Frequency Therapeutics — Hearing Loss Regeneration

[Darren H]

What compound did you get injected?

Dexamethasone.

 

[Diesel]

Could anyone comment on the odds of a Phase 3 trial in the US accepting non-US citizens as applicants?

And how likely would a joint US/European Phase 3 be with help from Astellas?

Odds of a US Clinical Site accepting non-US Citizens:

Low. While there isn't a citizenship requirement; you likely need to be a legal resident of the US. Also, need to be an established patient with a US-based doctors office to verify your required records for entrance. You'd need to be able to attend all of the follow-up appointments over the course of at least 90-days. You can only stay in the US for 90 days without an approved visa, so you'd need to leave an come back at least once.

Odds of joint US/EU Phase 3 with Astellas. Expect it.

 

[serendipity1996]

Odds of a US Clinical Site accepting non-US Citizens:

Low. While there isn't a citizenship requirement; you likely need to be a legal resident of the US. Also, need to be an established patient with a US-based doctors office to verify your required records for entrance. You'd need to be able to attend all of the follow-up appointments over the course of at least 90-days. You can only stay in the US for 90 days without an approved visa, so you'd need to leave an come back at least once.

Odds of joint US/EU Phase 3 with Astellas. Expect it.

Now that the UK has exited the EU, I do wonder whether it would therefore be unlikely that Phase 3 trials would have a location in Britain...

 

[Philip83]

Odds of a US Clinical Site accepting non-US Citizens:

Low. While there isn't a citizenship requirement; you likely need to be a legal resident of the US. Also, need to be an established patient with a US-based doctors office to verify your required records for entrance. You'd need to be able to attend all of the follow-up appointments over the course of at least 90-days. You can only stay in the US for 90 days without an approved visa, so you'd need to leave an come back at least once.

Odds of joint US/EU Phase 3 with Astellas. Expect it.

Thanks. I'm in Sweden, which I think is too small of a country to make a trial plausible. Within the EU I'm pretty sure I could technically join a trial, but I don't speak any other European language, so I'm fearing the word score tests would then bar me from participating. I guess maybe the UK is an option, although now they left the EU so might be unlikely because of that. Dammit...

 

[Trevor_phillips]

Do you think FX-322 could not only help hearing, but also vision?

I got visual disorders (Visual Snow Syndrome) after getting hearing loss from noise trauma. I want to know if FX-322 restores my hearing, would my brain consequently readjust my vision?

Thank you.

 

[david2017]

Thanks. I'm in Sweden, which I think is too small of a country to make a trial plausible. Within the EU I'm pretty sure I could technically join a trial, but I don't speak any other European language, so I'm fearing the word score tests would then bar me from participating. I guess maybe the UK is an option, although now they left the EU so might be unlikely because of that. Dammit...

I also live in Sweden and feel like you. If FX-322 works to restore hearing, I want to get it as soon as possible. But I don't know how

 

[Fields]

Thanks. I'm in Sweden, which I think is too small of a country to make a trial plausible. Within the EU I'm pretty sure I could technically join a trial, but I don't speak any other European language, so I'm fearing the word score tests would then bar me from participating. I guess maybe the UK is an option, although now they left the EU so might be unlikely because of that. Dammit...

Perhaps you could join a trial in the Netherlands. If I'm not mistaken, the audiology center I went to also offers their word score test in English. As such, I'd assume that other places that offer advanced audiograms might offer this option as well.

If a trial were ever to be run here, I'll make sure to inform you.

 

[FGG]

Do you think FX-322 could not only help hearing, but also vision?

I got visual disorders (Visual Snow Syndrome) after getting hearing loss from noise trauma. I want to know if FX-322 restores my hearing, would my brain consequently readjust my vision?

Thank you.

No one knows but it's possible as it might settle some of the central hyperexcitability. I also have visual snow and that would be great, if so.

 

[sensualmosquito]

I was reading into an NIH study about the challenges of hair cell regeneration, and I ran into a section describing "scar formation" in the organ of Corti. The cochlea appears to do this in order to prevent the escape of potassium ions from the endolymph into the perilymph, which could cause further damage (K+ is higher extracellularly in endolymph, which is the opposite from most of the rest of your body).

What I wonder is if the formation of these lesions will dramatically affect the efficacy of FX-322, or somehow make the regenerated hair cells work incorrectly (form in the wrong location or structural formation).

Another question which I can't seem to find an answer to is why mammals don't regenerate their hair cells in the first place. It seems that there isn't a conclusion on the matter from the research I have come across, which generates some concern for me as FX-322 could be interfering with some sort of mechanism we do not yet understand that could potentially make things worse. It's really hard to say right now, as this is just speculation and injecting a medication into the ear is much different than the endogenous evolution of the ear. It could still be very helpful; I just want to see more research done in this area to answer these potent questions. If we knew reason why the mammalian ear cannot regenerate in the adult, that could offer another angle of potential for restorative therapy.

