Frequency Therapeutics — Hearing Loss Regeneration

[Diesel]

This is why it's thought that there will be a Phase 2b/Phase 3 combined trial as members like @FGG and @Diesel have pointed out. That way it is going to enable Frequency Therapeutics to get paid for their two trials obligations and also enable them to complete the final phase trial too.

Agree. There's nothing in the wording in the 10-K that states the trials must be made separate. And, the real incentive is the final product cash payment + royalties.

 

[FGG]

Someone can correct me if I'm wrong, but I don't believe FX-322 had any effect on speech in noise in the Phase I/II trial, it only improved the Word Recognition Score. The theory right now is that damage to synaptic connections is what causes speech-in-noise hearing loss. Though we'll have a better idea if that's true within the next month (when the OTO-413 results come in).

There were already reports of improved tinnitus from the Phase I/II trial. My gut assumption is that in the next 1-5 years we're going to learn that there is no single cause or solution to tinnitus. Fixing hair cells will cure some, fixing synaptic connections others, etc etc.

The idea is that anything that interferes with hearing can give you "phantom cochlea" and therefore tinnitus. It could be any number of things or combo of them: hair cell loss, synaptopathy, ear drum rupture, hydrops, ETD, perilymph fistula etc etc.

It's clear it's not one structure, otherwise ear drum rupture, noise induced, Meniere's etc etc wouldn't all cause the symptom of tinnitus.

It's also clear it isn't stuck in the brain or due to brain damage because when the underlying cause can be treated, tinnitus is treated even long standing tinnitus.

It's not going to be hair cell loss in everyone but treating hair cell loss (as well as synaptopathy in areas without hair cell loss) is going to help a lot of noise induced and ototoxic tinnitus, for instance.

 

[tommyd87]

Agree. There's nothing in the wording in the 10-K that states the trials must be made separate. And, the real incentive is the final product cash payment + royalties.

Exactly. I am pretty positive that Astellas at the end of the day just wants to get the trials done so they can get approval in Europe or Asia or wherever they need to get approval in order to be able to provide the medicine. Most certainly things have changed regarding Europe since they no longer need to seek approval like they used to within the EU solely as was required before the agreement was signed between the EU and US to mutually recognise their trial outcomes and also actual medicine/treatment approvals.

 

[weab00]

It would be nice if people actually added some kind of explanation or justification for their pessimistic hot-takes lol.

Defensive pessimism

Sound familiar?

 

[Bill Arsenault]

Breaking your NDA is pathetic.

Do I really have to list all the reasons why?

 

[DSCHMVD]

I found a participant on Reddit.
Looks like FX-322 is ineffective.
Statistically speaking, a participant has only 20% chance to receive 4/4 placebo doses.
This guy had 80% chance of receiving minimal 1 shot of the real drug. He said that he doesn't feel any benefit.

 

[GlennS]

Defensive pessimism

Sound familiar?

View attachment 42001

This visual is simpler to grasp.

 

[DebInAustralia]

It's probably just going to improve speech in noise and word recognition. I don't think that will help tinnitus.

What are you basing that opinion upon?

 

[Darren H]

I've reached out to the person whose post I've shared. They've basically become a friend given our mutual experiences with SSHL so I won't disclose too much but they:

- Are thrilled with results so far.
- Confirmed improvements across 3 frequency bands, that have been retained after 8 months! (Actual audiograms, not recorded on phone etc).
- Had Word Recognition Score improvement.
- Noticed tinnitus improvement, but not as much as they'd hoped for. Concluded "maybe I didn't get all 4 shots of FX-322, just a mystery until March"

This sort of information makes me excited so I feel obliged to share given how important this is to some of us. That said, I do understand that we may have to take this with a pinch of salt, as someone suggested. Me personally, I'm going to ride into the Christmas assuming this is all accurate info. I reckon March will come around a lot sooner if I do so.

 

[DSCHMVD]

Defensive pessimism

Sound familiar?

View attachment 42001

The opposite is also true for defensive optimism.
I think rational pessimism/optimism is more healthy.

 

[tommyd87]

I've reached out to the person whose post I've shared. They've basically become a friend given our mutual experiences with SSHL so I won't disclose too much but they:

- Are thrilled with results so far.
- Confirmed improvements across 3 frequency bands, that have been retained after 8 months! (Actual audiograms, not recorded on phone etc).
- Had Word Recognition Score improvement.
- Noticed tinnitus improvement, but not as much as they'd hoped for. Concluded "maybe I didn't get all 4 shots of FX-322, just a mystery until March"

This sort of information makes me excited so I feel obliged to share given how important this is to some of us. That said, I do understand that we may have to take this with a pinch of salt, as someone suggested. Me personally, I'm going to ride into the Christmas assuming this is all accurate info. I reckon March will come around a lot sooner if I do so.

I don't think they will know what they got in March, mostly because the unblinding things does not happen until July.

Also, are there any available details on where their improvement was in terms of frequency? Were the improvements in the regular areas?

