Frequency Therapeutics — Hearing Loss Regeneration

[Diesel]

One thing that I would note from your comment is that while the CEO David Lucchino has indicated that there is a likelihood some people will still need a hearing aid after FX-322 due to it not going deep enough into the cochlea, I would still not rule out that they would not possibly work out a way to get the medicine deeper in the future.

The information which Frequency Therapeutics has released has always actually ended up being ultra conservative because they simply cannot risk falling afoul of the FDA rules. Therefore I equally wouldn't be surprised if Frequency Therapeutics was also being very cautious in commenting about the benefits of FX-322.

I refer back to where Frequency Therapeutics stated something along the lines that they didn't think FX-322 was going to be the medicine which would actually end up providing full regrowth, but that there are some pretty clever drug delivery guys so who actually knows what may end up happening. This tells me that the need to use FX-322 with hearing aids may not actually end up being a long term thing.

There could be every chance that I am wrong, however this gives me the impression that Frequency Therapeutics might actually go down the path of getting FX-322 out ASAP and work improving the benefit it can provide later on. This way Frequency Therapeutics can start assisting patients ASAP and work with improving things later.

Oh, I totally agree with you over the long-term. I'm speaking to expectations on what the drug we're talking about today is being positioned for. They're also speaking simply on what is known about the Phase 1/2.

If they show results that say the 4X dose group in the Phase 2A saw improvements down the 4 kHz or lower; the communications will change dramatically.

The best business case for FX-322 is to get the product producing revenue in its current state, even if it can't restore hearing completely. Having true cash flow gives them the ability to reinvest in the product development and expand into other hearing loss - related issues.

Lucchino has said that they intend for the drug to restore all hearing. I think it's just a matter of time (and money).

 

[all to gain]

Hair cells will continue to wear, even if regenerated. We cannot escape that part of the biology. Speaking of biology, it might be that the OHC/IHC that are regenerated are intermixed with original OHC/IHC with original wear. So, it's reasonable to predict that the original OHC/IHC will continue to wear out, thereby needing additional FX-322.

The durability isn't fully known of the new hair cells yet, either. It looks promising; but time and a ton of patients will tell. So, they probably made a conservative short-term estimate.

Also, consider the highest users of FX-322 - people in jobs/environment at a risk of daily high noise exposure. They'll probably be annual consumers of the stuff.

Also, it could be that they want to keep the faith with ENTs/Audiologists that are used to the annual visit model with hearing aids.

I was hoping that the new hair cells would be as good as new and would only wear out at the same rate as real hair cells. Maybe I'm being over optimistic?

Also tagging @FGG.

 

[FGG]

I was hoping that the new hair cells would be as good as new and would only wear out at the same rate as real hair cells. Maybe I'm being over optimistic?

Also tagging @FGG.

I think @Diesel is throwing out a theoretical possibility. I haven't seen signs that are more prone to loss.

 

[Michael01]

I wish they ran these trials in Australia. I'd be all over them in an instant. Heck I'd even think about flying into the U.S. to take part in a trial but I suspect that I wouldn't be eligible as a non-US citizen.

 

[all to gain]

If they show results that say the 4X dose group in the Phase 2A saw improvements down the 4 kHz or lower; the communications will change dramatically.

If that happens I'll be orgasmic.

May have to sell body parts or my soul to afford the drug though.

 

[Diesel]

I was hoping that the new hair cells would be as good as new and would only wear out at the same rate as real hair cells. Maybe I'm being over optimistic?

Also tagging @FGG.

Yes, correct. They probably are like new hair cells and wear at the same rate. But, as we know FX-322 will only replace damaged or missing cells. So, it's likely that some "worn" but not damaged cells will still be scattered throughout the population of new hair cells.

 

[FGG]

I wish they ran these trials in Australia. I'd be all over them in an instant. Heck I'd even think about flying into the U.S. to take part in a trial but I suspect that I wouldn't be eligible as a non-US citizen.

Phase 2a is done enrolling. By all accounts, the next trial will likely be worldwide.

