The Cell Factory is manufacturing clinical-grade EVs and exosomes, which can be used in multiple patent-protected applications in treatment of acute and chronic inflammations.
EVs’ therapeutic use in treatment of unmet medical needs in neurology will target a niche of untreatable-yet conditions like drug-resistant epilepsy and Crohn’s disease perianal fistulas.
A possibility of immediate use of EVs would be the key competitive advantage over the stem cell therapies. The other advantages of EVs are:
All these features make the EVs a vital alternative for allogenic stem cell therapies. It is expected that most of the allogenic MSC therapies will be replaced by MSC-derived extracellular vesicles in a near future.
EVs are viable alternative for allogenic mesenchymal stem cells (MSC) products. In most applications, the allogenic MSCs and EVs are injecting for an immediate short-term immunomodulatory activity in vivo. EVs are nanometer-size vesicles, which are secreted naturally by MSC. Their properties are similar to the origin MSC but in addition, EVs are more stable, easier to store and transport, safer, and cheaper in large-scale production. Therefore, EVs are offering new opportunities for development of safe and easy accessible therapeutics for treatment of unmet clinical needs i.e. Crohn’s disease, drug-resistant epilepsy in children. EVs are also very promising candidates for an immediate intervention in treatment of stroke, acute injuries of brain and spinal cord. In addition, EVs are offering better and cheaper alternative to the existing therapies using allogeneic MSCs i.e. arthritis, wound healing, diabetic ulcer etc.
Extracellular vesicles (EVs) and exosomes are nanometer-size particles secreted by different types of cells in vivo and in vitro. They contain proteins, growth factors, mRNA and other molecules encapsulated in a lipid sphere. All these factors are responsible for therapeutic effect of EVs. EVs have similar properties to the origin cells i.e. MSC, in terms of therapeutic activity. On the other hand EVs do not have the key disadvantages of stem cells i.e. low stability, viability issues, tumor and rejection risk. EVs can be easily and safely deliver into different tissues and organs in vivo. EVs are even less immunogenic when comparing to MSC what reduces the immune response and making them a universal vector for drug delivery. EVs’ high stability allows for easy transport and storage of the “ready-to-use” products. EVs can be cryopreserved in a very small volume without cryoprotectants, and can be used immediately after thawing without washing, what is very important for routine use at hospitals and immediate interventions, even outside the hospital. EVs’ properties will allow non-invasive routes of administration and application by the patients at home. All these features make the EVs a vital alternative for allogenic stem cell therapies in the near future.
EVs clinical projects:
- EVs use in treatment of acute and chronic drug-resistant epilepsy
The Cell Factory, a biotech business unit of Esperite group sponsors an international consortium of the leading teams in pediatric regenerative medicine to bring EVs technology to the clinic with niche application in treatment of untreatable-yet acute and chronic drug-resistant epilepsy.
Epilepsy is one of the most common brain diseases affecting about 1 in 100 children under 17-year old according to CDC. Epilepsy carries significant detrimental effects on the quality of life and can lead to a secondary brain damage. The disease can have different etiology, including stroke, brain trauma, and neuro-inflammation. Severity of the seizures is variable and the antiepileptic drugs are effective only in about 2/3 of the patients. CDC estimated annual costs related to epilepsy exceeds 15 billion USD in the United States alone.
- EVs use in treatment of inflammatory bowel disease
Esperite’s business unit The Cell Factory, in collaboration with Women’s and Children’s Health Department of the University of Padua and the Padua University Hospital have started a translational project on extracellular vesicles (including exosomes) first in man use in treatment of Crohn’s disease perianal fistulas.
Inflammatory bowel disease (IBD) encompasses a spectrum of diseases affecting gastrointestinal tract. The most common are Crohn’s disease and ulcerative colitis. IBD is a chronic and often recurring inflammation of the intestines with unknown cause and limited treatment options. In the most severe cases of Crohn’s disease, the patients suffer from perianal fistulas that significantly affects normal activity and may lead to complications such an increased risk of cancer and life-threating systemic inflammation. IBD affects approximately 0.5% of the western countries population and this number is rapidly increasing. There are over 0.5 million people in the US and over 1 million in Europe with Crohn’s disease, with over 10 new cases per 100.000 people every year. The annual cost of therapy exceeds 5 billion USD in the US only (CDC). Up to 50% of Crohn’s disease patients are affected with difficult to treat perianal fistulas, and 75% require surgery (CDC).
