Frequency Therapeutics — Hearing Loss Regeneration

[GregCA]

Don't forget that cochlear implants are also advancing at a rapid pace now and they are aiming to have one developed that sounds 99% like normal hearing very soon.

Can you provide any links to the cochlear implant that is 99 percent like normal hearing?

I would like to read about this too.

 

[Tezcatlipoca]

And where are the audiograms to prove that--rather than just wishy-washy WR scores?

We've beaten this horse to death.

 

[Diesel]

My belief: The drug does work for the right person, but between the formulation, delivery, hair cell distribution (random, particularly for IHC loss), other things like vascular changes, and many other unknowns, it's just not that effective, as is.

I'd say this is a highly realistic expectation. Even if it is a specific set of conditions that allow the drug to be effective, that's still groundbreaking in my opinion.

After the Phase 1/2 ended several years ago, anyone who holds this drug to the level of "cure all" has been kidding themselves. That includes the skeptics.

The fact is, even if it is a small sliver of a few million people worldwide that meet the criteria, it's that huge first step we all probably need to eventually getting treatment.

 

[Street Novelist]

Either the science is wrong, or FX-322 doesn't work.

It will be very interesting to see what happens if the severe hearing loss trial fails. What do they do at that point?

 

[Diesel]

Either the science is wrong, or FX-322 doesn't work.

It will be very interesting to see what happens if the severe hearing loss trial fails. What do they do at that point?

Proceed with a Phase 2 with only moderate - moderately severe hearing loss.

 

[Tezcatlipoca]

Either the science is wrong, or FX-322 doesn't work.

This is not a binary issue. They need to find the population it works on, the conditions, dosage, frequency.

 

[kiki]

"In the 112 study, the Company observed no significant treatment effect with FX-322 administration compared to placebo."​

Did any of the patients injected with FX-322 have any improvement?
I suspect that some people have made some improvements.

Does that mean it's not significant as a group?
As with Phase 2a, I want them to show personal patient data.

I suspect that some patients with presbycusis are primarily responsible for the reduction in hair cell death.

I think that in some patients, synaptopathy and the decline of the ionic environment are not the main causes.

Isn't "no placebo effect" evidenced by some (non-significant) improvement in the injected group, compared to that?

 

[Sunshine007]

What does the failure of age-related hearing loss mean in terms of how FX-322 may be working? Can we make any new hypotheses on the mechanism of action?

Earlier we thought FX-322 produced hair cells, just that multiple injections interfered in seeing results. Is age-related hearing loss in some way a different animal than other forms of sensorineural hearing loss?

 

[ThomasRobert]

What does the failure of age-related hearing loss mean in terms of how FX-322 may be working? Can we make any new hypotheses on the mechanism of action?

Earlier we thought FX-322 produced hair cells, just that multiple injections interfered in seeing results. Is age-related hearing loss in some way a different animal than other forms of sensorineural hearing loss?

Age-related hearing loss is mostly from arteries narrowed or blocked by a build-up of plaque that is made up of fatty deposits (smoking, cholesterol, high blood pressure, sugar levels), which then doesn't allow enough oxygen to reach the ear causing hair cell death and hearing loss.

 

[Hamsti]

Age-related hearing loss is mostly from arteries narrowed or blocked by a build-up of plaque that is made up of fatty deposits (smoking, cholesterol, high blood pressure, sugar levels), which then doesn't allow enough oxygen to reach the ear causing hair cell death and hearing loss.

View attachment 44996

Yep, and these plaques can also occur straight in your cochlea, unfortunately.

Especially since these blood vessels are very narrow.

 

[serendipity1996]

Age-related hearing loss is mostly from arteries narrowed or blocked by a build-up of plaque that is made up of fatty deposits (smoking, cholesterol, high blood pressure, sugar levels), which then doesn't allow enough oxygen to reach the ear causing hair cell death and hearing loss.

View attachment 44996

Age-related hearing loss is thought to be due in part to degeneration of the stria vascularis.

 

[Christiaan]

Yep, and these plaques can also occur straight in your cochlea, unfortunately.

Especially since these blood vessels are very narrow.

Another good reason to embrace a plant-based diet, as it is known to reduce and in some cases even reverse atherosclerosis So people, if you don't go vegan for the animals, do it for the sake of your ears

 

[xblaOG]

Anybody know when the day 210 read-out is?

 

[GlennS]

We've beaten this horse to death.

When has that stopped a Tinnitus Talk thread?

