Frequency Therapeutics — Hearing Loss Regeneration

[serendipity1996]

Also there's a pretty compelling case to be made for tinnitus arising out of hair cell damage as evidenced by the fact that restoring input with hearing aids can often reduce or alleviate a patient's tinnitus.

 

[Lucifer]

"Breakthrough Therapy status"? What do you mean?

What is fast track doing anyway? Having shorter test periods? Skipping some phases?

Not sure if skipping phases is a good thing honestly. I'm dealing with tinnitus for years and years, I can wait for one more year if they make sure it works better and it is safer.

If it's just about speeding up the admin side on the FDA side, then ok.

Well I hope they release it asap. Many people are suffering with tinnitus and hyperacusis and some people cannot wait another year. I do not want more people to end up like @Allan1967.

 

[Jorge1984]

Read the Dr. Sedley thread, he goes into it a bit more. Tinnitus brains are not damaged brains, they are normal brains (and possibly even more efficient brains at prediction of sound) reacting to damage.

What does that mean? Like if we find the root of the the tinnitus then we'll be able to get rid of it?

 

[FGG]

What does that mean? Like if we find the root of the the tinnitus then we'll be able to get rid of it?

If you treat the root cause, the brain will adapt to the normalized auditory system.

 

[ThomasRobert]

NO COVID-19 SLOWDOWN: Frequency Therapeutics Adds Another Recruitment Site for FX-322 Phase 2a Study

The update – which includes a new clinical trial site in Austin, Texas – was posted to ClinicalTrials.gov on April 10, 2020.

It looks like the FX-322 trial is still moving forward as expected, running on schedule.
The estimated study completion date (September 30, 2020) remains unchanged.

Link to official study page:
https://clinicaltrials.gov/ct2/show/NCT04120116

 

[Christiaan]

NO COVID-19 SLOWDOWN: Frequency Therapeutics Adds Another Recruitment Site for FX-322 Phase 2a Study

The update – which includes a new clinical trial site in Austin, Texas – was posted to ClinicalTrials.gov on April 10, 2020.

It looks like the FX-322 trial is still moving forward as expected, running on schedule.
The estimated study completion date (September 30, 2020) remains unchanged.

Link to official study page:
https://clinicaltrials.gov/ct2/show/NCT04120116

Great news. But is there a chance that the 3rd trial will be postponed until after the corona threat has been squashed?

 

[Lucifer]

NO COVID-19 SLOWDOWN: Frequency Therapeutics Adds Another Recruitment Site for FX-322 Phase 2a Study

The update – which includes a new clinical trial site in Austin, Texas – was posted to ClinicalTrials.gov on April 10, 2020.

It looks like the FX-322 trial is still moving forward as expected, running on schedule.
The estimated study completion date (September 30, 2020) remains unchanged.

Link to official study page:
https://clinicaltrials.gov/ct2/show/NCT04120116

I really do hope coronavirus does not delay the clinical trials and Phase 2a results are posted around that time.

 

[GregCA]

If you treat the root cause, the brain will adapt to the normalized auditory system.

That assumes that plasticity goes both ways, or course. I'm hopeful that it will, but on the other hand, we got this thing called entropy that tells us that physical processes sometimes only go a certain direction.

 

[FGG]

That assumes that plasticity goes both ways, or course. I'm hopeful that it will, but on the other hand, we got this thing called entropy that tells us that physical processes sometimes only go a certain direction.

We know from cochlear implant effects on long term tinnitus, entropy is not the case.

 

[ajc]

We know from cochlear implant effects on long term tinnitus, entropy is not the case.

I don't think that proves anything. If someone has a need for CIs, their hearing is very shit, so of course their tinnitus is then really bad. Give them CIs and their hearing improves and that helps mask tinnitus.

 

[FGG]

I don't think that proves anything. If someone has a need for CIs, their hearing is very shit, so of course their tinnitus is then really bad. Give them CIs and their hearing improves and that helps mask tinnitus.

They have done studies with implants turned on and off.

