Frequency Therapeutics — Hearing Loss Regeneration

[Jrblovsky]

I can't speak for hearing aids, since I don't have them, but I imagine having to go from an entry hearing aid to one of the more powerful ones isn't exactly great.

Regardless you still have a device to purchase and maintain. The power level doesn't really matter. It will still break and cost hundreds of dollars to repair.

@FGG has a point. You are correct, using a hearing aid would be much easier than a cochlear implant.

Regardless, hearing aids suck, plain and simple. They take the garbled up mess you hear and make it worse. If someone is on my left with my normal ear I hear fine. If they are on my right and someone is talking on my left or there is background noise I can't hear anything besides noise.

 

[Guywithapug]

Regardless, hearing aids suck, plain and simple. They take the garbled up mess you hear and make it worse. If someone is on my left with my normal ear I hear fine. If they are on my right and someone is talking on my left or there is background noise I can't hear anything besides noise.

I know what you mean, no matter how much I tweak the settings with my Starkey Livio Edge hearing aid app it's pretty brutal to be in the middle of a noisy restaurant. I have to turn the volume almost all the way down, essentially the same as taking the hearing aid out.

I prefer not using it at all and think I'd get used to the hearing imbalance between ears as the right captures everything I need while the left is good up to 2 kHz. If it just weren't for the damn tinnitus :/

 

[FGG]

If, as suggested in the interview @serendipity1996 posted, FX-322 could put some CI candidates in the hearing aid range (and potentially get rid of hearing aids for people in the hearing aid range), what i hope doesn't happen in that case, is for hearing aid companies to recoup their costs in lost market share by charging CI prices for hearing aids. But maybe insurance would cover it in that case (since often CIs are covered).

 

[Jack V]

Why would one pay thousands for a drug and still be required to pay thousands more for hearing aids? That isn't helpful at all.

Because we'll take the help from wherever we can get it.

If a drug provides a partial solution and a hearing aid helps on top of that, then I'm happy to pay for both. Happy to pay for any treatment that helps in any way.

 

[Jcmc]

"We don't see FX 322 eliminating hearing aids. We actually see it... it could potentially be used in combination. You might have a subject that might be a candidate for a cochlear implant, and they could potentially be treated and then moved to being a hearing aid candidate. And then there might be people that use hearing aids that could be treated and maybe they don't need to use hearing aids any longer."

 

[Diesel]

If, as suggested in the interview @serendipity1996 posted, FX-322 could put some CI candidates in the hearing aid range (and potentially get rid of hearing aids for people in the hearing aid range), what i hope doesn't happen in that case, is for hearing aid companies to recoup their costs in lost market share by charging CI prices for hearing aids. But maybe insurance would cover it in that case (since often CIs are covered).

Interesting thought. Hearing aid prices may depend on the price of FX-322. However, if the prices are driven up, it's likely insurance will be more willing to cover FX-322 as a first-pass treatment before covering hearing aids.

 

[Jcmc]

"We don't see FX 322 eliminating hearing aids. We actually see it... it could potentially be used in combination. You might have a subject that might be a candidate for a cochlear implant, and they could potentially be treated and then moved to being a hearing aid candidate. And then there might be people that use hearing aids that could be treated and maybe they don't need to use hearing aids any longer."

I think he's just taking care not to say stupid things.

 

[FGG]

"We don't see FX 322 eliminating hearing aids. We actually see it... it could potentially be used in combination. You might have a subject that might be a candidate for a cochlear implant, and they could potentially be treated and then moved to being a hearing aid candidate. And then there might be people that use hearing aids that could be treated and maybe they don't need to use hearing aids any longer."

Thanks. A lot of people probably read the comments and don't go back and listen or read the interview on their own.

 

[serendipity1996]

Thanks. A lot of people probably read the comments and don't go back and listen or read the interview on their own.

I also reckon that he probably necessarily has to be quite cautious in these sorts of interviews anyway e.g. not hyping up timelines too much etc. It would probably be quite a bold and possibly reckless statement if they were already claiming that it would obliterate the hearing aid industry.

 

[Orions Pain]

Carl LeBel can only speak to data that is known from the Phase 1/2 clinical trial. So based on that, they only saw improvements above 8 kHz. If outcomes start to look more like they're deeply penetrating the cochlea and creating improvements at frequencies that compete with hearing aids... the narrative will definitely shift.

