Frequency Therapeutics — Hearing Loss Regeneration

[Street Novelist]

Frequency Therapeutics may be able to potentially release FX-322 out in the market after they finish with their Phase 2a clinical trial if they can get Breakthrough Therapy designation.

That, or they allow everyone in the Phase 3 trial. But yes, the waiting is excruciating.

 

[Diesel]

Who knows. It really depends on the interpretation of "life threatening."

Most doctors will say it needs to be more evaluated and we're all full of crap about our suffering. See the ATA. However maybe they will find the brains to allow it. That is of course if the stuff actually works as intended. The anticipation is killing me.

Fast Track designation for FX-322 already acknowledges that the FDA sees hearing loss as life threatening or severely life altering. They can't say it applies for one designation and not the other.

To gain Breakthrough Therapy designation, in addition to the Fast Track requirements, which it has already met, FX-322 has to demonstrate a significant benefit compared to other therapies (not devices) in at least one primary measure. And show a favorable safety profile.

In my opinion, it has already met the primary endpoint with Word Score in the Phase 1/2. Phase 2A may tack a few more endpoints on, furthering the case.

 

[scotty03874]

More than likely not. If the Phase 2 trials are successful I have no problem standing in front of FDA with picket signs demanding they release the drug early.

I'll be there with you with a big check in my hand to get treated. I have no problem paying for compassionate use...

 

[Princebeyel]

Frequency Therapeutics may be able to potentially release FX-322 out in the market after they finish with their Phase 2a clinical trial if they can get Breakthrough Therapy designation.

Do you have a source for this claim?

 

[Lucifer]

Do you have a source for this claim?

No source, just speculation. If they do get Breakthrough Therapy designation, would this keep the timeline the same or speed up the process so we can either get FX-322 after the Phase 2a clinical trials or have a shorter pivotal Phase 3 clinical trial so we can get FX-322 sooner.

 

[Jrblovsky]

No source, just speculation. If they do get Breakthrough Therapy designation, this would keep the timeline the same or speed up the process so we can either get FX-322 after the Phase 2a clinical trials or have a shorter pivotal Phase 3 clinical trial so we can get FX-322 sooner.

Hopefully it shows big gains. If it showed 10 to 15 dB with one dose, I'm hoping for 40 to 60 dB gains with four. Anything less than that is a failure/not helpful in my opinion.

You figure if you have 80 dB losses across the board and recover 60 dB that is a homerun. If they show these type of results, everyone would be back to normal hearing thresholds and ready to go.

The people who have severe hearing loss need this the most. My hearing loss is not personally that bad but I can't imagine not being able to understand what people are saying and having to read lips.

Hoping for a success. Come on Carl!

 

[Lucifer]

Hopefully it shows big gains. If it showed 10 to 15 dB with one dose, I'm hoping for 40 to 60 dB gains with four. Anything less than that is a failure/not helpful in my opinion.

You figure if you have 80 dB losses across the board and recover 60 dB that is a homerun. If they show these type of results, everyone would be back to normal hearing thresholds and ready to go.

The people who have severe hearing loss need this the most. My hearing loss is not personally that bad but I can't imagine not being able to understand what people are saying and having to read lips.

Hoping for a success. Come on Carl!

I'm praying that with more doses of FX-322, it should go deeper in the round window but I'm also scared that additional doses do nothing without reformulating it.

 

[Keith Handy]

Hopefully it shows big gains. If it showed 10 to 15 dB with one dose, I'm hoping for 40 to 60 dB gains with four. Anything less than that is a failure/not helpful in my opinion.

Key point: these gains were at 8 kHz, and nothing above that was measured. So there could be a slope-shaped gain where 9-16 kHz would have read higher, and then hopefully with more doses that slope would work its way down further. Current trials are, I believe, measuring the 9-16 kHz range (extended audiogram).

Possibly something like this (oversimplifying)...

 

[TheGopher]

Hopefully FX-322 can also help with visual snow. I got visual snow a few months after my acoustic trauma (add insult to injury) so there has to be some correlation there as well, although I was under tremendous emotional trauma after all this so it's possible that was the cause and FX-322 won't fix that which would suck

 

[Diesel]

Key point: these gains were at 8 kHz, and nothing above that was measured. So there could be a slope-shaped gain where 9-16 kHz would have read higher, and then hopefully with more doses that slope would work its way down further. Current trials are, I believe, measuring the 9-16 kHz range (extended audiogram).

Possibly something like this (oversimplifying)...

