Frequency Therapeutics — Hearing Loss Regeneration

Sure, it's profit motivated, but the "do no harm" of the Hippocratic oath should be in effect, and by not looking at these upper ranges, collecting valid data for future research and themselves to base a diagnosis off of, is harmful. If it was all a money sink, then why did they ever stand up to cancer?

Audiologists seem to exist in this weird quasi-medical field. Like, they're medical adjacent, not actually in it.

 

What do you mean by this?

 

I saw the top rated ENT in my city and I live somewhere surrounded by research universities so you’d think 5 stars in a big city means a lot. My main complaints were hearing sensitivity, severe fullness and horrible tinnitus all of which that ENT attributed to some slight redness in my left nostril that he glanced at for a second. I was about a month out from a really bad cold.

I do think central gain CAN be an issue (perhaps for people who experience hyperacusis for a week or two) but I 100% agree with you that for those of us with severe sensitivity, pain, TTTS, and trigeminal nerve irritation it’s far beyond that and there is significant damage done somewhere. Why they don’t want to acknowledge that is beyond me and If sucks how even if you pull up a support group or forum of people displaying the same exact issues they’d just think of us as “people with anxiety disorders on the internet”.

I think ENTs don’t think that 16 kHz and beyond matters as far as tinnitus goes because there are tons of people with severe hearing loss that don’t have tinnitus so they are dumbfounded when people with “perfect” audiograms come in complaining of tinnitus.

 

I agree with what you say but I also think it's because ENTs and audiologists know they can't do anything beyond 8 kHz hearing damage. Surgery can't cure SNHL and the only treatment they have is hearing aids at and under 8 kHz. Hearing aids can't help people with hearing loss higher than 8 kHz and if the standard audiogram only shows hearing loss beyond 8 kHz, then they can't do anything at all, which makes them look incompetent and useless. I think it's this reason that many doctors are seemingly unsympathetic and do not take us seriously except to offer "habituation" because there is NOTHING they can do.

 

Well in their minds they’re not doing any harm. And cancer isn’t an invisible illness.

Join any support group or forum for neurological pain or invisible illnesses and all you’ll get is stories of people being misdiagnosed, walking out without being helped, doctors throwing up their hands and saying they can’t help or sending people off to psychiatrists. “Do no harm” doesn’t seem to hold much value these days

I’m not sure if it’s coming off that way but I’m not arguing with you btw we’re on the same team here and I agree with your statements

By me saying “ I understand” why ENT’s/audiologists do what they do I don’t mean to say I’m siding with them or thinking that it’s the right way of doing things. I think it’s wrong. I guess I just meant to say with the information they have/or lack of, as well as treatment options I see why they operate the way they do but that doesn’t mean it doesn’t need to change

 

So, FX-322 is designed to regenerate hearing only on ranges you have support cells. If you are deaf on your tinnitus tone frequency, if it's in the upper ranges, then you have moved past it. I should have explained if your loss is around 90 dB we aren't certain it would fix it.

 

I would sell everything I own to get rid of both hyperacusis and tinnitus.

 

I agree. I'm sure the average ENT has thought about this stuff too. They probably suggest habituation because they don't want a patient who could benefit from it to never try it. I am cautiously optimistic that after FX-322, Otonomy, Hough, etc. ENTs will magically become more thoughtful about this stuff because they know they can think out loud a bit more.

 

Yeah, sorry if I seem argumentative, that's not my intent either. Yeah, I see what you mean about the do no harm bit. Hopefully FX-322 changes that.

 

I see!

Since there are lots of us here with multi-tonal, hissing, static electrical zapping sort of tinnitus. I wonder what this means in terms of damage or loss and how it compares to just single tonal “eeee” sounds.

 

Then FX-322 could help with the other tones, or all the tones, depending on whether there's support cells in the area. Granted, I'm vainly hoping that getting a few of the support cells going sorta restarts the ear and has it fix upper levels too, but that's a long shot.

 

I see we've gotten back on the Tinnitus Anxiety Express!

Will FX-322 work for us? Are ENTs going to refuse to give it to us?!

The are two options today for "treating" SNHL and NIHL: Hearing aides and coping treatments. A prosthetic device and "here's some ways to deal with it that might work."

That's it for now. The bar is so embarrassingly low for a problem that effects millions.

This is why in the Phase 2A, Frequency is investigating using the STANDARD methods used in the clinic today as their primary outcomes.
- Word recognition in quiet, word recognition in noise, pure tone audiometry.