 

[tommyd87]

Oh, I totally agree with you over the long-term. I'm speaking to expectations on what the drug we're talking about today is being positioned for. They're also speaking simply on what is known about the Phase 1/2.

If they show results that say the 4X dose group in the Phase 2A saw improvements down the 4 kHz or lower; the communications will change dramatically.

The best business case for FX-322 is to get the product producing revenue in its current state, even if it can't restore hearing completely. Having true cash flow gives them the ability to reinvest in the product development and expand into other hearing loss - related issues.

Lucchino has said that they intend for the drug to restore all hearing. I think it's just a matter of time (and money).

We are absolutely on the same page then. I think the money factor is a relevant point because being able to sell FX-322 as soon as possible means that they can generate the required money to reinvest in the drug dose/delivery element of their work.

This would be a smart investment strategy since Frequency Therapeutics can then expand their operations and treatment candidates. This will obviously mean more sales and more revenue, thus delivering bigger financial returns to their investors.

 

[ThomasRobert]

Cynthia Feldmann will assist in pricing FX-322:

Frequency Therapeutics Appoints Cynthia Feldmann to its Board of Directors

 

[Diesel]

We are absolutely on the same page then. I think the money factor is a relevant point because being able to sell FX-322 as soon as possible means that they can generate the required money to reinvest in the drug dose/delivery element of their work.

This would be a smart investment strategy since Frequency Therapeutics can then expand their operations and treatment candidates. This will obviously mean more sales and more revenue, thus delivering bigger financial returns to their investors.

This is also why I think the price will NOT be outrageous for the drug. The volume strategy (fair price, large market willing to pay) is going to fare better for fueling ongoing research.

Besides, a large portion of the buyers of the 1.0 drug will be back for the revised version anyway.

 

[Paulmanlike]

The biggest question I would like an answer to is whether those with a normal audiogram like myself (up to 8 kHz) with no detectable sign of hearing loss can go and get a dose of FX-322 to resolve their tinnitus.

Tinnitus is more prevalent than hearing loss and I'm assuming it bothers more people generally speaking, I know hearing loss is not nice to suffer from, but I have seen many people deal with it, and I have gone through the depressive stages with it myself.

Now I know FX-322 is a drug for hearing loss. But given the complexity of tinnitus, I'm feeling a bit pessimistic that this could be the 'cure' we're all hoping for. Even a reduction by 50% I would pay thousands for.

My dream is once these phase 2 results are released, that all the participants had their tinnitus gone. How magical would that be?

But after reading about tinnitus over the years it's appearing the odds are not in our favour.

Sorry for negativity, I just want this to work. My tinnitus is getting me down. Just rings non-stop and it's relentless.

 

[Diesel]

Cynthia Feldmann will assist in pricing FX-322:

Frequency Therapeutics Appoints Cynthia Feldmann to its Board of Directors

Maybe. But they also need someone focusing on maximizing their investors' money, and working on production deals. Not to mention having plans for utilizing the "bonus" payments from Astellas. Board Members usually are involved for their independence and unique ability to get the company access to certain goals, maintain stability, etc.

 

[tommyd87]

This is also why I think the price will NOT be outrageous for the drug. The volume strategy (fair price, large market willing to pay) is going to fare better for fueling ongoing research.

Besides, a large portion of the buyers of the 1.0 drug will be back for the revised version anyway.

I reckon that you are absolutely right.

I absolutely cannot see Frequency Therapeutics charge crazy amounts for FX-322 considering their regular comparisons to the hearing aid market and also the fact that there will be people wanting further treatment when the revised dose does become available.

Also if Frequency Therapeutics does provide FX-322 to emerging markets like Thailand and charges a higher price for it to be obtained in America, I can potentially see American consumers become annoyed and even consider nipping off for a holiday in Thailand to get the treatment done lol. Therefore I think it will be a reasonable price in all markets where FX-322 will be provided.

 

[Diesel]

The biggest question I would like an answer to is whether those with a normal audiogram like myself (up to 8 kHz) with no detectable sign of hearing loss can go and get a dose of FX-322 to resolve their tinnitus.

