Frequency Therapeutics — Hearing Loss Regeneration

While I applaud any and all initiatives, this is what sometimes worries me. There's more causes of tinnitus but it seems like it's just not given any thought. I understand that they have to go with the most common, and probably most ''easy'' to fix though. Just hope that eventually everyone can have some relief. I guess it's good there's more research going on than ever, I just truly wish all of it would be focused on the mechanisms of tinnitus and how to treat/cure it and not whatever type of person can best deal with tinnitus. That doesn't help anyone.
If the Phase 2A tinnitus results are promising, where restoring IHC/OHC treats it as a symptom, I would expect a long-term shift in research. In any area of tinnitus research. The understanding of tinnitus in the case of SNHL/NIHL will be well known. As a result, research/commercial dollars may shift to other causes for treatment.
 
Agree with you - noxacusis seems to be a big unknown and it may well be better served by drugs that target the nerve fibers directly, like the new Retigabine or NaV 1.7 blockers. There's some interesting insights from the 2017 ARO event, at a conference hosted by Hyperacucis Research and the write-up from that included some discussion on the possible implications of regenerative approaches for hyperacusis (both loudness and pain) on pgs. 6-7: https://hyperacusisresearch.org/wp-content/uploads/2017/03/ARO-2017-Technical-Summary.pdf

I think one of the big unknowns is whether pain hyperacusis morphs into a self-perpetuating thing as you say so then hair cell regeneration may not be the way to go if the pain fibers retain sensitisation. But there's some interesting discussion there.
I still believe that to fix pain and loudness hyperacusis you need to fix the underlying issues in the ear such as OHCs, IHCs and synapses which FX-322, OTO-413 and Hough pill should do.

Even if Retigabine solves pain hyperacusis, if you stop the drug, does that mean pain hyperacusis comes back, therefore not fixing the underlying issue. I wouldn't want to take Retigabine long term, that's why I hope something like FX-322 could solve this issue.
 
I still believe that to fix pain and loudness hyperacusis you need to fix the underlying issues in the ear such as OHCs, IHCs and synapses which FX-322, OTO-413 and Hough pill should do.

Even if Retigabine solves pain hyperacusis, if you stop the drug, does that mean pain hyperacusis comes back, therefore not fixing the underlying issue. I wouldn't want to take Retigabine long term, that's why I hope something like FX-322 could solve this issue.
I think the thing about noxacusis (and just hyperacusis generally I guess) is that it is such a heterogeneous condition where the prognosis is really uncertain e.g. why do some cases resolve substantially whereas there are cases where it clearly becomes a chronic, intractable condition and seems to take on a life of its own.

Hyperacusis Research said on their Facebook page they get a lot of questions about Frequency's drug and whether it will help but they said they just don't know at this stage. I don't think we'll know until people report back after getting it. Fixing the underlying issue makes sense to me - I wouldn't be surprised if drugs like FX-322 helped for some people but equally wouldn't be surprised if it doesn't fix every case? Maybe an optimal solution would be 1) regenerative drug and 2) blocking the type 2 fibers if you have an especially entrenched case. I'm not sure, these are just my speculations and I don't have a scientific background.

Also, regarding Retigabine I guess the ideal solution would be to do local delivery administration in the ear to avoid systemic effects. I think that's what Paul Fuchs has mentioned.
 
I don't have loudness hyperacusis any more and I just mask my tinnitus as much as I can.
I know it's speculation, but do you think there's a chance FX-322 may help loudness hyperacusis? I have severe reactive tinnitus, which I am starting to think is more akin to hyperacusis than it is to proper tinnitus. It's odd because my baseline is moderate, but every consistent external noise has a debilitating and intrusive reactive overlay attached to it that I can't mask.
 
I know it's speculation, but do you think there's a chance FX-322 may help loudness hyperacusis? I have severe reactive tinnitus, which I am starting to think is more akin to hyperacusis than it is to proper tinnitus. It's odd because my baseline is moderate, but every consistent external noise has a debilitating and intrusive reactive overlay attached to it that I can't mask.
I believe it will, yes.
 
