Frequency Therapeutics — Hearing Loss Regeneration

[HootOwl]

Preclinical as in not in a live human being? As far as I know it's pretty darn hard to get a drug into the apex when delivered intratympanically. You'll probably need something better. As for Frequency's gel, this is what it said in their prospectus:

FX-322 is our proprietary thermoreversible polymer formulation that is administered through the eardrum, or intratympanically, into the middle ear in a procedure that takes approximately 10 to 15 minutes.

Right. Both were delivered intratympanically to mice. Part of the mechanism behind including a poloxamer involves surface tension, and the ability for a substance to continue onward until it meets resistance. Unless there is something severely and fundamentally different in a human cochlea, the same physical process would apply.

It's probably worth noting that Otonomy is in phase 3 for their IT dexamethasone drug which uses this same poloxamer as a part of their vehicle delivery to treat Meniere's in humans, and has shown to be pretty successful.

You need to be able to get at least below 1000Hz to see those kinds of results, and once you get to 250Hz you're basically already at the tip.

 

[Emgee]

Everyone reading this should SAVE this comment. As more is learned through each phase and each new iteration of drug, Frequency will shift their messaging from clarity to deeper restoration. It will all be driven on the (hopefully) promising data from each phase.

Fully agree. There would need to be a new trial for each reformulation, correct? I would presume at least an abbreviated additional trial would be required.

 

[Jurger]

Right. Both were delivered intratympanically to mice. Part of the mechanism behind including a poloxamer involves surface tension, and the ability for a substance to continue onward until it meets resistance. Unless there is something severely and fundamentally different in a human cochlea, the same physical process would apply.

It's probably worth noting that Otonomy is in phase 3 for their IT dexamethasone drug which uses this same poloxamer as a part of their vehicle delivery to treat Meniere's in humans, and has shown to be pretty successful.

You need to be able to get at least below 1000Hz to see those kinds of results, and once you get to 250Hz you're basically already at the tip.

Delivering a drug intratympanically to a mouse is not the same as delivering it to a live human. There's plenty of data out there that seems to suggest getting a drug to the lower frequencies is pretty difficult. That's one of the reasons they are pursuing intracochlear drug delivery.

 

[HootOwl]

Delivering a drug intratympanically to a mouse is not the same as delivering it to a live human.

Really? I have yet to come across this. Could you show me where you've seen this, I'm coming up short on my end. And wouldn't it still stand to reason that the inclusion of a poloxamer would result in the same physical process, regardless of species?

And agreed, it is usually very difficult to reach the lower frequencies which is probably why Otonomy is so close fisted with their patents. They were one of, if not the first, to consistently do so - and one of the ways was through the inclusion of the poloxamer. That's one of the reasons their Meniere's drug has seen success in human clinical trials, where other companies have failed. They're definitely getting something down to the low frequencies in therapeutic doses.

 

[FGG]

Delivering a drug intratympanically to a mouse is not the same as delivering it to a live human. There's plenty of data out there that seems to suggest getting a drug to the lower frequencies is pretty difficult. That's one of the reasons they are pursuing intracochlear drug delivery.

Worse case scenario, it could be injected surgically through newer techniques like canalostomy. It's not ideal but possible.

 

[sssing]

Really? I have yet to come across this. Could you show me where you've seen this, I'm coming up short on my end. And wouldn't it still stand to reason that the inclusion of a poloxamer would result in the same physical process, regardless of species?

And agreed, it is usually very difficult to reach the lower frequencies which is probably why Otonomy is so close fisted with their patents. They were one of, if not the first, to consistently do so - and one of the ways was through the inclusion of the poloxamer. That's one of the reasons their Meniere's drug has seen success in human clinical trials, where other companies have failed. They're definitely getting something down to the low frequencies in therapeutic doses.

For one, the size of cochleas between a mouse and a human is different.

 

[HootOwl]

For one, the size of cochleas between a mouse and a human is different.

