Compared to sabirnetug in that it was raised against protofibrils, which are soluble aggregates that are also toxic to neurons. So, you know, we view the plaque clearance as sort of a secondary effect on and as a consequence of shifting the equilibrium by reducing oligomers. The oligomers present, that there's a secondary effect that plaques are essentially addressable and reduced at those elevated dose levels. I think we're gonna see in this next study, you know, so ALTITUDE-AD is a Phase 2 study with two active arms versus placebo. We've used the Phase 1 data, target engagement information, and the PK data to select doses for the Phase 2, each of which we think may be therapeutically beneficial or efficacious and safe.
I think, you know, we'll, it'll be interesting to see whether the plaque reduction, you know, at the high dose level is consistent with some of these other agents that are more directed towards plaque. I think we, you know, we view the oligomer target as the primary means of opening up and sort of unlocking better clinical benefit.
Got it. Well, maybe let's dive a little bit deeper on the trial design and study objectives for the phase 2 ALTITUDE-AD. You just started dosing, but you know, how derisking or potentially validating are the results gonna be? And then I'm curious why the iADRS is the primary versus you know, some of the other measures of cognition.
Sure. So, the study design, as I said, is two active arms versus placebo. There'll be up to 180 subjects per cohort, so a total patient population of 540. The primary outcome for the study is the iADRS, which is a composite of both cognitive and functional measures. We'll also have secondary outcomes on CDR-SB and obviously all of the biomarker effects. You know, so I mean, that's the primary design. I think, you know, we've just kicked off. We just announced last week the first patient dosed. We had our investigator meeting late last week in Florida, and there's a lot of enthusiasm for what we're doing.
I think the study's designed as a Phase 2, so really reading out and having clarity on that differentiated outcome, you know, within a reasonable timeframe, we view as sort of the definitive proof of the oligomer hypothesis that we will, you know, we'll be looking at aspects of safety, tolerability, but really the efficacy piece is gonna going to be important for us.
You know, you mentioned the possibility of potentially doing an interim analysis, maybe in terms of thinking about a Phase 2. But does that mean a pivotal could initiate before we see overall completion of the Phase 2?
So yeah, we've. I think that possibility may exist. I think we are really not contemplating interims for any sort of data assessment or other elements. There is the possibility of using an interim to assess, you know, sort of early activities for Phase 3. I think what's really important about the ALTITUDE-AD study is maintaining its integrity as a potential registration study both for European and U.S. regulatory parties. And that's really the work that we undertook last year within a Type B interaction with the FDA and a phase 2 meeting, and then, more recently, feedback with the EMA. So, ALTITUDE-AD, if successful, could serve as the first of two pivotal studies. And at the end of ALTITUDE-AD, we'd be looking at launching a confirmatory phase 3 that would be a single global registration study.
Got it. And I wanna use my words carefully here, but FDA recently issued new guidelines regarding the development of Alzheimer's treatment, suggested a fundamental shift towards the use of biomarkers like plaque reduction. I again wanna be careful here, but does this suggest there may be a path towards accelerated approval if Altitude is positive?
So, Jason, yeah, I wanna be careful with my words as well. I think we've noted that guidance. I think it's really encouraging that the agency has kinda put, you know, open the door really extended the window for biomarker-based, accelerated approval. I mean, for our purposes and given the fact that we have at least one agent, maybe another coming online, you know, we're primarily focused on a clinical outcome, you know, cognitive benefit. If per chance it becomes more clear and we have the dataset to support a filing, certainly we would wanna pursue that.
But our primary focus really is on the execution and conduct of ALTITUDE-AD and reading out the phase 2 in a whole, you know, full dataset rather than kinda trying to see if we could find our way to some sort of, let's just leave it at that, I think.
Fair enough. Makes complete sense. Well, in the time we have left, I you know, a number of other anti- Abeta developers having some challenges. You know, uptake of patients, I think, is disappointing a lot of folks in the community for a variety of reasons. But when you think of sabirnetug's differentiated profile here, what gives you confidence that, you know, some of the issues that might have slowed down the uptake of these other agents may not necessarily apply to sabirnetug, you know, hopefully when it gets on the market?
Sure. So real quickly, I think the launch on Leqembi, right, which I think is the what you're referring to, is kinda gone as expected. I mean, the infrastructure is not in place. You know, our view is that there's a lot of pent-up demand. I think even leading centers haven't implemented sort of the protocols and put sort of the connective tissue between, you know, the infusion center and the radiologist and all of this. So I think it was a greenfield launch, so some of that infrastructure is now in place. You know, I think that even, you know, there's been an update on guidance. I think it's gonna go, and it's gonna be established mode of treatment, right?
I think that's where sabirnetug, having a differentiated mechanism and presumed outcomes in the ALTITUDE-AD study, sets up for a future choice for patients. I'll also comment on the investigator meeting, you know, as there's a lot of enthusiasm for the program. There's an appreciation for our target mechanism and a lot of enthusiasm also for the phase I dataset. But that just really informs why you would wanna put a patient into this research study even in the presence of approved and reimbursed products.
Great. Very exciting times for the field and for Acumen. Thank you so much for joining us.
Thanks, Jason.