I read the study in full, and recall them mentioning about a 10 dB improvement around 8 kHz.

"Comparison of baseline and Day 90 pure-tone thresh- olds showed no statistically significant differences between groups at any frequency. However, Day 90 pure-tone assessments showed that 4/15 FX-322-treated patient ears had 10 dB improvement at the highest test frequency (8 kHz), whereas no placebo-treated ears showed this level of improvement."​

Are we reading this as anything below 8 kHz there was no improvement at all for anyone?

Not too worried here since this was just one shot but the wording here kinda confused me.

Very interested in what the outcomes of these studies are in regards to higher frequencies and tinnitus. I hope they find some patterns in regards to the type of hearing loss, where it is, and the loudness/intrusiveness of tinnitus.

 

[Keith Handy]

I also reckon that he probably necessarily has to be quite cautious in these sorts of interviews anyway e.g. not hyping up timelines too much etc. It would probably be quite a bold and possibly reckless statement if they were already claiming that it would obliterate the hearing aid industry.

Basically the exact opposite of a snake oil salesman, which is exactly what we want to see/hear.

 

[Jrblovsky]

I also reckon that he probably necessarily has to be quite cautious in these sorts of interviews anyway e.g. not hyping up timelines too much etc. It would probably be quite a bold and possibly reckless statement if they were already claiming that it would obliterate the hearing aid industry.

That would be an amazing day in history. It can have the same fate as the DVD, non solid state hard drives, and CRT televisions. Every product has a life cycle and the hearing aid has been around way too long.
You can add audiologist to that list while were at it

 

[Jrblovsky]

If, as suggested in the interview @serendipity1996 posted, FX-322 could put some CI candidates in the hearing aid range (and potentially get rid of hearing aids for people in the hearing aid range), what i hope doesn't happen in that case, is for hearing aid companies to recoup their costs in lost market share by charging CI prices for hearing aids. But maybe insurance would cover it in that case (since often CIs are covered).

This would be just another reason for more low cost options to come into play. With deregulation occurring for over the counter hearing aids the big six can charge what they want and go out of business. It's like Blockbuster and Family Video... byeee...

 

[Guywithapug]

"We don't see FX 322 eliminating hearing aids. We actually see it... it could potentially be used in combination. You might have a subject that might be a candidate for a cochlear implant, and they could potentially be treated and then moved to being a hearing aid candidate. And then there might be people that use hearing aids that could be treated and maybe they don't need to use hearing aids any longer."

Wouldn't this then elude to there being a limitation on gains? I mean for some, a 5-10 dB gain would help but for others it would be a spit in the bucket.

 

[Diesel]

I read the study in full, and recall them mentioning about a 10 dB improvement around 8 kHz.

"Comparison of baseline and Day 90 pure-tone thresh- olds showed no statistically significant differences between groups at any frequency. However, Day 90 pure-tone assessments showed that 4/15 FX-322-treated patient ears had 10 dB improvement at the highest test frequency (8 kHz), whereas no placebo-treated ears showed this level of improvement."​

Are we reading this as anything below 8 kHz there was no improvement at all for anyone?

Not too worried here since this was just one shot but the wording here kinda confused me.

Very interested in what the outcomes of these studies are in regards to higher frequencies and tinnitus. I hope they find some patterns in regards to the type of hearing loss, where it is, and the loudness/intrusiveness of tinnitus.

Yep. Only improvements were at 8 kHz with a single dose. And it was by 4 patients that received FX-322.

With multiple doses, patients may see more significant improvements at and above 8 kHz, and/or improvements below 8 kHz, or a combination of both.

 

[Diesel]

Wouldn't this then elude to there being a limitation on gains? I mean for some, a 5-10 dB gain would help but for others it would be a spit in the bucket.

Every 10 dB in gain is 3x - 4x the sensitivity at the human ear. I think at the mild loss range, it would be harder to detect than say, moderate-severe.

 

[FGG]

Wouldn't this then elude to there being a limitation on gains? I mean for some, a 5-10 dB gain would help but for others it would be a spit in the bucket.

It only suggests it may not put people in the cochlear implant range at normal hearing. It doesn't at all mean the cap is at 5-10 dB.