Tinnitus is more prevalent than hearing loss and I'm assuming it bothers more people generally speaking, I know hearing loss is not nice to suffer from, but I have seen many people deal with it, and I have gone through the depressive stages with it myself.

Now I know FX-322 is a drug for hearing loss. But given the complexity of tinnitus, I'm feeling a bit pessimistic that this could be the 'cure' we're all hoping for. Even a reduction by 50% I would pay thousands for.

My dream is once these phase 2 results are released, that all the participants had their tinnitus gone. How magical would that be?

But after reading about tinnitus over the years it's appearing the odds are not in our favour.

Sorry for negativity, I just want this to work. My tinnitus is getting me down. Just rings non-stop and it's relentless.

FX-322 is not a cure for anything.

It is a treatment for hearing loss. Tinnitus is likely experienced as a symptom of hearing loss, in particular the loss of OHCs/IHCs.

If FX-322 treats those lost OHCs/IHCs by restoring them, then the symptom should be reduced as well.

This is the only explanation why some Phase 1/2 patients claimed their tinnitus improved.

I do not expect FX-322 to bring anyone's TFI score in the Phase 2a to zero. But, it stands to reason that we may see some significant improvement. And that's better than what we have today.

I would expect to see a relationship between improvements in the HF audiogram and a reduction in TFI score. That would be enough to prove that it's the IHCs/OHCs causing the problem.

 

[weab00]

I'm unclear on if the 10 dB improvement we saw with some participants is significant or not? So it isn't as meaningful for profound hearing loss because 10 dB restored is not very significant, but it could be extremely beneficial to mild-moderate hearing loss + tinnitus?

 

[tommyd87]

The biggest question I would like an answer to is whether those with a normal audiogram like myself (up to 8 kHz) with no detectable sign of hearing loss can go and get a dose of FX-322 to resolve their tinnitus.

Tinnitus is more prevalent than hearing loss and I'm assuming it bothers more people generally speaking, I know hearing loss is not nice to suffer from, but I have seen many people deal with it, and I have gone through the depressive stages with it myself.

Now I know FX-322 is a drug for hearing loss. But given the complexity of tinnitus, I'm feeling a bit pessimistic that this could be the 'cure' we're all hoping for. Even a reduction by 50% I would pay thousands for.

My dream is once these phase 2 results are released, that all the participants had their tinnitus gone. How magical would that be?

But after reading about tinnitus over the years it's appearing the odds are not in our favour.

Sorry for negativity, I just want this to work. My tinnitus is getting me down. Just rings non-stop and it's relentless.

I think that there has been a revision regarding not only the theories about tinnitus but also what is known about it too.

I don't think that the causes of tinnitus and/or ways of treating it are as complex as what has previously been thought. I specifically refer to the fact that there has been good progress made with medicine that has shown to reduce the impact of tinnitus. Furthermore, I think that there are also a few more indicators that tinnitus could be treated simply by only needing to recover hair cells etc.

I would note that FX-322 might not provide complete tinnitus relief. Although FX-322 has anecdotal accounts indicating that tinnitus has improved after administering it, it might not completely cure tinnitus. I have this view because the information to date does indicate that there is also benefit provided by synapse treatments and that the synapse treatments might have a better effect on tinnitus. I think that this is evidenced through the fact that treatments targeting synapses like the Hough Ear Institute Pill are also claiming to improve tinnitus, and that there are people like you with no measurable hearing loss but who regardless have tinnitus.

 

[tommyd87]

I'm unclear on if the 10 dB improvement we saw with some participants is significant or not? So it isn't as meaningful for profound hearing loss because 10 dB restored is not very significant, but it could be extremely beneficial to mild-moderate hearing loss + tinnitus?

10 dB is significant regardless. It can also mean that the patient getting FX-322 may actually move from moderate to mild hearing loss for example.

I think that the more critical focus should be on what were the improvements like in the very high frequencies and also what the benefit was with repeat dosing. I certainly think that there would have been bigger gains which were larger than 10 dB made in the very high frequencies. Furthermore, if the evidence is accurate, I think that there might also again be a bigger benefit gained through repeated dosing. I think that there has been some fairly positive evidence that there is a bigger benefit from repeat dosing because the first dose allows FX-322 to activate the regeneration process and then the subsequent doses provide the effect needed to allow growth.

