Frequency Therapeutics — Hearing Loss Regeneration

Seems difficult then to tease out the relative contribution of NMDA activation and OHC loss to tinnitus generation by salicylate.

 

I'm debating if I should buy their stock. If this shit works, I would imagine the gains would be exponential.

 

It might be a good idea to either wait until after the preliminary results in March or this Phase completes entirely. You'll probably miss out on some big profits there, but it'd be a lot safer. It's what I'm considering.

If they put forth really good results after this Phase, then I have little to no doubts this drug won't make it to market, and there's no way it's going to be a marketable treatment for hearing loss and not destroy profit margins.

 

Hopefully they show some good gains. I know everyone is banking on those high frequencies recovering which would be cool. Hopefully they can place a long needle into the round window and get deeper in there. Interesting to say the least. It would be amazing to wake up to silence again. It's absolutely disgraceful that there isn't something out already to help with this.

I surely would love to go trap shooting again someday.

 

Yeah, has that idea been considered? Using a longer needle? That makes perfect sense. Then they could push the drug farther into the cochlea.

 

But not too long a needle. Wouldn't want to hit the brain!

 

Using current injection methods, this damages the cochlea. Potentially damaging more than just the hair cells.

 

I wonder if they could use a very small tube and feed it in toward the apex. Deliver several doses as they move the tube out. The organ is so small I don't know if that is even possible. I'm sure they will come up with something.

 

The easiest path is keeping with the intratympanic injection and updating the formula of the delivery gel, or just giving more doses. A specially designed delivery gel that contained a more concentrated FX-322 that stayed adhered to the round window longer would mean more gets in. If it turns out 4x injections over 4 weeks gets FX-322 deeper, then it may just be a matter of condensing the injection schedule to get the concentration high enough to reach the apex. For example, why not 8x injections in 4 weeks?

After that, there are a few experimental ideas where a specially tuned earbud emits a low frequency tone causing the eardrum to work like a "pump" against the cochlea, which is believed to more-or-less stir the treatment deeper into the cochlea. The other is adhering a magnetic formula to the drug and using a magnet to "push" the drug deeper into the cochlea.

Frankly, I think we'll find out that they end up establishing an accelerated injection schedule with more doses.

 

To be honest, given how ridiculously difficult it is to access the cochlea, I am impressed this gel delivery mechanism was even developed.

 

According to my audiologist, if you damage the round window into the cochlea, shit can really hit the fan. I think it's more about absorption through close proximity. That's why only small amounts seem to get in and only so deep. But I digress... I should read up on it more.

 

I don't know enough about the anatomy of the cochlea. That's why I asked.

 

They have already been doing it with steroid injections.

 

This is just based on my intuition, but I think that once they got the molecule right, improving the delivery mechanism - as hard as it can be - will either be a problem of lower magnitude, or one that they will be extremely motivated in solving.

 

Does anyone know if you can lose hearing above 8000 Hz? A nurse told me that they only test up to 8000 Hz.

I'm asking because I was taught that our ears have a range from 20 Hz to 20000 Hz.

If that's true, can FX-322 fix all frequencies?

 

Anything new driving the FREQ stock price up today?

 

JP Morgan updated their price target today.

 

Yes, of course you can lose hearing above 8000 Hz. The higher frequencies are often the first to suffer damage.

 

Something like this could help get drugs into the inner ear:

https://www.entandaudiologynews.com/media/3129/entma14-shapiro-new.pdf

 

Link:
Why Anthem, Frequency Therapeutics And Vir Are Moving Today

 

Just a curious thought about this, and maybe it's mentioned somewhere in the past 447 pages...

The moment you have the gel in your cochlea, wouldn't your hearing be absolutely awful, and so might it be a difficult experience? How long does the gel have to stay in the cochlea, or how long does it take until it dissipates or whatever it does?

 

It would probably be at least somewhat affected until it fully diffuses. Might be a reason to do one ear at a time.

 

This is an excellent question and one that has come into mind several times. I remember hearing ear fullness as a potential side effect for a few hours, but I don't think that speaks to the fact you'll have goop in your ear.

 

I've had 3 intratympanic injections for SSHL and my experience was just fine. On each occasion, the doctor numbed my eardrum and 30 minutes later he injected me. The only sensation I had was the coldness of the gel and a slight loss of balance for a few minutes. I don't remember any significant fullness (I already had this anyway as a result of the SSHL), but this has since fully dissipated. I was just so relieved to be getting the treatment - I'm sure I would have taken any discomfort on the chin.

I assume he intentionally just about pierces the eardrum and injects. Pushing the needle in further could have catastrophic consequences, I would imagine. I too am not familiar at all with the anatomy of the ear but I'm pretty sure pushing in further wouldn't achieve any good anyway. There's only 2 places for the gel to go, into the round window or down the eustachian tube. The needle isn't pointed towards the round window anyway I would say.

Speculating ahead with regards to to FX-322 delivery, I assume the main challenge is ensuring that as little as possible bypasses the round window down the tube, and once the gel enters the round window, ensuring as much as possible gets down to the lower frequencies. Maybe a greater volume of gel might achieve this? And having us stand on our heads for 10 minutes Who knows, but I'm looking forward to reading how they achieve it, because I'm sure they will figure out a way.

 

I believe I have read that you should try not to swallow for 15 minutes after the injection...?

 

My ENT let me get up and leave whenever I was ready i.e. 2 minutes. I know a lot of people are told to stay put for maybe 20 odd minutes with their head leaning to one side/not swallowing etc. This makes sense and in hindsight wish I had done it. That said, I still feel as if I benefitted a decent amount from my procedures and what I did in the minutes thereafter.

 

The gel formulation is designed so that it stays up in the middle ear and doesn't drain. Carl LeBel mentioned that a patient will be able to sit up and leave with only some discomfort reported from the Phase 1/2 patients.

 

What compound did you get injected?

 

Could anyone comment on the odds of a Phase 3 trial in the US accepting non-US citizens as applicants?

And how likely would a joint US/European Phase 3 be with help from Astellas?

 

I had the same experience as you but my ENT made me lie down on my side for 30 minutes and yes, you're not supposed to swallow or it will go down the eustachian tube.