Frequency Therapeutics — Hearing Loss Regeneration

[FGG]

On a hypothetical basis, let's say Phase 2a results are announced during the spring of 2021. Let's also say the data shows that the drug is highly effective in meeting many primary and secondary outcome measures.

If the company's compassionate use/expanded access policy is revisited and granted as a result, how long does everyone think it will be until we can obtain access?

As long as it takes your doctor to file. Not sure how long that process is.

 

[ASilverLight]

It's embarrassing that some people can't process this. Imagine thinking "ringing in the ears is ringing in the ears," with how complicated the brain and inner ear are. And WORSE, these people have advanced training on these systems. How is it that a bunch of lay people on an internet forum understand the inner ear enough to see that these conditions can vary just based on really simple things like hidden hearing loss?

A funny thing about CBT is that your brain has to actually be capable of learning that sounds are okay. If sounds are not okay, it will only keep learning that they are not. You can't always just will your way.

I realize we repeat a lot of the same rants, but this cannot be forgotten. Researchers need to see the sheer number of people saying the same thing.

I have never, ever been able to filter sound. Any noise I have no control over bothers me and always has. EG if they were using leafblowers outside, I couldn't relax until they stopped.

While used to it more or less, tinnitus is the same. I have no control over it.

 

[FGG]

It will depend on how quickly the drug can be readily made available. I'd say 6 months to a year.

They listed not ramping up production as a reason for declining compassionate use for now, I would assume by the time they allow for it, they would have the means to provide it. But you are right! Clearly there would be a lag time after phase 2a to do this and 6 months to a year sounds like a reasonable guess.

 

[Diesel]

They listed not ramping up production as a reason for declining compassionate use for now, I would assume by the time they allow for it, they would have the means to provide it. But you are right! Clearly there would be a lag time after phase 2a to do this and 6 months to a year sounds like a reasonable guess.

I hope I'm being pessimistic, of course. I don't know the ins and outs of manufacturing a new drug. Frequency continues to mention the simplicity of FX-322, and we know one of the molecules is commonly used to treat migraines. So, perhaps Astellas is capable of ramping up production faster?

 

[Cernuto]

The FDA will string it along until they exhaust everything they have available to benefit their 'FDA approved for use' (aka money grab) process.

 

[tommyd87]

I hope I'm being pessimistic, of course. I don't know the ins and outs of manufacturing a new drug. Frequency continues to mention the simplicity of FX-322, and we know one of the molecules is commonly used to treat migraines. So, perhaps Astellas is capable of ramping up production faster?

The simple answer is that compassionate use hasn't been ruled out and Frequency Therapeutics is willing to reconsider it at a later point in time. In my opinion it seems that they will do it although they don't know when.

The FDA will string it along until they exhaust everything they have available to benefit their 'FDA approved for use' (aka money grab) process.

Do you know how the FDA finds ways to extend/delay the process for the approval? From what I have read they charge one fee for approval and that's it.

 

[Thuan]

The FDA will string it along until they exhaust everything they have available to benefit their 'FDA approved for use' (aka money grab) process.

Are you making that up or do you have occupational experience with that?

 

[TomBradyGOAT]

They listed not ramping up production as a reason for declining compassionate use for now, I would assume by the time they allow for it, they would have the means to provide it. But you are right! Clearly there would be a lag time after phase 2a to do this and 6 months to a year sounds like a reasonable guess.

You seem to be the smart person on the block. If you don't know the answer that is fine. I did a 20 kHz audiogram. After about 11 kHz you can start seeing a dip. Everything before is less than 15 dB. After it can go up to 40 dB I believe. Yet my tinnitus was measured at around 4 kHz which is a normal hearing loss frequency.

From your understanding, if they do a phase 2b, would my audiogram allow me to enroll in the clinical trial since I have hearing loss around 11-12 kHz and beyond? Or are they only looking for 8 kHz and below?

And since my tinnitus doesn't match where my audiogram hearing loss is at and acknowledging hidden hearing loss could be a factor, does FX-322 have a good chance of helping my tinnitus? It is in my head. Not coming through a particular ear. Started happening around drug withdrawals which can unmask hearing loss. I have no problems hearing in crowds at all - think restaurants pre-COVID-19. Didn't go to concerts.

Any thoughts would be appreciated.

 

[d'Wooluf]

The FDA will string it along until they exhaust everything they have available to benefit their 'FDA approved for use' (aka money grab) process.

Again with the FDA-bashing. I'm pretty sure the FDA doesn't make money at any point in this process. My conspiracy theory is that Frequency Therapeutics strung it along for months while they negotiated with Astellas and then filed the IPO. I don't have any proof for my theory either.

