Frequency Therapeutics — FX-345

[Diesel]

Question: I thought the delivery method is what decides how deep any drug can penetrate, not the drug itself?

I'm happy Frequency Therapeutics is pushing forward, but looking at recent history, they have proven to be way better at talking the talk than walking the walk. Sure, good communication is advantageous, especially when it comes to keeping the money coming in, but at some point I hope there will be some properly potent, concrete results also from the medical side.

Have you watched the R&D event video / read the November investor deck? I think they did a good job of bringing all the data together from the single dose trials; and highlighted a lot of lessons learned in trial design AND got more specific on patient target for FX-322. When looking at the trials individually, yeah, it's underwhelming, and you can tell they have struggled to fine tune their recruiting; but in aggregate, it does start to make sense the signal they're seeing, and how FX-345 can build on the learnings.

This science is young (PCA), and this is how they learn to get it to market + iterate it. We're seeing it happen in real-time.

If you haven't I would encourage that you take the hour or so and watch it.

https://investors.frequencytx.com/2021_Virtual_R-D_Event

 

[hopetohear]

I've been following FX-322 for a while now and am interested in how FX-345 will go, as I'm sure you all are.

Wondering what everyone thinks the timeline might be? Obviously guesswork at this point. Do we think they might not have to run as many Phase 2 trials this time around? Thoughts on if FX-345 will be the same target population as FX-322?

 

[ThomasRobert]

I've been following FX-322 for a while now and am interested in how FX-345 will go, as I'm sure you all are.

Wondering what everyone thinks the timeline might be? Obviously guesswork at this point. Do we think they might not have to run as many Phase 2 trials this time around? Thoughts on if FX-345 will be the same target population as FX-322?

My guess is a Phase 3 FX-322 trial will run simultaneously with a FX-345 phase 2/pivotal trial in 2023...

Since Frequency Therapeutics is on a fast track designator, an approval for the drug can come in 6 months after the above-mentioned trial in 2023.

 

[hopetohear]

That would be great!

Is it possible they might only need the one Phase 2 trial this time around? Also I'm guessing the fast track status is only for FX-322? Or for Frequency Therapeutics as a company, so it could cover FX-345?

Really hoping they've learnt from their mistakes and this next lot of trials etc run a whole lot smoother/faster.

 

[RingingBrother]

Wondering what everyone thinks the timeline might be? Obviously guesswork at this point. Do we think they might not have to run as many Phase 2 trials this time around? Thoughts on if FX-345 will be the same target population as FX-322?

I wish there was a way the FDA can just let us all try it now and assume the risks.

 

[Gb3]

Is it possible they might only need the one Phase 2 trial this time around? Also I'm guessing the fast track status is only for FX-322? Or for Frequency Therapeutics as a company, so it could cover FX-345?

Definitely not going to be faster considering they said some people take longer to achieve effect.

 

[Diesel]

I wish there was a way the FDA can just let us all try it now and assume the risks.

There is. It's called Compassionate Use. It's really not up the FDA, it's up to the company. I honestly don't see this happening with either of the FX's though.

 

[hopetohear]

Definitely not going to be faster considering they said some people take longer to achieve effect.

Ah yes, good point. Wishful thinking on my behalf.

 

[Philip83]

Have you watched the R&D event video / read the November investor deck? I think they did a good job of bringing all the data together from the single dose trials; and highlighted a lot of lessons learned in trial design AND got more specific on patient target for FX-322. When looking at the trials individually, yeah, it's underwhelming, and you can tell they have struggled to fine tune their recruiting; but in aggregate, it does start to make sense the signal they're seeing, and how FX-345 can build on the learnings.

This science is young (PCA), and this is how they learn to get it to market + iterate it. We're seeing it happen in real-time.

If you haven't I would encourage that you take the hour or so and watch it.

https://investors.frequencytx.com/2021_Virtual_R-D_Event

I read the deck, but haven't watched the video yet. And I agree with what you're saying, they are doing a great job at communicating details and that's good. But yeah, hopefully better results will come in time. In the past they've made it seem that it's sooner rather than later though, but it seems to be later. However it of course could have been an honest miss-estimation on their part and not only to callously "lure" investors in.

 

[RingingBrother]

There is. It's called Compassionate Use. It's really not up the FDA, it's up to the company. I honestly don't see this happening with either of the FX's though.

I wonder if Frequency Therapeutics has an email we can write and ask for that. I would sign a release form to try it.

