Frequency Therapeutics — Hearing Loss Regeneration

Sure thing, thanks for explaining. Different opinions, different views. I sincerely feel like it would make more sense that someone's hearing comes back gradually, day by day, month by month, as more and more cells on more frequencies establish connections over time, instead of a switch flipping on one moment to another.

I hope you understand where my skepticism comes from. Trial results just don't show this to be a silver bullet for hearing loss, which the video is portraying.

It would be absolutely great if I was wrong and I sincerely hope I am.

 

Do you think eventually they'll have a better formula to improve speech recognition? Seems the current formulas only improve certain frequencies. I'm aware if all goes well with FX-322/FX-345, others may want to jump in and improve hearing in other ways. I'm aware word recognition is subjective but improving speech understanding I feel is almost as important.

 

FX-322 has proven to help some but not others with word recognition scores and hearing at high frequencies (8000 Hz) detectable with the standard audiogram in a small study group. So, nobody knows what the future will bring. We hope for both...

 

Do you know why he was able to improve so much with FX-322 only reaching the high frequencies?

 

Nobody knows that answer at this point in time. It definitely was a strange but positive outcome. I wish we all could get the same results...

 

That plus the enthusiasm of some members who start giving hope to recent joiners when they talk about how they got tinnitus without any scientific reasoning. They only talk about the range of people’s tinnitus and how FX-322 will reach to 8000 Hz and FX-345 would work for the rest of frequencies.

I remember there was a member here two years ago who had drawn this perfect diagram on which drug will work for you based on the type of hearing loss you have. Whereby now we see that Otonomy is almost out of business and FREQ keeps postponing the release of the results with a failed trial.

It’s good to have hope and faith, but some people here are just pumping hope in an irrational way imo.

 

I haven't read this anywhere, is it opinion or is it now established as fact?

Those who have pummelled their ears over the years and never get tinnitus are the elephant in the room where the vast majority of current research and ideas about what tinnitus is, in my view.

I'm certainly not academically qualified in this area, but, the only common-sense conclusion I've ever been able to reach about why some people get tinnitus when others don't is that tinnitus patients are born with some kind of malfunction in the gating/filtering-systems that are able to keep the electrical activity from one processing centre of the brain discrete from another.

In other words, the tinnitus was always there in the tinnitus patient, unrecognisable with a full cohort of hearing cells but gradually exposed as those cells die off. Potentially good news for any tinnitus patient receiving hearing restoration therapy.

 

Yes, that is actually a pretty accurate description of what some of the science has found is occurring.

Tuning out the noise: Limbic-auditory interactions in tinnitus

When I say the brain is "rewiring", I'm referring to the gating mechanisms you mention. It seems that those who suffer from tinnitus have a dysfunction of that gating/filtering and end up having to hear their tinnitus when others don't.

 

Purely speculation on my part but to me it seems that is sort of a sweet spot for FX-322 responders. The biggest factors at play are the cochlear penetration of the drug and how the overall functionality of the subjects cochlea is before treatment. Since FX-322 only reaches the higher frequencies, you'd expect that patients with hearing damage concentrated only in the higher frequencies would be better responders.

If you are in the severe or profound category of hearing loss, you've lost enough function in both the high and low frequencies that restoring simply the high frequencies doesn't do much when your low frequency hair cells are still garbage. But if you're in the moderately-severe category, your low frequency hair cells are still healthy enough that when you restore the high frequency ones, they work nicely with the low ones and the subject sees more functional improvement.

 

That is the whole point of FX-345. Its an improvement on FX-322 in that their goal is to get the compounds deeper into the cochlea so that they can reach more hair cells and potentially see a more efficacious response.

 

Its completely fair to be skeptical. Just keep in mind that the brain can do some weird and amazing things. I'm not going to discount the chance of that guy's improvement actually being from the drug simply because it occurred seemingly instantly. It very well could be the case that the cochlear hair cells where growing in place in the weeks leading up to his improvement but it was actually his brain that finally rewired to accept the new input. Remember that those who habituate to their tinnitus can tune it out completely and not hear it but the instant they think about it, they can hear the tinnitus again, just like flicking a light switch.

 

Chad, a question for you. Correct me if I'm wrong but I'm assuming they haven't changed the drug cocktail mix of FX-322 that they tested during the safety trial 3 years ago. The drug showed to be safe but only showed improvements in word recognition scores and a few trial patients saw minimal hearing improvements with their audiograms (high frequency only). So why would we think the upcoming Phase 2b trial results render any different results? It's just a larger trial sample size, correct? Same drug, just more people... Am I missing anything here?

 

Ah OK, makes sense.

Of all the tinnitus papers I've trawled through, that Rauschecker one still stands up. This idea of something else going on upstream of the cochlear is really intriguing, as is in fact, these gating circuits because they seem to share a common modality across various neurological conditions.

