Frequency Therapeutics — Hearing Loss Regeneration

[Zugzug]

Now that the multi-dose door is closed for the foreseeable future, I wonder if they are considering a trial where both ears are given a single dose?

Seems difficult from a control perspective. If a sample size of N ears is required to demonstrate (presumably the standard 80%) statistical power, it only really leads to N/2 independent data "pairs." In other words, all of this stuff that we've been speculating about (studying word tests, guessing better, etc.) would have double the weight since the same person would supply two ears.

Then there's the nightmare of making sense of why one ear improved, while the other didn't. Moreover, there's the issue of double shot = double neuroplasticity improvement (central). So, while it would still be encouraging to see tinnitus improvements from a double shot, it may give a poor representation of how much hair cell + synapse repair really occurred in each ear. I totally understand your desire from a tinnitus and hyperacusis sufferer's perspective though. I'd love for them to double shot me.

Recruiting wise, it seems to add extra difficulty to a process that will already be a lot harder. I know we've been talking about things like demanding similar word scores at entrance as >= 6 months ago. To get recruited, a person would have to achieve this in both ears. Probably pretty hard, IMO.

 

[Diesel]

They measure each ear separately.

My last WR + WIN included a "both ears" test...

 

[Gb3]

Seems difficult from a control perspective. If a sample size of N ears is required to demonstrate (presumably the standard 80%) statistical power, it only really leads to N/2 independent data "pairs." In other words, all of this stuff that we've been speculating about (studying word tests, guessing better, etc.) would have double the weight since the same person would supply two ears.

Then there's the nightmare of making sense of why one ear improved, while the other didn't. Moreover, there's the issue of double shot = double neuroplasticity improvement (central). So, while it would still be encouraging to see tinnitus improvements from a double shot, it may give a poor representation of how much hair cell + synapse repair really occurred in each ear. I totally understand your desire from a tinnitus and hyperacusis sufferer's perspective though. I'd love for them to double shot me.

Recruiting wise, it seems to add extra difficulty to a process that will already be a lot harder. I know we've been talking about things like demanding similar word scores at entrance as >= 6 months ago. To get recruited, a person would have to achieve this in both ears. Probably pretty hard, IMO.

Exactly.

 

[Diesel]

Seems difficult from a control perspective. If a sample size of N ears is required to demonstrate (presumably the standard 80%) statistical power, it only really leads to N/2 independent data "pairs." In other words, all of this stuff that we've been speculating about (studying word tests, guessing better, etc.) would have double the weight since the same person would supply two ears.

Then there's the nightmare of making sense of why one ear improved, while the other didn't. Moreover, there's the issue of double shot = double neuroplasticity improvement (central). So, while it would still be encouraging to see tinnitus improvements from a double shot, it may give a poor representation of how much hair cell + synapse repair really occurred in each ear. I totally understand your desire from a tinnitus and hyperacusis sufferer's perspective though. I'd love for them to double shot me.

Recruiting wise, it seems to add extra difficulty to a process that will already be a lot harder. I know we've been talking about things like demanding similar word scores at entrance as >= 6 months ago. To get recruited, a person would have to achieve this in both ears. Probably pretty hard, IMO.

Thanks for clarifying!

 

[ThomasRobert]

Donlon Coatings just published their work on the new building for Frequency Therapeutics HQ...

Thoughts?

 

[Keith Handy]

Donlon Coatings just published their work on the new building for Frequency Therapeutics HQ...

Thoughts?

Nice flooring, but it's not the goop I'm interested in.

 

[Diesel]

Donlon Coatings just published their work on the new building for Frequency Therapeutics HQ...

Thoughts?

That's a big lab.

 

[ThomasRobert]

That's a big lab.

But why did they take this step without having concrete data? It's like burning money...

 

[Zugzug]

That's a big lab.

You know what they say about big labs, right?

Big scientific discoveries.

 

[Diesel]

But why did they take this step without having concrete data? It's like burning money...

I can't speak for scientific work... but from an engineering standpoint, usually when you can throw more engineers at a problem, or set of problems... you get more solutions more quickly.

We also have to keep in mind that they aren't just working on PCA in the inner ear and for MS. Langer himself at the January webinar mentioned that they are working on "10 other areas of the body"... so they're probably looking to discover as much as possible on the PCA front.

 

[FGG]

I can't speak for scientific work... but from an engineering standpoint, usually when you can throw more engineers at a problem, or set of problems ... you get more solutions more quickly.

We also have to keep in mind that they aren't just working on PCA in the inner ear and for MS. Langer himself at the January webinar mentioned that they are working on "10 other areas of the body"... so they're probably looking to discover as much as possible on the PCA front.

It looks the move was planned since at least last December too:

Frequency Therapeutics plans HQ move for early next year

 

[Aaron91]

Donlon Coatings just published their work on the new building for Frequency Therapeutics HQ...

Thoughts?

And none of the people working on the building are wearing ear protection.

Ironic.

 

[Zugzug]

And none of the people working on the building are wearing ear protection.

