The key activities for the proposed development of a Cymerus™ product can be summarised into the four critical areas described in more detail below. The Company will seek, wherever possible, to secure further intellectual property protection over any developments made in the course of conducting the development plan.
(i) Regulatory Strategy:
The Company has engaged regulatory experts to assist in defining a regulatory strategy and negotiating the complicated regulatory path for allogeneic cell-based therapeutic products. The initial objective of this work been met through the approval of a Phase 1 clinical trial with CYP-001, Cynata’s lead Cymerus™ therapeutic product.
Cynata has had successful and productive interactions with regulators in key jurisdictions, and will continue to do so as the development programs progress.
(ii) Product Manufacture, Manufacturing Process and Controls:
In February 2014, Cynata announced it had partnered with Waisman Biomanufacturing to undertake process development, scale-up and clinical-grade manufacture of Cynata’s proprietary Cymerus™ MSCs. Waisman is a Good Manufacturing Practice (GMP)-compliant facility that was specifically designed to manufacture of cellular therapies, gene therapies and other biologicals products. In February 2015, Cynata announced that the transfer and scale up of the process to a GMP-compliant manufacturing facility (Waisman Biomanufacturing) had been successfully completed. In addition to manufacturing MSCs using the Cymerus™ process, Waisman and other accredited laboratories subjected the MSCs to an extensive range of tests, to confirm that the cells have the characteristics required of MSCs for therapeutic use. The results of these tests form a key part of Cynata’s dossier that supported regulatory approval of its proposed clinical trial program.
(iii) Pre-clinical Testing:
Before use in human subjects, a potential Cymerus™ product must be tested to the satisfaction of the oversight authorities. The nature of the required tests vary, depending upon the choice of indication, availability of suitable test methods and the relevant regulations. Ultimately the goal of the pre-clinical program is to demonstrate the sterility, purity, potency, stability, safety and indicative efficacy of Cymerus™ MSCs.
Cynata has generated positive data in a number of studies of Cymerus™ MSCs in animal models of disease, including graft-versus-host disease (GvHD) critical limb ischaemia and asthma. Each of these studies showed that the MSCs had a profound effect, and no safety concerns were identified. Further studies are ongoing in models of idiopathic pulmonary fibrosis (IPF) and cardiovascular disorders, with additional proof of concept studies in the planning stage.
(iv) Clinical safety and efficacy:
It is necessary to demonstrate both safety and efficacy of Cynata’s potential products before approval for commercial sale may be sought. This will involve the conduct of a series of clinical tests (clinical trials).
Cynata has received regulatory approval to conduct the first Phase 1 clinical trial with Cymerus™ MSCs in patients with graft-versus-host disease (GvHD). This disease often follows a bone marrow transplant procedure and occurs when the immune cells in the donor material (the graft) attack the recipient’s tissues (the host) as “foreign”. Bone marrow transplants are used in the treatment of certain cancers including leukaemia.
Steroids are currently the first line treatment for GvHD, but this treatment is often unsuccessful. Additionally, some patients are unable to tolerate side effects caused by long term steroid treatment. When steroid treatment fails, the prognosis is very poor, with as many as 80% of patients dying from “steroid-refractory” GvHD.
MSCs have the ability to modulate a recipient’s immune response: consequently, MSCs may be useful treatments for diseases resulting from an immune response, such as GvHD. Numerous clinical trials of MSCs as a GvHD treatment have been conducted, most with very positive results.
Ultimately, Cynata expects the GvHD clinical program to pave the way for clinical trials in other indications, which may be conducted by either Cynata or its partners.