Frequency Therapeutics — Hearing Loss Regeneration

[brokensoul]

It's possible they could be going to JP Morgan for capital but the fact that Astellas financed them for $80m upfront and $525m as they face "commercial milestones" should be everything they need, even considering their new hiring for a superior gel formulation. Astellas Pharma is flush with cash, $11B in straight revenue in 2013.

Isn't the deal with Astellas for FX-322 alone?

 

[mrbrightside614]

Isn't the deal with Astellas for FX-322 alone?

Yup.

 

[FGG]

I hear what you're saying and both of you could be right, but at the moment I don't want to draw any speculative conclusions beyond the actual facts. This might create high expectations amongst some people here who don't look at the actual statement done by Chris Loose. Some people could be crushed if it turns out to be ineffective.

I think everyone should actually listen to the whole thing because tone matters too.

Here is the presentations page again:

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

 

[brokensoul]

Just look at the mess damage creates:

Even the "healthy" hair cells are no longer properly aligned.

 

[brokensoul]

I think everyone should actually listen to the whole thing because tone matters too.

Here is the presentations page again:

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

Fully agree on that.

Expected more discussion after I dropped the transcription on here.

 

[FGG]

Just look at the mess damage creates:

View attachment 36143

Even the "healthy" hair cells are no longer properly aligned.

Okay, but if clinically we find hearing and tinnitus improves does it matter if it's pretty?

In addition to what Pipeline told me when I asked that exact question and they said the regenerated outer hair cells (their drug only does outer and synapses) were phenotypically normal and were orientated correctly in the cochlea, we know hearing improved in FX-322 and it seems heavily implied that tinnitus did too imo so we can deduce that these details are perhaps not clinically meaningful.

The problem when you say "we should explore that", you mean "we should swap research papers" but we actually have clinical data starting to come out as to what this means functionally and in humans. I think clinical data >>>>>>> theoretical data.

Also images taken acutely may have zero to do with how tissue looks after inflammation subsides. Almost *all* these studies are acute. Let's look at clinical data of the drugs in trial to draw from instead.

Edit: sorry if I sound rude, I am just frustrated. We have actual phase 1 data with great results and it seems like people keep trying to find obscure papers detailing why things that are being shown to work already won't work. I shouldn't have directed that at you personally, @brokensoul, I think you have some great ideas.

Honestly, I think I spend way to much time on here and I need a break...

 

[HootOwl]

While it's not of scanning electron microscope quality, Sensorion has a picture on their site that shows even after widespread damage, the hair cells regenerated from their drug realign properly.

You could email them to ask about whether or not everything including the bundles are oriented properly but I think that's a needless rabbit hole. And this is a drug given acutely too so the regeneration and realignment would have to be near immediate, meaning that all that crazy damage you see in the Frequency Therapeutics pic would have to be sorted out rapidly.

So yeah, I'm not really worried about realignment really at all given the current clinical and research data we have (thanks Dan for answering our emails so quickly haha).

 

[Ben S]

Okay, but if clinically we find hearing and tinnitus improves does it matter if it's pretty?

In addition to what Pipeline told me when I asked that exact question and they said the regenerated outer hair cells (their drug only does outer and synapses) were phenotypically normal and were orientated correctly in the cochlea, we know hearing improved in FX-322 and it seems heavily implied that tinnitus did too imo so we can deduce that these details are perhaps not clinically meaningful.

The problem when you say "we should explore that", you mean "we should swap research papers" but we actually have clinical data starting to come out as to what this means functionally and in humans. I think clinical data >>>>>>> theoretical data.

Also images taken acutely may have zero to do with how tissue looks after inflammation subsides. Almost *all* these studies are acute. Let's look at clinical data of the drugs in trial to draw from instead.

Edit: sorry if I sound rude, I am just frustrated. We have actual phase 1 data with great results and it seems like people keep trying to find obscure papers detailing why things that are being shown to work already won't work. I shouldn't have directed that at you personally, @brokensoul, I think you have some great ideas.

I really agree with you that FX-322 is promising, however, the speech in noise test for me doesn't seem to reflect with real-life hearing in noise. I have aced plenty of these online tests and yet my hearing in noise and in other environments is pretty garbage. I believe that my synapses have been annihilated (FX-322 probably won't help me with that). Granted, I'm sure clinical speech in noise tests are more thorough and precise, but it still worries me. Hopefully patient testimonials will say that they have seen real-life improvements, and not just in clinical testing.

 

[Diesel]

I'll jump on this carousel with my opinion:

During the Phase 1/2, if any patient reported an increase in their tinnitus symptoms (loudness or frequency), it would have certainly been identified as a serious safety concern, regardless of hearing improvement. The trial would have ended there.

So we can deduce that FX-322 likely didn't make tinnitus worse. The last thing you'd want in a hearing regenerative drug an ototoxicity side-effect of some degree.

