Frequency Therapeutics — Hearing Loss Regeneration

It's been a while since I've posted this, but I think it needs to be near the top again:

Tinnitus Talk Podcast:

Re: Patients that received FX-322 in the Phase 1/2 trial.

"... there is anecdotal reports as patients have come back and visited with ENTs when they have had conversations with them about how they are doing. Some of them have offered that they have had improvements in tinnitus, there's nothing that we can quantitate there. Again, it adds to the excitement of the opportunity. "

- Carl LeBel, Frequency Therapeutics
It is incredibly likely the reason that Frequency Therapeutics refused to recognise the positive reports regarding tinnitus improvement is due to it being an unqualified fact from a research/trial perspective.

Pretty sure this is simply a nice way which Frequency Therapeutics can hint that there's the possibility of positive influence on tinnitus with FX-322, without violating their FDA obligation of not making misleading and/or false claims.
 
Frequency can only really "market" what they know the drug can address; and at this time it's high frequencies above 8 kHz and word score.

If the Phase 2A shows improvements deeper into the cochlea; where audiogram improve down to 6 kHz, 4 kHz, etc, where tinnitus improves, where pure tone averages improve, where quality-of-life scores improve, etc. Frequency will adjust their messaging to "market" these new findings immediately.

It's clear their strategy is to get this drug into the market ASAP even though it isn't a complete treatment. In doing so, Frequency will be able to create revenue and positive cash flow from the commercialization of FX-322, which in turn would enable them to invest in developing the "whole cochlea" drug/delivery method.
 
Exactly, I am confident that they will be able to develop a delivery method to distribute the drug across the entire cochlea. It would expand their addressable patient population considerably.

Additionally I don't think this would require any additional trials as the safety and efficacy of the drug should have been determined by then.
 
Frequency can only really "market" what they know the drug can address; and at this time it's high frequencies above 8 kHz and word score.

If the Phase 2A shows improvements deeper into the cochlea; where audiogram improve down to 6 kHz, 4 kHz, etc, where tinnitus improves, where pure tone averages improve, where quality-of-life scores improve, etc. Frequency will adjust their messaging to "market" these new findings immediately.

It's clear their strategy is to get this drug into the market ASAP even though it isn't a complete treatment. In doing so, Frequency will be able to create revenue and positive cash flow from the commercialization of FX-322, which in turn would enable them to invest in developing the "whole cochlea" drug/delivery method.
Very true. I would think that no additional clinical trials would be forthcoming for the "new and improved" FX-322 that reaches 4 kHz and beyond, at least I hope not.
 
Very true. I would think that no additional clinical trials would be forthcoming for the "new and improved" FX-322 that reaches 4 kHz and beyond, at least I hope not.
I thought I read somewhere that reformulations require abbreviated trials that generally take up to a year.

Is this accurate, @FGG?
 
Frequency can only really "market" what they know the drug can address; and at this time it's high frequencies above 8 kHz and word score.

If the Phase 2A shows improvements deeper into the cochlea; where audiogram improve down to 6 kHz, 4 kHz, etc, where tinnitus improves, where pure tone averages improve, where quality-of-life scores improve, etc. Frequency will adjust their messaging to "market" these new findings immediately.

It's clear their strategy is to get this drug into the market ASAP even though it isn't a complete treatment. In doing so, Frequency will be able to create revenue and positive cash flow from the commercialization of FX-322, which in turn would enable them to invest in developing the "whole cochlea" drug/delivery method.
Frequency Therapeutics cannot currently even market that FX-322 treats above 8 kHz because to date, they do not have any actual data or approved information which can support this claim. To do so would be a breach of the FDA regulations relating to making unfounded and also false claims about a treatment.

Thus the information disseminated to date has been largely speculative and also generic. This is despite the fact that logical and rational conclusions about FX-322 can be made.
Exactly, I am confident that they will be able to develop a delivery method to distribute the drug across the entire cochlea. It would expand their addressable patient population considerably.

Additionally I don't think this would require any additional trials as the safety and efficacy of the drug should have been determined by then.
Very true. I would think that no additional clinical trials would be forthcoming for the "new and improved" FX-322 that reaches 4 kHz and beyond, at least I hope not.
While I agree with your points overall, one thing that would need to be done by Frequency Therapeutics - if they determined that they could get better results with a reformulated medicine - is to at least take this new reformulation through the safety trials. As a result there would be a delay prior to its release, albeit brief.

