Frequency Therapeutics — Hearing Loss Regeneration

[RB2014]

Chief Development Officer and Chief Scientific Officer each buy 30,000 shares!

Can someone tell me this is a good sign and not just the usual answer of a 10b5-1 plan!?

Where did you get this info? Can you share the link? Is this the same Chief Scientific Officer that has been offloading shares all this time?

There will probably be another run up in the stock price before results from the next trials. It is probably a good sign though.

This is the FREQ Stock Chat thread (for Benefactors):

Frequency Therapeutics (FREQ)

 

[Gb3]

Chief Development Officer and Chief Scientific Officer each buy 30,000 shares!

Can someone tell me this is a good sign and not just the usual answer of a 10b5-1 plan!?

I think when they sell, that's part of the 105 whatever plan. Please someone correct me if I'm wrong. This is probably a good sign considering the price is so low right now.

 

[Tezcatlipoca]

Chief Development Officer and Chief Scientific Officer each buy 30,000 shares!

Can someone tell me this is a good sign and not just the usual answer of a 10b5-1 plan!?

Please God, Allah, Buddah, give us a win!

That would mean each of them bought about a third of a million dollars in shares.

 

[Diesel]

Chief Development Officer and Chief Scientific Officer each buy 30,000 shares!

Can someone tell me this is a good sign and not just the usual answer of a 10b5-1 plan!?

Restricted stock options. Part of their comp plan. Nothing to see here.

This is what they are selling from the 10b5-1 once they start maturing.

Also, this isn't really a stock chat item... it's just a normal business item. It's about retaining the leadership, and making sure they have something to lose/gain. Leadership has more to do with the product/company success than stock price.

 

[Lucifer]

Please God, Allah, Buddah, give us a win!

That would mean each of them bought about a third of a million dollars in shares.

I'm hoping that the age-related and severe hearing loss trials have great outcomes that somehow allow FX-322 to come out in the market as soon as possible.

I'm not sure how long I can wait for these treatments to come out.

 

[FGG]

I'm hoping that the age-related and severe hearing loss trials have great outcomes that somehow allow FX-322 to come out in the market as soon as possible.

I'm not sure how long I can wait for these treatments to come out.

If I remember correctly, your problem is mostly noxacusis, right? Are you taking steps to get as much natural healing on this (avoiding noise, setbacks, etc) as you can?

 

[Lucifer]

If I remember correctly, your problem is mostly noxacusis, right? Are you taking steps to get as much natural healing on this (avoiding noise, setbacks, etc) as you can?

Yea mainly noxacusis, but natural healing is not enough for me. I'm hoping something like FX-322 can get rid of the noxacusis.

I know many of you here are saying FX-322 is more likely to help loudness hyperacusis but I believe loudness hyperacusis and noxacusis are part of the same problem and that if you treat loudness hyperacusis then noxacusis will be treated as well.

When I compare both of my ears, the left ear is mainly loudness hyperacusis whereas the right ear is noxacusis and I notice that my right ear hear sounds a lot quieter than my left ear. This makes me wonder if restoring IHCs could help both loudness hyperacusis and noxacusis or whether OHCs need to be regrown to get rid of hyperacusis or both IHCs and OHCs need to be regrown.

Before getting hyperacusis and tinnitus, I noticed that my right ear had worse hearing than my left ear so maybe hearing loss in my right ear is causing the noxacusis.

 

[Greg Sacramento]

Restricted stock options. Part of their comp plan. Nothing to see here.

Also, this isn't really a stock chat item... it's just a normal business item. It's about retaining the leadership, and making sure they have something to lose/gain.

Leadership has more to do with the product/company success than stock price.

Ugh...

Use interface on graph - coins.

https://www.insiderscreener.com/en/company/frequency-therapeutics-inc

 

[roy1159]

I probably won't make it until FX-322 is out there (it probably won't make it to the market as it doesn't work anyway), but here's my realistic view on why its premise isn't so promising, based on current knowledge and my anecdotal case.

