Frequency Therapeutics — Hearing Loss Regeneration

[MikeAMFM]

Seems like the technology is available for a proper delivery system... very excited...

I look at my audiogram and have high hopes...

 

[Jurger]

There are actually a number of possible ways:

This, delivered surgically through Canalostomy, ultrasound microbubbles, Otomagnetics, reformulation, etc.

Yes. I think intracochlear injections with microneedles are likely the first step in better drug delivery. Seems to have the least regulatory and development hassles compared to other new methods. The other advantage is that you could use them to extract perilymph to do tests on. The ultimate scenario, from what I'm gathering from the literature, would be orally taken nanoparticle drugs that only deliver their payload in the inner ear.

For more on the microneedle: https://pubmed.ncbi.nlm.nih.gov/31746817/

 

[Jurger]

There are three things that might happen from what I can observe.

First, FX-322 makes it in all areas of the cells correctly and offers a helpful response.

Second, if it is initially concentrating in the higher frequencies and it shows effect to the areas of the cochlear which influence these to a greater extent from the first dosing or round of dosing and there is minimal effect to the lower frequencies from this course then I'd assume it could be possible that they should try to repeat the treatment.

It is possible that the amount of gel used may work fantastically for the upper range in the beginning but stops there because it is hitting that area first, and then does not progress further than it can treat. The second dose might then treat the other areas not reached in the first treatment because it can miss these, and then go straight to the treatable areas that were not affected in the initial dose.

Third, there's totally no benefit which would be unlikely.

It is incredibly obvious from the stuff shown to date that the two issues are FX-322's effect and also success of delivery. It somewhat seems that there is evidence of both and thus this is a major step for success.

I think it will be second scenario for now. Someone like me with hearing loss across the board in one ear might go to a downward slope audiogram.

 

[tommyd87]

I think it will be second scenario for now. Someone like me with hearing loss across the board in one ear might go to a downward slope audiogram.

I think that you might be right. I reckon the first trial tended to show what it targeted first and the second trial will indicate the operation of repeat doses. They then might look at the deferred dosing method after they see the results of this trial.

 

[Born To Slay]

So any chance we're still getting the results in September?

 

[FGG]

So any chance we're still getting the results in September?

No, on their last fireside (it's should be archived on their website still) they have said there is a COVID-19 related delay. They are aiming to keep the delay as short as possible, however.

 

[tommyd87]

No, on their last fireside (it's should be archived on their website still) they have said there is a COVID-19 related delay. They are aiming to keep the delay as short as possible, however.

I predict that the delay is probably caused by coronavirus related recruiting issues. I am aware that there was intel that they could complete the trial too with less people however I know they tend to want more and are a bit short still.

 

[FGG]

I predict that the delay is probably caused by coronavirus related recruiting issues. I am aware that there was intel that they could complete the trial too with less people however I know they tend to want more and are a bit short still.

Yes. They said they had a slight delay in recruiting but patients already recruited were going through the trial as normal because their testing centers were still open for patients. Hence small delay rather than large one.

 

[ASilverLight]

Hopefully we will get some results by the end of the year/early 2021 instead. Seems so far away... but if it's positive, worth the wait for many here.

 

[tommyd87]

Yes. They said they had a slight delay in recruiting but patients already recruited were going through the trial as normal because their testing centers were still open for patients. Hence small delay rather than large one.

Cheers cheers. Completely makes sense. Still seems they can complete the trial although now with a lower number of individuals. I reckon they think they can get positive results which I hope and think is a good sign.

 

[Born To Slay]

Yes. They said they had a slight delay in recruiting but patients already recruited were going through the trial as normal because their testing centers were still open for patients. Hence small delay rather than large one.

So by a slight delay, the info could come out like a month or two late?

 

[FGG]

So by a slight delay, the info could come out like a month or two late?

They didn't give an updated timeline. The interview can be found here:

https://investors.frequencytx.com/events-and-presentations

 

[xyz]

So by a slight delay, the info could come out like a month or two late?

Didn't they say that they are monitoring patients for 7 months? As they are now still recruiting then this will be probably beginning of 2021 earliest. But hopefully they release some preliminary results before the official results are published.

 

[tommyd87]

Didn't they say that they are monitoring patients for 7 months? As they are now still recruiting then this will be probably beginning of 2021 earliest. But hopefully they release some preliminary results before the official results are published.

I think that you're right. They will do a combination of both, the totality of results and also drip feed some info as has been happening now.

