Speaker 1
What we have is a drug that is essentially cytostatic in nature. And then, so it takes a drug, the drug takes time to become from cytostatic to cytotoxic. So when you get a patient with a recurrent disease, that tumor is very aggressive, and that tumor is proliferating. And so what happens in the patient is that this drug initially goes on. It's a battle between the drug and the tumor. And so depending on what phase of the cell cycle this drug is hitting the tumor at, you may see this patient basically not have an overall progression-free survival of six months, but have a longer overall survival time because the drug has an opportunity to catch up with the treatment. And I think that's the main reason why we have a discrepancy in some of these patients, depending on what part of the treatment cycle and what part of the cell cycle we're catching the patient at. Thank you, Don.
Speaker 0
Let me build on that. Let me build on that first. First of all, this is not a novel observation. There are other interventions, particularly immunotherapy, where you can see not so much a response, but you can see a prolonged survival, in effect, changing something from an acute disease to a chronic disease. And I'm sure the investors on this call would be very unhappy to realize that somebody would have to stay in this drug forever to sustain control of the disease. Of course you wouldn't. This is the thing that is something that is quite feasible, and you might be able to turn diseases like this into a chronic situation, and if the worst thing in their life is they have to stay on this drug for years and years and years to sustain their quality of life and not have a progression, even if you don't see a response, is anybody on this call really worried about that? no nobody's worried about that but you have to keep buying the drug but obviously that's part of uh being taken care of like having insulin for diabetes that may be what we're going to see in at least the population of these patients if that's the situation everybody everybody wins in
Speaker 3
that situation thank you okay our next question can you provide more context on the historical benchmark for median overall survival, or is recurrent GBM more appropriate given the lack of standardized benchmarks in IDH1 mutant grade 3 and grade 4 and higher grade 4 patient population in the study? Sure.
Speaker 2
So, thank you for that question. So, with respect to historical, as Dr. Friedman and Dr. Miller alluded to, really there has been no clear study that has been done on recurrent grade 4 IDH1 mutant patients. All other studies, including Stellar, Varingo, EORTC, they have been done on comparisons to IDH1 wild types. It was only less than a decade ago that we came up with this biomarker IDH1 mutant population. With that said, it is a different disease. However, as Dr. Chen alluded to, at recurrence, these patients, especially the grade four patients, act like the wild-type patient. The recurrence comes back, and it's very vengeful. And so we believe that in our phase three randomized trials, we will be, you know, the number of, with respect to median overall survival.
