Frequency Therapeutics — Hearing Loss Regeneration

[Jurger]

Thank you for saying this. So tired of reading "audiograms mean nothing" by people with losses in the super high frequencies/hidden hearing loss or even one single minor loss at one frequency.

I have losses in all frequencies in the severe/profound range, audiograms and their results do matter.

Me too, severe hearing loss in the right ear, flatlined on all frequencies. The audiogram feels like a test I can never pass. Improvement on that would be a dream come true.

 

[FGG]

Novartis already tried that and shut it down after 8 or so years.

Akouous has a method where they vent the oval window during injection (their drug can't go through middle ear because it's an AAV therapy) and I guess the pressure difference draws the drug through the whole cochlea. Seems way safer than Novartis' method. They have a genetic hearing loss drug. Would be interesting to read their safety data when available.

 

[Ed209]

No one EVER said this was or could be a cure, only a treatment.

Back in 2018, there was talk of petitioning the White House to get the drug released ASAP on the grounds that it was inhumane to withhold a treatment for tinnitus and hearing loss. I can't remember the exact words that were used, but a lot of people assumed there was a cure out there that was being withheld from the people.

This is where expectations have to be reigned in somewhat.

 

[weab00]

First stages of grief: shock, denial, bargaining.

 

[Jurger]

No one EVER said this was or could be a cure, only a treatment.

We can debate about what people in this thread said or didn't say, but this thread did not get to 527 pages on the assumption it would only increase word scores from 12 to 24 out of 50...in a small subset of patients... I also recall people being very depressed about the Phase 1/2 results at the time, before the rationalizing kicked off ("more injections will work better", "the audiogram barely showed improvement because they didn't test the >8000 Hz frequencies" etc.).

 

[Koz]

Me too, severe hearing loss in the right ear, flatlined on all frequencies. The audiogram feels like a test I can never pass. Improvement on that would be a dream come true.

For sure, I have had better hearing and quieter tinnitus during past audiograms not as bad as my current one. My hearing got progressively worse over a decade and the only thing I can think of is noise damage as I am involved in music and a lot of loud environments / headphone use. It stayed at the same level for years when I was extra extra precautious until it got worse again in 2018 after a loud event with no ear plugs. Its weird because my right ear is normal, its my left one that's a dud so people always say "oh well if it was just noise you'd have the other ear closer to the level of your bad one".

Normal MRIs. Specialists say different things, one says idiopathic (although mine was never sudden), another says it was congenital and I had no idea but it got worse as I grew older through other factors and then when I developed tinnitus and deep enough hearing loss in that ear did I finally catch onto it. Honestly, who even knows, I don't stress too much about it as my MRI is normal and there is no cure to reverse the hearing loss or tinnitus.

 

[FGG]

Me too, severe hearing loss in the right ear, flatlined on all frequencies. The audiogram feels like a test I can never pass. Improvement on that would be a dream come true.

A flatlined audiogram is very unusual. There is a study in the research paper voting thread where that particular presentation only may benefit from pitch training to reduce tinnitus (a few even got it eliminated entirely apparently). Per that study, there is something about all frequencies being equally off in exactly the same way that allows for brain retraining.

Check it out.

 

[Cernuto]

I think fixing the hair cells are one part of the puzzle. Restoring connection to the brain and making sure the brain is operating correctly to communicate with the connection are also required. I feel FX-322 is a step in the right direction, although not fully appreciated right now as we expected it to be a miracle cure.

 

[Zugzug]

Back in 2018, there was talk of petitioning the White House to get the drug released ASAP on the grounds that it was inhumane to withhold a treatment for tinnitus and hearing loss. I can't remember the exact words that were used, but a lot of people assumed there was a cure out there that was being withheld from the people.

I respect you a lot, but doesn't it seem disingenuous to superimpose an argument you had with someone in 2018, when the "X % of Biotechs fail" idea was extremely relevant. All of the bulls are new since then. To be honest, I've spent significantly more time doubting the treatment than believing in it. I also have the added lack of bias because I don't think the drug will help me in any meaningful way.

There's sometimes this belief that if someone is a bull, it must be because they are seeing it the way they want to see it. I just don't believe that was the case. I really think if it looked bad, I would have doubted it. I was wrong, but at least I put myself out there. I'm still looking into it and trying to understand what went wrong in the WR repeats.

 

[tomytl]

Today is the day we are back to zero in a quest of a hearing loss treatment.

If we look at the pipelines of companies working on hearing loss treatments, there is absolutely nothing which could hit the market anytime soon.

I am very very disappointed and sad.

If multi dosing doesn't enhance WR or hearing levels, it likely shows that the hair cells weren't really being stimulated by the drug. With WR scores, we do not have evidence that inner hair cells have been regenerated.

So I go back to the hole of suffering!

