Frequency Therapeutics — Hearing Loss Regeneration

#18,241
Ben Winders said:
Am I right in witnessing that the general sentiment is back to being more positive about FX-322?

But before, earlier this year, when the initial study results on repeat dosing were published, everyone was completely devastated...?
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Some users are painting that kind of a picture. Most people are just interested in diagnostics and figuring out more nuances of the drug in vivo (i.e. is there any IHC regrowth, etc.). There is some cautious optimism that trial 113 (Severe) will give us more information.

But no, the roller coaster ride is not here -- it's a strawman. Most people have hope diversification (in SPI-1005, OTO-313, OTO-413, PIPE-505, PIPE-307, XEN496, etc.) and just hope that FX-322 provides benefit to hearing research.
 
#18,244
Hey everyone, long time lurker finally officially joined the forum.

Are we getting new results in June or have they changed to H2?

Ben Winders, I thought you were busy researching the crap out of bananas :)? No effect...?
 
#18,245
Exit said:
Hey everyone, long time lurker finally officially joined the forum.

Are we getting new results in June or have they changed to H2?
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I wouldn't expect results from the Severe trial in June. It's still recruiting and not even fully active. I think it'll be closer to September.
 
#18,249
RingingBrother said:
Anyone know where you can request a trial be held in your city? And is there a way to avoid the placebo and just get the real thing if you get accepted?
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You're describing Expanded Access, which is not available for FX-322 right now.
 
#18,251
ThomasRobert said:
If anyone can advise please, if the cochlea is liquid, why is there a problem with the delivery?
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I can tell you it's liquid just from my general research.

The problem with the delivery method is that they can't directly inject. It has to go through the round window membrane.
 
#18,252
ThomasRobert said:
If anyone can advise please, if the cochlea is liquid, why is there a problem with the delivery?
Click to expand...
The liquid in the cochlea is called perilymph, it's highly viscous so the drug flows very slowly through it. The drug is also absorbed by the cells lining the cochlea as it flows through the perilymph. But first, the drug has to pass through the round window membrane and be absorbed into the perilymph.

The current intratympanic gel they are using probably has 1 or more issues: It doesn't stay long enough against the round window membrane allowing maximum drug to diffuse into the cochlea before leaving the middle ear. It doesn't have enough concentration of drug to diffuse more deeply into the highly viscous perilymph. Or, the formula of the drug itself gets absorbed too quickly by the lining of the cochlea before it can get deep enough.

Finally, I am not convinced direct injection into the cochlea is the savior many think it is. Poking a hole in a liquid filled compartment, then forcing an injection of drug into a highly viscous environment seems like the risks may outweigh the gains.
 
#18,253
Gb3 said:
I can tell you it's liquid just from my general research.

The problem with the delivery method is that they can't directly inject. It has to go through the round window membrane.
Click to expand...
It is already confirmed that FX-322 can pass through the Round Window.

The question was, once the drug has already passed through the Round Window and is inside the cochlea, everything there is liquid, so the drug can diffuse everywhere:

Capture.JPG
 
#18,254
Diesel said:
The liquid in the cochlea is called perilymph, it's highly viscous so the drug flows very slowly through it. The drug is also absorbed by the cells lining the cochlea as it flows through the perilymph. But first, the drug has to pass through the round window membrane and be absorbed into the perilymph.

The current intratympanic gel they are using probably has 1 or more issues: It doesn't stay long enough against the round window membrane allowing maximum drug to diffuse into the cochlea before leaving the middle ear. It doesn't have enough concentration of drug to diffuse more deeply into the highly viscous perilymph. Or, the formula of the drug itself gets absorbed too quickly by the lining of the cochlea before it can get deep enough.

Finally, I am not convinced direct injection into the cochlea is the savior many think it is. Poking a hole in a liquid filled compartment, then forcing an injection of drug into a highly viscous environment seems like the risks may outweigh the gains.
Click to expand...
Great info. So we can say these are the 2 possibilities going on preventing the full effect of the drug:

Capture.JPG
 
#18,256
ThomasRobert said:
It is already confirmed that FX-322 can pass through the Round Window.

