Frequency Therapeutics — Hearing Loss Regeneration

[WillBeNimble]

I disagree. The fact, it seems, that hearing can be restored at all is massive.

We, unfortunately, are just in the period when scientists are making initial attempts at this. If only we had been afflicted 30 years from now when, hopefully, hearing restoration will be bog standard practice.

Or we made it 30 years from now when legislation actual caught up to the modern world deciding they should be handing devices to minors that can reach 120 dB directly into their ears, and people actually protected hearing.

 

[WillBeNimble]

No.

You should, it's rather promising, especially at giving us some idea of what's actually causing the problem. Going around and naysaying every promising development doesn't help anyone. It just robs people of hope. I can understand a healthy skepticism, but not looking at the research, or creating some weird outcome where you suspect the researchers in a double blinded study have somehow manipulated the testing parameters in such a way to falsify the results to just say it's bunk, is frankly, absurd.

 

[UKBloke]

@FGG Carl mentioned Frequency Therapeutics are "midpoint" (I think was the word he used) along the development timeline for FX-322. Do you have a guesstimate on when this treatment will be available to the general public if all goes well?

 

[FGG]

@FGG Carl mentioned Frequency Therapeutics are "midpoint" (I think was the word he used) along the development timeline for FX-322. Do you have a guesstimate on when this treatment will be available to the general public if all goes well?

It depends on if they get Breakthrough Therapy status or not and how much of a COVID-19 delay ends up occurring. The best way to get the fastest access would be if they revisit Expanded/Compassionate Access after phase 2A and then decided to grant it.

 

[WillBeNimble]

@FGG perhaps we could make a FAQ that @Hazel could post on top of the thread? I feel a lot of these questions sort of repeat, and are cyclical in nature. Makes sense, the thread's too big to really parse through.

 

[AtlasFainted]

It depends on if they get Breakthrough Therapy status or not and how much of a COVID-19 delay ends up occurring. The best way to get the fastest access would be if they revisit Expanded/Compassionate Access after phase 2A and then decided to grant it.

Something that I haven't seen mentioned here (but I may have missed it) from the Tinnitus Talk Podcast is that LeBel more or less confirmed that Expanded Access is going to depend on phase 2A results.

To me this is great news. All we knew before was from Frequency's website, which stated they hadn't opened Expanded Access due to lack of data and capability restrictions.

Now we know the capability end of things is a non issue & that whether or not we get Expanded Access most likey hinges on what phase 2A results in particular look like.

This is a huge win for me personally. I had it set in my mind that they likely wouldn't do Expanded Access at all, or if they did, it wouldn't be until after the recruitment for the next trial is over, at the absolute earliest.

Now it seems like we could potentially get our hands on this as early as next year.

 

[FGG]

@FGG perhaps we could make a FAQ that @Hazel could post on top of the thread? I feel a lot of these questions sort of repeat, and are cyclical in nature. Makes sense, the thread's too big to really parse through.

Mostly the questions are covered in the Tinnitus Talk Podcast. The transcript should be easy to find.

What questions would you like to see covered that weren't in the podcast?

 

[Jurger]

A little off-topic perhaps, but any Europeans here with Frequency stock? What's the best way of going about buying it? If advertising is not allowed, a PM would be welcome.

 

[sssing]

You should, it's rather promising, especially at giving us some idea of what's actually causing the problem. Going around and naysaying every promising development doesn't help anyone. It just robs people of hope. I can understand a healthy skepticism, but not looking at the research, or creating some weird outcome where you suspect the researchers in a double blinded study have somehow manipulated the testing parameters in such a way to falsify the results to just say it's bunk, is frankly, absurd.

I seem to understand why @dan feels the way he does. He could have seen too many failed trials/attempts over the years, from AM-101 to Retigabine and I lost track of the rest. But at the same time, I can see the science and phase 1 results so far for FX-322 that there's something going on to cause the increase in word scores in treated ears. Or else I can't think of a better excuse. Dr. LeBel and @FGG pointed out that it's unheard of because these are people with stable moderate to severe hearing loss.

 

[Jurger]

I seem to understand why @dan feels the way he does. He could have seen too many failed trials/attempts over the years, from AM-101 to Retigabine and I lost track of the rest. But at the same time, I can see the science and phase 1 results so far for FX-322 that there's something going on to cause the increase in word scores in treated ears. Or else I can't think of a better excuse. Dr. LeBel and @FGG pointed out that it's unheard of because these are people with stable moderate to severe hearing loss.

