An Australian stem cell and regenerative medicine company

January 30, 2023

Regulatory approval for Cynata’s aGVHD trial

In late January, Cynata received regulatory approval for commencement of its phase 2 clinical trial in acute graft-versus-host disease (aGVHD). It mostly affects women, and nothing has yet been established as an optimal second line therapy for either acute or chronic GvHD. 

However, mesenchymal stromal cells (MSCs), those which Cynata manufactures, have shown substantial promise. Read the news here:

January 30, 2023

From approval to enrolment - the process of starting a clinical trial

For biotech investors, the news of approval of a new clinical trial by a regulatory body such as the FDA is a genuinely exciting milestone. But what many might not be aware of are the multiple steps involved in actually commencing a trial after the appropriate regulatory agency has given approval.  

This can lead to investor frustration and the misconception that perhaps things aren’t running smoothly when in reality, for complex, multicentre multinational trials to open all sites for enrolment, it can take up to twelve months post-approval. 

Here’s a topline summary of the steps that most biotechs and pharmaceutical companies will need to sequentially work through before recruitment of patients can begin. 

  1. Development of core study documents such as final study protocol, Investigator’s Brochure (a collection of clinical and non-clinical data about the investigational product), and Informed Consent Form (a document volunteer signs when they agree to participate in a clinical trial).
  2. Selection of a Clinical Research Organisation (CRO), the specialist company that actually runs the clinical trial on behalf of the drug company. This involves several bid defence meetings where quotes are analysed, and contract negotiation. 
  3. Clinical research site selection and feasibility (with potential sites often being in multiple countries), followed by site qualification visits at each site where more detailed assessments is conducted about the site personnel/equipment to ensure the site has adequate resources and patient population for successful study execution.
  4. Negotiation of budgets at individual study sites 
  5. Submission to local Regulatory Affairs (RA) and Ethics Committees (EC). These bodies review research proposals involving human participants to ensure they meet ethical standards and guidelines.
  6. Answering questions/requests from RA/EC to obtain approvals. Questions can range from pre-clinical package to risk/benefit assessments and further requests may involve conducting additional experiments.  
  7. Submissions to the Research Governance Office (RGO) at each site and further negotiations on study documents, and site budget. The Research Governance Office is the office within the hospital that administers the processes used by the institution to ensure that it is accountable for the research conducted under its auspices. To be properly governed, research must be conducted according to established ethical principles, guidelines for responsible research conduct, relevant legislation and regulations and institutional policy. This step alone can take up to six months. 
  8. Preparation of study plans including but not limited to: 
    • IP = Investigational Product manual
    • PVG = Pharmacovigilance plan (how to assess and report serious adverse reactions)
    • MMP = medical monitoring plan (the plan ensuring safety oversight and reviewing the protocol (e.g., study halting rules) and information about the study as it becomes available)
    • Lab manual
    • Clinical monitoring plan
    • Statistical Analyses plan
    • DM = data management plan etc.
  9. Build and validate the electronic data capture (EDC) database to be used to record all the data from the subjects in the trial
  10. Conduct Site Initiation visits at each site which involves training the site study team on study protocol, adverse event reporting data recording in EDC and other systems to be used during the study. 

As you can see, it’s not a short nor simple process. And, within this process, some of the steps may take multiple iterations even if appropriately undertaken. 

I appreciate that it’s difficult for already patient investors to continue to be patient but at the end of the day, designing good clinical trial strategies to ensure they have the best chance of reaching the intended end point and move to commercialization is imperative.

January 24, 2023

Getting to the trial start gate

Before you can even commence a clinical trial, there’s multiple steps to work through in preparation for the trial after the appropriate regulatory agency has given approval. These can take up to 12 months to work through but the correct trial set up is critical to the overall success of the trial. 

Cynata Chief Medical Officer Dr Jolanta Airey outlines the process here:

December 20, 2022

Cynata wrapped

In his final interview for the year, Dr Ross Macdonald sits down with Kalkine Media to discuss Cynata’s 2022 milestones, and how the Company is picking up the pace with its broad and diverse clinical trial pipeline.  

