Frequency Therapeutics — Hearing Loss Regeneration

[Philip83]

Based on the word score improvements from the Phase 1/2, looks like after 2 weeks improvements seem to be noticeable. May change with more injections.

Amazing.

 

[Gb3]

That's my understanding. The Outcomes Assessor is blind to whom received Placebo, 1,2,4 doses. They should know what site they participated in, but they may not know their baseline/day 0 assessment. They also have data on the progression of improvements (or lack there of).

The interim analysis provided to the Investigator could have consisted of a straight snapshot of all participants at 90 days; without reference to their baseline, and what facility they where they were treated. This keeps the investigator blind to their initial acceptance criteria of the patient.

It probably looked like an exported table like so:

DAY 90 Data:

View attachment 41542

If that is the case, the results must indicate pretty clearly who got what doses.

 

[Diesel]

If that is the case, the results must indicate pretty clearly who got what doses.

If there is a clear enough separation, creating "clusters" of 24 patients with notable improvements, it's possible. If LeBel did a good job finding a homogeneous group of 95 patients with really similar SNHL, that baseline would make establishing dosage/outcome clustering easier/more clear.

It's probably more likely that 12 per group that received FX-322 stood out, and the other 12 overlapped each other more. So, maybe they got 2 or 4 doses, but either way their outcomes are above the investigators average entry/day 0 range.

Either way, that finding would be enough to be confident in announcing an early analysis to the public.

 

[Am92]

If you don't have any "visible" hearing loss, but persistent chronic tinnitus after a physical trauma to the ear, would FX-322 still be beneficial to get rid of tinnitus, or is it just hearing loss related?

 

[ploughna]

My hearing drops off sharply from about 2 kHz and my tinnitus seems to have a strong 2 kHz component. If FX-322 is only capable of regenerating hair cells for much higher frequencies (10-15 dB improvement @ 8 kHz), does that suggest no potential improvement for people with lower frequency tinnitus?

Has there been any speculation on how low in frequency the 4 dose protocol currently being evaluated might go?

 

[HootOwl]

I'm on Prednisolone now. Hoping it will do something with an eventual inflammation in my cochlea or brain stem. I'm on it for a different reason though.

I wish you luck! Prednisone had very little penetrance for me, even with 2 weeks at a high dose, but some people have said it dramatically helped them. Crossing fingers you'll be in that camp.

 

[L34]

I guess none of us on Tinnitus Talk is a part of the clinical trial?

Was the criteria for participating very narrow?

 

[FGG]

If you don't have any "visible" hearing loss, but persistent chronic tinnitus after a physical trauma to the ear, would FX-322 still be beneficial to get rid of tinnitus, or is it just hearing loss related?

FX-322 regrows cochlear sensory hair cells.

If the physical trauma gave you non hair cell related pathology (e.g. damaged your ear drum, or gave you a perilymph fistula), it wouldn't help. Also if you have neck issues or TMJ after injury causing your tinnitus.

Pressure injuries after trauma can damage hair cells through inflammation though so it would depend on what was damaged. Get an extended audiogram (8 kHz to 16 kHz) if you want to be sure you don't have obvious hearing loss.

FX-322 isn't a "general" tinnitus drug (like OTO-313 aims to be especially acutely). It regenerates hair cells which is a common injury after noise trauma, certain ototoxins, and viral infection.

 

[FGG]

My hearing drops off sharply from about 2 kHz and my tinnitus seems to have a strong 2 kHz component. If FX-322 is only capable of regenerating hair cells for much higher frequencies (10-15 dB improvement @ 8 kHz), does that suggest no potential improvement for people with lower frequency tinnitus?

Has there been any speculation on how low in frequency the 4 dose protocol currently being evaluated might go?

No one yet knows any hard numbers. Luckily that info will be available soon.

 

[tommyd87]

My expectations after this conversation is that they have likely observed enough of a difference in outcomes after 90 days, that they may be able to infer who got Placebo, 1, 2 or 4 injections.

I think that this is possible. I also wonder whether they know if there might be increased benefit from more doses of FX-322.

 

[wwtsai]

I guess none of us on Tinnitus Talk is a part of the clinical trial?

Was the criteria for participating very narrow?

The trial included those with mild up to moderately severe hearing loss. I applied but was rejected because my moderate hearing loss was not severe enough. I'm assuming they wanted to get a diverse range of participants and the trial site had already met their mild/moderate quota.

If there are members participating they probably can't say anything due to an NDA.

 

[tbuzz89]

If there are members participating they probably can't say anything due to an NDA.

Definitely this. I'm not sure what the regulations are governing this, but even if they're allowed to admit that they are indeed part of a clinical trial for a hearing loss drug, not sure if they can specify any further details.

I tried applying to be a part of the trials as well, but didn't fit the six month timeline requirement (at the time) and would have probably been denied for the same reasons you did. My measurable hearing loss is bordering moderate (-25 dB) bilaterally at 3 kHz, but my tinnitus is somewhere around 12-13 kHz so I'm sure there's loss up in the high ranges as well.

