Frequency Therapeutics — Hearing Loss Regeneration

[Reinier]

To put in my two-penny worth.

I think high frequency hearing loss is not making hearing in noise more difficult.
Although 8 kHz is regarded as high frequency hearing, I see people on the forum mention frequencies like 12 kHz and 16 kHz.

The hidden hearing loss phenomenon (losing the higher sound level synapses on the hair cells) as the reason for this problem makes more sense to me.

Carl LeBel mentions in the interview (approximately at 44 minutes) that a hypothesis for the better word score could be that FX-322 switches on genes that set in motion the repair of synapses. That to me makes more sense than high frequency hearing loss being the reason for bad word scores. (I know he also mentions the high frequency hearing loss. But that is 8 kHz and not 12 or even 16 kHz).

Let us just hope we will find out sooner rather than later.

 

[sensualmosquito]

I hope that the phase 2a trials show more improvement in the pure tone category, since they saw 4/15 patients gain 10 dB improvements in 8 kHz in phase 1. That is right around where my hearing loss is so I'm hoping repeat dosing does better.

 

[UKBloke]

The hidden hearing loss phenomenon (losing the higher sound level synapses on the hair cells) as the reason for this problem makes more sense to me.

Makes more sense to me too. I also thought Carl LeBel's comment about hidden hearing loss meaning it was just something the medics hadn't found (or went looking for) was very astute. As a company, Frequency Therapeutics have really gone up in my estimation.

 

[Gabriel5050]

Prior experience with ENTs makes me think when FX-322 will be out I will go tell them about it and they will go "FX-what?... "

 

[AtlasFainted]

@MrCrybaby

I remember you saying you had similar fullness/popping symptoms to me and attributed it to middle ear muscles spasming. You expressed that you think FX-322 might remedy this.

I was wondering if you could provide any additional insights - mine constantly pop when I swallow or move my jaw, and of course I also have the fullness most of the time.

Have you tried a muscle relaxer to see if it mitigates the issue? I think I may have read on another thread somewhere that this worked for someone else. Thanks a ton for your time.

 

[El BUZZ]

Prior experience with ENTs makes me think when FX-322 will be out I will go tell them about it and they will go "FX-what?... "

No matter if that bunch of outdated scavengers don't know anything about it but I can't wait for the moment I can ask for it in an ENT consult.

 

[NewLionel]

@Paulmanlike & other FREQ investors:

What do you consider the risk to be to buy $10k worth of shares? I suppose if phase 2 results are positive, it could be a nice windfall?

I'm thinking of in investing too after listening to the Tinnitus Talk Podcast... if this drug works, what's the best case scenario? The share price multiplies by 10? By 100? It does seem like that would be possible?

 

[Diesel]

I'm thinking of in investing too after listening to the Tinnitus Talk Podcast... if this drug works, what's the best case scenario? The share price multiplies by 10? By 100? It does seem like that would be possible?

What I think is likely if the good news keeps rolling in:

DISCLAIMER:
I am basing my opinion on the few scholarly articles that study market reaction and overreaction to Clinical Trial outcomes and new drug releases. It's sparse and mostly focuses on cancer and other more well-known threatening illnesses.

OUTLOOK:
I'd peg it at $40-$50 / share up to 60-days following Phase 2A outcomes that are generally favorable and primary outcomes are the same as or better than Phase 1/2 Mod/Mod-Severe participants.

Breakthrough Therapy announcement would likely add another 35-50% after the Phase 2A bump. So, that might put it in a range of $55 - $75. Investors like when they see actions that speed up ROI.

Successive starts and favorable completions of a pivotal trial, EU/Asia trials, offer another set of increases in addition to the previously stated. At this point, there will likely be general audience attention for a Breakthrough Hearing Restoration drug. We're talking national news-worthy ABC/NBC/CBS; not the financial talking-head crap. They usually pick up drugs that are moving into Phase 3 and show promising results.

My own "back of napkin" calculation considering the initial US population this drug can help, and that it ends up being in the ballpark, competitive with hearing aides per treatment; assumes a $10-20B market cap sometime in 2023/24. Est Share price: $250 - $550 (assuming no splits or additional dilution).

