Frequency Therapeutics — Hearing Loss Regeneration

[FGG]

Someone can check my math since I have not spent more than five minutes on this. 4 patients out of 15 treated with the drug got about 110% increase in word scores. Since the average increase for all 15 patients was 30% it means that the remaining 11 patients got no increase in word scores. The information they choose to publish is kind of selective. But they are not the first company to do it. So 27% got a material increase while 73% saw no change at all. If my math is right then the outcome is not normal distribution but rather a digital outcome that seems a bit odd.

Of the 15, i think only 6 (have to go back and check) had moderate to severe audiogram changes.

People with mild losses generally have pretty normal word scores to start with.

I would also assume changes in the ultra high frequencies are more important for speech when you have bigger deficits up to 8000 Hz. I posted a study earlier in this thread about a subset of profoundly deaf people (based on standard audiogram) who had surprisingly good speech. It turned out that, though these people had profound loss up to 8000 Hz, they had normal hearing above 8000 Hz (rare for the profoundly deaf but it happens).

It seems likely that the limited speech and word information you get from the ultra high frequencies (probably has something to do with the "formants" of the lower frequencies is my guess, would probably have to ask an audiological researcher) becomes more important when you can't hear the lower frequencies well.

So really 4 out of 6 and there are lots of individual factors. But I can't think of any reason why for those 4 (but not for a single member of placebo) there would be a very significant increase in word scores if the drug didn't work.

The nice thing about this being IPO'd soon, though, is researchers who happen to be stock investors might start frequenting these threads and weighing in. As long as they aren't bears or bulls with an agenda, that will be really useful.

 

[Lucifer]

Wait a second, that second hand story about the guy in Regain that said his tinnitus improved...... I thought having tinnitus was an exclusion criteria for Regain?

It is but I think his hearing loss was worse than his tinnitus and hyperacusis or he lied about it and was able to be part of the trials.

 

[John Queen]

Someone can check my math since I have not spent more than five minutes on this. 4 patients out of 15 treated with the drug got about 110% increase in word scores. Since the average increase for all 15 patients was 30% it means that the remaining 11 patients got no increase in word scores. The information they choose to publish is kind of selective. But they are not the first company to do it. So 27% got a material increase while 73% saw no change at all. If my math is right then the outcome is not normal distribution but rather a digital outcome that seems a bit odd.

I think you're right somehow.
Later edit: I used the data from that document, and if I'm not mistaken, yes, for the others, the average improvement was around 0.5%.

But the others had only mild hearing loss, so it's likely that they had good baseline scores, thus also the improvement would look negligible on statistics. "Mild" hearing loss isn't such a big deal. Some could have almost 50/50 WR scores. If one had, for example, 40 out of 50 correct words, and after treatment 44, it's only a 10% improvement, but it's something... As long as I don't have the baselines, I can't form an opinion about it. I guess they tried to focus on the good things now, but I hope they will publish all the data + explanations for everything that happened.

And it's still unclear what exactly triggered improvement in those four. If it's due to regeneration of hair cells in the high-frequency region of the cochlea, I guess this might be a new discovery, namely that the high frequencies help a lot with word recognition. But that's only my hypothesis for the moment, and I'm not a specialist. This would be meaningful, since it is known that when hearing loss occurs, it first occurs in the high-frequency region in most cases.

 

[FGG]

Wait a second, that second hand story about the guy in Regain that said his tinnitus improved...... I thought having tinnitus was an exclusion criteria for Regain?

Wasn't it, "having tinnitus as the *main* complaint" the exclusion criteria or am I thinking of a different drug.

 

[John Queen]

Wait a second, that second hand story about the guy in Regain that said his tinnitus improved...... I thought having tinnitus was an exclusion criteria for Regain?

I think it was an exclusion criteria if your tinnitus is more of a problem for you than the hearing loss, because their aim was to test for improvements in hearing. (That does not mean the drug has no effect on tinnitus, just that they want to prove the drug works for hearing loss in the first place...)

 

[FGG]

I think you're right somehow.
Later edit: I used the data from that document, and if I'm not mistaken, yes, for the others, the average improvement was around 0.5%.