 

[patorjk]

This is old news, from 2018, so forgive me if this has been discussed already, but I was digging around and discovered that Frequency Therapeutics has at least once publicly discussed an internal alopecia (hair loss) program (timestamp: 3:00):



It looks like they had something that worked better than Minoxidil. It's kind of strange that they haven't talked about it recently. Maybe the program ran into problems?

Also fascinating is that that at the 1:00 mark they show a slide of progenitor cells in the body. They have a slide like this on their website (their current 2021 presentation), except it contains a few additions: Brain (most likely their MS program), Lungs, Intestine, and Skin (this has replaced Hair). I wonder if this is an indication of what they're currently looking into.

 

[AfroSnowman]

Every 10 dB in gain is 3x - 4x the sensitivity at the human ear. I think at the mild loss range, it would be harder to detect than say, moderate-severe.

It will be interesting to see what this does in the extended audiograms. Just because it showed 5-10 dB at 8 kHz, which was its apparent limit in the one dose study doesn't mean that the gains above 8 kHz might not have been substantially larger.

 

[Diesel]

Now that we're getting close to March, I think it's time to talk about expectations. I've put together a series of possible scenarios for the Phase 2A 90-Day Data:

The Worst Case: Multi-Dosing doesn't have any significant effect. It becomes a "bigger" Phase 1/2.

Description:
The data shows that all 3 dose cohorts basically reproduce what we saw in the single dose Phase 1/2, except with 72 patients instead of 15.

The Good:
Word score improvements continue to be clinically meaningful / statistically significant.
Similar improvement rate at 8 kHz + on audiogram, but nothing lower.

The Okay:
Tinnitus scores (TFI) show improvement trend, but is not significant amongst cohorts
EHF audiogram shows improvement but not significant.
Word-in-Noise score shows improvement, but slightly more significant.

The Bad:
No improvement below 8 kHz on audiogram.
Multi-dosing didn't work.


The "Meh" Case 1: Multi-Dosing works, but didn't go deeper per cohort.

Description:
Data shows that multi-dosing does have a stratified effect, but stays concentrated in the EHF (8 kHz+).

The Good:
Word score improvements continue to be clinically meaningful / statistically significant.
Word-in-Noise score shows improvement that is clinically meaningful / statistically significant.
EHF audiogram shows significant improvement (20 dB+, 30 dB+, etc).

The Okay:
4-dose show more improvements at 8 kHz (10 dB+, 20 dB+, etc) + on audiogram, but nothing lower in frequency.
Tinnitus scores (TFI) show improvement trend, and is stratified at each cohort level (more doses, lower TFI).

The Bad:
No improvement below 8 kHz on audiogram.


The "Meh" Case 2: Multi-Dosing works, goes deeper, but underwhelming response.

Description:
Data shows that multi-dosing does have a stratified effect in terms of depth, but the improvements are minor.

The Good:
Word score improvements continue to be clinically meaningful / statistically significant.

The Okay:
Word-in-Noise score shows improvement, but slightly more significant.
EHF audiogram shows improvement, but isn't groundbreaking (10-20 dB, etc).
4-dose improvements go below 8 kHz on audiogram (6 kHz, 4 kHz), but the gains don't get above 10 dB.
Tinnitus scores (TFI) show improvement trend, and is stratified at each cohort level (more doses, lower TFI).

The Bad:
No significant improvement in dB on normal audiogram above 10 dB at any given frequency.
Issues point to synaptopathy being a greater issue than anticipated (need PIPE-505, OTO-413).


The Ideal Outcome: Multi-Dosing goes deeper + significant response.

Description:
Data shows that multi-dosing does have a stratified effect in terms of depth, and the improvements are significant.

The Good:
Word score improvements continue to be clinically meaningful / statistically significant.
Word-in-Noise score shows improvement that is clinically meaningful / statistically significant.
EHF audiogram shows significant improvement from baseline(20 dB+, 30 dB+, etc).
4-dose improvements go below 8 kHz on audiogram (6 kHz, 4 kHz, 2 kHz), and show clear improvement per band: +30 dB @ 8 kHz, +20 dB @ 6 kHz, +10 dB @ 4 kHz.
Tinnitus scores (TFI) significant improvement trend, and is stratified at each cohort level (more doses, lower TFI).

