Frequency Therapeutics — Hearing Loss Regeneration

[FGG]

This may be a very dumb question, but is there any correlation between their stock price (which is doing very well) and how hopeful we should be?

I'm guessing everyone's answer will be "no" but thought it might be a good discussion point.

Short answer: no
Long answer: no, unfortunately but I'm optimistic, anyway.

 

[Lucifer]

This may be a very dumb question, but is there any correlation between their stock price (which is doing very well) and how hopeful we should be?

I'm guessing everyone's answer will be "no" but thought it might be a good discussion point.

At this stage we are not sure but the arrangement between Frequency Therapeutics and Astellas tells us that FX-322 works because Astellas would not have given them so much funding otherwise. There's not many start-ups that have received this much funding.

I have a very good feeling that this is the real deal.

 

[patorjk]

This may be a very dumb question, but is there any correlation between their stock price (which is doing very well) and how hopeful we should be?

I'm guessing everyone's answer will be "no" but thought it might be a good discussion point.

I would actually say strong stock performance should equal a little more hope. It's not a random value, so it does mean something. The stock price is related to what people think and how willing they are to put their money behind it. Obviously people can be wrong, but there wouldn't be as much money behind this stock if there wasn't a lot of promise.

That said, the stock has really been moving lately and it's left me scratching my head. I bought a handful of shares last year and I've been tempted to sell, but at this point I'm convinced FX-322 is the real deal, and it'll go up even more once the phase II study is released. That's probably what other stock holders think too, which is why the price is so high. There are a lot of unknowns though.

 

[MRItechssuck]

Has anyone gotten into, or even tried to get accepted into the trial?

 

[Lucifer]

Has anyone gotten into, or even tried to get accepted into the trial?

There were a few that tried to sign up for the trials but didn't meet the requirements. I have a feeling there are some people here who did get accepted but can't say anything due to the NDA.

 

[FGG]

Has anyone gotten into, or even tried to get accepted into the trial?

I tried and did not get in. I know several others here tried as well and were rejected for various reasons. There are quite a few exclusions including not having enough data points that show losses on audiogram (this was my issue), certain concurrent illness (e.g.. Meniere's), benzo or anti convulsant therapy, etc etc.

I'm suspicious at least *someone* got in from here but can't talk about it due to their restrictive NDA which I was told mentions social media strongly. If I had the inclination, I would go back through this thread and see if I could find someone(s) who suddenly stopped posting and contact them and see if that might be why but that seems a bit harassing.

 

[mrbrightside614]

Has anyone gotten into, or even tried to get accepted into the trial?

They'd have to sign NDA's which keeps them from reporting anything on social media.

 

[MrCrybaby]

Has anyone gotten into, or even tried to get accepted into the trial?

If someone got in they couldn't tell us due to the NDA. People have tried though.

 

[FGG]

Anyone think this drug might preferentially repair IHCs in vivo or at least at a lower dose (used in phase 1, for instance) repairs them first?

Frequency Therapeutics got a great response in people who had moderate to severe losses and it is reasonable to assume those folks have more IHC damage than the minor loss patients. There is definitely speech information at the UHF but what if IHCs got repaired in the sub 8000 Hz range too and that helped contribute to the dramatic word score increases. They kept emphasizing clarity is what they are improving with this drug in their JP Morgan presentation, which points to IHC/synapse imo and also said they are a "cochlear synaptopathy" drug only where hair cells are repaired in their Q and A. It's clear this drug does OHCs too (improvements seen at 8000 Hz) but i think this drug may help a lot more people with tinnitus than think it will help because their audiograms are normal.

Other thoughts?

 

[HootOwl]

I might get in now that I've crossed the 6 month threshold from my last audiogram. Dropped them off at the clinic and they said they would get back to me with the final answer sometime this week.

 

[Joeseph Stope]

Anyone think this drug might preferentially repair IHCs in vivo or at least at a lower dose (used in phase 1, for instance) repairs them first?

Frequency Therapeutics got a great response in people who had moderate to severe losses and it is reasonable to assume those folks have more IHC damage than the minor loss patients. There is definitely speech information at the UHF but what if IHCs got repaired in the sub 8000 Hz range too and that helped contribute to the dramatic word score increases. They kept emphasizing clarity is what they are improving with this drug in their JP Morgan presentation, which points to IHC/synapse imo and also said they are a "cochlear synaptopathy" drug only where hair cells are repaired in their Q and A. It's clear this drug does OHCs too (improvements seen at 8000 Hz) but i think this drug may help a lot more people with tinnitus than think it will help because their audiograms are normal.

