Frequency Therapeutics — Hearing Loss Regeneration

[100Hz]

I come down to this binary: either some hearing got fixed or multiple Phase 1 patients lied dramatically about word scores (not just a little) for some unknown reason. I don't see any other choice. The placebo effect doesn't give you results that have historically been impossible.

Yes, and not just lied dramatically but also happened to ALL get into the non-placebo group, right?

I'm really hoping that there are zero responders in the Phase 1b placebo groups, not a single one (along with continued improvement in WR scores for FX-322 groups of course). The likelihood that in all 3 trials there would be people dramatically bluffing their way into trials and ALL ending up in non-placebo groups seems very, very, unlikely. Unless something very sinister is going under the surface.

 

[FGG]

Yes, and not just lied dramatically but also happened to ALL get into the non-placebo group, right?

I'm really hoping that there are zero responders in the Phase 1b placebo groups, not a single one (along with continued improvement in WR scores for FX-322 groups of course). The likelihood that in all 3 trials there would be people dramatically bluffing their way into trials and ALL ending up in non-placebo groups seems very, very, unlikely. Unless something very sinister is going under the surface.

Right. Regardless of the recent trials, multiple Phase 1 participants did something that has historically not been possible with placebo effect: they doubled their word scores.

So unless *those* patients artificially deflated their word scores there are at least some super responders. If it happens to correspond to no EHF changes in the remaining arms, then some hearing effect unrelated to OHCs is happening and the only one that makes any sense to me would be if IHC repair happens on "first pass" but multiple injections can be damaging if spaced too close in time together.

If the drug truly doesn't work, Phase 1 participants would have to have deflated their word scores for a completely unknown reason (it wasn't a requirement for Phase 1) or they were somehow "plants" which calls the whole company in question (I really don't believe this with the long term reputations of those involved).

Otherwise some people are "super responders" beyond what could reasonably be explained by placebo so the drug has a hearing effect in some way for that population.

 

[GlennS]

Word score hearing did above a range that can't be reasonably attributed to placebo but no significant audiogram changes at the group level at least (which measure OHCs only).

This is where I get off the hype bus.

What other real metric is there to measure hearing? If the audiogram isn't improving, then their hearing isn't really improving, not in a way that would matter for most of us.

I don't want to be confrontational but all this talk of OHC vs. IHC sounds like bargaining to me.

A successful trial would mean significant word score increases over placebo.

A successful trial would mean significant audiogram improvement. The audiogram is the real red flag here.

 

[dd314]

How many times have we been here before?

A drug, a treatment, shows nothing much more than a hint of promise and then there appears to be some kind of anticipatory euphoria, probably whipped up by those with much to gain from an investment programme, and people start to throw their hard earned money at it.

My suggestion would be to let the doctors, scientists, big pharma get on with doing their job, while us sufferers explore more deeply what is available to us in the form of coping methods, deep relaxation, meditation, etc. without resorting to the psychologically damaging practice of 'cliff-hanging,' and the subsequent disappointment and despair that inevitably follows.

It is a sobering thought that in 200,000 years of human habitation on this planet, (some evangelical groups reduce that down to a mere 10,000 years of course), no agency has ever come up with anything to reduce the noise level of tinnitus by as much as one solitary decibel.

Time to just cool it, relax, meditate etc... in my humble opinion.
To put it in some context, I have suffered, and I do mean 'suffered' for over 30 years of my life.

Dave x
Jazzer
(the video man)

I disagree. I think staying on top on biomedical research is a good idea.

I donated money to The Bionics Institute recently and I never would have known they existed if I hadn't been keeping up with the news.

It's worth acknowledging that FX-322 clearly works when participants aren't lying about their word scores and multiple injections aren't mucking up people's middle ear passage.

 

[FGG]

This is where I get off the hype bus.

What other real metric is there to measure hearing? If the audiogram isn't improving, then their hearing isn't really improving, not in a way that would matter for most of us.

I don't want to be confrontational but all this talk of OHC vs. IHC sounds like bargaining to me.

A successful trial would mean significant audiogram improvement. The audiogram is the real red flag here.

There isn't a good other metric unfortunately and audiograms only measure OHCs.

But you have to admit it's noteworthy that some super responders in Phase 1 did something that has been historically impossible (doubling word scores).

I don't know that it's IHCs for sure obviously but it's my guess based on this being a hair cell drug, there being many more LGR5+ cells around IHCs and them developing first embryologcally. It could be synapses for all I know but it would be weird that speech in noise didn't do as proportionally well.

