Frequency Therapeutics — Hearing Loss Regeneration

We know from the Phase 1/2 that the brain readjusts to the newly created cells in those with SNHL and processes the new auditory signals. We also know from a few anecdotes that tinnitus may improve from the creation of the same cells. Two examples, in my opinion, of the brains ability to adapt in a positive way to changes in the auditory system.

 

I hope this does not mean bad news.

LinkedIn profile still shows him as working at Frequency Therapeutics as a Co-Founder and Vice President.

https://www.linkedin.com/in/will-j-mclean-phd-a66b7b11

 

Being a founder doesn't mean you have a managing position. Was he on that page before? I don't remember seeing him.

 

That's a very interesting field of research. Modeling the workings of the brain by computers!

 

Unfortunately, Will McLean's highly informative YouTube "Toward a Cure for Hearing Impairment" has been removed. Wished I had at least recorded the audio. Probably too many forward looking statements.

 

Same. That was such a good talk.

 

Direct perception:

Direct perception - Gibson's bottom up...

Restore the sensory input = reverse the disorder:

Molyneux's Question - Can It Be Solved?

Soon, we will be able to banish psychiatry from otology forever!

 

Is this something to be worried about in terms of the FX-322 Phase 2a clinical trial results due in March and May?

 

Lecture Toward a True Cure for Hearing...

Don't go to clipconverter.cc to download this clip for your personal reference.

 

No.

 

From what I can tell, this is the future as it pertains to neurology and understanding how this amazingly complex organ functions. There is still so much that is unknown about it despite us living in the 21st century. I'd really like to see some sort of renaissance in this field as both technology and medical research continues to progress.

 

No, he wasn't there before.

 

If we receive too many FX-322 injections, can it cause cancer?

 

Too much of anything causes cancer. Except maybe water.

 

No - their method doesn't lead to uncontrolled growth.

 

Anyone have any thoughts on the term “Radial” that Frequency Therapeutics trademarked back in October as a method for assessing hearing loss?

I’ve had some ideas on what they might be cooking up, especially with all the flaws they’ve been pointing out with the audiogram.

 

Whatcha thinking?

 

Regarding Radial, this is the academic article that sticks out the most:

Radial communication between the perilymphatic scalae of the cochlea. I: Estimation by tracer perfusion

And what do you mean by "flaws"? Flaws regarding coming to conclusions using an audiogram as a test in general? Or flaws with coming to conclusions using audiograms of individuals involved in the clinical trials?

 

Was this mentioned somewhere?

 

High oral doses caused cancer in rats. This was not shown by smaller localized doses (i.e. intratympanic use).

 

Interesting research. I should have clarified, the flaw is really in how doctors/patients think about the audiogram, and what it actually measures. For example, audiologists and patients seem to consider it the “gold standard” for hearing. How many people on here and on other hearing loss forums/communities say, “The doctor says my hearing is great/normal because all the 7 points on my audiogram are above the 20 dB horizon! Yet, I have screaming tinnitus, hyperacusis, distortions, and can’t hear shit in a noisy room!” Also, the audiogram doesn’t really give enough of a picture of the state of the patients condition. As discussed earlier in this thread, the specific pure tones used are really measuring the edge of octaves, but not necessarily where parts of speech exist. It also maxes out today at 8 kHz, unless you’re lucky enough to find an audiologist that will go to 16 kHz. It also only really measures OHC performance, yet IHC pay a pretty important role in understanding speech, music, etc.

I’ll take a deeper look at that research. I think they’re probably using Radial as a guide for determining how to dose FX-322 based on current measures (audiogram, word recognition, words-in-noise). And, since it’s going to be mum until those 90-day results are out, I might spend a little time sharing my thoughts with some visuals to keep us occupied.

 

I assume this follows from the fact that oral doses would lead the drug to become systemic, which then there's no telling what it might trigger.

Does it being localized guarantee that it will not escape the cochlea and thereby never become systemic? I am not sure how the flow of material into and out from the cochlea is modulated. What about when the gel is dispersed and the waste is discarded?

 

Do you think this could also be a potential solution for those who are likely to have some extent of hearing damage that is not visible on audiograms?

That still remains one of the concerns going forward, but if Frequency Therapeutics is also able to release a tool or technique that allows ENTs or audiologists to still determine damage in the ear (otherwise, how would they know the dosage?) that is excellent news.

 

Extensive pharmacokinetic studies are always part of pre-clinical work before any Phase 1 for any drug. They know how much and at what rate it diffuses into the bloodstream from the cochlea.

In addition, follow up studies during the phases have shown it to be safe.

Toxicities and adverse effects of any drug are highly dose dependent. This is a complete non-issue imo.

 

Based on what they're communicating so far, administration of FX-322 can "fit" within the current treatment paradigm. I think in the first "phase" of FX-322 being a commercial product, there simply won't be the industry-wide lift to adopt new testing methods to better understand/measure a patient's hearing loss; in fact, what may be needed doesn't exist. So, I think in the first "phase", Frequency Therapeutics needs to own communicating the method by which an audiologist/ENT take the current "standard" measures, convert them to a chart of some type to tell them how much FX-322 to dose someone over a period of time, and finally how to measure improvements afterwards using those "standard" measures today.

 

Ah, okay. My issue is that the current treatment paradigm doesn't seem to do much for those who have hidden hearing loss, since as you've mentioned doctors are always quick to tell their patients that they have "normal" or even "perfect" hearing when there's absolutely no way they know that for sure. I can't imagine professionals will be jumping to let patients get a shot of FX-322 when they can't find a discernible need for it, particularly as far as insurance goes.

I am just hoping that Frequency Therapeutics are aware of this issue and are seriously working towards being able to get help for those that may have normal audiograms, but given some of their communication regarding audiograms (such as that one post from a couple pages ago), there may be hope in this regard.

 

Below is an estimation of the number of subjects in Phase 2a who will report tinnitus improvement:

Total = 96
Non-placebo = 72
Estimated 70% have tinnitus = 50
Estimated 50% have unilateral tinnitus = 25 (only one ear injected, untreated ear still ringing)
Estimate 50% require 2 or more injections for tinnitus relief
25 - 1/3 x .5 x 25 = 21
1/3 being the fraction receiving less than 2 injections

There are many assumptions in this estimation (like disregarding placebo impact) but it does reveal that 21 subjects reporting TFI improvement would be a huge win.

 

I like your math. I think we should still consider 1 injection group as potential TFI responders, even if it isn't a lot. The Phase 1/2 showed some kind of benefit.

Next question is, if the responders are evenly distributed by group average (roughly 30% per group), will we see a stratified improvement per group? IE: 1x dose = average of 10% improvement, 2x = 20%, 4x = 40%?

 

This is exactly what I'm thinking through right now. How do they use data from word recognition, words-in-noise, audiogram, potential complaint of tinnitus, and convert that to a reliable dose schedule of FX-322?

One immediate concern is the doctors not giving enough if the first-go-round, and having to have the patient come back and pay for a "stronger" dose schedule.

 

Glad you are not my doctor.