And some folks in the trial apparently mentioned to the ENT their tinnitus improved.

 

[serendipity1996]

I seem to understand why @dan feels the way he does. He could have seen too many failed trials/attempts over the years, from AM-101 to Retigabine and I lost track of the rest. But at the same time, I can see the science and phase 1 results so far for FX-322 that there's something going on to cause the increase in word scores in treated ears. Or else I can't think of a better excuse. Dr. LeBel and @FGG pointed out that it's unheard of because these are people with stable moderate to severe hearing loss.

Yeah and I don't think we can really compare those past failures to FX-322 because we're now entering the realm of regenerative medicine. PCA has never been done before so it's a completely different method from those previous drugs.

 

[WillBeNimble]

Mostly the questions are covered in the Tinnitus Talk Podcast. The transcript should be easy to find.

What questions would you like to see covered that weren't in the podcast?

I agree they are mostly answered there. Namely just a brief overview of why this is as interesting to tinnitus patients as it is, when it might be out based on the different outcomes, where the research and data can be found.

I agree it's mainly in the Tinnitus Talk Podcast transcript, though. It was just a thought.

 

[WillBeNimble]

I seem to understand why @dan feels the way he does. He could have seen too many failed trials/attempts over the years, from AM-101 to Retigabine and I lost track of the rest. But at the same time, I can see the science and phase 1 results so far for FX-322 that there's something going on to cause the increase in word scores in treated ears. Or else I can't think of a better excuse. Dr. LeBel and @FGG pointed out that it's unheard of because these are people with stable moderate to severe hearing loss.

I can empathize with where he's coming from. Still, this, OTO-413, RL-81,Gateway Biotechnology, and Hough Ear Institute's Pill are all interesting research, and to say that in 20 years there is no hope for anything is drastic, especially without looking at the research. Trobalt also has helped people on Tinnitus Talk, so to say it was a complete failure is wrong. It was dangerous, that's for certain.

At the very least, if this works as intended, those with mild hearing loss on lower hf ranges will be able to restore it, and alleviate some of their tinnitus, making it less likely that people will just ignore it as they do now. This will inspire more people to acknowledge that noise can cause damage on the hf band, and hopefully lead us out of the dark ages of Audiology we're in right now.

 

[serendipity1996]

I can empathize with where he's coming from. Still, this, OTO-413, RL-81,Gateway Biotechnology, and Hough Ear Institute's Pill are all interesting research, and to say that in 20 years there is no hope for anything is drastic, especially without looking at the research. Trobalt also has helped people on Tinnitus Talk, so to say it was a complete failure is wrong. It was dangerous, that's for certain.

At the very least, if this works as intended, those with mild hearing loss on lower hf ranges will be able to restore it, and alleviate some of their tinnitus, making it less likely that people will just ignore it as they do now. This will inspire more people to acknowledge that noise can cause damage on the hf band, and hopefully lead us out of the dark ages of Audiology we're in right now.

Even if the first generation of hearing regeneration drugs are imperfect I'm also hoping it will help those of us who have a 'normal audiogram' but that nevertheless have sustained some sort of hearing damage (perhaps UHF loss) to result in tinnitus and hyperacusis. Hopefully this could 'fill in the gaps' and nudge our auditory systems back to normal. The technology will just keep improving with time but if FX-322 is approved I hope it could substantially improve quality of life for some of us even if we're not 100%.

 

[tommyd87]

10 dB improvement in 4/15 patients, I would call that rather insignificant.

If you break down the research bit by bit, I would say that this is significant. Single dose causing improvement like this has never been seen before. Basically the treatment has shown that half the participants who got the bigger dose experienced improvements.

I agree, but it does indicate there's potential for restoration. Improvements in ultra high frequencies in Phase 2 should tell us whether the issue is the drug getting to the frequencies that are included in a standard hearing test. If I'm reading Carl LeBel's comments correctly, that's what Frequency is also suspecting. Or maybe the 2 or 4 injections in Phase 2 will already yield more improvement in the 250-8000 Hz frequencies.

There are four things that you should look at regarding this from a hypothetical standpoint. Simply I would say that the bigger the hearing loss, the more probable it is that you will need more doses in order to see improvement.

> The drug doesn't do anything in the lower levels of the cochlea because it is absorbed at the higher frequencies based on a higher hearing loss there. Therefore this means more of the drug is needed to successfully regenerate hearing.

> The drug delivery does need to be reformulated release wise so it will diffuse further in the cochlea closer to the frequencies at or under 8 kHz.