The approval granted by the FDA to enable use of FX-322 will only cover the current treatment in terms of both size of the dose and also the medication mix. The positive aspect of needing to do this is that the medication has been shown to be extremely safe thus far. Hence there simply shouldn't be much trouble getting a new dose through the required processes.
 
Hopefully the theory that the more FX-322 doses you get the more benefit you receive from the drug is true and that it targets different areas from each dose.
 
I've got a question.

Let's say FX-322 gets FDA approved, passes efficacy, safety etc etc.

What are people's expectations? For example, do you think FX-322 will cure hearing loss and give you the hearing of a teenager again?

Or do you think it will more just help hearing aid users get more use out of their hearing aids (understanding clarity of speech rather than just amplifying the volume)?

I know it's all speculation at the minute and only proof of concept has been demonstrated in word scores so far.

I'm just curious.

Obviously also interested in the effects of tinnitus. Do you hold high expectations that it will cure tinnitus or just mask it with improvements in hearing?
 
Considering that some of the phase 1 subjects had substantial word recognition improvement while the drug (in their dose) only seemed to target areas above 7/8 kHz, I think it could replace hearing aids at least for some people assuming that they find a way to get the drug into the lower frequencies as well.

I expect improvement in tinnitus just like how hearing aids improve tinnitus for some sufferers thanks to more auditory input and additional masking. I don't expect it to magically cure tinnitus, more a reduction in perceived volume.
 
I've got a question.

Let's say FX-322 gets FDA approved, passes efficacy, safety etc etc.

What are people's expectations? For example, do you think FX-322 will cure hearing loss and give you the hearing of a teenager again?

Or do you think it will more just help hearing aid users get more use out of their hearing aids (understanding clarity of speech rather than just amplifying the volume)?

I know it's all speculation at the minute and only proof of concept has been demonstrated in word scores so far.

I'm just curious.

Obviously also interested in the effects of tinnitus. Do you hold high expectations that it will cure tinnitus or just mask it with improvements in hearing?
I suspect it will vary from person to person how well it works in the first commercial version.

If we accept that tinnitus experienced by the patient is a symptom of NIHL/SNHL, then FX-322 may eliminate or alleviate the symptom.

My relatively unscientific opinion is that patients that haves normal audiogram with high frequency tinnitus and high frequency hearing loss will probably see tinnitus symptoms resolved.

Those with a wider range of hearing loss and tinnitus will probably experience a balance of hearing improvement and reduced tinnitus. More new cells providing optimal signals to the auditory should help reduce the intensity from whatever remains that is damaged. Still I'm sure a welcome improvement.

Some may still require hearing aids that see some improvements but don't respond as well. But, they may not need ones that are as powerful, or only in certain situations.

Frequency has repeatedly said that they believe FX-322 causes the replacement of dead or damaged cells at the site of action with new cells.

I for one, am curious to learn how people with this type of improvement experience things beyond speech. For example, music and TV? Does the auditory system recalibrate for the restored cells? Does a system with old and new "parts" function in harmony?
 
So, aplogies if this has been answered before.

Any idea when Frequency Therapeutics will stop accepting new people to test FX-322? Any rough estimates?
 
I really don't see why restoring frequencies wouldn't reduce or stop tinnitus altogether.

There have already been several people on Tinnitus Talk who have seen huge reductions in tinnitus due to stem cell therapy. Therefore, since FX-322 is specific to progenitor cells and HCs, I'm sure the same results will be achievable or even more effective.

Also take note that the brain is neuroplastic and will adjust to changes in your body, however it may take many months until the tinnitus reduces or goes away. This is evident with people who had stem cell therapy on this site, who reported it took months to see major improvements in their tinnitus.
 
I suspect it will vary from person to person how well it works in the first commercial version.

If we accept that tinnitus experienced by the patient is a symptom of NIHL/SNHL, then FX-322 may eliminate or alleviate the symptom.

My relatively unscientific opinion is that patients that haves normal audiogram with high frequency tinnitus and high frequency hearing loss will probably see tinnitus symptoms resolved.

Those with a wider range of hearing loss and tinnitus will probably experience a balance of hearing improvement and reduced tinnitus. More new cells providing optimal signals to the auditory should help reduce the intensity from whatever remains that is damaged. Still I'm sure a welcome improvement.

