Frequency Therapeutics — Hearing Loss Regeneration

[Diesel]

Worth the watch:

 

[Gb3]

More of the same. Speech perception blah blah. Admitted they have not seen any audiogram improvement and are moving forward realizing this drug doesn't do that. No mention of tinnitus.

 

[Diesel]

More of the same. Speech perception blah blah. Admitted they have not seen any audiogram improvement and are moving forward realizing this drug doesn't do that. No mention of tinnitus.

Oh hey, company leadership being transparent about the known successes and shortcoming of their drug that is in development, but still believes based on patient feedback that it can help a lot of people. Sounds terrible!

Also, Franck also acknowledged that FX-322 is likely causing preferential growth of IHC and not OHC based on his response about seeing word scores increase and not audiogram.

 

[Survivor234]

Tinnitus isn't just from noise damage guys.

Sure but I don't see why you think this means we can't care about potential cures for noise-induced tinnitus. Noise-induced tinnitus is the sort of tinnitus that most people have and which most typically becomes permanent.

 

[sensualmosquito]

Even if they can't give me my hearing back, I would love to have the reactivity and ringing go down so that my hearing loss wasn't so obvious every day. If they can achieve that for me I'd gladly pay for it. Time will tell at this point.

 

[Gb3]

Also, Franck also acknowledged that FX-322 is likely causing preferential growth of IHC and not OHC based on his response about seeing word scores increase and not audiogram.

Then how come he didn't say that?

 

[Reed19]

Just curious, I don't know much.

What's stopping Frequency Therapeutics from creating something that can regenerate more hair cells? To me it seems it works but the amount of hair cells it regenerates is underwhelming when the dream drug would do every hair cell. What percent of hair cells grow in a targeted range? Could an approach where they wait a longer period of time for the hair cells to grow and then administer the drug again be effective?

I know there will be a version to go deeper in the cochlea but it seems like even then it might be far from ideal. Have we heard any type of research recently about increased effectiveness? Do you guys think there will be potential ever for a full restore?

 

[Geatly]

More of the same. Speech perception blah blah. Admitted they have not seen any audiogram improvement and are moving forward realizing this drug doesn't do that. No mention of tinnitus.

Bro, I had perfect hearing until recently, when I damaged my hearing just very slightly on construction site using a jackhammer.

My audiogram is perfect, I have no dB loss, I can hear everything.

Firstly, my problem is that sounds hurt my ears (hyperacusis). Secondly, since I am (or more likely was) a musician. I am not anymore able to really match pitches or filter out sounds as I could before that.

I didn't lose hearing threshold, what I have lost first is clarity, depth of sound understanding, possibility to filter out sounds.

They are god damn right about what they are saying, I am 100% the drug works, because I have read their data + the fact that FX-322 hits only frequencies up to 8000 Hz is reason it won't help ultimately to get back on 100% hearing, but it is far better than nothing.

FX-345 will hit a better part of cochlea, than we can see much greater improvements.

Then how come he didn't say that?

They said that it mostly restores IHC, not OHC, which are responsible for filtering and clarity. I have listened to most of their podcasts, and since I have damaged my hearing on construction site recently, I can ensure you they are goddamn right about that.

First you lose filtering and clarity. I have perfect thresholds, but clarity and filtering is fucked up, and it's depressing.

 

[Diesel]

Just curious, I don't know much.

What's stopping Frequency Therapeutics from creating something that can regenerate more hair cells? To me it seems it works but the amount of hair cells it regenerates is underwhelming when the dream drug would do every hair cell. What percent of hair cells grow in a targeted range? Could an approach where they wait a longer period of time for the hair cells to grow and then administer the drug again be effective?

I know there will be a version to go deeper in the cochlea but it seems like even then it might be far from ideal. Have we heard any type of research recently about increased effectiveness? Do you guys think there will be potential ever for a full restore?

See: FX-345.

 

[Diesel]

Bro, I had perfect hearing until recently, when I damaged my hearing just very slightly on construction site using a jackhammer.

My audiogram is perfect, I have no dB loss, I can hear everything.

Firstly, my problem is that sounds hurt my ears (hyperacusis). Secondly, since I am (or more likely was) a musician. I am not anymore able to really match pitches or filter out sounds as I could before that.