* It's not certain that EHF thresholds per se are the cause for problems understanding speech-in-noise in people with elevated EHF thresholds.
* Current diagnostics aren't enough to map the extent of hair cell damage, they should conduct the Békésy's audiogram and test a broadband of frequencies. Research showed that people with normal PTA often damage in the 'dead regions'.
* Older people have trouble understanding speech-in-noise because of auditory processing changes in the brain that are INDEPENDENT of hearing loss, how can they adjust that statistically?
* The presence of synaptopathy may be causing the problems for speech-in-noise and speech intelligibility, there are no conclusive methods yet to track cochlear neuropathy/synaptopathy in small doses (besides speech in noise which can have some value and ABR which is highly variable in humans).
*The changes in PTA thresholds they showed in the results aren't clinically meaningful.. test retest variabllity is usually 5 dB but often 10 dB changes can be seen. FX-322 doesn't work (yet?!).

This post isn't meant to discourage everyone, but we have to remember that mapping the different kind of dysfunctions in the ear isn't possible yet and companies will fail in the coming 10 years until diagnostics improve and the extent of synaptopathy and the mechanism of auditory processing disorder in normal hearing (according to PTA) in humans.

 

[ThomasRobert]

Where did you get this info? Can you share the link?

See the SEC Filings... To add, Chief Manufacture Officer buys 35,000 shares!

Chief Financial Officer also buys 30,000 shares!

 

[Diesel]

Ugh...

Use interface on graph - coins.

https://www.insiderscreener.com/en/company/frequency-therapeutics-inc

Huh?

 

[Trevor_phillips]

Yea mainly noxacusis, but natural healing is not enough for me. I'm hoping something like FX-322 can get rid of the noxacusis.

I know many of you here are saying FX-322 is more likely to help loudness hyperacusis but I believe loudness hyperacusis and noxacusis are part of the same problem and that if you treat loudness hyperacusis then noxacusis will be treated as well.

When I compare both of my ears, the left ear is mainly loudness hyperacusis whereas the right ear is noxacusis and I notice that my right ear hear sounds a lot quieter than my left ear. This makes me wonder if restoring IHCs could help both loudness hyperacusis and noxacusis or whether OHCs need to be regrown to get rid of hyperacusis or both IHCs and OHCs need to be regrown.

Before getting hyperacusis and tinnitus, I noticed that my right ear had worse hearing than my left ear so maybe hearing loss in my right ear is causing the noxacusis.

I have noxacusis too, but I definitely think that cochlear synaptogenesis drugs (OTO-413, PIPE-505) will provide more relief than FX-322, basing on the assumption that OHC Type 2 synapses are damaged/destroyed in noxacusis. If FX-322 does mostly regrow IHCs in vivo, then it will have a minor effect on noxacusis, unlike to hyperacusis.

 

[RichieTheKid]

What's the update on FX-322?

 

[FGG]

Yea mainly noxacusis, but natural healing is not enough for me. I'm hoping something like FX-322 can get rid of the noxacusis.

I know many of you here are saying FX-322 is more likely to help loudness hyperacusis but I believe loudness hyperacusis and noxacusis are part of the same problem and that if you treat loudness hyperacusis then noxacusis will be treated as well.

When I compare both of my ears, the left ear is mainly loudness hyperacusis whereas the right ear is noxacusis and I notice that my right ear hear sounds a lot quieter than my left ear. This makes me wonder if restoring IHCs could help both loudness hyperacusis and noxacusis or whether OHCs need to be regrown to get rid of hyperacusis or both IHCs and OHCs need to be regrown.

Before getting hyperacusis and tinnitus, I noticed that my right ear had worse hearing than my left ear so maybe hearing loss in my right ear is causing the noxacusis.

I'm not saying it's enough to just rely on natural healing and that it's still not life ruining (I have noxacusis now, too) but just to get you to a place where it is more endurable (symptomatically at least) since it will be a few years. That's all. It's obvious you are really hurting .

 

[serendipity1996]

I have noxacusis too, but I definitely think that cochlear synaptogenesis drugs (OTO-413, PIPE-505) will provide more relief than FX-322, basing on the assumption that OHC Type 2 synapses are damaged/destroyed in noxacusis. If FX-322 does mostly regrow IHCs in vivo, then it will have a minor effect on noxacusis, unlike to hyperacusis.

