Frequency Therapeutics — Hearing Loss Regeneration

Can we hear at 19 18 20 kHz after FX-322?
If the Phase 2a results show that participants that received FX-322 improved on their extended audiograms (9 kHz - 16 kHz), it's safe to assume that even higher frequencies improved.

However, I recall someone on this forum share research that showed that biologically, not all people can hear above something like 18 kHz. They presumably don't have the cells at all, so none to lose/none to gain.
 
this can not only delay recovery but also make it less likely.

Dr. Will Sedley talked about this too on the Tinnitus Talk Podcast. He said stress at the time of the insult contributes to maladaptive neuroplasticity in tinnitus.
Since my auditory injury early this year, I've been in an unending, suicidal, claustrophobic, majorly depressed panic attack. Uncoping stress to the maximum.

When you say "delay and make recovery unlikely" in light of maladaptive neuroplasticity... Are you referring to not being able to recover (reverse tinnitus) even after FX-322?
 
Since my auditory injury early this year, I've been in an unending, suicidal, claustrophobic, majorly depressed panic attack. Uncoping stress to the maximum.

When you say "delay and make recovery unlikely" in light of maladaptive neuroplasticity... Are you referring to not being able to recover (reverse tinnitus) even after FX-322?
Not at all! I should have worded that more carefully. I meant perception diminishing with time naturally on its own.
 
That was quick. They had no trouble in recruiting for this clinical trial but had trouble in recruiting for the Phase 2a clinical trials.
COVID-19 protocols are better established now. And it's a smaller group of participants.
 
Support cells aren't lost until they are replaced by flat epithelia which is a form of scarring. This doesn't start to happen until the profound range.

To produce hair cells at that point, researchers are looking at (in the future) transducing the fibroblasts in the scar into hair cells using viral vectored epigenetic modulators essentially.
Is it possible that there could be some people who have profound hearing loss in the very high frequencies, who would still benefit from FX-322?

For example, I look at that image with the photo of the missing hair cells with intact support cells and notice that the support cells were fairly intact. Isn't it therefore plausible that the support cells would generate regrowth even in a situation of profound hearing loss since they are still present?
 
Is it possible that there could be some people who have profound hearing loss in the very high frequencies, who would still benefit from FX-322?

For example, I look at that image with the photo of the missing hair cells with intact support cells and notice that the support cells were fairly intact. Isn't it therefore plausible that the support cells would generate regrowth even in a situation of profound hearing loss since they are still present?
It's possible. I talked to one researcher and she said people start to lose support cells in the profound range finally leading to an epithelial scar. We don't have imaging to see histology in a living patient to know if they have progressed to that point so I would say it would be worth a try at least.
 
I'd like to point something out re: support cells. We seem to keep discussing those support cells in cochlea pictures that are next to hair cells. However, Frequency Therapeutics describes the progenitor support cells as being underneath the hair cells.

Are we sure the LGR5+ "progenitor" support cells aren't just underneath those "filler" support cells pictured on damaged cochleas?

If so, could it be that in profound regions of loss cases, the progenitors lie just underneath?

Cite:

The cochlea is the organ within the ear that controls hearing. Within the cochlea are rows of inner and outer sensory (or hair) cells that help filter and tune sounds while also providing connections to the brain. When these cells are damaged – either by noise, age or infection – they do not naturally regenerate. This damage can lead to sensorineural hearing loss, the primary cause of 90 percent of all hearing loss.
But underneath these rows of sensory cells are the progenitor cells that created the original hair cells when we were in utero. FX-322 is made of two small molecules that, when combined, aim to turn on these progenitor cells and enable the growth of new sensory cells (while also creating new progenitor cells) and potentially restore hearing.​

Source:
https://investors.frequencytx.com/sec-filings/sec-filing/8-k/0001193125-20-127683
 
I'd like to point something out re: support cells. We seem to keep discussing those support cells in cochlea pictures that are next to hair cells. However, Frequency Therapeutics describes the progenitor support cells as being underneath the hair cells.

Are we sure the LGR5+ "progenitor" support cells aren't just underneath those "filler" support cells pictured on damaged cochleas?

If so, could it be that in profound regions of loss cases, the progenitors lie just underneath?