My deafness is in the left ear 4000 Hz, 40 dB.
The tinnitus is also in the left ear.

FX-322 treats frequencines from 8000 Hz upwards.

I'm disappointed.

Is it not possible to increase the concentration of this gel?
Is it possible to quadruple the concentration?

Phase1/2 is 0.05ml, 0.2ml.
The amount of medicine was four times.
 
I still believe that to fix pain and loudness hyperacusis you need to fix the underlying issues in the ear such as OHCs, IHCs and synapses which FX-322, OTO-413 and Hough pill should do.

Even if Retigabine solves pain hyperacusis, if you stop the drug, does that mean pain hyperacusis comes back, therefore not fixing the underlying issue. I wouldn't want to take Retigabine long term, that's why I hope something like FX-322 could solve this issue.
I'm wholly with you on this topic. The chart that showed sources of tinnitus tends to be fairly accurate. Also, there is other evidence of reducing tinnitus like hearing aids and implants. It is quite likely we will see similar (hopefully better) results post the treatment. Pretty positive times ahead.
 
They posted this yesterday:

https://investors.frequencytx.com/n...eutics-announces-42-million-private-placement

"The Company plans to use the net proceeds from the private placement to further advance the clinical development of FX-322, its lead product candidate in Phase 2a development for sensorineural hearing loss, by gaining additional insights regarding the patient populations and severity of hearing loss that FX-322 may treat."

Given that the drug worked best for moderate-severe patients in Phase 1/2, I'd say they're looking at going beyond 70 dB loss. Maybe also more focus on tinnitus and hyperacusis.
 
They posted this yesterday:

https://investors.frequencytx.com/n...eutics-announces-42-million-private-placement

"The Company plans to use the net proceeds from the private placement to further advance the clinical development of FX-322, its lead product candidate in Phase 2a development for sensorineural hearing loss, by gaining additional insights regarding the patient populations and severity of hearing loss that FX-322 may treat."

Given that the drug worked best for moderate-severe patients in Phase 1/2, I'd say they're looking at going beyond 70 dB loss. Maybe also more focus on tinnitus and hyperacusis.
I don't think there is any reason to think this won't work as long as you have target cells (cells that the drug exerts its effects on I mean) left (LGR+support cells), so this should have at least some benefit up to profound ( > 90dB) loss imo.
 
They posted this yesterday:

https://investors.frequencytx.com/n...eutics-announces-42-million-private-placement

"The Company plans to use the net proceeds from the private placement to further advance the clinical development of FX-322, its lead product candidate in Phase 2a development for sensorineural hearing loss, by gaining additional insights regarding the patient populations and severity of hearing loss that FX-322 may treat."

Given that the drug worked best for moderate-severe patients in Phase 1/2, I'd say they're looking at going beyond 70 dB loss. Maybe also more focus on tinnitus and hyperacusis.
Interesting. "Gaining additional insights on populations that FX-322 may treat"

I interpret this as a LARGE MARKET of potential customers that aren't being represented in the Phase 2A.

The optimist in me thinks that they may have realized a missed opportunity in the patients turned away from the Phase 2A that didn't fit their strict acceptance criteria. It very well could have been patients that have normal/mild-loss standard audiogram PTA but still presented tinnitus/hyperacusis.

An investigation that focused on tinnitus/hyperacusis measures with "normal/mild PTA" hearing loss would apply to a significantly large population. Consider the segment of members on this website that would fit into that broad category.

"Severity of hearing loss" may be an indicator that they are looking into the severe-to-profound levels of hearing loss.

I'm curious how they may proceed with gaining these additional insights? Can they do additional "trials" or experiments outside of an FDA clinical trial? OR setup a parallel trial, testing FX-322 for these other patient criteria?

Thoughts?

I'd also like to add that at this point, early participants have completed the Phase 2A. Dosing started in October of 2019. So, Frequency likely has some type of interim analysis / top-line readout from those that have completed. Perhaps there is something compelling?
 