Right, but most papers I've read imply despite size differentials, diffusion rates from IT shots remain relatively approximate. Drug efficacy is a different matter, but diffusion not so much. Again, at least from what I've come across.

Edit: and if I'm understanding poloxamers correctly, you could theoretically have a hundred corkscrews in a cochlea, in any species, and it would still travel throughout the whole thing, due to the properties of surface tension.

 

[WickedCarnival]

Anybody planning on saving these recordings?

https://www.businesswire.com/news/h...peutics-Present-Upcoming-Investor-Conferences

announced that Chief Executive Officer David L. Lucchino will present a company overview at the Jefferies Virtual Healthcare Conference and participate in a "fireside chat" at the Goldman Sachs Annual Global Healthcare Conference. Details for each event are as follows:

• Jefferies Virtual Healthcare Conference
  Presentation, Thursday, June 4 at 9 a.m. EDT
• Goldman Sachs Annual Healthcare Conference 2020
  Fireside chat, Tuesday, June 9 at 10:30 a.m. EDT

A live webcast of both presentations can be accessed on the investor section of Frequency's website, https://investors.frequencytx.com/ A replay of each presentation will be posted on the Frequency website for at least 30 days following each event.

 

[Mathieulh]

While all these investors meetings are going on, we, and many others, are still constantly suffering, despite Frequency Therapeutics legally allowed to sell FX-322 as we speak on compassionate grounds, I assume money is more important. So long as we don't have access to this drug, this is no more than vaporware as far as we are concerned.

This drug has been tested as safe for humans and no alternatives exist, what do we care about how much of a "dose" we need? We don't have anything else, just let us use it. Even if I had a billion dollars I still couldn't buy the darn thing, this is ridiculous.

It's not the FDA that's blocking anything, even if it was, which we know it isn't, there are plenty of other markets Frequency Therapeutics could sell FX-322 from.

The fact is, the only ones preventing us from accessing this is Frequency Therapeutics themselves. If they had anything more than money and greed in mind, and had any confidence in their drug, they would ramp up production now and make it available.

 

[Diesel]

While all these investors meetings are going on, we, and many others, are still constantly suffering, despite Frequency Therapeutics legally allowed to sell FX-322 as we speak on compassionate grounds, I assume money is more important. So long as we don't have access to this drug, this is no more than vaporware as far as we are concerned.

This drug has been tested as safe for humans and no alternatives exist, what do we care about how much of a "dose" we need? We don't have anything else, just let us use it. Even if I had a billion dollars I still couldn't buy the darn thing, this is ridiculous.

It's not the FDA that's blocking anything, even if it was, which we know it isn't, there are plenty of other markets Frequency Therapeutics could sell FX-322 from.

The fact is, the only ones preventing us from accessing this is Frequency Therapeutics themselves. If they had anything more than money and greed in mind, and had any confidence in their drug, they would ramp up production now and make it available.

https://www.frequencytx.com/expanded-access-policy/

Frequency Therapeutics understands there may be patients interested in obtaining access to our investigational products for treatment under an Expanded Access program. However, at this stage of the development of our products there is insufficient clinical data to support expanded access use and we are unable to manufacture our investigational drugs in the quantities that may be needed for expanded access purposes. Therefore, to ensure availability of materials for clinical trial research and the safety of potential patients, Frequency Therapeutics does not provide access to our investigational products through expanded access currently.​

Sounds like they want more clinical data before proceeding with Expanded Access. Perhaps the phase 2A will be sufficient?

 

[FGG]

While all these investors meetings are going on, we, and many others, are still constantly suffering, despite Frequency Therapeutics legally allowed to sell FX-322 as we speak on compassionate grounds, I assume money is more important. So long as we don't have access to this drug, this is no more than vaporware as far as we are concerned.

