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A helm was a therapy that was released in 2021.

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It received, uh, accelerated FDA approval in June of 2021.

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It's an IgG monoclonal antibody,

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and it targets the, uh, epitope on beta amyloid plaque.

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Now, this was the first potential disease modifying drug

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with FDA approval, uh, for Alzheimer's disease.

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I'm sure you've heard about it in the media.

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It was, uh, quite controversial that the FDA even

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approved this through its accelerated program.

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They were, um, two trials that Biogen, uh,

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conducted 3000 patients.

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And what they found in these trials is they successfully met

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their surrogate endpoint.

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Their surrogate endpoint was the removal

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of beta amyloid plaque, which they, uh, demonstrated on, uh,

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amyloid pets of the brain.

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And so they, we, they found

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that this drug actually successfully removed the beta

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amyloid plaque, but only one

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of the two trials met the primary endpoint.

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And the primary endpoint was improved cognition.

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And so it was only the high dose limb of one of the trials

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where they saw 23% improved cognition.

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But on the other trial, they didn't see

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any improved cognition.

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So again, um, they erased a lot

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of red flags about why the FDA even approved this.

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So I wanna just quickly review

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what accelerated FDA approval program is.

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So there's, they've been using the accelerated FDA approval

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program for many years for

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chemotherapy drugs and other things.

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But to meet the criteria for this program, it has

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to be three different criteria met.

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One is it must treat a serious condition.

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So we, we all know Alzheimer's disease is fatal.

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Number two, it must fill an unmet medical need.

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And we know that there was no other disease

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modifying therapy on the market.

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So it was an unmet need.

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And, and that's based on a surrogate endpoint.

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And the surrogate endpoint, uh, again, was the removal

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of the beta amyloid plaque,

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which we know it does a great job of.

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And that's thought to predict clinical benefit,

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but it's not itself a measure of clinical benefit.

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So it requires

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that a phase four confirmatory trial must be obtained.

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So Biogen is now in the works of performing this phase four,

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uh, clinical trial to see if there really is any

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truly improved cognition.

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'cause that's what they really weren't able

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to prove since only one

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of the trials showed 23% improvement,

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but the other one didn't at all.

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So this is a very important component

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of the accelerated FDA approval program.

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But you can see that, uh,

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helm did meet the criteria, uh, for this program.

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So this is, uh, a look at a baseline amyloid pet, uh,

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of one of the trial patients.

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This is placebo. And then, uh, this is at one year.

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And you can see the beta amyloid plaque.

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This is an amyloid pet.

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It's completely stable one year later in the placebo limb,

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but in the treated limb.

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One year later, you can see the removal

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of this beta amyloid PR from the brain.

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See, the red areas are kind of disappearing.

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So it did do a great job of kind of removing

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that beta amyloid plaque. And the

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Efficacy of clearing the beta amyloid

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plaque is dose dependent.

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So here's again, baseline.

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Um, and here's at the one year point,

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based on different doses, here's the placebo

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where there's no change.

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Here's three MIGS per kg

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where you see significant improvement,

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but much more improvement at six mgs per kg.

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And at the high dose limb, which is 10 mgs per kg, uh, we,

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you really cleared essentially all of the, uh,

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plaque here from the brain.

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And so the higher the dose, the better clearance

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of the plaque with this therapy.