When will the Frequency Therapeutics interview be released for Patreons of the Tinnitus Talk Podcast?

I'm incredibly grateful for this website, you guys are really on it! (y)
 
When will the Frequency Therapeutics interview be released for Patreons of the Tinnitus Talk Podcast?

I'm incredibly grateful for this website, you guys are really on it! (y)
Good timing - that day is today!

I and @Hazel are literally just now making some final preparations.

Look for the announcement in this thread no later than today at 8 pm (EDT, i.e. UTC/GMT -4 hours).
 
"Severity of hearing loss" may be an indicator that they are looking into the severe-to-profound levels of hearing loss.
Hopefully. If they have interim results that showed more effectiveness with the consistent redosing, then they might want to look into it more.

I'm hoping for an actual medical miracle here and that with the redosing, it sets up the process of continuous repair of upper frequencies as well. Either through a few hair cells and support existing at the higher frequencies to be enough to slowly culture back into working order, or through the activation of the support cell division that it sort of kicks off differentiation in higher frequencies too while the gel is present. Which, although the chances are slim, could end up happening as all they've tested so far is on recently damaged mice, removed human cells they they just damaged, and a singular dose patients.
 
I know it's speculation, but do you think there's a chance FX-322 may help loudness hyperacusis? I have severe reactive tinnitus, which I am starting to think is more akin to hyperacusis than it is to proper tinnitus. It's odd because my baseline is moderate, but every consistent external noise has a debilitating and intrusive reactive overlay attached to it that I can't mask.
I have a similar thing where the sounds that irritate my ear (pain hyperacusis symptoms) most i.e. artificial audio in turn produce a reactive tinnitus which seems to be the same frequency as the external noise. This results in a very piercing and abrasive reactive tinnitus that I can almost physically 'feel' as well as hear.
 


The time has finally come!

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➡️ Listen to the interview

This episode was produced with contributions from two awesome members of this community: @mrbrightside614 and @FGG. And behind the scenes – but no less important - @Markku and @Autumnly have worked hard to provide you with the best listening experience.

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My deafness is in the left ear 4000 Hz, 40 dB.
The tinnitus is also in the left ear.

FX-322 treats frequencines from 8000 Hz upwards.

I'm disappointed.

Is it not possible to increase the concentration of this gel?
Is it possible to quadruple the concentration?

Phase1/2 is 0.05ml, 0.2ml.
The amount of medicine was four times.
I think that in an indirect way they are trying to 'increase the concentration' by repeating that safe phase 1 dose four times. To increase the concentration in a single dose would maybe entail a new round of trials. They won't risk the unknown by using a different concentration on something as delicate as the cochlea. Like @FGG mentioned earlier, it makes sense for them to try and reach all frequencies.

Oh the Tinnitus Talk Podcast is out!!!
 
Interesting. "Gaining additional insights on populations that FX-322 may treat"

I interpret this as a LARGE MARKET of potential customers that aren't being represented in the Phase 2A.

The optimist in me thinks that they may have realized a missed opportunity in the patients turned away from the Phase 2A that didn't fit their strict acceptance criteria. It very well could have been patients that have normal/mild-loss standard audiogram PTA but still presented tinnitus/hyperacusis.

An investigation that focused on tinnitus/hyperacusis measures with "normal/mild PTA" hearing loss would apply to a significantly large population. Consider the segment of members on this website that would fit into that broad category.

"Severity of hearing loss" may be an indicator that they are looking into the severe-to-profound levels of hearing loss.

I'm curious how they may proceed with gaining these additional insights? Can they do additional "trials" or experiments outside of an FDA clinical trial? OR setup a parallel trial, testing FX-322 for these other patient criteria?

Thoughts?