 

[Sunshine007]

Age-related hearing loss is mostly from arteries narrowed or blocked by a build-up of plaque that is made up of fatty deposits (smoking, cholesterol, high blood pressure, sugar levels), which then doesn't allow enough oxygen to reach the ear causing hair cell death and hearing loss.

View attachment 44996

If it does lead to hair cell loss, shouldn't FX-322 be able to do its magic?

Do we summarize that no vascular build up is a necessary condition for FX-322 to work?

Another issue is people who have both NIHL and ARHL, should we not expect them to see any benefit?

 

[kiki]

If it does lead to hair cell loss, shouldn't FX-322 be able to do its magic?

Do we summarize that no vascular build up is a necessary condition for FX-322 to work?

Another issue is people who have both NIHL and ARHL, should we not expect them to see any benefit?

I want to confirm it. I want to see individual patient data. I don't think it's zero. If it is zero, the effect on NIHL is also suspected.

 

[kiki]

Age-related hearing loss is thought to be due in part to degeneration of the stria vascularis.

In other words, it means that the ionic environment is deteriorating. It means that the battery of the amplifier function has deteriorated. Is this wrong?

 

[Street Novelist]

This is all very suspect.

Frequency Therapeutics need definitive results from the severe hearing trial. If that doesn't produce results, I don't know how anyone can take them seriously.

Saying, well, let them do a trial for only moderate to moderately severe sounds desperate. Besides, most people with hearing loss only have mild to moderate.

 

[RB2014]

This is all very suspect.

Frequency Therapeutics need definitive results from the severe hearing trial. If that doesn't produce results, I don't know how anyone can take them seriously.

Saying, well, let them do a trial for only moderate to moderately severe sounds desperate. Besides, most people with hearing loss only have mild to moderate.

FREQ stock price reflects what you are thinking. I have never seen a drug get approved that would have so many restrictions on who can take it. There are usually side effects that must be disclosed, but to say you must be between certain ages and have a certain hearing threshold is going to be a hard sell.

 

[Diesel]

FREQ stock price reflects what you are thinking. I have never seen a drug get approved that would have so many restrictions on who can take it. There are usually side effects that must be disclosed, but to say you must be between certain ages and have a certain hearing threshold is going to be a hard sell.

I'm not sure what you're trying to say? Most drugs developed to treat specific conditions are highly specific.

Take a look at what's available for hearing loss today and you can see it with hearing aids. There are all kinds of limitations for hearing aids on who they can actually help, and it's even worse for cochlear implants.

I'd be hard pressed to believe that if someone with moderate - moderately severe hearing loss were at the ENT, struggling with their declining condition, and the doctors offered them a drug that could give them their hearing back, and may mean less expensive hearing aids, that they would consider sitting it out.

Also, think about what happened to the Phase 2A: People with hearing loss were desperate enough to maybe get drug, that they faked their word scores to get into the trial.

I think I agree with @Tezcatlipoca, this horse has been beaten to death.

 

[MrCrybaby]

Where it seems we stand:

• Phase 2a was a flop because instead of the Phase 1b successful patient subtype (moderate to severe loss on audiogram, poor word scores) and dose regime (single dose), they went for a new patient subtype (minimal loss on audiogram, poor word score) and a new dose regime (up to 4 doses, weekly interval)
• All eyes are now on the new moderate/severe Phase 1b, which will have a similar patient subtype to those who found success in the initial Phase 1b but in greater numbers
• Everyone is sad Frequency Therapeutics doesn't have Otonomy's top tier delivery medium
• While these negative results are frustrating they are taking us closer to narrowing down which patients will benefit most from hair cell regeneration and are part of the process
• You, reader, are a very cool cat

 

[Tezcatlipoca]

When has that stopped a Tinnitus Talk thread?

The fact that this forum can't even acknowledge that the audiogram is not a good diagnostic tool or that FX-322 working is not a binary issue is sad, really.

 

[Jurger]

I'm not sure what you're trying to say? Most drugs developed to treat specific conditions are highly specific.

Take a look at what's available for hearing loss today and you can see it with hearing aids. There are all kinds of limitations for hearing aids on who they can actually help, and it's even worse for cochlear implants.

I'd be hard pressed to believe that if someone with moderate - moderately severe hearing loss were at the ENT, struggling with their declining condition, and the doctors offered them a drug that could give them their hearing back, and may mean less expensive hearing aids, that they would consider sitting it out.

Also, think about what happened to the Phase 2A: People with hearing loss were desperate enough to maybe get drug, that they faked their word scores to get into the trial.

