So as we've spoken before, I think it's uh appropriate to consider um Nimbalekan as a novel cytokine like agent. Rather than just uh a next generation IL2 uh for a variety of reasons, and it may have been a the particular uh novel strategy of uh creating a circular molecule, uh, but there have been others who've tried to confer upon a to, uh, unusual properties. One was to pegalate it. Back, uh, Cus did this many, many years ago. And uh peelation was associated with a dramatic increase in the half-life, just as Nembalein has a half-life of somewhere between 4 and 8 hours, unlike the 15 minutes that conventional IL 2 has. Um, but the problem with the pegylate IL 2 is that you couldn't get rid of it when you didn't want it around anymore. And so the pegylate IL 2 that Cus had. was given at high doses like conventional IL2 and was associated with a rather dramatic and quite disturbing, um, intense, uh, exaggerated. Toxicity, uh, specifically, uh, renal insufficiency, uh. Uh, stasis, biliary stasis in the liver, uh, profound hypotension, tachycardia, etc. Uh, Nivvo was administered in combination with pegylate IL2, which was designed to not be functional until the peggyated portions of the molecule had been cleaved by endogenous hydrolases in the tissue by tumor. Um, what, what that meant because it was meant to be designed as an outpatient. Uh, agent was that by itself it had no essentially biologic activity at all, meaning any anti-tumor activity. Um, Up to the point where you started to see toxicity, including hypertension as you increase the dose. And so, uh, what was observed was the ability to give a combination with uh Nivvo, PD1 antibody, um, and in that instance, randomized studies uh demonstrated, uh, no, uh, additional efficacy associated with the peylate IL2 beyond what you would see with the Nevo by itself. What I think is quite different from Nembalekan is that you see single agent. Uh, efficacy in an outpatient setting with manageable toxicity, with prolonged half-life 4 to 8 hours, uh, so limited dosing, uh, regimen. Uh, with apparent, uh, anti-tumor effects. I think we'll know quite a bit more once we have the phase three, data in front of us, which should be coming out in 2025. But if, if it confirms the earlier phase one and phase two data, I think we we have the opportunity to see is the Nealleuin could uh have an expansive role beyond just the two tumor types that they Initially selected for their phase 3 trials but may be expanded to uh earlier indications and then other uh tumor types beyond that of just mucosal melanoma and ovarian cancer.
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