Stem cell and regenerative medicine company Cynata Therapeutics (ASX: CYP) has said that it has “met all clinical endpoints” in its phase 1 trial of flagship drug CYP-001 – for the treatment of steroid-resistant acute graft-versus-host disease (GvHD).
The milestone paves the way for Cynata’s proprietary Cymerus technology to enter phase 2 trials for the treatment of not only GvHD, but possibly other diseases such as critical limb ischemia (CLI).
CYP-001 is based on the company’s Cymerus mesenchymal stem cell (MSC) product candidate with Cynata confirming that its leading asset “demonstrated positive safety and efficacy data” which marks the completion of the primary evaluation period for all patients enrolled in the phase 1 trial.
The standout highlights from the preliminary results published today include an overall response rate of 93% with 14 out of 15 patients showing an improvement compared to their condition before the trial. The complete response rate was 53% while the overall survival “at least 87%”, according to Cynata.
Trialling a treatment for GvHD
The phase 1 trial was developed to include a primary evaluation period comprised of 100 days.
All treated patients received two infusions of CYP-001 with patients in “Cohort A” receiving a dose level of 1 million cells per kilogram of body weight, up to a maximum of 100 million cells per infusion.
Patients in “Cohort B” received 2 million cells per kg of body weight, up to a maximum of 200 million cells per infusion. Cynata says that the overall response rate by day 100 in Cohort B was 86% and the complete response rate was 57%.
“We are pleased to announce that CYP-001 has met all clinical endpoints in the first trial of a product based on our Cymerus stem cell technology platform, which validates its potential to generate safe and effective iPSC-derived MSC therapies,” said Dr Kilian Kelly, vice president at Cynata.
“The clinical results from patients in Cohorts A and B are highly encouraging, as all of the patients had failed to respond to corticosteroid therapy, the only approved treatment for GvHD. We look forward to advancing our Cymerus MSCs into Phase 2 trials for GvHD and other indications,” said Dr Kelly.
Following today’s results, Cynata is expected to publish a “formal clinical study report” (CSR) to support further clinical development and commercialisation of CYP-001 in GvHD. The company has also said it will provide the CSR to Fujifilm in accordance with a license option agreement signed by the companies.
Upon receipt, Fujifilm will have 90 days to exercise its license option and that the safety and efficacy data from the phase 1 trial will “support the advancement of additional Cymerus MSC product candidates directly to phase 2 trials in other indications”.
Cynata has confirmed it has begun planning for a phase 2 trial in its next indication – critical limb ischemia and will provide an update on “ongoing partnering discussions” and its proposed phase 2 trial in CLI “at the appropriate time”.
“Cynata is the only company with the ability to produce allogeneic MSC therapies at a commercial scale without the limitation of multiple donors. The positive data support the potential of Cymerus to generate ‘off-the-shelf’ stem cell therapies for multiple diseases providing significant opportunities for monetisation and commercial partnerships,” said Dr Ross Macdonald, CEO of Cynata.
The problem of GvHD
Steroid-resistant GvHD is a devastating disease with a high rate of mortality. In essence, the condition is a possible complication of a bone marrow or stem cell transplant from another person.
GvHD can cause diarrhoea, skin rashes and liver damage and tends to occur when particular types of white blood cell (T-cells) in the donated bone marrow or stem cells attack the host’s own body cells. GvHD can become prevalent in mild forms which are transitory and not life-threatening, whereas in other cases, GvHD can be fatal.
The only approved treatment for GvHD is corticosteroid therapy, which is typically only effective in about 50% of patients. When GvHD fails to improve or worsens despite steroid treatment, patients are described as having “steroid-resistant GvHD”. According to scientific research, the prognosis for these patients is poor, with mortality rates in excess of 90%.