This drug has been tested as safe for humans and no alternatives exist, what do we care about how much of a "dose" we need? We don't have anything else, just let us use it. Even if I had a billion dollars I still couldn't buy the darn thing, this is ridiculous.

It's not the FDA that's blocking anything, even if it was, which we know it isn't, there are plenty of other markets Frequency Therapeutics could sell FX-322 from.

The fact is, the only ones preventing us from accessing this is Frequency Therapeutics themselves. If they had anything more than money and greed in mind, and had any confidence in their drug, they would ramp up production now and make it available.

If there was a small demand for this drug ramping up production would be easy. There is a massive demand for this drug. A billionaire could cover the upfront costs, though. Then again, I'm sure exceptions for compassionate use are probably already granted to the very rich and powerful.

 

[AtlasFainted]

While all these investors meetings are going on, we, and many others, are still constantly suffering, despite Frequency Therapeutics legally allowed to sell FX-322 as we speak on compassionate grounds, I assume money is more important. So long as we don't have access to this drug, this is no more than vaporware as far as we are concerned.

This drug has been tested as safe for humans and no alternatives exist, what do we care about how much of a "dose" we need? We don't have anything else, just let us use it. Even if I had a billion dollars I still couldn't buy the darn thing, this is ridiculous.

It's not the FDA that's blocking anything, even if it was, which we know it isn't, there are plenty of other markets Frequency Therapeutics could sell FX-322 from.

The fact is, the only ones preventing us from accessing this is Frequency Therapeutics themselves. If they had anything more than money and greed in mind, and had any confidence in their drug, they would ramp up production now and make it available.

I think they may make it available after this trial. Their website says the following regarding expanded access:

"[...]At this stage of the development of our products there is insufficient clinical data to support expanded access use and we are unable to manufacture our investigational drugs in the quantities that may be needed for expanded access purposes[...]"

After phase 2a they should have dosing figured out along with safety (which has been established since phase 1), so they will need to update the portion regarding clinical data at the very least.

I'm hoping to be able to access FX-322 next year, but we'll see...

 

[xyz]

This drug has been tested as safe for humans and no alternatives exist, what do we care about how much of a "dose" we need? We don't have anything else, just let us use it. Even if I had a billion dollars I still couldn't buy the darn thing, this is ridiculous.

Well there is stem cell treatment. But I am not sure if this ever went through a safety trial. But I don't think it makes sense to ramp up production before the drug has shown efficacy. If we hear something positive from then in the fall I hope then they start production and open it for compassionate use.

 

[Emgee]

If all goes according to plan, should OTO-413 be released around the same time as FX-322? Anyone know the progress of the Hough pill?

 

[AtlasFainted]

If there was a small demand for this drug ramping up production would be easy. There is a massive demand for this drug. A billionaire could cover the upfront costs, though. Then again, I'm sure exceptions for compassionate use are probably already granted to the very rich and powerful.

This is why I'm ambitious. Having kids one day and not being able to afford or otherwise access a treatment that might save their lives (or my own life, leaving them alone without a father) is my #1 motivating factor.

Even if medicine were completely socialized (or completely free market), those with money and power will always have more access than those who don't. This is why I've focused far more on myself & less on politics recently...

 

[GregCA]

Even if I had a billion dollars I still couldn't buy the darn thing, this is ridiculous.

With a billion dollars you can buy the whole company. Twice.

 

[Lola808]

Has anyone here tried to be a part of the FX-322 clinical trial?

 

[Lucifer]

Has anyone here tried to be a part of the FX-322 clinical trial?

Some people have tried to sign up for the clinical trial but didn't get accepted due to the hearing loss not being severe enough.

There could have been Tinnitus Talk members who have been accepted into the trial but cannot say whether it reduced their tinnitus or not due to the non-disclosure agreement.

You might be able to tell by looking at members who were very active in the forums previously but haven't posted recently. This is a sign that they could have been part of the trials and are actually doing better.

 

[Rb86]

Has anyone here tried to be a part of the FX-322 clinical trial?