Pure speculation (and not Frequency Therapeutics related), but I find it curious that rTMS has been trialled not just on patients with tinnitus but also schizophrenia. The two conditions would seem completely unrelated, however, if the common-factor is a failure at the gating/filter level that allows one aspect of a system to leak over into its parent (whether that be aberrant audio into the audio processor, or in fact aberrant 'personality' into the central personality processing) then the gating model would make complete sense, as would a more-or-less common treatment protocol for treating patients with either condition.

 

@UKBloke, I always like reading your research conclusions and thoughts. I also notice that a lot of the off label medications given to tinnitus patients are antipsychotic types, which are prescribed to schizophrenia patients. I read an article about that too. Is this where musical tinnitus comes from?

 

One reason that there could be better results for this latest trial is that in previous trials, people with more severe hearing loss had better results so in this latest trial, they only recruited people from that category and not from the other categories that didn't have as good results.

 

Correct, they haven't changed the formulation for FX-322. You may look at it as "but only showed improvements in word recognition scores" but that is not how the audiology community & FDA sees it. FDA has already said they will accept word recognition improvements as the primary trial endpoint which essentially means FDA will approve FX-322 on word recognition alone if FREQ can prove efficacy over placebo. FREQ has had some subjects have MASSIVE improvements in word recognition scores in past trials. Subject 4 for example in the Phase 1/2 study had a baseline of 26 words (which is 6 words away from qualifying for a cochlear implant) and improved to 47 words at day 90. 47 words means that subject could potentially get by without hearing aids then. Seeing that there are no other therapeutic options out there, that is why the FDA is happy to approve FX-322 on word recognition alone.

As for why this time the results may be different, in the beginning FREQ was told by the FDA they would need to explore all the etiologies and severities of hearing loss if they wanted to apply for the broadest indication possible for FX-322 so that is what FREQ did with all their Phase 1 single dose studies. They found that they had a pretty consistent response in the moderate to moderately-severe range of hearing loss for both noise-induced and sudden hearing loss, around a 33% stat sig response rate on average that occurred across 2 independent trials. They found it doesn't work so well for age-related hearing loss and severe hearing loss with their other 2 studies. That is why some of their past studies have come back with positive data while others haven't. The current Phase 2b trial is specifically enrolling only those subjects that they believe have a chance to respond now. The analogy the company uses is that they now know where to go fishing when it comes to choosing who to put into their study and who not to.

All that being said, if the current trial can prove efficacy, it means that FREQ is targeting the right pathway and it bodes very well for FX-345 which in theory should generate even more efficacious outcomes.

 

I guess that is a decent point to make.

 

If FX-322/FX-345 had been developed and released for trials 25 years ago, it would have been approved with relative ease.

People's expectations and fussiness way higher these days.

 

That's an interesting point. I don't know too much about musical tinnitus but yes, perhaps the gating/filtering model could be a rational hypothesis.

 

I thought those with severe hearing loss had the best improvement compared to mild hearing loss.

Edit: I think it was only severe hearing loss that was noise induced/sudden and not age related.

 

No, it was those with moderate hearing loss who saw the biggest improvement.

 

Would someone with severe/profound hearing loss still be able to improve?

 

The best responders were those with moderate/severe hearing loss across previous trials. I think 5-10% had improvement with severe/profound hearing loss.

 

You would have to look back at their slides from one of the presentations. They did a good job showing what group responded better.

 

Slide 27 is what you are all discussing I believe.

 

So looking at that slide, they have not tested FX-322 in people with severe-profound hearing loss, but only those with mild to the low end of severe hearing loss? Best responders were those with moderately severe hearing loss caused by SSNHL.

 

Hey Chad, if this trial is successful, what number do you think the stock could jump up to again? Is it possible to get back up to $50's per share like back in February 2021? Fingers crossed for both hearing improvement and financial gains. But hearing improvements are FAR more important to me for my quality of life!

I currently have 21,000 shares. My cost/average is just under $2.00. What are your thoughts on the stock forecast if we get positive results and get to Phase 3 (Fast Track), then hopefully get through FDA approval? What's your opinion?

 

I see FREQ shares are at about $5/share so you would have a nice profit so far if your average is about $2/share. I hope their intratympanic formula is a success long term, whenever that may be. I haven’t been following them lately since their last year’s trial failure. After their stock dropped to about $1/share, I wasn’t much of a believer in any success.

 

This was partly fueled by the bubble in all stocks around the same time so highly unlikely it will bounce right back, if ever. Stock prices after the dotcom bubble took 15 years to get back to ATH with some never recovering.

 

Really depends what share price we end up at right before data drop. I think it's reasonable that we could double up overnight to anywhere from $10 to $20 on good data. If FX-322 proves efficacy, it revalidates their entire platform and it's game on from there. If FX-345 also comes back with positive data 6 months later, then we may start seeing that $40-$50+ range. Or I could be completely wrong and Phase 2b data comes back negative and we fall back down below $1.

The share price has no effect on the outcome of their trials and has been pretty disconnected from the underlying fundamentals of the company. It only affects their ability to raise capital in the future to keep the company funded. At $1, the company was being valued at 1/3 of their cash pile which was near bankruptcy levels yet the company had and still has enough funding to see 3 more trial results before they run out of cash.