The only explanation for the drug actually doing nothing at all but doubling word scores in Phase 1 is patient or company fraud. And I'm in the camp that doesn't buy that at this point.

 

[GBB]

There isn't a good other metric unfortunately and audiograms only measure OHCs.

But you have to admit it's noteworthy that some super responders in Phase 1 did something that has been historically impossible (doubling word scores).

I don't know that it's IHCs for sure obviously but it's my guess based on this being a hair cell drug, there being many more LGR5+ cells around IHCs and them developing first embryologcally. It could be synapses for all I know but it would be weird that speech in noise didn't do as proportionally well.

The only explanation for the drug actually doing nothing at all but doubling word scores in Phase 1 is patient or company fraud. And I'm in the camp that doesn't buy that at this point.

I also agree that there is no fraud. Anyone who insists there is is a conspiracy theorist imo. Most of management were already comfortable in life, and some were independently wealthy and approaching retirement.

 

[HootOwl]

I don't know that it's IHCs for sure obviously but it's my guess based on this being a hair cell drug, there being many more LGR5+ cells around IHCs and them developing first embryologcally.

I wonder if needing the IHC to be regenerated first is due to the specifics of the progenitor activation pathway. Perhaps because it works similar to how hair cells develop in-utero. Without the signal from the IHC, the OHC can't form. I wish it was possible to watch regeneration in real time from mice explants. I'd be interested to see what actually regenerates first.

We know this pathway is different from Notch inhibition, and Notch inhibition allows for OHC regeneration without IHC regeneration (what Pipeline is doing). So it could be a pathway issue.

 

[GlennS]

There isn't a good other metric unfortunately and audiograms only measure OHCs.

Wut? Audiograms measure hearing. A tone goes in and either you hear it or you don't. What do you see people often post here? Audiograms. Audiograms document hearing loss. An improved audiogram would verify restoration of hearing. An unchanged audiogram would point to no restoration of hearing in any real-world sense, regardless of any partial structural changes that may have still taken place in the cochlea. And that's what matters--end results. (Now, I guess it's possible tinnitus would subside even without restoring hearing at tinnitus frequencies but I seriously doubt it.)

As far as word scores, they are going to be highly variable because of how it's possible to guess. When I got my testing done in many cases I was reaching for a guess because I knew some of the consonants were hard to distinguish. The brain is a very good guessing machine which is why it's been proven that you can read text riddled with typos. Measuring your hearing individually tone by tone is far far more revealing.

So I think all this talk of OHC vs. IHC is getting lost in the weeds and not seeing the big picture.

 

[FGG]

Wut? Audiograms measure hearing. A tone goes in and either you hear it or you don't. What do you see people often post here? Audiograms. Audiograms document hearing loss. An improved audiogram would verify restoration of hearing. An unchanged audiogram would point to no restoration of hearing in any real-world sense, regardless of any partial structural changes that may have still taken place in the cochlea. And that's what matters--end results. (Now, I guess it's possible tinnitus would subside even without restoring hearing at tinnitus frequencies but I seriously doubt it.)

As far as word scores, they are going to be highly variable because of how it's possible to guess. When I got my testing done in many cases I was reaching for a guess because I knew some of the consonants were hard to distinguish. The brain is a very good guessing machine which is why it's been proven that you can read text riddled with typos. Measuring your hearing individually tone by tone is far far more revealing.

So I think all this talk of OHC vs. IHC is getting lost in the weeds and not seeing the big picture.

OHCs increase loudness, IHCs affect clarity. The audiogram doesn't test for how faithfully you hear the beep, just that you hear it. This is why it is a reliable test for OHCs only.

 

[Zugzug]

Sorry, I was just recovering from grief and shock.

I wish someone could explain which of the ongoing studies has got the trial design fixed (without fakes and cheaters)?

View attachment 44258

Which of the studies got the trial design fixed:

FX-322-111
FX-322-202
FX-322-112
FX-322-113

Are they all with trial design flaws, and no proper, accurate hearing tests?

Another question, FX-322-111 study showed 10% improvement which is not an accurate and real improvement, so why are we hoping for better results from FX-322-202 & FX-322-112?

As a side note, I hold Frequency Therapeutics accountable for this pure gross negligence.