Other thoughts?

I am not clear on what you mean exactly by: "I think this drug will help a lot more people with tinnitus than (I) think it will help because their audiograms are normal."

You mean it will do more than help those with sensorineural hearing loss -- i.e. help those with tinnitus too?

 

[MrCrybaby]

I might get in now that I've crossed the 6 month threshold from my last audiogram. Dropped them off at the clinic and they said they would get back to me with the final answer sometime this week.

I was just thinking of asking you about this, good luck!

 

[FGG]

I am not clear on what you mean exactly by: "I think this drug will help a lot more people with tinnitus than (I) think it will help because their audiograms are normal."

You mean it will do more than help those with sensorineural hearing loss -- i.e. help those with tinnitus too?

No, I mean I think it will help those with inner hair cell damage who have normal audiograms (which only show outer hair cell damage). I'm speculating that it may be especially useful for them.

I looked up embryologic development of the cochlea last night and it appears the IHCs also develop first. If they are preferentially recovered, I wonder if it's because OHCs apparently don't develop until after IHCs are in place.

 

[mrbrightside614]

I might get in now that I've crossed the 6 month threshold from my last audiogram. Dropped them off at the clinic and they said they would get back to me with the final answer sometime this week.

Pulling for you extremely hard even though your presence on the forum would be sorely missed.

Just got my extended audiogram back. 15dB difference between the right (-5dB) and left ear (10dB) at 16kHz. My brain is so fucking dumb that it can't cope with the fact that I don't have bat-like hearing in my left anymore, fighting tooth and nail to register this useless shrill tone. At least I can assume that a 10dB reduction would likely obliterate the worst thing that's ever happened to me. Normal speech in noise results, slightly better in the left actually (+1 word).

 

[Tweedleman]

No, I mean I think it will help those with inner hair cell damage who have normal audiograms (which only show outer hair cell damage). I'm speculating that it may be especially useful for them.

I looked up embryologic development of the cochlea last night and it appears the IHCs also develop first. If they are preferentially recovered, I wonder if it's because OHCs apparently don't develop until after IHCs are in place.

This gives me so much freaking hope. Still not sure what's to blame for the lack of clarity and intensity in my right ear (which performs the same as my left on my "normal audiogram"), but if it actually is IHC loss then I can't wait. Would it not be impossible for some IHC loss to occur after unprotected exposure to what was probably 120dB of roaring death metal in a small venue for close to 2 hours?

I really should get an extended audiogram done as well. I inquired but the audiologist was perplexed why I asked for one and said, "well you've probably lost most of them already." I am 26.

 

[FGG]

This gives me so much freaking hope. Still not sure what's to blame for the lack of clarity and intensity in my right ear (which performs the same as my left on my "normal audiogram"), but if it actually is IHC loss then I can't wait. Would it not be impossible for some IHC loss to occur after unprotected exposure to what was probably 120dB of roaring death metal in a small venue for close to 2 hours?

I really should get an extended audiogram done as well. I inquired but the audiologist was perplexed why I asked for one and said, "well you've probably lost most of them already." I am 26.

I'm 42 and it was clear my extended audiogram was highly abnormal, even age adjusted. An extended audiogram would be very useful imo. In my case, it is what led confirmation to my presumptive ototoxic diagnosis (my severe loss over 10000 Hz was exactly symmetrical bilaterally).

Often if you have enough damage to outer hair cells, imo it's not unreasonable to assume you could have damaged synapses and/or IHC at other frequencies.

 

[FGG]

@Tweedleman, this is an old study, maybe you could find something more recent but it looks like, at least in rabbits, noise can damage IHCs even without damaging OHCs.

https://link.springer.com/article/10.1007/BF00456330

Edit: Damaging any of these structures doesn't always mean permanent damage no matter what it is btw. If it's still early, you may not even need biotech's help.

 

[HootOwl]

Pulling for you extremely hard even though your presence on the forum would be sorely missed.

Thanks man (hug). I still don't know if I can go through with it because of the tympanogram but I figure one step at a time. And then there's the 25% chance of placebo

Honesty I might wait to see if the "exciting news" from Hough will be the start of their phase 2 trial. I think ultimately I'd prefer to risk placebo for a pill than 4 IT injections of placebo.

 

[Edg71908]

Any idea if FX-322 would help myself?

35 days ago I had a cold which turned into an ear infection/ruptured ear drum. The day my eardrum ruptured I had vertigo for 8 hours and lost all my hearing in my right ear. Tried steroids at day 16 and at day 22 started a series of 3 steroid injections. Still NO hearing (profound) and some tinnitus. Who know a cold virus could be so life changing! Trying to stay positive and hope in the next year this could help!

