Frequency Therapeutics — Hearing Loss Regeneration

[Piet]

Hi @Bambam0, @AfroSnowman, @Tezcatlipoca, @Zugzug, @Diesel, @FGG!

I just want to add, on behalf of Tinnitus Hub, that we are more than willing to facilitate such an effort. I agree such initiatives should be well coordinated — though of course anyone is free to lobby on their own behalf, but doing this as a community will be much more impactful! Grassroots activism has always been part of who we are and it's a major part of why we run this community. If the Phase 2 90-Day readout is positive, I feel like a working group should be formed.

+1

 

[Tezcatlipoca]

I suppose the focus should be on compassionate use access?

I think we should try everything. Let the FDA and Frequency Therapeutics tell us no; let's not limit ourselves.

 

[Zugzug]

Hi @Bambam0, @AfroSnowman, @Tezcatlipoca, @Zugzug, @Diesel, @FGG!

I just want to add, on behalf of Tinnitus Hub, that we are more than willing to facilitate such an effort. I agree such initiatives should be well coordinated — though of course anyone is free to lobby on their own behalf, but doing this as a community will be much more impactful! Grassroots activism has always been part of who we are and it's a major part of why we run this community. If the Phase 2 90-Day readout is positive, I feel like a working group should be formed.

I can help. I'm really hoping (though not counting on for sure) that their top line reveal is detailed. Obviously, it eventually would be in the published paper, but this is where I provide the most value.

 

[Zugzug]

So I have been looking at the Phase 1b paper and I've noticed that Frequency Therapeutics is slightly underselling their conclusion for the results. My argument is somewhat technical so before I write it up, I want to pose the following question to someone more knowledgeable.

Once a drug moves on to the next phase, how important are previous phase results for helping the drug to get approved?

Please, no one freak out. It's not that big.

 

[Gb3]

Hi @Bambam0, @AfroSnowman, @Tezcatlipoca, @Zugzug, @Diesel, @FGG!

I just want to add, on behalf of Tinnitus Hub, that we are more than willing to facilitate such an effort. I agree such initiatives should be well coordinated — though of course anyone is free to lobby on their own behalf, but doing this as a community will be much more impactful! Grassroots activism has always been part of who we are and it's a major part of why we run this community. If the Phase 2 90-Day readout is positive, I feel like a working group should be formed.

Add me in. As a father of two children under the age of three, tinnitus has greatly taken away from the father I want to be! Ever since my sudden hearing loss and tinnitus onset on 12/19 I spiraled into a deep depression and now I'm on antidepressants that make me drowsy all the time. People need to see what this awful affliction can do to people and how it affects their families and loved ones as well.

BTW: my kids are adorable!

 

[Bambam0]

Hi @Bambam0, @AfroSnowman, @Tezcatlipoca, @Zugzug, @Diesel, @FGG!

I just want to add, on behalf of Tinnitus Hub, that we are more than willing to facilitate such an effort. I agree such initiatives should be well coordinated — though of course anyone is free to lobby on their own behalf, but doing this as a community will be much more impactful! Grassroots activism has always been part of who we are and it's a major part of why we run this community. If the Phase 2 90-Day readout is positive, I feel like a working group should be formed.

Yeah this would most definitely carry more weight coming from you guys - if you can organize this, I'm confident a lot of us would go to bat to get the word out/write letters/make calls etc. Cart ahead of the horse but so is this entire thread lol.

Thanks again for all you guys do here!

EDIT: This probably makes sense to do even if safety profile stays consistent and there's even marginal improvement in TFI scores. Amirite?

 

[Diesel]

So I have been looking at the Phase 1b paper and I've noticed that Frequency Therapeutics is slightly underselling their conclusion for the results. My argument is somewhat technical so before I write it up, I want to pose the following question to someone more knowledgeable.

Once a drug moves on to the next phase, how important are previous phase results for helping the drug to get approved?

Please, no one freak out. It's not that big.

