Frequency Therapeutics — Hearing Loss Regeneration

[Jrblovsky]

Guys, do you think there is anything we can do collectively to try to get expanded access/compassionate use offered ASAP?

I'm the type of person who has been googling Frequency Therapeutics everyday (literally every fucking day) for every single update for the past 4 years.

I unfortunately wasn't able to participate in the clinical trials.

I'm honestly at my limit. This is crushing my soul.

We are all in the same spot. I haven't left my bed in two days. Wait for the Phase 2 results. It may not even work and you would be wasting your time.

 

[Gb3]

If hidden hearing loss is hearing in noisy environments, then it would appear that FX-322 may help. They just tweeted about hidden hearing loss, and this slide shows that there is a probable trend in Word-In-Noise improvement.

View attachment 43375

Well I have high frequency hearing loss starting at 4000 Hz and really struggle to hear in background noise. I just think in regards to hidden hearing loss that it just isn't identifiable on an audiogram, especially a standard one. There is most likely hearing loss in the higher frequencies.

 

[Still-Hope]

What might make more sense in my opinion is to first make the audiogram simply more granular. So, instead of having the most common: 250 Hz - 500 Hz - 1000 Hz - 2000 Hz - 4000 Hz - 6000 Hz - 8000 Hz, add detail to areas where consonants and vowels are clustered, this would help align the audiogram with word deficiencies.

View attachment 43075

So perhaps we expand it to: 250 Hz, 300 Hz, 400 Hz, 500 Hz, 750 Hz, 1000 Hz, 1200 Hz, 1500 Hz, 1800 Hz, 2000 Hz, 2200 Hz, 3000 Hz, 4000 Hz, 5000 Hz, 6000 Hz, 8000 Hz, 10 kHz, 12 kHz, 14 kHz, 16 kHz.

From there, I don't know if it exists, but I wonder if there is a way to reproduce parts of speech as an audiogram. FOR example, an audiogram that tests how well I can hear the "f" sound, or "t" sound, or "r" sound. If I understand how the cochlea functions correctly, this would also give clinicians a better idea of specific ranges of deficit.

Once regenerative medicines are on the market, these upgrades may help doctors also understand where recovery is taking place, and if more doses are needed of FX-322. So, for example, if my baseline word score was 25/50, and I had deficits in the 2200 Hz - 8000 Hz range, and deficits hearing "k", "t", "f", "sh", it might help the doctor know what the first series of dosages might look like.

Then, on a return visit, if my word score was 40/50, which is good, but has room for improvement. A second pass at this advanced audiogram might show that I still have deficits between 2000 Hz and 4000 Hz, and with "k" and "t" letter sounds. Again, this would help the doctor target the appropriate dosage level.

Here in France, after having passed an audiogram from 40 Hz to 16 kHz with an ENT, I've done one more audiogram (more precise as you described) with an audiologist.

He checked a lot more frequencies, especially in the areas where I had losses, and tinnitus.

And it showed a lot more information about my hearing loss. (See the attached result).

Also, as a music producer and sound engineer, what you say about word recognition and vowels / consonants is very relevant. We learn this in audio mixing technique, each vowel and consonant corresponds to a frequency zone.

@Diesel, do you have a background in medicine, you seem to know a lot? Or are you self-taught? I hope after all the effort you've given making this difficult topic understandable to us stupid people you get relief from FX-322 as soon as possible.

Definitely! Massive thanks, @Diesel!

 

[Diesel]

Here in France, after having passed an audiogram from 40 Hz to 16 kHz with an ENT, I've done one more audiogram (more precise as you described) with an audiologist.

He checked a lot more frequencies, especially in the areas where I had losses, and tinnitus.

And it showed a lot more information about my hearing loss. (See the attached result).

Also, as a music producer and sound engineer, what you say about word recognition and vowels / consonants is very relevant. We learn this in audio mixing technique, each vowel and consonant corresponds to a frequency zone.

