Frequency Therapeutics — Hearing Loss Regeneration

[Jrblovsky]

What sources of cochlear damage would we not expect FX-322 to heal? I would imagine impact related trauma and congenital disorders it would not. Would we expect typical viral and ototoxic damage to improve with FX-322 or just noise induced damage?

Anything related to hair cell damage. This has been discussed and debated many times. I think it will help both groups.

 

[Jrblovsky]

I think people have been taking that snippet too literally. What he seems to be saying in a general way is that they expect FX-322 to improve hearing. The appropriate treatment option after that may change depending on where you end up on the curve. Like you, I'm encouraged that he thinks that FX-322 might help people with close to profound hearing loss.

You asked for an audiologist and you got Khalil Gibran? Cool.

My take on what he said is that if you are in the severe/profound range you will be able to avoid a cochlear implant and use a hearing aid. I think that is a stretch. I guess if they get people from profound into moderate/mild loss it may help. However, as I have stated before hearing aids are crap. However, if they address hidden hearing loss along with hair cells they can get it to help. To me a hearing aid makes everything loud and still a garbled mess if there is any background noise. I have moderately severe losses in nearly every frequency including the lows in my right ear. Normal hearing in left ear.

 

[patorjk]

Interesting job posting.

https://www.frequencytx.com/jobs/co-op-delivery-innovation/

"Work closely with project scientists to carry out experiments to develop novel polymer-based, small molecule inner ear drug delivery systems."

Sounds like they are working on a better gel.

I wonder if this confirms that the Phase 2a results will be one of your "meh" scenarios. This posting is new, it's not even on LinkedIn yet. The description mentions that "the Co-Op will support the development of the next generation of treatments for hearing loss" - basically FX-322 version 2.

Based on the math you showed a few weeks ago, they would have been delivered the data in early February, which means they probably have some idea of what the data shows. They probably had it in the back of their mind that they needed a new gel, and the Phase 2a data reinforces that.

I still think we'll see good results, but I have a feeling the first version of FX-322 is going to be for high frequency hearing loss / word clarity only.

 

[Diesel]

I think people have been taking that snippet too literally. What he seems to be saying in a general way is that they expect FX-322 to improve hearing. The appropriate treatment option after that may change depending on where you end up on the curve. Like you, I'm encouraged that he thinks that FX-322 might help people with close to profound hearing loss.

In every interview LeBel is clearly responding conservatively when it comes to the release timeline for FX-322 and how well he thinks it will treat SNHL. I suspect he's offering the minimum expected case from a 1 dose scenario.

In the last few interviews/webcasts, you can tell questioning seems to dance around this "cure" idea for FX-322 and SNHL without it being said directly. I suspect that if the Phase 2A results look promising, Frequency Therapeutics is going to have a tough time keeping a lid on those types of expectations.

 

[Princebeyel]

My take on what he said is that if you are in the severe/profound range you will be able to avoid a cochlear implant and use a hearing aid. I think that is a stretch. I guess if they get people from profound into moderate/mild loss it may help. However, as I have stated before hearing aids are crap. However, if they address hidden hearing loss along with hair cells they can get it to help. To me a hearing aid makes everything loud and still a garbled mess if there is any background noise. I have moderately severe losses in nearly every frequency including the lows in my right ear. Normal hearing in left ear.

Isn't he just being conservative though?

I mean he'd seem like an incompetent ass if he just straight up said yea I'm going to eliminate the hearing aid industry.

I have hearing aids now in the severe range. I agree with you. As I can't enjoy anything in loud environments or where multiple things are happening at once. I'm truly rooting for Frequency Therapeutics to help me get my life back.

 

[Piney]

I seem to remember you at one point were considering cochlear implants. They said in a recent interview that @serendipity1996 posted that people in the cochlear implant range may still need hearing aids afterward (where people in the hearing aid range could potentially just get the drug).

A zero word score probably was flagged as in the cochlear implant range and as they don't give you hearing aids after to test your word scores, I could see why this would be an exclusion factor, unfortunately.

I do understand now why they use these limiting factors. Since I only got 3 or 4 WR correct and I believe I needed 8 to move on, my worry was the drug would be useless due to lack of supporting cells and they know it.

