Frequency Therapeutics — Hearing Loss Regeneration

[FGG]

Jesus Christ.

The more I read these kind of stories the more I'm wondering whether audiologists have an ulterior motive to see this drug fail.

Frequency Therapeutics should be in complete control of the process from start to finish otherwise we will never know where we stand.

I think she was saying this was just to get a baseline to apply for the trial, not that it happened during the trial.

I think if anything it's less that the audiologists are scheming (although anything is possible but these are testing center audiologists) and either:

1) Not calibrated or executed correctly. (One told me it's very hard to calibrate for the EHF and many don't have much experience with it and that it was an additional reason they don't like to do it separate from the hearing aid range).

2) the patients themselves may have had exaggerated their EHF losses to try to get more data points for a worse PTA for the trial. Knowing from long term medical records people lied about word scores makes this way more likely than it would otherwise seem.

3) the drug is just that much more selective in vivo for IHCs preferentially, which can't be measured on audiogram.

4) there is some serious in vivo issue with penetrance or activation in vivo.

 

[Diesel]

Another thought I had. The EHF audiogram is not standard. Almost no one has years of data on this in their medical record. Most people likely got it specifically to be in the trial. As a result, this could be faked (unfortunately).

The other thing, too, is that they strongly recruited for sudden hearing loss based on my interview in the main study arm (I won't reveal what they asked me specifically because revealing things like this is part of the problem). This group does not necessarily have worse EHF (many people only get mid range notches with acoustic trauma, for instance). So these measurements could mostly reflect exaggerated/faked selection data.

This is different than age-related hearing loss where there is a much stronger tendency for the EHF area to wear down first.

Interesting perspective, and insight. In the Phase 1/2, I believe it was about 50-50 for SSHNL + NIHL. I don't recall if specifically the data showed how either SSNHL v NIHL responded.

I'm going to continue to hold out for the Age-Related + Severe results to take any extreme position.

I would expect that the marketers / investor relations people at the firm are now considering how to ease investor / patient unrest. They're certainly getting feedback from institutions about transparency. Wouldn't surprise me if in April and on, they start offering monthly updates to gain some trust back.

 

[Diesel]

Maybe this is an absolutely nutty thing to say, but is it unreasonable to administer lie detecting tests with the hearing tests?

To be clear, the drug could have failed anyways. I'm not fully on the train of it only failed from lying. But this test seems, by nature, almost impossible to control without a test. If someone enrolls in the study, they are almost by default, desperate to get in and get the drug.

I would put a penalty in writing, that should a participant be detected as faking any tests, they will be required to reimburse Frequency Therapeutics + the providers for costs associated with the test. I bet many would think twice before signing a paper that shows they'll owe something like $50k if they get caught.

 

[Coleoptere]

What is Audion Therapeutics up to these days?

They had Regain (LY3056480) tested successfully in Phase 1 back in 2019.

It says on regainyourhearing.eu that they started testing (pre-COVID-19) whether the drug affects the ability to hear (= Phase 2?)

The clinical study was conducted at University College London, University of Tubingen and the University of Athens. After showing safety and tolerability of the GSI, 44 patients were treated in a study looking at efficacy of the drug. Efficacy results demonstrated improvements in performance in several hearing tests in up to 35 % of patients, warranting further product evaluation.

...and there it stopped...

 

[athan86]

Interesting perspective, and insight. In the Phase 1/2, I believe it was about 50-50 for SSHNL + NIHL. I don't recall if specifically the data showed how either SSNHL v NIHL responded.

I'm going to continue to hold out for the Age-Related + Severe results to take any extreme position.

I would expect that the marketers / investor relations people at the firm are now considering how to ease investor / patient unrest. They're certainly getting feedback from institutions about transparency. Wouldn't surprise me if in April and on, they start offering monthly updates to gain some trust back.

Trust is like glass. If it cracks, it is permanent. However, i really hope that they find the solutions.

 

[Zugzug]

I would put a penalty in writing, that should a participant be detected as faking any tests, they will be required to reimburse Frequency Therapeutics + the providers for costs associated with the test. I bet many would think twice before signing a paper that shows they'll owe something like $50k if they get caught.

I don't think it would have an impact. There needs to be a fundamentally different design. It's impossible to prove someone intentionally said "new" instead of "mew." The company would be bluffing as they would never pay the legal fees to push that lawsuit.

 

[HootOwl]

I think she was saying this was just to get a baseline to apply for the trial, not that it happened during the trial.

Yes, correct.

 

[FGG]

The clinical study was conducted at University College London, University of Tubingen and the University of Athens. After showing safety and tolerability of the GSI, 44 patients were treated in a study looking at efficacy of the drug. Efficacy results demonstrated improvements in performance in several hearing tests in up to 35 % of patients, warranting further product evaluation.

...and there it stopped...

