Frequency Therapeutics — Hearing Loss Regeneration

[scotty03874]

Did anyone here buy a ticket to the conference? That would be able to keep us updated as the information comes in?

Can you buy the ticket online?

 

[Zugzug]

What do you mean exactly by caught something? You mean a mistake in their own analysis or a bad readout?

In any case, you've just made me consider the alternative: would Frequency Therapeutics present at a conference so close to official readout knowing their drug is a dead duck? My point being that even if they don't present their results before or at the conference, surely they would know enough by now to determine whether or not their product is viable. If it wasn't, would they still go ahead with Wednesday, only to present bad data a week or two later? That would be quite humiliating for both Will and Kevin given their positions in the company.

What I mean, I guess, is it's easy to catch mistakes that are likely harmless, but would always force a company to lean on the side of caution.

As far as the question of "would they avoid presenting if the results were bad?" (but could, otherwise), I think the answer to that is no. The results would eventually leak and that could be their time to discuss what "went wrong," which probably wouldn't be much. Maybe I'm Mr. Sunshine here, but I think even if the results are underwhelming, this is not a failed operation. A better delivery method will come sooner than later.

I really think the results are positive -- at least positive enough. There's a wide range of uncertainty, but I feel a lot of certainty that it's not a total flop.

 

[Diesel]

I really think the results are positive -- at least positive enough. There's a wide range of uncertainty, but I feel a lot of certainty that it's not a total flop.

If they recruited right in the Phase 2A, they should have found 95 participants that had similar hearing conditions in at least 1 ear to those "responders" in the Phase 1/2. IE: Those 4-6 patients that showed the impressive word score improvements, SNR improvements, long-term performance, and the 8 kHz improvement.

The math is already on their side for at least 1 dose across all 74 participants that received the drug. I just have a hard time seeing it any other way.

The only thing that gives me any pause is how significant those averages are going to look across each dose cohort. If it isn't obvious in the group average, there may be some spinning to do; and we'll all have to wait until they pick apart the individual results to show the "prime responders" for each cohort.

 

[Zugzug]

I have a super glass is half empty question. Let me qualify this by saying, I do not believe this, but I am offering another side.

If the results were underwhelming (but not bad), is it possible that they would still hire Kevin Franck, as a means of showing faith in the product that ultimately just needs better delivery? Maybe he believes in the team, believes in the direction of regenerative medicine, and has some clout to influence the field by making sure everyone understands that there are roadblocks associated with this operation?

Is that an insane thing to propose?

 

[Diesel]

I have a super glass is half empty question. Let me qualify this by saying, I do not believe this, but I am offering another side.

If the results were underwhelming (but not bad), is it possible that they would still hire Kevin Franck, as a means of showing faith in the product that ultimately just needs better delivery? Maybe he believes in the team, believes in the direction of regenerative medicine, and has some clout to influence the field by making sure everyone understands that there are roadblocks associated with this operation?

Is that an insane thing to propose?

This is a possibility. That they need a good salesman to get the "good enough" product in the market. If they know multi-dosing didn't work as expected, but a single dose still provides a consistent benefit from the Phase 1/2; it's possible that a well known thought-leader could help position the first gen product as complementary to current solutions (hearing aids and nothing). This is not bad in my opinion. It's actually common for other 1st gen products to enter the market positioned as complementary to a dominant product.

At the very least it sets them up to establish distribution, access to patients, and most importantly, cash flow to reinvest into "2.0"

 

[FGG]

I have a super glass is half empty question. Let me qualify this by saying, I do not believe this, but I am offering another side.

If the results were underwhelming (but not bad), is it possible that they would still hire Kevin Franck, as a means of showing faith in the product that ultimately just needs better delivery? Maybe he believes in the team, believes in the direction of regenerative medicine, and has some clout to influence the field by making sure everyone understands that there are roadblocks associated with this operation?

Is that an insane thing to propose?

It's possible but leaving a high profile position to do damage control for a new employer is probably a pretty unusual thing to do.

 

[Zugzug]

If they recruited right in the Phase 2A, they should have found 95 participants that had similar hearing conditions in at least 1 ear to those "responders" in the Phase 1/2. IE: Those 4-6 patients that showed the impressive word score improvements, SNR improvements, long-term performance, and the 8 kHz improvement.

The math is already on their side for at least 1 dose across all 74 participants that received the drug. I just have a hard time seeing it any other way.

The only thing that gives me any pause is how significant those averages are going to look across each dose cohort. If it isn't obvious in the group average, there may be some spinning to do; and we'll all have to wait until they pick apart the individual results to show the "prime responders" for each cohort.

I completely agree with you. But, I just want to add that they describe the statistics as exploratory and "descriptive only." I put that in quotes because they do shoot out some p-values, which require a null hypothesis and a decision on doing a one-tailed or two-tailed test.