Here's what has me concerned. Although we can probably assume that Phase 2a has the most discrepancies (although I don't think it amounts to that much), there is at least some motivation for Trial FX-322-111 as well. Hopefully, it is less for FX-322-112 and FX-322-113 since I would think older people and people with actual severe audiograms would be less likely to lie. Who knows though?

Anyways, besides the fact that there weren't audiogram changes, even the WR improvements are pretty underwhelming in open-label FX-322-111. Keep in mind that it was not placebo controlled so if there were people that deflated their baseline scores, there wouldn't be a counterbalance effect; it would simply help the results.

To only see 34% improve WR by >=10% is really not that good at all under these circumstances. I guess we could see super responders in the severe group (I predict this will be the best trial), but it's not going to override the other failures.

Let's just call it straight: Phase 2a was a disaster. All of this talk about working towards pivotal is just corporate speak. There's no doubt they will have to redo Phase 2.

The science is real though and this stuff about company fraud or whatever is total, emotional overreaction nonsense. Occam's razor says that we are trying to achieve a breakthrough in science and ran into natural speedbumps.

There is still reason to believe that there will be a treatment for hearing loss, but it simply got pushed back in the timeline.

 

[HootOwl]

Wut? Audiograms measure hearing. A tone goes in and either you hear it or you don't. What do you see people often post here? Audiograms. Audiograms document hearing loss. An improved audiogram would verify restoration of hearing.

I recommend reading this. Keep in mind, as FGG has said, audiograms do not measure IHC loss. The article is mostly focused on synaptopathy, but it has several very important points regarding the function of IHC:

"About 95 percent of sound input to the brain comes from the ear's inner hair cells."

"These inner hair cells are like spark plugs in an 8-cylinder engine," says Salvi. "A car won't run well if you remove half of those spark plugs, but people can still present with normal hearing thresholds if they've lost half or even three-quarters of their inner hair cells."

I don't think the IHC theory is too far fetched. In fact, in the absence of additional data (which we will get from the full readout in June) it strikes me as a pretty good fit.

 

[GlennS]

OHCs increase loudness, IHCs affect clarity. The audiogram doesn't test for how faithfully you hear the beep, just that you hear it. This is why it is a reliable test for OHCs only.

From an academic perspective it might be useful to know if the drug helps part of the audio system but if it doesn't reduce tinnitus symptoms it's still a bust.

 

[FGG]

Here's what has me concerned. Although we can probably assume that Phase 2a has the most discrepancies (although I don't think it amounts to that much), there is at least some motivation for Trial FX-322-111 as well. Hopefully, it is less for FX-322-112 and FX-322-113 since I would think older people and people with actual severe audiograms would be less likely to lie. Who knows though?

Anyways, besides the fact that there weren't audiogram changes, even the WR improvements are pretty underwhelming in open-label FX-322-111. Keep in mind that it was not placebo controlled so if there were people that deflated their baseline scores, there wouldn't be a counterbalance effect; it would simply help the results.

To only see 34% improve WR by >=10% is really not that good at all under these circumstances. I guess we could see super responders in the severe group (I predict this will be the best trial), but it's not going to override the other failures.

Let's just call it straight: Phase 2a was a disaster. All of this talk about working towards pivotal is just corporate speak. There's no doubt they will have to redo Phase 2.

The science is real though and this stuff about company fraud or whatever is total, emotional overreaction nonsense. Occam's razor says that we are trying to achieve a breakthrough in science and ran into natural speedbumps.

There is still reason to believe that there will be a treatment for hearing loss, but it simply got pushed back in the timeline.

I don't think older people are any more or less reliable than younger people but the data from the severe group is what I'm watching now.

 

[Jazzer]

I feel like a spectator at a wild goose chase.

I'll maintain my composure and await the resultant conclusion, just as I did with all of the other projected miracle cures, like 'MuteButton,' and Bi-Modal Stimulation.'

Must go - meditation calls... xx

 

[FGG]

From an academic perspective it might be useful to know if the drug helps part of the audio system but if it doesn't reduce tinnitus symptoms it's still a bust.

LeBel said there were anecdotes. At least enough to add it to Phase 2. Unless you don't believe him, would it matter what structure got fixed if it could help?

 

[HootOwl]

Let's just call it straight: Phase 2a was a disaster. All of this talk about working towards pivotal is just corporate speak. There's no doubt they will have to redo Phase 2.

This is what really, truly hits me. My worst case scenario was that Phase 2 would show the same benefits from Phase 1, with no real additional improvements. And that Frequency would try to move full steam ahead with the efficacy shown from Phase 1/2, get to market, and then go balls to the wall on reformulation.