Considering their drug depletes support cells (which are necessary long term for hair cell survival) to transduce to hair cells, I think the decision to halt further trials was more a safety one (i.e. the gains might be temporary and further degradation may happen). Audion wouldn't have halted the trial if it was just good news in a vacuum.

 

[NewLionel]

FREQ Stock Price Falls Over 70% Pre-Market: Why It Happened

Sounds like FREQ is moving forward with further tests and a single dosage strategy.

 

[TRAK]

For those of us that have been watching the stock price drop before the news, there's little doubt that info leaked.

You don't need to be an expert in finance to see that insiders were selling (you wouldn't execute all these trades if results were looking great).

When you have nearly 100 employees, it's impossible for everyone to keep quiet.

 

[FGG]

I don't think it would have an impact. There needs to be a fundamentally different design. It's impossible to prove someone intentionally said "new" instead of "mew." The company would be bluffing as they would never pay the legal fees to push that lawsuit.

Right. They would have to either rely on the severe patients who would have more extensive records generally and who couldn't fake word scores so easily and/or people who have years of EHF results.

If that anecdote from @Gb3 is correct, then maybe Frequency Therapeutics already suspects the severe arm will be more reliable?

 

[Jack Straw]

Not necessarily. When I did my word score testing I said "I'm not sure" at several points and then my audiologist increased the decibel level so that I could hear it more clearly. I didn't have to actually come up with a different word.

This was for qualifying though, I'm not sure how they operated the WR trial at the testing centers. But if your audiologist was testing like mine, then faking your way into the trial at least would not have been difficult.

Me and @Ed209 have discussed this type of issue in the past. Even if different audiologists are used, or different equipment, the results will vary. This can cause a skew in the overall data.

 

[HootOwl]

I'm still trying to square away these results with the phase 1 data, because this is all very confusing. I didn't expect phase 2a data to be astounding (I was almost certain penetrance would still be a problem) but to show no difference from placebo is so vastly different from the statistical differences presented in phase 1 is just very odd.

I know Diesel and FGG are mulling over preferential dispersement to IHC, but I wonder too if what we're seeing is a combination of fraudulent entry into the trial and the ceiling effect.

Didn't phase 1 have 4 or so non-responders because their losses were too mild and too low frequency? Could someone more knowing than me (and with better memory, damn this brain fog) help clarify?

 

[Tezcatlipoca]

Right. They would have to either rely on the severe patients who would have more extensive records generally and who couldn't fake word scores so easily and/or people who have years of EHF results.

If that anecdote from @Gb3 is correct, then maybe Frequency Therapeutics already suspects the severe arm will be more reliable?

I think this goes along with what I was trying to say the other day. We know that 1 injection works. Let them get it to market with the single dose regime and then finance further development with the revenue from that. We know it can work, at least theoretically. Let FREQ figure out how.

 

[RichieTheKid]

Artificial Cochlear Sensory Epithelium with Functions of Outer Hair Cells Mimicked Using Feedback Electrical Stimuli

Has anyone seen this?

 

[FGG]

For those unfamiliar with the recruitment process, the qualifying test is done through your own audiologist, then I believe a new baseline is conducted at the testing facility. But that first foot in the door is not standardized as far as I know.

Yep. This is correct.

 

[Jack Straw]

For those of us that have been watching the stock price drop before the news, there's little doubt that info leaked.

You don't need to be an expert in finance to see that insiders were selling (you wouldn't execute all these trades if results were looking great).

When you have nearly 100 employees, it's impossible for everyone to keep quiet.

If anyone is surprised that insider trading is rampant in the stock market, they shouldn't be in the market. The game is clearly rigged on some level because the SEC doesn't do shit about it. Look at the GME fiasco and it is a perfect example. Look at KODAK in June of 2020, right before the news came out of the merger there was MASSIVE stock purchasing and options. Surely the SEC would look into that because it is obviously insider trading right? WRONG! SEC is a joke and needs to actually step up and do something.

I am not surprised at all with the sell off prior to the news.

 

[annV]

I think this goes along with what I was trying to say the other day. We know that 1 injection works. Let them get it to market with the single dose regime and then finance further development with the revenue from that. We know it can work, at least theoretically. Let FREQ figure out how.

Actually no. The final phase 2a results in late Q2 this year will be the final nail in the coffin if they say there has been no improvement in tinnitus. That's what most of us here care about, not fixing a tiny bit of ultra high frequency hearing loss... If at Day 90 there was no tinnitus improvement, I doubt there will be at Day 210.

 

[Tezcatlipoca]

Actually no. The final phase 2a results in late Q2 this year will be the final nail in the coffin if they say there has been no improvement in tinnitus. That's what most of us here care about, not fixing a tiny bit of ultra high frequency hearing loss... If at Day 90 there was no tinnitus improvement, I doubt there will be at Day 210.