 

[d'Wooluf]

They listed not ramping up production as a reason for declining compassionate use for now

I was under the impression that it was two readily-available ingredients. It's not for retail sale, so you don't have to worry much about packaging. You could probably mix up a bucketful that would give you a thousand doses. Then again, I know nothing about producing medicines, so shoot me down in flames.

Too much trouble for not enough financial return is my guess.

 

[Billy_Shears]

I've heard that FX-322 phase 2a clinical trial is currently about 3/4 of the way complete as of August 5, 2020. It is still not known if the study will be complete by September 30, 2020 as there is still a need for additional participants. A trial study takes 210 days, so we are looking at the summer of 2021 before we hear any news from Frequency Therapeutics on phase 2a.

If successful AND if needed, my take is that Phase 3 would be in 2022.

Curiously, I've often wondered about the numerical term "322", theorizing that their goal for market must be March, 2022. Still could be, I suppose.

 

[sssing]

"Some" donated cochleas were actually "hundreds" - Source from the JP Morgan recording in January.

I am making a guess, it could be the temporal bone bank in MEEI. Then it would be a substantial number. It is not easy to get temporal bones so I think maybe they studied the temporal bones from MEEI.

 

[Lucifer]

I've heard that FX-322 phase 2a clinical trial is currently about 3/4 of the way complete as of August 5, 2020. It is still not known if the study will be complete by September 30, 2020 as there is still a need for additional participants. A trial study takes 210 days, so we are looking at the summer of 2021 before we hear any news from Frequency Therapeutics on phase 2a.

If successful AND if needed, my take is that Phase 3 would be in 2022.

Curiously, I've often wondered about the numerical term "322", theorizing that their goal for market must be March, 2022. Still could be, I suppose.

How do you know 3/4 of the clinical trial has been completed? Do you have a link or article that states this?

 

[tommyd87]

I've heard that FX-322 phase 2a clinical trial is currently about 3/4 of the way complete as of August 5, 2020. It is still not known if the study will be complete by September 30, 2020 as there is still a need for additional participants. A trial study takes 210 days, so we are looking at the summer of 2021 before we hear any news from Frequency Therapeutics on phase 2a.

If successful AND if needed, my take is that Phase 3 would be in 2022.

Curiously, I've often wondered about the numerical term "322", theorizing that their goal for market must be March, 2022. Still could be, I suppose.

There have been three things that have been commented on/said about the trial.

Firstly, Frequency Therapeutics has not actually updated the stock market on the trial being delayed and hasn't changed the date on the trial page either. If it is the case that they know they have to change the date due to possible delays and have not updated this, then they risk penalties from the financial regulators for not doing so.

Secondly, Frequency Therapeutics has stated quite clearly that they will not be changing the date of when they will start releasing results of the trial unless there are some significant delays. I know that they have said on multiple occasions that they are pretty confident that they can get the results they need without having the maximum trial participants and that they can arrange more participants later on if need be.

Thirdly, I'm not positive if this was from an analyst or an insider, but there was an indication that Frequency Therapeutics could start turning a profit two years from now. Noting this, it is likely that they would need to release FX-322 next year in order for this to turn out to be accurate.

 

[Lucifer]

There have been three things that have been commented on/said about the trial.

Firstly, Frequency Therapeutics has not actually updated the stock market on the trial being delayed and hasn't changed the date on the trial page either. If it is the case that they know they have to change the date due to possible delays and have not updated this, then they risk penalties from the financial regulators for not doing so.

Secondly, Frequency Therapeutics has stated quite clearly that they will not be changing the date of when they will start releasing results of the trial unless there are some significant delays. I know that they have said on multiple occasions that they are pretty confident that they can get the results they need without having the maximum trial participants and that they can arrange more participants later on if need be.

Thirdly, I'm not positive if this was from an analyst or an insider, but there was an indication that Frequency Therapeutics could start turning a profit two years from now. Noting this, it is likely that they would need to release FX-322 next year in order for this to turn out to be accurate.

I really hope it is the case that they release FX-322 next year but that is highly unlikely. You never know.

 

[tommyd87]

I really hope it is the case that they release FX-322 next year but that is highly unlikely. You never know.

What makes you think, out of interest, that it is highly unlikely?

 

[Lucifer]

What makes you think, out of interest, that it is highly unlikely?

They did say they have a pivotal phase to do after their current Phase 2a trial and wouldn't that take another year? If they get Breakthrough Therapy status, then maybe it will be possible for them to release FX-322 next year.

 

[FGG]

Firstly, Frequency Therapeutics has not actually updated the stock market on the trial being delayed and hasn't changed the date on the trial page either. If it is the case that they know they have to change the date due to possible delays and have not updated this, then they risk penalties from the financial regulators for not doing so.