I think I agree with @Tezcatlipoca, this horse has been beaten to death.

FX-322, a word score drug - even in the best case scenario - will not supplant hearing aids or cochlear implants in any way. You will always need hearing aids to benefit from increased word scores because of the amplification required. I also don't think FX-322 will influence the kind of hearing aid you can get by with. The difference between an expensive hearing aid and a cheaper one is not so much a word score difference, but things like better algorithms, Bluetooth connection, personalization via an app etc. And even if there was a difference in word scores between categories of hearing aids, why would you dampen any word score improvements you got from FX-322 with a cheaper aid? The whole point is to hear better, not to save money.

If you want to revolutionize hearing loss treatment, you will need word scores + audiogram improvements. Not because audiograms are infallible, but because amplification is an integral part of hearing. I think that doesn't get appreciated enough around here.

 

[tommyd87]

FX-322, a word score drug - even in the best case scenario - will not supplant hearing aids or cochlear implants in any way. You will always need hearing aids to benefit from increased word scores because of the amplification required. I also don't think FX-322 will influence the kind of hearing aid you can get by with. The difference between an expensive hearing aid and a cheaper one is not so much a word score difference, but things like better algorithms, Bluetooth connection, personalization via an app etc. And even if there was a difference in word scores between categories of hearing aids, why would you dampen any word score improvements you got from FX-322 with a cheaper aid? The whole point is to hear better, not to save money.

If you want to revolutionize hearing loss treatment, you will need word scores + audiogram improvements. Not because audiograms are infallible, but because amplification is an integral part of hearing. I think that doesn't get appreciated enough around here.

What I don't agree with is that FX-322 is simply a word score medicine. At this stage we haven't seen definitive proof/evidence that this is all it can treat, especially when we have seen some evidence that it has apparently improved the results as a part of an audiogram.

What I do agree with however is that loudness is actually a key element of hearing and improving word recognition scores. This has been shown definitively to be the case through the fact that although people might be able to perform really well on word score tests, they need significant amplification to do so. Something that does need to be improved and does sometimes come as a part of certain types/better types of hearing aids is higher quality microphones for example, which improve the quality and range of what can be heard.

 

[tommyd87]

I'm not sure what you're trying to say? Most drugs developed to treat specific conditions are highly specific.

Take a look at what's available for hearing loss today and you can see it with hearing aids. There are all kinds of limitations for hearing aids on who they can actually help, and it's even worse for cochlear implants.

I'd be hard pressed to believe that if someone with moderate - moderately severe hearing loss were at the ENT, struggling with their declining condition, and the doctors offered them a drug that could give them their hearing back, and may mean less expensive hearing aids, that they would consider sitting it out.

Also, think about what happened to the Phase 2A: People with hearing loss were desperate enough to maybe get drug, that they faked their word scores to get into the trial.

I think I agree with @Tezcatlipoca, this horse has been beaten to death.

I'd just like to know what the limitations are on hearing aids and/or CIs relating to who they can actually help.

 

[GlennS]

the audiogram is not a good diagnostic tool

Anyone who claims an audiogram is a poor diagnostic tool for measuring hearing should not be taken seriously on this board. Digging in your heels and suggesting you somehow represent the objective truth is not going to get you far.

Is it the only metric? No. But a treatment purporting to restore hearing that can't point to improved audiogram results isn't a very promising treatment, especially considering how word recognition scores can vary depending on how hard and effectively one guesses.

To claim otherwise is to engage in the bargaining stage of denial, period.

I really am getting Lenire vibes here insofar as it seems that any time there are marginal but so-called "statistically significant" improvement stats it seems to more or less fall within the gray area of placebo. Only when a treatment shows a more dramatic improvement can I really stop thinking it's just glorified placebo. I can very easily expect some wishy washy testimonial videos should FX-322 continue. If they water down this treatment to that extent where people struggle to articulate how it helped them, well, it's a bust in my book. And what would those dramatic metrics be, you might ask? Improved audiograms, like showing they can suddenly hear in a frequency that was almost wiped out, because that is what one should expect for a drug claiming to restore hearing. It should be able to go from literally nothing to something. In this respect, for Frequency Therapeutics to attempt to discount audiograms defies all common-sense and is a huge red flag. That some people here are buying into this logic hook, line and sinker is sad.

 

[OptimusPrimed]

Anyone who claims an audiogram is a poor diagnostic tool for measuring hearing should not be taken seriously on this board. Digging in your heels and suggesting you somehow represent the objective truth is not going to get you far.

