Brian Sullivan: Great. Well, thanks. So, geda’s tolerability profile is a function of two features of the drug. One is that it’s administered IV intravenously, which means it avoids the GI tract and the liver. Because PI3K-alpha, which is one of the targets of geda and which is one of the targets of available therapy, regulates glycolic activity which takes place in liver. Avoiding the liver allows you to avoid essentially inducing high levels of hypoglycemia, which is one of the primary adverse reactions associated with PI3K drugs. And the second feature of the drug relates to its PK profile, and that’s a function of its chemical structure, which is that it has a very balanced volume of distribution of around 40 liters. And what that essentially means is that it doesn’t get retained excessively in the liver, which is in comparison to some other drugs that have been IV administered which had very high volumes of distribution and were retained in the liver 50-fold higher concentrations than in plasma.
So, it’s a combination of the route of administration, which is a necessary but not sufficient condition to minimize the toxicity. It’s also a feature of the PK profile and its balanced volume of distribution. As far as dose reductions, in our Phase 1b study, we had dose intensity levels of roughly 90%. So, there will be a very structured approach to dose reductions. But overall, patients stay on the drug for the most part at the 180-milligram dose level. The dosing intensity was comparable to palbociclib. So, we think that, essentially, the drugs are somewhat equally tolerable as a result. So, there’s nothing that would expect us to see anything different in the Phase 3 study.
Boris Peaker: Great. Maybe if I could squeeze in one more just on prostate cancer. Obviously, there’s a lot of discussion on PSMA-targeting therapies, particularly in the pre-chemo setting. We just saw some data at ESMO. We’re expecting other data readout from companies soon. How do you see that impacting kind of your development pathway to geda plus enzalutamide in these patients?
Brian Sullivan: Sure. Well, we’ll see. I mean, it’s a function of the data that we report. If the data that we report is consistent with what’s been reported in clinical studies that were done with an earlier-generation PAM inhibitor that is no longer under development, then we think geda would be on track to potentially offering a standard of care that was superior to PSMA-targeted therapies. Even if it was just comparable — and again, I’m just describing scenarios, not projecting anything. But even if it was just comparable, the radiographic progression-free survival was just comparable to the PSMA. We think that we would have an advantage relative to the challenges involved in administering that class of drugs. But it’s early days.
But ultimately, as is the case in most of these settings, the efficacy will really determine the strategy going forward and the penetration that you could hope to expect. But we don’t think that the bar is raised to a level with those drugs that will create an impediment for us to be successful.
Boris Peaker: Great. Thanks for taking my questions.
Brian Sullivan: You’re welcome.
Operator: Our next question comes from Gil Blum with Needham & Co. Please go ahead.
Gil Blum: Hey, good morning everyone. Thanks for taking our question. Just a quick one on use of proceeds. You guys recently had the financing. Just trying to understand if you expect the majority of these proceeds to be used to maybe extend the cash runway, or is it more to expand the footprint, to invest in prostate cancer program? Thank you.
Brian Sullivan: Thanks, Gil. We raised the incremental $50 million, which really came over the threshold. It was an unsolicited inquiry, and we concluded that. It was — would be favorable for us to extend the runway. The money we had raised and had on our balance sheet prior factored in development costs associated with the Phase 1b/2 study. And so, for the most part, this incremental infusion of cash will primarily extend our cash run rate, which again, in this environment, having additional runway, we think, is just very prudent. And so, we concluded that it was an opportunity for us to bolster the balance sheet and really — can’t say eliminate, but certainly reduce the potential balance sheet risk associated with our programs. Hello?