View attachment 43381

Thank you for sharing this. I wish here in the US, we all got this much attention to detail on the audiogram. It might be more telling in helping us understand our condition. Oh yay, I see you work in sound/audio! I'd love to pick your brain about the tinnitus you experience!

Just curious, when I look at your audiogram, I see some significant dips at 3 kHz - 4 kHz, 6 kHz-ish, and 10 kHz - 12 kHz.

Do the tinnitus sound(s) that you experience sound like they are in the range of losses? Like do you hear a sound that somewhat sounds like a 3 kHz - 4 kHz sine wave or tone?

If so, when you put in ear plugs in a quiet setting, is the tinnitus at those ranges amplified or more defined?

I always ask this, because I believe that FX-322 even causing a mild improvement (like 10 dB) in those areas of deficiency, may be enough to give the brain signal to eliminate the tinnitus experienced at least in a normal setting.

 

[Still-Hope]

Thank you for sharing this. I wish here in the US, we all got this much attention to detail on the audiogram. It might be more telling in helping us understand our condition. Oh yay, I see you work in sound/audio! I'd love to pick your brain about the tinnitus you experience!

Just curious, when I look at your audiogram, I see some significant dips at 3 kHz - 4 kHz, 6 kHz-ish, and 10 kHz - 12 kHz.

Do the tinnitus sound(s) that you experience sound like they are in the range of losses? Like do you hear a sound that somewhat sounds like a 3 kHz - 4 kHz sine wave or tone?

If so, when you put in ear plugs in a quiet setting, is the tinnitus at those ranges amplified or more defined?

I always ask this, because I believe that FX-322 even causing a mild improvement (like 10 dB) in those areas of deficiency, may be enough to give the brain signal to eliminate the tinnitus experienced at least in a normal setting.

You're welcome!
Thank you for sharing useful knowledge, I'm happy to contribute best as I can!

I can answer you with certainty, being a person who has listened to sine waves for years, being a producer of electronic music...

When at the very beginning I had only one tinnitus sound, it was precisely located at 3200 Hz, I rechecked myself several times. And this was the biggest dip I had in my ear on the first audiogram I did. This confirms in a factual way that the tinnitus was exactly at the biggest dip on my audiogram.

Unfortunately then it started modulating (between 3000 Hz and 4000 Hz). The scientific reasons I do not know... but my own interpretation is that my hearing loss has continued to progress a bit... Who knows... Stress may have played a factor too?! This remains my own interpretation.

Unfortunately for me, a few weeks later... Because of stress, focusing on it, progressive hearing loss, or a neurological process that I have no knowledge of at all, I started hearing several other tinnitus sounds.

It is therefore now difficult to identify them precisely in what exact frequencies they sit... because they modulate, mix with each others and change gradually during the day...

But I can almost say for sure that yes, they are all in the frequency areas where I have the biggest hearing loss...

So my intuition (in view of my own experience) is definitely yes, tinnitus sits in frequencies that the brain no longer receives. It's 100% sure that is one factor.

For the rest I don't know... apparently there are probably many other neurological mechanisms involved...

About the earplugs, I don't use them anymore, because sometimes I have the feeling that I'm hearing all these tinnitus sounds moving in my whole head... Lol. So I never do this

 

[Diesel]

You're welcome!
Thank you for sharing useful knowledge, I'm happy to contribute best as I can!

I can answer you with certainty, being a person who has listened to sine waves for years, being a producer of electronic music...

When at the very beginning I had only one tinnitus sound, it was precisely located at 3200 Hz, I rechecked myself several times. And this was the biggest dip I had in my ear on the first audiogram I did. This confirms in a factual way that the tinnitus was exactly at the biggest dip on my audiogram.

Unfortunately then it started modulating (between 3000 Hz and 4000 Hz). The scientific reasons I do not know... but my own interpretation is that my hearing loss has continued to progress a bit... Who knows... Stress may have played a factor too?! This remains my own interpretation.

