Frequency Therapeutics — Hearing Loss Regeneration

[Ed209]

One problem is the rudimentary audiogram which often only goes up to 8 kHz. Extended high-frequency audiogram can show hearing loss in those upper frequencies but this test is rarely carried out. If you get perfect results from that too, you can still have hidden hearing loss.

The problem I have with this reasoning is that just about everybody has hearing loss in those upper frequencies, so testing and finding hearing loss there doesn't really tell us all that much (although, I'd still prefer it if they did). You will find a minefield of people with varying degrees of hearing loss (both in a traditional audiogram up to 8 kHz and those who only show upper losses), and those who have tinnitus as a symptom.

You are only getting an extra octave's worth of information for the average person by including the higher frequencies (depending on age, of course) because most 30 odd year-olds can only hear up to around 16 kHz. It should be expected that everyone will have damage of some kind, though, unless they are small children or something.

The crux of this argument cannot be settled until the hypothesis is put to the test, and that can't happen until someone manages to restore hearing loss so we can see what happens. Both sides have well thought out ideas of what could be happening to cause it.

 

[ploughna]

In their April corp. presentation, they do mention cash to see them into 2024 - I thought they had said 2023 previously? Result of recent actions and/or some additional funding?

 

[GlennS]

Ya, I've noticed the same article circulating about a patient that can hear better in a restaurant. I agree it seems like they are doing a rescue media campaign right now. We will just have to wait to see if the current trials will show any improvement.

That MIT article about hearing regeneration is circulating around on Google news in one shape or form or another almost like the algorithm has been gamed into viral status.

 

[Chad Lawton]

In their April corp. presentation, they do mention cash to see them into 2024 - I thought they had said 2023 previously? Result of recent actions and/or some additional funding?

Likely a combination of the recent layoffs and time passing as we get closer to 2024 so they can more accurately estimate spending. It's unlikely they've secured additional financing as they would have disclosed if they did.

 

[dbeats]

Everything is still on track. They laid off 30% of their workforce in order to preserve capital. This move ensures that they will see data on FX-322, FX-345 and FREQ-162 before they run out of money. If these trials are successful, the stock should recover nicely and then they should have no issue doing a share offering. They may even be able to bring in a partner on FREQ-162 that could result in milestone payments much like they did with Astellas.

I get the impression that their drugs are well developed already, so surely part of the lay-offs were redundant staff?

 

[Chad Lawton]

I get the impression that their drugs are well developed already, so surely part of the lay-offs were redundant staff?

Pretty much. They trimmed the fat where they could in order to get their cash pile to last longer.

 

[Joeseph Stope]

It's pity projects like this are unavailable to the common investor. If this was a DeFi project I'm sure many of us would gladly contribute our hard earned cash. Buying stock now is not supportive. If we could give them new funding it would be far more beneficial. Hopefully in the future the ordinary person can participate in fundraisers. In fact in crypto it is easy now, but not for a company that needs this kind of cash. If everyone who suffers from hearing loss could contribute €1,000 if they can afford it, we would have a treatment far faster.

As I pointed out to much abuse, Wall St. doesn't give a damn about the moral benefits.

It unfortunately is all about the $.

Frequency Therapeutics looks goosed from a funding perspective unfortunately.

A thought struck me the other day, so no harm in sharing my unscientific mind with someone of a finance background.

The Liberman study of hidden hearing loss seemed to bring out the hope that restoring the cochlea's higher frequencies might be of benefit to hearing-in-noise tests and perhaps also to alleviating tinnitus.

But in the experiment of March this year one of the reasons explained for the non-success was that FX-322 only penetrated the cochlea to the region of (correct me if I'm wrong) 8,000 Hz.

But surely this would have been more than enough to provide therapy to the upper regions of the hearing frequency scale and to cure any hidden hearing loss. No?

I'm sure the financial heavy-hitters are top-heavy into the research findings. Well wouldn't you if you had parked a few million in a company's stock.

What am I on about at all? Well a man's got a mind and sometimes he gets a notion.

 

[Padraigh Griffin]

In their April corp. presentation, they do mention cash to see them into 2024 - I thought they had said 2023 previously? Result of recent actions and/or some additional funding?

View attachment 49917

That is enough cash to see them through the end of 2023. Same as before. Hopefully FX-345 is a blockbuster.

 

[Diesel]

In their April corp. presentation, they do mention cash to see them into 2024 - I thought they had said 2023 previously? Result of recent actions and/or some additional funding?

View attachment 49917

Correct. They revised the cash availability into 2024. Could this have been the reason for some of the stock price recovering? Possibly one of them. Could also be the MIT article that has been pretty hot the past few days on social media.