I'd also like to add that at this point, early participants have completed the Phase 2A. Dosing started in October of 2019. So, Frequency likely has some type of interim analysis / top-line readout from those that have completed. Perhaps there is something compelling?
With regards to expanding the patient population (for example with regards to severity of hearing loss), I don't see why a Phase 2b trial couldn't include those patients. I do think they will expand to severe/profound. They are already testing mild hearing loss patients in Phase 2a, so the only way of expanding would be with patients beyond moderate-severe hearing loss.
 
With regards to expanding the patient population (for example with regards to severity of hearing loss), I don't see why a Phase 2b trial couldn't include those patients. I do think they will expand to severe/profound. They are already testing mild hearing loss patients in Phase 2a, so the only way of expanding would be with patients beyond moderate-severe hearing loss.
According to the Clinical Trial site, yes... the inclusion criteria states "Pure Tone Audiometry (PTA) within 26-70 dB in the ear to be injected." 26 dB PTA appears to be in the middle of the Mild range. However, they have stated that they're screening for patients that match those that had "the most room for improvement" similar to the Phase 1/2. So, it's likely they have a secondary screening process that accepts participants in the Moderately-Moderately Severe PTA range. More room for improvement, more significant results. This also aligns with the primary outcomes of the Phase 2A, which is what the FDA will use as a final measurement for approving the drug.

Also, in an interview a while ago, they mentioned the "ceiling effect" they noticed with Mild Patients mixed in the Phase 1/2. Ceiling effects are not good in this type of trial, where you can improve hearing only so much.

It stands to reason, that people with Normal/Mild Hearing loss represent a larger, much more substantial market (age, status, resources, marketability) than those further down the PTA levels. So, why not setup a parallel study that focuses on improving tinnitus on a huge sample market, where they wont see improvements in PTA, but they may see improvements in UHF audiograms, tinnitus, and potentially speech-in-noise hearing loss. This creates a market for "preventative care" or "hearing health" that we see with dentists/eye doctors. If this is the direction, it would enable ENTs/Audiologists to encourage annual checkups on hearing, and offer FX-322 as a "preventative" to restore hearing before it leads to tinnitus / hearing aides / multiple injections.

I would hazard to guess if any of us had an annual UHF/Speech-in-noise type test, that is often a precursor to hearing loss, we may not have the losses that led to our tinnitus. So, in this future state where FX-322 is available, it could be used a tool to maintain cochlear health to mitigate the risk of UHF/speech-in-noise loss often associated with SNHL/NIHL.

Huge potential here.
 
Just finished the Tinnitus Talk Podcast. It was very well done. It's sad that Carl only had an hour (I could probably have listened for several), but it was nice to hear him offer up to come back after Phase 2a. The interview and analysis was also very good.
 
It stands to reason, that people with Normal/Mild Hearing loss represent a larger, much more substantial market (age, status, resources, marketability) than those further down the PTA levels. So, why not setup a parallel study that focuses on improving tinnitus on a huge sample market, where they wont see improvements in PTA, but they may see improvements in UHF audiograms, tinnitus, and potentially speech-in-noise hearing loss. This creates a market for "preventative care" or "hearing health" that we see with dentists/eye doctors. If this is the direction, it would enable ENTs/Audiologists to encourage annual checkups on hearing, and offer FX-322 as a "preventative" to restore hearing before it leads to tinnitus / hearing aides / multiple injections.

I would hazard to guess if any of us had an annual UHF/Speech-in-noise type test, that is often a precursor to hearing loss, we may not have the losses that led to our tinnitus. So, in this future state where FX-322 is available, it could be used a tool to maintain cochlear health to mitigate the risk of UHF/speech-in-noise loss often associated with SNHL/NIHL.

Huge potential here.
I mean, I doubt they'll take that model. Annual ENT and Audiologist would be a bit extreme, but it would give them a better understanding of what causes tinnitus, and something to do about hearing loss, so I could see it becoming a greater part of doctor visits. And, if it resolves acute tinnitus in the upper frequencies, as I expect it would, then I can't imagine people would treat tinnitus as they do now, where there's nothing that can be done, so eh. I believe it would increase understanding of it, though I worry it would also lead to other possible solutions being brought to a close. If you find a way to resolve acute tinnitus, you have effectively resolved the issue for everyone that comes after, making a solution to the chronic case less profitable. It's essentially the CGP Grey video where you're asked which side of the line of curing death do you want to be on.