Unfortunately for me, a few weeks later... Because of stress, focusing on it, progressive hearing loss, or a neurological process that I have no knowledge of at all, I started hearing several other tinnitus sounds.

It is therefore now difficult to identify them precisely in what exact frequencies they sit... because they modulate, mix with each others and change gradually during the day...

But I can almost say for sure that yes, they are all in the frequency areas where I have the biggest hearing loss...

So my intuition (in view of my own experience) is definitely yes, tinnitus sits in frequencies that the brain no longer receives. It's 100% sure that is one factor.

For the rest I don't know... apparently there are probably many other neurological mechanisms involved...

About the earplugs, I don't use them anymore, because sometimes I have the feeling that I'm hearing all these tinnitus sounds moving in my whole head... Lol. So I never do this

This was incredibly informative; thank you for sharing your experience.

 

[Pharz]

No, you're thinking of the word recognition (WR) score - that test is a "words in quiet" test. 4 patients saw statistically significant WR score improvements. I've attached the slide from their presentation which shows the difference between the two tests. A ~30% improvement was seen overall in the Words in Quiet test, while a ~20% improvement overall was seen in the Words in Noise test.

View attachment 43360

In my post I was referring to the Words in Noise test, which did not achieve statistical significance - but it is the subject of Frequency Therapeutics' tweet. Also of interest is that this type of hearing is supposedly improved by increasing synaptic connections (what OTO-413 does). Though Frequency Therapeutics may be trying to say that new hair cells help too.

Is 30% improvement over 30 days not significant? I think for people who are dealing with this this problem even 10% is good news.

 

[Lucifer]

Is 30% improvement over 30 days not significant? I think for people who are dealing with this this problem even 10% is good news.

Remember, this was with one dose of FX-322 only. In the current Phase 2a clinical trial, some participants will be able to get 4 doses of FX-322 which should make the results look even better if additional doses of FX-322 allow it to reach deeper in the round window.

 

[ThomasRobert]

During Phase 2a, there will be candidates who will receive 4 doses of FX-322.

90-day results are scheduled to be published in March and 120-day results are expected in June.

Question:

Would the candidates have received the 4 doses before the 90 days? Or would it be 2 doses during the first 90 days and the other 2 doses after the 90 days?

 

[Jrblovsky]

Remember, this was with one dose of FX-322 only. In the current Phase 2a clinical trial, some participants will be able to get 4 doses of FX-322 which should make the results look even better if additional doses of FX-322 allow it to reach deeper in the round window.

Praying for large gains. Some of us have massive losses. 10 dB isn't going to do much in my case.

 

[Diesel]

During Phase 2a, there will be candidates who will receive 4 doses of FX-322.

90-day results are scheduled to be published in March and 120-day results are expected in June.

Question:

Would the candidates have received the 4 doses before the 90 days? Or would it be 2 doses during the first 90 days and the other 2 doses after the 90 days?

Everyone in the Phase 2A FIRST received 4 doses in the first 30 days of the trial, or, 1 per week. So it would have looked like this:

1x Dose of FX-322:

Week 1: FX-322 - Week 2: Placebo - Week 3: Placebo - Week 4: Placebo

2x Dose of FX-322

Week 1: FX-322 - Week 2: FX-322 - Week 3: Placebo - Week 4: Placebo

4x Dose of FX-322

Week 1: FX-322 - Week 2: FX-322 - Week 3: FX-322 - Week 4: FX-322

0x Dose of FX-322 (Placebo)

Week 1: Placebo - Week 2: Placebo - Week 3: Placebo - Week 4: Placebo


After the "Week 4" dose, the clock starts on the follow-up visits.

15 Days, 30 Days, 90 Days, 120 Days, 150 Days, 180 Days, 210 Days


For the 90-Day Results, they will show what those "Dose Groups" did on average at the 90-Day follow-up on most of the endpoints:

Speech intelligibility as measured by WR and WIN testing
Pure Tone Audiometry measures at frequencies from 0.25 kHz to 16 kHz
Partial data on measures of FX-322 on tinnitus, impact on QoL
Safety profile

So, we'll see exactly what the Placebo, 1x, 2x, 4x groups did on average 90 days from their last dose.

