RNA interference

Now, APOC3 is another really interesting target that has now been validated to, uh, essentially intervene in the most severe conditions of elevated triglycerides by enabling us to reduce acute pancreatitis.

Um, and we have essentially two different genetic medicines, RNAi and ASOs, that have been approved for that.

Our goal is to provide a permanent or a curative genetic solution for that, those same patient populations with that third program.

And actually, what's interesting is that both our second and our third program are funded by the California Institute for Regenerative Medicine.

These high throughput screens are very powerful in that sense.

So we'd used a lot of RNAi or knockdown screens and that's how we got some insights into VSG expression control.

And we'd used other screens and we decided more recently to develop this massive parallel reporter assay.

So the way this worked was to take a reporter gene, which could look at positive or negative control.

So treatment failures were about 50%.

But the mechanism had not been understood.

And we used one of our RNAi screens to find out which knockdowns would generate resistance to molassoprol.

And we found a water and glycerol transport channel, which was a real surprise actually at the time because the molecules that passed through those channels previously were only up to about 100 Daltons.

Right.

Because, um, injecting RNAi or, um, in-interfer- short interfering RNAs that is, or, um, uh, you know, putting worms into an environment with an abundance of inhibitory RNAs as an experiment is very different than worms experiencing something and then passing on that acquired trait to their offspring.

Um, and it is, it's a world apart in my opinion-

It's just much more-

In today's Pharmaceutical Executive Daily, Apter Pharma and Asiso Therapeutics partner to advance ACT-101, an inhaled antisense therapy for cystic fibrosis.

Moonwalk Biosciences closes a $70 million Series B to advance its Adipose-targeted RNAi platform for obesity toward first in human studies.

And Sebastian Arana of Millipore Sigma explains why multimodality manufacturing flexibility costs more in complexity than in equipment.

Aptar Pharma's Nanopharm subsidiary partners with Asaso Therapeutics to advance ACT-101, an inhaled antisense oligonucleotide designed to target the underlying disease mechanisms of cystic fibrosis rather than just manage symptoms.

Nanofarm will lead formulation development and device assessment work to support the program's path toward clinical evaluation, pairing a SESO's oligonucleotide platform with Aptar's inhalation delivery expertise.

Moonwalk Biosciences closes its $70 million Series B, co-led by Alpha Wave and YK BioVentures, with participation from Eli Lilly, Gowrong Ventures, Arch Venture Partners, Kusla Ventures, and Future Ventures, to advance its Adipose-targeted RNAi platform for obesity and cardiometabolic disease.

The company's SIRNA therapeutics are designed to selectively hit fat tissue through non-incretin pathways, aiming to cut body weight while preserving lean muscle with dosing as infrequent as twice yearly.

The funding will push lead candidate MWW101 into first in human studies expected in late 2027 and expand Moonwalk's broader pipeline and discovery platform.

Yeah, absolutely.

And I was going to talk about, you mentioned a lot of soybean traits and new soybean traits, but on the corn side, one of the big ones that people are asking about too is, should I spend that extra cost and get that new SmartStax Pro with that RNAi or these more expensive trade options? Is it worth it? And then also on top of that, do you need to have insecticide out there too? If you have a lot of corn rootworm beetles and corn rootworm larvae in your fields.

Is this necessary and is it worth that added cost?

Much like I talked about with soybean cyst nematode, where if you can get a BT trait, you can get genetic tolerance through a natural trait, and you can also get a seed treatment or even an in-furrow type treatment.

By taking multiple shots at a problem, you're much better off.

With corn rootworm, this year we had done some research and just did root digs and looked at root feeding, where we had just a straight SmartStax Pro.

So the best current trait that's out there in terms of control, because you've got BTEs and you've got RNAi.

Boy, it still got chewed up.

But Stifel said they don't see a commercial impact for this drug.

Rather, they pointed to potential shifts in Alnylam's ongoing Phase 3 program for its next-gen RNAi therapy.

For this one, Steifel said the company could direct further enrollment toward monotherapy and make results from that group the primary outcome.

Yeah, I mean, certainly learn from others' failures if you can and improve the outcomes for patients.

And I had that experience with microRNAs.

And then that fall, RNAI won, or siRNAs won the Nobel Prize.

Happened to be given to a graduate student at Phil at the time.

And so then I was like, well, this is obviously the most exciting thing that could ever be studied.

And you need data that speaks to the problems that you're trying to solve.

Alnylam's conviction behind this RNAi platform means that all of the data, pretty much every piece of data they've generated since founding Alnylam, is likely informative, has something to offer for any program that you might want to build on top of this platform.

And in other words, all of the data they've generated is relevant training data for models for all of their programs.

That's just not true for other companies in the space, not even close.

CAMPOY- But where would you think, which entity would you think is going to be bullish on building another platform? Well, one that has already built a first platform and is very successful with that.

And so not only are we now building models together with Alnylam using their data, but not only their data, in close collaboration with their team, for their existing platform.

But the vision for this collaboration ultimately is that we actually take all of that data, all of those insights, whether insights of humans or of machines, and use it to enable adjacent but novel platforms that allow the company and us as partners to go significantly beyond even what you can do with RNAi.

And when it comes to partnerships like this, and I think partnerships as a whole are obviously increasingly important in this AI ecosystem regardless of, frankly, the industry, whether it's biotech, whether it's healthcare, health life sciences, whether it's something as simple as communications or food services, right? Partnerships matter because I think partnerships allow companies to go further than they could ever go by themselves.

Despite the, the, the wonderful name of gene silencing, does it really do much, if anything, on top of a stabilizer, which most patients are on today? Uh, our friend John Maraganore would, would certainly argue that, uh, this data set today from Cardio Transform is very specific to an antisense molecule, which is eplontersen, and it does not necessarily have read-through to vortasiran.

Vortasiran, of course, is Alnylam's RNAi, uh, based therapy for ATTR.

Uh, and I think there's some validity to that.

We, we just don't have as much data on vortasiran in this setting on top of, uh, a stabilizer.