I never predicated that the whole phase would be bricked. It just feels awful.

 

[Zugzug]

This is what really, truly hits me. My worst case scenario was that Phase 2 would show the same benefits from Phase 1, with no real additional improvements. And that Frequency would try to move full steam ahead with the efficacy shown from Phase 1/2, get to market, and then go to balls to the wall on reformulation.

I never predicated that the whole phase would be bricked. It just feels awful.

Same. My worst case scenario was that additional doses would do literally nothing and that the treatment vs placebo comparisons would be a mixed bag of statistically meaningful improvements.

In Phase 1/2, the only test where group average differences weren't significant was PTA. And obviously, the prize of Phase 1/2 were the super responders.

I think it's at least fair to wonder if those responders deflated their word scores. Even at least some of the 3 rock stars.

 

[Ed209]

How many times have we been here before?

A drug, a treatment, shows nothing much more than a hint of promise and then there appears to be some kind of anticipatory euphoria, probably whipped up by those with much to gain from an investment programme, and people start to throw their hard earned money at it.

My suggestion would be to let the doctors, scientists, big pharma get on with doing their job, while us sufferers explore more deeply what is available to us in the form of coping methods, deep relaxation, meditation, etc. without resorting to the psychologically damaging practice of 'cliff-hanging,' and the subsequent disappointment and despair that inevitably follows.

It is a sobering thought that in 200,000 years of human habitation on this planet, (some evangelical groups reduce that down to a mere 10,000 years of course), no agency has ever come up with anything to reduce the noise level of tinnitus by as much as one solitary decibel.

Time to just cool it, relax, meditate etc... in my humble opinion.
To put it in some context, I have suffered, and I do mean 'suffered' for over 30 years of my life.

Dave x
Jazzer
(the video man)

Dave, it wasn't long ago that the hype was building around Autifony's AUT00063, SciFluor's SF0034, and Auris Medical's AM-101 (Keyzilen). They had similarly disappointing results that devastated a lot of people. I saw how emotionally attached people were getting with the idea that these drugs were going to save them.

When I saw the same happening with FX-322, I wanted to help people take a step back, and not get emotionally attached, but I ultimately failed. There were people hailing this as the new cure 3 years ago, and this built an immense amount of hype that got a little out of control, in my opinion (with the vacuum of human clinical data that was available).

It's not nice to see people's hopes get crushed, but they shouldn't be built up that high in the first place. Biotech is a notoriously cut throat industry where experimental compounds come and go quicker than Hugh Hefner had girlfriends.

Reserve the excitement for the day when a meaningful breakthrough is made, and the clinical data is made public. Forget over-the-top headlines and clickbait.

With that said, I see no problem, whatsoever, with people discussing this trial on a scientific level, such as how @FGG, @Diesel, @Zugzug, @Aaron91, etc, have been doing.

 

[HootOwl]

From an academic perspective it might be useful to know if the drug helps part of the audio system but if it doesn't reduce tinnitus symptoms it's still a bust.

It's important to understand what structure is being fixed and to what extent, so that we don't keep seeing the same erroneous "I knew FX-322 was never a miracle cure!" posts over and over.

If you understand what a drug fixes, you can better understand your chances of the drug fixing you.

 

[Jazzer]

Dave, it wasn't long ago that the hype was building around Autifony's AUT00063, SciFluor's SF0034, and Auris Medical's AM-101 (Keyzilen). They had similarly disappointing results that devastated a lot of people. I saw how emotionally attached people were getting with the idea that these drugs were going to save them.

When I saw the same happening with FX-322, I wanted to help people take a step back, and not get emotionally attached, but I ultimately failed. There were people hailing this as the new cure 3 years ago, and this built an immense amount of hype that got a little out of control, in my opinion (with the vacuum of human clinical data that was available).

It's not nice to see people's hopes get crushed, but they shouldn't be built up that high in the first place. Biotech is a notoriously cut throat industry where experimental compounds come and go quicker than Hugh Hefner had girlfriends.

Reserve the excitement for the day when a meaningful breakthrough is made, and the clinical data is made public. Forget over-the-top headlines and clickbait.

With that said, I see no problem, whatsoever, with people discussing this trial on a scientific level, such as how @FGG, @Diesel, @Zugzug, @Aaron91, etc, have been doing.

Totally agree with everything you've stated here Ed.