Kopke also said in the Tinnitus Talk Podcast it jives with his clinical experience as well. He was asked about tinnitus being "stuck in the brain" and he saw clinical evidence it was not. He would probably be one of the best experts to ask about that since he is very rare combination of a researcher as well as an Otologist seeing patients (until he retired a few months ago).

 

[Diesel]

Back on the tinnitus doom and gloom carousel I see! Allow me to give you some perspective from what is already publicly known about FX-322.

If we are to agree that tinnitus is a symptom of sensorineural/noise-induced hearing loss; where the most common damage likely occurred to one or more IHC/OHC cells or to the synapses of these cells. Then, we might conclude that the tinnitus symptom may be treated by restoring the IHC/OHC or synapses. We might also agree that most experience tinnitus at a frequency (Hz) where / around where damage occurred.

I propose that for the time being, we need to look no further than page 23 on Frequency's most recent presentation:

Considering this slide alone.

I argue that it is HIGHLY likely that the 4 participants that had a 25%+ improvement at 8 kHz, also had improvements ABOVE 8 kHz (8 kHz - 22 kHz). It was simply not tested due to limits of the standard audiogram in the Phase 1/2.

I believe it stands to reason that this improvement in hearing at 8 kHz is a result in new IHC/OHC (and synapses) being restored in the tested range by FX-322. There is no other explanation.

So, if the IHC/OHC (and synapses) are restored at and above 8 kHz, then it is clear the brain is receiving proper signals from the new, functioning cells.

Therefore, if we agree on the statement re: tinnitus as a symptom; doesn't it stand to reason that if any of these 4 patients experiencing tinnitus symptoms at or above 8 kHz, the symptom would also be reduced?

 

[all to gain]

Back on the tinnitus doom and gloom carousel I see! Allow me to give you some perspective from what is already publicly known about FX-322.

If we are to agree that tinnitus is a symptom of sensorineural/noise-induced hearing loss; where the most common damage likely occurred to one or more IHC/OHC cells or to the synapses of these cells. Then, we might conclude that the tinnitus symptom may be treated by restoring the IHC/OHC or synapses. We might also agree that most experience tinnitus at a frequency (Hz) where / around where damage occurred.

I propose that for the time being, we need to look no further than page 23 on Frequency's most recent presentation:

View attachment 38172

Considering this slide alone.

I argue that it is HIGHLY likely that the 4 participants that had a 25%+ improvement at 8 kHz, also had improvements ABOVE 8 kHz (8 kHz - 22 kHz). It was simply not tested due to limits of the standard audiogram in the Phase 1/2.

I believe it stands to reason that this improvement in hearing at 8 kHz is a result in new IHC/OHC (and synapses) being restored in the tested range by FX-322. There is no other explanation.

So, if the IHC/OHC (and synapses) are restored at and above 8 kHz, then it is clear the brain is receiving proper signals from the new, functioning cells.

Therefore, if we agree on the statement re: tinnitus as a symptom; doesn't it stand to reason that if any of these 4 patients experiencing tinnitus symptoms at or above 8 kHz, the symptom would also be reduced?

Surely the slide is saying that 25%+ of the participants had a 10dB improvement and not that participants had a 25%+ improvement?

Will the percentage go significantly up as the trials progess? Only 25%+ seems a bit disheartening to me, but if I remember correctly the participants were only given one dose. Correct?

 

[AtlasFainted]

Little bit irritated at

Back on the tinnitus doom and gloom carousel I see! Allow me to give you some perspective from what is already publicly known about FX-322.

If we are to agree that tinnitus is a symptom of sensorineural/noise-induced hearing loss; where the most common damage likely occurred to one or more IHC/OHC cells or to the synapses of these cells. Then, we might conclude that the tinnitus symptom may be treated by restoring the IHC/OHC or synapses. We might also agree that most experience tinnitus at a frequency (Hz) where / around where damage occurred.

I propose that for the time being, we need to look no further than page 23 on Frequency's most recent presentation:

View attachment 38172

Considering this slide alone.

I argue that it is HIGHLY likely that the 4 participants that had a 25%+ improvement at 8 kHz, also had improvements ABOVE 8 kHz (8 kHz - 22 kHz). It was simply not tested due to limits of the standard audiogram in the Phase 1/2.