 

[AfroSnowman]

Praying for large gains. Some of us have massive losses. 10 dB isn't going to do much in my case.

I don't know your case, but my understanding is that dB scale is logarithmic, so a 10 dB improvement would mean a doubling of your hearing at the frequencies that it reaches from your current baseline.

 

[Diesel]

I don't know your case, but my understanding is that dB scale is logarithmic, so a 10 dB improvement would mean a doubling of your hearing at the frequencies that it reaches from your current baseline.

It's actually 3x - 4x the sensitivity for the human ear for every 10 dB increment of improvement. There are some varied views on how this is measured.

So, if you had a baseline of 50 dB loss at 8 kHz, and improved to 40 dB, your ear is now 3 - 4x more sensitive to 8 kHz. A move from the same 50 dB baseline to 30 dB would mean your ear is now 9x - 16x more sensitive to 8 kHz.

 

[ThomasRobert]

Everyone in the Phase 2A FIRST received 4 doses in the first 30 days of the trial, or, 1 per week. So it would have looked like this:

1x Dose of FX-322:

Week 1: FX-322 - Week 2: Placebo - Week 3: Placebo - Week 4: Placebo

2x Dose of FX-322

Week 1: FX-322 - Week 2: FX-322 - Week 3: Placebo - Week 4: Placebo

4x Dose of FX-322

Week 1: FX-322 - Week 2: FX-322 - Week 3: FX-322 - Week 4: FX-322

0x Dose of FX-322 (Placebo)

Week 1: Placebo - Week 2: Placebo - Week 3: Placebo - Week 4: Placebo


After the "Week 4" dose, the clock starts on the follow-up visits.

15 Days, 30 Days, 90 Days, 120 Days, 150 Days, 180 Days, 210 Days


For the 90-Day Results, they will show what those "Dose Groups" did on average at the 90-Day follow-up on most of the endpoints:

Speech intelligibility as measured by WR and WIN testing
Pure Tone Audiometry measures at frequencies from 0.25 kHz to 16 kHz
Partial data on measures of FX-322 on tinnitus, impact on QoL
Safety profile

So, we'll see exactly what the Placebo, 1x, 2x, 4x groups did on average 90 days from their last dose.

So basically next month's results will be either a Pass or Failure for Frequency Therapeutics.

Wow.

 

[Jrblovsky]

It's actually 3x - 4x the sensitivity for the human ear for every 10 dB increment of improvement. There are some varied views on how this is measured.

So, if you had a baseline of 50 dB loss at 8 kHz, and improved to 40 dB, your ear is now 3 - 4x more sensitive to 8 kHz. A move from the same 50 dB baseline to 30 dB would mean your ear is now 9x - 16x more sensitive to 8 kHz.

I can agree with that. When I had a 25 dB loss at 8 kHz everything sounded very near normal. Now at a 75 dB loss at 8 kHz everything seems dull.

 

[AfroSnowman]

It's actually 3x - 4x the sensitivity for the human ear for every 10 dB increment of improvement. There are some varied views on how this is measured.

So, if you had a baseline of 50 dB loss at 8 kHz, and improved to 40 dB, your ear is now 3 - 4x more sensitive to 8 kHz. A move from the same 50 dB baseline to 30 dB would mean your ear is now 9x - 16x more sensitive to 8 kHz.

Reading this gets me excited. I had some weird ultimately unknowable stuff go down that led to the noise in my head, but regardless of the cause it is in the high frequency range 12-16 kHz that I have most of my hearing loss 40-55 dB and all of the tinnitus. I can imagine that if I had a 10 dB gain, much less a 20 dB in those frequencies it really could easily make enough of a difference that I would fall into that lucky category of non-intrusive tinnitus non-sufferers.