I'm used to being deaf in that ear, tinnitus cure is my main goal.

 

[frpp]

I could just be talking out of my ass but in my opinion Frequency Therapeutics should just buy Otonomy. They have the cash and Otonomy's market cap is really low right now. That would end the gel issue and give them a speech in noise and tinnitus drug all under one better managed roof.

 

[Philip83]

I could just be talking out of my ass but in my opinion Frequency Therapeutics should just buy Otonomy. They have the cash and Otonomy's market cap is really low right now. That would end the gel issue and give them a speech in noise and tinnitus drug all under one better managed roof.

These are my thoughts exactly!

 

[Philip83]

Some only have hearing loss in one ear.

Sure, but the tests could still be done with two ears. But yeah, bigger problem with the ceiling effect then of course.

 

[Jrblovsky]

Isn't he just being conservative though?

I mean he'd seem like an incompetent ass if he just straight up said yea I'm going to eliminate the hearing aid industry.

I have hearing aids now in the severe range. I agree with you. As I can't enjoy anything in loud environments or where multiple things are happening at once. I'm truly rooting for Frequency Therapeutics to help me get my life back.

I hope so brother. Me too, this shit really blows.

If I had a cure for hearing loss and I knew it would obliterate my competition I would probably make some bold statements, but that's just me.

 

[Keith Handy]

I could just be talking out of my ass but in my opinion Frequency Therapeutics should just buy Otonomy. They have the cash and Otonomy's market cap is really low right now. That would end the gel issue and give them a speech in noise and tinnitus drug all under one better managed roof.

I know nothing about business, but wouldn't this divert cash resources away from everything they're currently focusing on? And how would this "end the gel issue"?

 

[Jrblovsky]

I do understand now why they use these limiting factors. Since I only got 3 or 4 WR correct and I believe I needed 8 to move on, my worry was the drug would be useless due to lack of supporting cells and they know it.

I'm used to being deaf in that ear, tinnitus cure is my main goal.

If they can fix the deafness I would imagine your tinnitus would dramatically lower in volume and eventually go away entirely. These guys WILL figure it out. There WILL be a treatment that ends this tormented hell. Just remember that all these idiot so called "specialists" also said the internet would be a flop, Amazon would never make it, and the guys at Intel were wasting their time. I don't bother listening to opinions honestly from anyone whom is deadset in their ways. Things change all the time, evolving and improving. This will be cured and hopefully real fuckin soon. Keep the faith.

 

[Björn Andersson]

Sorry for being uneducated. What is considered moderate/severe hearing loss?

According to my audiologist I only have minor hearing loss, but my audiogram shows -50 dB at 8 kHz on both ears. I would consider that moderate.

Since my tinnitus seems to be in that range I would consider myself a good candidate for FX-322. Hopefully it treats reactivity as well. I would not say I have hyperacusis but my tinnitus reacts badly to noise, for example driving my car or watching tv at moderate volume.

 

[Piet]

So when FX-322 comes to the market, how long will it take for it to become available in foreign countries at your ENT or hospital?

 

[Diesel]

I could just be talking out of my ass but in my opinion Frequency Therapeutics should just buy Otonomy. They have the cash and Otonomy's market cap is really low right now. That would end the gel issue and give them a speech in noise and tinnitus drug all under one better managed roof.

Not gonna happen.

 

[Diesel]

I wonder if this confirms that the Phase 2a results will be one of your "meh" scenarios. This posting is new, it's not even on LinkedIn yet. The description mentions that "the Co-Op will support the development of the next generation of treatments for hearing loss" - basically FX-322 version 2.

Based on the math you showed a few weeks ago, they would have been delivered the data in early February, which means they probably have some idea of what the data shows. They probably had it in the back of their mind that they needed a new gel, and the Phase 2a data reinforces that.

I still think we'll see good results, but I have a feeling the first version of FX-322 is going to be for high frequency hearing loss / word clarity only.

I remain cautiously optimistic. I think the "meh" scenarios I outlined would point to either larger dosing being needed per shot to get a significant effect, or moving the dosing closer together in time to get the concentration of the two small molecules in the cochlea high enough to have an effect.