Some may still require hearing aids that see some improvements but don't respond as well. But, they may not need ones that are as powerful, or only in certain situations.

Frequency has repeatedly said that they believe FX-322 causes the replacement of dead or damaged cells at the site of action with new cells.

I for one, am curious to learn how people with this type of improvement experience things beyond speech. For example, music and TV? Does the auditory system recalibrate for the restored cells? Does a system with old and new "parts" function in harmony?
I believe FX-322 will help us if our tinnitus is in the high frequencies.

Once Frequency Therapeutics comes up with a new formulation that allows it to reach the lower frequencies as well this should help everyone who has tinnitus caused by noise damage.

In the current Phase 2a clinical trial for FX-322 they are testing out whether with additional doses it targets the lower frequencies too and seeing if we get more benefit in our hearing but also in reducing tinnitus.
 
I think the idea that FX-322 is only effectively working at 8 kHz+ is actually somewhat misguided and premature at this stage.

So far, it seems fairly logical and also obvious that the treatment will target the higher frequencies first based on the way which we know the cochlear works. We also know this was assumed to have occurred after considering the results in the phase 1/2 trial. What we also know is FX-322 worked to regrow cells across the board when evaluated in the lab. Hence we cannot assume that Frequency Therapeutics' treatment aim is to only target the upper frequencies, as the trial outcome actually directly contradicts what Frequency Therapeutics' lab outcome was. Furthermore, looking at the various information releases we have had from Frequency Therapeutics indicates that their aim is to treat not just the very high frequencies but treat all the frequencies.

As a result, I think that there are some who incorrectly think that Frequency Therapeutics are wanting FX-322 to treat the upper frequencies exclusively. People are making these claims solely off the outcomes in the phase 1/2 safety trial. This is all while ignoring the fact that Frequency Therapeutics have employed a different dosing regime in the current trial and that the statements made by Frequency Therapeutics relating to FX-322 also are not indicative of the fact.

Not even Frequency Therapeutics knows at this time what the treatment is able to do in humans since they are currently investigating methods to provide wider performance with FX-322. Frequency Therapeutics have actually not made definitive claims regarding FX-322 and its performance yet since it is incredibly premature to do so.
It is interesting that in their updated August corporate presentation on their website they have decreased the frequency of action down to around 6500 Hz from 8000 Hz according to the graphic on page 17. They may have updated that number based on reviewing the still blinded results from phase 2a.
 
What are people's expectations? For example, do you think FX-322 will cure hearing loss and give you the hearing of a teenager again?
My expectations have lowered by quite a lot. I was hoping for full restoration of my hearing, now expect some improvement in comprehension in conjunction with hearing aids. I'm just going by what's been reported. Even out of the four in phase 1b that showed significant improvements in word recognition scores, I'd say (without going back and checking) that three out of those four would still need hearing aids. If multiple dosing improves significantly on the results we've seen so far, then party time.
 
I suspect it will vary from person to person how well it works in the first commercial version.

If we accept that tinnitus experienced by the patient is a symptom of NIHL/SNHL, then FX-322 may eliminate or alleviate the symptom.

My relatively unscientific opinion is that patients that haves normal audiogram with high frequency tinnitus and high frequency hearing loss will probably see tinnitus symptoms resolved.

Those with a wider range of hearing loss and tinnitus will probably experience a balance of hearing improvement and reduced tinnitus. More new cells providing optimal signals to the auditory should help reduce the intensity from whatever remains that is damaged. Still I'm sure a welcome improvement.

Some may still require hearing aids that see some improvements but don't respond as well. But, they may not need ones that are as powerful, or only in certain situations.

Frequency has repeatedly said that they believe FX-322 causes the replacement of dead or damaged cells at the site of action with new cells.

I for one, am curious to learn how people with this type of improvement experience things beyond speech. For example, music and TV? Does the auditory system recalibrate for the restored cells? Does a system with old and new "parts" function in harmony?
When, not if, Frequency Therapeutics can eventually one day deliver FX-322 (assuming clinical trials phase 2 and 3 provides proof of regeneration of hair cells) throughout the cochlea that includes all frequencies with success then it is reasonable to believe that the sound waves we all have come to know as tinnitus will be eliminated and potentially cured. I understand that statement is very optimistic but it is within reason in my opinion.
 