They are adding PTA at more frequencies and also more cohort groups. Should be doable, and also, they obviously needed the methods outlined before the data analysis in order to resist the urge of being overzealous with statistical assumptions. That should help.

You're absolutely right though. The fact that they are recruiting for responders is something that briefly slips my mind, but is super important.

 

[Diesel]

It's possible but leaving a high profile position to do damage control for a new employer is probably a pretty unusual thing to do.

Good point. Usually you see management activity when a firm is already trending downwards and the image/product line/narrative needs improved. IE: Hiring pros to do damage control.

See: Volkswagen Diesel-Gate Aftermath.

 

[FGG]

This is a possibility. That they need a good salesman to get the "good enough" product in the market. If they know multi-dosing didn't work as expected, but a single dose still provides a consistent benefit from the Phase 1/2; it's possible that a well known thought-leader could help position the first gen product as complementary to current solutions (hearing aids and nothing). This is not bad in my opinion. It's actually common for other 1st gen products to enter the market positioned as complementary to a dominant product.

At the very least it sets them up to establish distribution, access to patients, and most importantly, cash flow to reinvest into "2.0"

Either way you'd be talking about something that hearing aids could complement. Odds are good that version 1.0 won't penetrate the whole cochlea and even in some of the best case scenarios (let's say it gets down to 2000 Hz and restores most hearing in a stratified way (etc)), you would *still* need hearing aids if you had substantial widespread loss because speech information goes all the way down to about 100 Hz.

 

[Tezcatlipoca]

Can you buy the ticket online?

I found the right link for the conference, sorry about the earlier:

https://hearinghealthmatters.bmeurl.co/BD568E1

It's $200 dollars a ticket...

 

[Zugzug]

Good point. Usually you see management activity when a firm is already trending downwards and the image/product line/narrative needs improved. IE: Hiring pros to do damage control.

See: Volkswagen Diesel-Gate Aftermath.

You survived so the damage control must have been successful. I'm glad you did.

 

[paul mclean]

Tomorrow right?

 

[Diesel]

You survived so the damage control must have been successful. I'm glad you did.

LOL. One day my time will end, and I shall be reborn as, "Battery."

 

[F-u-T]

Frequency Therapeutics' Twitter account has posted a lot about speech clarity and intelligibility in the last few months or so. I think we are going to see results with info that we pretty much already know. FX-322 restores hair cells in the EHF range, improves word scores, noise clarity, and a little improvement with noise loudness in 8 kHz and above.

I think they will pitch FX-322 as a compliment to hearing aids at this conference.

 

[tommyd87]

View attachment 43973 View attachment 43974 View attachment 43975

Frequency Therapeutics' Twitter account has posted a lot about speech clarity and intelligibility in the last few months or so. I think we are going to see results with info that we pretty much already know. FX-322 restores hair cells in the EHF range, improves word scores, noise clarity, and a little improvement with noise loudness in 8 kHz and above.

I think they will pitch FX-322 as a compliment to hearing aids at this conference.

They have been posting about that also before they started streaming a lot of this sort of stuff over their Twitter too.

I think that there is a possibility that we might also see benefit below 8000 Hz, at maybe just say 6000 Hz.

I think that there is also the fact that this tends to be consistent with what Frequency Therapeutics has stated would happen with their treatment at least in the interim. It is almost certain that we will see another version at some point or see the benefits from a redosing such as by giving people a higher dose of the medicine or more shots of the medicine as well.

 

[Tezcatlipoca]

The conference is tomorrow!

 

[spacehunter]

The conference is tomorrow!

For some reason Les Misérables' "One Day More" (caution: link leads to a song on YouTube) really comes into my mind when thinking about what might be about to come.

Really hope we get our own revolution in some sense...

 

[Aaron91]

For what it's worth, Frequency Therapeutics are still recruiting:

https://www.frequencytx.com/careers/current-opportunities/

They also seem to be recruiting a student as a part of a co-op programme that will focus on drug delivery.

It would appear that this position is to support whoever they recruited a few months ago for drug delivery. Here are their two key responsibilities:

1. Work closely with project scientists to carry out experiments to develop novel polymer-based, small molecule inner ear drug delivery systems.
2. With guidance, establish an in vitro assay best simulating conditions of the middle ear. Help to design systematic experiments to compare release profiles from various formulations and analyze results to guide in vivo studies with the goal of establishing an in vitro-in vivo correlation

So I think this tells us what we all suspect already: that Frequency Therapeutics can't reach the lower end of the cochlea, but that their results must still be good enough to proceed with their current programme. I find the second point quite interesting, in that they are almost specifying how important it is for the release profiles in vitro to be reflected in vivo (i.e. in their clinical work).