In Europe current treatment of Crohn’s disease is focused on anti-TNF-alpha therapy whereas anti-integrin biologics are an alternative available in the US. Unfortunately, perianal fistulas often do not respond to these systemic treatments. Several clinical trials are ongoing to target perianal fistulas using allogenic mesenchymal stem cells (MSCs) with very positive results.
Our approach is focused on using extracellular vesicles (including exosomes) derived from mesenchymal stem cells (MSCs) for the first time in the treatment of inflammation responsible for Crohn’s disease perianal fistulas.
The Cell Factory is developing new therapies using autologous stem cells derived from cord blood and cord tissue stored at Esperite’s CryoSave biobank.
The indications listed above can be divided into following categories:
Autologous stem cells are targeted to the niche applications of advanced regenerative medicinal products where the transplanted cells are expected to replace a damaged organ or tissue. These applications require using HLA-matched cells to reduce risk of a transplant rejection. Autologous perinatal stem cells derived from cord blood and cord tissue stored in Esperite’s biobank CryoSave, offer best quality starting material for cell reprogramming and manufacturing of advanced cell therapy medicinal products. The Cell Factory in collaboration with CryoSave are developing new applications for autologus perinatal stem cells. The key projecs are focused on treatments of the unmet medical needs in pediatric neurology i.e. Cerebral Palsy.
Autologous perinatal stem cells can be stored in private biobanks i.e. Esperite’s CryoSave during the lifetime of the donor. Esperite’s biobank CryoSave, one of the world’s largest stem cell bank has over 300.000 samples of cord blood and cord tissue stored. This gives our company an opportunity to develop new personalized therapies dedicated for our clients. Emerging new technologies in cell reprogramming and in tissue engineering are providing the missing tools for using autologous perinatal cells.
Autologous stem cells clinical project:
MSCs and Cord Blood stem cells use in treatment of cerebral palsy.
Our clinical trial aims to demonstrate safety and preliminary efficacy of sequential intravenous infusion of the ex vivo expanded MSC and cord blood stem cells in treatment of Cerebral Palsy. The study will use, for the first time in clinical research, autologous MSC derived from cryopreserved cord tissue.
Cerebral Palsy is a devastating disease diagnosed in 1 per 326 children according to CDC, with no available treatment. 17 Million People worldwide live affected by cerebral Palsy (CPIRF).
26 billion USD is spending every year to accommodate the life of these patients in the US (WHO).
The Cell Factory produces highest quality stem cells and EVs according to GLP/GMP guidelines, using proprietary technology for expansion of MSC in serum-free defined media with no use of animal-derived components at any stage. The Cell Factory controls the entire production process: procurement of starting materials (international), transport (international), processing, storage, cell extraction and expansion, EVs production and purification, final product preparation and release (international).
The Cell Factory production process (GLP/GMP):
R&D (GLP) and bioproduction (GMP), including a quality control, are performed by qualified personnel in house. All of the work is done in built-for-purpose facilities in Belgium: GLP labs and 12 GMP certified clean rooms (class B) dedicated for cell processing, cryopreservation, R&D and bioproduction.
Product design process follows a comprehensive analysis of scientific, medical, regulatory and commercial aspects. Production process is designed according to GLP/GMP standards and follows the international guidelines dedicated for production and clinical use of medicinal products i.e. ATMP, biologicals. One of the key objectives of The Cell Factory is using the best quality raw materials and ancillary products in R&D and in production process.
EVs can be produced at lease 10x more efficiently and cheaper when comparing to MSC equivalent.
Stem cells expansion is performed in the most efficient culture systems using 3D microcarrier beads. The Cell Factory’s proprietary closed cell culture system produces high purity EVs using enzyme-free cell passage technology and proprietary sequential filtration system for EVs extraction and purification. This approach is possible due a high purity and quality of MSC cultures. Effectively our method of the EVs purification is simplified what reduces a time and risk of EVs damage and contamination. In addition, our closed system can be automated and the production process can be performed in a lower sterility grade lab environment. This has a significant impact on EVs’ low production costs, low footprint and process scalability.