Either way, that's honestly good news because those aren't impossible problems to solve. If they're working on it now, that's good news because it could mean by the time FX-322 "1.0" is out in the market, they could have already done a lot of the lab work to get FX-322 "2.0" released soon afterwards.

I suspect the end goal for FX-322 is that one shot is enough to do one "regenerative pass" in the whole human cochlea like they show in the guinea pig models. It's promising to see they are focusing on that already.

 

[Diesel]

I know nothing about business, but wouldn't this divert cash resources away from everything they're currently focusing on? And how would this "end the gel issue"?

It would divert cash, time, and resources away from moving/developing FX-322 through the clinical trials. Frequency Therapeutics would also need to absorb the risk that Otonomy currently carries with the current drugs in clinical trials. So, absorbing OTO-413, OTO-313, and the extended release gel could put FX-322 being released in a reasonable timeframe at risk. So, why would they want to do that? Why would we want that to happen if we want FX-322 ASAP.

Secondly, not much is really known about Otonomy's gel, but it's likely that what FX-322 needs to reach more deeply into the cochlea isn't even compatible with it.

Third, Frequency Therapeutics is expanding its Progenitor Cell Activation platform after FX-322. They have a lot of research in-progress to use the same approach as FX-322 to activate progenitors elsewhere in the body. Acquiring Otonomy wouldn't benefit the expansion of this platform.

 

[Guywithapug]

Sorry for being uneducated. What is considered moderate/severe hearing loss?

According to my audiologist I only have minor hearing loss, but my audiogram shows -50 dB at 8 kHz on both ears. I would consider that moderate.

Since my tinnitus seems to be in that range I would consider myself a good candidate for FX-322. Hopefully it treats reactivity as well. I would not say I have hyperacusis but my tinnitus reacts badly to noise, for example driving my car or watching tv at moderate volume.

At -50 dB you are in the moderate hearing loss area of the spectrum, I have roughly the same for 8 kHz and the tinnitus was piercing before it turned to a hiss. The reactivity is also debilitating so I understand what you are going through.

If your hearing loss was a result of damaged hair cells then FX-322 should help, since 8 kHz appears to be the current limitation for for current formulation/delivery method. Common consensus here is that tinnitus is a result of hearing loss, so hearing restoration should alleviate the tinnitus. I am another example of this as I had no tinnitus until I lost a significant amount of higher frequency hearing.

 

[GlennS]

These guys WILL figure it out. There WILL be a treatment that ends this tormented hell. Just remember that all these idiot so called "specialists"

I've read posts just like this in Susan Shore's thread last year, and before that, Neuromod. I've learned not to allow such sentiment to work me into a lather.

 

[FGG]

It would divert cash, time, and resources away from moving/developing FX-322 through the clinical trials. Frequency Therapeutics would also need to absorb the risk that Otonomy currently carries with the current drugs in clinical trials. So, absorbing OTO-413, OTO-313, and the extended release gel could put FX-322 being released in a reasonable timeframe at risk. So, why would they want to do that? Why would we want that to happen if we want FX-322 ASAP.

Secondly, not much is really known about Otonomy's gel, but it's likely that what FX-322 needs to reach more deeply into the cochlea isn't even compatible with it.

Third, Frequency Therapeutics is expanding its Progenitor Cell Activation platform after FX-322. They have a lot of research in-progress to use the same approach as FX-322 to activate progenitors elsewhere in the body. Acquiring Otonomy wouldn't benefit the expansion of this platform.

Since the proprietary compound in FX-322 diffuses further than the VPA, it's not the diffusion distance of the gel per se but something about the properties of the VPA molecule (which could be solved with a different gel possibly but maybe not Otonomy's gel).

 

[throwaway]

If otonomy is likely to fail, how are we going to regenerate synapse loss?

 

[ThomasRobert]

Sorry for being uneducated. What is considered moderate/severe hearing loss?

According to my audiologist I only have minor hearing loss, but my audiogram shows -50 dB at 8 kHz on both ears. I would consider that moderate.

Since my tinnitus seems to be in that range I would consider myself a good candidate for FX-322. Hopefully it treats reactivity as well. I would not say I have hyperacusis but my tinnitus reacts badly to noise, for example driving my car or watching tv at moderate volume.

This is the cochlea. FX-322 can easily reach 8,000 Hz... So no worries.

