CTX cell lineStroke Disability
Current progress: Phase II
CTX cell lineCritical Limb Ischaemia
Current progress: Phase 1
hRPC lineRetinitis Pigmentosa
Current progress: Phase II
hRPC lineCone Rod Dystrophy
Current progress: Pre-clinical
CTX-derived exosomesIn evaluation
Current progress: Pre-clinical
Using our unique and scaleable stem cell technologies, we have created a pipeline of commercially focused stem cell therapy candidates addressing significant areas of unmet medical need. These therapeutic candidates are based around two core stem cell assets, our CTX neural cell line and our human retinal progenitor cells (hRPC). Our exosome platform is yielding encouraging early pre-clinical data across a range of potential indications which are being investigated further.
We have used our cell expansion and screening technologies to develop “off-the-shelf” stem cell therapies for serious conditions such as stroke where the patient populations are significant and few if any alternative treatments exist. Unlike conventional drug treatments which typically address the symptoms of disease, the potential of stem cell treatments such as ours is to address the underlying causes of the target disease. Our stem cell treatments have been shown in pre-clinical testing to stimulate natural repair mechanisms in the organs affected by the disease in question, leading to a reduction in the associated functional impairments.
Our lead CTX cell therapy candidate is a therapy for the treatment of patients left disabled by the effects of a stroke. Our second application for the CTX cells is for the treatment of critical limb ischaemia. Both treatments are currently in clinical development. The characteristics of the CTX cell line give ReNeuron some distinct technical and competitive advantages. The CTX cell line has been taken through a full manufacturing scale-up and quality-testing process. As such, it represents a standardised, clinical and commercial-grade cell therapy product capable of treating all eligible patients presenting with the diseases targeted, without the need for additional immunosuppressive drug treatments. There will be no need to re-derive and test new cell lines for subsequent clinical trials or for the market – all such cells can simply be expanded from the existing banked and tested product.
The clinical trials of our CTX stem cell therapy candidates for stroke and critical limb ischaemia utilise a cryopreserved formulation of the CTX stem cell line, designated CTXcryo. We have generated data demonstrating the equivalence of CTXcryo drug product to the original non-cryopreserved formulation. CTXcryo will provide the business with major commercial and competitive advantages in terms of the availability of a genuine off-the-shelf cell-based treatment with a competitive cost of goods and a shelf life enabling shipping to, and storage at, clinical sites on a global basis.
Pre-clinical and clinical results from our technologies and stem cell products have been published extensively in peer-reviewed scientific journals (please refer to the publications section). We have recently announced positive data from the PISCES II Phase II clinical trial of our CTX cell therapy candidate for stroke disability. Safety and efficacy data from this study will be presented at forthcoming stroke and rehabilitation medical conferences and published in due course.
Human retinal progenitor cells (hRPC)
Human retinal progenitor cells are cells that differentiate into components of the retina. These cells are used allogeneically, with cells from a single source being administered to multiple patients, and are grown using a patented low-oxygen cell expansion technology licensed from the Schepens Eye Research Institute at Harvard Medical School. Through our collaboration with Schepens we have developed the ability to scale up the manufacturing of the hRPCs. Using this technology, we have established a GMP-compliant hRPC cell bank to provide future drug product.
We have received regulatory approval from the US Food and Drug Administration (FDA) to commence a Phase I/II clinical trial in the US with our hRPC therapy candidate for retinitis pigmentosa (RP). This study marks the initiation of clinical trial activity in the US with our therapeutic programmes. Recruitment and treatment of the first and second dose cohort in a total of six patients has been completed.
ReNeuron is also intending to expand its clinical programme to another retinal disorder, Cone Rod Dystrophy with a Phase II trial to be run alongside the RP trial.
Exosomes are nanoparticles, released by cells, and contain a number of active proteins and micro RNAs. They are believed to play a key role in cell-to-cell communication, modulate cellular immunity and promote the activation of regenerative or repair programmes in diseased or injured cells. Our CTX cells release large amounts of exosomes when grown in the laboratory enabling us to purify and characterise them. These exosomes have been tested at differing concentrations in a range of early in vitro pre-clinical disease models with positive results. We aim to use the CTX technology and exosome platform to expand our pipeline. We have filed a number of patents around composition, characterisation, manufacturing and therapeutic uses of the exosome platform. We are exploring the potential of our CTX cell-derived exosome platform and its role in targeting multiple indications. Data produced to date from in vivo pre-clinical studies indicate a potential therapeutic benefit in wound healing, glioma and ophthalmology.
We have used our unique stem cell technologies to develop cell-based therapies for significant disease conditions where the cells can be readily administered “off-the-shelf” to any eligible patient without the need for additional drug treatments.
ReNeuron’s stem cell products are allogeneic, enabling the treatment of many patients from the same cell bank in an off-the-shelf manner. Our programmes have been built around our unique and highly efficient stem cell expansion technologies enabling, from a single tissue sample, the growth of selected human stem cells into banks of quality-assured stem cell lines. ReNeuron has developed a product variant that can be shipped to clinical sites and stored there in a cryopreserved form. These developments will provide us with major commercial and competitive advantages in terms of the availability of a genuine off-the-shelf, low cost-of-goods cell-based treatment with a shelf life enabling shipping to, and storage at, clinical sites on a global basis.
CTX is an immortalised neural cell line which has been generated using our proprietary cell expansion and cell selection technology and then taken through a full manufacturing scale-up and quality-testing process. Because CTX is derived from a single donor, there should be complete consistency between cell banks and no risk of the variability which can arise when multiple donors are needed for cell supply. All cells used in CTX-based treatments can simply be expanded from the existing banked and tested product. There will therefore be no need to re-derive and test new CTX cell lines for subsequent clinical trials or for the market.
We have developed a proprietary, cryopreserved variant of our lead CTX stem cell line enabling an extended shelf-life, (designated CTXcryo), which will be deployed in all current and future CTX-based clinical trials and for eventual in-market use.
Human retinal progenitor cells
hRPCs are cells that differentiate into components of the retina. These cells are used allogeneically and are grown using a patented low-oxygen cell expansion technology licensed from the Schepens Eye Research Institute at Harvard Medical School. Through our collaboration with Schepens we have developed the ability to scale up manufacturing of hRPCs using this technology and have established GMP-compliant hRPC cell banks to provide future drug product.
We have also developed a cryopreserved variant of our hRPCs enabling an extended shelf-life which will be deployed in all current and future clinical trials for retinal disorders and for eventual in-market use.
Cells often communicate via exosomes, nano-sized packages of information released by the cell for absorption by other cells in close proximity. These packages of information contain a variety of proteins, genetic material and other cargo which have the ability to induce functional changes in recipient cells. Under certain conditions, exosomes produced by stem cells initiate repair and regeneration. However depending on the state of the cell and its environmental stimuli, stem cells have the ability to communicate different information and induce different functional changes. We have therefore developed a technology by which a permanent stem cell line, already in clinical trials as a stem cell therapy, can be cultured under different environments to produce therapy specific agents and can be harvested at a commercially relevant scale. The ability to produce a commercially valuable therapeutic product from stem cell derived exosomes demands a standardised stem cell producer line appropriately sourced and isolated, manufactured to GMP, grown in serum-free conditions and (ideally) already having demonstrated patient safety. In the stem cell field, our CTX cell line uniquely meets all these conditions.