Of course I want research to continue.

Every one of us is in need of relief if not cure.

Personally I am in no shape to finance it myself, hence my determination to make a video where I asked for support and investment into both research and into Tinnitus Talk.

It has currently achieved 3.8k views.
(i.e. - I made the effort I was capable of.)

But just as you have said, I hate to see people's hopes dashed, as I hate to experience this situation myself.
Perhaps because of my age I have grown fatalistic.
My thoughts and my concern goes out to every one of us sufferers.

Dave xx
Jazzer

 

[Zugzug]

It's important to understand what structure is being fixed and to what extent, so that we don't keep seeing the same erroneous "I knew FX-322 was never a miracle cure!" posts over and over.

If you understand what a drug fixes, you can better understand your chances of the drug fixing you.

100%. The mindset of not caring about the little milestones is not scientific at all. Science is slow and evolves from small incremental changes.

Back when I did math research, my biggest mistake was almost always believing something was true and then not proving it to something far simpler. Discovery, on an intellectual or scientific level, requires almost a painful amount of small steps that aren't required for implementation, once the result is known.

Just think about an MRI. Tons of people use these machines like it's nothing. But at one point, there wasn't even the basic notion of what electromagnetism was.

The "it's all a hoax" mentality comes from people who have probably never done science themselves. I remember back when I did research, I would probably have dozens of ideas per day to pursue that would fail almost every day for years.

We need to manage expectations. The drug works in a lab, but has major delivery issues. For sure, the first step is making sense of whether or not the drug is helping word scores from in vivo gains.

In the words of what one of the top mathematicians in the world once told me, "you don't walk before you crawl."

 

[100Hz]

Anyways, besides the fact that there weren't audiogram changes, even the WR improvements are pretty underwhelming in open-label FX-322-111. Keep in mind that it was not placebo controlled so if there were people that deflated their baseline scores, there wouldn't be a counterbalance effect; it would simply help the results.

@Zugzug, thanks, I didn't realize that study was non placebo controlled. It looks like FX-322-112 is though but I can't find whether or not FX-322-113 is placebo controlled or not, do you know? All I can find is that it has a similar study design as ARHL study. (Leads me to believe also double blind placebo controlled).

FX-322 Phase 1b – 111 Study Mild to Severe SNHL (open-label - not placebo controlled)
FX-322 Phase 1b – 112 Study Mild to Moderately Severe Age Related HL (double blind - placebo controlled)
FX-322 Phase 1b – 113 Study Severe SNHL ?

 

[RB2014]

Dave, it wasn't long ago that the hype was building around Autifony's AUT00063, SciFluor's SF0034, and Auris Medical's AM-101 (Keyzilen). They had similarly disappointing results that devastated a lot of people. I saw how emotionally attached people were getting with the idea that these drugs were going to save them.

When I saw the same happening with FX-322, I wanted to help people take a step back, and not get emotionally attached, but I ultimately failed. There were people hailing this as the new cure 3 years ago, and this built an immense amount of hype that got a little out of control, in my opinion (with the vacuum of human clinical data that was available).

It's not nice to see people's hopes get crushed, but they shouldn't be built up that high in the first place. Biotech is a notoriously cut throat industry where experimental compounds come and go quicker than Hugh Hefner had girlfriends.

Reserve the excitement for the day when a meaningful breakthrough is made, and the clinical data is made public. Forget over-the-top headlines and clickbait.

With that said, I see no problem, whatsoever, with people discussing this trial on a scientific level, such as how @FGG, @Diesel, @Zugzug, @Aaron91, etc, have been doing.

It was the same thing with the Novartis trial. We spent years discussing... It works, it works, it works... Then the clinical trials come and it doesn't work. It has been said by experts many times that hearing regeneration is more complicated than everyone thinks.

Personally, I would stay away from the stock at this point. I don't see any good news coming out in the near future.

 

[Zugzug]

@Zugzug, thanks, I didn't realize that study was non placebo controlled. It looks like FX-322-112 is though but I can't find whether or not FX-322-113 is placebo controlled or not, do you know? All I can find is that it has a similar study design as ARHL study.

FX-322 Phase 1b – 111 Study Mild to Severe SNHL (open-label - not placebo controlled)
FX-322 Phase 1b – 112 Study Mild to Moderately Severe Age Related HL (double blind - placebo controlled)
FX-322 Phase 1b – 113 Study Severe SNHL ?