View attachment 43313

From an audiogram perspective, this would explain why word score increased the way it did in Phase 1/2. It's likely there was an upward slope in gains above 8 kHz up to a normal range. This would make fricatives in the English language easier to distinguish; and since English is full of fricatives, it would explain why the score jumped the way it did.

 

[Jrblovsky]

I'm praying that with more doses of FX-322, it should go deeper in the round window but I'm also scared that additional doses do nothing without reformulating it.

I don't know why they would need to reformulate.

A cell is a cell regardless. The medicine should affect the supporting cells the same way regardless if it is located in the apex or further up by the basal turn.

The reason I say this is look at the pics from Otonomy. It shows the cells before and after treatment and they recovered regardless of location. They just need to get the medication in there.

 

[Robert Logan]

Sorry for another probably very daft / obvious question (it is inspiring how "clued-up" so many of you are the various aspects of this, from science to business)...

What are the chances of FX-322 entirely falling through at this stage? I don't mean arriving later than hoped for, or being less effective than hoped for... I mean absolutely nothing comes of it for the public?

I ask because I know that this has happened to treatments before, including to a potentially world—altering Alzheimer's drug that was eventually totally recalled due to bad reactions among some who were tested with it.

 

[Koz]

Hopefully FX-322 can also help with visual snow. I got visual snow a few months after my acoustic trauma (add insult to injury) so there has to be some correlation there as well, although I was under tremendous emotional trauma after all this so it's possible that was the cause and FX-322 won't fix that which would suck

Nah, I would wager that your visual snow is directly linked to the trauma in your cochlea. Funnily enough, I met an Otologist recently who knows perfectly well about visual snow (rather than the usual "what's that? never heard of it" shit), which took me by surprise. Visual snow is a symptom of the overreactive firings in your brain due/recompensating to the cochlear trauma. The same way symptoms like ear fullness, pain etc. pop up when there's no evidence of secondary ear disease. Visual snow is one of the ways the brain manifests this change in neural activity (from the from cochlear trauma.

Someone asked this same question many pages ago and the fact of the matter is, in theory, you'd think a reversal back to normal should have a domino effect of overall reversal but the fact is, nobody knows yet because:

A. We don't know anyone with visual snow in the current trials who has come out and said anything about any changes.

B. They aren't testing for it as a criterion of the current trials.

Time will tell. From my own experience with visual snow and a lot of anecdotal evidence I've read online, it seems like the onset of it comes after acoustic trauma for many people, I personally wasn't under any emotional trauma when mine popped up but I did have my hearing worsen not long before.

 

[Lucifer]

I don't know why they would need to reformulate.

A cell is a cell regardless. The medicine should affect the supporting cells the same way regardless if it is located in the apex or further up by the basal turn.

The reason I say this is look at the pics from Otonomy. It shows the cells before and after treatment and they recovered regardless of location. They just need to get the medication in there.

I meant in terms of changing the delivery method if the drug does not go deeper in the round window with additional doses using the current delivery method.

 

[FGG]

Sorry for another probably very daft / obvious question (it is inspiring how "clued-up" so many of you are the various aspects of this, from science to business)...

What are the chances of FX-322 entirely falling through at this stage? I don't mean arriving later than hoped for, or being less effective than hoped for... I mean absolutely nothing comes of it for the public?

I ask because I know that this has happened to treatments before, including to a potentially world—altering Alzheimer's drug that was eventually totally recalled due to bad reactions among some who were tested with it.

From my perspective, extremely low.

Alzheimer's drugs are somehow always used as a metric for bearish biotech investors but keep in mind it's among the very least successful class of drugs to make it to the market.

 

[Jrblovsky]

What are the chances of FX-322 entirely falling through at this stage? I don't mean arriving later than hoped for, or being less effective than hoped for... I mean absolutely nothing comes of it for the public?

I ask because I know that this has happened to treatments before, including to a potentially world—altering Alzheimer's drug that was eventually totally recalled due to bad reactions among some who were tested with it.

It's absolutely possible that could happen. Look at the drug Trobalt. It worked great for tinnitus off label but would turn your skin blue. All drugs have risks. So does walking down the street, flying on an airplane, and literally everything else in life.

The Phase 1 trial showed the drug was tolerated well so I don't see safety being a problem.

The main concern now is that the drug actually provides meaningful improvement with multiple doses. If it does, it will be a game changer. If not, it's a flop.

 

[Jrblovsky]

I meant in terms of changing the delivery method if the drug does not go deeper in the round window with additional doses using the current delivery method.

Sorry I misunderstood. I wonder if there is a way to pump the stuff into the inner ear?

