Frequency Therapeutics — Hearing Loss Regeneration

Maybe inject the drug, put patient on a rotisserie, rotate for 45 minutes until done.

 

Just released today 10 minutes ago:

Frequency Therapeutics Announces Publication of Phase 1/2 Data Showing Hearing Improvements in Acquired Sensorineural Hearing Loss Patients Receiving FX-322

 

Stock just shot up after hours.

 

I'm out of my element, but I wonder if it could be combined with a spec of DMSO?

 

Old news! Lol.

 

Has anyone mentioned the microwick/tampon method yet?

 

If FX-322 showed similar results to OTO-413, that would be so good. We saw that even in speech in noise there were some improvements and if FX-322 can reach deeper in the round window with additional doses I don’t see how this drug can fail.

 

Even though it was old, Frequency Therapeutics tweeted about these results today.

 

No, no, hear me out. Three words: Trained delivery microbes.

 

I have some questions.

They mention Phase 2a studying tinnitus. Is that what's been completed or is that what's coming?

Also, a science question for those who can hazard a guesstimate...

I now have 4 sounds... 1 in my left ear is low rumbly which I only hear indoors or very quiet places. Most any noise, even the fridge running cancels it out. The most recent one starting last night is a super high pitched whistle in my right only resulting from sound... (someone talking loud enough, if I whistle it does it, etc).

So the question is, how can one aspect be cancelled by sound and one only happen as a result of sound (stops as soon as the causing sound stops)?

 

Yahoo Finance does not show this, neither do any other platforms I know of. Maybe they haven't updated it yet.

 

Should be $57.60, not $87.60. It's spiking up and down in the after hours right now.

 

I just looked as well, can't see anything either.

 

So the 90 day results for Phase 2a clinical trial will be coming out sometime March and this will include whether there were tinnitus improvements and also if word scores in both quiet and noise improved as well.

 

This is an official, published peer-reviewed journal article of their Phase 1/2 study. These results were already somewhat known, this just summarizes it and puts it into an official published document format.

The one we are all awaiting is Phase 2, in which they added tinnitus as a secondary measure. 90 day readout is at the end of Q1 2021, which is March 2021, and the study is estimated to be completed in May, 2021.

https://clinicaltrials.gov/ct2/show/NCT04120116

 

Post and pre-market numbers are regularly false hopes. Never rely on them...

 

I found this particularly interesting from the study:

"Those subjects with elevated EHF thresholds also had broader psychophysical tuning curves at 2 kHz. This suggests that hearing loss in the EHF region removes or at least reduces information vital to speech recognition tasks and introduces distortion in the mid- frequency region deemed crucial for speech intelligibility."​

Is this suggesting that losses in the extended high frequency caused the brain to change the tuning of the OHC in the cochlea at lower-frequency ranges to compensate for the losses? As if to imply the brain is trying to "stretch" the remaining hair cells to compensate for losses?

In doing so, I could see how distortions and hyperacusis might be present as the brain is over-utilizing surviving damaged structures.

 

I’m going to be laughing my ass off if FX-322 works for pain and loudness hyperacusis. I’ll be proving the doctors and specialists wrong, that the reason for hyperacusis is due to OHC loss and how they were saying restoring hearing doesn’t make the hyperacusis go away. It will be the biggest fuck you to the doctors and specialists.

 

In the paper they released today, they state that only 6 of the patients treated with FX-322 were capable of statistically significant Word Recognition Score improvements (the others already had scores of 90%+). In one of their previous presentations they actually showed the data for these 6 patients (attached). When I saw this slide last year, I didn't realize these were the only individuals capable of statistically significant improvement. Knowing that makes this slide seem much more impressive to me.

 

If so, it's all the more fortunate that the higher frequencies are the easiest to reach with FX-322.

 

I'm glad you brought this up. It's triggering when someone here posts something like, “yeah, my ENT said it was only a handful of people so that doesn't show much” and dismiss that 100% of the people that had room for improvement showed it. I'm glad in the recent publication they showed data down to the patient level for many of these data points that would otherwise be dismissed. Says a lot about the drug and a lot about the commitment of the company.

 

True if you have high frequency hearing loss. A select few have been blessed with both.

They won't care regardless.

 

The stock has tinnitus!