If things start looking bad for some reason... $15.

 

[NewLionel]

What I think is likely if the good news keeps rolling in:

DISCLAIMER:
I am basing my opinion on the few scholarly articles that study market reaction and overreaction to Clinical Trial outcomes and new drug releases. It's sparse and mostly focuses on cancer and other more well-known threatening illnesses.

OUTLOOK:
I'd peg it at $40-$50 / share up to 60-days following Phase 2A outcomes that are generally favorable and primary outcomes are the same as or better than Phase 1/2 Mod/Mod-Severe participants.

Breakthrough Therapy announcement would likely add another 35-50% after the Phase 2A bump. So, that might put it in a range of $55 - $75. Investors like when they see actions that speed up ROI.

Successive starts and favorable completions of a pivotal trial, EU/Asia trials, offer another set of increases in addition to the previously stated. At this point, there will likely be general audience attention for a Breakthrough Hearing Restoration drug. We're talking national news-worthy ABC/NBC/CBS; not the financial talking-head crap. They usually pick up drugs that are moving into Phase 3 and show promising results.

My own "back of napkin" calculation considering the initial US population this drug can help, and that it ends up being in the ballpark, competitive with hearing aides per treatment; assumes a $10-20B market cap sometime in 2023/24. Est Share price: $250 - $550 (assuming no splits or additional dilution).

If things start looking bad for some reason... $15.

Thanks for the info, this is a very interesting read. So basically the window to invest is up until phase 2A results. I think this sounds like an investment with a lot of potential

 

[Paulmanlike]

I'm thinking of in investing too after listening to the Tinnitus Talk Podcast... if this drug works, what's the best case scenario? The share price multiplies by 10? By 100? It does seem like that would be possible?

This isn't a stock for the faint hearted/risk averse.

While everything is looking very good for now, there are some things I would consider before investing in FREQ.

- You don't have just a financial investment in this company - presuming you're on Tinnitus Talk you have hearing loss and/or tinnitus, you also have an emotional investment in the company. Your judgment can become cloudy. (See below).

- This isn't an ordinary biotech - it's difficult to compare it to say Alzheimer's drugs in trials that rarely make it to market because this has never been done before. No regenerate therapy for the cochlea exists. Nobody can tell you the 'chance' of success, only speculate.

- I would also like to remind investors what happened to the Auris Medical stock, EARS. On the IPO it was $6 a share. Today it trades at less than a dollar. I don't know if they've done a rev stock split since then but it's a stock I wouldn't touch (at least at this moment in time). I remember considering investing in them however I realised that AM-101 I had too much emotional investment in. I then learnt more and more about tinnitus and realised that drugs that claim to reduce or cure tinnitus are incredibly high risk and it would be unwise.

On the other hand, I am an investor of FREQ at an amount I'm prepared to lose because if their phase 2 or phase 3 fails, the price can drop significantly before you even have a chance to sell it. That is, I'm comfortable with losing the full amount.

Bottom line; you must be prepared to lose every penny in biotechnology stocks.

 

[Lucifer]

This isn't a stock for the faint hearted/risk averse.

While everything is looking very good for now, there are some things I would consider before investing in FREQ.

- You don't have just a financial investment in this company - presuming you're on Tinnitus Talk you have hearing loss and/or tinnitus, you also have an emotional investment in the company. Your judgment can become cloudy. (See below).

- This isn't an ordinary biotech - it's difficult to compare it to say Alzheimer's drugs in trials that rarely make it to market because this has never been done before. No regenerate therapy for the cochlea exists. Nobody can tell you the 'chance' of success, only speculate.

- I would also like to remind investors what happened to the Auris Medical stock, EARS. On the IPO it was $6 a share. Today it trades at less than a dollar. I don't know if they've done a rev stock split since then but it's a stock I wouldn't touch (at least at this moment in time). I remember considering investing in them however I realised that AM-101 I had too much emotional investment in. I then learnt more and more about tinnitus and realised that drugs that claim to reduce or cure tinnitus are incredibly high risk and it would be unwise.