I believe it stands to reason that this improvement in hearing at 8 kHz is a result in new IHC/OHC (and synapses) being restored in the tested range by FX-322. There is no other explanation.

So, if the IHC/OHC (and synapses) are restored at and above 8 kHz, then it is clear the brain is receiving proper signals from the new, functioning cells.

Therefore, if we agree on the statement re: tinnitus as a symptom; doesn't it stand to reason that if any of these 4 patients experiencing tinnitus symptoms at or above 8 kHz, the symptom would also be reduced?

This! Research threads aren't the place to prove the "misery loves company" trope.

This drug is extremely promising; we're looking at actual hearing regeneration. For most people, their tinnitus is inextricably linked to hearing loss.

In my opinion, this thread will deteriorate quickly if it becomes a place to post anxiety-driven doubts (you can literally come up with these endlessly, about anything).

 

[GlennS]

IMHO, even if tinnitus persists, restoring high frequency hearing side by side with tinnitus would at least allow masking to be more effective.

 

[AtlasFainted]

Great news. But is there a chance that the 3rd trial will be postponed until after the corona threat has been squashed?

As I understand it, there might not be a phase 3 trial. The drug has been fast-tracked by the FDA, and I believe they are also applying for 'breakthrough therapy' status. Meaning it could go straight to the market if approved.

Even if there were a phase 3 trial, I think it's unlikely that we won't be over this coronavirus stuff when the time comes. Of course, others might crucify me for being so optimistic!

 

[Diesel]

Surely the slide is saying that 25%+ of the participants had a 10dB improvement and not that participants had a 25%+ improvement?

Will the percentage go significantly up as the trials progess? Only 25%+ seems a bit disheartening to me, but if I remember correctly the participants were only given one dose. Correct?

I stand corrected! Even so, a 10dB improvement is greater than a 25% improvement, considering decibels are measured on a logarithmic scale. If I recall correctly, a 10dB improvement would represent something like a 4X improvement to the human ear.

I'd also like to point out that they don't mention improvements below 10dB, perhaps it is not considered significant to show a 5dB improvement, for example.

All participants in Phase-1/2 received a single dose.

 

[GregCA]

Surely the slide is saying that 25%+ of the participants had a 10dB improvement and not that participants had a 25%+ improvement?

You are correct, that is the way to read the chart. 4/15 = 26.6%, which is roughly where that bar chart lands.

I don't know that a hearing improvement at a frequency can be measured in percentages - it's not the right unit. PTA measures this in decibels, so we can measure how much softer, in dB, the patient is able to hear the tone.

Also this doesn't say what the improvements look like for the 4 people who improved. Perhaps one of them has a 20 dB improvement. All we know is that the criterion to be counted in that bar chart is to have an improvement of 10 dB or more.

 

[Diesel]

I'd like to circle back to this chart I shared earlier, as I'd like to discuss clarifying my understanding.

How 10dB is perceived in terms of increased loudness:
When sound is increased in decibels, for every 10dB increase, it is sensed/perceived as being TWICE (2x) as loud by the recipient.

In the case of this slide (correct me if I'm wrong):
We would reverse it in terms of loudness, to measure sensitivity. Therefore a 10dB improvement at 8kHz, would indicate the patient is able to sense an 8kHz tone at half the perceived volume after the FX-322 treatment.

Made-up, theoretical example:
One of the 4 patients had an audiogram baseline at 8kHz of 45dB, and after FX-322 improved to 35dB. In this example their hearing at this frequency would have improved from Moderate to Mild.

 

[AtlasFainted]

I'd like to circle back to this chart I shared earlier, as I'd like to discuss clarifying my understanding.

View attachment 38190

How 10dB is perceived in terms of increased loudness:
When sound is increased in decibels, for every 10dB increase, it is sensed/perceived as being TWICE (2x) as loud by the recipient.

In the case of this slide (correct me if I'm wrong):
We would reverse it in terms of loudness, to measure sensitivity. Therefore a 10dB improvement at 8kHz, would indicate the patient is able to sense an 8kHz tone at half the perceived volume after the FX-322 treatment.