 

[Diesel]

Reading this gets me excited. I had some weird ultimately unknowable stuff go down that led to the noise in my head, but regardless of the cause it is in the high frequency range 12-16 kHz that I have most of my hearing loss 40-55 dB and all of the tinnitus. I can imagine that if I had a 10 dB gain, much less a 20 dB in those frequencies it really could easily make enough of a difference that I would fall into that lucky category of non-intrusive tinnitus non-sufferers.

Yeah, I am not a scientist, but I suspect that tinnitus experienced by those with NIHL / SNHL is a matter of a certain level of missing signal by enough damaged/missing hair cells in a particular area of the cochlea. Every time someone shares on here an audiogram, I ask about their tinnitus. Many have shared that the dips are what their tinnitus sounds like. This is the case for me as well. Typically the dips on the audiogram drop to anywhere from 30 dB to 70 dB where people are able to distinguish the tinnitus tone/noise/whatever.

I suspect then, that if potentially all or at least enough hair cells are replaced in those areas where the dip exists (and therefore the tinnitus is most prominent), then the sensation should begin to be resolved.

I also suspect that the performance of the hearing in those "tinnitus zones" may not necessarily need to go back to the "World-War 2 Era Audiogram" definition of normal hearing above 20 dB. I think its easy to get hung up on the measurements while forgetting about the biological changes taking place.

So, for @Still-Hope's audiogram shared a few comments, back, at 6 kHz, it may only take enough hair cells to give a 10-15 dB gain; still not "normal" on the classic audiogram, but that's enough signal for the brain to no longer produce tinnitus.

 

[scotty03874]

I can agree with that. When I had a 25 dB loss at 8 kHz everything sounded very near normal. Now at a 75 dB loss at 8 kHz everything seems dull.

I agree. When I was -40 dB it did not even affect my hearing in my opinion but once I had the surgery on my middle ear and now I'm -65 dB it is completely different and entirely dull sounding. If I could go from -65 dB back up to -40 dB I would be thrilled.

 

[Guywithapug]

I agree. When I was -40 dB it did not even affect my hearing in my opinion but once I had the surgery on my middle ear and now I'm -65 dB it is completely different and entirely dull sounding. If I could go from -65 dB back up to -40 dB I would be thrilled.

Same. I was at -40 dB at 4 kHz and everything sounded clear and normal to me. Now at -65 dB, I have fullness and sounds are slightly dull as well. Word recognition remains at 100%. Tinnitus tone matches the affected frequency.

I'll also add that when my tinnitus is really quiet, I can readily notice the hearing deficit in my bad ear around sounds. However, when it is roaring, I don't notice the deficit really. I think that really supports the tinnitus tone/frequency dip theory being discussed, as the brain is filling in the missing signal.

Does anyone else experience this?

 

[Keith Handy]

It's anyone's guess, but my gut instinct, based on a lot of recent reading, is that an OHC repair approach could well help us, especially given that FX-322 may also in places regrow synapses as well. I'll be making a thread soon in the hyperacusis subforum as to why I think this is the case.

Just so you know, I've been checking every so often for this thread.

 

[Keith Handy]

Expectations for the timing of the upcoming Day-90 release:

Frequency Therapeutics owes a Q4/2020 Press Release in February; which typically includes an outlook for 2021. It's highly likely that in that PR, they'll specify a date in March where they will disclose the 90-day Phase-2A Interim results in a webcast or in a PDF, or both, that they'll then file with the SEC.

I do not think it will be an unexpected release. It would be beneficial to set a specific date in March.

If I could speculate, they may only need to give a week's notice.

Their last few quarterly press releases were mid-month. Their previous Q4 release was in March, not February.

 

[AfroSnowman]

Same. I was at -40 dB at 4 kHz and everything sounded clear and normal to me. Now at -65 dB, I have fullness and sounds are slightly dull as well. Word recognition remains at 100%. Tinnitus tone matches the affected frequency.