They don't have to issue a public statement about their clinicaltrials page not being up to date. They aren't going to "get in trouble with the SEC" for that. The clinicaltrials page date is always just an estimate, it's not a legal document.

They said there is a delay and they hope to keep it as short as possible.

 

[Emgee]

What makes you think, out of interest, that it is highly unlikely?

I think the only way it could be accessible next year would be through expanded access, and even that would be a stretch in my opinion.

We still need:

• Phase 2a results (I expect spring/summer 2021)
• The revisiting/allowance of expanded access policy by Frequency Therapeutics
• Ramped-up production so the drug could be readily available
• Individual filing through our doctors/ENTs to obtain access

If Breakthrough Therapy designation is granted and there are no more required phases for approval, I personally believe we still wouldn't see the drug on the market until at least 2022. I hope I'm wrong, but I think COVID-19 put a dent into the timeline. The Phase 2a participant pool isn't full at this time.

 

[FGG]

You seem to be the smart person on the block. If you don't know the answer that is fine. I did a 20 kHz audiogram. After about 11 kHz you can start seeing a dip. Everything before is less than 15 dB. After it can go up to 40 dB I believe. Yet my tinnitus was measured at around 4 kHz which is a normal hearing loss frequency.

From your understanding, if they do a phase 2b, would my audiogram allow me to enroll in the clinical trial since I have hearing loss around 11-12 kHz and beyond? Or are they only looking for 8 kHz and below?

And since my tinnitus doesn't match where my audiogram hearing loss is at and acknowledging hidden hearing loss could be a factor, does FX-322 have a good chance of helping my tinnitus? It is in my head. Not coming through a particular ear. Started happening around drug withdrawals which can unmask hearing loss. I have no problems hearing in crowds at all - think restaurants pre-COVID-19. Didn't go to concerts.

Any thoughts would be appreciated.

They are looking for: "Pure Tone Audiometry (PTA) within 26-70 dB in the ear to be injected".

They have not listed that you have to any loss below 8000 Hz in their inclusion/exclusion parameters. To reach this while having a normal audiogram under 8000 Hz, you might need more data points showing loss over 8000 Hz. For instance, if you only had an extended audiogram at 12000 Hz instead of a full 8000 Hz to 16000 Hz extended audiogram at 10000 Hz, 12000 Hz, 14000 Hz and 16000 Hz, your average might not reach the parameters.

It's possible they want people who have losses under 8000 Hz exclusively but they have not explicitly said that and it is not listed as a trial parameter.

I would say apply if you are interested and they will let you know during your interview if you qualify or not.

As far as having a 4000 Hz tone not visible on your audiogram, how did you get this "measured"? Normally people try to tone match themselves but it would be nice/refreshing if am audiologist actually tried to help you do this as possibly implied by the passive tense.

Anyway, tinnitus is caused by lack of input. It doesn't have to be outer hair cell (which is what the audiogram measures). You could be inner hair cell damage or synapse damage at 4000 Hz while having outer hair cell damage at the ultra high frequencies.

 

[Thuan]

Anyway, tinnitus is caused by lack of input. It doesn't have to be outer hair cell (which is what the audiogram measures). You could be inner hair cell damage or synapse damage at 4000 Hz while having outer hair cell damage at the ultra high frequencies.

If someone has cochlear synaptopathy damage in the IHC, would there be a dip in the audiogram under 8 kHz? What are the metrics and indicators for cochlear synaptic damage vs classical hair cell damage?

 

[FGG]

If someone has cochlear synaptopathy damage in the IHC, would there be a dip in the audiogram under 8 kHz? What are the metrics and indicators for cochlear synaptic damage vs classical hair cell damage?

Inner hair and synapse damage do not show up on an audiogram.

Edit: a "speech in noise" test is used to evaluate synaptopathy but this only applies to widespread synapse loss in important speech frequencies. There isn't a good test for more selective loss antemortem.

 

[BBakkers]

Inner hair and synapse damage do not show up on an audiogram.

From my understanding, FX-322 does generate inner hair cells, right?

 

[Thuan]

Inner hair and synapse damage do not show up on an audiogram.

Edit: a "speech in noise" test is used to evaluate synaptopathy but this only applies to widespread synapse loss in important speech frequencies. There isn't a good test for more selective loss antemortem.

I just researched and indeed it does not show up on the audiogram. Is there a reason why it would not show up on the audiogram? Aren't the inner hair cells the neural connectors and the outer hair cells the mechanical transducers? For example, we have a mic (OHC mechanical transducers) and a mic line (IHC neural circuitry) to the computer. If the mic line is damaged, it doesn't really matter if the mic pics up signals or not because the line is disconnected. If it's disconnected, we wouldn't hair any sound at all. Is my understanding wrong on this?