The Okay:
Obviously doesn't go deeper into cochlea.
Hearing isn't restored to "like new" after 4 doses.
FX-322 is still many years from product.

 

[Diesel]

This is old news, from 2018, so forgive me if this has been discussed already, but I was digging around and discovered that Frequency Therapeutics has at least once publicly discussed an internal alopecia (hair loss) program (timestamp: 3:00):

It looks like they had something that worked better than Minoxidil. It's kind of strange that they haven't talked about it recently. Maybe the program ran into problems?

Also fascinating is that that at the 1:00 mark they show a slide of progenitor cells in the body. They have a slide like this on their website (their current 2021 presentation), except it contains a few additions: Brain (most likely their MS program), Lungs, Intestine, and Skin (this has replaced Hair). I wonder if this is an indication of what they're currently looking into.

They have a patent-pending for using their PCA approach to restore hair follicle cells. According to Langer, they have "10 other" opportunities that they are investigating within their labs.

I suspect that they don't want to distract from their focus on hearing loss / FX-322 as it will clearly become their cash-cow product. Also, delivery method has to be a challenge for some of these.

Lucchino specifically mentions that any therapeutic that has competition will be hard to ask a premium for. There's a TON of competition in the normal hair-loss space in terms of treatments & alternatives.

I think about where they are seeing progenitor cells in eye, for example. I wonder how that would be delivered? Would they inject some gunk into your eyeball? Same with hair follicles... is it supposed to be a cream that you rub on your dome?

 

[FGG]

This is old news, from 2018, so forgive me if this has been discussed already, but I was digging around and discovered that Frequency Therapeutics has at least once publicly discussed an internal alopecia (hair loss) program (timestamp: 3:00):

It looks like they had something that worked better than Minoxidil. It's kind of strange that they haven't talked about it recently. Maybe the program ran into problems?

Also fascinating is that that at the 1:00 mark they show a slide of progenitor cells in the body. They have a slide like this on their website (their current 2021 presentation), except it contains a few additions: Brain (most likely their MS program), Lungs, Intestine, and Skin (this has replaced Hair). I wonder if this is an indication of what they're currently looking into.

They mentioned cartilage before, too.

Once they get a blockbuster drug approved, they can fund multiple studies simultaneously.

Look at Sarepta, a few years ago they got their first drug approved. Check out their 43 drug pipeline now:

https://www.sarepta.com/products-pipeline/pipeline

 

[FGG]

I think about where they are seeing progenitor cells in eye, for example. I wonder how that would be delivered? Would they inject some gunk into your eyeball?

Probably. That's how it's done with Luxturna.

 

[patorjk]

Now that we're getting close to March, I think it's time to talk about expectations. I've put together a series of possible scenarios for the Phase 2A 90-Day Data:

The Worst Case: Multi-Dosing doesn't have any significant effect. It becomes a "bigger" Phase 1/2.

Description:
The data shows that all 3 dose cohorts basically reproduce what we saw in the single dose Phase 1/2, except with 72 patients instead of 15.

The Good:
Word score improvements continue to be clinically meaningful / statistically significant.
Similar improvement rate at 8 kHz + on audiogram, but nothing lower.

The Okay:
Tinnitus scores (TFI) show improvement trend, but is not significant amongst cohorts
EHF audiogram shows improvement but not significant.
Word-in-Noise score shows improvement, but slightly more significant.

The Bad:
No improvement below 8 kHz on audiogram.
Multi-dosing didn't work.


The "Meh" Case 1: Multi-Dosing works, but didn't go deeper per cohort.

Description:
Data shows that multi-dosing does have a stratified effect, but stays concentrated in the EHF (8 kHz+).

The Good:
Word score improvements continue to be clinically meaningful / statistically significant.
Word-in-Noise score shows improvement that is clinically meaningful / statistically significant.
EHF audiogram shows significant improvement (20 dB+, 30 dB+, etc).

The Okay:
4-dose show more improvements at 8 kHz (10 dB+, 20 dB+, etc) + on audiogram, but nothing lower in frequency.
Tinnitus scores (TFI) show improvement trend, and is stratified at each cohort level (more doses, lower TFI).