Providing clinically meaningful data for these STANDARD measures gives ENTs a new THIRD option to help people that are deficient in any of these areas. The benefits will be easily understood by the ENT, and integrated into their treatment process. BONUS: The treatment fits their current methods without requiring new types of testing, procedures to learn, etc.

If FX-322 continues to provide meaningful outcomes using STANDARD measures, it's going to be stocked at the ENT office. No question.

Frequency is also investigating a number of Secondary Outcome measures that might also be useful in the clinical settings. These are definitely forward-looking... but can be useful for ENTs:

Extended High Frequency (8 kHz-16 kHz) Audiometry AND Tinnitus Assessment (TFI).

All ENTs need to see here is a meaningful improvement in the High Frequency and/or Tinnitus Assessment in the Phase 2A and/or Phase 3.

We'll assume they already have the products on the shelves for treating the patients that require the STANDARD care. Why not prescribe the treatment to a patient complaining of high frequency tinnitus?

The bottom line:

ENTs are so limited when it comes to treating hearing loss. The bar is so low. If FX-322 works for the STANDARD care today, the ENTs will stock it in their office. They can't just choose to ignore secondary outcomes when they have the ability to treat folks with a medicine that is on-hand.

Bonus thoughts:

If Frequency obtains enough meaningful data; it's possible they may be able to draw a significant correlation between:

- Improvements in HF Audiogram correlating with lowered Tinnitus Functional Index Score.
- Improvements in HF Audiogram correlating with Speech-In-Noise improvements.
- Number of doses correlating with a reduction in TFI score.

If these outcomes become clinically meaningful, doctors cannot just ignore them, or refuse to treat based on a prior standard.

 

Some of them seem to have an inkling of awareness that there's more going on in the cochlea than their textbooks teach, and they'll lend credence to your symptoms. But they can't diagnose shit so their medical explanation is at best a nebulous guess going off of their simplistic understanding and diagnostics. The ENTs theory on my sound sensitivity, muffled hearing, ear crackling and tinnitus was all due to "oversensitized middle ear muscles."

The best consultation I had was with a lowly hearing aid instrumentation tech who straight up told me I did damage (even with a normal audiogram), put just like that. But he was a drummer and did a number on his own ears, so he knew from experience that some shit can get f'd up beyond the comprehension of standard hearing care.

 

I think you are wrong Will. something can still be damaged in the area to cause it. For instance what if there is enough hearing loss that you can still make out the sound but it's different than if you had all of the hair cells. And yes there could be several other contributing factors. Also I think most high frequency tinnitus is well within the hearing range. I'm not sure if it's your posts but I have seen it come up several times where I see the individual say something that I don't think is scientifically correct and unnecessarily pessimistic. I can go try to look it up again and make this more organized and speak directly to those posts, and make this more well written but I think my point is in here. Yes, you do still need some support cells.

I guess we will know when we try it And we get more data and results.

 

It’s a shame Carl LeBel didn’t talk about patients with severe or profound hearing loss and possible effects the drug might have on them on the Tinnitus Talk Podcast interview. Right now they’re only accepting patients up to 70 dB hearing loss, but in the press release with regards to the private placement, they said they would use the proceeds to gain better insight into the ‘severity’ of the hearing loss FX-322 might treat. That could either mean they are going beyond 70 dB or have indication it doesn’t work that well for more severe hearing loss.

 

Well, then if you damaged something but it's not showing up on the audiogram, it could be hidden hearing loss, which OTO-413 is looking to treat. Which, there's some possibility of FX-322 treating a bit of that too if I recall correctly, though that wasn't the main intent. At least Carl LeBel made it sound like it might happen as well. It certainly happens for the hair cells that do regrow.

I would agree that most high frequency tinnitus is well within the hearing range. The keyword is most. And if you damaged your hearing at the edge, and then aged 20 years, losing hearing and hair cells at the standard pace, either your tinnitus on that range frequency should die or it will stick around, with you functionally deaf on that range. I'll admit, I don't know which one happens. Nor does any doctor, because we don't study this enough. Now, is that pessimistic? Maybe. Yet, if it's 10% of the patients that have that scenario, then it is a concern. I don't see that as pessimistic, I see it as looking at all possibilities. Further, I fail to see any hope that the drug helps these people as well as I am pessimistic. We just don't know the full scope yet, as we don't have data on how the brain responds to new hair cells, nor the ear when so many support cells are dividing.

