EHA 2022 | Phase Ib study of Orca-T in patients with advanced hematologic malignancies

Orca-T is a precision engineered allogeneic cell therapy with the goal of curative consolidation in advanced hematologic malignancies. I can give you a little bit of background so that you can put it into perspective, in that the majority of patients with acute leukemias will require allogeneic stem cell transplant for cure. However, the majority of these patients will have some sort of quality of life impairment, most commonly due to chronic graft-versus-host disease. Orca-T seeks to reduce chronic graft-versus-host disease in order to improve quality of life without impairing the curative potential of allogeneic stem cell transplantation.

I’ll tell you a little bit about the standard allo transplant product and then the trial design. It’ll help put into perspective. The standard allo graft in hematopoietic cell transplantation is a heterogeneous mixture of many types of cells. In comparison, Orca-T is separated into three specific components: components number one are hematopoietic stem cells, component number two are conventional T-cells, and component number three are highly purified T-regulatory cells. Patients receive infusions of the T-regulatory cell component two days prior to the conventional T-cell component. That separation allows for the T-regulatory cells to travel to the solid organs, create an immune barrier that protects, potentially, against graft-versus-host disease. So that by the time the conventional T-cells arrive at the solid organs, there’s less potential for graft-versus-host disease.

The trial design is a Phase Ib multi-center trial with a primary objective of safety, but we’re also looking at transplant outcomes as well and some activity for efficacy. Patients receive myeloablative conditioning therapy. The exact regimen is at the discretion of the treating physician. And then on day zero of the transplantation, patients receive the hematopoietic stem cells followed by the infusion of the T-regulatory cells. Subsequently, on day plus two, patients receive the infusion of conventional T-cells. This is followed by tacrolimus single agent graft-versus-host disease prophylaxis running at a relatively low trough of five to 10.

So in regards to the safety, we looked at two major outcomes; graft failure rates and also rates of infection. So in regard to graft failure rates, we saw that only two out of 137 patients on the trial had graft failure, and that is about half the rate of the historical control. In regard to infections, we showed that grade three or greater infections occurred in only 10% of patients, and that relatively low rate is attributable to the favorable immune reconstitution that occurs with this strategy. In regard to efficacy, we looked at mainly for graft-versus-host disease rates and also in regard to relapse rates. So for acute graft-versus-host disease, grade three and above, we saw a rate of only 4%, in comparison to our historical control core cohort which was 16%. In regard to rates of grade two or greater chronic graft-versus-host disease, that was only 5%, in comparison to closer to around 38% on the historical control cohort. In regard to relapse rate, we showed that relapse rate is not increased with the Orca-T strategy. And our one-year relapse was 20%, compared to the historical control cohort which was about 35%.

Quality of life is one of the most important things in patients who received allogeneic stem cell transplantation. This is a curative treatment modality, but the big unmet need is making the quality of life better for patients who go through this because it’s a lot on the patient, it’s a lot on their family. It’s a lot of time invested. So there’s a huge unmet need to improve the quality of life. And what we’re showing with the data that I presented today is that graft-versus-host disease with Orca-T is low. And with that, that suggests that quality of life should be better when we have longer term follow up on the Phase III trial. And this occurs, potentially, without compromising the curative potential of allogeneic transplantation.