13 ms·

Disclosure: I own FREQ stock. The failure of the prior trial was suspected, and I believe it, due to a refractory response by overdosing the inner ear with too

Disclosure: I own FREQ stock. The failure of the prior trial was suspected, and I believe it, due to a refractory response by overdosing the inner ear with too frequent administrations of the drug, and then testing for effect too soon. I bet even those candidates of the phase IIa trial though would, if checked on now, show some improvement. Animal research has shown that natural cochlear hair cell regeneration and resultant hearing restoration is very real, we mammals just don't have the natural cellular signaling to redifferentiate those base cells - small molecule drugs like FX322 do exactly that. I am optimistic they'll eventually find the right dosing regimen to see reliable and optimal clinical effect, and it will be a seismic advance in medicine.

taf2 5y ago
Looks like FREQ stock got really beat down over the last few months- any idea what happened was it the negative outcome of the study you mentioned?
- lr4444lr 5y ago
  There was suspected fraud on the part of the C(E?)O that he was soliciting investor money (and sold stock himself) with advance knowledge of the disappointing results of the trial I was mentioning and did not disclose it. Class action suits were filed. The trials preceding the Phase IIa results were all extremely promising, and even the Phase IIa one showed statistically significant effect on a sound discrimination, which many long time hearing sufferers can tell you is even more frustrating a problem than the inability to perceive sound. Biomedical research stocks are inherently risky. I could be deluding myself, but my lay reading of the research, and as someone who has suffered from tinnitus for a long time brought on my noise overexposure, I think there is a very promising shot at this drug. Maybe FREQ will not be the ones to realize it and some other company will take the patent into real life clinical medicine, and FREQ is certainly not the ONLY company pursuing this angle. But their successes so far have kept me holding the stock, and I keep buying more.
  - victor106 5y ago
    Interesting. Thanks for the honesty. What other companies are working on this problem?
  - trompetenaccoun 5y ago
    The study also found an improvement in the placebo group: https://www.businesswire.com/news/home/20210323005208/en/Frequency-Therapeutics-Releases-New-Data-from-Two-FX-322-Clinical-Studies-Plans-to-Advance-Single-Dose-Regimen https://www.businesswire.com/news/home/20210323005208/en/Fre... Interesting approach, I'd love to see it work. But given the mixed results plus the class action lawsuits that still seem unsettled (at least I didn't find any news), this doesn't really seem investable to me. Biotech startups are risky enough even without such problems.
Thebroser 5y ago
“Animal research has shown that natural cochlear hair cell regeneration and resultant hearing restoration is very real” - Although exciting, we also need to remember that translatability rates from animal models to humans is notoriously low, usually in the single digits for most therapeutic areas. This is some cool tech, but just wanted to point it out that success in animal models =/= we will eventually get to see the realized treatment.
- gumby 5y ago
  > Although exciting, we also need to remember that translatability rates from animal models to humans is notoriously low, usually in the single digits for most therapeutic areas. This is true of humans as well -- there are plenty of programs that get interesting and clear results in Phase 2 (the dose ranging phase: essentially "what dosage is most efficacious") that die in Phase 3 (roughly: "OK, how does that dose really work on a statistically significant population that also represents the demographics of the country"). These studies are so expensive that nobody goes into Phase 3 unless they believe Phase 2 pretty certainly demonstrated that the drug works, and well. It's also hard to figure out just how the animal's hearing is improving (you can't simply ask). I'm sure they have some experiments, but growing the hairs back may be necessary but not sufficient. Look at all those Alzheimers programs aimed at removing the plaque that haven't demonstrated any value in the clinic. The plaque might not even be alzheimers itself -- it could merely be the body's response to some different underlying effect of the disease. The choice of animal is very important, and the FDA cares a lot. Mice are popular because they are cheap. I worked on a program years ago that used guinea pigs because mice couldn't get the disease. We didn't use rats as the compound caused cancer in rats, and someone else had had their program derailed because the FDA required a separate analysis and study to demonstrate that the cancer was specific to rats and not other species (rats get lots of cancers). For our program the FDA required some studies in (non-guinea) pigs before they were willing to allow any human trials.
  - JohnBooty 5y ago
    It's also hard to figure out just how the animal's hearing is improving (you can't simply ask) This seems relatively easy, right? Play a sound at a given frequency, associate it with a food reward. Like Pavlov's dog, but vary the frequency of the bell. Oversimplification obviously, and "easy" is extreme relative to all the other hard parts involved but that part seems very doable
Traubenfuchs 5y ago
Why would they deliberately come up with a study design that harms their evaluation, trust, reputation, etc. and not one that optimized for best lab-condition results, like any sensible hair loss product company, for example?
- lr4444lr 5y ago
  I don't think any failure was deliberate. This is the cutting edge of cochlear medical research, and mistakes will happen. Perhaps they thought a little was good and more would be better? I am neither an employee or board member.
christmm 5y ago
Do you have more links, which make you have confidence in FX-322 and related treatments ?
samstave 5y ago
I have increasing;y bad tinnitus. Will this help with that? I hear a permanent and constant low-volume very high pitch "squeal" in my ears at all times, I was never a big loud music listener, and I have always brought ear-plugs to loud events - and have had no big ear-rupturing moments (such as a gun firing close to my head without protection etc...
- biellls 5y ago
  I would be interested to know that too. I imagine it would depend on the kind of tinnitus as it can be independent on hearing loss.
- dazc 5y ago
  I had odd bouts of tinitus as a teenager, like you, no obvious causes. It went away and came back with a vengence about 15 years ago. That lasted a year or so but over time it's become more of a minor irritation than a major handicap. I guess, my brain has trained itself to deal with it? The only tip I can give you is to always have some kind of background sound that you can focus on rather than the buzzing in your own head. Also, avoid earplugs and headphones, they just create a wierd feedback loop.
  - adriand 5y ago
    The best advice I ever got about my tinnitus was from my mom, who has worse tinnitus than I do: "just forget about it". I know that might sound difficult, but honestly, just try. When you notice it, reassure yourself that it's not really a big problem, and then turn your attention to other things. If you are successful with this, eventually you will only notice it when you remember that you have it and listen for it. A couple of the things I used to tell myself when it troubled me more than it does now: - There's nothing you can do about this, so just forget about it. - We all accumulate damage as we age. None of us are going into the grave in prime condition and if we do, that's a mark of a life not well-lived. - The fact I can hear this noise means I'm alive: "I hear ringing, therefore I am". These may not be helpful to you, so invent your own! The other thing I would recommend is getting a hearing test. If it turns out you have hearing loss, then treatment for that (e.g. hearing aids) may reduce your tinnitus (one theory is that tinnitus is caused by your brain "turning up the gain" on your "audio inputs", so that when you have a hearing aid, your brain no longer needs to do that, and your tinnitus diminishes). If it turns out you don't have hearing loss, then you can reassure yourself that your tinnitus is not a sign of any damage. I had always assumed my tinnitus was the result of damage due to a lot of music events but it turns out I have excellent hearing, which helps me ignore my tinnitus, because I no longer view it as proof that I hurt myself. You may also notice that certain things make your tinnitus worse. For instance, if I have a few drinks, mine gets noticeably louder. But because I know the alcohol will wear off, I just ignore it because it's temporary.
FLORESFIB 5y ago