 

[tommyd87]

Carl LeBel mentioned in the Goldman Fireside chat that they are trying to answer the following hypothesis in the Phase 2A with the 2x and 4x dose cohorts. By delivering more doses, do one or more of the following happen:

- Improvements in the same hearing range among more participants ie: greater response. (same as the Phase 1/2, 8kHz+)
- Improvements into the lower frequency ranges (Below 8kHz)
- A combination of both

I am not a scientist. If the perilymph in the cochlea has some diffusion capability; after multiple doses in a weekly interval, I don't see how FX-322 wouldn't have penetrated more deeply. It seems to stay concentrated at effective levels for about 2 weeks-or-so based on the immediate improvements in the Phase 1/2.

I think the thing to note also is not only did the drug show improvement in the longer term over the 3 months where it kept improving but also again the fact that FX-322 had a significant improvement in patients who were dosed once only in one ear. Easily the biggest alarm bell moment was this as I am almost certain getting the same results in both ears will lead to even bigger improvements. I expect that there will be further improvement with multiple doses and again with working on both ears.

 

[AtlasFainted]

What do you all think about how FX-322 will be administered? Do you think they'll charge per dose, or give everyone the same amount once they sort out whether or not 4 doses is more effective than 1 or 2?

I guess I'm bored and just want to muse about it...

Part of me feels like if 4 doses proves to be more effective for the majority of people with noticable hearing loss/tinnitus, that will be the standard treatment plan moving forward.

Still have fingers crossed for expanded use opening up alongside the next trial.

 

[Lucifer]

What do you all think about how FX-322 will be administered? Do you think they'll charge per dose, or give everyone the same amount once they sort out whether or not 4 doses is more effective than 1 or 2?

I guess I'm bored and just want to muse about it...

Part of me feels like if 4 doses proves to be more effective for the majority of people with noticable hearing loss/tinnitus, that will be the standard treatment plan moving forward.

Still have fingers crossed for expanded use opening up alongside the next trial.

I believe if 4 doses of FX-322 is to be the most effective treatment with everyone then I think they will charge it per set of 4.

It is still hard to predict how many doses we need since each person's hearing loss is different and the hearing tests might not even be that accurate for someone who suffers from hyperacusis.

 

[dan]

I believe if 4 doses of FX-322 is to be the most effective treatment with everyone then I think they will charge it per set of 4.

It is still hard to predict how many doses we need since each person's hearing loss is different and the hearing tests might not even be that accurate for someone who suffers from hyperacusis.

I'll keep taking doses until my tinnitus is heard only in a quiet room.

 

[d'Wooluf]

Easily the biggest alarm bell moment was this as I am almost certain getting the same results in both ears will lead to even bigger improvements.

They would have tested both ears individually, surely? Otherwise they wouldn't be able to say that there was no improvement in the non-treated ear.

Part of me feels like if 4 doses proves to be more effective for the majority of people with noticable hearing loss/tinnitus, that will be the standard treatment plan moving forward.

I really hope not. That means we all get to wait four times as long for treatment and pay four times as much.

They said they had a slight delay in recruiting

It was about 3 months from when the trial started to when COVID-19 became an issue. They couldn't recruit <100 people in three months? I mean people jump up and down about the FDA, but I see no signs that Frequency Therapeutics have been in a great hurry.

 

[Jurger]

What do you all think about how FX-322 will be administered? Do you think they'll charge per dose, or give everyone the same amount once they sort out whether or not 4 doses is more effective than 1 or 2?

I guess I'm bored and just want to muse about it...

Part of me feels like if 4 doses proves to be more effective for the majority of people with noticable hearing loss/tinnitus, that will be the standard treatment plan moving forward.

Still have fingers crossed for expanded use opening up alongside the next trial.

I think the ENT will have some liberty to decide what amount of injections is best for the individual patient. If someone has mild hearing loss, one or two injections might be enough. What insurance companies will do is probably different in each country.

I can also see some off label use for patients with profound hearing loss who don't want a cochlear implant just yet.

 

[tommyd87]

They would have tested both ears individually, surely? Otherwise they wouldn't be able to say that there was no improvement in the non-treated ear.

I really hope not. That means we all get to wait four times as long for treatment and pay four times as much.

It was about 3 months from when the trial started to when COVID-19 became an issue. They couldn't recruit <100 people in three months? I mean people jump up and down about the FDA, but I see no signs that Frequency Therapeutics have been in a great hurry.

One ear was given FX-322 and they were tested before and after as I understand their comments.

I'm pretty positive patients needing multiple doses doesn't require repeat purchasing of the dose. It doesn't make logical business sense to charge people more for every dose due to needing more as it is needing to be commercially friendly for them to make big profits.

think the operations of frequency arent totally to blame with trial matters

 

[Emgee]

If the first formulation is intended to address high-frequency hearing loss, then why is the standard pure tone audiometry a primary outcome measure in phase 2a as opposed to the extended high-frequency audiometry (secondary outcome measure)?