I'll also add that when my tinnitus is really quiet, I can readily notice the hearing deficit in my bad ear around sounds. However, when it is roaring, I don't notice the deficit really. I think that really supports the tinnitus tone/frequency dip theory being discussed, as the brain is filling in the missing signal.

Does anyone else experience this?

I have the opposite experience. I have a really different hearing profile than you do, no loss at lower frequencies, mild loss >4 kHz, moderate >12 kHz, and the tinnitus is all at the ultra high frequencies, but when I am having the rare mild tinnitus day it is almost like I don't have hearing loss at all, but when the tinnitus is really raging hearing becomes more challenging.

 

[Ilias T]

I have been following this research for a long time. I am very confident that FX-322 will work and succeed in all clinical trials. Hearing loss and ringing are not rare. Their stock also went up by a lot which shows that investors are also confident.

I hope that the price of FX-322 will be affordable if they release it. I believe it will be affordable.

 

[Aaron91]

Just so you know, I've been checking every so often for this thread.

Sorry, @Keith Handy! I've been quite busy this week and it's a post I really want to make my time with in terms of accumulating all my sources and building my thesis, so I'd rather not rush it. Hopefully should have it to you guys within the week!

 

[Bill Arsenault]

I cannot even begin to truly imagine the fear and horror severe tinnitus sufferers experienced back in the day.

Alone with no help or hope in sight and no threads to read when unable to fall asleep.

So grateful for everyone here.

 

[Jrblovsky]

I cannot even begin to truly imagine the fear and horror severe tinnitus sufferers experienced back in the day.

Alone with no help or hope in sight and no threads to read when unable to fall asleep.

So grateful for everyone here.

This thread is inspiring and depressing at the same time. If FX-322 doesn't work, it's going to be 10 years minimum before another treatment is available.

 

[Diesel]

This thread is inspiring and depressing at the same time. If FX-322 doesn't work, it's going to be 10 years minimum before another treatment is available.

The only concern right now is how well multiple doses improve hearing function. If multiple doses don't go any deeper/improve performance, they'll need to change the gel or delivery method.

As long as FX-322 still maintains a favorable safety profile, it's coming to the market in a single-dose form. There's no alternative treatment, and even the single dose outcome from the Phase 1/2 would be beneficial to millions worldwide.

 

[Robert Logan]

What do people imagine the cost of FX-322 will be?

I'm blessed to have lived in the UK and have usually relied on the NHS, so while I have contributed to some drugs, I have no sense about these things. I looked into private tinnitus treatments here, but those measures amounted to around the £6000 mark! (And of course were not guaranteed to work...)

 

[Keith Handy]

The only concern right now is how well multiple doses improve hearing function. If multiple doses don't go any deeper/improve performance, they'll need to change the gel or delivery method.

What if they were to follow the injection and absorption with controlled exposure to a specially engineered sound, to help move fluids around in the cochlea and spread the FX-322 molecules further from the base? Sort of stirring up the fluid via the ear's own mechanism?

I've also had a thought about extended audiograms. Obviously we need them, but at least from watching that video about the hurdles in healthcare—namely billable time, and the need to see all scheduled patients in a day—every extra minute of the audiologist's attention is precious and finite.

So why couldn't the extended audiogram process be automated? You set the patient up with the headset and the machine, initiate the test, leave for 10 to 15 minutes to do other tasks, and the machine records the patient's responses via a presses of a button or other input device. The machine is programmed to choose tones and levels the same way a live audiologist would, based on responses.

This way everybody could see if they have narrow dips or sharp dropoffs, similar to the ones shown earlier in this thread, which often seem to correspond with tinnitus frequencies, and wouldn't show up on a standard test.

 

[FGG]

What if they were to follow the injection and absorption with controlled exposure to a specially engineered sound, to help move fluids around in the cochlea and spread the FX-322 molecules further from the base? Sort of stirring up the fluid via the ear's own mechanism?

Sound travels from the Oval Window to the Round Window so I'm not sure how that would work. I doubt it makes a difference either way but this diagram at least makes me wonder if sound deprivation for a few weeks might produce better results.