 

[F-u-T]

Outcomes and decision making are not the same thing. I sure hope you don't live your life in such a way that doesn't involve probabilities of outcomes, but only retroactively basing things off of outcomes.

Actually, if anything, my non-outcome-based decision-making regret is not investing more. I went to bed last night wondering if I should have invested more.

What if it was a mega boom today? This is how life works...

I was thinking the same thing the last couple of days. I wanted to buy more stock in case it boomed!

 

[HootOwl]

Haha, thanks for lightening the mood.

I hope this isn't coming across as me making light of the situation... I, like several others, did not have high hopes for greater penetrance (although a part of me was really hoping they'd push to 5 kHz or so with repeat dosing), but I truly thought there would be 30-40 dB gains in the EHF and 15-20 around 8 kHz.

I considered this to be a decent first pass at a revolutionary drug, and I'm just feeling deeply deflated that we didn't even see that. So I seek refuge in the memes.

I still think there is something missing from this puzzle, that isn't completely accounted for even if those with severe HL had been given the placebo arm in phase 1 and shown the same improvements as the treatment arm.

As someone who experienced short lived hearing loss and muffedness in my right ear it's difficult to imagine jumping from 30 words on the WRT, to 60 - all from the placebo effect. Hearing loss is very difficult to hack in that way. You kind of don't hear the words or you do.

Edit: I should add that I have both EHF t and very low (sub 2k) severe t, so I'm the same boat of "this drug, at least in its current iteration, will not do much for me." At most it would knock out my electric hissing and not much else so I was optimistic, but cautious. This is all assuming my notches are OHC, and not isolated synaptopathy or inflammation.

 

[HootOwl]

There would have to be a leap in technology. We don't have it yet. But hopefully a company will be able to develop one.

Also, it doesn't have to be getting deeper mechanically. It could be a more complex development of drug. Finding something that's able to easily penetrate the bone that surrounds the cochlea.

Columbia is actually working on this.

3D-Printed Microneedles Create Precise Perforations in Human Round Window Membrane in Situ

3D-Printed Microneedles Open Ears to New Treatments

 

[Jurger]

A flatlined audiogram is very unusual. There is a study in the research paper voting thread where that particular presentation only may benefit from pitch training to reduce tinnitus (a few even got it eliminated entirely apparently). Per that study, there is something about all frequencies being equally off in exactly the same way that allows for brain retraining.

Check it out.

I'll check it out, thanks. By the way, a flat audiogram is not that uncommon in idiopathic sudden sensorineural hearing loss. They come in all kinds of crazy variations, even in reverse slope.

 

[Zugzug]

I was thinking the same thing the last couple of days. I wanted to buy more stock in case it boomed!

I clicked "genius," because it's refreshing to see someone use their brain. Hmm... who should I be mad at? Reality or the suffering, suicidal people volunteering their time to supply information to a community? It's a tough one. I can't figure it out.

 

[FGG]

I hope this isn't coming across as me making light of the situation... I, like several others, did not have high hopes for greater penetrance (although a part of me was really hoping they'd push to 5 kHz or so with repeat dosing), but I truly thought there would be 30-40 dB gains in the EHF and 15-20 around 8 kHz.

I considered this to be a decent first pass at a revolutionary drug, and I'm just feeling deeply deflated that we didn't even see that. So I seek refuge in the memes.

I still think there is something missing from this puzzle, that isn't completely accounted for even if those with severe HL had been given the placebo arm in phase 1 and shown the same improvements as the treatment arm.

As someone who experienced short lived hearing loss and muffedness in my right ear it's difficult to imagine jumping from 30 words on the WRT, to 60 - all from the placebo effect. Hearing loss is very difficult to hack in that way. You kind of don't hear the words or you do.

Exactly. I can't make myself hear the frequencies I lost no matter how much I want to.

 

[Aaron91]

Let's remind ourselves that Frequency Therapeutics are still blinded at the individual level, which may explain their sheepishness today. I too would be lost for words if I only had group data that went against my expectations with no individual level insight. Remember, the whole bear thesis was born out of the individual data, not group data.

 

[Koz]

A flatlined audiogram is very unusual. There is a study in the research paper voting thread where that particular presentation only may benefit from pitch training to reduce tinnitus (a few even got it eliminated entirely apparently). Per that study, there is something about all frequencies being equally off in exactly the same way that allows for brain retraining.

Check it out.

It's not as unusual as you might think (link below). My left ear is practically flat across the severe/profound. Obviously the first port of call was an MRI which came back normal at the time.

I have also come across a research paper that indicates that it's not out of the norm to have one ear be far more susceptible to noise damage than the other ear like the current medical field thinks.

Effects of blast and acoustic trauma: assessment of hearing status on war veterans

 

[Jurger]

On a positive note, it seemed to me a lot of companies have hair cell regeneration drugs in their pipeline that don't seem to materialize (Otonomy's OTO-6XX, Sound Pharmaceuticals' SPI-5557, Akouos' unnamed drug). Maybe because they wanted to see what FX-322 would do. Hopefully they'll feel more confident to take risks now that FX-322 is more or less out of the picture.