Well that sucks.

 

[Ed209]

This is literally life destroying news. Hopefully OTO-6xx comes through.

The odds were against this from the beginning. It reminds me of the discussions I had with JohnAdams, way back in the day, where I felt he was getting far too carried away and promising too much. He said some crazy stuff.

Over the years, we have seen many potential drugs come and go. It's not an easy problem to solve. The euphoria and optimism always tends to grow closer to the results being revealed, but people must remain realistic. It's not over for Frequency Therapeutics, by any means, but the results are kind of what I expected, which is why I didn't invest in it. It'll be a long hard road getting this into clinical use, but I truly hope they find a way. Patience is key.

This is why one should never convince themselves that something is the cure based on a preclinical compound. It's not a healthy state of mind to get yourself into, in my opinion.

 

[FGG]

Artificial Cochlear Sensory Epithelium with Functions of Outer Hair Cells Mimicked Using Feedback Electrical Stimuli

Has anyone seen this?

Interesting, looks like they could make a better cochlear implant with that.

 

[rei]

I hate to state a truism here but, failure is part of success.

I also think that the writing was on the wall the minute they started looking to hire a scientist to help developing a new delivery method/hydrogel.

The positive is that they'll be able to learn and design both better studies and delivery methods. The negative is the process will take longer than any of us want it to take.

I don't often comment here because I don't have much to offer to the conversation, but I give this thread a quick read everyday and I am very thankful for everyone's contributions. I have learned a lot and over this past year and I've learned to cope much better with my tinnitus largely because of Tinnitus Talk and this thread in particular has served as a wonderful distraction. If we were all standing in line waiting for a hearing/tinnitus drug, I'd let all of you get in line in front of me.

 

[Jack Straw]

Interesting, looks like they could make a better cochlear implant with that.

Isn't this similar to bimodal stimulation?

 

[Aaron91]

I'm still trying to square away these results with the phase 1 data, because this is all very confusing. I didn't expect phase 2a data to be astounding (I was almost certain penetrance would still be a problem) but to show no difference from placebo is so vastly different from the statistical differences presented in phase 1 is just very odd.

I know Diesel and FGG are mulling over preferential dispersement to IHC, but I wonder too if what we're seeing is a combination of fraudulent entry into the trial and the ceiling effect.

Didn't phase 1 have 4 or so non-responders because their losses were too mild and too low frequency? Could someone more knowing than me (and with better memory, damn this brain fog) help clarify?

Phase 1 indeed had non-responders in both the placebo group and the treatment group. The reason many of us were confident was because we still saw gains in the moderate/severe group. However, on reflection, the bears were right. You can't ignore the fact that there were far more potential responders in the treatment group than the placebo group. The argument being, the placebo group didn't respond the first time round to placebo because their baseline was much higher relatively speaking to the treatment group.

To put it simply: the hearing of the placebo patients was far better overall than of those who received FX-322.

Notice how there is only one circle to the left of the red line, whereas there are 6 diamonds. Many of us here didn't consider that a big deal, but the reality is that it was a very small sample size. It's possible if there were 5 more circles to the left of the red line, we would see some of them improve.

 

[Toby1972]

So, who again ridiculed my opinions? Please report back here again.

And that may sound esoteric when I posted yesterday that I have an inspiration, something is coming up...

Yes, yesterday there was a very important 50/50 decision in the private sector (which I could not influence) and it was negative. I had a feeling that this is related to something negative that occurs almost at the same time. Just this bad FX-322 news.

I tied my only hope of living a normal life to the FX-322.

 

[Jim Vasilakis]

So there has been no change in tinnitus whatsoever? Not even a tiny 5 dB change?

 

[rid0871]

They never had anything in the first place. Just a way to make a few people a couple of bucks. So sad.

 

[RichieTheKid]

Interesting, looks like they could make a better cochlear implant with that.

Artificial mixed with biologic may be the best way forward for now.

 

[Chinmoku]

Devastated. After all that has been said and done, we end up with nothing but WR improvements that cannot even be linked to EHF? Waiting 2+ years looked already impossible with these symptoms but I was trying, living one hour at a time. Now what?

I don't care much about the financial loss, I always viewed it as a gamble, I'll keep the position, but it's the lack of good news on treatment that is destroying me.

And people faking tests to enter the trial? WTF.

I can't hold on any longer.

...

 

[Aaron91]

So, who again ridiculed my opinions? Please report back here again.

And that may sound esoteric when I posted yesterday that I have an inspiration, something is coming up...

Yes, yesterday there was a very important 50/50 decision in the private sector (which I could not influence) and it was negative. I had a feeling that this is related to something negative that occurs almost at the same time. Just this bad FX-322 news.

I tied my only hope of living a normal life to the FX-322.

You were right, Toby, at least for now. Can I still have that beer though?