 

[Diesel]

If otonomy is likely to fail, how are we going to regenerate synapse loss?

We don't know that. But, we do know they need a win. If bankruptcy were to take place, a pharma company would likely absorb the company for their patent/research portfolio. Which would include OTO-413, OTO-313, etc.

Otherwise, PIPE-505 is another potential to restore synapses.

 

[Zugzug]

This is the cochlea. FX-322 can easily reach 8,000 Hz... So no worries.

View attachment 43534

Not to be a downer, but the Phase 1b results don't indicate that it "easily" helps 8,000 Hz (at least with one dose). There was no statistically significant pure tone audiogram differences between the treated and placebo groups.

What is true is that there were "things to note" regarding this. From the published paper:

Multiple doses could make the result even more pronounced, but we don't know yet. Their pharmacokinetics study did show the two drugs reaching the Scala Tympani at the location that corresponds with 8,000 Hz, which is promising.

 

[Diesel]

Not to be a downer, but the Phase 1b results don't indicate that it "easily" helps 8,000 Hz (at least with one dose). There was no statistically significant pure tone audiogram differences between the treated and placebo groups.

What is true is that there were "things to note" regarding this. From the published paper:

View attachment 43535

Multiple doses could make the result even more pronounced, but we don't know yet. Their pharmacokinetics study did show the two drugs reaching the Scala Tympani at the location that corresponds with 8,000 Hz, which is promising.

Unfortunately, they don't disclose where in the audiogram that gain took place, either. So, did the patients go from 50 dB to 40 dB, or from like 80 dB to 70dB? We know they were of moderate hearing loss.

Fortunately the Phase 2A 90-day results should help understand that, as Frequency Therapeutics intends to show a group-level average baseline at each pure tone, and the average threshold improvement.

 

[FGG]

If otonomy is likely to fail, how are we going to regenerate synapse loss?

A major could buy them out at a bargain if they end up having money issues and still release the drug under the new pharma company but that would be unlikely needed, more cash would flow in if any of the drugs tested work.

Novavax failed for years but now that they have a vaccine that works ample cash is flowing in.

If the drug works, money won't be an issue. It isn't for other biotechs that fail a few times before getting a blockbuster. As long as they can show good Phase 2 data, they are golden and they are funded until then.

But to make you feel better, PIPE-505 and the Hough Ear Institute Pill are also synapse drugs.

 

[Jrblovsky]

I've read posts just like this in Susan Shore's thread last year, and before that, Neuromod. I've learned not to allow such sentiment to work me into a lather.

The drugs segment is nothing like that sham bullshit like Neuromonics and related garbage. Drugs actually aim to treat the underlying problems.

 

[ajc]

The drugs segment is nothing like that sham bullshit like Neuromonics and related garbage. Drugs actually aim to treat the underlying problems.

Everyone here drooled over AM-101 and AUT00063 at the time. Hype was strong. Both failed.

 

[Jrblovsky]

Not to be a downer, but the Phase 1b results don't indicate that it "easily" helps 8,000 Hz (at least with one dose). There was no statistically significant pure tone audiogram differences between the treated and placebo groups.

What is true is that there were "things to note" regarding this. From the published paper:

View attachment 43535

Multiple doses could make the result even more pronounced, but we don't know yet. Their pharmacokinetics study did show the two drugs reaching the Scala Tympani at the location that corresponds with 8,000 Hz, which is promising.

I don't know why everyone is freaking out that it won't work. It may not, but it just as well could. I understand the doom and gloom as much as the next guy, but it only takes one breakthrough and you're golden. Remember 10 years ago ALL scientists said it was impossible to fix sensorineural hearing loss. You now have seven or eight companies working on cure.

 

[Zugzug]

Unfortunately, they don't disclose where in the audiogram that gain took place, either. So, did the patients go from 50 dB to 40 dB, or from like 80 dB to 70dB? We know they were of moderate hearing loss.

Fortunately the Phase 2A 90-day results should help understand that, as Frequency Therapeutics intends to show a group-level average baseline at each pure tone, and the average threshold improvement.

I'm practically salivating over the larger sample sizes. Good or bad, there should be a ton to infer from the Phase 2a results.