Thanks guys!

 

[brokensoul]

I really should get an extended audiogram done as well. I inquired but the audiologist was perplexed why I asked for one and said, "well you've probably lost most of them already." I am 26.

ENTs knowledge is outdated. Extended audiograms must become standard. Ignore the ENT and go for it.

Remember you may have lost lots of synapse ribbons per hair cell and that will not be clear from an audiogram, but will affect your hearing capabilities.

You have not lost most of the UHF region, that is a downright insane and idiotic statement to make for an ENT. You're 26 and for your age you should have up to 17kHz if your ears are healthy. In either case you will still have hearing above 8kHz given your standard audiogram is excellent up to 8kHz. It's not going to drop off to zero beyond 8kHz.

 

[brokensoul]

No, I mean I think it will help those with inner hair cell damage who have normal audiograms (which only show outer hair cell damage). I'm speculating that it may be especially useful for them.

I looked up embryologic development of the cochlea last night and it appears the IHCs also develop first. If they are preferentially recovered, I wonder if it's because OHCs apparently don't develop until after IHCs are in place.

I'm puzzled by this.

Why do audiograms (and OAE tests as well in fact) only test OHCs?

If that's true then ENTs are even more full of **** than I already thought when they say that your hearing is fine after an audiogram.

 

[brokensoul]

I might get in now that I've crossed the 6 month threshold from my last audiogram. Dropped them off at the clinic and they said they would get back to me with the final answer sometime this week.

Awesome. Rooting for you.

Do we agree on some secret language now or do we work that out later? Maybe post some rocking banana emoticons if your tinnitus improves?



What category of hearing loss do you have?

 

[brokensoul]

Anyone think this drug might preferentially repair IHCs in vivo or at least at a lower dose (used in phase 1, for instance) repairs them first?

Frequency Therapeutics got a great response in people who had moderate to severe losses and it is reasonable to assume those folks have more IHC damage than the minor loss patients. There is definitely speech information at the UHF but what if IHCs got repaired in the sub 8000 Hz range too and that helped contribute to the dramatic word score increases. They kept emphasizing clarity is what they are improving with this drug in their JP Morgan presentation, which points to IHC/synapse imo and also said they are a "cochlear synaptopathy" drug only where hair cells are repaired in their Q and A. It's clear this drug does OHCs too (improvements seen at 8000 Hz) but i think this drug may help a lot more people with tinnitus than think it will help because their audiograms are normal.

Other thoughts?

Why would the small molecules get deeper into the cochlea for IHCs than for OHCs? I don't see why it would be any different for IHCs.

They emphasise clarity in regards to the >8kHz region, because their solution is limited in the sense that it does not get beyond the base of the cochlea. In fact 8kHz may seem like it's beyond halfway the cochlea, but in reality it's still the basal region. If you look at a cochlear diagram you quickly see the compound barely enters the cochlea if it only reaches 8kHz. Their hydrogel will need to improve drastically for it to reach the apex and hence they adjusted objectives and expectations towards intelligibility (clarity), because they attribute clarity to the UHF region. In that sense, without improving the hydrogel, it will look as if this is an absolute success. In my opinion all their clarity statements refer to UHF improvements, both IHC and OHC.

David Luchino only answered the cochlear synaptopathy question in the sense that the hair cells grow and the nerve endings form ribbon synapses and connect to them. It is definitely not a cochlear synaptopathy drug although that was not that explicitly stated, but definitely implied.

FX-322 regenerates both IHCs and OHCs in the same proportion (although obviously different in absolute numbers). As demonstrated in their 2017 publication.

I would love to have a more in-depth understanding on various aspects of the differences between IHCs and OHCs. I've spent some time studying the difference in functionality in-depth. How they work physiologically and what they're really responsible for when it comes to hearing. It still does not click 100%, but must admit I have not yet spent enough time on it. It is clear though that they are very different. I feel the difference between them is completely overlooked and hardly ever discussed. Even Frequency Therapeutics doesn't touch on this.

Maybe that's why I'm missing what you're speculating about.

 

[FGG]

I'm puzzled by this.

Why do audiograms (and OAE tests as well in fact) only test OHCs?

If that's true then ENTs are even more full of **** than I already thought when they say that your hearing is fine after an audiogram.

Because hearing a tone in quiet only requires you to have 20% of your IHCs working. There really isn't a good test for this, although apparently an electrocochleagram can give you a clue about widespread damage at least according to one study I read but few audiologists seem to be aware of these studies.

