VIDEO: Novel therapies showing promise in myelofibrosis

I'm always excited and always hopeful in this space because I do think there's a lot of momentum. There's a lot of focus both from federal funding which I hope stays in place, pharmaceutical interest, philanthropy and an invested laboratory and clinical group of investigators that are very collaborative in trying to develop novel therapies that really improve our patient's lives with myelofibrosis, particularly as we're talking about some of those drugs that I'm excited about and we've seen really nice data from ASH, American Society Hematology, meeting in 2024 would be navtemadlin, the MDM2 inhibitor for wild-type p53 patients in the BOREAS study, randomized phase three study demonstrating efficacy from a spleen symptom and disease modification with bone marrow fibrosis reduction, driver mutation reduction, circling CD34 cell reduction in patients who have failed ruxolitinib so this is really an unmet need. The survival is poor in these patients.

We need better therapies to salvage those responses and that was clearly done with navtemadlin dosed at 240 milligrams seven days in a row out of a 28-day cycle. The program is now moving towards the POIESIS study so that's an exciting next step that we're looking forward to and that's an active trial globally enrolling patients with myelofibrosis that are treatment naive and then giving them ruxolitinib and that added, like an 18 week period assessing response, suboptimal responders, those that don't have spleen and symptom response that are adequate then get randomized to placebo or the addition of navtemadlin evaluating this active agent in a more upfront or earlier line of therapy. If we enjoyed seeing that data breakdown in the single agent in the relapse refractory setting, I'm really anticipating that the results will be even more exciting and in line with the potential for disease modification as a combination in the suboptimal responders.

The other trials that we really need to keep an eye on are the ongoing MANIFEST-2. We need to continue to see that study readout with pelabresib plus ruxolitinib versus placebo plus ruxolitinib in the JAK inhibitor-naive space. We'll see some 72 week data coming up at the EHA meeting. We're looking for continued durability of response in spleen and symptom burden as well as signals for overall survival benefit in a clean toxicity profile. Other trials that need to be looked at are the SENTRY study, that's the Karyopharm selinexor plus rux versus placebo plus rux in the JAK inhibitor-naive space very much like MANIFEST-2. That's gonna read out hopefully next year and that's gained a lot of momentum in enrolling patients and is a rational way of treating patients with myelofibrosis.

And then of course we cannot forget about imetelstat, the telomerase inhibitor, the phase three single agent relapse refractory setting still ongoing. Again, hopefully we'll get some signals next year on that. And that's an overall survival endpoint, only study with that as an endpoint. And now of course the drug is approved for transfusion dependent lower risk MDS so that really sort of ups the ante. And we have some data that we presented at ASH as a combination in suboptimal responders with ruxolitinib showing that it has safety profile and some early hints of activity. And then I'll just let, name some other drugs that really are still at sort of top of mind and remain of interest. Nuvisertib, TP-3654 which is the PIM1 kinase inhibitor, single agent, right? Particularly very nice symptom improvement with stability in the blood counts. We're gonna continue to watch that program evolve. I think that's an important one.

Luspatercept approved again for lower risk transfusion dependent MDS patients. This subcutaneous active in ligand trap dosed every three weeks is ongoing. We're gonna probably see some readout later this year in the independent study. So it's a add-on to ruxolitinib. We've seen 30% transfusion independence with the phase two. We're gonna see if that reads out and is superior in a phase three setting that might expand the label for MF patients with anemia on ruxolitinib.