As our global population ages, degenerative conditions associated with ageing, such as diabetes, stroke, and heart disease, are on the rise, accounting for 23 per cent of the total disease burden globally.1 So too are the costs associated with delivering a high standard of healthcare to our ageing citizens, placing a punishing financial burden on a shrinking younger population. Cynata Therapeutics, an ASX-listed clinical stage stem cell technology company is working to prolong our “healthspan” so that we can live better for longer.
by Dr Ross Macdonald
The Burden of Age-Related Diseases
The United Nations estimate a global average life expectancy of 72.6 years in 2019 – the global average today is higher than in any country back in 1950.2 And new research suggests we could live to 150!3
But as populations get older, the treatment cost burden of age-related diseases rises, putting increased pressure on governments and younger generations to support a high standard of healthcare. Moreover, GDP can slow down due to a decline in labour force growth.
According to the International Monetary Fund (IMF), many advanced economies already have a declining working-age population. In Europe, it will fall by more than 20 per cent between 2015 and 2055, with an attendant decline in GDP growth.4
In Australia alone, total healthcare expenditure is projected to increase faster than ever over the next 40 years, increasing from 19 per cent of total government spending in 2021-22 to 26 per cent in 2060-61.5
But it’s not just about the cost and the economic impacts. It’s about our quality of life as we age. Healthy life expectancy is different to life expectancy. Healthy life expectancy is the number of years lived without a disability that impacts considerably on the quality of life.
In high-income countries, according to Our World in Data, people tend to spend more years with disability or disease burden than in countries with lower incomes (around 10-11 years versus 7-9 years at lower incomes). With modern medicines extending our life span without necessarily improving it, why live longer if we are unable to enjoy those extra years by living a productive and active lifestyle?
Typically, most medicines only provide symptomatic relief for age-related diseases such as osteoarthritis, chronic pain, diabetes etc., without preventing progression (worsening) of the disease.
If we are to enjoy a longer lifespan then our healthspan must be lengthened. And this is done by addressing the underlying health problem, hence the rapidly growing interest in stem cell medicines, with their powerful properties of repair and regeneration.
The Technology and Trials
Cynata’s proprietary Cymerus™ stem cell technology provides a potential treatment that may be able to halt and even perhaps reverse many of the health conditions that afflict us as we grow old. It can do so through addressing the underlying disease process and by solving one of the fundamental challenges to the industrialisation of stem cells in medicine, that is, the ability to manufacture these exciting products consistently and reproducibly at scale.
The particular type of stem cell receiving the most interest (with over 1,000 clinical trials having been initiated) is called a mesenchymal stem cell (MSC). Because of their regenerative capabilities and profound effects on modulating the immune system, MSCs are being intensively studied in a wide range of diseases, particularly degenerative diseases of ageing. Through a proprietary manufacturing process, Cynata’s Cymerus MSCs are highly consistent and potent, making them ideal candidates as potential new medicines.
Cynata has a broad and robust clinical development pipeline with multiple active trials and near-term catalysts for conditions that include those caused by ageing:
- Phase 3 clinical trial in osteoarthritis (OA) funded by National Health and Medical Research Council (NHMRC);
- Clinical trial in acute respiratory distress (ARDS) which includes looking at the treatment of COVID-related respiratory failure;
- Clinical trial for diabetic foot ulcers (DFU);
- Completed a clinical trial in a devastating condition called graft-versus-host disease (GvHD) in which all safety and efficacy endpoints were met; and
- Multiple successful pre-clinical studies in multiple clinical targets including heart disease and cancer.
The Company’s first Phase 3 trial is its SCUlpTOR (structure-modifying treatment for medial tibiofemoral osteoarthritis) osteoarthritis trial with the University of Sydney as its sponsor. The trial aims to enrol a total of 440 patients with osteoarthritis of the knee and is designed to assess the effect of CYP 004, Cynata’s Cymerus mesenchymal stem cell (MSC) product for osteoarthritis, compared to placebo on clinical outcomes and knee joint structure over a two-year period.
Put simply, the trial hopes to find out whether or not stem cell injections into the knee improve symptoms and slow disease progression in people with mild to moderate knee OA to improve underlying disease and therefore quality of life. There is no current cure for osteoarthritis and current medicines simply treat the symptoms, leaving the underlying disease in the joint to progress and get worse.
Patient enrolment has been steadily growing. Following enrolment, each participant receives injections of Cymerus MSCs (or placebo in the case of the control group) on three occasions over a one-year period with continued follow-ups for an additional year, with results expected in 2024.
Diabetic Foot Ulcers
Foot ulcers that are very slow to heal are a frequent complication in patients with diabetes. They can severely impact the quality of life and often result in hospitalisation, amputation, and even death. Existing treatment options often fail to heal diabetic foot ulcers (DFU) in a timely manner, if at all, and so new and more effective treatments are urgently needed. The estimated market value for diabetic foot ulcer treatments is already approaching US$10 billion, and that figure is likely to grow significantly in the future. Cynata’s Phase I DFU trial opened for recruitment in late December 2021. A total of 30 patients will be randomly assigned to receive CYP-006TK (a polymer-coated silicon dressing seeded with MSCs) or standard care of treatment. The treatment period will be four weeks, and each patient will be evaluated for a total of 24 weeks. The trial is expected to complete during CY22.