 

[Jurger]

For what it's worth, Frequency Therapeutics are still recruiting:

https://www.frequencytx.com/careers/current-opportunities/

They also seem to be recruiting a student as a part of a co-op programme that will focus on drug delivery.

It would appear that this position is to support whoever they recruited a few months ago for drug delivery. Here are their two key responsibilities:

1. Work closely with project scientists to carry out experiments to develop novel polymer-based, small molecule inner ear drug delivery systems.
2. With guidance, establish an in vitro assay best simulating conditions of the middle ear. Help to design systematic experiments to compare release profiles from various formulations and analyze results to guide in vivo studies with the goal of establishing an in vitro-in vivo correlation

So I think this tells us what we all suspect already: that Frequency Therapeutics can't reach the lower end of the cochlea, but that their results must still be good enough to proceed with their current programme. I find the second point quite interesting, in that they are almost specifying how important it is for the release profiles in vitro to be reflected in vivo (i.e. in their clinical work).

Apparently they're already doing a study on drug delivery for FX-322. Their February presentation says this on page 25:

"The Company is also conducting an open-label Phase 1 safety study looking at the administration conditions for FX-322"​

Can't find the study anywhere. Anyone know anything about this?

 

[Aaron91]

Apparently they're already doing a study on drug delivery for FX-322. Their February presentation says this on page 25:

"The Company is also conducting an open-label Phase 1 safety study looking at the administration conditions for FX-322"​

Can't find the study anywhere. Anyone know anything about this?

That's quite an eagle-eyed observation, I'm not sure that's been mentioned before. "Administration conditions" does sound very vague though. Any thoughts on why this would refer to drug delivery specifically? My interpretation of "administration conditions" would be anything from the polymer itself to how the patient is positioned i.e. whether they're lying down for an hour or whether they are are hanging them upside down for 10 minutes (not even joking with this).

 

[Koz]

That's quite an eagle-eyed observation, I'm not sure that's been mentioned before. "Administration conditions" does sound very vague though. Any thoughts on why this would refer to drug delivery specifically? My interpretation of "administration conditions" would be anything from the polymer itself to how the patient is positioned i.e. whether they're lying down for an hour or whether they are are hanging them upside down for 10 minutes (not even joking with this).

I think someone posted a few weeks ago they were hiring an intern for drug delivery as well, it was in their job listings. It does seem like they are working on better delivery methods for the future.

 

[Jurger]

That's quite an eagle-eyed observation, I'm not sure that's been mentioned before. "Administration conditions" does sound very vague though. Any thoughts on why this would refer to drug delivery specifically? My interpretation of "administration conditions" would be anything from the polymer itself to how the patient is positioned i.e. whether they're lying down for an hour or whether they are are hanging them upside down for 10 minutes (not even joking with this).

We'd need more information on the study to be sure, but given that they've had multiple vacancies for drug delivery researchers in the recent past, I'm thinking the study is about drug delivery. I interpret that broadly by the way. It could be they're researching new gels, new ways other than intratympanic injection to get the drug into the cochlea, patient conditions etc.

 

[Diesel]

That's quite an eagle-eyed observation, I'm not sure that's been mentioned before. "Administration conditions" does sound very vague though. Any thoughts on why this would refer to drug delivery specifically? My interpretation of "administration conditions" would be anything from the polymer itself to how the patient is positioned i.e. whether they're lying down for an hour or whether they are are hanging them upside down for 10 minutes (not even joking with this).

On a positive note, this open-label study is why they might already have an idea of what the Phase 2A multi-dose outcomes look like. They've already multi-dosed people in this study. But, it looks like that disclosure was added in February 2021, so they could have just started.

 

[100Hz]

I had an Ultra High Frequency audiogram done and the results were more or less what I expected and also threw up a caveat I was hoping for. I'd like to share for analysis on one of the current theories (below).

@FGG @Diesel @Aaron91 @serendipity1996

This is an overview of my symptoms.

Standard audiogram is pretty normal to 8 kHz.

Extended audiogram reflects what I think is going on with my ears pretty accurately. An average of approx 10 dB lower for left ear across the range except for at 14 kHz. This 14 kHz left ear value is significant to me because the left ear tests were all dull in comparison to the right ear except for one range which I think was 14 kHz and was like a gun shot in my left ear at each volume increment (physically startling - this was the caveat I was hoping for, something going against the trend). I reckon this 14 kHz region is where my hyperacusis / noxacusis is.

I've got a few theories on it, this is the main one. It's apparent there is more ultra high frequency hearing loss in the left ear in general but if it was the 14 kHz range of tests for the left ear that was so much more startling (extra gain-like), it makes me think there's something different about the damage in this area and I wonder if this is something to do with increased ribbon count around this frequency (increasing the likelihood of type II action potential). I suppose it actually doesn't even matter where this startling frequency was, I'm just assuming it is 14 kHz as this is where the trend was bucked.

