Avidity Biosciences

I'd, uh, I'd maybe add just two, two other kinda data points to this one.

Um, you know, the, the setbacks of Delbrex, uh, for Novartis after the, the very sizable, uh, Avidity acquisition.

You know, we, we, we've heard, y- you know, s- somewhat putting a chill in terms of appetite for large deals for assets that aren't fully de-risked, so, you know, that may, may be playing a role as well.

If you look a little bit deeper into the rising ins- interest rates and what's going on on the, uh, on the macroeconomic scale, uh, and you juxtapose that to continuing to see very, very aggressive rising drug prices at launch, right? The industry responding to all the criticism of about drug spend and drug prices essentially by doubling and tripling down on even higher and higher drug prices, uh, especially as you kinda see the political landscape shift a little bit as we get closer to the midterms.

So im-im-im-immediately you knew This data is not positive.

Um, little did we know that the Novartis is going to follow it up, um, thereafter with data from Avidity, um, which also, uh, was not positive, and it led Novartis, uh, to be down a lot, about fourteen percent.

Uh, to go back to Ionis, Ionis was only down very incrementally, um, because it was largely expected for the Lp little A Phase III to not work.

Um, Ionis then, uh, that's Monday morning, and then for Varis, which, um, I know I think Brian's going to talk about this, um, had their own Phase III data in hereditary angioedema.

Um, uh, I cover Dyne.

So, you know, this was, uh, sort of an important da-data set, um, as they have a competitive DM one product with, with a lot of similarities, right? So, so I think, you know, we could sort of copy and paste a lot of what we're talking about with LP little A to, um, um, DMPK knockdown, which is sort of the, the, uh, target of these drugs to, um, he-help, uh, um, correct splicing in patients with, with DM one, a large, you know, muscle disease, um, orphan indication, but relatively large for, for sort of a, a orphan mu-- uh, muscle disease.

Um, so look, I mean, this was, uh, a, uh, another big issue for Novartis, right? They did this twelve billion dollar acquisition of Avidity, um, you know, less than a year ago.

And, and look, Avidity, you know, it-it's a platform.

Now a larger study has to show whether they hold up.

Now to Novartis, where the harbor miss puts part of the Avidity acquisition's growth case in doubt.

Deldesiren failed the primary hand-opening time endpoint in myotonic dystrophy type 1.

It was one of three late-stage neuromuscular programs in that $12 billion deal with launches planned before 2030.

Three days after that, they announced the negative outcome for the Horizon phase three outcomes trial for pelacarsen, which is their ASO targeting Lp(a), which was probably the biggest study that everyone was looking forward to this year, the biggest outcome.

And then today we had the news of their failed phase three trial for DM1, which was the Harbor phase three trial, which they had acquired through the takeout of Avidity Biosciences, which I think was a $12 billion takeout earlier this year.

So what had been a great [laughs] run, it seemed like for Novartis, uh, I guess, uh, what is it? Everything comes in threes.

So this was three pretty bad outcomes in the space of a little over a week.

And that treatment was the centerpiece of the company's roughly 12 billion.

acquisition of Avidity Biosciences last year.

The other key trial setback we saw came on Friday when Novartis said its cholesterol-lowering drug failed to meet the main goal in a phase three trial because it did not significantly improve cardiovascular outcomes.

Guggenheim analysts did tell me that the study was incredibly high risk, but the results are casting uncertainty on the broader class of drugs targeting what we call bad cholesterol.