FX-322 is not a cure for anything.

It is a treatment for hearing loss. Tinnitus is likely experienced as a symptom of hearing loss, in particular the loss of OHCs/IHCs.

If FX-322 treats those lost OHCs/IHCs by restoring them, then the symptom should be reduced as well.

This is the only explanation why some Phase 1/2 patients claimed their tinnitus improved.

I do not expect FX-322 to bring anyone's TFI score in the Phase 2a to zero. But, it stands to reason that we may see some significant improvement. And that's better than what we have today.

I would expect to see a relationship between improvements in the HF audiogram and a reduction in TFI score. That would be enough to prove that it's the IHCs/OHCs causing the problem.

This is a very interesting but very clever and very accurate way of explaining what FX-322 actually does. Definitely not the way which I had thought about FX-322, however it makes absolute logical sense.

 

[Gb3]

As a hearing aid wearer I can tell you I would pay 5x if they could get rid of my hearing aids and give me back my normal hearing. Taking them in and out, cleaning them, repairing them, not having to wear them everyday. My hearing aids cost $13k.

I see FX-322 working with hearing aids and not replacing them. "We can get you 15 dB, better word clarity and for the remaining 50 dB, here is a hearing aid..."

They really need to get in the 50 dB to 60 dB improvement range in order to replace a hearing aid. Most people live with 10 dB to 20 dB hearing loss and it doesn't bother them.

I'm also curious what everyone thinks of FX-322's potential? How many dB do you think it can bring back? I'm down 110 dB at 8 kHz... This is why I don't see 10 dB as being a big deal, but I can imagine someone with a 40 dB loss thinking 10 dB will get them a little closer back to baseline.

Your hearing aids really cost $13,000?

 

[tommyd87]

Your hearing aids really cost $13,000?

That is really ridiculous. Mine won't cost anywhere near that amount and I am in Australia where the costs of them are notoriously over priced. I am pretty sure that if people are paying that amount for hearing aids then the benefit provided by FX-322 even at $5000 per ear will smash them out of the park in terms of performance and value.

 

[Billy_Shears]

The biggest question I would like an answer to is whether those with a normal audiogram like myself (up to 8 kHz) with no detectable sign of hearing loss can go and get a dose of FX-322 to resolve their tinnitus.

Tinnitus is more prevalent than hearing loss and I'm assuming it bothers more people generally speaking, I know hearing loss is not nice to suffer from, but I have seen many people deal with it, and I have gone through the depressive stages with it myself.

Now I know FX-322 is a drug for hearing loss. But given the complexity of tinnitus, I'm feeling a bit pessimistic that this could be the 'cure' we're all hoping for. Even a reduction by 50% I would pay thousands for.

My dream is once these phase 2 results are released, that all the participants had their tinnitus gone. How magical would that be?

But after reading about tinnitus over the years it's appearing the odds are not in our favour.

Sorry for negativity, I just want this to work. My tinnitus is getting me down. Just rings non-stop and it's relentless.

If your tinnitus is caused by noise-induced hearing loss it would have to be derived from those high frequencies from 8-20 kHz I would think. IF that is the case, FX-322 would likely be of substantial benefit. An extended audiogram would indicate this prognosis. It's a question with no answer until next Spring 2021, but hope and positive anticipation is greater than ever before - hang in there!

As for FX-322 being a cure to sensorineural hearing loss through regenerating outer and inner hair cells in the higher frequencies (and soon, lower frequencies) - it has proven to restore clarity in speech, word recognition scores, and speech-in-noise scores with clinical significance. With my mild-moderate SNHL and associated tinnitus, I consider this a cure. Clarity bolds well.

 

[Jurger]

I'm unclear on if the 10 dB improvement we saw with some participants is significant or not? So it isn't as meaningful for profound hearing loss because 10 dB restored is not very significant, but it could be extremely beneficial to mild-moderate hearing loss + tinnitus?