The Bad:
No improvement below 8 kHz on audiogram.


The "Meh" Case 2: Multi-Dosing works, goes deeper, but underwhelming response.

Description:
Data shows that multi-dosing does have a stratified effect in terms of depth, but the improvements are minor.

The Good:
Word score improvements continue to be clinically meaningful / statistically significant.

The Okay:
Word-in-Noise score shows improvement, but slightly more significant.
EHF audiogram shows improvement, but isn't groundbreaking (10-20 dB, etc).
4-dose improvements go below 8 kHz on audiogram (6 kHz, 4 kHz), but the gains don't get above 10 dB.
Tinnitus scores (TFI) show improvement trend, and is stratified at each cohort level (more doses, lower TFI).

The Bad:
No significant improvement in dB on normal audiogram above 10 dB at any given frequency.
Issues point to synaptopathy being a greater issue than anticipated (need PIPE-505, OTO-413).


The Ideal Outcome: Multi-Dosing goes deeper + significant response.

Description:
Data shows that multi-dosing does have a stratified effect in terms of depth, and the improvements are significant.

The Good:
Word score improvements continue to be clinically meaningful / statistically significant.
Word-in-Noise score shows improvement that is clinically meaningful / statistically significant.
EHF audiogram shows significant improvement from baseline(20 dB+, 30 dB+, etc).
4-dose improvements go below 8 kHz on audiogram (6 kHz, 4 kHz, 2 kHz), and show clear improvement per band: +30 dB @ 8 kHz, +20 dB @ 6 kHz, +10 dB @ 4 kHz.
Tinnitus scores (TFI) significant improvement trend, and is stratified at each cohort level (more doses, lower TFI).

The Okay:
Obviously doesn't go deeper into cochlea.
Hearing isn't restored to "like new" after 4 doses.
FX-322 is still many years from product.

I honestly think your "Meh" cases are the most likely. However, I think you're missing how good the tinnitus improvements could be if the drug just handles high frequency hearing (at this stage). If people report back that their tinnitus is 90% or completely gone, that's a huge deal imo.

 

[Jrblovsky]

Now that we're getting close to March, I think it's time to talk about expectations. I've put together a series of possible scenarios for the Phase 2A 90-Day Data:

The Worst Case: Multi-Dosing doesn't have any significant effect. It becomes a "bigger" Phase 1/2.

Description:
The data shows that all 3 dose cohorts basically reproduce what we saw in the single dose Phase 1/2, except with 72 patients instead of 15.

The Good:
Word score improvements continue to be clinically meaningful / statistically significant.
Similar improvement rate at 8 kHz + on audiogram, but nothing lower.

The Okay:
Tinnitus scores (TFI) show improvement trend, but is not significant amongst cohorts
EHF audiogram shows improvement but not significant.
Word-in-Noise score shows improvement, but slightly more significant.

The Bad:
No improvement below 8 kHz on audiogram.
Multi-dosing didn't work.


The "Meh" Case 1: Multi-Dosing works, but didn't go deeper per cohort.

Description:
Data shows that multi-dosing does have a stratified effect, but stays concentrated in the EHF (8 kHz+).

The Good:
Word score improvements continue to be clinically meaningful / statistically significant.
Word-in-Noise score shows improvement that is clinically meaningful / statistically significant.
EHF audiogram shows significant improvement (20 dB+, 30 dB+, etc).

The Okay:
4-dose show more improvements at 8 kHz (10 dB+, 20 dB+, etc) + on audiogram, but nothing lower in frequency.
Tinnitus scores (TFI) show improvement trend, and is stratified at each cohort level (more doses, lower TFI).

The Bad:
No improvement below 8 kHz on audiogram.


The "Meh" Case 2: Multi-Dosing works, goes deeper, but underwhelming response.

Description:
Data shows that multi-dosing does have a stratified effect in terms of depth, but the improvements are minor.

The Good:
Word score improvements continue to be clinically meaningful / statistically significant.

The Okay:
Word-in-Noise score shows improvement, but slightly more significant.
EHF audiogram shows improvement, but isn't groundbreaking (10-20 dB, etc).
4-dose improvements go below 8 kHz on audiogram (6 kHz, 4 kHz), but the gains don't get above 10 dB.
Tinnitus scores (TFI) show improvement trend, and is stratified at each cohort level (more doses, lower TFI).