It is interesting that in their updated August corporate presentation on their website they have decreased the frequency of action down to around 6500 Hz from 8000 Hz according to the graphic on page 17. They may have updated that number based on reviewing the still blinded results from phase 2a.
I'm not so sure August had an update to that graphic [1]. Slide 17 looks the same in this document and it's dated for May of this year:

https://sec.report/Document/0001564590-20-025267/

However, I looked the document up on archive.org and noticed that there was a significant change (though in the opposite direction: from 3500Hz to 6500Hz - it's slide 22):

https://web.archive.org/web/2019120...ic-files/6d161090-16f5-49f4-9606-8caceb5a88a1

That change seems very significant. I wonder if the change was due to the results of their exploratory study into the delivery of FX-322 [2]. If it was, the good news is that we know their graphics are accurate. The bad news is that there's definitely a problem with getting to the lower frequencies. 6500Hz and above is still good, but it's kind of strange that they can't seem to get to the lower frequencies.

[1] https://investors.frequencytx.com/static-files/6d161090-16f5-49f4-9606-8caceb5a88a1
[2] https://investors.frequencytx.com/n...eutics-shares-clinical-data-exploratory-study
 
I'm not so sure August had an update to that graphic [1]. Slide 17 looks the same in this document and it's dated for May of this year:

https://sec.report/Document/0001564590-20-025267/

However, I looked the document up on archive.org and noticed that there was a significant change (though in the opposite direction: from 3500Hz to 6500Hz - it's slide 22):

https://web.archive.org/web/2019120...ic-files/6d161090-16f5-49f4-9606-8caceb5a88a1

That change seems very significant. I wonder if the change was due to the results of their exploratory study into the delivery of FX-322 [2]. If it was, the good news is that we know their graphics are accurate. The bad news is that there's definitely a problem with getting to the lower frequencies. 6500Hz and above is still good, but it's kind of strange that they can't seem to get to the lower frequencies.

[1] https://investors.frequencytx.com/static-files/6d161090-16f5-49f4-9606-8caceb5a88a1
[2] https://investors.frequencytx.com/n...eutics-shares-clinical-data-exploratory-study
They updated that cochlea graphic right around the same time as releasing the perilymph study. I would imagine their compliance reviewed that graphic and suggested making the graphic reflect what is actually known from actual data. So, before when it was deeper was probably just inaccurate.

If multiple doses used in the Phase 2A are able to reach more deeply into the cochlea, they will certainly update this graphic. It will probably show the depths that each additional dose is able to reach based on data from patients in each dose cohort.
 
I've got a question.

Let's say FX-322 gets FDA approved, passes efficacy, safety etc etc.

What are people's expectations? For example, do you think FX-322 will cure hearing loss and give you the hearing of a teenager again?

Or do you think it will more just help hearing aid users get more use out of their hearing aids (understanding clarity of speech rather than just amplifying the volume)?

I know it's all speculation at the minute and only proof of concept has been demonstrated in word scores so far.

I'm just curious.

Obviously also interested in the effects of tinnitus. Do you hold high expectations that it will cure tinnitus or just mask it with improvements in hearing?
FX-322 is essentially a curative therapy so I think it could significantly improve hearing loss for many people. Since this is the first generation of regenerative treatments, I wouldn't necessarily expect a 0-100 difference whereby someone with very severe loss has their hearing restored to that of a teenager's. But I do think it will be of benefit to many people. If you look at the way Frequency have spoken about their drug and even the wording on their website, I think their ultimate aim is to supplant hearing aids and not simply be an adjunct therapy. They seem like a very ambitious and driven company and I can imagine that they will want to perfect their drug. Even if the first version is better suited to tackling high frequency hearing loss, they'll find a way to improve their delivery method to address the entire cochlea. Perhaps I am an optimist but the technology will just keep on improving year on year so even if FX-322 1.0 is imperfect, there's no reason they wouldn't improve future formulations of it.

For those of us with 'normal' audiograms, I'm hopeful that FX-322 will take care of our high frequency hearing losses and hopefully improve tinnitus and hyperacusis as a result. I do suspect that most of us noise-induced folks probably have a mixed pathology of hair-cell loss and synaptopathy so we'll probably need a synapse drug too to get full relief.
 