 

[ASilverLight]

What I'm worried about is health care providers not prescribing/recommending the treatment for those with tinnitus, but whose hearing tests come back fine. We all know that they don't tell us everything...

But that's a worry for the future.

 

[Tweedleman]

If the first formulation is intended to address high-frequency hearing loss, then why is the standard pure tone audiometry a primary outcome measure in phase 2a as opposed to the extended high-frequency audiometry (secondary outcome measure)?

I think it has to do with the fact that hearing care "professionals" currently cling to the PTA as the gold standard and if they're going to make an impact with investors etc. they'll want to demonstrate some kind of efficacy in that frequency range first and foremost. The UHF range is criminally undervalued by health care, not considered essential to hearing.

 

[FGG]

What I'm worried about is health care providers not prescribing/recommending the treatment for those with tinnitus, but whose hearing tests come back fine. We all know that they don't tell us everything...

But that's a worry for the future.

All this means is you may have to pay out of pocket and/or call around.

 

[AtlasFainted]

It was about 3 months from when the trial started to when COVID-19 became an issue. They couldn't recruit <100 people in three months? I mean people jump up and down about the FDA, but I see no signs that Frequency Therapeutics have been in a great hurry.

So I think there's 3 things going on here.

1.) COVID-19 has slowed things down in general

2.) Frequency is looking for a very specific level of hearing loss where FX-322 will shine

3.) The older you are, the more likely you have hearing issues. Older people are more at risk with covid so this would make it even more difficult to find willing patients...

Also, and this just my opinion, but I think Frequency has every incentive to get this drug approved as quickly as possible. They are part of the market, and as such, they have competition and also accountability to shareholders.

The same cannot be said for the FDA.

 

[tommyd87]

So I think there's 3 things going on here.

1.) COVID-19 has slowed things down in general

2.) Frequency is looking for a very specific level of hearing loss where FX-322 will shine

3.) The older you are, the more likely you have hearing issues. Older people are more at risk with covid so this would make it even more difficult to find willing patients...

Also, and this just my opinion, but I think Frequency has every incentive to get this drug approved as quickly as possible. They are part of the market, and as such, they have competition and also accountability to shareholders.

The same cannot be said for the FDA.

Out of interest I'm intrigued as to why you think the FDA are actually not interested in getting this approved as from what I have seen they are holding discussions with them.

 

[tommyd87]

I believe if 4 doses of FX-322 is to be the most effective treatment with everyone then I think they will charge it per set of 4.

It is still hard to predict how many doses we need since each person's hearing loss is different and the hearing tests might not even be that accurate for someone who suffers from hyperacusis.

Well we will be made I am guessing to pay for every dose in Australia as I am certain it will be set up like every other drug delivered over multiple doses. For example the hepatitis drug is a multi dose treatment that is the same cost each course and you need to take all courses to deliver immunity. It is intelligent from a business perspective as more doses means more $ but basically that will also mean that someone who requires one jab isn't forced to pay the same as a boy like me who needs four and again will favourably encourage more people to take up the treatment.

 

[AtlasFainted]

Out of interest I'm intrigued as to why you think the FDA are actually not interested in getting this approved as from what I have seen they are holding discussions with them.

Individuals in the FDA probably are interested in getting it approved. I'm just saying there's a big difference between

- A biotech (Frequency) that has to work to survive, has competition, has accountability to shareholders, and a vested interest in FX-322.

- A government agency (FDA) that is tax funded, has no competition (monopoly), no shareholders to answer to, and is primarily interested in covering their asses.

I'm sure there are good people in the FDA, and the FDA in its own way is held accountable... through bureaucratic processes such as reviews and annual budgets.

However there's a lot of room for things to get shifted around there, it's not as clear cut as what keeps businesses like Frequency accountable.

I strongly believe that the reform that the FDA has recently expressed interest in would have had happened decades ago if they had anything remotely resembling competition.

All new drugs & treatments take years & years to come out because of federal FDA policies, after countless lives that could have been saved are ruined or lost.

Right to try is a step in the right direction, but nowhere near enough in my opinion.

 

[d'Wooluf]

I'm pretty positive patients needing multiple doses doesn't require repeat purchasing of the dose. It doesn't make logical business sense to charge people more for every dose due to needing more as it is needing to be commercially friendly for them to make big profits.

You can be sure that the ENT will charge you fees for each injection. What Frequency Therapeutics will charge is anybody's guess. The capacity of the ENT's to do the injections will determine supply. If demand far exceeds supply it makes sense from a purely business point of view to charge for each injection.