taf2 5y ago

Looks like FREQ stock got really beat down over the last few months- any idea what happened was it the negative outcome of the study you mentioned?

lr4444lr 5y ago
There was suspected fraud on the part of the C(E?)O that he was soliciting investor money (and sold stock himself) with advance knowledge of the disappointing results of the trial I was mentioning and did not disclose it. Class action suits were filed. The trials preceding the Phase IIa results were all extremely promising, and even the Phase IIa one showed statistically significant effect on a sound discrimination, which many long time hearing sufferers can tell you is even more frustrating a problem than the inability to perceive sound. Biomedical research stocks are inherently risky. I could be deluding myself, but my lay reading of the research, and as someone who has suffered from tinnitus for a long time brought on my noise overexposure, I think there is a very promising shot at this drug. Maybe FREQ will not be the ones to realize it and some other company will take the patent into real life clinical medicine, and FREQ is certainly not the ONLY company pursuing this angle. But their successes so far have kept me holding the stock, and I keep buying more.
- victor106 5y ago
  Interesting. Thanks for the honesty. What other companies are working on this problem?
- trompetenaccoun 5y ago
  The study also found an improvement in the placebo group: https://www.businesswire.com/news/home/20210323005208/en/Frequency-Therapeutics-Releases-New-Data-from-Two-FX-322-Clinical-Studies-Plans-to-Advance-Single-Dose-Regimen https://www.businesswire.com/news/home/20210323005208/en/Fre... Interesting approach, I'd love to see it work. But given the mixed results plus the class action lawsuits that still seem unsettled (at least I didn't find any news), this doesn't really seem investable to me. Biotech startups are risky enough even without such problems.