The data from each successive phase should build on the data from the previous phase. However, each phase also has different outcomes of focus.

Phase 1 is primarily safety. Phase 2 efficacy / side effects. Phase 3 adverse reactions / interactions.

Of note, the hearing performance outcomes that we've all been debating here for about 2 years actually WON'T APPLY to the final decision-making by the FDA. Those outcomes were considered secondary.

The primary outcomes from the Phase 2A, however, will.

Likewise, in the Phase 3, if the hearing performance outcomes look a little less impressive than the Phase 2A (due to a larger, more varied patient group), it won't matter so much, because the primary outcoems should focus more on side effects and interactions.

 

[AfroSnowman]

Hi @Bambam0, @AfroSnowman, @Tezcatlipoca, @Zugzug, @Diesel, @FGG!

I just want to add, on behalf of Tinnitus Hub, that we are more than willing to facilitate such an effort. I agree such initiatives should be well coordinated — though of course anyone is free to lobby on their own behalf, but doing this as a community will be much more impactful! Grassroots activism has always been part of who we are and it's a major part of why we run this community. If the Phase 2 90-Day readout is positive, I feel like a working group should be formed.

Count me in.

 

[FGG]

So I have been looking at the Phase 1b paper and I've noticed that Frequency Therapeutics is slightly underselling their conclusion for the results. My argument is somewhat technical so before I write it up, I want to pose the following question to someone more knowledgeable.

Once a drug moves on to the next phase, how important are previous phase results for helping the drug to get approved?

Please, no one freak out. It's not that big.

The pivotal phase is what they use. You don't progress to that phase if there is a problem preventing approval.

Not sure if this is what you mean but you are supposed to use terms like "may help" etc because the larger trials are the more confirmatory ones.

What are you referring to specifically?

 

[Aaron91]

Hi @Bambam0, @AfroSnowman, @Tezcatlipoca, @Zugzug, @Diesel, @FGG!

I just want to add, on behalf of Tinnitus Hub, that we are more than willing to facilitate such an effort. I agree such initiatives should be well coordinated — though of course anyone is free to lobby on their own behalf, but doing this as a community will be much more impactful! Grassroots activism has always been part of who we are and it's a major part of why we run this community. If the Phase 2 90-Day readout is positive, I feel like a working group should be formed.

Count me in, @Hazel.

 

[Hazel]

Good to hear all those positive responses and readiness to take action! We'll pick up this discussion as soon as the results are out

Add me in. As a father of two children under the age of three, tinnitus has greatly taken away from the father I want to be! Ever since my sudden hearing loss and tinnitus onset on 12/19 I spiraled into a deep depression and now I'm on antidepressants that make me drowsy all the time. People need to see what this awful affliction can do to people and how it affects their families and loved ones as well.

This is a bit of a side note, but we have an ongoing project to collect stories about how tinnitus affects people, which we will use for awareness raising once we've collected enough of them. You can help out by leaving your story here.

 

[Street Novelist]

Hi @Bambam0, @AfroSnowman, @Tezcatlipoca, @Zugzug, @Diesel, @FGG!

I just want to add, on behalf of Tinnitus Hub, that we are more than willing to facilitate such an effort. I agree such initiatives should be well coordinated — though of course anyone is free to lobby on their own behalf, but doing this as a community will be much more impactful! Grassroots activism has always been part of who we are and it's a major part of why we run this community. If the Phase 2 90-Day readout is positive, I feel like a working group should be formed.

Add me as well. Whatever I can do, I will.

 

[Zugzug]

The data from each successive phase should build on the data from the previous phase. However, each phase also has different outcomes of focus.

Phase 1 is primarily safety. Phase 2 efficacy / side effects. Phase 3 adverse reactions / interactions.

Of note, the hearing performance outcomes that we've all been debating here for about 2 years actually WON'T APPLY to the final decision-making by the FDA. Those outcomes were considered secondary.