I offer three scenarios (could be multiple choice):

Scenario A: Testimonials/Qualitative Feedback
As @FGG mentioned a few pages back, they probably had access to patient testimonials. It is reasonable that one or more patients mentioned that their tinnitus got quieter, reduced in frequency, or even went away. Without any way to quantify this data, especially without a baseline, they chose to add it to Phase 2A.

Scenario B: Feedback
Frequency has mentioned more than once that they continue to review their data and PCA model with ENTs and Audiologists; especially in gathering feedback for modeling the Phase 2 trial. This was mentioned in the November webcast (which isn't on the site). Perhaps tinnitus was at the top of the list?

Scenario C: Marketability - Frequency needs to make money on its investment.
Although FX-322 data so far indicates that it likely can improve hearing at high frequencies; It is highly likely that if this version 1.0 makes it into the market, it will not regenerate hearing at all ranges. This presents a marketing challenge. How do you market a product that is only does half a job? You gather data on alternative selling points! It would make good business sense for the product to be marketed with claims of XX% reduction in tinnitus symptoms. In the event that its a hard sell initially as a hearing restoration drug (because it won't fully do that), it may be really good at generating cash as a NIHL/SNHL tinnitus reduction drug until they get the gel formulation/full cochlea delivery figured out.

Just my $.02.

 

[MrCrybaby]

Hi guys, I strongly agree with what @FGG has said.

The goal is not to have beautiful, perfect, new-born-baby cochlea. We don't need our ears to be the neurological equivalent of a play boy bunny. We just need them to work.

If you have been to fireworks show, take the train every day, have stood near a construction site in the city while waiting for a bus, or been to a concert you have damage to your cochlea.

Please stop picking apart these images of stained rat cochlea under an electron microscope like you have cochlear body dysmorphia. If I showed you a good and bad cochlea side by side they'd probably look identical to the naked eye. Even if my new hair cells aligned to spell out "Epstein didn't kill himself" I'd be happy if my tinnitus and hyperacusis improved. Isn't that what we /actually/ want?

I feel like this is turning into the "reasons FX-322 will never work and we're all doomed forever" thread. Even if the neurons and stria and brain are messed up there is literally no signal without a hair cell. It will definitely improve things even if it doesn't fully fix you because nothing else matters without it. Barring conductive loss of course. This is a hair cell drug. If your prime obsession is a supermodel perfect cochlea with not a cell out of place leave this thread behind and look at Chen's work.

Also, be wary of totally irrelevant studies. This is not a stem cell treatment, it never has been. That paper proves that stem cells are a scam for tinnitus, which we already knew. Clinically.

I get it though, life is rough. All we can do now now is wait patiently like cats for our food bowl to be filled with study data from frequency. Until then we're just being back seat scientists. Frequency Therapeutics knows what they're doing. They have investors to please and they have a kick butt drug and we've just got to wait for the good word. Until then, try not to get stressed about it. I love you all and I believe in you, you can make it through the wait!

 

[Serouj]

Will phase 3 be global?

 

[Lucifer]

Will phase 3 be global?

Maybe depending on a few things such as positive results for Phase 2a, getting Breakthrough Therapy status approved by the FDA and if it goes directly to Phase 3.

If it's global it will be run by Astellas and who knows which locations they will operate at.

 

[d'Wooluf]

If it's global it will be run by Astellas and who knows which locations they will operate at

They're a Japanese company and the Japanese government has indicated that it wants to facilitate research in regenerative medicine (I posted something a while back) so my guess would be...

 

[Lucifer]

They're a Japanese company and the Japanese government has indicated that it wants to facilitate research in regenerative medicine (I posted something a while back) so my guess would be...

That's great news. Would this mean FX-322 gets released quicker in Japan?

 

[all to gain]

I'm moving to Japan.

 

[d'Wooluf]

Would this mean FX-322 gets released quicker in Japan?

I think it's possible.

 

[Pink Noise]

I'm moving to Japan.

Same.

 

[Danad]

Hello, new to Tinnitus Talk and wanted to jump in on this. After flying navy jets off carriers for 8 years I had about a 40 dB shift above 4000 Hz but no tinnitus. Attended a concert in 2017 (with earplugs) and voila, here I am. Mine is narrow band noise between 7 kHz and 11 kHz, which sometimes resolves to a tonal sine wave. I get total residual inhibition (lasting about 10 sec) when listening to the same generated sound.

After exhaustive research it was apparent that SNHL induced tinnitus could only be reversed with hearing restoration and things did indeed seem bleak. The vast majority of studies indicate that when missing frequencies are restored tinnitus subsides when the hearing loss is temporary such as with earwax. IMHO FX-322 will indeed do that for tinnitus above a range of 3-5 kHz with a high degree of probability. (The naysayers are cracking up now).

Two things are very obvious:
1. money talks and the infusion of capital into Frequency Therapeutics is beyond speculative.
2. Adding tinnitus to the secondary outcomes would not have happened unless the previous trial indicated a trend benefit.