Kind of glad this is the case for me as FX-322 targets those high ranges first, from what we understand.

 

[tommyd87]

The trial included those with mild up to moderately severe hearing loss. I applied but was rejected because my moderate hearing loss was not severe enough. I'm assuming they wanted to get a diverse range of participants and the trial site had already met their mild/moderate quota.

If there are members participating they probably can't say anything due to an NDA.

That tends to then be better because it is importantly demonstrating that FX-322 might work with higher levels of hearing loss.

Definitely this. I'm not sure what the regulations are governing this, but even if they're allowed to admit that they are indeed part of a clinical trial for a hearing loss drug, not sure if they can specify any further details.

I tried applying to be a part of the trials as well, but didn't fit the six month timeline requirement (at the time) and would have probably been denied for the same reasons you did. My measurable hearing loss is bordering moderate (-25 dB) bilaterally at 3 kHz, but my tinnitus is somewhere around 12-13 kHz so I'm sure there's loss up in the high ranges as well.

Kind of glad this is the case for me as FX-322 targets those high ranges first, from what we understand.

I think that the criteria was you had to have moderate hearing loss in multiple frequencies. I think it is good that FX-322 hits the upper frequencies first. Thus it will provide the most benefit and more likely treat what people mostly need. Actually at this time I think it is likely that FX-322 will be reworked if it isn't able to get down to lower frequencies. I think that there is no plausible way that Frequency Therapeutics will stop before they get it working well.

 

[vttbx]

Ah okay, my cochlea is so inflamed at this point even 70 decibel noise exposures has caused worsenings so perhaps I'm being overly cautious.

Like how some people have had MRIs with both ear plugs and muffs and even that wasn't enough protection, and their tinnitus spiked.

50% of my ear buds was actually still enough to irritate my hair cells and give me phantom sounds for a day... man I read responses like this and then I think are my ears just super fucked...

I think my experiences have just steered me in the direction of being too cautious, but it sounds like I'm probably in the minority when it comes to the extent of inflammation and sensitivity in my cochlea.

The ABR test was just a bad decision on my part even though my doctor requested it. I should have opted for the MRI with earmuffs and earplugs, but sometimes they use a brace for your head that doesn't allow the muffs to be worn. The OAE doesn't seem to offer much more than the audiometry, so I would avoid it just to be safe.

 

[sssing]

I was thinking about FX-322's mechanism of action and I don't understand why the signalling is turned on in the small intestine but turned off in the cochlea.

Since the LGR5 progenitor cells are relatively similar in these two areas, why did those in the cochlea get no more signalling after the third trimester whereas those in the small intestines keep receiving signalling from the brain or I'm not sure what?

Shouldn't they get the same signalling as those in the small intestines?

 

[grate_biff]

Shouldn't they get the same signalling as those in the small intestines?

Something obviously went terribly wrong with evolution. Why we even have pain receptors in our cochlea, making my life virtually unlivable is beyond me.

 

[weab00]

Something obviously went terribly wrong with evolution. Why we even have pain receptors in our cochlea, making my life virtually unlivable is beyond me.

It's to protect the cochlea from extremely loud levels of noise, but the threshold is compromised for hyperacusis ears probably due to sensitized type II pain afferents.

But I agree, the body is cruel and fucked up.

 

[Philip83]

My hearing drops off sharply from about 2 kHz and my tinnitus seems to have a strong 2 kHz component. If FX-322 is only capable of regenerating hair cells for much higher frequencies (10-15 dB improvement @ 8 kHz), does that suggest no potential improvement for people with lower frequency tinnitus?

Has there been any speculation on how low in frequency the 4 dose protocol currently being evaluated might go?

This might just be my wishful thinking, but I have a feeling that it's plausible that if FX-322 does a very good job at repairing frequencies from let's say 4000 Hz (is that what has been hinted?) and upwards really well, your hearing system will be restored to the point where a mild to moderate tinnitus noise at lower frequencies probably will go away because of all the new sound input taking precedence over it. The new sound input will "mask" the lower tinnitus tones, so to say.

Again, just my guess though.

 

[Diesel]

This might just be my wishful thinking, but I have a feeling that it's plausible that if FX-322 does a very good job at repairing frequencies from let's say 4000 Hz (is that what has been hinted?) and upwards really well, your hearing system will be restored to the point where a mild to moderate tinnitus noise at lower frequencies probably will go away because of all the new sound input taking precedence over it. The new sound input will "mask" the lower tinnitus tones, so to say.

Again, just my guess though.

The latter half has been something I have been wondering might be the case as well as it relates to tinnitus. And increase of signal from newly generated hair cells gives the brain a lot more information to work with and ends up mitigating the undesirable effects of what untreated hair cells remain. Almost like giving a car a "tune up." The new parts help the original equipment function at manufacturer specification.