Since Frequency Therapeutics tested patients with noise in speech, I would assume that FX-322 will also help with cochlear synaptic damage (under section "54:37 Potential benefits for 'hidden hearing loss'")?

 

[FGG]

I just researched and indeed it does not show up on the audiogram. Is there a reason why it would not show up on the audiogram? Aren't the inner hair cells the neural connectors and the outer hair cells the mechanical transducers? For example, we have a mic (OHC mechanical transducers) and a mic line (IHC neural circuitry) to the computer. If the mic line is damaged, it doesn't really matter if the mic pics up signals or not because the line is disconnected. If it's disconnected, we wouldn't hair any sound at all. Is my understanding wrong on this?

Since Frequency Therapeutics tested patients with noise in speech, I would assume that FX-322 will also help with cochlear synaptic damage (under section "54:37 Potential benefits for 'hidden hearing loss'")?

You can lose the majority of inner hair cells before it shows up on audiogram because audiogram does not reflect quality of signal, it's a binary "yes" or "no". Can you hear this or not?

Very few things selectively destroy inner hair cells in that large number preferentially before they affect OHCs. In fact, the only things I have come across in my reading are platinum based chemotherapeutics in select cases and Macrolides.

 

[TomBradyGOAT]

They are looking for: "Pure Tone Audiometry (PTA) within 26-70 dB in the ear to be injected".

They have not listed that you have to any loss below 8000 Hz in their inclusion/exclusion parameters. To reach this while having a normal audiogram under 8000 Hz, you might need more data points showing loss over 8000 Hz. For instance, if you only had an extended audiogram at 12000 Hz instead of a full 8000 Hz to 16000 Hz extended audiogram at 10000 Hz, 12000 Hz, 14000 Hz and 16000 Hz, your average might not reach the parameters.

It's possible they want people who have losses under 8000 Hz exclusively but they have not explicitly said that and it is not listed as a trial parameter.

I would say apply if you are interested and they will let you know during your interview if you qualify or not.

As far as having a 4000 Hz tone not visible on your audiogram, how did you get this "measured"? Normally people try to tone match themselves but it would be nice/refreshing if am audiologist actually tried to help you do this as possibly implied by the passive tense.

Anyway, tinnitus is caused by lack of input. It doesn't have to be outer hair cell (which is what the audiogram measures). You could be inner hair cell damage or synapse damage at 4000 Hz while having outer hair cell damage at the ultra high frequencies.

Thanks. The audiologist matched my tinnitus using his equipment. Same one who did my 20 kHz test.

 

[Billy_Shears]

How do you know 3/4 of the clinical trial has been completed? Do you have a link or article that states this?

I inquired at one of the clinical trial locations about being recruited for the study and I asked them about the September 30th date. Their reply was that they are about 3/4 through the trial period and may possibly go past that date - still unknown as of now.

 

[AtlasFainted]

I hope I'm being pessimistic, of course. I don't know the ins and outs of manufacturing a new drug. Frequency continues to mention the simplicity of FX-322, and we know one of the molecules is commonly used to treat migraines. So, perhaps Astellas is capable of ramping up production faster?

They listed not ramping up production as a reason for declining compassionate use for now, I would assume by the time they allow for it, they would have the means to provide it. But you are right! Clearly there would be a lag time after phase 2a to do this and 6 months to a year sounds like a reasonable guess.

Carl LeBel on Expanded Use during the Tinnitus Talk Podcast:

"[...]firstly and importantly our position on expanded access is due to really the fact that we don't fully feel that we've been able to characterise the safety profile of the drug yet. And so loosening the philosophy of sharing drug, this is a hard time to do that. We don't understand the risk-benefit profile just yet. So I think that we're certainly interested once we get this next set of data that we can revisit that based on what the profile looks like[...]"

He also goes on to say that this info will possibly be revealed during this current phase of development.

I know their website states that production is a reason that they aren't offering expanded use, but I'd trust the much more recent info, which is straight from the horse's mouth so to speak.

In my opinion, the podcast confirms that a lack of data regarding the safety profile is the primary reason expanded use is not being offered. I don't think production is an issue or he would have mentioned as much. I think Astella has the resources to pump out FX-322 almost immediately, as soon as they & Frequency decide that's what they want to do.

Of course, things might take longer, but I think there's a solid chance we could gain access to this by mid 2021.

 

[FGG]

Thanks. The audiologist matched my tinnitus using his equipment. Same one who did my 20 kHz test.

They are only measuring up to 16000 Hz. Off hand, I doubt they would use 16000 Hz to 20000 Hz as data points but I could be wrong.

 

[Padraigh Griffin]

Simple question... Will FX-322 help with all the different types of tinnitus?

Such as head Tinnitus, stress induced, pulsatile, somatosensory?