I unfortunately did not think to ask what that exact frequency was at the time and only thought of it after I'd started analyzing on the way home. I would put the frequency around 14 kHz though, up there but definitely not in the heights of the 16 kHz - 20 kHz range which were pretty obvious. I'm hopeful for FX-322 for noxacusis for this scenario to be able to restore these high frequency hair cells (apart from maybe one or two special factors).

 

[FGG]

We'd need more information on the study to be sure, but given that they've had multiple vacancies for drug delivery researchers in the recent past, I'm thinking the study is about drug delivery. I interpret that broadly by the way. It could be they're researching new gels, new ways other than intratympanic injection to get the drug into the cochlea, patient conditions etc.

Most likely, but it could also be something more left field like plugging up the Eustachian tube so it doesn't open up and drain in response to the middle ear fluid pocket.

Part of me did the have the thought a while ago that maybe a possible reason multiple injections would get more penetrance is it increases the odds of at least one with less drainage. Just thinking out loud, though.

 

[Diesel]

 

[patorjk]

That's quite an eagle-eyed observation, I'm not sure that's been mentioned before. "Administration conditions" does sound very vague though. Any thoughts on why this would refer to drug delivery specifically? My interpretation of "administration conditions" would be anything from the polymer itself to how the patient is positioned i.e. whether they're lying down for an hour or whether they are are hanging them upside down for 10 minutes (not even joking with this).

I interpret it to mean the conditions relating to how the shot is administered. So I don't think they're testing a new gel at this point. I've never had an intratympanic injection, but I would guess having someone lay on their side for a few hours vs having them get up right away could lead to different outcomes if the drug is draining out of the inner ear too fast. They could be doing this in preparation for Phase 3 so that they get the best outcomes for that trial.

 

[dd314]

View attachment 43973 View attachment 43974 View attachment 43975

Frequency Therapeutics' Twitter account has posted a lot about speech clarity and intelligibility in the last few months or so. I think we are going to see results with info that we pretty much already know. FX-322 restores hair cells in the EHF range, improves word scores, noise clarity, and a little improvement with noise loudness in 8 kHz and above.

I think they will pitch FX-322 as a compliment to hearing aids at this conference.

Or they barge in waving a magic drug that renders all hearing aids obsolete.

 

[FGG]

I interpret it to mean the conditions relating to how the shot is administered. So I don't think they're testing a new gel at this point. I've never had an intratympanic injection, but I would guess having someone lay on their side for a few hours vs having them get up right away could lead to different outcomes if the drug is draining out of the inner ear too fast. They could be doing this in preparation for Phase 3 so that they get the best outcomes for that trial.

That's a really good point. Phase 3 preparations make sense, too.

 

[Zugzug]

I had an Ultra High Frequency audiogram done and the results were more or less what I expected and also threw up a caveat I was hoping for. I'd like to share for analysis on one of the current theories (below).

@FGG @Diesel @Aaron91 @serendipity1996

This is an overview of my symptoms.

View attachment 43980

Standard audiogram is pretty normal to 8 kHz.

Extended audiogram reflects what I think is going on with my ears pretty accurately. An average of approx 10 dB lower for left ear across the range except for at 14 kHz. This 14 kHz left ear value is significant to me because the left ear tests were all dull in comparison to the right ear except for one range which I think was 14 kHz and was like a gun shot in my left ear at each volume increment (physically startling - this was the caveat I was hoping for, something going against the trend). I reckon this 14 kHz region is where my hyperacusis / noxacusis is.

View attachment 43978

I've got a few theories on it, this is the main one. It's apparent there is more ultra high frequency hearing loss in the left ear in general but if it was the 14 kHz range of tests for the left ear that was so much more startling (extra gain-like), it makes me think there's something different about the damage in this area and I wonder if this is something to do with increased ribbon count around this frequency (increasing the likelihood of type II action potential). I suppose it actually doesn't even matter where this startling frequency was, I'm just assuming it is 14 kHz as this is where the trend was bucked.

I unfortunately did not think to ask what that exact frequency was at the time and only thought of it after I'd started analyzing on the way home. I would put the frequency around 14 kHz though, up there but definitely not in the heights of the 16 kHz - 20 kHz range which were pretty obvious. I'm hopeful for FX-322 for noxacusis for this scenario to be able to restore these high frequency hair cells (apart from maybe one or two special factors).

You have a dip that looks like it's possible for FX-322 to help. It's interesting to me that 14 kHz was the most startling. Is it possible that your ears/brain was less caught by surprise at 16 kHz after already experiencing 14 kHz? Either way, with noxacusis, you are definitely someone that should be of interest to researchers. There should be a clinical trial for people with your audiogram.