Type 2 synapses are different from Type 1 synapses - they are not destroyed or damaged by noise - in fact they have been shown to remain intact in damaged regions of the cochlea and may even increase in number following acoustic trauma (whereas Type 1s decrease in number).

 

[FGG]

I probably won't make it until FX-322 is out there (it probably won't make it to the market as it doesn't work anyway), but here's my realistic view on why its premise isn't so promising, based on current knowledge and my anecdotal case.

* It's not certain that EHF thresholds per se are the cause for problems understanding speech-in-noise in people with elevated EHF thresholds.
* Current diagnostics aren't enough to map the extent of hair cell damage, they should conduct the Békésy's audiogram and test a broadband of frequencies. Research showed that people with normal PTA often damage in the 'dead regions'.
* Older people have trouble understanding speech-in-noise because of auditory processing changes in the brain that are INDEPENDENT of hearing loss, how can they adjust that statistically?
* The presence of synaptopathy may be causing the problems for speech-in-noise and speech intelligibility, there are no conclusive methods yet to track cochlear neuropathy/synaptopathy in small doses (besides speech in noise which can have some value and ABR which is highly variable in humans).
*The changes in PTA thresholds they showed in the results aren't clinically meaningful.. test retest variabllity is usually 5 dB but often 10 dB changes can be seen. FX-322 doesn't work (yet?!).

This post isn't meant to discourage everyone, but we have to remember that mapping the different kind of dysfunctions in the ear isn't possible yet and companies will fail in the coming 10 years until diagnostics improve and the extent of synaptopathy and the mechanism of auditory processing disorder in normal hearing (according to PTA) in humans.

FX-322 obviously won't help synaptopathy and it is a really common problem but OTO-413 is very promising for that. PIPE-505 has potential too, we just haven't seen any results yet (results in June).

 

[kiki]

Phase II results, with almost 100 participants, were devastating. FX-322 showed no signal at all, with no difference between drug and placebo. FX-322 simply worked no better than sugar water.

I thought about it by looking at the two slides of the latest presentation.

Slide 16 states "Incidence higher across all groups than in single dose studies".

And it has been described as "No discernible hearing improvement over placebo observed."

Let's make a Phase2a graph under the condition of "Exceeding Absolute 10%" like the graph of Slide 17. The graph would look like 40% (placebo), 55% (x1), 50% (x2), 45% (x4), for example.

In this case, for example, if you change "Exceeding Absolute 10%" to "Exceeding Absolute 20%", can you see a more accurate difference between the drug and the placebo?

Isn't 10% their standard as well as 10 dB in PTA?

Attention:
Are cheaters evenly distributed in each group?
Are each fraud about the same?(40 word→ 30 word? 40 word→ 20 word? etc)
What's the impact of the the ceiling effect?

In the "final report", I would like you to show me the corrected version of the "Interim report" .

 

[roy1159]

FX-322 obviously won't help synaptopathy and it is a really common problem but OTO-413 is very promising for that. PIPE-505 has potential too, we just haven't seen any results yet (results in June).

Often there is mixed pathology, and as it turns out - synapses and IHC have a more major role in suprathreshold hearing function, for example speech in noise ability.

 

[FGG]

Often there is mixed pathology, and as it turns out - synapses and IHC have a more major role in suprathreshold hearing function, for example speech in noise ability.

I don't disagree. There is evidence so far that FX-322 has very good IHC response based on the Word Score results.

 

[GlennS]

The rats' hearing did improve in pre-clinical

What were their word scores?

 

[weab00]

I probably won't make it until FX-322 is out there (it probably won't make it to the market as it doesn't work anyway), but here's my realistic view on why its premise isn't so promising, based on current knowledge and my anecdotal case.

B-but the three super responders from Phase 1! (copes harder)

 

[Diesel]

B-but the three super responders from Phase 1! (copes harder)

I actually like that @roy1159 gave a dissenting point of view with reasonable explanations to back it up. Even though I disagree with the premise in the introduction.