 

[2noist]

I wonder if Frequency Therapeutics has an email we can write and ask for that. I would sign a release form to try it.

Hardly any reason to ask, they know people would be lining up for compassionate use. Didn't they say in some interview that they will revisit the compassionate use in future?

 

[Gb3]

Hardly any reason to ask, they know people would be lining up for compassionate use. Didn't they say in some interview that they will revisit the compassionate use in future?

It's on their website. It's not an option at this time.

 

[RingingBrother]

It's on their website. It's not an option at this time.

When do you think they would allow compassionate use if they have good results in their trials?

Also, is it me or is taking a needle in my ear utterly terrifying?

Just had one in my right ear for steroids, it wasn't so bad.

 

[Gb3]

When do you think they would allow compassionate use if they have good results in their trials?

Prolly never. If it works, it would come to market, if it doesn't, then why would you want it.

 

[Chad Lawton]

Question: I thought the delivery method is what decides how deep any drug can penetrate, not the drug itself?

Not necessarily. In this case, it is the composition of the gel.

I believe they have found a way to design their gel so that it can hold a higher dose of a more potent GSK3 inhibitor while still retaining its gel like properties. The problem with FX-322 is that they couldn't increase the potency by simply adding more drug to the mix because the gel would not retain its desired viscosity at the desired temperature if they did so. FX-322 is likely penetrating just as deeply into the cochlea as FX-345 is but the amount that makes it past 8 kHz is not potent enough to be therapeutically active versus this more highly potent compound which doesn't take nearly as high of levels to activate the progenitor cells. Someone correct me if I'm wrong.

As for the the purple fading out until 1.5 kHz, it appears this way as a result of the gradient applied to the cochlea in the background. Look at the FX-322 cochlea they used in that same presentation and that same area is shaded the same color. It looks like FX-345 fades out around 3 kHz.

 

[Philip83]

As for the the purple fading out until 1.5 kHz, it appears this way as a result of the gradient applied to the cochlea in the background. Look at the FX-322 cochlea they used in that same presentation and that same area is shaded the same color. It looks like FX-345 fades out around 3 kHz.

If I may speculate with some hopeful bias, I do think reaching further into the cochlea, even with the same amount of drug, could make a difference for the treatment as a whole.

Covering only a quarter of a flesh-wound with bandage is going to make way less of a difference, even for that particular part, then if you cover a bigger part or the whole wound.

 

[Jim51042]

they have proven to be way better at talking the talk than walking the walk.

I disagree with that assessment. Talking the talk would be more like promoting their product to investors and never testing it. Frequency Therapeutics injected people in their trials aka they tangibly did something.

 

[aorelia]

Trying to understand the science around this. If someone has hearing loss around 5 kHz, but no hearing loss above that, would the drug still reach that 5 kHz level?

 

[Philip83]

I disagree with that assessment. Talking the talk would be more like promoting their product to investors and never testing it. Frequency Therapeutics injected people in their trials aka they tangibly did something.

I did use the word "better" for that reason.

 

[Jim51042]

I did use the word "better" for that reason.

Fair enough.

It's just my view that the commenters can view different companies maybe not equivalently. I'm specially talking about all the love Decibel Therapeutics was receiving back in 2017/2018. They were taking in ton of cash yet had no interest in human testing on the horizon and were entirely focused on a prevention drug. I didn't understand the commenters' praise/celebration then and don't get it now.

 

[Jim51042]

would the drug still reach that 5 kHz level?

My understanding is it would reach 5 kHz and frequencies above.

If someone has hearing loss around 5 kHz, but no hearing loss above that

You have hearing loss above 5 kHz. You may not realize you have hearing loss because you haven't been tested to 16 kHz or 20 kHz but at least somewhere in the 20 kHz range some of your hair cells have died.

 

[kiki]

My guess is a Phase 3 FX-322 trial will run simultaneously with a FX-345 phase 2/pivotal trial in 2023...

Since Frequency Therapeutics is on a fast track designator, an approval for the drug can come in 6 months after the above-mentioned trial in 2023.

I don't think Phase 3 is necessary for FX-322 because there are no competing drugs.

What about if FX-322 is approved, is FX-345's competitor FX-322? Do you need Phase 3 for FX-345?

 

[kiki]

I suspect your strategy is correct here. Get FX-322 to market and create cashflow. Then, bring FX-322 patients back in for the more robust FX-345 treatment.