Is it the only metric? No. But a treatment purporting to restore hearing that can't point to improved audiogram results isn't a very promising treatment, especially considering how word recognition scores can vary depending on how hard and effectively one guesses.

To claim otherwise is to engage in the bargaining stage of denial, period.

I really am getting Lenire vibes here insofar as it seems that any time there are marginal but so-called "statistically significant" improvement stats it seems to more or less fall within the gray area of placebo. Only when a treatment shows a more dramatic improvement can I really stop thinking it's just glorified placebo. I can very easily expect some wishy washy testimonial videos should FX-322 continue. If they water down this treatment to that extent where people struggle to articulate how it helped them, well, it's a bust in my book. And what would those dramatic metrics be, you might ask? Improved audiograms, like showing they can suddenly hear in a frequency that was almost wiped out, because that is what one should expect for a drug claiming to restore hearing. It should be able to go from literally nothing to something. In this respect, for Frequency Therapeutics to attempt to discount audiograms defies all common-sense and is a huge red flag. That some people here are buying into this logic hook, line and sinker is sad.

I am living proof that the audiogram is a poor diagnostic tool to measure hearing. I have perfect audiogram scores but my hearing in my right ear is horribly distorted at particular frequencies. The audiogram measures 9 tones. It is inadequate, especially in measuring hidden hearing loss.

 

[ThomasRobert]

Anyone who claims an audiogram is a poor diagnostic tool for measuring hearing should not be taken seriously on this board. Digging in your heels and suggesting you somehow represent the objective truth is not going to get you far.

Is it the only metric? No. But a treatment purporting to restore hearing that can't point to improved audiogram results isn't a very promising treatment, especially considering how word recognition scores can vary depending on how hard and effectively one guesses.

To claim otherwise is to engage in the bargaining stage of denial, period.

I really am getting Lenire vibes here insofar as it seems that any time there are marginal but so-called "statistically significant" improvement stats it seems to more or less fall within the gray area of placebo. Only when a treatment shows a more dramatic improvement can I really stop thinking it's just glorified placebo. I can very easily expect some wishy washy testimonial videos should FX-322 continue. If they water down this treatment to that extent where people struggle to articulate how it helped them, well, it's a bust in my book. And what would those dramatic metrics be, you might ask? Improved audiograms, like showing they can suddenly hear in a frequency that was almost wiped out, because that is what one should expect for a drug claiming to restore hearing. It should be able to go from literally nothing to something. In this respect, for Frequency Therapeutics to attempt to discount audiograms defies all common-sense and is a huge red flag. That some people here are buying into this logic hook, line and sinker is sad.

So let's say before taking FX-322, you hear this:

And after taking FX-322, you actually hear it clearer like this:

Wouldn't you be satisfied?

I believe improvement in Word Scores (to hear clearer) is a great step...

 

[Zugzug]

Anyone who claims an audiogram is a poor diagnostic tool for measuring hearing should not be taken seriously on this board. Digging in your heels and suggesting you somehow represent the objective truth is not going to get you far.

Is it the only metric? No. But a treatment purporting to restore hearing that can't point to improved audiogram results isn't a very promising treatment, especially considering how word recognition scores can vary depending on how hard and effectively one guesses.

Since word clarity doesn't do it for you, let me try a different line of questions.

What if a drug was close to helping OHC growth and achieving this highly coveted audiogram improvement, but was abandoned prematurely? Do you think that's smart? Do you think FX-322, exactly as it stands today, is just as close to curing hearing loss as a placebo injection?

I think you are misunderstanding what everyone is afraid of. It's more along the lines of giving up on something too soon than it is along the lines of "Wah! The drug kicks so much ass right now; I know it. Feed my denial!"

Do you want FX-322 to be totally abandoned right now? Yes or no? If your answer is "no," then it kind of doesn't make any sense at all to not want more granular metrics in order to progress it further. If your answer is "yes," then trust me, you are being more emotional than all of the people you are bashing.

 

[Guywithapug]

I think the audiogram is a poor diagnostic tool in a sense that it won't tell you why an individual has hearing issues. It can be useful because it does indicate deficits along the hearing frequency spectrum and allows hearing aids to be programmed according to hearing thresholds.

The audiogram along with WIN give clues about the type of hearing loss an individual has but aren't definitive.

Many have expectations at this point of a hearing test to point specifically to the cause of the hearing deficit and condition, like IHC, OHC, synaptopathy, nerve atrophy etc. I'm not sure we're going to see something like this, at least anytime soon.

Just my $0.02.