In my opinion, it was a good move to reduce staff and keep cash available to move their 3 drug pipeline as far as they can. They may have given themselves up to another 6-months of reserves.

 

[Cernuto]

Nice interactive here:
https://www.frequencytx.com/speech-perception/

Looks like it focuses on addressing high-frequency hearing loss.

 

[GlennS]

Seems like FREQ is spending more time on marketing than R&D these days.

 

[Geatly]

Seems like FREQ is spending more time on marketing than R&D these days.

Marketing is important thing these days + it's important to explain people how does it work etc. They anyway can't do much in public domain right now, since they are in clinical trials with FX-322 and FX-345 going in clinical trials in autumn, so I don't know what do you expect them to do? I bet their scientists work on a daily basis on new formulas etc.

 

[scotty03874]

Pretty much. They trimmed the fat where they could in order to get their cash pile to last longer.

I just bought $7500 worth of FREQ. I hope they have good news and the stock spikes back up to $25 range. You never know.

When is the reporting of the NEW Phase 2a study coming out?

 

[Chad Lawton]

I just bought $7500 worth of FREQ. I hope they have good news and the stock spikes back up to $25 range. You never know.

When is the reporting of the NEW Phase 2a study coming out?

Nice, hold on to it for a couple of years and I think you will be nicely rewarded. New Phase 2 results are due Q4 of this year or Q1 of next year. In the meantime, we have FX-345 IND filing and initiation of that Phase 1 trial as well, hopefully in Q3, with results expected in the first half of next year.

 

[scotty03874]

Nice, hold on to it for a couple of years and I think you will be nicely rewarded. New Phase 2 results are due Q4 of this year or Q1 of next year. In the meantime, we have FX-345 IND filing and initiation of that Phase 1 trial as well, hopefully in Q3, with results expected in the first half of next year.

If the NEW Phase 2a results are positive, this could easily jump up to $20. I have 10,000 shares currently... more hoping for the hearing improvement results than the money by farrrrr!

 

[Geatly]

If the NEW Phase 2a results are positive, this could easily jump up to $20. I have 10,000 shares currently... more hoping for the hearing improvement results than the money by farrrrr!

I wish I could buy shares somewhere, but since I am from fcking Slovakia, can't find a broker for FREQ.

 

[Mentos]

I wish I could buy shares somewhere, but since I am from fcking Slovakia, can't find a broker for FREQ.

I'm in Poland and I managed to buy via Polish banking. You should be able to find one operating on NY stock market.

 

[Chad Lawton]

If the NEW Phase 2a results are positive, this could easily jump up to $20. I have 10,000 shares currently... more hoping for the hearing improvement results than the money by farrrrr!

Very nice! I've got 20,000 shares myself. I look at it as it's either going to make me a lot of money by going back to $30+ or it's going to 0 and I get a nice tax write off for a decade lol. I do fear that even if Phase 2b results are positive that the market may have a muted response to it as the space isn't very well understood. OTIC recently released some early data for OTO-413 that was positive and the stock barely moved. But if we can land positive results for FX-345 and FREQ-162, then we should be sitting pretty good.

 

[djdavid]

FREQ rises 42% in the stock market. Is there any good news about FX-322 that justifies this rise?

Please be careful when investing in a stock like this. The reason for the 42% rise is probably that the stock is heavily shorted. When the stock spikes like this, it's very likely to be because the shorters took profits on the shorts (essentially buying the stock). This is extremely speculative, only speculate what you can afford to lose. The stock is down 97% from the high but that doesn't mean that it couldn't go down more. Traders will play these games again and again.

 

[Eliot Martin]

Can someone please explain how the 5 subjects in the image above started to lose the benefits from FX-322 after only a couple of years? From what I know, it takes tens of years for someone to start losing hair cells even if exposed to high levels of noise. Can anyone intelligent explain?

 

[dbeats]

View attachment 50229

From what I know, it takes tens of years for someone to start losing hair cells even if exposed to high levels of noise.

This is incorrect. Outer hair cells are extremely delicate, and NIHL is indeed caused by exposure to loud noises over time, but also from very loud short sounds such as gunshots. We're not talking tens of years, we're talking seconds, minutes, and hours depending on the sound pressure level.

 

[Eliot Martin]

This is incorrect. Outer hair cells are extremely delicate, and NIHL is indeed caused by exposure to loud noises over time, but also from very loud short sounds such as gunshots. We're not talking tens of years, we're talking seconds, minutes, and hours depending on the sound pressure level.