And by then, there will probably be another FX-3XX in the works that goes even deeper once everyone gets FX-345.

And the big thing is the success fee paid by Astellas.

It is very important to show that FX-322 is an active drug (especially in HFPTA) and get FDA approval.

If successful, they can sign a better deal with Astellas for FX-345.

 

[dbeats]

Does FX-345 aim to also fix existing hair cells, or is it mainly to generate new and functional hair cells?

 

[Philip83]

Does FX-345 aim to also fix existing hair cells, or is it mainly to generate new and functional hair cells?

I don't think there is any official info yet other than it reaching further into the cochlea.

 

[star-affinity]

This is fascinating research. However, they do not even use the word tinnitus in the presentation. Realistically, when could those of us with regular old tinnitus hope to have this available to them? Also, is it me or is taking a needle in my ear utterly terrifying?

I'm thinking that if one has tinnitus and hearing loss at that and a hearing aid help alleviate the tinnitus it would likely also help reduce (or even silent) the tinnitus with repaired hair cells.

Sounds reasonable?

If the hearing aid doesn't alleviate the tinnitus (which I understand it doesn't for most people?), maybe the problem is more complex and more of a neurological thing in the brain.

What I am curious about is how well the repaired and resurrected hair cells are expected to function; how will the signal they transport to the brain be perceived? Hopefully just as good as the original cells, because if there will be some "glitchy" or distorted kind of signal, maybe it's after all better to not hear those frequencies? Just a thought.

I guess we'll see when the first human hair cells in a living person will get regrown – hoping for the best.

I did hear in a presentation that if a missing hair cell returns its synapses automatically connects back – pretty awesome if that's the case. Anyone recognize that? Here, somewhere in this presentation from Hearing Health Foundation:



In that presentation the researchers seem pretty certain that curing hearing-loss won't help tinnitus. Sucks bad if that is the case. I would much prefer to get rid of the tinnitus than the hearing loss if I had to choose. And still the hearing loss makes me cry if I listen to songs that I know and remember how they sounded before the hearing loss and tinnitus.

About the needle in the ear – agree it seems scary, but I understand it's a relatively harmless thing when listening to people with experience from intratympanic injections.

 

[dbeats]

I'm thinking that if one has tinnitus and hearing loss at that and a hearing aid help alleviate the tinnitus it would likely also help reduce (or even silent) the tinnitus with repaired hair cells.

Sadly, it could be a lot more complex than this.

In my opinion, the extra gain from hearing aids help mask the tinnitus, just like listening to white noise or music. So not actually reducing it, just frequency masking, which in turn you would experience as a reduction.

But maybe someone else has some input on this...

 

[AfroSnowman]

I don't believe that hearing aids can significantly help any but the most modest 'turn a fan on in the room' type of tinnitus though I imagine that it may reduces some of the distress. I say this based on my experience of having relatively severe tinnitus, I could turn up the volume of a white noise maker to 120 dB and I'm sure it would overwhelm the sound of tinnitus but the sound precept is still being created regardless of the amount noise in the environment. Hearing aids don't change that. I do wonder if regeneration, like cochlear implants, would create a stimulation of the inner hair cells that would suppress tinnitus regardless of the presence of exterior sound.

 

[Diesel]

Sadly, it could be a lot more complex than this.

In my opinion, the extra gain from hearing aids help mask the tinnitus, just like listening to white noise or music. So not actually reducing it, just frequency masking, which in turn you would experience as a reduction.

But maybe someone else has some input on this...

It could also be more simple. There are anecdotes on this site where people with tinnitus have it improve or go away completely, and often at the same time notice audiograms improve. In these cases, something clearly healed in the ear. Is it the hair cells, synapses, or something else? It could be one or all of the above. But it stands to reason that if scientists observe missing hair cells in cochleas extracted from people with hearing loss and tinnitus, then restoring those same hair cells should reverse the tinnitus experienced from missing signal input.

 

[dbeats]

It could also be more simple. There are anecdotes on this site where people with tinnitus have it improve or go away completely, and often at the same time notice audiograms improve. In these cases, something clearly healed in the ear. Is it the hair cells, synapses, or something else? It could be one or all of the above. But it stands to reason that if scientists observe missing hair cells in cochleas extracted from people with hearing loss and tinnitus, then restoring those same hair cells should reverse the tinnitus experienced from missing signal input.

Maybe, maybe not. You are removing the brain from the equation though, but it's just speculation at this point. Hopefully time will tell.