But the others had only mild hearing loss, so it's likely that they had good baseline scores, thus also the improvement would look negligible on statistics. "Mild" hearing loss isn't such a big deal. Some could have almost 50/50 WR scores. If one had, for example, 40 out of 50 correct words, and after treatment 44, it's only a 10% improvement, but it's something... As long as I don't have the baselines, I can't form an opinion about it. I guess they tried to focus on the good things now, but I hope they will publish all the data + explanations for everything that happened.

And it's still unclear what exactly triggered improvement in those four. If it's due to regeneration of hair cells in the high-frequency region of the cochlea, I guess this might be a new discovery, namely that the high frequencies help a lot with word recognition. But that's only my hypothesis for the moment, and I'm not a specialist. This would be meaningful, since it is known that when hearing loss occurs, it first occurs in the high-frequency region in most cases.

It wouldn't be a new discovery. They have been researching the role of ultra high frequencies in speech since the 70s:

https://www.ncbi.nlm.nih.gov/pubmed/114908/

 

[Coleoptere]

The information they choose to publish is kind of selective. But they are not the first company to do it. So 27% got a material increase while 73% saw no change at all.

I think they do not have more data to present at the moment so yes selective. They need to do more testing and have more opportunity for learning.

Unfortunately with FDA procedures it will take many years. When it is introduced in the market place it will already be an 'old drug' provided it comes that far. But let us be optimistic.

 

[d'Wooluf]

They treated only one ear I think. The word recognition tests are given to both ears? I'm guessing that's what they do. So, if both ears had been treated, the word recognition scores might have been even better?

 

[Street Novelist]

Are they still planning on holding the next trial this year?

 

[Mr Mister]

It wouldn't be a new discovery. They have been researching the role of ultra high frequencies in speech since the 70s:

https://www.ncbi.nlm.nih.gov/pubmed/114908/

After researching it for over 40 years you would think they have more than: "…may contribute to their speech comprehension and control".

It is very easy to test your theory with a home studio and a pair of Genelecs. Cut 250 – 8000 Hz just below your word comprehension threshold. Then boost above 8000 Hz as much as you want. You can also do another test by first eliminating completely below 8000 Hz and then boost above 8000 Hz. You will realise that no amount of boosting 10000 - 16000 Hz will make you understand spoken words any better.

 

[Reinier]

Somewhat disappointed that they did not see improved pure-tone thresholds across the frequency range of 500 to 8,000 Hz. Although they do mention that 4 people have improved thresholds at 8 kHz. Especially with research like this they must have been testing above 8 kHz. I can understand they want to see if perhaps the drug works better at the base of the cochlea. There is no mention of this.

Elated to read that the word recognition has been improved. So where does this come from? More hair cells should mean improved hearing threshold? Is this cochlear amplifier principle misunderstood? Could it be that outer hair cells are not regenerated? How long does it take for regenerated hair cells to form connections?

Perhaps after all the hearing test up to 8 kHz suffices and we don't need to hear frequencies over 8 kHz to get good word recognition in noisy surroundings. Makes sense if you look at audio spectrum of speech.

 

[RB2014]

They treated only one ear I think. The word recognition tests are given to both ears? I'm guessing that's what they do. So, if both ears had been treated, the word recognition scores might have been even better?

They test word recognition per ear. So these tests are only from the single treated ear.

People score better with both ears... but this is a fair test for that single ear. I know where you were going with this though...

 

[FGG]

After researching it for over 40 years you would think they have more than: "…may contribute to their speech comprehension and control".

It is very easy to test your theory with a home studio and a pair of Genelecs. Cut 250 – 8000 Hz just below your word comprehension threshold. Then boost above 8000 Hz as much as you want. You can also do another test by first eliminating completely below 8000 Hz and then boost above 8000 Hz. You will realise that no amount of boosting 10000 - 16000 Hz will make you understand spoken words any better.

I would actually like to hear someone try this who has a confirmed normal audiogram up to 16000 Hz. I have severe to profound loss over 11000 Hz (and also some brain stem hearing issues) or i would try it.