I would also argue such a world where we don't have the losses that led to our tinnitus could already exist. It just requires that doctors, the school system, the media to properly warn and explain the dangers. There's a huge amount of people who feel that hearing loss is something that happens when you get old, not when you're young. They underestimate the damage and loudness of the things they're doing. If, once a year your GP gave you a brief 15 minute lecture on how precious hearing is, checked that you weren't being careless by asking a few questions, like "Have you ever used your EarPods at high volume? Have you experienced ringing in your ears in the past year?" and explained the dangers, that it's not just losing hearing but getting stuck with tinnitus and hyperacusis, then I could see a huge number of people adjusting their habits. If it was properly explained in health class or in a final hearing check before leaving high school, I think a lot of us would have been spared. I certainly would have taken more precautions.
 
I would also argue such a world where we don't have the losses that led to our tinnitus could already exist. It just requires that doctors, the school system, the media to properly warn and explain the dangers. There's a huge amount of people who feel that hearing loss is something that happens when you get old, not when you're young. They underestimate the damage and loudness of the things they're doing. If, once a year your GP gave you a brief 15 minute lecture on how precious hearing is, checked that you weren't being careless by asking a few questions, like "Have you ever used your EarPods at high volume? Have you experienced ringing in your ears in the past year?" and explained the dangers, that it's not just losing hearing but getting stuck with tinnitus and hyperacusis, then I could see a huge number of people adjusting their habits. If it was properly explained in health class or in a final hearing check before leaving high school, I think a lot of us would have been spared. I certainly would have taken more precautions.
So, If I am understanding this correctly. You are suggesting institutionalizing hearing loss education by coordinating government, institutional, and private entities? I don't see it happening; too ideological. People can't even get it into their heads to wear a facemask to prevent the spread of COVID-19 in the US where daily data is presented to them via the media, government, and private entities coordinating.

In a lot of ways what you're describing is happening, since the 1990's; Music player / phone makes issue warnings. There are warnings for tools about hearing loss. The WHO claims that Hearing Loss is the #2 economic health threat, only behind global warning. YET, research has indicated that hearing loss and tinnitus are on the rise amongst a younger demographic and is expected to increase over the next 20 years. So, it doesn't seem to be enough just to take the pamphlet and questionnaire approach.

Plus, its impossible to prevent accidents/environmental factors where hearing loss unfortunately occurs; Airbags come to mind, or living near a railway or construction zone. Occupational / military situations.

Giving private practices new tools/techniques to gain repeat business is far a better fit for the current model. Potential for profit drives adoption in this industry.
 
So, If I am understanding this correctly. You are suggesting institutionalizing hearing loss education by coordinating government, institutional, and private entities? I don't see it happening; too ideological. People can't even get it into their heads to wear a facemask to prevent the spread of COVID-19 in the US where daily data is presented to them via the media, government, and private entities coordinating.

In a lot of ways what you're describing is happening, since the 1990's; Music player / phone makes issue warnings. There are warnings for tools about hearing loss. The WHO claims that Hearing Loss is the #2 economic health threat, only behind global warning. YET, research has indicated that hearing loss and tinnitus are on the rise amongst a younger demographic and is expected to increase over the next 20 years. So, it doesn't seem to be enough just to take the pamphlet and questionnaire approach.

Plus, its impossible to prevent accidents/environmental factors where hearing loss unfortunately occurs; Airbags come to mind, or living near a railway or construction zone. Occupational / military situations.

Giving private practices new tools/techniques to gain repeat business is far a better fit for the current model. Potential for profit drives adoption in this industry.
Making quieter tools and devices will be a start. Especially quieter MRIs and dentist tools.
 