Yeah, they are both double-blind. Here are the links to the clinical trials.

FX-322 Clinical Trials

Details are in the top two links. The problem is that since they are Phase 1b studies, the sample sizes are smaller and the statistical inferences are considered more exploratory.

 

[Zugzug]

Sincere question:

If Phase 2a was a raging success, would all of the doubters come on here and say "thank God we had the people hyping this drug up. I didn't understand the science and I was wrong. I'm glad there were people that did."

Of course not. One of the reasons why I am forcing myself to be a bear is because this forum lacks bears that study the science. This is not really how it's supposed to work. What should happen is that I look at the science objectively, formulate opinions, and then become a bear or a bull based on my opinions. I pretty much have to take the bear position because most of the current bears fall more into the "it's all a hoax" crowd.

This forum could really benefit from someone who knows molecular biology who has good reasons as to why VPA + CHIR shouldn't improve audiograms. I don't have the skillset to be this person. All I can do is look at the statistics and look for ways to frame the data from a position of doubt.

 

[GlennS]

LeBel said there were anecdotes.

The running theory here was that reduced tinnitus was a byproduct of improved hearing. Since the data now suggest no improved hearing then that raises doubts tinnitus can improve. The burden is on Frequency Therapeutics to supply hard data rather than just 2nd hand anecdotes. Remember that even Lenire had video testimonials and we can see how that one turned out.

 

[FGG]

The running theory here was that reduced tinnitus was a byproduct of improved hearing. Since the data now suggest no improved hearing then that raises doubts tinnitus can improve. The burden is on Frequency Therapeutics to supply hard data rather than just 2nd hand anecdotes. Remember that even Lenire had video testimonials and we can see how that one turned out.

Of course. And doubling word scores in Phase 1 points to improved hearing. The test is designed to weed out significant amount of "good guesses" as you suspected. Or it would be a completely useless test in general.

And placebo cannot account for it because it doesn't match historical controls. So either it's fraud (in either the Phase 1 patients or the company) or there is a hearing effect.

The audiogram measures a small part of hearing; OHCs only. It's 100% not a "broad hearing test." This is not a theory, this is well known in hearing physiology.

 

[Zugzug]

The running theory here was that reduced tinnitus was a byproduct of improved hearing. Since the data now suggest no improved hearing then that raises doubts tinnitus can improve. The burden is on Frequency Therapeutics to supply hard data rather than just 2nd hand anecdotes. Remember that even Lenire had video testimonials and we can see how that one turned out.

Anecdotes are basically worthless. Sometimes tinnitus improves with time, diet, stress, sleep, randomness. Even Curcumin helps my tinnitus sometimes.

I think the results have told us that the first step of diagnostics is not tinnitus. It's making sense of the super responders in WR and whether they were legit or not.

What is it about their medical records that may make the shitty drug delivery work better? What kind of hair cell loss did they have? Etc.

 

[lymebite]

The audiogram measures a small part of hearing; OHCs only. It's 100% not a "broad hearing test." This is not a theory, this is well known in hearing physiology.

Agree 100 percent.

Among those of us suffering with hyperacusis, a common typical hyperacusis patient profile is someone who experienced some kind of damage to the auditory system from either too much noise exposure over time or an acoustic shock, and has a so-called "perfect" audiogram but debilitating hyperacusis and tinnitus.

We can hear the tones just fine but something is clearly damaged in the hearing system and causes auditory symptoms not related to hearing tones at various frequencies. We need something fixed in the hearing system that does not involve the part that enables hearing tones.

 

[FGG]

Anecdotes are basically worthless. Sometimes tinnitus improves with time, diet, stress, sleep, randomness. Even Curcumin helps my tinnitus sometimes.

I think the results have told us that the first step of diagnostics is not tinnitus. It's making sense of the super responders in WR and whether they were legit or not.

What is it about their medical records that may make the shitty drug delivery work better? What kind of hair cell loss did they have? Etc.

I agree but I think "it has to improve OHCs on first pass or it can't help tinnitus" isn't backed up by anything either.

The anecdotes are encouraging simply because the company thought they were strong enough to add THI to Phase 2a (tinnitus wasn't part of Phase 1 so the anecdotes must have been pretty strong imo for the testing centers to bring the testimonial info to Frequency Therapeutics). I give that way more weight than an average anecdote but of course hard data is needed.

I completely reject the idea that only OHCs are responsible for tinnitus though (which i know you weren't saying).