The Bad:
No significant improvement in dB on normal audiogram above 10 dB at any given frequency.
Issues point to synaptopathy being a greater issue than anticipated (need PIPE-505, OTO-413).


The Ideal Outcome: Multi-Dosing goes deeper + significant response.

Description:
Data shows that multi-dosing does have a stratified effect in terms of depth, and the improvements are significant.

The Good:
Word score improvements continue to be clinically meaningful / statistically significant.
Word-in-Noise score shows improvement that is clinically meaningful / statistically significant.
EHF audiogram shows significant improvement from baseline(20 dB+, 30 dB+, etc).
4-dose improvements go below 8 kHz on audiogram (6 kHz, 4 kHz, 2 kHz), and show clear improvement per band: +30 dB @ 8 kHz, +20 dB @ 6 kHz, +10 dB @ 4 kHz.
Tinnitus scores (TFI) significant improvement trend, and is stratified at each cohort level (more doses, lower TFI).

The Okay:
Obviously doesn't go deeper into cochlea.
Hearing isn't restored to "like new" after 4 doses.
FX-322 is still many years from product.

If the last scenario occurs, that verifies the drug actually works and the dosing/delivery needs adjustment/improvement.

Everything else you have mentioned is a good thought but does not hit the mark. I would imagine the drug will be ripped apart if this occurs. Maybe back to formula.

I hope you're right and they have better than anticipated results.

I honestly think your "Meh" cases are the most likely. However, I think you're missing how good the tinnitus improvements could be if the drug just handles high frequency hearing (at this stage). If people report back that their tinnitus is 90% or completely gone, that's a huge deal imo.

Unless it totally abates tinnitus the bogus audiology doctors and self help idiots will still claim it doesn't help. Maybe if it shows massive improvements on the TFI but I don't know.

 

[Princebeyel]

Is it possible to receive more than four doses of FX-322 for people in the severe hearing loss range?

 

[Orions Pain]

I honestly think your "Meh" cases are the most likely. However, I think you're missing how good the tinnitus improvements could be if the drug just handles high frequency hearing (at this stage). If people report back that their tinnitus is 90% or completely gone, that's a huge deal imo.

It will suck if the tinnitus improvement is major, but multi-dosing doesn't do much for frequencies below 8 kHz so they decide not to go through to Phase 3. What are the chances of them switching gears and releasing this primarily as a tinnitus treatment?

Again probably too early in the game for this sort of speculation. Phase 2 is going to give us good insight imo. I can't help but view this all through a tinnitus lens even though it's primarily for hearing loss.

 

[Orions Pain]

Is it possible to receive more than four doses of FX-322 for people in the severe hearing loss range?

If I'm looking at the right place, the severe hearing loss trial is only doing a single dose as of right now. Phase 1b is the safety trial. If that proceeds to Phase 2, they'll likely do more than one injection. How many, I think it is too early to say.

The Phase 2 where they are doing 4 shots is for SNHL that is stable. The criteria was:

1. Pure Tone Audiometry (PTA) within 26-70 dB in the ear to be injected

 

[Jrblovsky]

Every 10 dB in gain is 3x - 4x the sensitivity at the human ear. I think at the mild loss range, it would be harder to detect than say, moderate-severe.

I disagree with you. After I had my hearing loss, I was at a 40 dB loss at 8 kHz. After steroids it recovered to 25 dB, and it actually went to 20 dB on one test. I could tell at 20 dB that it was near normal and the 8 kHz tinnitus tone was gone.

I am now at a 75 dB loss for reasons unknown and I doubt improvements at 10 kHz would help hear anything. It may turn the eeeee down a notch or two but that's about it.

 

[FGG]

I honestly think your "Meh" cases are the most likely. However, I think you're missing how good the tinnitus improvements could be if the drug just handles high frequency hearing (at this stage). If people report back that their tinnitus is 90% or completely gone, that's a huge deal imo.

Why would that be most likely?

I truly do not believe they'd start a multi dose trial just to show it doesn't make a difference. There was pre-clinical work that was part of that decision (and I assume multi dose explant studies). They are way too together of a company imo not to at least have some idea before putting it to trial.