The primary outcomes from the Phase 2A, however, will.

Likewise, in the Phase 3, if the hearing performance outcomes look a little less impressive than the Phase 2A (due to a larger, more varied patient group), it won't matter so much, because the primary outcoems should focus more on side effects and interactions.

The pivotal phase is what they use. You don't progress to that phase if there is a problem preventing approval.

Not sure if this is what you mean but you are supposed to use terms like "may help" etc because the larger trials are the more confirmatory ones.

What are you referring to specifically?

I figured as such. It's probably meaningless, but I'm going to write it up for myself and see where it goes. Basically, their statistical tests make total sense for a safety study, but their conclusions read like an efficacy study. I am arguing that they can highlight the results better under their (correct) conservative methods.

For all I know, they are in line with other clinical trials. If this is the case, then I am essentially just teaching myself something about the industry.

 

[Ehren M]

Hi @Bambam0, @AfroSnowman, @Tezcatlipoca, @Zugzug, @Diesel, @FGG!

I just want to add, on behalf of Tinnitus Hub, that we are more than willing to facilitate such an effort. I agree such initiatives should be well coordinated — though of course anyone is free to lobby on their own behalf, but doing this as a community will be much more impactful! Grassroots activism has always been part of who we are and it's a major part of why we run this community. If the Phase 2 90-Day readout is positive, I feel like a working group should be formed.

I am also eager to contribute in any way possible.

 

[Gb3]

There was a trade earlier... 200k shares were bought @ $39.50. That's an investment of $7.9m...

How do you find these things out?

 

[Pharz]

Hi @Bambam0, @AfroSnowman, @Tezcatlipoca, @Zugzug, @Diesel, @FGG!

I just want to add, on behalf of Tinnitus Hub, that we are more than willing to facilitate such an effort. I agree such initiatives should be well coordinated — though of course anyone is free to lobby on their own behalf, but doing this as a community will be much more impactful! Grassroots activism has always been part of who we are and it's a major part of why we run this community. If the Phase 2 90-Day readout is positive, I feel like a working group should be formed.

Count me in as well!

 

[Ehren M]

Definitely coordinated. Although all of the sufferers deserve to write letters individually, there are strategic ways to doing this. And it's not just level of suffering. I consider my suffering level to be high, but I'm not the person that's going to change minds with bad hyperacusis, but stupidly good extended audiograms.

The best chances are to stay consistent with the company's goals, which appear to be EHF range hair cell loss, until we know otherwise. Fortunately, thanks to heroic behind-the-scenes work, Tinnitus Talk is on the map, having landed interviews with big names, including Carl LeBel. We need to accumulate (sorry if that's dehumanizing) sufferers where FX-322 would almost surely help.

It may help to also research precedence based on safety and added benefit for other conditions. Another thought is to include people who have tried CBT or antidepressant therapy without success.

It's tricky because if the wrong person reads these letter(s), they will think that a bunch of depressed people are in their own heads, as opposed to needing hair cell regeneration.

Your concerns regarding tinnitus sufferers being perceived by the FDA as delusional depressed people would be ameliorated by having medical professionals endorse the interests of tinnitus suffers in FX-322. Is that an option?

 

[FGG]

I can help. I'm really hoping (though not counting on for sure) that their top line reveal is detailed. Obviously, it eventually would be in the published paper, but this is where I provide the most value.

I almost get the impression you think of yourself as "mostly a math dude" but you are a fantastic writer/communicator, too imo.

 

[Keith Handy]

I almost get the impression you think of yourself as "mostly a math dude" but you are a fantastic writer/communicator, too imo.

This thread is full of impressive and thoughtful people.

 

[AfroSnowman]

Your concerns regarding tinnitus sufferers being perceived by the FDA as delusional depressed people would be ameliorated by having medical professionals endorse the interests of tinnitus suffers in FX-322. Is that an option?