I didn't lose hearing threshold, what I have lost first is clarity, depth of sound understanding, possibility to filter out sounds.

They are god damn right about what they are saying, I am 100% the drug works, because I have read their data + the fact that FX-322 hits only frequencies up to 8000 Hz is reason it won't help ultimately to get back on 100% hearing, but it is far better than nothing.

FX-345 will hit a better part of cochlea, than we can see much greater improvements.

They said that it mostly restores IHC, not OHC, which are responsible for filtering and clarity. I have listened to most of their podcasts, and since I have damaged my hearing on construction site recently, I can ensure you they are goddamn right about that.

First you lose filtering and clarity. I have perfect thresholds, but clarity and filtering is fucked up, and it's depressing.

I suspect that your experience is a lot more common than is represented by the commenters in this thread, and possibly on Tinnitus Talk in general. It does seem really common on more broad Acquired SNHL sites, where the patients didn't get tinnitus. I did some recent googling on Kevin Franck at Frequencycy Therapeutics, as he has a fairly prominent background, and found that in prior content on hearing loss, he tended to speak more on patients with mild losses first experiencing sound distortion, and things like dysacusis, which are not really measurable at the mild level on standard clinical assessments.

Secondly, I've come to notice that there's a fairly vocal minority on this website that are overly skeptical of progress of any hearing loss drug if they don't show improvements in audiometry. Even though the treatments are showing promise in other prominent tests IE: FX-322 with CNC word score, OTO-413 with SIN. Both don't help improve audiograms to my knowledge, but are massive steps to treat an un-met need. The community doesn't yet know if just improving hearing in these areas might be enough to make tinnitus/hyperacusis a little more livable, or may simply reduce progression of the disorder. It's starting to evolve into a cult of negativity. Don't bother feeding into their comments, there's no gain to be had.

 

[Guywithapug]

Even if they can't give me my hearing back, I would love to have the reactivity and ringing go down so that my hearing loss wasn't so obvious every day. If they can achieve that for me I'd gladly pay for it. Time will tell at this point.

This. So much this. Except mine is hissing instead of ringing and the reactivity to certain sounds just adds another layer of difficulty to cope. I've kind of gotten used to it and some days the reactivity is much lower, those days are angelic.

 

[Gb3]

Yes, the drug definitely works. Just look at the stock price. I had a lot of excitement about FREQ at first too but you can't ignore their lackluster trial outcomes.

 

[UKBloke]

there's no gain to be had.

There's a pun in there somewhere.

But seriously...

There can be a culture of negativity but to be fair tinnitus patients have endured the sh*tty end of the stick for many years regarding treatment. I've had tinnitus now for over 30 years and despite all the research that's flowed under the bridge, what clinicians said/did back then at the time of my diagnosis still seems to stand today for the most part: here's your masker, go home and get used to it.

Having said that I think what Frequency Therapeutics have achieved to date is pretty remarkable I watched that video you posted last night and found it really interesting. Kevin Franck's statement about FX-322's potential positive effect on hearing clarity summed it up for me when he said that they have patients who can hear volume but can't make words out It's a simple statement but I'd never thought of it that way.

I think the main thing peeps should remember is that FX-322 isn't a tinnitus treatment, and although there seems to be good reason to suggest that addressing aspects of hearing loss may ameliorate tinnitus we just don't know right now.

Nevertheless, I personally do see good reason to remain optimistic. And the one thing we absolutely do know at this moment is that we are going to get the data, either Q4 this year or Q1 next year.

 

[Champ]

I suspect that your experience is a lot more common than is represented by the commenters in this thread, and possibly on Tinnitus Talk in general. It does seem really common on more broad Acquired SNHL sites, where the patients didn't get tinnitus. I did some recent googling on Kevin Franck at Frequencycy Therapeutics, as he has a fairly prominent background, and found that in prior content on hearing loss, he tended to speak more on patients with mild losses first experiencing sound distortion, and things like dysacusis, which are not really measurable at the mild level on standard clinical assessments.