Watch the 15 minute video here

December 12, 2022

Stem cell medicine helping us live better for longer

By Dr Ross Macdonald, CEO Cynata Therapeutics

Originally appeared in Asia Pacific Biotech News. Adapted from original. 

As our global population ages, degenerative conditions associated with ageing, such as osteoarthritis, diabetes, stroke, and heart disease are on the rise, accounting for 23% 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. At Cynata Therapeutics, we are working to prolong our “healthspan” so that we can live better for longer. 

The problem – The burden of diseases of the aging

The United Nations estimate a global average life expectancy of 72.6 years for 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 diseases of ageing rises, putting increased pressure on governments and younger generations to support a high standard of healthcare.  Moreover, GDP can slow due to a decline in labour force growth. 

According to the IMF, many advanced economies already have a declining working-age population. In Europe it will fall more than 20 percent 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% of total government spending in 2021-22 to 26% 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 quality of life.  

In high income countries, according to Our World in Data, people tend 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, what is the point in living 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 diseases of the ageing 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 also 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 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 1000 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 aging:

  • Phase 3 clinical trial in osteoarthritis (OA) funded by National Health and Medical Research Council (NHMRC)
  • 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
  • Multiple successful pre-clinical studies in relevant clinical targets including heart disease and cancer


The Company’s first Phase 3 trial is the SCUlpTOR (structure-modifying treatment for medial tibiofemoral osteoarthritis) osteoarthritis trial, with the University of Sydney as 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 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, meaning the underlying disease in the joint progresses and gets 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 CY2025. 

Diabetic Foot Ulcers

Foot ulcers that are very slow to heal are a frequent complication in patients with diabetes.  They can severely impact quality of life, and often result in hospitalisation, amputation and even death. Existing treatment options often fail to heal diabetic ulcers (DFU) in a timely manner, if at all, so new and more effective treatments are urgently needed. The estimated market value for diabetic foot ulcer treatments is already approaching US$10b, 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 in CY2023.

Graft-Versus-Host Disease 

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 under an IND (cleared by the US FDA in May 2022), and in other countries, expected to commence in 1Q23.  

Japan leading the way

Japan has invested heavily in stem cell medicine to combat its aging population and the reliance on high care. In 2020, the median age of population for Japan was 48.36 years and growing at an average annual rate of 5.68%.[6].  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 development of new regenerative medicines and underscores that 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.  FUJFILM is a ~6% 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. The 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 and the United States, and other countries, have implemented their own policies and programs 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 having been allocated to finance the Institute’s programs.

The future

The team here 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, we hope to prolong people’s activity and health span versus lifespan, allowing people to enjoy active lives for as long as possible, enjoying the freedom of movement and doing what they love. 



  1. 1.       Prince MJ, Wu F, Guo Y, Gutierrez Robledo LM, O'Donnell M, Sullivan R, Yusuf S. The burden of disease in older people and implications for health policy and practice. Lancet. 2015 Feb 7;385(9967):549-62. doi: 10.1016/S0140-6736(14)61347-7. Epub 2014 Nov 6. PMID: 25468153.
  2. 2.              Roser, M, Ortiz-Ospina, E, & Ritchie, H (2013, revised in 2019) Life Expectancy, Published online at 
  3. 3.              Pyrkov, T.V., Avchaciov, K., Tarkhov, A.E, et al. Longitudinal analysis of blood markers reveals progressive loss of resilience and predicts human lifespan limit. Nat Commun 12, 2765 (2021).
  4. 4.              Lee, R, & Mason, A (2017) International Monetary Fund, Cost of Aging, Finance & Development, Vol 54, No. 1 
  5. 5.              The Commonwealth of Australia (2021) Intergenerational Report: Australia over the next 40 years, Published online at 
  6. 6.              Brown, R, McKelvey M, Ryan S, et. al. (2020), The Impact of Aging in Acute Respiratory Distress Syndrome, A Clinical and Mechanistic Overview, Frontiers in Medicine, Vol 7
  7. 7.              O’Neill, A (2019) Japan: Media age of the population from 1950 to 2050, Statista published online at