 

[tommyd87]

I found a participant on Reddit.
Looks like FX-322 is ineffective.
Statistically speaking, a participant has only 20% chance to receive 4/4 placebo doses.
This guy had 80% chance of receiving minimal 1 shot of the real drug. He said that he doesn't feel any benefit.

View attachment 42005
View attachment 42006

There are two elements I take away from this.

Firstly, receiving only one shot of FX-322 has been shown to be largely ineffective if you look at the outcomes from Phase 1/2. This is because while benefit was obtained, it was minimal in a number of participants who needed it.

Secondly, there is also a 20% chance that they obtained complete placebo doses. Due to the information we were provided during the first trial, there was no benefit demonstrated in the placebo group whatsoever which was probably what Frequency Therapeutics was wishing to happen.

Hence this in no way demonstrates that FX-322 is ineffective.

 

[Lucifer]

I've reached out to the person whose post I've shared. They've basically become a friend given our mutual experiences with SSHL so I won't disclose too much but they:

- Are thrilled with results so far.
- Confirmed improvements across 3 frequency bands, that have been retained after 8 months! (Actual audiograms, not recorded on phone etc).
- Had Word Recognition Score improvement.
- Noticed tinnitus improvement, but not as much as they'd hoped for. Concluded "maybe I didn't get all 4 shots of FX-322, just a mystery until March"

This sort of information makes me excited so I feel obliged to share given how important this is to some of us. That said, I do understand that we may have to take this with a pinch of salt, as someone suggested. Me personally, I'm going to ride into the Christmas assuming this is all accurate info. I reckon March will come around a lot sooner if I do so.

Still good that he had tinnitus improvements. Either he needs more doses for it to improve or he may need a synapse drug instead to completely get rid of it.

I wish we had more details about if it works for both pain and loudness hyperacusis.

 

[Ozwel]

If two shots are improving tinnitus, I'm in for as many shots as needed to restore my ear cells.

The question is "if 4 shots are safe, are 10 safe as well?". We may never know until one tries...

 

[FGG]

I've reached out to the person whose post I've shared. They've basically become a friend given our mutual experiences with SSHL so I won't disclose too much but they:

- Are thrilled with results so far.
- Confirmed improvements across 3 frequency bands, that have been retained after 8 months! (Actual audiograms, not recorded on phone etc).
- Had Word Recognition Score improvement.
- Noticed tinnitus improvement, but not as much as they'd hoped for. Concluded "maybe I didn't get all 4 shots of FX-322, just a mystery until March"

This sort of information makes me excited so I feel obliged to share given how important this is to some of us. That said, I do understand that we may have to take this with a pinch of salt, as someone suggested. Me personally, I'm going to ride into the Christmas assuming this is all accurate info. I reckon March will come around a lot sooner if I do so.

We will obviously know way more in March but assuming this anecdote is accurate he/she

A) got way more than minor functional hearing improvements from the drug as they are "thrilled."

B) confirms hair cell recovery affects tinnitus / it's not "stuck in the brain."

If this person had noise induced loss especially, they likely

a) had at least some degree of bilateral involvement b) have at least some degree of synaptopathy in areas without hair cell loss as well c) if they had widespread enough damage to need 3 bands improved, they probably also had damage closer to the apex than the "x" amount of shot provided. d) may not have had hearing fully restored to normal in those bands with the treatment they received.

I would say this is another anecdote (like the ones LaBel mentioned) that show fx-322 treats tinnitus due to hair cell loss but bilateral treatment and increased dosing (as well as treating synaptopathy) would surely give a greater tinnitus impact.

 

[Diesel]

I've reached out to the person whose post I've shared. They've basically become a friend given our mutual experiences with SSHL so I won't disclose too much but they:

- Are thrilled with results so far.
- Confirmed improvements across 3 frequency bands, that have been retained after 8 months! (Actual audiograms, not recorded on phone etc).
- Had Word Recognition Score improvement.
- Noticed tinnitus improvement, but not as much as they'd hoped for. Concluded "maybe I didn't get all 4 shots of FX-322, just a mystery until March"

This sort of information makes me excited so I feel obliged to share given how important this is to some of us. That said, I do understand that we may have to take this with a pinch of salt, as someone suggested. Me personally, I'm going to ride into the Christmas assuming this is all accurate info. I reckon March will come around a lot sooner if I do so.

Which 3 bands did they see improvement in?

 

[Diesel]

We will obviously know way more in March but assuming this anecdote is accurate he/she

A) got way more than minor functional hearing improvements from the drug as they are "thrilled."

B) confirms hair cell recovery affects tinnitus / it's not "stuck in the brain."

If this person had noise induced loss especially, they likely

a) had at least some degree of bilateral involvement b) have at least some degree of synaptopathy in areas without hair cell loss as well c) if they had widespread enough damage to need 3 bands improved, they probably also had damage closer to the apex than the "x" amount of shot provided. d) may not have had hearing fully restored to normal in those bands with the treatment they received.