On the other hand, I am an investor of FREQ at an amount I'm prepared to lose because if their phase 2 or phase 3 fails, the price can drop significantly before you even have a chance to sell it. That is, I'm comfortable with losing the full amount.

Bottom line; you must be prepared to lose every penny in biotechnology stocks.

AM-101 was only for the treatment of tinnitus whereas FX-322 is for the treatment of hearing loss and maybe for tinnitus. In the clinical trials FX-322 showed an improvement in people's hearing and these results can't be a placebo because you can't magically gain hearing. It's either you hear better or you don't.

To be honest I think FX-322 is more likely to succeed than fail from the clinical trial results so far. If FX-322 ends up getting better results in Phase 2a I can't see them failing. If it ends up reducing tinnitus, and also hyperacusis, that's even better.

 

[Paulmanlike]

AM-101 was only for the treatment of tinnitus whereas FX-322 is for the treatment of hearing loss and maybe for tinnitus. In the clinical trials FX-322 showed an improvement in people's hearing and these results can't be a placebo because you can't magically gain hearing. It's either you hear better or you don't.

To be honest I think FX-322 is more likely to succeed than fail from the clinical trial results so far. If FX-322 ends up getting better results in Phase 2a I can't see them failing. If it ends up reducing tinnitus, and also hyperacusis, that's even better.

This is an example @Lucifer of your "emotional investment". I'll point some things out.

"AM-101 was ONLY for the treatment of tinnitus"

ONLY??? There is not a single drug out there that is proven to reduce tinnitus and those that 'might help some' come with severe side effects. Even those drugs are not reliable for a reduction/elimination of tinnitus. Also, the market for ONLY tinnitus is huge. The number 1 related veteran disability is tinnitus, followed by hearing loss.
Also, tinnitus is incredibly homogeneous and complex and has baffled doctors over the years. When a cure for tinnitus is truly made; you'll know about it.

"It's either you hear better or you don't"

That's a fair comment regarding efficacy but clinical trials need to prove it is also safe, reliable methods of administering the drugs to the cochlear need to be found (that itself is very difficult), dosing, adverse effects, the list goes on... then you get onto the business side; Frequency Therapeutics are a business like any other business. They are new and they can go under at any time.

"I think it's more likely to succeed than fail, I can't see them failing"

I don't want to bring negativity but if we are talking as investors; the odds in the past are against you with biotechnology. It's 11% of drugs that goes from preclinical to FDA approval across the whole range, however as previously discussed this has never been done before so you can't apply it here strictly because PCA is new in terms of applying it to regenerate the cochlea.

When Auris Medical did their IPO, I had the same optimism because I wanted it to succeed beyond financial gain, however, I held back and thought to myself, would a normal everyday investor put everything he had into them and that answer was certainly no.

Do not put anything into FREQ that you are not prepared to lose. That's my investor head on. I'm comfortable with it being a high risk/high reward stock.

 

[Lucifer]

This is an example @Lucifer of your "emotional investment". I'll point some things out.

"AM-101 was ONLY for the treatment of tinnitus"

ONLY??? There is not a single drug out there that is proven to reduce tinnitus and those that 'might help some' come with severe side effects. Even those drugs are not reliable for a reduction/elimination of tinnitus. Also, the market for ONLY tinnitus is huge. The number 1 related veteran disability is tinnitus, followed by hearing loss.
Also, tinnitus is incredibly homogeneous and complex and has baffled doctors over the years. When a cure for tinnitus is truly made; you'll know about it.

"It's either you hear better or you don't"

That's a fair comment regarding efficacy but clinical trials need to prove it is also safe, reliable methods of administering the drugs to the cochlear need to be found (that itself is very difficult), dosing, adverse effects, the list goes on... then you get onto the business side; Frequency Therapeutics are a business like any other business. They are new and they can go under at any time.

"I think it's more likely to succeed than fail, I can't see them failing"

I don't want to bring negativity but if we are talking as investors; the odds in the past are against you with biotechnology. It's 11% of drugs that goes from preclinical to FDA approval across the whole range, however as previously discussed this has never been done before so you can't apply it here strictly because PCA is new in terms of applying it to regenerate the cochlea.