Made-up, theoretical example:
One of the 4 patients had an audiogram baseline at 8kHz of 45dB, and after FX-322 improved to 35dB. In this example their hearing at this frequency would have improved from Moderate to Mild.

The fact that most people lose hearing in the higher frequencies (> 8kHz) first is what has me the most optimistic about this drug.

As you stated earlier, the most improvement on the standard audiogram was at the highest measured frequency (8kHz) & logic would dictate that this trend continues into the higher frequencies.

The majority here (including me) have higher-pitched tinnitus as a result of some hearing loss. Phase 1 trials were done with a safety dose, on people with really messed up hearing, with a standard (meaning laughably outdated) audiogram, and still demonstrated improvement.

I am in the camp that thinks tinnitus is a direct symptom of hearing loss. This drug seems to treat the frequencies that I and most others are affected by the most.

Once you also factor in that the head of research is willing to do the Tinnitus Talk Podcast and that tinnitus is being looked at during phase 2 trials, everything to me seems to indicate good news.

Even for the people who have damage at lower frequencies that the drug hasn't reached, there's a good chance this is due to:

1.) The low doses administered during Phase 1.

2.) FX-322's delivery vehicle, which can be changed without going through trials again.

 

[FGG]

The fact that most people lose hearing in the higher frequencies (> 8kHz) first is what has me the most optimistic about this drug.

As you stated earlier, the most improvement on the standard audiogram was at the highest measured frequency (8kHz) & logic would dictate that this trend continues into the higher frequencies.

The majority here (including me) have higher-pitched tinnitus as a result of some hearing loss. Phase 1 trials were done with a safety dose, on people with really messed up hearing, with a standard (meaning laughably outdated) audiogram, and still demonstrated improvement.

I am in the camp that thinks tinnitus is a direct symptom of hearing loss. This drug seems to treat the frequencies that I and most others are affected by the most.

Once you also factor in that the head of research is willing to do the Tinnitus Talk Podcast and that tinnitus is being looked at during phase 2 trials, everything to me seems to indicate good news.

Even for the people who have damage at lower frequencies that the drug hasn't reached, there's a good chance this is due to:

1.) The low doses administered during Phase 1.

2.) FX-322's delivery vehicle, which can be changed without going through trials again.

Agree, but with your last point, thought I should mention that they have to go through a very abbreviated trial for a new formulation. I read the average for this sort of trial was 12 months.

 

[JohnDoe8776059]

This is a large thread so it's probably been answered already. But I do wonder: Could this 100% cure SIHL? Like could it guarantee a full recovery for all (if not, almost all) patients?

Could it reach to a point where the regeneration could be as good as regenerating skin from a paper cut? Or is SIHL like a scar, where you can heal some of it but not completely?

 

[ThomasC]

Anyone know if FX-322 can help genetic hearing loss? I have bilateral and symmetrical hearing loss above 6kHz which is genetical I guess (at least it is not noise or drug induced). I have moderately severe hearing loss above 6kHz (like 50-65 dB). In 8 years, since I have had tinnitus, my hearing has not changed.

I'm asking this because it's not mentioned in the exclusion criteria, they just say that their drug is for SHL which is quite a broad cause of hearing loss. Genetic hearing loss is a cause of SHL.

My hearing between 0 Hz and 5000 Hz is normal.

 

[AtlasFainted]

Agree, but with your last point, thought I should mention that they have to go through a very abbreviated trial for a new formulation. I read the average for this sort of trial was 12 months.

Yikes. Does this apply even if the new formula is made up of the same ingredients as other vehicles that are already approved?

I'll be going for the original stuff when it comes out regardless but that's potentially sad for people who have damage across all frequencies.

 

[FGG]

This is a large thread so it's probably been answered already. But I do wonder: Could this 100% cure SIHL? Like could it guarantee a full recovery for all (if not, almost all) patients?

Could it reach to a point where the regeneration could be as good as regenerating skin from a paper cut? Or is SIHL like a scar, where you can heal some of it but not completely?

If you had depleted your support cells (which can occur especially with severe to profound loss), this probably wouldn't restore your hearing well.