I tried. Was turned down and not told why, even though I met their listed criteria. Believe me, I pressed them to tell me why.

 

[FGG]

Has anyone here tried to be a part of the FX-322 clinical trial?

At least 4 or 5 of us but I'm not aware of anyone getting in.

 

[Lola808]

At least 4 or 5 of us but I'm not aware of anyone getting in.

I tried as well. My hearing loss was not severe enough.

On another note does anyone think FX-322 will help for hyperacusis? I've always had hypercausis I think and that was why I would wear my headphones so loud. Ironic right.

 

[Pink Noise]

You need an extended audiogram to assess this better.

Frequency reportedly addresses up to moderately severe losses. Otonomy have a drug in pre-clinical for severe losses but that's probably 5-8 years away.

By the time you have profound losses, though, you have often lost too many support cells for this approach. There are some researchers working on profound losses, though. I corresponded with one who said it could be 15-20 years away, however because you have to first regenerate support cells (and their correct architecture) from so called "Flat epithelia". I have profound loss at my apex and around 13kHz and higher so I probably have to wait 15-20 years to hear music again (the apex losses severely distort it because I hear wobbly oscillations with no tone), assuming my KV3.1 channels and/or strial potassium channels aren't an additional hurdle. High dose Azithromycin toxicity is the devil.

At this point, I'm mostly cheering the rest of you on. I have semi given up for my own situation given just how destructive prolonged high dose Macrolides are.

We'll see if I make it until then.

Hi @FGG - just spotted this whilst reading through the thread. You mentioned in your cases that the restoration >13kHz would be required for you to hear music again, would the restoration of these frequencies reduce recruitment/distortions you experience?

I'm hearing crazy distortions developed over the last few days / week and its really getting me down. As a music producer I'm finding it truly devastating. I feel tearful when it affects my work. I feel like I have to write as much music as I can before my ears totally crap out. I have mild loss beyond 4kHz and like you cannot hear beyond 13khz although I feel like another test is required.

I'm aware FX-322 addresses beyond 6kHz, however do you reckon addressing ultra high frequencies could indirectly address lower tinnitus tones / distortion( through recruitment)?

 

[Croaker]

I tried as well. My hearing loss was not severe enough.

On another note does anyone think FX-322 will help for hyperacusis? I've always had hypercausis I think and that was why I would wear my headphones so loud. Ironic right.

According to the most recent stuff I've read on hyperacusis, it is thought to be contained to the peripheral nervous system, as opposed to tinnitus. The type 2 nerve fibers are hyperexcitable and as a result are communicating pain. It's possible that fixing the reason the nerves are irritated will fix the hyperexcitability too.

I kinda doubt it though, I think they'll need separate treatment like potassium channel openers/nav 1.7 inhibitors to calm down. I have no detectable hearing loss on a standard audiogram, so I'm hoping there's minor damage up high. Otherwise I have no idea what will treat me.

 

[Lucifer]

I tried as well. My hearing loss was not severe enough.

On another note does anyone think FX-322 will help for hyperacusis? I've always had hypercausis I think and that was why I would wear my headphones so loud. Ironic right.

Usually when you have hyperacusis, depending on if it's loudness (when you hear things more louder and clearly) or pain (things don't seem loud but cause you pain at lower thresholds), you don't tend to increase the volume of your music.

Are you sure that you have hyperacusis? It could be reactive tinnitus that you have?

 

[FGG]

Hi @FGG - just spotted this whilst reading through the thread. You mentioned in your cases that the restoration >13kHz would be required for you to hear music again, would the restoration of these frequencies reduce recruitment/distortions you experience?

I'm hearing crazy distortions developed over the last few days / week and its really getting me down. As a music producer I'm finding it truly devastating. I feel tearful when it affects my work. I feel like I have to write as much music as I can before my ears totally crap out. I have mild loss beyond 4kHz and like you cannot hear beyond 13khz although I feel like another test is required.