It is interesting that in their updated August corporate presentation on their website they have decreased the frequency of action down to around 6500 Hz from 8000 Hz according to the graphic on page 17. They may have updated that number based on reviewing the still blinded results from phase 2a.
I think that there is a high likelihood of Frequency Therapeutics getting FX-322 working below 8000 Hz. However, I also question whether this has been done based off of results in the trials to date. While this is entirely possible, I don't think this is likely as Frequency Therapeutics would have not been able to use those trial results officially considering they are not verified and incomplete.

Furthermore, I have repeatedly noticed that Frequency Therapeutics has not ever made anything other than conservative conclusions and claims about FX-322 to date. They have also been very obviously trying not to infringe the rules regarding the reporting of the treatment's performance set by the FDA.
 
When, not if, Frequency Therapeutics can eventually one day deliver FX-322 (assuming clinical trials phase 2 and 3 provides proof of regeneration of hair cells) throughout the cochlea that includes all frequencies with success then it is reasonable to believe that the sound waves we all have come to know as tinnitus will be eliminated and potentially cured. I understand that statement is very optimistic but it is within reason in my opinion.
I would simply say your prediction is accurate although I assume that if someone has tinnitus from TMJ for example that it would not be alleviated with FX-322 or similar treatments.
 
Is it stupid to be afraid that doctors won't give you FX-322 because you don't have hearing loss/have only mild hearing loss?

I suspect I have some hearing loss above 8 kHz and I hope it will improve my tinnitus.
 
FX-322 is essentially a curative therapy so I think it could significantly improve hearing loss for many people. Since this is the first generation of regenerative treatments, I wouldn't necessarily expect a 0-100 difference whereby someone with very severe loss has their hearing restored to that of a teenager's. But I do think it will be of benefit to many people. If you look at the way Frequency have spoken about their drug and even the wording on their website, I think their ultimate aim is to supplant hearing aids and not simply be an adjunct therapy. They seem like a very ambitious and driven company and I can imagine that they will want to perfect their drug. Even if the first version is better suited to tackling high frequency hearing loss, they'll find a way to improve their delivery method to address the entire cochlea. Perhaps I am an optimist but the technology will just keep on improving year on year so even if FX-322 1.0 is imperfect, there's no reason they wouldn't improve future formulations of it.

For those of us with 'normal' audiograms, I'm hopeful that FX-322 will take care of our high frequency hearing losses and hopefully improve tinnitus and hyperacusis as a result. I do suspect that most of us noise-induced folks probably have a mixed pathology of hair-cell loss and synaptopathy so we'll probably need a synapse drug too to get full relief.
Regarding the normal audiograms and possible high frequency hearing loss that may be causing tinnitus, FX-322 just regenerates hair cells, doesn't it, and wouldn't address cochlear synaptopathy - where the synapses are damaged but the hearing cells are intact? That's why it may not work for tinnitus if one of the proposed theories of tinnitus is correct, i.e. tinnitus originates from synaptic damage and not hearing cells that have been damaged or destroyed?
 
Is it stupid to be afraid that doctors won't give you FX-322 because you don't have hearing loss/have only mild hearing loss?

I suspect I have some hearing loss above 8 kHz and I hope it will improve my tinnitus.
Go to another doctor in that case. There will always be ones that would.
 
Are you sure? I thought most tinnitus was somatic in nature?
There are two definitions of "somatic tinnitus" and the confusion is from the fact that they get interchanged a lot.

1) tinnitus from a somatic cause (e.g., neck or TMJ).

2) tinnitus you can modulate somatically (e.g., by moving your jaw).

Most tinnitus is in category 2 but most is not in category 1. You can and often do have cochlear injury and still be able to affect loudness and pitch with your jaw, etc.
 
Regarding the normal audiograms and possible high frequency hearing loss that may be causing tinnitus, FX-322 just regenerates hair cells, doesn't it, and wouldn't address cochlear synaptopathy - where the synapses are damaged but the hearing cells are intact? That's why it may not work for tinnitus if one of the proposed theories of tinnitus is correct, i.e. tinnitus originates from synaptic damage and not hearing cells that have been damaged or destroyed?
Tinnitus arises from interference of input (that's why hydrops without synapse or hair cell damage can cause tinnitus from cochlear origin) and the brain reacting with "phantom cochlea". Either hair cell or synapse damage (or both) will reduce input.
 

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