Thebroser 5y ago

“Animal research has shown that natural cochlear hair cell regeneration and resultant hearing restoration is very real” - Although exciting, we also need to remember that translatability rates from animal models to humans is notoriously low, usually in the single digits for most therapeutic areas. This is some cool tech, but just wanted to point it out that success in animal models =/= we will eventually get to see the realized treatment.

gumby 5y ago
> Although exciting, we also need to remember that translatability rates from animal models to humans is notoriously low, usually in the single digits for most therapeutic areas. This is true of humans as well -- there are plenty of programs that get interesting and clear results in Phase 2 (the dose ranging phase: essentially "what dosage is most efficacious") that die in Phase 3 (roughly: "OK, how does that dose really work on a statistically significant population that also represents the demographics of the country"). These studies are so expensive that nobody goes into Phase 3 unless they believe Phase 2 pretty certainly demonstrated that the drug works, and well. It's also hard to figure out just how the animal's hearing is improving (you can't simply ask). I'm sure they have some experiments, but growing the hairs back may be necessary but not sufficient. Look at all those Alzheimers programs aimed at removing the plaque that haven't demonstrated any value in the clinic. The plaque might not even be alzheimers itself -- it could merely be the body's response to some different underlying effect of the disease. The choice of animal is very important, and the FDA cares a lot. Mice are popular because they are cheap. I worked on a program years ago that used guinea pigs because mice couldn't get the disease. We didn't use rats as the compound caused cancer in rats, and someone else had had their program derailed because the FDA required a separate analysis and study to demonstrate that the cancer was specific to rats and not other species (rats get lots of cancers). For our program the FDA required some studies in (non-guinea) pigs before they were willing to allow any human trials.
- JohnBooty 5y ago
  It's also hard to figure out just how the animal's hearing is improving (you can't simply ask) This seems relatively easy, right? Play a sound at a given frequency, associate it with a food reward. Like Pavlov's dog, but vary the frequency of the bell. Oversimplification obviously, and "easy" is extreme relative to all the other hard parts involved but that part seems very doable

Traubenfuchs 5y ago

Why would they deliberately come up with a study design that harms their evaluation, trust, reputation, etc. and not one that optimized for best lab-condition results, like any sensible hair loss product company, for example?

lr4444lr 5y ago
I don't think any failure was deliberate. This is the cutting edge of cochlear medical research, and mistakes will happen. Perhaps they thought a little was good and more would be better? I am neither an employee or board member.

christmm 5y ago

Do you have more links, which make you have confidence in FX-322 and related treatments ?

samstave 5y ago

I have increasing;y bad tinnitus. Will this help with that? I hear a permanent and constant low-volume very high pitch "squeal" in my ears at all times, I was never a big loud music listener, and I have always brought ear-plugs to loud events - and have had no big ear-rupturing moments (such as a gun firing close to my head without protection etc...

biellls 5y ago
I would be interested to know that too. I imagine it would depend on the kind of tinnitus as it can be independent on hearing loss.
dazc 5y ago
I had odd bouts of tinitus as a teenager, like you, no obvious causes. It went away and came back with a vengence about 15 years ago. That lasted a year or so but over time it's become more of a minor irritation than a major handicap. I guess, my brain has trained itself to deal with it? The only tip I can give you is to always have some kind of background sound that you can focus on rather than the buzzing in your own head. Also, avoid earplugs and headphones, they just create a wierd feedback loop.
- adriand 5y ago
  The best advice I ever got about my tinnitus was from my mom, who has worse tinnitus than I do: "just forget about it". I know that might sound difficult, but honestly, just try. When you notice it, reassure yourself that it's not really a big problem, and then turn your attention to other things. If you are successful with this, eventually you will only notice it when you remember that you have it and listen for it. A couple of the things I used to tell myself when it troubled me more than it does now: - There's nothing you can do about this, so just forget about it. - We all accumulate damage as we age. None of us are going into the grave in prime condition and if we do, that's a mark of a life not well-lived. - The fact I can hear this noise means I'm alive: "I hear ringing, therefore I am". These may not be helpful to you, so invent your own! The other thing I would recommend is getting a hearing test. If it turns out you have hearing loss, then treatment for that (e.g. hearing aids) may reduce your tinnitus (one theory is that tinnitus is caused by your brain "turning up the gain" on your "audio inputs", so that when you have a hearing aid, your brain no longer needs to do that, and your tinnitus diminishes). If it turns out you don't have hearing loss, then you can reassure yourself that your tinnitus is not a sign of any damage. I had always assumed my tinnitus was the result of damage due to a lot of music events but it turns out I have excellent hearing, which helps me ignore my tinnitus, because I no longer view it as proof that I hurt myself. You may also notice that certain things make your tinnitus worse. For instance, if I have a few drinks, mine gets noticeably louder. But because I know the alcohol will wear off, I just ignore it because it's temporary.

FLORESFIB 5y ago