> The several dose method sees improvements at all frequencies for the fact that the treatment is actually absorbed at the upper ranges first, fixes these, then you need further injections in order to treat the lower ranges literally because the dose doesn't reach those frequencies due to its size.

> The dose delivered needs to be increased in order to treat more areas in a single shot so it reaches more areas.

 

[tommyd87]

I can empathize with where he's coming from. Still, this, OTO-413, RL-81,Gateway Biotechnology, and Hough Ear Institute's Pill are all interesting research, and to say that in 20 years there is no hope for anything is drastic, especially without looking at the research. Trobalt also has helped people on Tinnitus Talk, so to say it was a complete failure is wrong. It was dangerous, that's for certain.

At the very least, if this works as intended, those with mild hearing loss on lower hf ranges will be able to restore it, and alleviate some of their tinnitus, making it less likely that people will just ignore it as they do now. This will inspire more people to acknowledge that noise can cause damage on the hf band, and hopefully lead us out of the dark ages of Audiology we're in right now.

I reckon their intention is in the long term to get this working with all frequency ranges, based on reading their trial information. What I mean by long term is not too far in the future but basically it might not be as quick as they can make the treatment work with only the very high frequencies.

I reckon that the trouble is not that they cannot get it working with the lower frequencies, rather it is a matter of delivery dosing. Hence it is why they are looking at things like reformulation and several dosing options to see the effects. The evidence is there, it is just a matter of obviously working through the treatment aspects thoroughly. The reality is Freq foremost wants to achieve this.

 

[grate_biff]

I spoke to the lead ear surgeon in my country. I mentioned FX-322 to her and how it worked. We talked about the round window and she told me 20% of us do not have a permeable window, but she also said the medicine might as well diffuse through the oval window. Hopefully Frequency Therapeutics are aware of this.

If it diffuses trough the oval window shouldn't it then reach the lower frequencies first?

 

[patorjk]

Mostly the questions are covered in the Tinnitus Talk Podcast. The transcript should be easy to find.

What questions would you like to see covered that weren't in the podcast?

If you break down the research bit by bit, I would say that this is significant. Single dose causing improvement like this has never been seen before. Basically the treatment has shown that half the participants who got the bigger dose experienced improvements.

Actually, I thought this at first too, but it's a little more nuanced. The 4 responders were all from the "Moderate to Moderately Severe" group, and all 6 of the individuals in this group had improvements (it's just that only 4 had statistically significant improvements). It's unclear how many of these people got the bigger dose (some of the 4 could have had a small dose - there were 7 large doses and 8 small doses).

Frequency has noted that it's hard to get statistically significant results from people with "Mild" hearing loss, since there is limited room for improvement (especially since they weren't doing a Pure tone audiometry above 8kHz). For Phase 2a, they're trying to recruit people like the 4 responders in the "Moderate to Moderately Severe" group. And they're giving everyone a big dose.

So there's a possibility that when the Phase 2a results come in, they could say that everyone who got a single dose had statistically significant hearing improvements.

 

[reeseth]

A little off-topic perhaps, but any Europeans here with Frequency stock? What's the best way of going about buying it? If advertising is not allowed, a PM would be welcome.

I bought some easily here in Sweden. I used avanza.se. No problem buying NASDAQ stocks. What country are you in?

 

[Jurger]

I agree they are mostly answered there. Namely just a brief overview of why this is as interesting to tinnitus patients as it is, when it might be out based on the different outcomes, where the research and data can be found.

I agree it's mainly in the Tinnitus Talk Podcast transcript, though. It was just a thought.

I agree. New visitors are not likely to scroll down a 25 page transcript of a podcast and put it all in the right context. If they even find the transcript. Besides, new information/data is bound to come out sooner or later, rendering the transcript (partly) out of date.

 

[serendipity1996]

I spoke to the lead ear surgeon in my country. I mentioned FX-322 to her and how it worked. We talked about the round window and she told me 20% of us do not have a permeable window, but she also said the medicine might as well diffuse through the oval window. Hopefully Frequency Therapeutics are aware of this.

If it diffuses trough the oval window shouldn't it then reach the lower frequencies first?