Secondly, I've come to notice that there's a fairly vocal minority on this website that are overly skeptical of progress of any hearing loss drug if they don't show improvements in audiometry. Even though the treatments are showing promise in other prominent tests IE: FX-322 with CNC word score, OTO-413 with SIN. Both don't help improve audiograms to my knowledge, but are massive steps to treat an un-met need. The community doesn't yet know if just improving hearing in these areas might be enough to make tinnitus/hyperacusis a little more livable, or may simply reduce progression of the disorder. It's starting to evolve into a cult of negativity. Don't bother feeding into their comments, there's no gain to be had.

We use extremely old (and I'd say, outdated) ways of evaluating a person's audiological improvement using these drugs. If they can show the cochlea is regenerating, I don't care what the old tests say, that is progress forward. This is a hard problem that many researchers and drug developers have been taking seriously for the better part of 2 decades now and we're making so much progress right now that any new problem researchers run into that they have to move past can really get the pessimists riled up.

We need to realize we're going to see multiple solutions to our hearing loss / tinnitus problems in our lifetime whether we're an optimist or pessimist. It's a solvable problem and these people's jobs and careers depend on producing positive results.

This is amazing! Screenshot from the video. Imagine how much better you could hear if your ear repaired itself that much!

This video is wild, everyone should watch it. This drug looks really promising, some of these test subjects show shocking improvement. I know we've been researching how the cochlea works for a while but it's amazing to see the research come to fruition like it is here.

 

[Joeseph Stope]

We use extremely old (and I'd say, outdated) ways of evaluating a person's audiological improvement using these drugs. If they can show the cochlea is regenerating, I don't care what the old tests say, that is progress forward. This is a hard problem that many researchers and drug developers have been taking seriously for the better part of 2 decades now and we're making so much progress right now that any new problem researchers run into that they have to move past can really get the pessimists riled up.

We need to realize we're going to see multiple solutions to our hearing loss / tinnitus problems in our lifetime whether we're an optimist or pessimist. It's a solvable problem and these people's jobs and careers depend on producing positive results.

View attachment 48644

This is amazing! Screenshot from the video. Imagine how much better you could hear if your ear repaired itself that much!

This video is wild, everyone should watch it. This drug looks really promising, some of these test subjects show shocking improvement. I know we've been researching how the cochlea works for a while but it's wild to see the research come to fruition like it is here.

IIRC this photo is of a lab guinea pig or something... not a human?

But yes, it seems that progress is marching on.

It cheers me up sometimes to read about that guy Helmholtz from about 200 (?) years back who discovered that the cochlea inner pathway is like a piano with the lower notes at the apex and the scale rising till you get to the base.

We need a few more geniuses like him but in the absence of which, we'll have to content ourselves with the incremental steps of our research workers and professors.

Another interesting character was a fellow called Kemp. Have I got it right? He overturned the conventional thinking (of the time) that the brain perceives sound by mechanical means. When he suggested first that the mechanical transfer of sound is turned to electrical energy along the nerves, he was laughed out of the lecture hall.

Overcoming these assumptions of the conventional wisdom often brings progress forward in leaps and bounds.

 

[Diesel]

We need a few more geniuses like him but in the absence of which, we'll have to content ourselves with the incremental steps of our research workers and professors.

I mean... Bob Langer?

https://en.wikipedia.org/wiki/Robert_S._Langer

...Jeff Karp?

https://en.wikipedia.org/wiki/Jeffrey_Karp

 

[OptimusPrimed]

We use extremely old (and I'd say, outdated) ways of evaluating a person's audiological improvement using these drugs. If they can show the cochlea is regenerating, I don't care what the old tests say, that is progress forward. This is a hard problem that many researchers and drug developers have been taking seriously for the better part of 2 decades now and we're making so much progress right now that any new problem researchers run into that they have to move past can really get the pessimists riled up.

We need to realize we're going to see multiple solutions to our hearing loss / tinnitus problems in our lifetime whether we're an optimist or pessimist. It's a solvable problem and these people's jobs and careers depend on producing positive results.

View attachment 48644

This is amazing! Screenshot from the video. Imagine how much better you could hear if your ear repaired itself that much!

This video is wild, everyone should watch it. This drug looks really promising, some of these test subjects show shocking improvement. I know we've been researching how the cochlea works for a while but it's amazing to see the research come to fruition like it is here.

This is in vivo buddy. I guess once drugs like OTO-413, FX-322 and FX-345 hit the market we will have somewhat of an idea as to whether regenerating hair cells will reverse tinnitus.

