large-scale production of ultra-pure VE according to GMP guidelines, using a defined support without xenos or serum, without the use of animal components or human platelet lysates . stage of the production process. Production is carried out in a closed, scalable bioreactor, including downstream processing based on the integrated sequential filtration system. The Cell Factory has set new standards in drag production, in which electric vehicles continuously secrete through extended MSCs, allowing multiple harvests during a production cycle. This approach significantly reduces the risk of contamination, production time, staff, the use of GMP Labs and the cost of products. Indeed, the production of a single dose of EV is now up to 10 times less expensive than the dose equivalent of allogeneic MSCs, and these costs will be further reduced in the future. A closed and semi-automated production system, fully defined culture media and an ISO / GLP based quality badurance system facilitate the transfer of technology as planned in collaboration with international partners. Electric vehicles will soon become a viable alternative to many allogeneic stem cell therapies and will be able to target niche indications that go beyond the current cellular therapies, namely immediate anti-inflammatory interventions in neurology.
VE, including exosomes are natural nanoscale biological particles secreted by different cell types in vivo and in vitro. They contain proteins, growth factors, mRNA and other molecules responsible for the therapeutic effect of MSCs. In addition, electric vehicles have several advantages over allogeneic MSCs: production costs up to 10 times lower, no risk of uncontrolled proliferation and differentiation, risk of lower immune response, penetration across the blood-brain barrier -Encephalic and easy and safe delivery in different tissues and organs in vivo. The high stability facilitates the transport and storage of "ready-to-use" products.
Mode of action The Cell Factory's drug candidates focus on immunomodulating and suppressing innate and acquired immune systems. In collaboration with our academic and clinical partners, we have demonstrated that CF-MEV drug candidates inhibit the proliferation, differentiation, and production of B-cell antibodies. CF-MEVs induce cell apoptosis Conventional T activated and induce regulatory T cells increasing the ratio Treg / Teff. The co-culture of VE (CF-MEV drug candidates) with PBMCs resulted in a significant reduction in the number of NK cells in degranulation (CD56 + CD107a +). PBV exposure of K562-stimulated PBMCs induced a significant reduction in CD56 + IFN-y + cells compared to co-culture with parental MSCs. (references: 1,2,3,4).
In vitro data has been confirmed in several in vivo models. For example, electric vehicles have been injected intraperitoneally into a murine model of DSS-induced ulcerative colitis. The treatment of EEVs showed an improved activity index and a less severe reduction in colon length. RT-PCR of colon tissue showed a significant reduction in IL-1B and COX2 in animals treated with EV virus. A subsequent in vivo study demonstrated an increased anti-inflammatory effect of second-generation EV annexin. (references: 5.6).
Another in vivo model of bronchopulmonary dysplasia (BPD) induced by hyperoxia in rats was used to demonstrate the anti-inflammatory effect and protective effect of VE on the lungs. Electric vehicles have been injected intratracheally to demonstrate the effectiveness of this non-invasive method. VE-treated animals showed a significant increase in total cell count and a decrease in mean alveolar volume compared with simulated animals. The treatment of electric vehicles prevented the increase of the medial thickness of the small pulmonary vessels. (references: 7,8).
The cell factory is looking for investors and opportunities for research collaboration to further develop drugs and EV manufacturing technologies.
CF-MEV-107: Crohn's Disease
Inflammatory bowel disease (IBD) encompbades a wide range of diseases affecting the gastrointestinal tract. The most common are Crohn's disease and ulcerative colitis. IBD is a chronic and often recurrent inflammation of the intestines, the cause of which is unknown and limited treatment options. In the most severe cases of Crohn's disease, patients suffer from peribad fistulas that significantly affect the regular activity and may lead to complications such as an increased risk of cancer and systemic inflammation involving the life threatening. In Europe, the current treatment of Crohn's disease is focused on anti-TNF-alpha therapy, while the anti-integrin biological agents are an alternative available in the United States. Peribad fistulas often do not respond to these systemic treatments. Several clinical trials are underway to target peribad fistulas using allogeneic mesenchymal stem cells (MSCs) with very positive results.
