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 CTXneural 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 that typically address the symptoms of disease, the potential of stem cell treatments such as ours, address the underlying causes and/or effects 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 treatment for patients left disabled by the effects of a stroke. The characteristics of the CTX cell line provide 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 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 announced positive data from the Phase II clinical trial (PISCES II) of our CTX cell therapy candidate for stroke disability at the 2018 International Stroke Conference. Safety and efficacy data presented at the conference not only showed CTX therapy was safe and well-tolerated, but produced clinically meaningful and sustained improvement in the level of disability and dependence as well as motor function in disabled stroke patients.
Another potential application for the CTX cells is for the treatment of critical limb ischaemia (CLI). CLI is the severe ‘end stage’ manifestation of peripheral arterial disease and is caused by chronic lack of blood supply to the leg due to obstruction of blood flow in the peripheral arteries. The condition is characterised by pain at rest and lesions of the leg. We have completed recruitment in a Phase I clinical trial of our CTX cell therapy in limb ischaemia patients, with no significant adverse events reported post administration of the CTX cells via intramuscular injections but then made the decision to put the CLI programme is on hold in order to focus on the significant opportunity presented by our stroke disability programme and our expanded retinal disease programmes.
Human retinal progenitor cells (hRPC)
Human retinal progenitor cells are cells that differentiate into components of the retina. These hRPC cells are used allogeneically, which means cells from a single source are capable of treating multiple patients. Through our long-standing collaboration with the Schepens Eye Research Unit at Harvard Medical School, we have developed the ability to scale up the manufacturing of the hRPCs using a patented low-oxygen cell expansion technology. Further, using this technology, we have established a GMP-compliant hRPC cell bank to provide future drug product.
Currently, our hRPC cell therapy candidate is being evaluated in an ongoing phase I/IIa clinical trial in the US in subjects with a blindness-causing inherited retinal disease, retinitis pigmentosa (RP). This open-label dose escalation study is being undertaken at the Massachussets Eye and Ear Infirmary in Boston, MA, to evaluate the safety, tolerability, and preliminary efficacy in subjects with advanced RP. We expect short-term read-outs from this phase I/IIa trial in the first half of 2019, with a phase IIb study commencing soon thereafter.
We are also intending to expand testing of our hRPC cell therapy candidate into subjects with another retinal disorder, cone-rod dystrophy (CRD) in a phase II trial that would run in parallel with the phase IIb trial in RP.
Exosomes are nanoparticles, released by cells, and contain a number of active proteins and micro RNAs, which are short non-coding RNAs capable of regulating gene expression, that are believed to play a key role in cell-to-cell communication. A growing body of evidence demonstrates that exosomes can modulate cellular immunity and/or 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.
ExoPr0, our first CTX-derived exosome therapeutic candidate, has demonstrated potential as both a novel therapeutic candidate as well as a drug delivery vehicle in established pre-clinical disease models. We intend to commence clinical development activities with Exopr0 in 2019, as previously indicated.
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.
We possess unique and highly efficient stem cell expansion technologies that can derive banks of quality-assured stem cell lines from single tissue samples. Consequently, our programmes have been built around this capability to produce stem cell products that are allogeneic – capable of treating many patients with one product in an off-the-shelf manner. Further, we have developed product variants that can be stored in a cryopreserved form and that are capable of shipment to clinical sites around the world. Such developments provide us with several major commercial and competitive advantages in terms of availability of such a genuine, effective, stable, and readily available therapy for a wide range of current clinical indications with significant unmet medical needs.
CTX is an immortalised neural cell line generated using our proprietary cell expansion and cell selection technology. Once selected, the CTX cell line was taken through a full manufacturing scale-up and quality-testing process to demonstrate complete consistency between batches with no risk of product variability. This assures that all cells used in CTX-based treatments can simply be expanded from the existing banked and tested cell products. Further, there will be no need to re-derive and/or test new CTX cell lines for subsequent clinical trials, and ultimately 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
We have developed a manufacturing process for the isolation and scaled expansion of hRPCs using a defined culture formulation and environment to enable GMP-grade drug product that retain stable hRPC genotype and phenotype. This hRPC platform represents a unique approach to treat degenerative retinal diseases by producing an allogeneic, off the shelf product, capable of protecting host photoreceptor cells and/or replacing lost photoreceptors. Furthermore, through our long-standing collaboration with the Schepens Eye Research Institute at Harvard Medical School in Boston, MA, we have established GMP-compliant hRPC cell banks to provide future allogeneic drug product.
We have also developed a proprietary cryopreserved variant of our hRPC cell therapy drug candidate, which provides an extended shelf-life that can be deployed in our current and future clinical trials, and for eventual utility in the market.
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 developed a technological process enabling us to produce exosomes from a cell line, such as our proprietary CTX neural stem cell line (described above) under different culture conditions, which can in turn 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.