Are any drugs coming to repair hair cells that have been damaged by noise but are still semi functional?

 

[ringingfeet]

We'll know more about the effects of FX-322 on tinnitus after the current 208 trial.
Since there will be TFI measures done as a secondary endpoint.

The results should be in by Q3/2022 or Q1/2023.

 

[Jurger]

Then how come he didn't say that?

It was a missed opportunity. The presenter asks the question at 25:45. Franck says 'there's a story there that kind of makes sense' but he doesn't actually explain it.

Anyway, we'll see how the 208 study unfolds. If it's still the case 65% of patients don't improve and those that do can lose their gains within two years, it's gonna be an uphill battle getting this commercialized.

 

[Diesel]

It was a missed opportunity. The presenter asks the question at 25:45. Franck says 'there's a story there that kind of makes sense' but he doesn't actually explain it.

Anyway, we'll see how the 208 study unfolds. If it's still the case 65% of patients don't improve and those that do can lose their gains within two years, it's gonna be an uphill battle getting this commercialized.

Brian Taylor:

In your trial you've seen an improvement in word recognition scores, but you haven't seen an improvement in audibility. Now, to me that's a really interesting finding. Could you talk a little bit more about that?

Kevin Franck:

Sure. So, of course when we started [...] we were looking for effects on everything. [...] So, when we saw speech perception but we didn't see audibility, it made us scratch our heads and say, "well why could that be?" You know, we've got really bright scientists and biologists and we've all learned enough about the auditory system that there is a story there that kind of makes sense. (1)You know the parts of the auditory system that deal with detection are often different parts of the auditory system that deal with suprathreshold types of activities. (2)And, you know these speech perception tests are presented well into people's sensation levels so we don't have to deal with things that are right near audibility.

1.
The parts of the auditory system that deal with detection : Inner Hair Cells
are often different parts of the auditory system that deal with suprathreshold types of activities : Outer Hair Cells

2.
These speech perception tests are presented well into people's sensation levels so we don't have to deal with things that are right near audibility.

In other words: The Speech Perception tests are loud enough, that the OHC aren't needed to pick up speech sound entering the ear, therefore the new IHC are enough to show an improvement.

 

[DimLeb]

I believe all the current tests we have (audiogram, SIN, ABR etc) are just not enough, inconclusive and subjective. I don't know why it is not apparent to the science community that these tests don't reveal even half the truth.

I guess they need something to base their measurements on, but it's just like trying to drive blindfolded. The need for new tests, that ACTUALLY show what the f*ck is going on in the cochlea, is greater than ever. The sound perception tests should come after that.

 

[Gb3]

It was a missed opportunity. The presenter asks the question at 25:45. Franck says 'there's a story there that kind of makes sense' but he doesn't actually explain it.

I think he just glossed over it because they thought it should but it didn't.

 

[Chad Lawton]

Anyway, we'll see how the 208 study unfolds. If it's still the case 65% of patients don't improve and those that do can lose their gains within two years, it's gonna be an uphill battle getting this commercialized.

65% don't improve to a degree that is measurable on current clinical tests; it doesn't mean FX-322 does nothing for them. In the slide I have attached, look at the 71 patients in the treatment group. Notice how the cluster of data points are more concentrated above the baseline rather than having an even distribution both above and below it like the untreated group does. On rough estimation, it looks like approximately 21 treated patients fall below their original baseline while the remaining 50 landed above it. This trend suggests that the majority of patients may experience an ever so slight improvement in WR scores but it isn't measurable as being clinically significant. Sure, the retake variability is + or - 3 words but there is still clearly a trend there.

You may think that is an insignificant improvement for these people but it could make the difference of being able to now faintly hear the oven timer go off or the doorbell ring for some. That is why they have designed their patient questionnaire RADIAL, so they can capture those improvements that aren't being caught by standard clinical tests.

Secondly, vast majority of patients do not lose all of their gains; they lose some of their statistically significant gains but still remain well above baseline; the company has repeatedly said this.

It will not be an uphill battle to get it commercialized; the FDA has already agreed on speech perception as the primary endpoint for the current Phase 2 trial and there are currently zero approved pharmaceutical treatments for hearing loss so I'm sure the FDA will be happy to approve any drug that is shown to be safe and that shows any improvement at all on any clinical hearing exam.

