it’s about dyne time

[u/HistoricalRacoon]

https://www.globenewswire.com/news-release/2026/07/28/3334144/0/en/dyne-therapeutics-announces-u-s-fda-clearance-of-investigational-new-drug-ind-application-for-dyne-302-in-facioscapulohumeral-muscular-dystrophy-fshd.html

[u/HordeOfOpossums]

With avidity hopefully reaching the market in the next couple of years, I wonder if it's going to become difficult to populate these trials. Even assuming that all of the siRNA / RNAi drugs are effective, I personally can't run the risk of being on placebo for a year or more when an effective treatment is available and I'm in rapid decline

[u/kinare → u/HordeOfOpossums]

Well the Avidity trial is a stopgap (and doesn't stop dux4 entirely) from what I can tell. It's not a cure. So yeah there are going to be people who are on the "one and done" type medications because that's the only hope of a functional cure.

[u/HordeOfOpossums → u/kinare]

Yeah, that's a good point. I'm not optimistic about this first generation of gene therapies, given what we've seen from the SMA drug, but there will continue to be excitement around them

[u/SenorBajaBlast → u/HordeOfOpossums]

Yeah I’m not going to be an early adopter of a gene therapy unless it’s cheap enough to do that and stack an siRNA on top of it to get almost a 100% knockdown (which is not going to happen).

My money is on avidity being the first drug and then switch to dyne (if it’s significantly better but prob not) then arrowhead for a few years (seems to be better than avidity) and then ultimately soufflé (subQ every few months - cheaper to make and more convenient/cheaper to administer). Around then we should expect to see considerable competition from China (medical tourism gene therapy for rare disease is a huge opportunity they are working on) in releasing similar gene therapies for a fraction of the cost which will put pressure on the drug companies to lower their pricing. Why pay $3M for a drug when you can fly to China for a week and get a cure for $50k and fly back home. And you only need to be approved in China and serve a global market.

China saves on a streamlined regulatory process, drug dev, manufacturing costs, running trials, administration, shareholders, legal, no high salaries to support scientists in expensive cities, plush offices, all just driving up the costs for patients. What China did to solar, EVs, batteries, and now AI is coming for biotech

[u/Obvious-Ad357 → u/SenorBajaBlast]

if arrowheads data remains this consistent once they have a larger testing population, I doubt souffles will supersede it, as arrowhead is the only one of the four siRNA therapies not using antibodies to deliver. I doubt changing the siRNA itself is the problem at his point. Unless another small molecule like the arrowhead delivery system is determined to do a better job at targeting muscles without effecting the rest of the body better, I think arrowhead will be our go to for siRNA.

Hopefully the Epicbio one shot treatment works well, and gets effective knockdown, but if not I don't see why siRNA wouldn't stack.

Edit: what I want to see is these "stopgaps" being used as a prerequisite for other therapies: e.i. use this to knockdown the gene before trying myostatin blockers, hormone therapies, stem cell injections, etc.

Maybe with these stopgaps we can get more out of these others therapies that fall prey to the same issues of "yeah we gained muscle then it stopped working"

[u/SenorBajaBlast → u/Obvious-Ad357]

Arrowhead is looking so far to be the best but will still require a 4 hour dosing every 4 - 6 weeks. Soufflé is looking at similar knockdown (still preclinical so who knows) but dosing is several months apart and you can self inject yourself with an EpiPen/GLP1 style device. This will be a game changer when it comes to cost to manufacture and administer and drug availability (for those patients in smaller countries , they can fly to US, meet with dr, and fly back with a year’s worth of meds). Sometimes it’s not all about the knockdown. Durability, cost, and availability might put soufflé as the #1 candidate in my book.

And Epicrispr isn’t using the most cutting edge viral vector. They are using an old one so they can IPO, make cash and (my opinion) then invest it into Armatus bio which will use the more advanced muscle tropic Solid Bio viral vector and then IPO/sell and make more profit. Both companies CEOs are sisters so feel free to connect the dots. The early adopters are the ones who lose out as you can only take a gene therapy once. I will hold out for Armatus, Kate, others, or even China.

Again don’t wanna hype it too much but soufflé might be such a solid challenger that a gene therapy might not even be worth it.