Acute Respiratory Distress
Respiratory distress or failure, which may ultimately present as acute respiratory distress syndrome (ARDS), is a serious medical problem and is now the main reason for the admission of COVID-19 patients to the ICU. Treatment remains supportive with a mortality rate ranging from 25–40 per cent, with increased morbidity and mortality in the elderly population. ARDS accounts for approximately 10 per cent of all ICU admissions and almost 25 per cent of patients require mechanical ventilation.
Age is widely reported as a risk factor for the development of ARDS.6
Cynata’s MEseNchymal coviD-19 (MEND) clinical trial is looking to investigate the early efficacy of Cynata’s Cymerus™ MSCs in patients with respiratory failure, who meet the well-established criteria for ARDS with patient enrolment in progress. 12 critically infected patients randomised will receive Cymerus MSC infusions, in addition to standard of care, while 12 patients will be randomised to the control group and will receive the current standard of care only.
Graft-versus-host disease (GvHD) is a devastating condition that occurs in patients who have undergone a bone marrow transplant as part of their treatment of cancer. 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 GvHD in a Phase 1 trial. Planning for a Phase 2 clinical trial in acute GvHD is currently underway. Cynata plans to execute its US development strategy by conducting a Phase 2 acute GvHD trial in the US (subject to FDA approval).
Japan Leading The Way
Japan has invested heavily in stem cell medicine to combat its ageing population and the reliance on high care. In 2020, the median age of the population for Japan was 48.36 years and growing at an average annual rate of 5.68 per cent.7 This is a substantial increase from the median of 22.35 years in 1950. The median age is expected to reach 54.7 by 2050.
In 2014, two laws were introduced in Japan to provide a fast track to the market for stem-cell-based treatments and other types of regenerative medicine. This highly progressive initiative places Japan at the forefront of the development of new regenerative medicines and underscores the Country’s desire to ensure its citizens can enjoy a productive and active old age.
Cynata has an active exposure on many fronts in Japan. It has a strategic partnership with global giant FUJIFILM, one of the leading companies in the regenerative medicine space. FUJIFILM is a ~6 per cent shareholder in Cynata. Furthermore, in January of this year, Cynata received a Decision to Grant from the Japanese Patent Office for a patent application covering its proprietary Cymerus™ mesenchymal stem cell technology. This was especially exciting for the Company given Japan’s leadership in regenerative medicine.
Along with Japan’s many initiatives to address the health issues associated with ageing, Europe, the United States, and other countries, have implemented their own policies and programmes to enhance the development pathway for regenerative medicines. For example, in 2004, California created the publicly funded California Institute for Regenerative Medicine with over US$8 billion allocated to finance the Institute’s programmes.
The team at Cynata is committed to harnessing the body’s own regenerative and repair processes into new medicines to relieve disease and enhance our quality of life. By developing treatments that address the underlying disease, Cynata hopes to prolong people’s activity and health span vs lifespan. CEO Dr. Ross Macdonald wants people to enjoy active lives for as long as possible, enjoying the freedom of movement and doing what we love.
About Cynata Therapeutics Limited
Cynata Therapeutics Limited is an Australian stock exchange (ASX) listed, clinical-stage stem cell and regenerative medicine company focused on the development of therapies 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) (the discovery of which resulted in a Nobel Prize) to achieve economic manufacture of stem cell therapy products, specifically mesenchymal stem cells (MSCs), at commercial scale without the limitation of multiple donors.
- Prince, M. J., Wu, F., Guo, Y., Robledo, L. M. G., O’Donnell, M., Sullivan, R., & Yusuf, S. (2015). The burden of disease in older people and implications for health policy and practice. The Lancet, 385(9967), 549-562.
- Roser, M., Ortiz-Ospina, E., & Ritchie, H. (2013, May). Life Expectancy. Our World in Data. Retrieved from https://ourworldindata.org/life-expectancy
- Willingham, E. (2021, May 25). Humans Could Live up to 150 Years, New Research Suggests. Scientific American. Retrieved from https://www.scientificamerican.com/article/humans-could-live-up-to-150-years-new-research-suggests/
- Lee, R., & Mason, A. (2017, March). Cost of Aging. International Monetary Fund -- Finance & Development. Retrieved from https://www.imf.org/external/pubs/ft/fandd/2017/03/lee.htm
- Liotta, M. (2021, June 29). Ageing population and per-person health costs to rise. NewsGP. Retrieved from https://www1.racgp.org.au/newsgp/professional/ageing-population-and-per-person-health-costs-to-r
- Brown, R., McKelvey, M. C., Ryan, S., Creane, S., Linden, D., Kidney, J. C., ... & Weldon, S. (2020). The impact of aging in acute respiratory distress syndrome: a clinical and mechanistic overview. Frontiers in Medicine, 734.
- O’Neill, A. (2021, September 8). Japan - median age of the population 1950-2050. Statista. Retrieved from https://www.statista.com/statistics/604424/median-age-of-the-population-in-japan/
About the Author
Dr Ross Macdonald, Managing Director and Chief Executive Officer, Cynata Therapeutics
Dr Macdonald has over 30 years’ experience and a track record of success in pharmaceutical and biotechnology businesses, having developed and/or licensed 17 products throughout his career.
At Cynata, he is committed to developing and commercialising stem cell medicines that harness the body’s own processes to regenerate damaged and diseased tissue.