When Auris Medical did their IPO, I had the same optimism because I wanted it to succeed beyond financial gain, however, I held back and thought to myself, would a normal everyday investor put everything he had into them and that answer was certainly no.

Do not put anything into FREQ that you are not prepared to lose. That's my investor head on. I'm comfortable with it being a high risk/high reward stock.

You may be right about me having an emotional investment in hoping FX-322 to succeed and yea it may also fail too. I just believe the scientists that spent years on proving the efficacy actually understand how the drug works compared to previous clinical trials.

Even if it does not cure tinnitus, FX-322 would allow people to regain their hearing back which is something that has never been done before so it still would be a success either way.

 

[FGG]

You may be right about me having an emotional investment in hoping FX-322 to succeed and yea it may also fail too. I just believe the scientists that spent years on proving the efficacy actually understand how the drug works compared to previous clinical trials.

Even if it does not cure tinnitus, FX-322 would allow people to regain their hearing back which is something that has never been done before so it still would be a success either way.

I think what @Paulmanlike was alluding to (correct me if I'm wrong) is that it is a cardinal rule of investing not to invest in stocks you have an emotional attachment to because you will not be thinking strictly logical about them.

This is not to say what FX-322 will or won't do for tinnitus but rather, it is a general good philosophy that unless you have a ton of cash to potentially burn, you should spend time looking at all aspects of a stock including financials, management etc.

Biotech value is subject to a lot of things that have nothing to do with whether a drug works including insurance coverage, the market as a whole (if the whole market goes down so do individual biotech stocks because index funds have shares of them and people need to sell to free up cash in a bad economy), laws on distribution to other countries, etc.

I personally think Frequency will do well but I'm not taking out a home equity loan to buy more shares. There is always risk.

 

[tbuzz89]

I'm not sure if this is something has been addressed on this thread yet, so apologies in advance for not scrolling back through the thousands of prior posts!

Do we know if Frequency has recruited a suitable amount of enrollees for the Phase 2a trials across the country? Their qualification requirements are pretty stringent and was wondering if anyone has any insight. I wouldn't want to see a delay due to lack of qualified participants.

 

[tommyd87]

You may be right about me having an emotional investment in hoping FX-322 to succeed and yea it may also fail too. I just believe the scientists that spent years on proving the efficacy actually understand how the drug works compared to previous clinical trials.

Even if it does not cure tinnitus, FX-322 would allow people to regain their hearing back which is something that has never been done before so it still would be a success either way.

The truth though is there is no knowledge how any drug will work in someone in the real/human setting until it is tried as opposed to the research environment.

This is absolutely a part of the trial process and if it doesn't take place you don't know the things that we do, like with FX-322, such as that the treatment was safe, the drug did do what their aim was when the dose was injected in a person and we saw improvement in hearing as well as obviously hair cell regeneration too.

 

[FGG]

One question I wished was asked was how will they know the true effect on tinnitus without tone matching?

The people with UHF tinnitus were way more likely imo to be the positive anecdotes from phase 1 and since the drug has better delivery or binding there in those regions in that phase, I was wondering how they could separate that out in phase 2a without matching the tones.

 

[Jaysterk]

Thanks, that's a great idea, it never occurred to me that an intratympanic steroid injection that permeates would be a good way to raise this question for ENTs not familiar with FX-322. The precise permeability characteristics of the two substances might vary, but it's an excellent parallel.

The surgery is reversible. My ENT confirmed this to me. The doctor that invited the surgery was his mentor. I asked him this question specifically and he confirmed that it is in fact reversible. (I don't have the surgery).

 

[Jaysterk]

mine constantly pop when I swallow or move my jaw, and of course I also have the fullness most of the time.

I have the same thing in one ear.

 

[dan]

You may be right about me having an emotional investment in hoping FX-322 to succeed and yea it may also fail too. I just believe the scientists that spent years on proving the efficacy actually understand how the drug works compared to previous clinical trials.

Even if it does not cure tinnitus, FX-322 would allow people to regain their hearing back which is something that has never been done before so it still would be a success either way.

10 dB improvement in 4/15 patients, I would call that rather insignificant.