 

[FGG]

I was reading into an NIH study about the challenges of hair cell regeneration, and I ran into a section describing "scar formation" in the organ of Corti. The cochlea appears to do this in order to prevent the escape of potassium ions from the endolymph into the perilymph, which could cause further damage (K+ is higher extracellularly in endolymph, which is the opposite from most of the rest of your body).

What I wonder is if the formation of these lesions will dramatically affect the efficacy of FX-322, or somehow make the regenerated hair cells work incorrectly (form in the wrong location or structural formation).

Another question which I can't seem to find an answer to is why mammals don't regenerate their hair cells in the first place. It seems that there isn't a conclusion on the matter from the research I have come across, which generates some concern for me as FX-322 could be interfering with some sort of mechanism we do not yet understand that could potentially make things worse. It's really hard to say right now, as this is just speculation and injecting a medication into the ear is much different than the endogenous evolution of the ear. It could still be very helpful; I just want to see more research done in this area to answer these potent questions. If we knew reason why the mammalian ear cannot regenerate in the adult, that could offer another angle of potential for restorative therapy.

The epithelial scar forms when you have lost all sensory and support cells in an area and you get "flat epithelia" to prevent ion loss. This occurs after the profound range (>90 dB loss) and they are trying to research helping those people through viral ventured transduction of the epithelial cells into support cells. Some estimate this is 10-15 years away though.

 

[Diesel]

I was reading into an NIH study about the challenges of hair cell regeneration, and I ran into a section describing "scar formation" in the organ of Corti. The cochlea appears to do this in order to prevent the escape of potassium ions from the endolymph into the perilymph, which could cause further damage (K+ is higher extracellularly in endolymph, which is the opposite from most of the rest of your body).

What I wonder is if the formation of these lesions will dramatically affect the efficacy of FX-322, or somehow make the regenerated hair cells work incorrectly (form in the wrong location or structural formation).

Another question which I can't seem to find an answer to is why mammals don't regenerate their hair cells in the first place. It seems that there isn't a conclusion on the matter from the research I have come across, which generates some concern for me as FX-322 could be interfering with some sort of mechanism we do not yet understand that could potentially make things worse. It's really hard to say right now, as this is just speculation and injecting a medication into the ear is much different than the endogenous evolution of the ear. It could still be very helpful; I just want to see more research done in this area to answer these potent questions. If we knew reason why the mammalian ear cannot regenerate in the adult, that could offer another angle of potential for restorative therapy.

Many many pages ago, the "scar" discussion was brought up and stirred much anxiety. It turns out the "scar" is the support cells filling in for missing OHC/IHC. If it were the case where a scar prohibited regrowth or the performance of the new cells, we probably wouldn't see the word score improvements that we've seen in the Phase 1/2. Also, scarring in the sense of other organs implies a therapeutic window, where none is mentioned in any of the trials for FX-322.

As it relates to the long-term effects of PCA small molecule drugs being injected into the body to enable regeneration; it may take decades of millions of doses to understand the true systemic effects over the course of a human's lifetime. So far, a small set of patients have been injected once over the course of up to 3 years, and no severe long term effect has caused the project to be suspended. If you are planning to wait for something more conclusive before taking the drug, it may be quite a long wait. Right now, it's also known that no intervention following the onset of hearing loss only leads to a more accelerated decay of hearing function.

I'm not really sure we'll ever fully know why mammals cannot regenerate certain cells while other species can. I suppose if a common ancestor way back in the evolutionary chain to early invertebrates was able to be studied, scientists might be able to point to exactly what changed in the biology. But, I am so low on knowledge in this area. And frankly, considering most drugs make the body do something it shouldn't naturally, I'm not sure of the practicality of that level of understanding.

 

[Philip83]

If a trial were ever to be run here, I'll make sure to inform you.

That would be great, thanks!

 

[Philip83]

Another thought that hit me today. Since ear pain / hyperacusis / noxacusis is thought to, at least in part, be a symptom of a chronic inflammation, is there any reason to think regrowing hair cells will reverse inflammation? Or is it pretty much a given that we need another drug/treatment for that?

 

[Diesel]

Another thought that hit me today. Since ear pain / hyperacusis / noxacusis is thought to, at least in part, be a symptom of a chronic inflammation, is there any reason to think regrowing hair cells will reverse inflammation? Or is it pretty much a given that we need another drug/treatment for that?

Not proven.

 

[Cernuto]

One little drop of this has a slight chance to potentially be the silver bullet that cures the 12 kHz screech in my ear, and here I am waiting for whoever knows how many months for the moment to try it. What a reality...

