Frequency Therapeutics — Hearing Loss Regeneration

It's real

 

So I won't be helped then? I can only hear up to 12,000 Hz so far. According to the graph, shouldn't I be able to be helped with FX-322?

As for the rest of your post, based on what you're saying, do you believe that Susan Shore would not adequately fix tinnitus? I actually have the opposite opinion from you. I believe that there are more possibilities of failure from this approach than from Susan Shore's (which aims to directly meddle with the neurons causing the tinnitus).

Frequency Therapeutics' approach can certainly fix and eliminate hearing loss and that would be an achievement but I struggle to believe that this would eliminate tinnitus in every case. The source of tinnitus is in those overactive neurons; not everyone with SNHL has tinnitus. Subduing those connections seems like a better way forward (and far more cheaper too) than eliminating hearing loss.

Once again, there is a possibility that what you suggest could eliminate some people's noise-induced tinnitus. But I don't think it's something that can consistently remove tinnitus. I believe (may be wrong) that, after a while, tinnitus becomes centralized in the brain. As a result, only a neurological solution would help with that.

By the way, feel free to correct me on anything I say. I am still learning.

Yeah this is why my tinnitus is annoying. Everything sounds so muddled (at least in comparison to before) to the extent that I can't even properly hear rain. As a result, despite my tinnitus being objectively quieter than I think a majority of people's tinnitus, I can still hear it because my hearing has degraded to the degree that it has.

 

Why would you believe that FX-345 could reach that far back but not Otonomy? How are they expecting to reach that far back?

Also for Otonomy, I believe they patented the way they were going to reach that deep so I think that counts for something. Its drug delivery is not based on the drug itself. I don't have good information on the topic so I could be wrong. Maybe you know about this and have a response?

 

I want Otonomy to show evidence. I can't believe their gel actually penetrates the entire cochlea just because they have a patent. Why is it just a claim? Do they have evidence from clinical trials?

I think there was a patent that FX-322 also reached 4 kHz. But it didn't actualize.

 

I believe FX-322 can reach at least 8 kHz. This is due to the fact that a few of the patients in the Phase 1b trials had improvements in their audiograms at 8 kHz.

Anything lower than 8 kHz may require FX-345.

 

Speaking of audiograms, to what degree were there improvements at 8 kHz? Is it to the level of "normal" hearing? I guess that depends on the actual amount of damage within the cochlea but I am still interested in knowing.

 

Slide P33 in October 2019.

It was an improvement of 10 dB or more. In a slide created after this, probably one year later, one of the four had an improvement of 15 dB.



P22 on the same slide.

They said it would reach up to 4 kHz. 4 kHz is the area where noise first attacks and destroys hair cells. With FX-345 they aim to reach deeper than 4 kHz.

 

Thank you for your time!

How does this compare with normal hearing?

 

Unfortunately, I only know that it has improved by 10 dB or more. These four people seemed to be the same people with moderate hearing loss with significantly improved word recognition. It was announced that these four people had moderate hearing loss.

But, I think there may be people with mild hearing loss who improve to "normal hearing" at 8 kHz, if FX-322 can be cumulatively effective with multiple injections at appropriate intervals. Even if a single injection only provides an improvement of 5 dB.

 

So does that mean "it didn't reach levels of normal hearing" or "I don't know if it reached levels of normal hearing"?

Also how does that work? How can it be cumulative? It's not like you'll end up with extra regenerated hair cells.

By the way, do the progenitor cells disappear after regeneration or do they remain (so, for instance, if your regenerated hair cells got damaged, could you get the treatment again)? Because, according to the Tinnitus Talk Podcast interview, Frequency Therapeutics' approach to hair cell regeneration is to make use of progenitor cells which stem cell therapy destroys.

Furthermore, what do you know about the recent reports that those administered FX-322 reported changes after the trials were done?

 

FX-322 induces an asymmetrical division of cells creating both a new hair cell and a new progenitor cell.

