While a hematopoietic stem cell transplant is the best option for some patients with blood cancer, the procedure can lead to dangerous complications, such as graft-versus-host disease. Three entrepreneurs launched Orca Bio a few years ago with a potential solution — and at ASH, they unveiled some early data showing patients in two trials were largely able to avoid the devastating side effect.
Just 3% of patients on Orca-T — Orca Bio’s second generation cell therapy for blood disorders — experienced moderate-to-severe chronic GvHD in two studies, compared to 43% of patients who received standard of care allogeneic hematopoietic stem cell transplants (alloHSCT), the biotech announced on Saturday.
The results were pooled from 109 patients in a Phase Ib multi-center study and a Phase I/II single-center study, who had acute myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndromes, myelofibrosis and other hematological malignancies.
While they were single-arm studies, Orca pulled data from a group of 95 matched patients undergoing alloHSCT to compare the results. CEO and co-founder Ivan Dimov admitted it’s not the ‘gold standard’ approach, but remains confident in the results.
‘I think Orca-T is showing almost a complete obliteration of really horrible, chronic GVHD and you can look at the charts there, it’s going from 40% down to pretty much nothing,’ he said in an interview ‘And the very few patients that get something, become very manageable.’
Patients on Orca-T saw an 87% chronic-GvHD-free survival rate, compared to a 45% rate in those who were on standard of care (p<0.0001), Orca announced at ASH. Meanwhile, overall survival rates with Orca-T were 90%, compared to 78% in the control group (p<0.03).
Dimov founded Orca along with Jeroen Bekaert and Nate Fernhoff a few years ago, after becoming intrigued by the legendary Irv Weissman’s cell purification work while studying at Stanford. Novartis — then Sandoz — had purchased Weissman’s spinout SyStemix in the ’90s, then scrapped it due to practical challenges. But Bekaert, Dimov and Fernhoff saw potential.
‘Bone marrow transplant, you could argue, is the most widely accepted cell therapy out there, and it’s been around for 50 years. It’s a miracle, it actually cures people when they have terminal cancer,’ Dimov said. ‘And yet, it hasn’t really evolved much.’
That’s where Orca comes in.
What typically happens with a bone marrow transparent, is you take apheresis blood (blood that’s been separated into its different components) from a fully matched donor, and infuse it into the patient after conditioning them. The overall goal is to reboot a patient’s blood-forming systems. But this process can result in GvHD, which occurs when immune cells from the donor attack the patient’s healthy cells.
Orca, on the other hand, concocts a secret recipe of sorts. Instead of just ‘putting in all the cells,’ as Dimov puts it, the scientists build a ‘designer immune system,’ combining specific immune cells and stem cells to create a mixture that’s optimal for safety and efficacy.
The stem cells, he says, are like engineers: ‘They’re going to go into the body, build out the factories, then over time build out the full repertoire of an entire healthy immune system.’
This summer, the approach landed Orca $192 million in fresh Series D funding and rare unicorn status — and a few months later, they snagged the FDA’s regenerative medicine advanced therapy (RMAT) designation.
‘Chronic GvHD is a new disease that usually lasts for a lifetime,’ Dimov said. ‘People have to change their lifestyles completely, but they feel extremely guilty because they’re a survivor right? They should be happy that they didn’t die of cancer, and yet they have this horrible new existence.’
Orca plans on initiating a Phase III trial in early 2022, which Dimov says will be randomized.
https://endpts.com/ash-a-cell-therapy-startup-with-roots-in-irv-weissmans-lab-nearly-wipes-out-a-chronic-side-effect-in-early-trials/