A middle ear perfusion seems about half would go down your eustachian tube. Maybe not, I don't know.

 

[FGG]

I wonder if there is a way to pump the stuff into the inner ear?

A middle ear perfusion seems about half would go down your eustachian tube. Maybe not, I don't know.

Multiple injections may very well solve this problem. Although, Otonomy might have more of the right idea with extended release (because the drug diffusion rate is more consistently higher).

 

[Jack V]

The Phase 1 trial showed the drug was tolerated well so I don't see safety being a problem.

Phase I was 9 people with severe to profound hearing loss.

That first toe in the water let them proceed, but hardly shows that FX-322 is well tolerated and safe across a broader population.

 

[Gb3]

Sorry I misunderstood. I wonder if there is a way to pump the stuff into the inner ear?

A middle ear perfusion seems about half would go down your eustachian tube. Maybe not, I don't know.

You will have to lie down on your side for probably like 30 minutes and not swallow so as much of the drug as possible can get through. After one of my steroid shots I got up after the 30 minutes and some of the liquids started leaking out my ear.

 

[Jack V]

Sorry for another probably very daft / obvious question (it is inspiring how "clued-up" so many of you are the various aspects of this, from science to business)...

What are the chances of FX-322 entirely falling through at this stage? I don't mean arriving later than hoped for, or being less effective than hoped for... I mean absolutely nothing comes of it for the public?

From what I can gather, there's a lot of "green flags" suggesting it's moving in the right direction.

However, when I ask that very question to someone in the field, they shrug their shoulders and say it could absolutely fail, as many drugs do.

Truth is, while there's very real cause for optimism, we just don't know.

 

[Jrblovsky]

Multiple injections may very well solve this problem. Although, Otonomy might have more of the right idea with extended release (because the drug diffusion rate is more consistently higher).

I hope something comes of this and it's positive. Everything has been negative lately. They need a breakthrough.

You will have to lie down on your side for probably like 30 minutes and not swallow so as much of the drug as possible can get through. After one of my steroid shots I got up after the 30 minutes and some of the liquids started leaking out my ear.

That is true. Everytime I do the steroid injections, I have a little leakage as well.

 

[Jrblovsky]

Phase I was 9 people with severe to profound hearing loss.

That first toe in the water let them proceed, but hardly shows that FX-322 is well tolerated and safe across a broader population.

True. However I would imagine that if the drug was horribly unsafe someone would have had a bad reaction.

I never put all my eggs in one basket being most things fail. However I need something to cling onto. I know living with this for the rest of my miserable life sure as hell isn't it.

 

[Diesel]

You will have to lie down on your side for probably like 30 minutes and not swallow so as much of the drug as possible can get through. After one of my steroid shots I got up after the 30 minutes and some of the liquids started leaking out my ear.

FX-322 is suspended in an agent that gels when it warms up when injected; so that it does not leak out of the ear drum injection site or down the eustachian tube.

 

[Jrblovsky]

FX-322 is suspended in an agent that gels when it warms up when injected; so that it does not leak out of the ear drum injection site or down the eustachian tube.

I wonder if the Frequency Therapeutics scientists have considered methods used for cochlear implants for delivering the drugs? The round window insertion is only one method used.

 

[serendipity1996]

I wonder if the Frequency Therapeutics scientists have considered methods used for cochlear implants for delivering the drugs? The round window insertion is only one method used.

Isn't cochlear implantation an invasive surgical procedure?

 

[FGG]

I wonder if the Frequency Therapeutics scientists have considered methods used for cochlear implants for delivering the drugs? The round window insertion is only one method used.

Surgical methods for CI are extremely damaging. Often you can lose remaining hair cells during CI implantation (the electrical stimulation bypasses this so you can still hear after).

There is an alternative surgical approach for delivering meds that starts at the apex called canalostomy. This has a risk to vestibular hair cells rather than hearing ones (but you only need one good vestibular ear to function after PT, ask me how I know ). As far as I know this hasn't yet been attempted on humans yet though.

Novartis had a hair cell drug that had to be infused directly into the cochlea since it was an AAV treatment. The surgery itself probably did more harm than good (it may have even damaged cells they were trying to transduce with the viral vectors) and their drug failed.

Companies like Akouous have drugs for genetic deafness and have an AAV platform. They described that they have their own unique surgical approach for this in one presentation awhile ago without actually describing the technique. If that's true, they may have the surgical answer for direct drug infusion since AAV drugs depend on it. I'm following them to see how they progress.

 

[Jrblovsky]

Isn't cochlear implantation an invasive surgical procedure?

