Frequency Therapeutics — Hearing Loss Regeneration

[serendipity1996]

They tried and failed. They will try again and other companies will try. Sadly I think treating only the ear is a big mistake. Maybe our great grandkids will be around to see a treatment that works for this. Surely not in my lifetime and I'm 38.

Could you elaborate on treating only the ear being a big mistake?

 

[Street Novelist]

@GlennS, stop. Just stop. If you don't believe in the drug, get out. We are all tired of your s@*!

 

[FGG]

@GlennS, stop. Just stop. If you don't believe in the drug, get out. We are all tired of your s@*!

I wasn't trying to suggest he leave. An echo chamber isn't good, either. Just frustrated that everything I said was being misrepresented and dismissed out of hand without trying to understand my points.

 

[Keith Handy]

Sadly I think treating only the ear is a big mistake.

No research team is going to come up with something that treats more than one part of the problem initially. Once there are treatments for multiple aspects of tinnitus, coming from different labs, they could certainly be combined.

 

[Zugzug]

@GlennS, stop. Just stop. If you don't believe in the drug, get out. We are all tired of your s@*!

To be fair, I think it's good to have a variety of perspectives. I think there's something big that he's missing (I didn't understand this until recently as well).

There's a lot of speculation and theories after the Phase 2a failure. The stuff about inner hair cell prioritization and all of this other stuff is fair, but speculative. Why exactly the trial failed is speculative.

The fact that inner and outer hair cells do completely different things is not. It really is true that someone can hear a word in a perfectly normal volume for them, but it sounds like gibberish. This didn't make any sense to me when I first thought about it. I thought maybe not hearing words was a combination of like straining and lack of clarity. When I really understood what was going on was when I watched Dr. Cliff's YouTube video about how for the WR test, the volume is set at a comfortable level for the listener to normalize for OHC loss.

Even if one takes the most pessimistic view possible, which is that the drug failed or it didn't and no bullshit about it, it's still definitely the case that WR and PTA are measured differently. The nuance to this, though, is that there is a correlation between having both types of loss, even though they are different.

Hypothetically, we should be prepared (we are not there yet, I am not being too bullish too soon) for the first hearing regeneration drug to possibly help one type first. I think PIPE-505 (synapse drug) purportedly may regenerate outer hair cells. Hence, if that drug makes it out of Phase 1, we may see some weird results as well.

To be clear, FX-322 doesn't have results yet. But this distinction is definitely not speculative.

 

[Lucifer]

To be fair, I think it's good to have a variety of perspectives. I think there's something big that he's missing (I didn't understand this until recently as well).

There's a lot of speculation and theories after the Phase 2a failure. The stuff about inner hair cell prioritization and all of this other stuff is fair, but speculative. Why exactly the trial failed is speculative.

The fact that inner and outer hair cells do completely different things is not. It really is true that someone can hear a word in a perfectly normal volume for them, but it sounds like gibberish. This didn't make any sense to me when I first thought about it. I thought maybe not hearing words was a combination of like straining and lack of clarity. When I really understood what was going on was when I watched Dr. Cliff's YouTube video about how for the WR test, the volume is set at a comfortable level for the listener to normalize for OHC loss.

Even if one takes the most pessimistic view possible, which is that the drug failed or it didn't and no bullshit about it, it's still definitely the case that WR and PTA are measured differently. The nuance to this, though, is that there is a correlation between having both types of loss, even though they are different.

Hypothetically, we should be prepared (we are not there yet, I am not being too bullish too soon) for the first hearing regeneration drug to possibly help one type first. I think PIPE-505 (synapse drug) purportedly may regenerate outer hair cells. Hence, if that drug makes it out of Phase 1, we may see some weird results as well.

To be clear, FX-322 doesn't have results yet. But this distinction is definitely not speculative.

I can't wait for PIPE-505 results. It looks very promising and would be way ahead of OTO-413 If they can go to Phase 2 next.

 

[Zugzug]

No research team is going to come up with something that treats more than one part of the problem initially. Once there are treatments for multiple aspects of tinnitus, coming from different labs, they could certainly be combined.

This is spot on. Obviously, we have the power of hindsight so I don't say this as if I predicted it, but their failure is a classical scientific mistake (which scientists make often) of getting too far ahead of themselves. If anything, they should reduce the number of variables even more. Make the goals super attainable and super simple. For now, forget about tinnitus or some cracking the 8 kHz PTA barrier or whatever.

Simple: Word clarity and a robust trial design for proving it, along with education on IHC vs OHC loss if they can make it work.

 

[Diesel]

If anything, they should reduce the number of variables even more. Make the goals super attainable and super simple.

Winner. All reading this thread pro- and con- should understand that this is what much of the discussion revolves around. The expectations should also be that the product itself will probably address a single component of / single initial population of hearing loss.

 

[FGG]

Winner. All reading this thread pro- and con- should understand that this is what much of the discussion revolves around. The expectations should also be that the product itself will probably address a single component of / single initial population of hearing loss.