If they can get 10 dB improvement in multiple frequencies it might be significant for some patients, but 10 dB only in the 8 kHz frequency is really not that great. Now, improvements in ultra high frequencies might result in additional benefit, but it's not entirely clear yet how that works. Audiologists don't test those frequencies, hearing aids don't cover them. What we ultimately need is something that has the ability to improve the entire 250-8000 Hz range.

 

[Emgee]

If your tinnitus is caused by noise-induced hearing loss it would have to be derived from those high frequencies from 8-20 kHz I would think. IF that is the case, FX-322 would likely be of substantial benefit. An extended audiogram would indicate this prognosis. It's a question with no answer until next Spring 2021, but hope and positive anticipation is greater than ever before - hang in there!

As for FX-322 being a cure to sensorineural hearing loss through regenerating outer and inner hair cells in the higher frequencies (and soon, lower frequencies) - it has proven to restore clarity in speech, word recognition scores, and speech-in-noise scores with clinical significance. With my mild-moderate SNHL and associated tinnitus, I consider this a cure. Clarity bolds well.

If the first formulation can penetrate below 8000 Hz due to multiple doses, that would have massive implications on the hearing world. If not, treating high frequencies is still a game changer as high and low frequencies would be able to be helped at least in some regard (hearing aids, FX-322, etc.) We know a reformulation will be made to get deeper into the cochlea at some point. The company has expressed their interest in doing so. Right now, they are focused on delivering strong Phase 2a results that warrant Breakthrough Therapy designation from the FDA. If that's granted as I expect it to be, we will be that much closer to reducing the severity of our tinnitus affliction.

 

[Diesel]

If they can get 10 dB improvement in multiple frequencies it might be significant for some patients, but 10 dB only in the 8 kHz frequency is really not that great. Now, improvements in ultra high frequencies might result in additional benefit, but it's not entirely clear yet how that works. Audiologists don't test those frequencies, hearing aids don't cover them. What we ultimately need is something that has the ability to improve the entire 250-8000 Hz range.

Let's expand on FX-322 showing the 10 -15 dB improvement at 8 kHz. What they are showing is the edge of cochlea where FX-322 was concentrated enough to be effective in one dose.

What it seems they are showing without saying is: if the drug is working from the highest frequencies down to 8 kHz in one dose, it likely caused more than 10db of improved sensitivity in the higher range.

So, it stands to reason FX-322 did cause improvements of at least 10 dB at multiple frequencies: 10 kHz, 12 kHz, 16 kHz.

I know it is unrealistic, but it would be great to see an improved standard audiogram with more frequencies tested, i.e: 5 kHz, 7 kHz, etc.

 

[Joeseph Stope]

I also wouldn't mind people slowing down with posting in this thread and do so only when new information actually comes up. I don't think this is the place for discussing things like stock trades as I remember seeing here.

Of course we should stay broadly on topic... And in this category it is or should be about research -- well that's the title of it.

But a bit of circumspection would be required. The heavyweights such as 100 Hz, tommyd87 et al. are simply tops when analysing spiral ganglion nuclii and we awe-struck rustics can only gaze on in amazement.

The really heavy duty stuff is in the academic inner circles or maybe in the FREQ and OTIC boardrooms.

But it has to be translated down the line to the not so well initiated. Like us.

How the companies are reacting and how the public will react, I believe are or can be of benefit to us all. Just for example: @Bakkers from Holland was talking of organizing a trip over to Stateside with some friends so as to take part in a trial. Well, if you have to do a 14-day COVID-19 quarantine in some hotel somewhere... then there's the flight costs too... it might be much more practical if Frequency Therapeutics or Astellas did some trials in Europe.

Duh, I hope they have the people in place who know how to inject the inner ear tympanic membrane.

At the Oppenheimer Virtual Fall Healthcare Life Sciences & MedTech Summit CEO of Frequency Therapeutics David Lucchino divulged something about the pricing of FX-322.

Cochlear implants cost sometimes $50,000 - $100,000 so FX-322 will be expensive!!

