Frequency Therapeutics — Hearing Loss Regeneration

[AtlasFainted]

I don't think it would have any effect on ETD. ETD really has nothing directly to do with the cochlea.

Maybe it isn't ETD as per @MrCrybaby.

I assumed it was ETD after doing some research on my symptoms, but he nailed what my symptoms are and it makes more sense, given when they arose.

 

[serendipity1996]

Those are exactly my symptoms. Thanks so much!

Sometimes I can get the fullness to go away after popping them, but normally only for a few seconds, and a few minutes at the most.

I've never had these issues before, it's just too much of a coincidence to not be related. Just one more reason to look forward to FX-322.

If your tinnitus arose following acoustic trauma then I would say it's much more likely that your ear fullness etc is related to that. It seems a lot of ENTs really are not familiar with the full spectrum of symptoms that can arise as a result of acoustic trauma and therefore end up receiving a diagnosis of ETD.

 

[patorjk]

Something I've found rather hard to follow is the dose size difference between Phase I/II and Phase IIa. Do we know the answers to the below questions? And if so, what are they?

* Is there any difference in the dose size between Phase I/II and Phase IIa?
* Does dose refer to the amount of liquid that is injected in or the concentration of the drug?
* Is there any difference in the concentration of the drug in the dose between Phase I/II and Phase IIa?

 

[Lola808]

FX-322 with respects to regeneration, who here feels it will regenerate both inside cochlea and outside cochlea, for those who have hyperacusis with pain?

 

[AtlasFainted]

If your tinnitus arose following acoustic trauma then I would say it's much more likely that your ear fullness etc is related to that. It seems a lot of ENTs really are not familiar with the full spectrum of symptoms that can arise as a result of acoustic trauma and therefore end up receiving a diagnosis of ETD.

Yep, I did have an acoustic trauma about a month before all my symptoms showed up.

Feeling a lot better now that I know I should be able to get this fixed within the next year or two.

Don't know what I'd do without you guys... probably tons more time spent worrying and researching instead of living.

 

[ASilverLight]

My symptoms are more like crackling and other noises when swallowing or yawning, no ear fullness. Occasionally a pop but that's maybe once a month or less (and only when I'm too late to block a sneeze). I do occasionally feel like my eardrum moves, again only when i swallow. Happens randomly and not often.

Also get clicking when I talk sometimes. Had all of these issues when having a cold many times in my life and I continue suffering from nasal congestion (barely able to breathe through my nose).

Maybe it's a combination of both in my case.

 

[Gb3]

Do you guys think that hearing restoration could also curb or possibly erase ETD symptoms?

Mine started shortly after my tinnitus did, and at times it's more annoying than the tinnitus itself.

I'm not very well versed on what causes ETD but I can't help but think it's related to hearing loss in some way, at least for me.

Ever since my onset of ISSHL in my left ear (6months ago) i have ear fullness in my good ear. Constant like stuffy ear with pooping and cracking. I can hear my breath through my ear. I never had any ear problems prior to my hearing loss.

 

[serendipity1996]

FX-322 with respects to regeneration, who here feels it will regenerate both inside cochlea and outside cochlea, for those who have hyperacusis with pain?

Do you mean inner hair cells and outer hair cells? Both are located within the cochlea and I believe FX-322 will address both.

 

[AtlasFainted]

Ever since my onset of ISSHL in my left ear (6months ago) i have ear fullness in my good ear. Constant like stuffy ear with pooping and cracking. I can hear my breath through my ear. I never had any ear problems prior to my hearing loss.

Yeah both of mine feel full and pop/crack when I fully extend my jaw or swallow.

I also get mild ear pain maybe once a day, for a few seconds. I guess that would make sense if the inner ear muscles are spasming and being overworked.

Has to be related to hearing loss... I'm kind of scared that mine has more to do with synaptopathy than loss of hair cells, because that would mean more time waiting.

Time will tell I suppose.

 

[serendipity1996]

Yeah both of mine feel full and pop/crack when I fully extend my jaw or swallow.

I also get mild ear pain maybe once a day, for a few seconds. I guess that would make sense if the inner ear muscles are spasming and being overworked.

Has to be related to hearing loss... I'm kind of scared that mine has more to do with synaptopathy than loss of hair cells, because that would mean more time waiting.

Time will tell I suppose.

Which companies have synaptopathy drugs in the pipeline - is it Hough Ear Institute and Otonomy? Pipeline Therapeutics and Sound Pharmaceuticals too?