 

[FGG]

I'm not sure if this is something has been addressed on this thread yet, so apologies in advance for not scrolling back through the thousands of prior posts!

Do we know if Frequency has recruited a suitable amount of enrollees for the Phase 2a trials across the country? Their qualification requirements are pretty stringent and was wondering if anyone has any insight. I wouldn't want to see a delay due to lack of qualified participants.

They are still recruiting at all of their testing sites. They have attributed at least part of their delay in recruiting to COVID-19 and not their inclusion parameters.

If you aren't already, you can follow the status of testing with this link:

https://clinicaltrials.gov/ct2/show/NCT04120116?term=Fx+322&draw=2&rank=2

 

[Jurger]

They are still recruiting at all of their testing sites. They have attributed at least part of their delay in recruiting to COVID-19 and not their inclusion parameters.

If you aren't already, you can follow the status of testing with this link:

https://clinicaltrials.gov/ct2/show/NCT04120116?term=Fx+322&draw=2&rank=2

What's weird is that the study completion date hasn't been changed (yet).

 

[Jurger]

10 dB improvement in 4/15 patients, I would call that rather insignificant.

I agree, but it does indicate there's potential for restoration. Improvements in ultra high frequencies in Phase 2 should tell us whether the issue is the drug getting to the frequencies that are included in a standard hearing test. If I'm reading Carl LeBel's comments correctly, that's what Frequency is also suspecting. Or maybe the 2 or 4 injections in Phase 2 will already yield more improvement in the 250-8000 Hz frequencies.

 

[FGG]

What's weird is that the study completion date hasn't been changed (yet).

My guess is rather than continually update that info, they are probably waiting until they have a better idea of updated timeline.

 

[dan]

My guess is rather than continually update that info, they are probably waiting until they have a better idea of updated timeline.

Admit it, there wont be a cure, not in 5 years, not in 20 years.

 

[FGG]

Admit it, there wont be a cure, not in 5 years, not in 20 years.

Out of curiosity, have you listened to the Tinnitus Talk Podcast and read the studies?

 

[all to gain]

10 dB improvement in 4/15 patients, I would call that rather insignificant.

I disagree. The fact, it seems, that hearing can be restored at all is massive.

We, unfortunately, are just in the period when scientists are making initial attempts at this. If only we had been afflicted 30 years from now when, hopefully, hearing restoration will be bog standard practice.

 

[Jurger]

Admit it, there wont be a cure, not in 5 years, not in 20 years.

For me personally, I'm not banking on a cure. I just want my hearing loss reduced a bit. I'm not counting on discarding my hearing aids any time soon.

 

[dan]

Out of curiosity, have you listened to the Tinnitus Talk Podcast and read the studies?

No.

 

[FGG]

@dan,

I think the podcast transcript might make you feel more optimistic. A few points that might be less obvious:

--A 10 dB change means something is twice as loud. That's not insignificant. Factoring that on with doubling word scores, restoring hearing is happening. Those results are unprecedented. If you don't believe it, ask your audiologist what they think of the doubling word score results.

--Frequency believes the audiogram changes were much greater above 8000 Hz, that's why they are measuring 8000 Hz to 16000 Hz in phase 2A. They also believe multiple dosing should likely have an additive effect in terms of penetrance, but they don't know the range yet. They are measuring 250 Hz to 16000 Hz so we will know after 2A. Based on pre-clinical studies and the recent German cochlear explant studies, the drug does reach therapeutic concentrations and results in hair cell growth in the cochlea in humans.

--On the Tinnitus Talk Podcast, they mentioned while not having data yet because it wasn't an endpoint in phase 1, they did have anecdotes that tinnitus improved.

This later is a huge deal for tinnitus sufferers because in order for Frequency to have this info, patients reported it significant enough to their ENTs (there were 3 different practices in the San Antonio area used for phase 1) for them to report it to Frequency. Frequency was blinded to the study which means they got the testimonials from the ENTs after full completion of Phase 1 and not directly from these patients and these testimonials must have been strong enough (and likely from more than one ENT) for them to add tinnitus to their phase 2a endpoint. ENTs must have told Frequency "I know you weren't checking for tinnitus in phase 1, but we are hearing good reports."