Similarly, if you had cochlear synaptopathy, this would not address that.

Also, (at least with this first formulation) if you had low frequency hearing loss that wouldn't yet be addressed by FX-322 at this time.

As far as "full recovery" it seems very promising for up to moderately severe HF hearing loss at least due to hair cell loss. Especially noise induced.

There are some unknowns, though. For instance (off the top of my head) would the anti-mitotic properties of retained cochlear platinum after Cisplatin prevent progenitor cell activation in cancer patients?

I would say the noise induced folks are going to be very happy and others will at least get some improvement (in the frequencies the drug reaches).

These kinds of questions will likely be addressed on the Tinnitus Talk Podcast, when it happens.

 

[FGG]

Yikes. Does this apply even if the new formula is made up of the same ingredients as other vehicles that are already approved?

I'll be going for the original stuff when it comes out regardless but that's potentially sad for people who have damage across all frequencies.

Yes. IIRC, the shortened trial is to make sure the drug works as claimed with the new vehicle and/or concentration.

Honestly, in that scenario, the people with damage in lower frequencies will probably have an easier time waiting a year than the previous year imo, knowing their day will come.

 

[AtlasFainted]

If you had depleted your support cells (which can occur especially with severe to profound loss), this probably wouldn't restore your hearing well.

Similarly, if you had cochlear synaptopathy, this would not address that.

Also, (at least with this first formulation) if you had low frequency hearing loss that wouldn't yet be addressed by FX-322 at this time.

As far as "full recovery" it seems very promising for up to moderately severe HF hearing loss at least due to hair cell loss. Especially noise induced.

There are some unknowns, though. For instance (off the top of my head) would the anti-mitotic properties of retained cochlear platinum after Cisplatin prevent progenitor cell activation in cancer patients?

I would say the noise induced folks are going to be very happy and others will at least get some improvement (in the frequencies the drug reaches).

These kinds of questions will likely be addressed on the Tinnitus Talk Podcast, when it happens.

My fingers are crossed for the podcast to be out soon & the drug accessible ASAP... c'mon breakthrough status!

I had a dream last night where I became president and abolished the FDA so people that need drugs which are hung up in trials could access them. It may sound extreme but it shows you how deep in my subconscious this stuff has reached...

I feel like drugs such as these should be able to go to an "early market" where you can go ahead and get your dose if you sign a disclaimer or something.

 

[ttzlff2]

If you had depleted your support cells (which can occur especially with severe to profound loss), this probably wouldn't restore your hearing well.

Under what circumstances/conditions do supporting cells die, precisely? Age? Medication? Others? What are the conditions for them to remain intact? Does anybody here on Tinnitus Talk know? I have not yet gathered any usable information on this yet from the sources I consulted so far...

 

[all to gain]

I stand corrected! Even so, a 10dB improvement is greater than a 25% improvement, considering decibels are measured on a logarithmic scale. If I recall correctly, a 10dB improvement would represent something like a 4X improvement to the human ear.

I'd also like to point out that they don't mention improvements below 10dB, perhaps it is not considered significant to show a 5dB improvement, for example.

All participants in Phase-1/2 received a single dose.

Yeah, I wasn't trying to be picky, just wanted to make sure I was reading it correctly

I also thought about those who may have had improvements below 10dB. It would be good to know if they all had an improvement... even if minimal... just for out own morale if nothing else!

Am I correct in saying that the participants in the current trial are getting four doses?

This is exciting stuff.

Also this doesn't say what the improvements look like for the 4 people who improved. Perhaps one of them has a 20 dB improvement. All we know is that the criterion to be counted in that bar chart is to have an improvement of 10 dB or more.

I hope we will get told the exact improvements at sometime.

Really looking forward to seeing what four doses will do now.

 

[Juan]

It has probably a good chance of getting breakthrough status since the US army has a vested interest in improving the hearing of its soldiers (just not in developing a fix for it).

I think soldiers already have in ear earplugs or earmuffs attached to their helmets, designed to increase or dampen the sound in combat. It is similar to those active protection earmuffs for shooting, but better.