 

[AtlasFainted]

Something I've found rather hard to follow is the dose size difference between Phase I/II and Phase IIa. Do we know the answers to the below questions? And if so, what are they?

* Is there any difference in the dose size between Phase I/II and Phase IIa?
* Does dose refer to the amount of liquid that is injected in or the concentration of the drug?
* Is there any difference in the concentration of the drug in the dose between Phase I/II and Phase IIa?

- They are giving 1, 2, and 4 doses to different test groups
- The dose is the drug & the delivery vehicle (this is a gel)
- Concentration is the same. Changing the concentration or delivery vehicle requires an additional FDA trial that takes a year before it is legally allowed to hit the market. (Which in my view is plain ridiculous).

 

[Diesel]

Something I've found rather hard to follow is the dose size difference between Phase I/II and Phase IIa. Do we know the answers to the below questions? And if so, what are they?

* Is there any difference in the dose size between Phase I/II and Phase IIa?
* Does dose refer to the amount of liquid that is injected in or the concentration of the drug?
* Is there any difference in the concentration of the drug in the dose between Phase I/II and Phase IIa?

1. No difference is "dose" size. FREQ has confirmed this in a couple conference interviews. The only difference is the randomized quantity of doses over a 4 week period (1x, 2x, 4x).
2. I don't believe this is confirmed. I assume it's concentration, since only so much volume can be injected in the middle ear.
3. No difference. A dose is a dose according to FREQ.

Side note: They have said they're using the same dose in both Phases with the hope of replicating similar results in the single-dose Phase 2A cohort as what was seen in the Phase 1/2.

Side side note: They essentially confirmed in their recent perilymph study that the dosage is concentrated enough in the cochlea to cause the desired reaction (progenitor cell activation).

 

[Born To Slay]

Do you guys think that hearing restoration could also curb or possibly erase ETD symptoms?

Mine started shortly after my tinnitus did, and at times it's more annoying than the tinnitus itself.

I'm not very well versed on what causes ETD but I can't help but think it's related to hearing loss in some way, at least for me.

Personally, I think inner ear damage can cause reactions in the middle ear. So in my view, it's possible that fixing the inner damage will restore dysfunctional middle ear.

 

[AtlasFainted]

Personally, I think inner ear damage can cause reactions in the middle ear. So in my view, it's possible that fixing the inner damage will restore dysfunctional middle ear.

I hope so, for my sake and other's.

The thing is the technology exists to regenerate inner/outer hair cells, and also to regenerate synapses. It exists right now.

It's just a matter of waiting years for the FDA to either.

- Approve the drugs
- Go through reform so that drugs can be approved quicker
- Change their current stance (possibly via legislation) so that drugs can be provisionally approved and hit the market sooner

Or *maybe* if we're lucky, Frequency will decide to devote resources away from trials and towards opening up expanded use.

FX-322 is the only possible candidate we have to look forward to in the next 2 years. Sigh.

 

[Lucifer]

I hope so, for my sake and other's.

The thing is the technology exists to regenerate inner/outer hair cells, and also to regenerate synapses. It exists right now.

It's just a matter of waiting years for the FDA to either.

- Approve the drugs
- Go through reform so that drugs can be approved quicker
- Change their current stance (possibly via legislation) so that drugs can be provisionally approved and hit the market sooner

Or *maybe* if we're lucky, Frequency will decide to devote resources away from trials and towards opening up expanded use.

FX-322 is the only possible candidate we have to look forward to in the next 2 years. Sigh.

I do hope that the theory of restoring the OHCs, IHCs and synapses causes the brain/ear to reset to make the hyperacusis and tinnitus go away.

We basically have around 3-4 months approximately till the Phase 2a clinical trial results come out. I hope they announce expanded access soon.

 

[Emgee]

If Phase 2a turns out successful, I really hope expanded access is opened up. Hopefully, there's a question regarding expanded access for the Tinnitus Talk Podcast with Frequency Therapeutics.

Between recruitment, the trial itself, and the publishing of results, Phase 3 is going to take a while.

 

[Xojo]

My memory is a bit hazy on this, but way back before the trials, I remember Frequency Therapeutics mentioning that they had several different compounds that they could test in order to get the deepest penetration into the cochlea.

Does anyone know if they already did pretests that whittled it down to FX-322 or do they still have several other compounds to try after FX-322 trials are over?

