hRPC lineRetinitis Pigmentosa
Current progress: Phase II
CTX cell lineStroke Disability
Current progress: Phase II
ReNeuron has two Phase 2 stem cell therapy candidates, addressing significant areas of unmet medical need, that are available for out-licence outside of China. These therapeutic candidates are based around two core stem cell assets, the human retinal progenitor cell line (hRPC) and the CTX neural cell line (CTX).
Stem cell therapy assets available for out-license
We have used our cell expansion and screening technologies to develop “off-the-shelf” stem cell therapies for serious conditions, such as retinitis pigmentosa and stroke disability, 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.
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 the Company’s 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.
ReNeuron’s hRPC cell therapy candidate, initially as a fresh formulation but laterly in its cryopreserved formulation, is being evaluated in an ongoing phase 1/2a 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 five sites in the US, UK and Spain to evaluate the safety, tolerability, and preliminary efficacy in subjects with advanced RP. We have reported positive long-term data from the Phase 2a part of this study. Following receipt of regulatory approval from both the FDA and MHRA the Phase 2a study was expanded by 9 additional patients. Following a review of the latest data the Company intends to out-license its RP programme assets (outside of China) following completion of the current clinical data package for the ongoing phase 1/2a clinical trial.
ReNeuron’s hRPC cell therapy candidate has the potential to be expanded into other retinal disorders, such as cone-rod dystrophy (CRD).
ReNeuron’s 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 the CTX stem cell therapy candidates for stroke utilise a cryopreserved formulation of the CTX stem cell line, designated CTXcryo. The Company has generated data demonstrating the equivalence of CTXcryo drug product to the original non-cryopreserved formulation.
Pre-clinical and clinical results from the Company’s technologies and stem cell products have been published extensively in peer-reviewed scientific journals (please refer to the publications section).
The Company announced positive data from the Phase 2 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.
Following a strategic review, ReNeuron took the decision to terminate an ongoing Phase 2b clinical trial (PISCES III) of its CTX cell therapy candidate in the US with continued development to be via partnerships. Fosun Pharna have an exclusive licence agreement for the development, manufacture and commercialisation of the CTX programme in the People’s Republic of China (China) but the CTX cell therapy candidate is available for licensing in stroke disability and other indications outside of China.
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.
Human retinal progenitor cells (hRPCs)
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.
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.