 

[tommyd87]

This might just be my wishful thinking, but I have a feeling that it's plausible that if FX-322 does a very good job at repairing frequencies from let's say 4000 Hz (is that what has been hinted?) and upwards really well, your hearing system will be restored to the point where a mild to moderate tinnitus noise at lower frequencies probably will go away because of all the new sound input taking precedence over it. The new sound input will "mask" the lower tinnitus tones, so to say.

Again, just my guess though.

I think that this is very plausible. I'm pretty sure that it will benefit people greatly until a redosed/reformulated version is available, which will also work with the lower frequencies.

The latter half has been something I have been wondering might be the case as well as it relates to tinnitus. And increase of signal from newly generated hair cells gives the brain a lot more information to work with and ends up mitigating the undesirable effects of what untreated hair cells remain. Almost like giving a car a "tune up." The new parts help the original equipment function at manufacturer specification.

I think that the increased signal most certainly will assist with the issues such as tinnitus and also any other related issues. I think this is why there will be a benefit from the first treatment of FX-322, and also actually why a lot of people will take this treatment up even if they later need to have a redosed version which will work with the lower frequencies.

 

[Sam Bridge]

I tried applying to be a part of the trials as well, but didn't fit the six month timeline requirement (at the time) and would have probably been denied for the same reasons you did. My measurable hearing loss is bordering moderate (-25 dB) bilaterally at 3 kHz, but my tinnitus is somewhere around 12-13 kHz so I'm sure there's loss up in the high ranges as well.

Kind of glad this is the case for me as FX-322 targets those high ranges first, from what we understand.

Moderate hearing loss is 40+ dB. 25 dB hearing loss is mild.

 

[Philip83]

Moderate hearing loss is 40+ dB. 25 dB hearing loss is mild.

This is one of those arbitrary decisions by the medical professionals that I just don't agree with. My hearing loss starts at about 10 dB, quickly slopes down to 20 dB, and then falls of a cliff at around 7000 Hz into 40+ dB. When I have audiograms and the doctor then tells me I have "mild hearing loss", I'm like, what the hell are you talking about? My hearing is absolute bollocks! 40 dB is a MASSIVE amount of hearing loss, and this is considered moderate? It's just weird to me.

 

[ThomasC]

This is one of those arbitrary decisions by the medical professionals that I just don't agree with. My hearing loss starts at about 10 dB, quickly slopes down to 20 dB, and then falls of a cliff at around 7000 Hz into 40+ dB. When I have audiograms and the doctor then tells me I have "mild hearing loss", I'm like, what the hell are you talking about? My hearing is absolute bollocks! 40 dB is a MASSIVE amount of hearing loss, and this is considered moderate? It's just weird to me.

40 dB of hearing loss is between mild and moderate. It's not massive. My hearing loss is moderate above 7 kHz but the rest is normal, and I don't feel I have hearing problems, except when I'm surrounded by too much background noise.

 

[Philip83]

40 dB of hearing loss is between mild and moderate. It's not massive. My hearing loss is moderate above 7 kHz but the rest is normal, and I don't feel I have hearing problems, except when I'm surrounded by too much background noise.

It's all on an individual basis I guess. I just feel mathematically also, the difference between 0 dB loss and 40 dB loss is not something I would label as "mild" at least. I have about the same loss as you then I guess, and I do feel my hearing loss is substantial. Not in a "this extremely affects my everyday life" -kind of loss, but I do remember to some extent what my hearing used to be, and that's a huge difference.

During a brief period I tried hearing aids (but couldn't continue with them because my hyperacusis went through the roof) and omg my hearing felt 10x better, which is not a "mild" improvement in my opinion.

 

[tbuzz89]

Moderate hearing loss is 40+ dB. 25 dB hearing loss is mild.

I classify it as moderate as everything sounds muffled. This is most likely due to "hidden" hearing loss and damage in the frequencies above 8 kHz that don't normally get measured. If I've learned anything from this forum, it's that the perception of hearing loss is very subjective among different people.

 

[Philip83]

How many injections did the patients get at a maximum in the phase 2 trial? I can only read "4x weekly" from the charts. So was it four times over the span of one week, and that's it?

 

[TrevorSanders]

How many injections did the patients get at a maximum in the phase 2 trial? I can only read "4x weekly" from the charts. So was it four times over the span of one week, and that's it?

I believe the injections were spaced over 4 weeks, 1 injection every week. And yes, the maximum non-placebo injections a patient could have received is 4.

 

[FGG]

How many injections did the patients get at a maximum in the phase 2 trial? I can only read "4x weekly" from the charts. So was it four times over the span of one week, and that's it?

4x weekly means 4 weekly doses were given (to that cohort) total, not that they were all given in a week.

 

[Street Novelist]

How many injections did the patients get at a maximum in the phase 2 trial? I can only read "4x weekly" from the charts. So was it four times over the span of one week, and that's it?

I thought it meant 1 shot a week for 4 weeks.

 

[Lucifer]

I thought it meant 1 shot a week for 4 weeks.

That's correct. I hope that by the end of March we will get good news that additional doses of FX-322 help with restoring hair cells.