 

Slide P28 from March 2021:

 

The most important metric I think people here are looking at is a reduction in tinnitus severity, something that neither WR scores or audiograms give us, but between the two, improved high frequency hearing would logically have a stronger correlation.

 

What do you think is the reason why TFI was not published in Phase 2a?

1) It really didn't work.
2) Since there were many improvements in placebo, it could not be said that it was effective in comparison.
3) There was improvement in the medication group, but because there were many improvements in placebo due to improvement in word recognition and high frequency, the reason (correlation) could not be found and they could not publish it.
4) Something else.

 

1.

 

I doubt they are hiding good news.

Considering that Neuromod released data to suggest their treatment worked and it really doesn't, I now have a pretty big barrier before I get onto the hype train.

 

I feel like it could be 3.

We did hear some anecdotes from Carl LeBel that there were tinnitus improvements in some patients. We should know more by the end of this year with the single dose Phase 2b trial.

 

Wasn't that only after the initial safety trial though with a handful of patients? Since then there had been no mention of tinnitus? Or did I miss some other news?

I just cannot fathom that they wouldn't say "hey you know what, during our trials we had a few folk who reported an improvement in their tinnitus."

How would that take away from anything or muddy the waters? Surely it would just be a positive signal. I really want there to be some hope and positive news from any of these drugs, I really do, but after speaking to a community of patients, i.e. Tinnitus Talk Podcast, prior to the trials and knowing how much some people need hope to cling onto holding back any sort of positive feedback would seem unusually cruel?

 

This was the Phase 1b trial with a single dose of FX-322 that saw some patients with lower tinnitus level so hopefully the Phase 2b trial has similar outcomes to Phase 1b.

 

They state that Phase 2a could not confirm the effect of the drug for at least two reasons. One is the unusual effect of placebo and the other is multiple injections per week.

In addition, I think that the short-term multiple injections that inhibited the effect also include placebo injections.

I think Phase 2b without these two points may give the same result as Phase 1b.

 

That was not in their data. It was anecdotal reports. Are we just making stuff up now?

 

Was TFI a survey item in Phase 1b?

Since there was an anecdote about improving tinnitus, wasn't it adopted as a survey item in Phase 2a?

Originally, FX-322 is a drug whose purpose is not to improve tinnitus but to restore hearing.

 

I think some patients had improvements in Phase 1b so they decided to add it into Phase 2a but now they will redo the trial again with the single dose of FX-322 in Phase 2b which should give similar results to Phase 1b but with more patients.

 

Frequency Therapeutics to Present 2022 Business and Pipeline Overview at the 40th Annual J.P. Morgan Healthcare Conference

Company to Review Milestones for its Phase 2b Study of FX-322, the Near-Term Clinical Plan for its Second Hearing Restoration Asset, FX-345, and Selection of a Lead Candidate for its Novel Multiple Sclerosis Program that Has Shown Potent Pre-Clinical Data

 

40th Annual J.P. Morgan Healthcare Conference

Has anyone had a look at the video yet? Did they say anything that hasn’t been stated yet such as more information about the severe hearing loss trial results or the current Phase 2b trial?

 

I listened to most of it. More of the same. Focused on word recognition again. No mention of actual hearing improvement or tinnitus.

 

Word recognition improvement = actual hearing improvement.

 

Thought so. I did look at the presentation slides and with the severe hearing loss trial the information was the same as the last presentation slides for it.

Only thing that I thought might be new is mentioning that they will finish dosing participants for the Phase 2b trial in Q3/2022 and release results in Q4/2022 or Q1/2023 and if the phase is successful they will move on to the pivotal phase.

 

Ah, keep telling yourself that. I have 45-50 WRS and I can’t hear shit out of my left ear.

 

Seems not great news from Frequency Therapeutics. If they are not able to recover that much of the hearing, there is no hope for us with tinnitus, right?

Maybe this may help people with very mild hearing loss.