 

[Lucifer]

My memory is a bit hazy on this, but way back before the trials, I remember Frequency Therapeutics mentioning that they had several different compounds that they could test in order to get the deepest penetration into the cochlea.

Does anyone know if they already did pretests that whittled it down to FX-322 or do they still have several other compounds to try after FX-322 trials are over?

I think right now they are focusing on getting the drug out in its current delivery method but they will surely create a better delivery method that can target all frequencies later on. They had a job posting a couple of months ago hiring someone to create a new delivery method.

 

[Jurger]

I do hope that the theory of restoring the OHCs, IHCs and synapses causes the brain/ear to reset to make the hyperacusis and tinnitus go away.

We basically have around 3-4 months approximately till the Phase 2a clinical trial results come out. I hope they announce expanded access soon.

They were still recruiting a few weeks ago and are following patients for 210 days. I think data release in Q2/2021 is more likely.

 

[BBakkers]

They were still recruiting a few weeks ago and are following patients for 210 days. I think data release in Q2/2021 is more likely.

So recruiting is finally done?

 

[annV]

So recruiting is finally done?

No it's not done. They are still recruiting.

 

[BBakkers]

No it's not done. They are still recruiting.

Thanks, but Pfff.

 

[sssing]

No it's not done. They are still recruiting.

How do you know that btw?

 

[NewLionel]

Cough cough... please recruit me!!!

 

[Emgee]

I have a friend who said his audiologist suffered sudden hearing loss, which brought about tinnitus. He was given steroids which restored his hearing; however, the tinnitus remains to this day.

The brain shouldn't have a preference in regard to maladaptive plasticity, correct? In theory, restored auditory input should lead to diminished tinnitus. My hypothesis is that maybe his hearing was restored but not completely, leaving him with a mild loss, and thus keeps tinnitus going. Or, maybe cochlear synaptopathy is at play and is undetected. I'm curious as to what others think.

 

[Emgee]

How do you know that btw?

I can confirm as I spoke with a receptionist at one of the clinics.

 

[FGG]

I have a friend who said his audiologist suffered sudden hearing loss, which brought about tinnitus. He was given steroids which restored his hearing; however, the tinnitus remains to this day.

The brain shouldn't have a preference in regard to maladaptive plasticity, correct? In theory, restored auditory input should lead to diminished tinnitus. My hypothesis is that maybe his hearing was restored but not completely, leaving him with a mild loss, and thus keeps tinnitus going. Or, maybe cochlear synaptopathy is at play and is undetected. I'm curious as to what others think.

You can lose some input (or retain some input loss in his case) without noticeable audiogram changes or even noticeable hearing changes.

Did his tinnitus stay at the same level?

 

[Jim51042]

We basically have around 3-4 months approximately till the Phase 2a clinical trial results come out. I hope they announce expanded access soon.

Can someone remind me their current plan/timeline assuming a successful Phase 2a.

Will they go to a Phase 2 or 3? When would that next Phase take place and how long would it last?

 

[Diesel]

I have a friend who said his audiologist suffered sudden hearing loss, which brought about tinnitus. He was given steroids which restored his hearing; however, the tinnitus remains to this day.

The brain shouldn't have a preference in regard to maladaptive plasticity, correct? In theory, restored auditory input should lead to diminished tinnitus. My hypothesis is that maybe his hearing was restored but not completely, leaving him with a mild loss, and thus keeps tinnitus going. Or, maybe cochlear synaptopathy is at play and is undetected. I'm curious as to what others think.

It depends on the definition of "restored hearing"... To an audiologist, that might mean up to 8 kHz, with tinnitus (due to losses) in the finer OHC/IHC above 8 kHz.

My expectation about FX-322 and the other drug trials that are en-vogue amongst this community are that we all probably have a mixed bag of dead cells, damaged cells, and synaptopathy. None of these drugs alone are going to be the silver bullet that "cures" tinnitus.

Any of them though will lead to a significant improvement in hearing or otherwise, and considering how low the bar is in this field, we should be pretty damn happy about that.

 

[Emgee]

You can lose some input (or retain some input loss in his case) without noticeable audiogram changes or even noticeable hearing changes.

Did his tinnitus stay at the same level?

That's what I inquired. He says he didn't ask, but intends to next time he sees him. My friend said the audiologist used his experience to caution the idea that hearing regeneration will have guaranteed results/resolve tinnitus. However, the audiologist is aware of current research and will try regenerative medicine when it is available. Interesting.