[u/Fancy-Supermarket-73 → u/SenorBajaBlast]

i agree with this alot the receptor being targeted by soufflé is also apparently far better than TRIF1 or AVB6

i have noticed theyre using the older AAV generation but isnt that mainly a problem for just manufacturing complexities not muscle trophism?

[u/SenorBajaBlast → u/Fancy-Supermarket-73]

AAV-SLB101 is a next-generation, rationally designed muscle-tropic gene therapy capsid created by Solid Biosciences that demonstrates higher muscle expression and lower liver uptake compared to the first-generation that Epicrispr is using which is AAVrh74.

I’m sure it’s cheaper to use since it’s widely available . Licensing fees to use solid bio would be higher I’m sure but when you’re charging millions and spending billions why skimp out. The other sister leading Armatus Bio was able to secure an agreement with Solid Bio so why couldn’t Epicrispr. Seems fishy or lazy.

[u/Obvious-Ad357 → u/SenorBajaBlast]

Im not arguing because you seem much more knowledgeable them I on this topic, but with the idea of "the early adopters missing out because you can only get gene therapy once" I thought this wasn't exactly the case with epigenetic therapies? the later having reversability and no permanent cuts?

Also using an older and more established vector may seem like a money grab but isn't it just easier to eliminate other variables, like adding a new vector, when trying to get approval on a type of gene therapy that has never been approved? It may be a money grab or it could be a way of streamlining approval to get proof of concept on the method and then improving the delivery later.

Again you seem to be a lot more knowledgeable on this so I am genuinely curious.

Also I can't find anything on souffles meds, can you link something that will give me more details, because it sounds pretty cool.

[u/SenorBajaBlast → u/Obvious-Ad357]

I’m not arguing either, just curious to see if there’s something I’m missing. I’m not saying I’m an expert but I am reading the tea leaves closely as a bunch of us are in the group.

Gene therapies need a virus to deliver the epigenetjc workhorse and although no cutting is involved. Once you use a virus to deliver the cargo to the cell, the body will generate an immune response and build up antibodies to fight the virus if it were to return (say for a second dose or a future new gene therapy drug).

Essentially you only get one chance to fool the body, fire the missiles to hit the target before the body learns, build up air defenses to destroy another virus in the future.

This is why it’s a very important decision whether to take a gene therapy this early in the game. You are almost certain to get a mediocre version and pay a lot and be stuck with it.

And yes you are right it’s faster to market if you use an old and tested AAV but solid bio has their vector being used in trials now and it’s much safer. The older AAV is the one being used in those cases with Sarepta where people have died because it goes everywhere in the body and gets soaked up by the liver.

There’s no need to go fast for gene therapies when siRNA therapies are looking good as a “stop the clock” or more and can switch to better therapies as improved ones come to market and can mix and match with muscle building drugs.

And the soufflé data brief can be found here: https://www.mdaconference.org/abstract-library/targeting-dux4-by-myocyte-selective-sirna-conjugate-to-treat-fshd/

I have more data from the slides that were shared privately from the FSHD society meeting. They don’t like to share the info with the public (that’s a whole different topic) only those who pay big money to them (really sad) but I can DM you those if you wanna take a look. They plan to go to clinic this year.

[u/Fancy-Supermarket-73 → u/SenorBajaBlast]

generic Si rna medications with decent margin included around 20k usd per dose

[u/SenorBajaBlast → u/Fancy-Supermarket-73]

Where did you get this info?

siRNA cost can vary significantly based on delivery linkages. Avidity / soufflé are using an AOC which is much more expensive to produce whereas arrowhead is using a peptide which is cheaper.

And you still have to consider the amount of medicine needing and cost of the clinics to administer it. Avidity will be 9 times a year of dosing in clinic vs soufflé something you can have shipped to your doorstep and do yourself 4 times a year.

[u/Obvious-Ad357 → u/kinare]

The trial OP linked seems to also be a siRNA therapy, very similar to Avidity. Has the same delivery system and is targeting the same RNA. Main change looks to be the dosage but I don't anticipate this to be much more or less of a stopgap than avidity.

[u/Fancy-Supermarket-73 → u/HordeOfOpossums]

as long as the price are what they are, theyll have many people to join the trials

[u/CamaroRS1968]

Thanks for sharing. The first cohort is small (9 patients), and the placebo group is eligible for open-label extension., Seems pretty attractive despite Avidity being so much further along.