Hi, my name is John Mascarenes. I'm coming to you from the Icahn School of Medicine at Mount Sinai in New York City. And we'll be talking about the advancing progress being made in targeting mutant calore for those patients with essential thrombocytemia or myelofibrosis harboring a calore mutation. The European Hematology Association meeting here in Milan, we're going to be presenting for the first time the initial results of the first in human mutant calore antibody. We'll call it 33989, in-site compound in patients with essential thrombocytemia. These are patients with ET that have failed a prior line of therapy and have elevated platelet counts and are in need of therapy. This phase 1B study was evaluating 33989 in dose cohorts ranging all the way from 24 milligrams to all the way up to 2,500 milligrams. We did not have a dose-limiting toxicity, which is remarkable. In fact, the toxicity profile was really clean, which was very satisfying. And I would even say out of the 20 years of treating patients with various therapies on study, this was the best tolerated therapy that I've had the good fortune of being involved with. This antibody, which selectively targets the mutant calore protein that's expressed on the malignant cells in patients with ET and MF that harbor this molecular abnormality, binds directly to the complex on the surface of those cells, internalizes that complex, and turns that cell off, thereby leading to the death of that cell. That's what the preclinical modeling would suggest. And what I'm happy to say is in the clinical findings, we're seeing very significant rapid normalization of blood counts, particularly the platelet count, as well as reductions in other elements, whether it might be spleen, markers like LDH. And probably most provocatively is the very rapid reduction in the mutant calore PCR product itself, the measurable indirect burden of the disease from the bone marrow. So a marker that would suggest we're really reducing the burden of disease, while bone marrow biopsy substantiating changes in the bone marrow, like reduction in the malignant mega caricytes and near normalization or close to normalization of hematopoiesis, really suggesting that this antibody, particularly at the higher doses and particularly over a prolonged period of time, may have the ability to induce remissions and change the natural course of this disease. So that's more to come to see over time whether we achieve that goal. But I do feel confident in saying very well tolerated drug, no dose limiting toxicity and preliminary data suggesting not just control of platelet counts, but likely disease modification. Message to the patient community. I do see a lot of hope for the future in the way these drugs are being developed. So whether it's the mutant calore antibody or other approaches to mutant calore, I would strongly encourage patients to reach out to their physicians to look for centers where these therapies are being offered in clinical trials. That's how the field moves forward. That's how you can get access to these therapies earlier, because it does take time to get to the commercial space. And this is one example, I think, of an innovative, likely transformative therapies. And there are others like mutant selective JAK2 tyrosine kinase inhibitors or type 2 JAK2 inhibitors, as well as combination therapies up front like the selenexor and the Navtomatalin approach and many other therapies that offer a chance to improve upon the disease state and hopefully change the disease course for these chronic diseases. So please think about clinical trials and reach out if possible.
HealthTree • June 30, 2025