It is. However the surgeon inserts the electrode into the cochlea by pushing it in there. Hypothetically this could be done by cutting a hole in the eardrum and then patching it. The main part that involves cutting is the receiver that is mounted into the skull behind the ear. My point is they do electrode insertions several different ways; one being round window insertion.

However, I wonder if possible another way would be useful in delivering the drugs into the ear? I'm going to look more into it. I don't know if they drill a hole or how that works.

Surgical methods for CI are extremely damaging. Often you can lose remaining hair cells during CI implantation (the electrical stimulation bypasses this so you can still hear after).

There is an alternative surgical approach for delivering meds that starts at the apex called canalostomy. This has a risk to vestibular hair cells rather than hearing ones (but you only need one good vestibular ear to function after PT, ask me how I know ). As far as I know this hasn't yet been attempted on humans yet though.

Novartis had a hair cell drug that had to be infused directly into the cochlea since it was an AAV treatment. The surgery itself probably did more harm than good (it may have even damaged cells they were trying to transduce with the viral vectors) and their drug failed.

Companies like Akouous have drugs for genetic deafness and have an AAV platform. They described that they have their own unique surgical approach for this in one presentation awhile ago without actually describing the technique. If that's true, they may have the surgical answer for direct drug infusion since AAV drugs depend on it. I'm following them to see how they progress.

Interesting. I'm just wondering if the process they use to insert the electrode array may be useful for sending drugs in instead. I wonder if they could as you mentioned pump the drug in starting at the apex and work them out? This would make sure that all frequencies are supplied with the drug. I don't know, just wondering. Being I have another three hours before I will be able to fall asleep I'm just thinking out loud.

 

[FGG]

Interesting. I'm just wondering if the process they use to insert the electrode array may be useful for sending drugs in instead. I wonder if they could as you mentioned pump the drug in starting at the apex and work them out? This would make sure that all frequencies are supplied with the drug. I don't know, just wondering. Being I have another three hours before I will be able to fall asleep I'm just thinking out loud.

The inflammatory effects from just drilling a hole in the cochlea are apparently pretty substantial, not just the insertion process in CIs.

I think this is why canalostomy seems like a better surgical option since it throws vestibular cells under the bus instead. It also starts at the apex and you could access perilymph or endolymph from that site. Possibly the reason it hasn't been tried on humans is that it's not ideal to damage vestibular cells but I'm sure many people would take that risk. It took me a good year of physical therapy to have normal balance again after losing most of my right sided vestibular function, though, so I could see that being a deterrent.

I'm really wondering what Akouous is doing to solve this like I said because AAV ear drugs (at least so far) cannot be given intratympanically and have to be infused directly into the cochlea. It would be nice if they go into this as their gene therapy results come out.

All of this might not be at all necessary for FX-322 though. It may be as simple as multiple injections or extended release.

Hope you get sleep. I stay up a lot thinking of this stuff too.

 

[Shizune]

Nah, I would wager that your visual snow is directly linked to the trauma in your cochlea. Funnily enough, I met an Otologist recently who knows perfectly well about visual snow (rather than the usual "what's that? never heard of it" shit), which took me by surprise. Visual snow is a symptom of the overreactive firings in your brain due/recompensating to the cochlear trauma. The same way symptoms like ear fullness, pain etc. pop up when there's no evidence of secondary ear disease. Visual snow is one of the ways the brain manifests this change in neural activity (from the from cochlear trauma.

Someone asked this same question many pages ago and the fact of the matter is, in theory, you'd think a reversal back to normal should have a domino effect of overall reversal but the fact is, nobody knows yet because:

A. We don't know anyone with visual snow in the current trials who has come out and said anything about any changes.

B. They aren't testing for it as a criterion of the current trials.

Time will tell. From my own experience with visual snow and a lot of anecdotal evidence I've read online, it seems like the onset of it comes after acoustic trauma for many people, I personally wasn't under any emotional trauma when mine popped up but I did have my hearing worsen not long before.

Shocked your otologist actually knew and connected it. Keep them under glass and clone them.

It seems most people I've encountered on this forum with the usual acoustic trauma -> tinnitus, have visual snow syndrome. I'm a bit worried that I don't have it; it'd imply to me that it isn't my cochlea damaged but something else. But as you said, it's just one of many potential symptoms, right? I'm just worried because it seems to make up the majority.

I would think FX-322 would help with it to a degree by that logic. I just hope that us without visual snow syndrome but with tinnitus and hyperacusis can still be helped. I basically pray every day that my cochlea is fried, which is a bit screwed up. Really hoping it helps every symptom.