Cynata Therapeutics, a biotech company specializing in therapeutics, has opened its Limited (ASX: CYP), a leading clinical-stage biotechnology company specialising in cell therapeutics, is pleased to announce that the mesenchymal COVID-19 (MEND) trial has begun enrolling patients. The study is intended to research efficacy of the company’s proprietary Cymerus mesenchymal stem cells (MSCs) in use for adults diagnosed with severe cases of the virus.
Outsourcing-Pharma (OSP) recently spoke with Cynata CEO Ross MacDonald (RM) about the MEND trial, and how the pandemic has impacted its operations.
OSP: Please tell us about Cynata Therapeutics—who you are, what you do, key services and capabilities, and what sets your Cymerus technology apart from the rest?
RM: Cynata Therapeutics is an Australian stock exchange listed clinical-stage stem cell and regenerative medicine company focused on the development of cell therapy products based on Cymerus, a proprietary therapeutic stem cell platform technology. Cymerus overcomes the challenges of other production methods by using induced pluripotent stem cells (iPSCs) to achieve economic manufacture of mesenchymal stem cells (MSCs), at commercial scale without the limitation of multiple donors.
Any requirement for multiple donors creates major issues around product consistency as every donor is different and so too are cells derived from them. Manufacture of Cynata’s Cymerus MSC products is outsourced to Waisman Biomanufacturing in Madison, WI.
OSP: Could you please provide a little bit more information about the indications Cymerus has been tested on/used for prior to now, and why your team believes it could be effective on COVID-19 patients?
Cynata’s lead product candidate CYP-001 met all clinical endpoints and demonstrated positive safety and efficacy data for the treatment of steroid-resistant acute graft-versus-host disease (GvHD) in a Phase 1 trial. Cynata is now advancing its Cymerus MSCs into Phase 2 trials for severe complications arising from COVID-19, GvHD, critical limb ischemia and into a Phase 3 trial for osteoarthritis.
In addition, Cynata has demonstrated utility of its Cymerus MSC technology in preclinical models of asthma, diabetic wounds, heart attack, sepsis, acute respiratory distress syndrome (ARDS) and cytokine release syndrome.
In the case of COVID-19, patients suffering severe complications typically present with respiratory distress and it is this condition, along with sepsis and cytokine release syndrome (or cytokine storm), that is the major cause of morbidity and mortality in these patients. Cynata has reported compelling data in pre-clinical models of all three, creating a solid foundation for the MEND clinical trial.
OSP: What can you tell us about the MEND Trial enrollment effort—i.e. anticipated length of enrollment time, how you selected the centers in NSW, etc.?
RM: The MEND Trial is an open-label, randomized controlled clinical trial to investigate early efficacy of Cymerus MSCs in 24 adult patients admitted to intensive care with COVID-19 and respiratory distress. Twelve patients will be randomized to receive Cymerus MSC infusions, in addition to standard of care, while 12 patients will be randomised to the control group and will receive current standard of care.
The primary efficacy endpoint will be improvement in PaO2/FiO2 ratio (a measure of hypoxemia, a low level of oxygen in the blood caused by compromised lung function) by Day 7. Safety and tolerability up to Day 28 will also be a primary endpoint.
Given the uncertainties surrounding the progress of the pandemic in the region around the study centers it is presently difficult to predict recruitment rates. The study centers were specifically selected as they provide care for a large population in the western region of Sydney in New South Wales; one of the centers is among the largest hospitals in Australia.
OSP: What kinds of challenges does the current pandemic present to your recruitment effort, and can you tell me how your team is working to overcome and bypass those challenges?
RM: The pandemic has created major challenges globally for the pharmaceutical and biotech industry as clinical trials are delayed or curtailed as authorities seek to ensure adequate health care resources to deal with expected or actual COVID-19 patient numbers. In Cynata’s case this has specifically impacted our proposed Phase 3 clinical trial in osteoarthritis patients where, because of the pandemic, the University of Sydney (the sponsor of the trial) advised that the newly approved trial should not commence trial participant involvement (first visits) until further notice.
Cynata continues to work with the Chief Investigator, Professor David Hunter, to continue to prepare for the trial to be ready to commence enrolment as soon as possible. Our proposed trial in COVID-19 patients is, of course, directly related to the current pandemic and enrollment in that trial is now open.
OSP: What else would you like to tell our readers about the trial, or your company?
RM: MSCs represent a very promising therapeutic approach to a range of important diseases and we are now seeing regulatory authorities around the world starting to approve therapeutic products based on MSCs. Cynata is the leading company worldwide developing a new approach to manufacturing MSC products that does not rely on multiple tissue donations from multiple donors.
The FDA has recently and clearly indicated that a reliance on manufacturing strategies that require multiple donors results in very substantial and unresolved questions around product consistency. Cynata’s proprietary Cymerus technology provides a very practical solution.