I would say this is another anecdote (like the ones LaBel mentioned) that show fx-322 treats tinnitus due to hair cell loss but bilateral treatment and increased dosing (as well as treating synaptopathy) would surely give a greater tinnitus impact.

Appears to be a person with SSHL, so it's possible that FX-322 didn't get deep enough to improve all lost frequencies.

From a tinnitus improvement standpoint, they may have noticed high frequency tinnitus improve, but not lower frequency. (Since the drug didn't reach far enough). This is still significant as a treatment.

 

[FGG]

Appears to be a person with SSHL, so it's possible that FX-322 didn't get deep enough to improve all lost frequencies.

From a tinnitus improvement standpoint, they may have noticed high frequency tinnitus improve, but not lower frequency. (Since the drug didn't reach far enough). This is still significant as a treatment.

SSHL in just one ear?

 

[Diesel]

SSHL in just one ear?

Unknown. There are no specific mentions of documented hearing loss in both ears being an acceptance criteria, or only 1 ear affected being an exclusion criteria. So, it's possible.

 

[FGG]

Unknown. There are no specific mentions of documented hearing loss in both ears being an acceptance criteria, or only 1 ear affected being an exclusion criteria. So, it's possible.

Right. Even though I quoted you, I was more inquiring if the mole knew...

 

[Princebeyel]

There are two elements I take away from this.

Firstly, receiving only one shot of FX-322 has been shown to be largely ineffective if you look at the outcomes from Phase 1/2. This is because while benefit was obtained, it was minimal in a number of participants who needed it.

Secondly, there is also a 20% chance that they obtained complete placebo doses. Due to the information we were provided during the first trial, there was no benefit demonstrated in the placebo group whatsoever which was probably what Frequency Therapeutics was wishing to happen.

Hence this in no way demonstrates that FX-322 is ineffective.

Now I definitely don't want to join the severe hearing loss trial if I'm only getting one shot! Fml man. I don't know how much longer I can go on like this!

 

[FGG]

Now I definitely don't want to join the severe hearing loss trial if I'm only getting one shot! Fml man. I don't know how much longer I can go on like this!

This is why anecdotes delay trials btw, and why breaking NDAs is a bad idea.

 

[Diesel]

Now I definitely don't want to join the severe hearing loss trial if I'm only getting one shot! Fml man. I don't know how much longer I can go on like this!

Do it if you can. Your participation still helps move the entire trial process along.

 

[Philip83]

Now I definitely don't want to join the severe hearing loss trial if I'm only getting one shot! Fml man. I don't know how much longer I can go on like this!

Why is one worse than none?

 

[Princebeyel]

Do it if you can. Your participation still helps move the entire trial process along.

I really want to but now I'm afraid that if I do and don't see improvement, I'll be kicking myself in the ass saying I should've waited for more doses, since an exclusion criteria is not having previously participated in the trials.

 

[Diesel]

I really want to but now I'm afraid that if I do and don't see improvement, I'll be kicking myself in the ass saying I should've waited for more doses, since an exclusion criteria is not having previously participated in the trials.

We don't even know what the Phase III will entail; assuming that is what you're waiting for. And still, there's a chance you get placebo even after waiting.

Either way, you'll probably end up going to an ENT for more doses.

So, why not join now knowing you're helping moving the Severe 1B forward for the betterment of humanity?

 

[Princebeyel]

We don't even know what the Phase III will entail; assuming that is what you're waiting for. And still, there's a chance you get placebo even after waiting.

Either way, you'll probably end up going to an ENT for more doses.

So, why not join now knowing you're helping moving the Severe 1B forward for the betterment of humanity?

I am so confused on what to do. I do want to help out but I need help too and I'm afraid I won't get it. I do not know man. I'm just really down after reading through here this am.

 

[Ozwel]

Now I definitely don't want to join the severe hearing loss trial if I'm only getting one shot! Fml man. I don't know how much longer I can go on like this!

Trust me, you are stronger than you think. I was 19 when my life changed, I'm now 35. I can still remember my 20th birthday with the family. In my country we have an idiom "we're not 20 everyday" as if we should enjoy life before it's too late. Now when I hear "we're not 20 everyday" I always reply with "fortunately".

It took me about a year and a half to accept to live with this, I have no doubt you'll do the same and I guess you have better chance to get a cure in a few years unlike me 15 years ago

 

[GlennS]

- Noticed tinnitus improvement, but not as much as they'd hoped for

Both a glimmer of hope and reason for defensive pessimism. Par for the course.

If two shots are improving tinnitus, I'm in for as many shots as needed to restore my ear cells.

The question is "if 4 shots are safe, are 10 safe as well?". We may never know until one tries...

This assuming it doesn't reach a point of diminishing returns.

 

[Ozwel]

Both a glimmer of hope and reason for defensive pessimism. Par for the course.

This assuming it doesn't reach a point of diminishing returns.

I guess one important point will be the ENT's ability to inject the liquid as far as possible too. Not sure if it's as simple as injecting the liquid right behind the eardrum or if it's way more technical.