Ironic.

Maybe the photo op is a power move. Like no worries, our drug will just fix these people right up. Then after the recording is done, they all put on their Peltors.

 

[Tezcatlipoca]

And none of the people working on the building are wearing ear protection.

Ironic.

 

[GlennS]

But why did they take this step without having concrete data? It's like burning money...

Hubris. Hardly unique with risky startups.

 

[OptimusPrimed]

Hubris. Hardly unique with risky startups.

Only a matter of time before one of these companies or research labs makes a big breakthrough and we have some therapies for treating, if not curing, hearing loss. The potential market is huge; big pharma knows this. Huge unmet demand.

If I were a betting man I'd say that within 10 years a treatment or cure is a realistic possibility. Stark contrast from 2007 when I got my acoustic trauma and tinnitus and regenerating hair cells and cochlear synapses was just an idea.

 

[rid0871]

But why did they take this step without having concrete data? It's like burning money...

Because it's the only thing of value they have; real estate property. Just saying.

 

[Tezcatlipoca]

Because it's the only thing of value they have; real estate property. Just saying.

But it's a lease...

 

[GBB]

Because it's the only thing of value they have; real estate property. Just saying.

Are you under the understanding that in the event that the company shuts down, management gets to keep the proceeds from the disposition of real estate? If so, big oof to your brain

They would only be entitled to these assets to the extent they hold the superceding tranche(s) of debt/equity that are given first repayment in the event of bankruptcy - this is held by institutional investors/creditors.

 

[AfroSnowman]

Hot off the press.

Frequency Therapeutics Provides Business Updates and Reports First Quarter 2021 Financial Results

 

[ThomasRobert]

Hot off the press.

Frequency Therapeutics Provides Business Updates and Reports First Quarter 2021 Financial Results

So no improvement in FX-322-112 study?

 

[Diesel]

So no improvement in FX-322-112 study?

Interesting. Maybe there is more weight to synaptopathy being the primary cause for hearing loss and not hair cell loss. I believe in the video shared in one of the synaptopathy drug threads (OTO-413 or PIPE-505), the presenter showed that average hair cell counts remained pretty consistent throughout the life span of the cochleas sampled.

It's also possible that the hair cells did regrow, but a synaptopathy drug is needed to increase neurite growth from the original, degraded nerve, and to the new hair cell. That is speculation, however.

This also helps validates that with Moderate or worse SSNHL/NIHL cases, that there is a level of insult / death to hair cells where FX-322 may provide a benefit. It's not conclusive, however.

I guess it all comes down to that severe arm.

 

[Willlly]

We are learning so much from these studies. It's all good news for the future even if the individual studies don't make it out to be a wonder drug.

I think the next big reveal will be PIPE-505 if it shows that synapse regeneration is responsible for most hearing loss, in which case you might need FX-322 to fix destroyed hair cells and PIPE-505 to sort out your synapses elsewhere.

 

[Zugzug]

Based on current plans and assumptions, the Company expects its existing cash, cash equivalents and short-term investments will be sufficient to fund its operations into 2023. This guidance does not include potential future milestones which could be received from Astellas for continued FX-322 development.

Good to see that.

Also, it looks like the ARHL trial was a sham. None of the participants had SSNHL or noise-induced hearing loss so perhaps not that surprising.

Looks like we still have to wait for end of Q2 for the Severe trial results. I hope it reveals something, but with the 4:1 treatment: placebo ratio, it's probably going to be more individual super responders with groupwide statistical significance being difficult to prove or even trust.

 

[Gorbeh3]

• Noise-induced hearing loss
• Age-related hearing loss
• Antibiotic related hearing loss (ototoxicity?)
• Viral/bacterial related hearing loss
• Congenital hearing loss (genetic?)
• Other types of hearing loss?

What are the odds that FX-322 works for some but not for others?

 

[Diesel]

• Noise-induced hearing loss
• Age-related hearing loss
• Antibiotic related hearing loss (ototoxicity?)
• Viral/bacterial related hearing loss
• Congenital hearing loss (genetic?)
• Other types of hearing loss?

What are the odds that FX-322 works for some but not for others?

It's really not a matter of "odds"... All you have to do is look at Frequency Therapeutics' investor deck to see how they're positioning FX-322. It's clear that the focus is on that patient population with SNHL. Which includes noise and may include ototoxic drugs.

 

[Kleiner]

"To date, Frequency has shown statistically significant hearing benefits in multiple, independent FX-322 studies"​

Independent studies? What are they talking about?

 

[Nobody19]

So the age-related hearing loss trial was a failure too...

 

[Chad Lawton]

"To date, Frequency has shown statistically significant hearing benefits in multiple, independent FX-322 studies"​

Independent studies? What are they talking about?

Independent from each other. 2 separate studies.

 

[Diesel]

"To date, Frequency has shown statistically significant hearing benefits in multiple, independent FX-322 studies"​

Independent studies? What are they talking about?

FX-322-201
FX-322-111

Multiple.