 

[FGG]

What were their word scores?

The rats had improved ABRs and when sacrificed they had some OHC and IHC regrowth.

 

[FGG]

I actually like that @roy1159 gave a dissenting point of view with reasonable explanations to back it up. Even though I disagree with the premise in the introduction.

He outlined why it wouldn't work for synaptopathy anyway. But I'm not sure people thought it would for the most part.

 

[Diesel]

He outlined why it wouldn't work for synaptopathy anyway. But I'm not sure people thought it would for the most part.

Thanks for catching me up, I didn't look too deeply into the responses. Frequency Therapeutics have reiterated numerous times that FX-322 wouldn't work for cases where hair cells were present with underlying synaptopathy. If that is the case of his remarks, then I suppose they are invalid as it relates to dismissing FX-322.

 

[FGG]

Thanks for catching me up, I didn't look too deeply into the responses. Frequency Therapeutics have reiterated numerous times that FX-322 wouldn't work for cases where hair cells were present with underlying synaptopathy. If that is the case of his remarks, then I suppose they are invalid as it relates to dismissing FX-322.

To be fair his other point was the audiogram findings but that's been discussed to death for 20 pages.

 

[Thuan]

Just recently found out about the results from FX-322's Phase 2a clinical trial. I'm quite disheartened but I can't say I'm surprised as I previously had serious doubt and critical view of the FX-322 model.

If we all just disconnect from our bias and look at it from an engineering and mechanical point of view, regenerating cochlear hair cells alone is not the answer. You also need to have functional neuronal connections. Analogous to this is, you can't just reattach an arm and expect full recovery. Many times the nerves don't reattach. Similarly, you can't just expect renewed cochlear hair cells will reattach neuronally either.

As for our ears, I don't believe that simply regenerating cochlear hair cells is the solution but it is a significant discovery. The issue is if those hair cells can correctly reattach back to the central nervous system, to the auditory nerve. If not, then the regenerated cochlear hair cells are defective structures.

As some have previously pointed out that the "founder" of Frequency Therapeutics (serious conflict of interest here) says the regenerated hair cells do reattach back but their animals study data did not show this. The study mentioned neuronal growth but did not show if it actually connected back to the main nerve. If it did, then I'm sure they would have shown it in their research paper because this is as significant as regenerating cochlear hair cells.

The hair cell regeneration from their animal studies is strong (although I think independent scientific verification will nail this debate). But, I think the next key development is making further research into correct cochlear hair cell reconnections and I hope Frequency Therapeutics can survive financially to do further research.

Additionally, of course, there are opinions out there that says hearing loss isn't all that related to damaged ear structures but is related to our CNS rewiring and the loss of ability to process auditory signals. That is a possibility for a subset of hearing issues but FX-323 model is not targeting that so having doubts in this train of thought leads to nowhere.

Anyway, I hope you're all doing well or as well as we can be with tinnitus.

 

[Lucifer]

I have noxacusis too, but I definitely think that cochlear synaptogenesis drugs (OTO-413, PIPE-505) will provide more relief than FX-322, basing on the assumption that OHC Type 2 synapses are damaged/destroyed in noxacusis. If FX-322 does mostly regrow IHCs in vivo, then it will have a minor effect on noxacusis, unlike to hyperacusis.

Noxacusis could also be OHC related as well. In the Phase 1b trials they only did a hearing test up to 8 kHz and some of the patients had improvement in their audiogram at the highest frequency that was tested which was 8 kHz. If there was an improvement in 8 kHz, then there should be an improvement as well between 8-20 kHz, but that wasn't tested.

 

[Tezcatlipoca]

If we all just disconnect from our bias and look at it from an engineering and mechanical point of view

I think calling it bias is wrong. Why would we look at it from an "engineering and mechanical" POV?

It's regenerative medicine.

 

[GregCA]

The rats had improved ABRs and when sacrificed they had some OHC and IHC regrowth.

Oh so it's the sacrifice that triggered the OHC and IHC regrowth? Maybe that's what was missed in the human trial.