An Australian stem cell and regenerative medicine company


Graft-versus-host-disease (GvHD) is Cynata’s first target indication and a Phase I clinical trial has been completed using the lead Cymerus™product candidate, CYP-001.  Data from the study has been published in a front-page article in Nature Medicine, underscoring the significance of Cynata's landmark clinical trial [3].

What is Graft-versus-host-disease?

GvHD may occur following a bone marrow transplant or similar procedure, when immune cells (white blood cells) in the donor material (the graft) attack the recipient’s tissues (the host) as “foreign”. GvHD is usually treated with steroids; however, when steroid medication fails – which happens in up to 50% of patients – the outcome is usually fatal. Approximately 30,000 allogeneic bone marrow transplants are undertaken each year [1] and around 35%-50% of recipients will develop acute GvHD [2]. So while acute GvHD is a rare condition it is nevertheless a major medical challenge.

The data

Cynata obtained favourable efficacy and safety data in a preclinical study in a mouse model of GvHD, conducted at the University of Massachusetts Amherst (UMass), USA. This data provided a sound basis for proceeding to a clinical trial in GvHD.

Following approval from the U.K. regulatory agency, Cynata then progressed to a Phase I clinical trial of CYP-001, in acute steroid-resistant GvHD. The study was conducted at a number of clinical sites (leading transplantation centres) in Australia and the United Kingdom. The trial commenced in 2017, and was notable as it was the first clinical trial worldwide involving an allogeneic (cells from a donor) iPSC-derived product to receive regulatory approval. When it was completed in August 2018, it became the first completed clinical trial worldwide involving iPSC-derived cells. A total of 16 patients were enrolled in the trial, with the Primary Evaluation Period being the first 100 days after the initiation of CYP-001 treatment. One patient was unable to be treated, meaning a total of 15 patients received CYP-001.

All treated patients received two infusions of CYP-001. Patients in Cohort A received a dose level of 1 million cells per kilogram of bodyweight, up to a maximum of 100 million cells per infusion. Patients in Cohort B received 2 million cells per kg of bodyweight, up to a maximum of 200 million cells per infusion.

The Primary Evaluation revealed exceptional safety and efficacy data with results as follows:

  • Overall Response rate by Day 100 was 86.7% – 13 out of 15 patients showed an improvement in GvHD severity by at least one grade compared to baseline
  • Complete Response rate by Day 100 was 53% – GvHD signs and symptoms completely resolved in 8 out of 15 patients
  • Overall survival at Day 100 was at least 87%
  • No treatment-related serious adverse events or safety concerns were identified

These data have now been published in the prestigious journal Nature Medicine [3].

At 2-year follow-up overall survival was 60% (9 out of 15 patients) which compares favourably with previously published outcomes: an overall survival rate of just 17% after two years has been reported in patients with steroid-resistant acute GvHD who received standard of care treatment [4].  Furthermore, in a  review article summarising numerous studies with bone marrow and adipose tissue derived MSCs in patients with steroid-resistant acute GvHD only six of the studies reviewed reported two year survival in MSC-treated patients, which ranged from 16.6% to 40% [5].

IND Clearance

In 2022 Cynata submitted an IND application to the US FDA and subsequently received clearance of that IND to enable the conduct of a Phase 2 clinical trial in acute GvHD.  Clearance confirms that the FDA is satisfied with both the clinical and preclinical data as well as the manufacturing and quality control data on the product that was submitted in support of this application. This achievement represents a hugely important milestone in the development of CYP-001 and the Cymerus platform.  In August 2023, recruitment opened in this trial, which will seek to recruit approximately 60 patients with high risk aGvHD, at clinical centres in a number of countries, including the US and Australia. Participants will be randomised to receive either CYP-001 or placebo, in addition to corticosteroids. The primary objective of the trial is to assess efficacy of CYP-001 in subjects with high risk aGvHD by Overall Response Rate (ORR) at Day 28.

[1] Gratwohl, A. et al Haematologica. 2013 Aug;98(8):1282-90.


[3] Bloor, A.J.C. et al Nat Med. 2020 Nov;26(11):1720-1725

[4] Westin JR, et al.  Adv Hematol. 2011; 2011:601953

[5] Elgaz, S. et al.  Transfus Med Hemother.46:27-34 (2019)..