 

[GlennS]

Another thought that hit me today. Since ear pain / hyperacusis / noxacusis is thought to, at least in part, be a symptom of a chronic inflammation, is there any reason to think regrowing hair cells will reverse inflammation? Or is it pretty much a given that we need another drug/treatment for that?

Not proven.

Nor disproven. My bet is yes.

 

[frpp]

Another thought that hit me today. Since ear pain / hyperacusis / noxacusis is thought to, at least in part, be a symptom of a chronic inflammation, is there any reason to think regrowing hair cells will reverse inflammation? Or is it pretty much a given that we need another drug/treatment for that?

I'm not sure whether regrowing hair cells will stop inflammation but SPI-1005 should and it will most likely be out before FX-322.

 

[Philip83]

Not proven.

Nor disproven. My bet is yes.

In my twenties I had chronic inflammation in my wrist for years. Once I started going to the gym regularly, the inflammation went away and hasn't come back since. I guess I rebuilt muscle cells and that helped fight the inflammation in this case. Maybe the same will be true for hair cells.

 

[serendipity1996]

In my twenties I had chronic inflammation in my wrist for years. Once I started going to the gym regularly, the inflammation went away and hasn't come back since. I guess I rebuilt muscle cells and that helped fight the inflammation in this case. Maybe the same will be true for hair cells.

If inflammation is stemming from structural damage (e.g., damaged hair cells/synapses), then surely it would resolve once you have fixed the underlying damaged structures? I'm not educated or well-versed in biology though or the science behind inflammation so I'm really not sure.

 

[Damien0000]

we probably wouldn't see the word score improvements

Sorry for the silly question, but you're talking about the test of repeating the word you hear in your ears to see if you hear well? If so, can my score be considered perfect when you hear these words perfectly well and can repeat them without a problem?

 

[Gb3]

Sorry for the silly question, but you're talking about the test of repeating the word you hear in your ears to see if you hear well? If so, can my score be considered perfect when you hear these words perfectly well and can repeat them without a problem?

Yes, if you can repeat them all, it would be a perfect score.

 

[Piney]

FX-322 results, as of now, haven't shown helping tinnitus or increasing the volume of sound heard for those with hearing loss.

Shouldn't Otonomy be getting more traffic or am I wrong?

 

[serendipity1996]

FX-322 results, as of now, haven't shown helping tinnitus or increasing the volume of sound heard for those with hearing loss.

Shouldn't Otonomy be getting more traffic or am I wrong?

I feel like this is sort of comparing apples and oranges though since one is a hair cell drug and the other is targeted at synapses. I think we will need both of these in tandem to achieve the best outcome to be honest.

 

[Rb86]

FX-322 results, as of now, haven't shown helping tinnitus or increasing the volume of sound heard for those with hearing loss.

Shouldn't Otonomy be getting more traffic or am I wrong?

Clarity improvement I believe has been documented by word score tests. Subtle but important.

 

[Jrblovsky]

FX-322 results, as of now, haven't shown helping tinnitus or increasing the volume of sound heard for those with hearing loss.

They are finishing a clinical trial in a few months to show if the drug truly works to restore hearing. There is no doubt that it replaces damaged hair cells. Hopefully they have good results. This could be a life changing drug for many people.

 

[Gb3]

FX-322 results, as of now, haven't shown helping tinnitus or increasing the volume of sound heard for those with hearing loss.

Shouldn't Otonomy be getting more traffic or am I wrong?

Go home Piney.

 

[Kam75]

Why are you guys already talking about Phase 3 when Phase 2a is not even finished yet?

Does this mean that they will skip Phase 2b?

It seems I missed a development.

 

[Philip83]

FX-322 results, as of now, haven't shown helping tinnitus or increasing the volume of sound heard for those with hearing loss.

Shouldn't Otonomy be getting more traffic or am I wrong?

In Phase 1, one dose showed 10-15 dB increase in volume at 8 kHz. In March we will get the results of what four doses can do, also up to 16 kHz.

 

[Bartoli]

It doesn't mean you have profound hearing loss. For instance, I have moderately severe hearing loss above 8 kHz (tested multiple times) but I can't hear anything through headphones.

So the headphones in the audiology booth were able to emit a more powerful signal?

 

[Diesel]

Why are you guys already talking about Phase 3 when Phase 2a is not even finished yet?

Does this mean that they will skip Phase 2b?

It seems I missed a development.

Many suspect there will be a combined Phase 2b/3 pivotal trial.

Considering the pipeline of in-progress trials (SNHL Phase 2a, Age-Related Hearing Loss Phase 1b, Severe SNHL Phase 1b) that are intended to end this year, if all produce positive outcomes by Q3/2021, it's possible that final pivotal trial is all that is needed in 2022. Frequency Therapeutics also mentioned in their most recent webcast that they are planning a pivotal trial in 2022, so it likely won't be a standalone Phase 2b.