Cite:

The cochlea is the organ within the ear that controls hearing. Within the cochlea are rows of inner and outer sensory (or hair) cells that help filter and tune sounds while also providing connections to the brain. When these cells are damaged – either by noise, age or infection – they do not naturally regenerate. This damage can lead to sensorineural hearing loss, the primary cause of 90 percent of all hearing loss.
But underneath these rows of sensory cells are the progenitor cells that created the original hair cells when we were in utero. FX-322 is made of two small molecules that, when combined, aim to turn on these progenitor cells and enable the growth of new sensory cells (while also creating new progenitor cells) and potentially restore hearing.​

Source:
https://investors.frequencytx.com/sec-filings/sec-filing/8-k/0001193125-20-127683
What I was told:

Anything that doesn't look histological like a "flat, epithelial scar" is going to have support cells, yes.

And that end stage scaring doesn't begin to happen until the profound stage.

Has nothing to do with any particular picture.
 
What I was told:

Anything that doesn't look histological like a "flat, epithelial scar" is going to have support cells, yes.

And that end stage scaring doesn't begin to happen until the profound stage.

Has nothing to do with any particular picture.
So therefore it is possible to be in the profound stage and still have support cells present?
 
So therefore it is possible to be in the profound stage and still have support cells present?
Since profound is when you start to lose support cells (again per one researcher I talked to), then yes it's possible but without being able to image the inner ear, you would be guessing if you have progressed to epithelial scarring or not.

I would say it's worth trying the drug in that case anyway since it seems low risk in its safety profile.
 
Another supposed cause of idiopathic sudden sensorineural hearing loss is possible vascular issues.

Does anyone know if poor blood flow will hinder FX-322?

Once the blood flow is disrupted can it be fixed or return to normal? Would an MRI pick up on this?
 
Okay, thanks a lot. So the better the hearing was before the injury (noise trauma for example), the better the results will be with FX-322?
This is actually also another unknown at this time. There is no evidence to suggest either way whether someone with better hearing or worse hearing will benefit more from FX-322 as there are no outcome to support this. The information from the Phase 1/2 trial gave us details only about their improvement and nothing else.
 
None of that says anything about hair cells. I suppose the free radical damage they refer to is run of the mill inflammatory damage, though. If that damages hair cells specifically, I don't see why that would exclude FX-322 from working personally.
I know it doesn't say anything about hair cells specifically, however I would suggest that the comment about noise hearing loss does. I agree also at this stage that there is nothing to say FX-322 wouldn't work in this case.
 
So Frequency Therapeutics' stock had a pretty dramatic rise (hitting $42 a share) over the last 2-3 weeks, and late last week it plunged down to $30 a share.

It's unclear what triggered the run-up, but I noticed that the plunge coincided with Otonomy's OTO-413 results (it came the day after). I wonder if stock traders don't realize that FX-322 and OTO-413 treat different things?

It's kind of interesting to watch the stock. Its movement seems very irrational.
 
So Frequency Therapeutics' stock had a pretty dramatic rise (hitting $42 a share) over the last 2-3 weeks, and late last week it plunged down to $30 a share.

It's unclear what triggered the run-up, but I noticed that the plunge coincided with Otonomy's OTO-413 results (it came the day after). I wonder if stock traders don't realize that FX-322 and OTO-413 treat different things?

It's kind of interesting to watch the stock. Its movement seems very irrational.
Stocks with small market caps tend to be more volatile, i.e. irrational. After a run up some people usually take some profit, so the dip is nothing out of the ordinary. Could be some correlation with the Otonomy trial, but I'm skeptical about it being the main driver.
 
Many professional money managers bought shares at low prices. From that point they knew that enthusiasm from retail - Dick and Jane with subject matter conditions would invest. From this, volume was low, but price did move up with the help of Dick and Jane.

Then money managers, not hedge funds thought that price was becoming a little too expensive for Dick and Jane to continue investing so they took some profit. They also wanted a small shake out from retail - Dick and Jane before reinvestment. All professional managers, including bio hedge fund managers will be watching the investors' presentations on January 19, where price may go back up a few points.

From there on, any data that would support future FDA approvals will drive the price up considerably. Any approvals will rocket price.
 

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