I think that in an indirect way they are trying to 'increase the concentration' by repeating that safe phase 1 dose four times. To increase the concentration in a single dose would maybe entail a new round of trials. They won't risk the unknown by using a different concentration on something as delicate as the cochlea. Like @FGG mentioned earlier, it makes sense for them to try and reach all frequencies.

Oh the Tinnitus Talk Podcast is out!!!
I think attempting multiple doses is much easier to try to do for now than trying to restart using a bigger dose.

Doing this and then recognising and understanding that this provides positive effects and benefit is much simpler than needing to start from scratch. Also at this time there is no information in regards to what multiple doses do in terms of outcomes.

This is also beneficial from the perspective that there is the ability for Frequency Therapeutics to continue to proceed with trials and treatment uninhibited so they can recognise, report and even commence providing the treatment from specialists.

If this has been successful and they can commercially offer the treatment then they can go back and try doing this with a bigger dose while also being able to provide the treatment to patients. Pretty much no one will actually care if they have to go through four doses to get the treatment as compared with one.
 
My deafness is in the left ear 4000 Hz, 40 dB.
The tinnitus is also in the left ear.

FX-322 treats frequencines from 8000 Hz upwards.

I'm disappointed.

Is it not possible to increase the concentration of this gel?
Is it possible to quadruple the concentration?

Phase1/2 is 0.05ml, 0.2ml.
The amount of medicine was four times.
It treats frequencies upwards from 8000 Hz according to the trial information thus far. You need to remember that they have tested one dose only so far so they do not know the full facts around multiple doses etc. Supposedly in vitro this worked within all areas and thus it is a matter of getting it delivered to all parts of the ear.
 
It treats frequencies upwards from 8000 Hz according to the trial information thus far. You need to remember that they have tested one dose only so far so they do not know the full facts around multiple doses etc.
Once they release FX-322 out to the public with their current delivery method it shouldn't take too long to release the new delivery method if they have created one. I heard it takes about a year to test out a new delivery method once it's out.
 
Music player / phone makes issue warnings. There are warnings for tools about hearing loss. The WHO claims that Hearing Loss is the #2 economic health threat, only behind global warning. YET, research has indicated that hearing loss and tinnitus are on the rise amongst a younger demographic and is expected to increase over the next 20 years. So, it doesn't seem to be enough just to take the pamphlet and questionnaire approach.

Plus, its impossible to prevent accidents/environmental factors where hearing loss unfortunately occurs; Airbags come to mind, or living near a railway or construction zone. Occupational / military situations.

Giving private practices new tools/techniques to gain repeat business is far a better fit for the current model. Potential for profit drives adoption in this industry.
Posted the response in the awareness thread, as that's more what this discussion is.

To summarize my points: Anti-Smoking campaigns were effective and brought smoking from 42% in 1965 to 23% in 2000, down to 14% in 2019. The problem is that the warnings lack any context, and if you just tell people "This can hurt you at some point in the future" many ignore it.

A solution that has profit will help raise awareness though, and actually give ENTs and doctors more of a reason to care about it, I agree. I still wouldn't see something like a dentist office scenario, but I could see the ads for FX-322 bringing attention to hearing loss in general, which has a higher chance of actually happening and therefore would be more effective. Although, I think going over it in health class or the doctors now could help too.
 
Posted the response in the awareness thread, as that's more what this discussion is.

To summarize my points: Anti-Smoking campaigns were effective and brought smoking from 42% in 1965 to 23% in 2000, down to 14% in 2019. The problem is that the warnings lack any context, and if you just tell people "This can hurt you at some point in the future" many ignore it.

A solution that has profit will help raise awareness though, and actually give ENTs and doctors more of a reason to care about it, I agree. I still wouldn't see something like a dentist office scenario, but I could see the ads for FX-322 bringing attention to hearing loss in general, which has a higher chance of actually happening and therefore would be more effective. Although, I think going over it in health class or the doctors now could help too.
Good point about gaining more profit with the use of FX-322 ads. Maybe this will allow people to treat hearing loss seriously but they also need to talk about hyperacusis and tinnitus.
 

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