The other thing would be to get the military side into it. As we all know tinnitus is the most common disability of service members. Assuming FX-322 becomes a viable treatment, we should make a serious effort to reach out to the military community as calling them names and dismissing their injuries is politically and culturally problematic.

 

[Lucifer]

The other thing would be to get the military side into it. As we all know tinnitus is the most common disability of service members. Assuming FX-322 becomes a viable treatment, we should make a serious effort to reach out to the military community as calling them names and dismissing their injuries is politically and culturally problematic.

This; the only way to get people to understand our suffering is to get those who got hearing loss, tinnitus and hyperacusis from working in the military, especially those earplug victims as they should have gotten the best ear protection available but 3M fucked up by using cheap foam to make the product.

When it comes to ear protection it needs to be the best product that provides the best protection from loud sounds which these people didn't get.

 

[Diesel]

This; the only way to get people to understand our suffering is to get those who got hearing loss, tinnitus and hyperacusis from working in the military, especially those earplug victims as they should have gotten the best ear protection available but 3M fucked up by using cheap foam to make the product.

When it comes to ear protection it needs to be the best product that provides the best protection from loud sounds which these people didn't get.

I'm honestly not too worried about the military or VA getting involved pre-ordering mass quantities of FX-322 once it is in production. They produce their own stats pointing to the high rate of enlisted disability from hearing loss and the ongoing costs to cover hearing aids, and other hearing-related treatments for veterans.

 

[Tezcatlipoca]

I'm honestly not too worried about the military or VA getting involved pre-ordering mass quantities of FX-322 once it is in production. They produce their own stats pointing to the high rate of enlisted disability from hearing loss and the ongoing costs to cover hearing aids, and other hearing-related treatments for veterans.

But can the military "pressure" the FDA into really fast tracking the approval of the drug?

 

[d'Wooluf]

It's been discussed in the past, but this was quite a while ago and my memory is fuzzy.

I posted a link yesterday. It looks kind of promising.

https://www.tinnitustalk.com/attachments/local-drug-delivery-entire-cochlea-pdf.43894/

 

[AfroSnowman]

But can the military "pressure" the FDA into really fast tracking the approval of the drug?

I think politically there is no stronger group possible.

 

[Diesel]

But can the military "pressure" the FDA into really fast tracking the approval of the drug?

The last "president" couldn't for COVID-19, so neither can the DoD for hearing loss.

The military can and has sponsored its own experimental drug trials on soldiers in the recent past, and they've done so outside of the jurisdiction of the FDA.

 

[Diesel]

I posted a link yesterday. It looks kind of promising.

https://www.tinnitustalk.com/attachments/local-drug-delivery-entire-cochlea-pdf.43894/

Interesting stuff... except for the part about delivering the drug through the Eustachian Tube. Hard cringe. I'd rather have a hole poked in my eardrum.

 

[d'Wooluf]

except for the part about delivering the drug through the Eustachian Tube.

Where did you get the part about the Eustachian Tube? I couldn't find anything in the article. There's a supplemental 'information' file.

Quote:
5 μl of 100 mM sodium salicylate solution in Hanks' Balanced Salt Solution were placed on the RW using pipettes. The solution was removed from the RW using paper wicks to observe the wash out effect.

Edit: They opened up the middle ear cavity.

 

[Gb3]

Where did you get the part about the Eustachian Tube? I couldn't find anything in the article. There's a supplemental 'information' file.

Quote:
5 μl of 100 mM sodium salicylate solution in Hanks' Balanced Salt Solution were placed on the RW using pipettes. The solution was removed from the RW using paper wicks to observe the wash out effect.

Edit: They opened up the middle ear cavity.

The picture shows it going up the Eustachian tube.

 

[d'Wooluf]

The picture shows it going up the Eustachian tube.

And through the eardrum. I see what you mean but I put it down to a badly designed diagram. I think it means that the drug starts 'here' (outside the round window).

... [edit] or it doesn't matter where the drug comes from. Once it's in the middle ear, the vibration does its thing.