 

[Coleoptere]

Considering their drug depletes support cells (which are necessary long term for hair cell survival) to transduce to hair cells, I think the decision to halt further trials was more a safety one (i.e. the gains might be temporary and further degradation may happen). Audion wouldn't have halted the trial if it was just good news in a vacuum.

The vacuum was also financial. The EU was the sponsor of the trial. So the results are there to be continued by a commercial party. And that did not happen. Maybe the results were not convincing enough or maybe not enough was done to get parties involved. We will never know...

 

[FGG]

Let's remind ourselves that Frequency Therapeutics are still blinded at the individual level, which may explain their sheepishness today. I too would be lost for words if I only had group data that went against my expectations with no individual level insight. Remember, the whole bear thesis was born out of the individual data, not group data.

Do you mean to say the bear thesis was born out of group data?

 

[r34d1ng]

On a positive note, it seemed to me a lot of companies have hair cell regeneration drugs in their pipeline that don't seem to materialize (Otonomy's OTO-6XX, Sound Pharmaceuticals' SPI-5557, Akouos' unnamed drug). Maybe because they wanted to see what FX-322 would do. Hopefully they'll feel more confident to take risks now that FX-322 is more or less out of the picture.

Good luck finding funding after Otividex's second failure and FX-322, though.

 

[Mathieulh]

FX-322 was my only hope. I have waited over 2 years, tortured to no end by tinnitus, only to learn this drug doesn't do anything or work at all, with no proper candidate to alleviate my suffering anytime soon.

I will now start putting my things in order and put an end to my suffering. It is sad it has come to this but I can't live like this.

I have heard Pegasos does accept tinnitus sufferers as potential candidates.

 

[Diesel]

I wonder now if the OTO-413 trial had a similar issue... did they ever disclose why they want to re-run the Phase 1?

 

[Ed209]

I respect you a lot, but doesn't it seem disingenuous to superimpose an argument you had with someone in 2018, when the "X % of Biotechs fail" idea was extremely relevant. All of the bulls are new since then. To be honest, I've spent significantly more time doubting the treatment than believing in it. I also have the added lack of bias because I don't think the drug will help me in any meaningful way.

Zugzug, the 2018 reference was a direct response to Aaron91 when he said no one had ever said it was a cure. Many of the members who were there during those times are still here now, and that is when most of the hype was built. I think too many may have taken the cure talk to heart, and this can lead to a huge disappointment. I haven't read this thread much recently, so it's not related to any recent discussions.

I wasn't trying to be provocative in any way, and I respect everybody here immensely.

We deserve a treatment that works.

 

[weab00]

Does anyone else figure this thread will sizzle out and die like the Lenire and Audion Therapeutics ones if day 210 results are just as bad? The only drugs I remain hopeful for are Ebselen and the reformulated Trobalt.

Now I understand why veterans are so jaded towards miracle cures. It just doesn't work like that.

 

[Cernuto]

FX-322 was my only hope. I have waited over 2 years, tortured to no end by tinnitus, only to learn this drug doesn't do anything or work at all, with no proper candidate to alleviate my suffering anytime soon.

I will now start putting my things in order and put an end to my suffering. It is sad it has come to this but I can't live like this.

I have heard Pegasos does accept tinnitus sufferers as potential candidates.

Stick around for SPI-1005.

 

[Zugzug]

Zugzug, the 2018 reference was a direct response to Aaron91 when he said no one had ever said it was a cure. I haven't read this thread much recently, so it's not related to any recent discussions.

I wasn't trying to be provocative in any way, but I feel many may have been expecting more than they should have. I respect everybody here immensely, and we deserve a treatment that works.

In that case, it could be a misunderstanding. I thought by ever, he meant of the main people deep diving recently, which is true. We were doing all sorts of analysis and looking at the pharmacology graphs, the statistics, the preclinicals, etc. I don't think anyone who deep dived expected a miracle. I would even go as far as say that no changes for multiple doses was something people were prepared for.

I don't think most people expected this. If they did, they wouldn't have invested on their own free will.

 

[Zugzug]

Does anyone else figure this thread will sizzle out and die like the Lenire and Audion Therapeutics ones if day 210 results are just as bad? The only drugs I remain hopeful for are Ebselen and the reformulated Trobalt.

Now I understand why veterans are so jaded towards miracle cures. It just doesn't work like that.

I don't think so. Science is hard. Definitely a huge punch, but I don't see FX-322 as some big waste. Really, we all have to be honest that the delivery is simply trash.

 

[Matchbox]

New Kv7.1 drugs are the only thing I have any real hope in. It's already had a track record of proof of concept on humans here.