The question was, once the drug has already passed through the Round Window and is inside the cochlea, everything there is liquid, so the drug can diffuse everywhere:

View attachment 45270
Click to expand...
This is a rather complex problem, and one that I admittedly don't fully understand. Here's an accessible article that may help. The following quote may be useful.
Drug removal from the inner ear can occur through a number of routes, for example, by diffusion into adjacent fluid compartments (e.g., into CSF via the cochlear aqueduct), through metabolism by inner ear cells, or by export across the BLB into the vascular or lymphatic system.
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In other words, the stria vascularis maintains endocochlear potential. The inner ear fluids are constantly being updated to maintain a suitable environment. So it's not as simple as there just being a static fluid. Yes, some of the problem is the gel not fully absorbing by the round window and some of it is the drug getting absorbed at the base, but it's sort of a "race" to the apical region as the body tries to clear it.
 
#18,261
RingingBrother said:
Does FX-322 work best for noise-induced hearing loss, or another type of hearing loss?
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I think FX-322 works best with noise-induced hearing loss as long as the noise-induced hearing loss is between mild to moderately severe.

They have tried age-related hearing loss and it didn't seem to work. Now we have the severe hearing loss trial results coming out before they start their their repeat of Phase 2 trials with mild-moderately severe patients with single dose only. If severe hearing loss trial results are good, they will also add severe patients as well to the new trial.
 
#18,264
This guy explains clearly the cochlea.

There are some interesting facts that I think everyone here should know, e.g., sound vibrations make liquid move around inside the cochlea, the functions of inner and outer hair cells, and information on the feedback loop.

In one part of the video he mentions outer hair cells receive the information from the brain? So then it vibrates and creates the sound accordingly? Interesting...

Video Link:

 
#18,265
ThomasRobert said:
This guy explains clearly the cochlea.

There are some interesting facts that I think everyone here should know, e.g., sound vibrations make liquid move around inside the cochlea, the functions of inner and outer hair cells, and information on the feedback loop.

In one part of the video he mentions outer hair cells receive the information from the brain? So then it vibrates and creates the sound accordingly? Interesting...
Click to expand...
I have understood that outer hair cells act like muscles, so they can move (make stiffer or looser) membrane(s), for example when we want to better hear weak sounds. It also works the other way around, so if there is a sound that is too loud, they act then too. As in the video clip mentioned, there are more functions to outer hair cells, as "fine tuning" sound.
 
#18,266
For anyone curious, what that guy is describing is the MOC reflex. Basically you have a feedback loop where sound enters the ear, runs through the OHC via mechanism vibration, transmits to the IHC where the signal then becomes chemical along the auditory nerve, and is finally shuffled across various channels to the auditory cortex.

But within milliseconds of the chemical signal entering the brain, the brain in turn relays information back to the OHC via the efferent system (ie: MOC).

MOC is what basically allows you to "tune sounds in or out". For example, like how you can focus on the television, while your parents talk in the background. Or if you're attempting to hear a sound more clearly on side of your head vs the other.

That attempt to either heighten or dampen your hearing is an engagement of MOC. It's a feedback process, but the sound always starts as frequency dependent vibrational input from the ear.

The only exception might be severe blunt force trauma to the auditory cortex, or a disorder that involves maladaptive auditory processing - like schizophrenia. Otherwise, your brain doesn't generate noise or sound without some sort of peripheral involvement.

IHC have their own efferent system as well by the way - LOC. But it serves a different function from what I understand.
 
#18,267
Capture.JPG


Gentle Reminder - Goldman Sachs Conference is tomorrow.

To avoid confusions on the timing, below are the actual timings depending on where you are:

EDT 8:00am
Panama 7:00am
New York 8:00am
France 2:00pm
Germany 2:00pm
Russia 3:00pm

They might allow to ask questions in the end, so make sure you're prepared.

Anyone can register and watch, link:

https://investors.frequencytx.com/e...achs-42nd-annual-global-healthcare-conference
 
#18,269
Diesel said:
Nothing new in terms of content, but interesting website addition. Looks like they're trying to remedy the insane amount of email they're getting from patients with hearing loss + tinnitus:

https://www.frequencytx.com/patients/
Click to expand...
I notice that they only talk about speech intelligibility. Have they given up on improving the actual hearing thresholds?
 

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