What do you attribute the dramatic increase in word scores of those 4 who had moderate to severe loss while no placebo subject had the same response?

Whether or not my theory about ultra high frequency holds, it's clear the drug had an effect.

 

[FGG]

I would actually like to hear someone try this who has a confirmed normal audiogram up to 16000 Hz. I have severe to profound loss over 11000 Hz (and also some brain stem hearing issues) or i would try it.

What do you attribute the dramatic increase in word scores of those 4 who had moderate to severe loss while no placebo subject had the same response?

Whether or not my theory about ultra high frequency holds, it's clear the drug had an effect.

Actually rethinking this. Someone with a normal audiogram wouldn't have made any brain compensation for speech.

BUT, We could simulate this exactly if we found someone with moderate to severe hearing loss up to 8000 Hz (the cohort who saw improvements with FX-322) but who have normal hearing above 8000 Hz. Then, we could make above 8000 Hz inaudible and see if word scores decrease.

Does anyone on this forum have this type of hearing loss?

 

[JohnAdams]

Someone with ear grommets needs to make some gel with ly411575 in it and drop it into their ear canal.

it's clear the drug had an effect.

It was clear enough to Astellas.

 

[RB2014]

Actually rethinking this. Someone with a normal audiogram wouldn't have made any brain compensation for speech.

BUT, We could simulate this exactly if we found someone with moderate to severe hearing loss up to 8000 Hz (the cohort who saw improvements with FX-322) but who have normal hearing above 8000 Hz. Then, we could make above 8000 Hz inaudible and see if word scores decrease.

Does anyone on this forum have this type of hearing loss?

I seriously doubt you are going to find someone with moderate/severe hearing loss up to 8 kHz and then good above 8 kHz. It usually doesn't work like that. They also usually don't even test past 8 kHz anyway so no one would really know.

What do you attribute the dramatic increase in word scores of those 4 who had moderate to severe hearing loss while no placebo subject had the same response?

Increase in word scores with no increase in audiogram. That is the million dollar question. The only real explanation is the one you mentioned previously. If they had a gain of 10 dB at 8 kHz, then we could assume a gain at the higher frequencies as well. That's why they want to test past 8 kHz.

or... the data is not correct.
or... they used the same words the second time around and the people in the medicated group picked it up quicker than the placebo group... It was such a small sampling of people its a possibility.
or... There is more to hearing and understanding than we currently know.

 

[FGG]

I seriously doubt you are going to find someone with moderate/severe hearing loss up to 8 kHz and then good above 8 kHz. It usually doesn't work like that. They also usually don't even test past 8 kHz anyway so no one would really know.
What do you attribute the dramatic increase in word scores of those 4 who had moderate to severe hearing loss while no placebo subject had the same response?

Increase in word scores with no increase in audiogram. That is the million dollar question. The only real explanation is the one you mentioned previously. If they had a gain of 10 dB at 8 kHz, then we could assume a gain at the higher frequencies as well. That's why they want to test past 8 kHz.

View attachment 31973

or... the data is not correct.
or... they used the same words the second time around and the people in the medicated group picked it up quicker than the placebo group... It was such a small sampling of people its a possibility.
or... There is more to hearing and understanding than we currently know.

It's not common but people with that hearing profile do exist. The study I linked earlier mentioned people with that hearing profile. They are a very useful population to study.

This forum is large enough that maybe someone knows someone like that. Worth asking at least.

 

[JohnAdams]

I'm about to make my own FX-322 and find a veterinarian to inject me.

 

[FGG]

I'm about to make my own FX-322 and find a veterinarian to inject me.

As a veterinarian, I would have no clue how to give an intratympanic injection .

 

[JohnAdams]

As a veterinarian, I would have no clue how to give an intratympanic injection .

You stick a small gauge syringe into the ear and avoid the bones and inject.

 

[jeff W]

Maybe the ones with Meniere's?

May I ask your eye colour and your parents roots? Just curious.