This doesn't go into specifics but the press release from their perilymph analysis study stated that: "study results showed measurable concentrations of FX-322 in every patient and that anatomical factors did not prevent the active agents of FX-322 from reaching the cochlea." So I presume this is something they have factored in to their analysis and shouldn't hinder successful delivery of the drug.

https://hearinghealthmatters.org/hearingnewswatch/2020/frequency-therapeutics-fx-322-inner-ear/

 

[FGG]

I agree. New visitors are not likely to scroll down a 25 page transcript of a podcast and put it all in the right context. If they even find the transcript. Besides, new information/data is bound to come out sooner or later, rendering the transcript (partly) out of date.

New data would also be a problem with a stickied Q and A.

 

[FGG]

This doesn't go into specifics but the press release from their perilymph analysis study stated that: "study results showed measurable concentrations of FX-322 in every patient and that anatomical factors did not prevent the active agents of FX-322 from reaching the cochlea." So I presume this is something they have factored in to their analysis and shouldn't hinder successful delivery of the drug.

https://hearinghealthmatters.org/hearingnewswatch/2020/frequency-therapeutics-fx-322-inner-ear/

Their gel is different enough where I am not sure permeability of the usual liquids (e.g. IT steroids) would apply.

 

[UKBloke]

It depends on if they get Breakthrough Therapy status or not and how much of a COVID-19 delay ends up occurring. The best way to get the fastest access would be if they revisit Expanded/Compassionate Access after phase 2A and then decided to grant it.

Let's hope the FDA are feeling charitable. I wanted to ask your view on one more thing. Can we think of FX 322 as essentially a pharmacological stem cell therapy? I'm often reminded of @attheedgeofscience's amazing journey curing himself with stem cells and Trobalt (thankfully without the horrible side effects). If FX 322 is something along the lines of stem cell therapy, and if Thanos et al can produce a more friendly kv7 channel modulator then I do think we're entering a very exciting new phase of treatment.

 

[Zugzug]

AM-101 was only for the treatment of tinnitus whereas FX-322 is for the treatment of hearing loss and maybe for tinnitus.

Maybe this is an emotional opinion I have, but I feel better about the chances of improving tinnitus/hyperacusis (if they are from hearing damage) with hearing loss treatment than a specific tinnitus treatment. Unless the hyperacusis is proven to be caused by the brain.

 

[FGG]

Let's hope the FDA are feeling charitable. I wanted to ask your view on one more thing. Can we think of FX 322 as essentially a pharmacological stem cell therapy? I'm often reminded of @attheedgeofscience's amazing journey curing himself with stem cells and Trobalt (thankfully without the horrible side effects). If FX 322 is something along the lines of stem cell therapy, and if Thanos et al can produce a more friendly kv7 channel modulator then I do think we're entering a very exciting new phase of treatment.

It's a progenitor cell activator. It activates progenitor cells already in your body. Progenitor cells are further along in differentiation than stem cells and the ones affected by FX-322 are the population already in your cochlea.

I haven't seen any evidence that stem cells (at least currently) integrate into the cochlea and their benefits seem to be usually limited to local delivery and from the anti-inflammatory properties of the exosomes and not integration of stem cells.

 

[tommyd87]

It's a progenitor cell activator. It activates progenitor cells already in your body. Progenitor cells are further along in differentiation than stem cells and the ones affected by FX-322 are the population already in your cochlea.

I haven't seen any evidence that stem cells (at least currently) integrate into the cochlea and their benefits seem to be usually limited to local delivery and from the anti-inflammatory properties of the exosomes and not integration of stem cells.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4040847/

Old obviously, but this is an article on stem cells in the ear.

 

[Lucifer]

I didn't expect this but Frequency Therapeutics posted an update on their Twitter about the Tinnitus Talk Podcast interview.

 

[Lucifer]

Maybe this is an emotional opinion I have, but I feel better about the chances of improving tinnitus/hyperacusis (if they are from hearing damage) with hearing loss treatment than a specific tinnitus treatment. Unless the hyperacusis is proven to be caused by the brain.

Yeah I agree, if hyperacusis and tinnitus are due to hearing damage then I believe FX-322 will help us. I have more faith that hearing treatment will treat both hyperacusis and tinnitus rather than a specific treatment for tinnitus as it would not be solving the underlying issues in the ear.

 

[Diesel]

One question I wished was asked was how will they know the true effect on tinnitus without tone matching?

The people with UHF tinnitus were way more likely imo to be the positive anecdotes from phase 1 and since the drug has better delivery or binding there in those regions in that phase, I was wondering how they could separate that out in phase 2a without matching the tones.

It could be inferred that the tinnitus was in the UHF. If UHF audiogram improvements directly correlate with a significant decrease in TFI score. Unfortunately they won't know the exact tinnitus tone(s).