But why did ALL of them start to LOSE those gains? Just asking out of curiosity.

 

[Diesel]

But why did ALL of them start to LOSE those gains? Just asking out of curiosity.

I suspect it was because the entire 15k hair cells weren't restored. So, the new ones are there, but existing hair cells deeper in the cochlea that still are aged/damage still continued to wear, causing a loss in hearing. Or, the regenerated hair cells just aren't as good/complete as the original equipment.

 

[Eliot Martin]

I suspect it was because the entire 15k hair cells weren't restored. So, the new ones are there, but existing hair cells deeper in the cochlea that still are aged/damage still continued to wear, causing a loss in hearing. Or, the regenerated hair cells just aren't as good/complete as the original equipment.

Well, if the hair cells are weaker, then they should stop this PCA nonsense and let the grand daddy of inner ear disorders (which is Otonomy) do the job for them! We don't want weak hair cells!

 

[dbeats]

Well, if the hair cells are weaker, then they should stop this PCA nonsense and let the grand daddy of inner ear disorders (which is Otonomy) do the job for them! We don't want weak hair cells!

It's all speculation. These are businesses trying to deliver a product into a market where there are no current therapeutic options. Stop acting entitled.

 

[Geatly]

Well, if the hair cells are weaker, then they should stop this PCA nonsense and let the grand daddy of inner ear disorders (which is Otonomy) do the job for them! We don't want weak hair cells!

Nobody really knows what is reason behind it, if it is happening at all, maybe it's not, and there is another reason behind it.

 

[RingingBrother]

But why did ALL of them start to LOSE those gains? Just asking out of curiosity.

Looks like maybe a minor correction where the hearing level stabilizes. It seems to hold steady a year later except for subject 5. Who knows if they went to a ton of concerts in between the exams.

 

[Chad Lawton]

View attachment 50229

Can someone please explain how the 5 subjects in the image above started to lose the benefits from FX-322 after only a couple of years? From what I know, it takes tens of years for someone to start losing hair cells even if exposed to high levels of noise. Can anyone intelligent explain?

It appears that some of the hearing benefits gained from FX-322 fade over time but subjects don't lose all of the benefit. This is consistent from both their Phase 1/2 trial as well as their FX-322-111 study where a number of subjects lost statistical significance but still retained clinical significance.

I speculate this waning benefit has to do with the anatomy of the cochlea and the amount of space the new hair cells have to fit into. If you look at the image I have attached which is from the Lgr5 study published in 2017, look at the images in Row E at the bottom left. The mouse cochlea had 6 rows of outer hair cells after FX-322 after treatment when they normally only have 3 rows before treatment much like humans. This is most likely caused by every single outer hair cell going through mitosis due to FX-322. The ear naturally functions with 3 rows of outer hair cells so I would hypothesize that when you increase it to 6 rows of outer hair cells, not all the new hair cells survive and some either die off or are cleared by the body in the years following FX-322 treatment. Or maybe the inner ear struggles to provide enough blood/nutrients to that many hair cells which causes some to die off? That's my hypothesis anyways.

 

[Geatly]

It appears that some of the hearing benefits gained from FX-322 fade over time but subjects don't lose all of the benefit. This is consistent from both their Phase 1/2 trial as well as their FX-322-111 study where a number of subjects lost statistical significance but still retained clinical significance.

I speculate this waning benefit has to do with the anatomy of the cochlea and the amount of space the new hair cells have to fit into. If you look at the image I have attached which is from the Lgr5 study published in 2017, look at the images in Row E at the bottom left. The mouse cochlea had 6 rows of outer hair cells after FX-322 after treatment when they normally only have 3 rows before treatment much like humans. This is most likely caused by every single outer hair cell going through mitosis due to FX-322. The ear naturally functions with 3 rows of outer hair cells so I would hypothesize that when you increase it to 6 rows of outer hair cells, not all the new hair cells survive and some either die off or are cleared by the body in the years following FX-322 treatment. Or maybe the inner ear struggles to provide enough blood/nutrients to that many hair cells which causes some to die off? That's my hypothesis anyways.

That's actually amazing if it produces more rows, of course if it works properly.

 

[Chad Lawton]

That's actually amazing if it produces more rows, of course if it works properly.

Based on all the preclinical and clinical data we've seen so far, I believe it works properly. The 33% average response rate we have been seeing makes sense when you consider how little cochlear penetration FX-322 has and the heterogeneity of hearing loss. I'm hopeful that FX-345 will at least double the response rate to over 66% and that we will see minor/modest audiogram improvements in the 6 kHz to 8 kHz range at a minimum.