 

[jeff W]

The question is does Frequency Therapeutics truly believe in FX-322? The IPO value of the business would be at least 10 times higher after completion of successful phase 2 so from financial perspective it doesn't make sense to IPO it on the verge of a presumed breakthrough. Current owners have deep pockets and they could easily finance phase 2 without an IPO. Development would be faster without all the burden that comes from added regulations and requirements of a public listing.

However, it is easy to see why they want to IPO the business now as there are so many uncertainties. No credible sign of efficacy, true safety remains untested as they need to increase dosing substantially in the next phase and drug delivery is an issue as they claim the drug did not reach inner cochlea. Positive part is that following their development is quite interesting and with public listing they are required to provide more information and more frequently to the public.

That is a conservative estimate, that brown envelope that Dept of Defense gave them a year ago (I believe) had terms attached, I bet it was early access or exclusivity for military hospitals. Forget private funds, Uncle Sam could write them a cheque for a billion dollars based off good phase 2 data.

 

[Earing]

Will it repair damaged bits or only regrow new parts?

 

[85dB T]

The question is does Frequency Therapeutics truly believe in FX-322? The IPO value of the business would be at least 10 times higher after completion of successful phase 2 so from financial perspective it doesn't make sense to IPO it on the verge of a presumed breakthrough. Current owners have deep pockets and they could easily finance phase 2 without an IPO. Development would be faster without all the burden that comes from added regulations and requirements of a public listing.

However, it is easy to see why they want to IPO the business now as there are so many uncertainties. No credible sign of efficacy, true safety remains untested as they need to increase dosing substantially in the next phase and drug delivery is an issue as they claim the drug did not reach inner cochlea. Positive part is that following their development is quite interesting and with public listing they are required to provide more information and more frequently to the public.

How does the $625 million from the Japanese Company factor into your perspective? (I don't know, just asking.)

 

[d'Wooluf]

or... the data is not correct.
or... they used the same words the second time around and the people in the medicated group picked it up quicker than the placebo group... It was such a small sampling of people its a possibility.
or... There is more to hearing and understanding than we currently know.

or... new synaptic connections? Is that possible? Note the improvement in hearing-in-noise for the same four people. Side note: My hearing is in the same ballpark as the four with the improved word recognition scores. If I got that improvement, I'd be over the moon.

 

[dmorg]

I've been following this thread off and on for quite some time. And I really do appreciate and enjoy reading the different insights from everyone which carry both hope and pragmatism. I do tend to oversimplify things to a fault sometimes. And at risk of sounding like a weather forecaster hedging their forecast, I think we are in for a big bag mixed results at every stage of these clinical trials. We may have to settle for the treatment being effective for some and less effective for others. The researchers will simply not know the precise "why" of the results due to the location and difficulty of accessing the cochlea. Until they have the diagnostics to "see" the inner ear of us humans and the mechanisms at play, they will be working relatively blind. Right?

 

[JohnAdams]

or... new synaptic connections? Is that possible? Note the improvement in hearing-in-noise for the same four people. Side note: My hearing is in the same ballpark as the four with the improved word recognition scores. If I got that improvement, I'd be over the moon.

Same here.

We may have to settle for the treatment being effective for some and less effective for others.

Totally agree.

 

[Badger19]

I wonder if people without hearing loss would be eligible for this (or a similar) treatment?

I had a hearing test done a few days ago and the ENT told me my hearing is amazing. Yet here I am with tinnitus and fullness in one ear.

 

[JohnAdams]

I wonder if people without hearing loss would be eligible for this (or a similar) treatment?

Well if we find out it's not, how hard do you think it would be to fake a hearing test?

 

[FGG]

I wonder if people without hearing loss would be eligible for this (or a similar) treatment?

I had a hearing test done a few days ago and the ENT told me my hearing is amazing. Yet here I am with tinnitus and fullness in one ear.

I would get an extended audiogram up to 16000 Hz if possible. Lots of people with hearing loss look normal on a standard audiogram.

This drug may not work for you if you truly have normal pure tone hearing (on extended audiogram) but something like OTO-413 might help, assuming it works, if you have a synaptopathy, aka "hidden hearing loss."