Epidemiology and market size (CF-MEV-107). ITNs affect about 0.5% of the population in Western countries and this number is growing rapidly. Crohn's disease has more than 0.5 million people in the United States and more than one million in Europe, and more than 10 new cases per 100,000 people each year. The annual cost of treatment exceeds $ 5 billion in the United States alone (CDC). Up to 50% of Crohn's patients have difficult to treat peribad fistulas and 75% require surgery (according to the CDC), which estimates the potential size of the CF-MEV-107 market .
CF-MEV-132: Bronchopulmonary dysplasia
Bronchopulmonary Dysplasia (BPD) is a serious disease of the respiratory system that occurs in children born prematurely (less than 30 weeks of gestation). The lungs of babies with DBP are not well developed and patients need oxygen therapy and intensive care immediately after birth. DBP has serious long-term consequences for patients, and the disease is the leading cause of death in the first month of life in developed countries.
The current treatment for DBP is focused on mechanical ventilation and oxygen therapy immediately after birth and surfactant supplementation. Mechanical ventilation and oxygen treatment result in hyperoxia and severe inflammation that can damage the lungs. As a result, inflammation impedes lung development, a significant reduction in lung surface area, a lower number of alveoli and impaired lung vasculature. Effectively, the lungs can not provide enough air to the body, resulting in impaired development and metabolic functions.
Our approach is focused on the use of the drug candidate CF-MEV-132 (extracellular vesicles derived from mesenchymal stem cells) to inhibit pulmonary inflammation and improve the regeneration process in premature babies with DBP. CF-MEV-132 treatment will complement life-saving therapies, namely. oxygen treatment, ventilation and surfactant treatment.
Epidemiology and market size (CF-MEV-132). Bronchopulmonary dysplasia occurs in app. 30% of children born before term (less than 30 weeks of gestation). DBP incidents are correlated with low gestational age at birth and more than 90% of extremely immature babies are affected by the disease. The costs badociated with BPD are considerable and extend throughout the life of patients with the disease. It has been estimated that the average time of hospitalization of a premature infant with BPD is on average 94 days and that the annual cost per patient ranges from 400,000 USD to over 700,000 USD (reference: 9 ).
CF-MEV-117: Acute and Chronic Drug-Resistant Epilepsy
The Cell Factory is developing a drug candidate MSC-EV (CF-MEV-117) for the treatment of persistent epilepsy, both acute and chronic, of the drug. Epilepsy has significant adverse effects on the quality of life and can result in secondary brain damage. The etiology of the disease may be different: stroke, brain trauma and neuroinflammation.
Epidemiology and market size (CF-MEV-117). According to the CDC, epilepsy is one of the most common brain diseases and affects about 1 child over 100 years old under 17 years of age. Seizure severity is variable and antiepileptic drugs are effective in only about two-thirds of patients. The CDC estimates that the annual costs related to epilepsy exceed 15 billion USD in the United States alone.
CF-MEV-126: Stroke
Stroke is one of the most devastating and incurable diseases. Brain damage following a stroke is correlated with inflammation, which plays a key role in the brain's response to a stroke. Next-generation EV drugs contain additional genetic cargo (miRNA) or have bound surface molecules (ie annexin V) to enhance their anti-inflammatory and neuroprotective properties.
The stability and small size of electric vehicles will allow CF-MEV-126 to be used outside the hospital immediately after stroke, reducing brain damage and improving the recovery process . Another advantage of electric vehicles, compared to MSCs and other cell therapies, is their penetration across the blood-brain barrier, which is crucial for any effective treatment targeting the central nervous system.
Epidemiology and market size (CF-MEV-126). Central nervous system diseases are among the most devastating for patients and their loved ones. Neurological disorders lead to significant additional costs related to hospitalization and re-education, often eliminating patients and their loved ones from the labor market.
Stroke is the second leading cause of disability in Europe and 10 to 35% of these patients die within 28 to 30 days. The current treatment of stroke is very limited and focused on general care and rehabilitation. In the 27 EU countries, the annual cost of stroke is estimated at 27 billion euros (WHO). The number of strokes in Europe is expected to increase from 1.1 million in 2000 to 1.5 million per year by 2025 due to the aging of the population.
References:
1. Budoni, M., Fierabracci, A., Luciano, R., Petrini, S., Ciommo, V. Di, Muraca, M., (2013). The immunosuppressive effect of mesenchymal stromal cells on B lymphocytes is mediated by membrane vesicles. Cell Transplantation, 22 (2), 369-379.