 

[Tweedleman]

@Tweedleman, this is an old study, maybe you could find something more recent but it looks like, at least in rabbits, noise can damage IHCs even without damaging OHCs.

https://link.springer.com/article/10.1007/BF00456330

Edit: Damaging any of these structures doesn't always mean permanent damage no matter what it is btw. If it's still early, you may not even need biotech's help.

Well it's only been a little over two months. I really hope the damage isn't permanent. I understand ears take forever to heal, it's just each day that I wake up and feel the same the more I lose hope and look to biotech. I am going to seek out an extended audiogram.

 

[HootOwl]

Awesome. Rooting for you.

Do we agree on some secret language now or do we work that out later? Maybe post some rocking banana emoticons if your tinnitus improves?



What category of hearing loss do you have?

Omg don't tempt me with the banana emoticon secret language.

But there's still a substantial chance I'll get rejected if they've recruited enough and don't need anymore people with my notches. Because right now my hearing loss is concentrated between 13-17 kHz. Biggest notch is 35-40 dB at 16 kHz in both ears.

 

[FGG]

Why would the small molecules get deeper into the cochlea for IHCs than for OHCs? I don't see why it would be any different for IHCs.

They emphasise clarity in regards to the >8kHz region, because their solution is limited in the sense that it does not get beyond the base of the cochlea. In fact 8kHz may seem like it's beyond halfway the cochlea, but in reality it's still the basal region. If you look at a cochlear diagram you quickly see the compound barely enters the cochlea if it only reaches 8kHz. Their hydrogel will need to improve drastically for it to reach the apex and hence they adjusted objectives and expectations towards intelligibility (clarity), because they attribute clarity to the UHF region. In that sense, without improving the hydrogel, it will look as if this is an absolute success. In my opinion all their clarity statements refer to UHF improvements, both IHC and OHC.

David Luchino only answered the cochlear synaptopathy question in the sense that the hair cells grow and the nerve endings form ribbon synapses and connect to them. It is definitely not a cochlear synaptopathy drug although that was not that explicitly stated, but definitely implied.

FX-322 regenerates both IHCs and OHCs in the same proportion (although obviously different in absolute numbers). As demonstrated in their 2017 publication.

I would love to have a more in-depth understanding on various aspects of the differences between IHCs and OHCs. I've spent some time studying the difference in functionality in-depth. How they work physiologically and what they're really responsible for when it comes to hearing. It still does not click 100%, but must admit I have not yet spent enough time on it. It is clear though that they are very different. I feel the difference between them is completely overlooked and hardly ever discussed. Even Frequency Therapeutics doesn't touch on this.

Maybe that's why I'm missing what you're speculating about.

My speculation about IHCs isn't based on diffusion differences in the structures but rather on the contributions to "clarity." I think it's due to OHC and IHC growth in the ultra high frequencies *and* possibly also an increase in IHCs slightly more distally. This is my own speculation and i don't think an unreasonable one but it is still speculation.

It turns out, embryologically, IHCs are fully formed before OHCs form. I also wonder if there was a signal OHCs need from IHCs to form as there is with many complex structures that form.

With a large enough FX-322 dose, I am not sure this would matter as both should regenerate but i was contemplating the results and I think it's possible at the phase 1 dose, more IHCs were formed for one reason or another.

They have said they are only a synaptopathy drug in areas where the hair cell regrew and formed new synapses. IHC synapses are what is lost in "cochlear synaptopathy." They are mentioning IHCs specifically here.

 

[FGG]

To add to my esoteric IHC theory based on "clarity" findings in phase 1, if it did turn out to be true, this diagram could also explain why. There appear to be more LGr5+ plus cells immediately adjacent to OHCs.

Again, this is just my theory.

 

[jeff W]

They asked an otologic surgeon, not a researcher. I wouldn't take that quote too seriously. My first otologist *literally* wrote the otology surgery textbook and hadn't even heard of Frequency Therapeutics (this was post phase 1 results even).

So you found this out too! There is an unspoken rule in otology that cellular repair does not occur in the ear, hence hearing loss and vestibular damage cannot be reversed, only "adapted/compensated for". If Schuknecht were alive I do believe he would be following Frequency Therapeutics with great excitement.

I have heard shocking stories from this man (who goes to the symposiums)

 

[Tweedleman]

I would love to have a more in-depth understanding on various aspects of the differences between IHCs and OHCs. I've spent some time studying the difference in functionality in-depth. How they work physiologically and what they're really responsible for when it comes to hearing.

So would I. I did some quick searching but the material out there is extremely dense and went way over my head. Anybody else here able to break it down?