I see the scenario provided though as possible, and perhaps my own, as I can't find my "tone" for the life of me. If you know your tones, I would assume that you're able to still hear it, and therefore should have enough support cells to work with.

Bottom line is: Support cells are needed. Most with tinnitus will have them on the range. Get an extended audiogram when it's safe and if you're capable to let you know where the damage may be. My scenario may be bunk, but under the current science, I believe it's possible for some, but I hope it's as close to 0 as possible. I am certain that it does not cover the majority of cases.

 

Anyone have any idea when Frequency Therapeutics will release the results on phase 2a? All this speculation is nuts!

 

That's not a bad guess. I'm having them all cut surgically due to oversensitivity.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156190/

 

He did say in the interview, however, that he thought it might work on anyone without flat epithelial. That means they aren't excluding 70-90 dB losses in that statement at least (which is still pretty deaf) and it can even be interpreted that he implied it will help that subset too.

Generally, the only people who have progressed to that profound level (over 90 dB loss) have end-stage, long term progressive hearing loss or severe ototoxic damage in those frequencies.

 

All that is known publically is:

--originally in September 2020.
--delayed due to COVID-19.
--they intend to keep the delay as short as possible.
--they are still recruiting for phase 2A.

So my guess is spring 2021 (total guess).

 

Oof, I would still place it in 2020. Fingers crossed for an October or November release.

 

Tinnitus Talk Podcast:

"... there is anecdotal reports as patients have come back and visited with ENTs when they have had conversations with them about how they are doing. Some of them have offered that they have had improvements in tinnitus, there’s nothing that we can quantitate there. Again, it adds to the excitement of the opportunity. "

- Carl LeBel, Frequency Therapeutics

 

They are following/testing patients for months after dosing and are still recruiting. It's August.

No way they make October or November, unfortunately, IMO.

 

Their Phase 1 study chose mild, moderate, and severe hearing loss patients. Phase 1 is primarily testing for adverse side effects but FX-322 was also doing an informal efficacy measurement along the way. They can't include people with profound hearing loss because those are not people that can be measured for adverse effects.

What if the drug causes people to lose hearing? If you already have profound hearing loss, then when measuring a drug for safety that could potentially worsen hearing is not measurable in people with profound hearing loss. However, the informal hearing measurement (double word score counts in 4/6 patients of moderate/severe hearing loss) was mentioned in the podcast but just not the type of patients.

I also initially thought it was a shame to not do efficacy measurements along with safety but there is a reason for it because it's not practicable on the standpoint of measuring safety.

 

I hear ya. I'm a designer and I generally work on the computer all day and there are times when I have to work on something tedious that takes hours to complete. My mp3 library on my computer helped me so much in being productive. It could make any boring process fun. Not anymore though. Now it's just a depressing reminder of the state of my ears. On top of it sounding low quality, I don't have my loudness sensitivity anymore so I can't tell when it is too loud or not. So I figure it's best not to listen to it.

The other scary thing is that while I take great precautions in not further damaging my ears, I still notice my hearing slowly declining over the years. Throughout a given year, there are still dozens of instances when there are loud noises that I wasn't prepared for - a metal object crashing on the floor right next to me, kids screaming in my ear, a loud horn going off. These things will make my ears ring and my tinnitus worse. My guess is I lose a fraction of a decibel each time and over time it adds up.

In regards to FX-322, I don't know. It feels so far off that it's still like a pipe dream to me. It's a small hope to cling on to, but sometimes I wonder if that hope is helpful or not. Considering the tiny frequency range that it affects, I might be better off trying to forget about it altogether.

 

Tiny frequency range? It affects from 8 kHz and above right now, so long as there are support cells.

 

There was a post saying that they won't be delaying results as they would have to inform the stock market of this by now, noting that they should know whether they can release the trial results in time or not. Either they have not announced a delay yet or they are going to try and release some preliminary results after September and further results later on.

 

With regards to FX-322, don't forget that they have only used a small single safety dose thus far so it's far too early to make any conclusive statements about the frequency range it will affect.

 

It's small due to the logarithmic nature of sound frequencies.

 

I think we're getting too caught up in the measured range of the sound frequencies and not focusing enough on how meaningful they are from a biological standpoint. For some reason, treating that small range has resulted in significantly improved word scores in both quiet and noise. It's also resulted to anecdotal reports of tinnitus improvement. This is what we know from testing it on a small group of 15 people.

That small range of hearing may have a huge meaning to a lot of people.