Below is an audio file snippet from their last Q&A:

 

[all to gain]

Hello, new to Tinnitus Talk and wanted to jump in on this. After flying navy jets off carriers for 8 years I had about a 40 dB shift above 4000 Hz but no tinnitus. Attended a concert in 2017 (with earplugs) and voila, here I am. Mine is narrow band noise between 7 kHz and 11 kHz, which sometimes resolves to a tonal sine wave. I get total residual inhibition (lasting about 10 sec) when listening to the same generated sound.

After exhaustive research it was apparent that SNHL induced tinnitus could only be reversed with hearing restoration and things did indeed seem bleak. The vast majority of studies indicate that when missing frequencies are restored tinnitus subsides when the hearing loss is temporary such as with earwax. IMHO FX-322 will indeed do that for tinnitus above a range of 3-5 kHz with a high degree of probability. (The naysayers are cracking up now).

Two things are very obvious:
1. money talks and the infusion of capital into Frequency Therapeutics is beyond speculative.
2. Adding tinnitus to the secondary outcomes would not have happened unless the previous trial indicated a trend benefit.

Below is an audio file snippet from their last Q&A:

I would hate to be those men who stand on the deck top when the jets take off. They must all have tinnitus, at the very least, surely.

 

[Tweedleman]

IIRC isn't one of the OTO or PIPE drugs already able to reach the apex? If they can then would FX not eventually be able to do the same?

Would a subsequent formulation of FX require an entirely fresh round of these protracted clinical trials? Or could it hit the market faster on the basis of 1.0 already being approved?

 

[FGG]

I really agree with you that FX-322 is promising, however, the speech in noise test for me doesn't seem to reflect with real-life hearing in noise. I have aced plenty of these online tests and yet my hearing in noise and in other environments is pretty garbage. I believe that my synapses have been annihilated (FX-322 probably won't help me with that). Granted, I'm sure clinical speech in noise tests are more thorough and precise, but it still worries me. Hopefully patient testimonials will say that they have seen real-life improvements, and not just in clinical testing.

They did word score, not speech in noise for phase 1. They added speech in noise as an additional measure in phase 2.

 

[GlennS]

I would hate to be those men who stand on the deck top when the jets take off. They must all have tinnitus, at the very least, surely.

People who work on the tarmac at a normal airport all wear those old-school headphone looking things. Wouldn't the same be true on an aircraft carrier? I'm not saying you wouldn't wind up getting exposed to noise eventually regardless but I can't imagine they're out there completely unprotected.

 

[Danad]

Well that was a problem since in addition to flying, I stood duty as a Landing Signal Officer (LSO) grading pilot's landings and occasionally waving off the unsafe approaches. Every aircraft that landed would go full power anticipating a missed wire (bolter) and that would just rattle your insides. That set the groundwork for the tinnitus 20+ years later. Many of my fellow LSOs acquired hearing loss/tinnitus.

 

[Diesel]

They did word score, not speech in noise for phase 1. They added speech in noise as an additional measure in phase 2.

They did do words-in-noise in Phase 1. Page 28 of the January 2020 presentation deck.

 

[Danad]

Maybe these were already posted previously, below are 2 discussions from co-founders of Frequency Therapeutics and they suggest that hearing restoration translates to tinnitus suppression:

 

[Momme]

They did word score, not speech in noise for phase 1. They added speech in noise as an additional measure in phase 2.

FGG I got my results.

Will FX-322 help my tinnitus? What do the results tell you?

 

[FGG]

They did do words-in-noise in Phase 1. Page 28 of the January 2020 presentation deck.

I had forgotten that, thanks.

 

[FGG]

FGG I got my results.

Will FX-322 help my tinnitus? What do the results tell you?

You have some OHC damage. FX-322 will help with that at least.

 

[all to gain]

Well that was a problem since in addition to flying, I stood duty as a Landing Signal Officer (LSO) grading pilot's landings and occasionally waving off the unsafe approaches. Every aircraft that landed would go full power anticipating a missed wire (bolter) and that would just rattle your insides. That set the groundwork for the tinnitus 20+ years later. Many of my fellow LSOs acquired hearing loss/tinnitus.

How loud was it in dB? How loud was it in the cockpit when flying? What aircraft were you flying? Super Hornets?

People who work on the tarmac at a normal airport all wear those old-school headphone looking things. Wouldn't the same be true on an aircraft carrier? I'm not saying you wouldn't wind up getting exposed to noise eventually regardless but I can't imagine they're out there completely unprotected.

Believe it or not, but where I am they don't all wear hearing protection. Only one of the ground crew was wearing ear muffs for my last flight, and when he saw me wearing some he was very surprised.

I can't see even the best hearing protection in the world doing much for those guys on aircraft carriers. They are right next to the aircraft.

In this video it doesn't look like even all of the LSOs have hearing protection:



And look how loud the aircraft are on take off:

 

[Joeseph Stope]

I seem to have stumbled onto this site at a very gripping and compelling time for inner ear problems.

The docs can now access the cochlea and they are trying to do a repair job by imitating nature.