DAVID LUCCHINO:
"I'm still evolving our understanding of this as we really work in partner with the FDA to understand exactly the true, we think, impact of our therapy. So it's hard for me to speak in any absolutes. We know that the market is absolutely substantial and the unmet clinical need is very, very high. We think that hearing aids will continue to have a real role and be a good option for patients, though we think having a therapy that can truly start to heal someone's hearing and create a healthy cochlea, if you will, is going to be a very strong value proposition both with or without hearing aids. I think that specifics around pricing and regulatory, those really need to be managed and played out appropriately. I think that we're aware of what hearing aids are priced at, and we're aware of what cochlear implants are priced at, and how hearing aids are handled from a regulatory standpoint and our goal is to deliver a highly effective therapy and do it in a way where we can continue to build out a very successful company that investors will recognize for years and years to come."

A brilliant scoop, right on the ball!

 

[Jurger]

Let's expand on FX-322 showing the 10 -15 dB improvement at 8 kHz. What they are showing is the edge of cochlea where FX-322 was concentrated enough to be effective in one dose.

What it seems they are showing without saying is: if the drug is working from the highest frequencies down to 8 kHz in one dose, it likely caused more than 10db of improved sensitivity in the higher range.

So, it stands to reason FX-322 did cause improvements of at least 10 dB at multiple frequencies: 10 kHz, 12 kHz, 16 kHz.

I know it is unrealistic, but it would be great to see an improved standard audiogram with more frequencies tested, i.e: 5 kHz, 7 kHz, etc.

The problem is that even if it does restore hearing in those ultra high frequencies, it doesn't help you get normal hearing. Most people have some degree of ultra high frequency hearing loss and do fine. Sure, I would take it, it's better than nothing. But it doesn't come close to restoring hearing in the 250-8000 Hz range.

By the way, in a standard hearing test, they test every frequency between 250-8000 Hz. So on the chart you can see where you're at at 3000, 5000, 7000 Hz etc.

 

[FGG]

By the way, in a standard hearing test, they test every frequency between 250-8000 Hz. So on the chart you can see where you're at at 3000, 5000, 7000 Hz etc.

They don't test every frequency. That's thousands of frequencies, you'd be there all week. Or did you mean they test every kHz, i.e. you had 3000 Hz, 5000 Hz and 7000 Hz specifically tested?

 

[all to gain]

I know Frequency Therapeutics is saying that the drug can get to 8 kHz, but originally they said 6 kHz, didn't they?

Do we, and they, still think it can get down to 6 kHz, and that they are now saying 8 kHz just to make sure they don't fall foul of the rules and regulations, i.e. playing on the safe side?

 

[Jurger]

They don't test every frequency. That's thousands of frequencies, you'd be there all week. Or did you mean they test every kHz, i.e. you had 3000 Hz, 5000 Hz and 7000 Hz specifically tested?

I mean that a normal audiogram roughly shows where you are at at every frequency between 250 Hz and 8000 Hz. So yes, including 3000 Hz, 5000 Hz and 7000 Hz.

 

[FGG]

I mean that a normal audiogram roughly shows where you are at at every frequency between 250 Hz and 8000 Hz. So yes, including 3000 Hz, 5000 Hz and 7000 Hz.

It doesn't though. The lines on an audiogram are to show a pattern. It doesn't indicate every frequency was measured. Each time you press the button, you are indicating when you hear one single frequency.

 

[Jurger]

I know Frequency Therapeutics is saying that the drug can get to 8 kHz, but originally they said 6 kHz, didn't they?

Do we, and they, still think it can get down to 6 kHz, and that they are now saying 8 kHz just to make sure they don't fall foul of the rules and regulations, i.e. playing on the safe side?

You're referring to a picture they have in their corporate presentation. I believe it showed the drug getting to a little under 8000 Hz (about 6500 Hz I think). I think that's just an estimate, extrapolated from their Phase 1/2 results. Frequency Therapeutics hopes multiple injections will result in the drug improving more frequencies. We'll see what happens. If not, they have a problem on their hands. At least as a hearing loss treatment.