I'm aware FX-322 addresses beyond 6kHz, however do you reckon addressing ultra high frequencies could indirectly address lower tinnitus tones / distortion( through recruitment)?

My problem with music turned out to be profound apex loss (100Hz and below). It's very very rare and instead of hearing low tones, i hear vibratory oscillations for lack of a better word and it distorts everything. A big clue is I can't hear thunder properly even next to my house but I can feel it and sense vibrations. I *also* have HF loss but that's not what is making everything that distorted. At least for me.

It took me ages to figure this out and i ended up talking to a researcher who is familiar with severe Azithromycin ototoxicity (decimates the base and apex in kind of a reverse cookie bite pattern).

 

[Pink Noise]

My problem with music turned out to be profound apex loss (100Hz and below). It's very very rare and instead of hearing low tones, i hear vibratory oscillations for lack of a better word and it distorts everything. A big clue is I can't hear thunder properly even next to my house but I can feel it and sense vibrations. I *also* have HF loss but that's not what is making everything that distorted. At least for me.

It took me ages to figure this out and i ended up talking to a researcher who is familiar with severe Azithromycin ototoxicity (decimates the base and apex in kind of a reverse cookie bite pattern).

Ah I see.

I hope FX-322 can help us all. I'm pinning my hopes on that too. These 9 months have been hell. Making music without fully enjoying the process. It sounds like there are wurly tubes spun over the top of any complex sound.

 

[Lucifer]

Ah I see.

I hope FX-322 can help us all. I'm pinning my hopes on that too. These 9 months have been hell. Making music without fully enjoying the process. It sounds like there are wurly tubes spun over the top of any complex sound.

I also hope it helps with hyperacusis and tinnitus as well. Who would have known that these type of issues existed. I had no bloody idea.

I feel like a bloody idiot for not knowing these issues existed and have lots of regrets :'(

 

[Lola808]

Usually when you have hyperacusis, depending on if it's loudness (when you hear things more louder and clearly) or pain (things don't seem loud but cause you pain at lower thresholds), you don't tend to increase the volume of your music.

Are you sure that you have hyperacusis? It could be reactive tinnitus that you have?

I have reactive tinnitus in my left ear. I am sitting in mostly silence right now and don't hear anything but if I am exposed to noise then I get high frequency feedback till it calms down. It's debilitating. I have hyperacusis in the right ear as I hear everything and it causes initial pain in the ear and then in the face.

 

[Emgee]

I have reactive tinnitus in my left ear. I am sitting in mostly silence right now and don't hear anything but if I am exposed to noise then I get high frequency feedback till it calms down. It's debilitating. I have hyperacusis in the right ear as I hear everything and it causes initial pain in the ear and then in the face.

I have exactly the same condition but in my right ear. I hope FX-322 will work for us. I think hearing restoration should lead to a normalized auditory system, which would reduce or remove any component of reactive tinnitus. It really is debilitating.

How long have you had this issue? I've talked to many who have dealt with this and the majority have experienced it fading over time. It really might be a form of hyperacusis. There seems to be a sound-sensitivity element to it.

 

[AtlasFainted]

I have reactive tinnitus in my left ear. I am sitting in mostly silence right now and don't hear anything but if I am exposed to noise then I get high frequency feedback till it calms down. It's debilitating. I have hyperacusis in the right ear as I hear everything and it causes initial pain in the ear and then in the face.

I think there's a good chance that FX-322 & other upcoming drugs will help you if your problems are hearing loss related.

While you wait time also has a good chnace of mitigating your symptoms a bit...

My ears pop a lot (they didn't do that before my hearing loss symptoms kicked in).

While there's a chance this could be related to some other issue, I really do feel like getting some hearing back will fix my popping issue along with the tinnitus.

In the meantime I plan to focus on what I can control. Only way to not become a total shadow of yourself while you wait for the right medicine.