 

I know they won’t but it’s going to feel good for myself that I will prove them wrong if FX-322 works.

 

This is a good question, so I decided to investigate a bit more.

I think the first thing to note is that there is a difference between psychophysical tuning curves and frequency threshold curves - the reason for making this distinction will become more obvious down below. The difference, as far as I understand it, is that psychophysical tuning curves are estimated through behavioural responses in subjects, whereas frequency threshold curves, at least to my understanding, are measured through obtaining the different action potentials in OHC neurons at given thresholds and frequencies, typically by placing an electrode on the neuron. It's important to note that the latter can only be typically done ex vivo (perhaps with the exception of a zebrafish, as its OHCs are on its skin), hence why we resort to psychophysical tuning curves for live subjects. But the pertinent point is that psychophysical tuning curves may not always be representative of what's happening at a peripheral level in the cochlea, because our measurements have to go through an extra point in the signal chain: the brain.

Setting the above to the side for a moment, it's not immediately obvious to me how the OHC neuron can "stretch" its responsiveness across different frequencies, because this would mean changing the OHC action potential response at those given frequencies, which is a very physiological/mechanical feature as far as I understand it. Having said this, we know the brain can do some amazing things, and one of the quotes further down below would suggest your thesis is possible.

Before I come on to that, I should say that it wouldn't surprise me if action potentials/synaptic capacitance changed merely in response to exposure from noise, either due to inflammation or some other peripheral mechanism. In fact, the Baldri et al. study, which frequency paraphased, does seem to allude to this:

"impaired peripheral mechanisms ... are thought to influence the characteristics of the auditory filter estimated psychophysically".​

This would seem to be a more obvious pathway for how an OHC neuron can change/stretch its tuning curve, because the neuron is now receiving information from an OHC that has changed on a structural level.

What would seem more obvious to me is that the brain could, in response to EHF loss, adjust its own interpretation of peripheral information once received at a central level. With this in mind, the Badri et al. study gave the following as an explanation for the broader psychophysical tuning curve response at 2 kHz. The interesting thing to note is that it alludes to both possibilities: the brain "stretching" the OHC response, as you put it, but also the brain changing the peripheral information at a central level:

"Another possibility is that the broader filters in this population result from an impairment in central processes themselves or their influences on the periphery. The idea that impairments in central processes may contribute to altered tuning, even when the periphery appears to be normal, gains some support from a report by Sanes and Constantine-Paton (1985). They showed that frequency tuning curves in the inferior colliculus of mice who were raised in an environment of continuous clicks were wider than those of controls, especially on the high side, even though the two groups had identical cochlear thresholds."​

What implications this all may have for those of us with hyperacusis is something I still need to get my head around.

 

I feel you buddy. I know two people in particular that are going to get nasty emails about the subject if FX-322 helps noxacusis.

 

Share price is tanking... Any ideas why?

 

Look at the IBB, the entire biotech sector is down today.

 

The whole market is doing pretty bad today.

 

The whole market is taking a bath right now. The more complex answer though seems to be because of rising bond yields and a movement out of more riskier stocks [1]:

A sharp rise in yields on U.S. government bonds in recent days has sapped investors’ appetite for riskier assets, including stocks. Shares in technology companies, which have powered the broader market higher for much of the past year, are seen as particularly vulnerable, thanks to high valuations. Their profits become less valuable in today’s terms when investors apply a higher discount rate, thanks to rising 10-year Treasury yields, recently 1.37%.

The rise in bond yields “naturally does cause investors and cause markets to re-examine the view on equities,” said Paul Jackson, global head of asset allocation research at Invesco. Investing in government bonds is beginning to look more attractive for the first time in months, he said.

But “the level at which bond yields become truly problematic for equities is a long way from where we are now,” Mr. Jackson added.

...

Some investors say they are already re-evaluating their portfolios though. Most of those moves involve pulling some money out of growth stocks, which have been on a tear since the stock market’s plunge last year, and putting some of those gains into reopening stocks and other companies more tied to the economy.
​

$FREQ is a riskier stock and some people are just moving their money around, re-balancing to better take advantage of the economy.

[1] https://www.wsj.com/articles/global-stock-markets-dow-update-02-23-2021-11614070664?mod=hp_lead_pos1