2. Del Fattore, A., Luciano, R., Pascucci, L., Goffredo, B.M., Giorda, E., Scapaticci, M., (2015). Immune-regulatory effects of extracellular vesicles derived from mesenchymal stem cells on T cells. Cell transplantation, 24 (12), 2615-27.
3) Alessandra Fierabracci, Raffaele Simeoli, Valeria La Marca, Kelly Van Wemmel, Marijke Buvé, Silvia Balosso, Laura Papetti, Maurizio Muraca, Annamaria Vezzani, Federico Vigevano and Marcin Jurga; Activity tests for the evaluation of clinical grade MSC-EV anti-inflammatory properties for the treatment of drug-resistant epilepsy in children; ISEV meeting 2018.
4. Valeria La Marca, Raffaele Simeoli, Marcin Jurga, Kelly Van Wemmel, Marijke Buvé, Federico Vigevano and Alessandra Fierabracci; Immunomodulatory activity of extracellular vesicles derived from clinical grade mesenchymal stem cells on human NK cell activities; ISEV meeting 2018.
5. Del Fattore A, Luciano R, Fierabracci A, Muraca M., M. M. (2014). Microparticles derived from mesenchymal stem / stromal cells exhibit anti-inflammatory activity in an animal model of ulcerative colitis. Cytotherapy, 16 (4), S25.
6. Anna Maria Tolomeo, Martina Piccoli, Michela Pozzobon, Michele Grbadi, University of Padua, Italy, Chiara Franzin, Marcin Jurga, Alessandra Fierabracci, Melania Scarpa, Andrea Porzionato, Ignazio Castagliuolo, Maurizio Muraca; Extracellular vesicles (EV) linked to annexin a5 (An5) from mesenchymal stromal cells (MSCs) show enhanced and specific anti-inflammatory effects; ISEV meeting 2018.
7. Patrizia Zaramella, Andrea Porzionato, Arben Dedja, Chiara Franzin, Diego Guidolin, Raffaele De Caro, Marcin Jurga, Eugenio Baraldi and Maurizio Murac; Extracellular vesicles (EVs) derived from intratracheal mesenchymal stromal / stromal cells significantly improve morphological and biochemical parameters in an animal model of bronchopulmonary dysplasia; ISEV meeting 2018.
8. Porzionato A, Zaramella P, A Dedja, D Guidolin, K Van Wemmel, V Macchi, M Jurga, G Perilongo, R Caro, E Baraldi and Muraca; Intratracheal administration of extracellular vesicles derived from mesenchymal stem cells reduces lung injury in a bronchopulmonary dysplasia model in the rat. Am J Physiol Pulmonary Cell Mol Physiol. October 4, 2018 [Epub ahead of print]9. María Álvarez Fuente, 2018, Infant bronchopulmonary dysplasia and its economic impact (source: www.sciencetrends.com).
About ESPERITE
ESPERITE is a diversified global biotechnology group leader in regenerative and precision medicine. Founded in 2000, the holding group is headquartered in the Netherlands, is listed on Euronext Amsterdam and Paris and operates in more than 30 countries.
ESPERITE transforms the power of advanced technologies and scientific breakthroughs into high quality products that bring the future of the drug to customers at an affordable price.
THE CELL FACTORY is a biotechnology company, a grant from the Esperite Group, developing the highest quality therapeutic tools for affordable regenerative medicine. The Cell Factory focuses on the development, clinical translation and commercialization of biologic drugs and autologous extracellular stem cell (EV) therapeutics. The goal of Cell Factory is to become a leader in the development and production of extracellular vesicle drugs in the treatment of various indications, such as inflammatory diseases, graft-versus-host disease (GvHD) after Organ and solid cell transplants, arthritis, multiple sclerosis, cystic fibrosis, stroke to brain and spinal cord trauma, newborn encephalopathy and type 1 diabetes, among others.
To find out more about the Esperite Group, or to book an interview with Frédéric Amar, CEO: +31 575 548 998 – [email protected] or visit the websites www.esperite.com and www.cell-factory.com.
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This press release contains inside information as referred to in Article 7 (1) of Regulation (EU) No 596/2014 (Market Abuse Regulation).
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