Regardless of what the drug may or may not have potential for with alternative dosing schedules or even re-formulation, I think it makes the most sense for the company to look towards designing trials for approval for the people with clarity/IHC/word score issues first and then suss out the finer points after that point (and patients themselves would be quick to realize exactly what the drug does and doesn't do).

 

[Lucifer]

@Chad Lawton, whereabouts in the Frequency Therapeutics presentation did they mention audiogram improvements in Phase 1b?

If this is true, then it proves both that OHCs can regrow with FX-322 and the positive anecdote of improving in 3 frequency bands.

If they can space out the dosing next time, we would know if it can continue regrowing OHCs.

 

[Zugzug]

If this is true, then it proves both that OHCs can regrow with FX-322 and the positive anecdote of improving in 3 frequency bands.

Sad to say, an anecdote can't be a proof

 

[Tezcatlipoca]

Regardless of what the drug may or may not have potential for with alternative dosing schedules or even re-formulation, I think it makes the most sense for the company to look towards designing trials for approval for the people with clarity/IHC/word score issues first and then suss out the finer points after that point (and patients themselves would be quick to realize exactly what the drug does and doesn't do).

Exactly this, even without audiogram changes the WR score improvements give argument for approval.

 

[Lucifer]

Sad to say, an anecdote can't be a proof

I originally thought there were no audiogram improvements in Phase 1b, but then @Chad Lawton said that there were audiogram improvements.

I know the positive anecdote can't be proof but it would be good to find out how many doses of FX-322 he got. He said he may have gotten 2 doses of FX-322 but I have a feeling he may have only got one dose of FX-322. That's why he had improvements in 3 frequency bands.

 

[Brian P]

Could you elaborate on treating only the ear being a big mistake?

Tinnitus becomes a brain problem after the ear is damaged. You could cut the auditory nerve and still hear the ringing.

 

[Tezcatlipoca]

Tinnitus becomes a brain problem after the ear is damaged. You could cut the auditory nerve and still hear the ringing.

Oh boy.

 

[serendipity1996]

Tinnitus becomes a brain problem after the ear is damaged. You could cut the auditory nerve and still hear the ringing.

I don't really think it's a "mistake" on Frequency Therapeutics' part though as FX-322 as it's ultimately a hearing-loss treatment and not primarily aimed at tinnitus.

 

[HootOwl]

Oh boy.

Who wants to tell him?

 

[Lucifer]

In these trials, how would they know if OHCs or synapses have regrown? Aren't both of these part of speech in noise?

 

[Zugzug]

Tinnitus becomes a brain problem after the ear is damaged. You could cut the auditory nerve and still hear the ringing.

April Fool's.

 

[Diesel]

Who wants to tell him?

1... 2... 3... NOT IT.

 

[Tezcatlipoca]

Who wants to tell him?

Let's leave it to the science guys to do so.

 

[Street Novelist]

In these trials, how would they know if OHCs or synapses have regrown? Aren't both of these part of speech in noise?

I don't think there's any way to know that because you can't see inside the cochlea.

 

[Lucifer]

I don't think there's any way to know that because you can't see inside the cochlea.

I think so far we can tell that IHCs and OHCs were regrown due to improvement in word scores and audiograms. There were also improvement in word scores in noise but I have no clue if that relates to OHC, IHC or synapses.

 

[FGG]

I think so far we can tell that IHCs and OHCs were regrown due to improvement in word scores and audiograms. There were also improvement in word scores in noise but I have no clue if that relates to OHC, IHC or synapses.

Words in noise is most linked to synapses (especially in the most important speech ranges) but it's also linked to EHF hearing.

 

[Diesel]

Let's leave it to the science guys to do so.

Ahem... the proper term is "Wannabe Scientists"... thank you.

 

[Jrblovsky]

The stock price is a bargain right now. If they can get positive outcomes for both age-related and severe hearing loss sufferers I expect the share price to go back up to $20-$30 and any announcement of the pivotal phase will make it go back up to $60 or more. This is a good time to get back in.

If FX-322 shows no change in the upcoming trials, the stock will be worth pennies on the dollar. I guess if you can afford to lose money then go for it. Money would be better spent at the casino.

 

[Lucifer]

Words in noise is most linked to synapses (especially in the most important speech ranges) but it's also linked to EHF hearing.

Thanks @FGG. I guess that means both OHCs and synapses may have been regrown to have some improvement in word scores in noise.

 

[FGG]

Thanks @FGG. I guess that means both OHCs and synapses may have been regrown to have some improvement in word scores in noise.

Technically it could even be related to IHCs reconnecting and resynapsing too. It's probably the least useful of the test for localizing overall imo.

 

[Lucifer]

If FX-322 shows no change in the upcoming trials, the stock will be worth pennies on the dollar. I guess if you can afford to lose money then go for it. Money would be better spent at the casino.

Money spent on Frequency Therapeutics would be way better than spending money at a casino. At a casino you're more likely to lose than win.

 

[Zugzug]

Ahem... the proper term is "Wannabe Scientists"... thank you.

FGG is a credentialed audiologist with a YouTube series. I'm not sure what you're talking about.

Also, I wouldn't exactly consider an elite meth cooker to be a "wannabe."