 

[Gb3]

65% don't improve to a degree that is measurable on current clinical tests; it doesn't mean FX-322 does nothing for them. In the slide I have attached, look at the 71 patients in the treatment group. Notice how the cluster of data points are more concentrated above the baseline rather than having an even distribution both above and below it like the untreated group does. On rough estimation, it looks like approximately 21 treated patients fall below their original baseline while the remaining 50 landed above it. This trend suggests that the majority of patients may experience an ever so slight improvement in WR scores but it isn't measurable as being clinically significant. Sure, the retake variability is + or - 3 words but there is still clearly a trend there.

You may think that is an insignificant improvement for these people but it could make the difference of being able to now faintly hear the oven timer go off or the doorbell ring for some. That is why they have designed their patient questionnaire RADIAL, so they can capture those improvements that aren't being caught by standard clinical tests.

Secondly, vast majority of patients do not lose all of their gains; they lose some of their statistically significant gains but still remain well above baseline; the company has repeatedly said this.

It will not be an uphill battle to get it commercialized; the FDA has already agreed on speech perception as the primary endpoint for the current Phase 2 trial and there are currently zero approved pharmaceutical treatments for hearing loss so I'm sure the FDA will be happy to approve any drug that is shown to be safe and that shows any improvement at all on any clinical hearing exam.

View attachment 48656

Hearing the doorbell or timer go off would fall on pure tone.

 

[Chad Lawton]

Hearing the doorbell or timer go off would fall on pure tone.

Okay, lets correct my analogy then. It would help them distinguish the doorbell from their microwave beep.

 

[Gb3]

Okay, lets correct my analogy then. It would help them distinguish the doorbell from their microwave beep.

More like distinguishing from someone saying "hat" or "bat."

 

[ZFire]

This. So much this. Except mine is hissing instead of ringing and the reactivity to certain sounds just adds another layer of difficulty to cope. I've kind of gotten used to it and some days the reactivity is much lower, those days are angelic.

Hopefully, your reactivity will go away eventually. Since you have fluctuating days where the reactivity is much lower, I see that as a really good sign imo.

 

[Damocles]

65% don't improve to a degree that is measurable on current clinical tests; it doesn't mean FX-322 does nothing for them.

This is the most relevant sentence that has been written in this thread in a long time, and also serves as documentable evidence that the @Chad Lawton is in fact a GigaChad.

Just to share some anecdotal experience which backs up several users hypothesis:

I suffer from severe reactive tinnitus that has stabilised over the last 7 years, and oftentimes feels moderate, unless I trigger a temporary spike via mild to moderate sound exposure (within the sphere of sounds that aggravate my tinnitus).

The last hearing test I took (albeit 10 years ago, but just after the onset of my severe tinnitus) detected no hearing loss in either ear. My hearing to this day, is in the realms of super-human. I know my upstairs neighbours credit card number from hearing it told over the phone, through a thick concrete ceiling (I haven't made any purchases with it... yet).

But the chances of me having no hearing loss? Nul.

The concerts I went to + the volumes x hours I spent listening to music on headphones = the equivalent of standing alongside a couple thousand controlled explosions over the course of a decade.

I know I have hearing loss; I also know there is currently no technology that can detect that hearing loss.

So I remain convinced, if this (or any other drug in the future) can regenerate CHCs and/or IESs to even a minuscule degree (meaning not overtly demonstrable in current tests), and doing so treats noise-induced tinnitus (like mine) as per the theory; then we are onto a winner that is only going to win more over time.

 

[Survivor234]

What's stopping Frequency Therapeutics from creating something that can regenerate more hair cells?

I think that it should work (and to some extent it has) but they don't know why it isn't working. Barring killing someone and cutting out their ear, there isn't really a way to determine why more ear hair cells aren't being generated or to even see the distribution of hair cells in the human ear after the injection of FX-322.

 

[Gb3]

I think that it should work (and to some extent it has) but they don't know why it isn't working. Barring killing someone and cutting out their ear, there isn't really a way to determine why more ear hair cells aren't being generated or to even see the distribution of hair cells in the human ear after the injection of FX-322.

One problem is drug delivery. The other is it may not work on the human ear.