Frequency Therapeutics — Hearing Loss Regeneration

[Guywithapug]

You're not wrong. Only 15 or 20 percent of new drugs that start clinical trials actually become licensed.

I'm thinking nothing but positivity for the outcome of FX-322, it will be regarded as a clinical breakthrough for the hearing impaired and for those who suffer from relentless tinnitus.

A few years from now many of us will not reside on this forum in search of hope, we will no longer be bound by our sensory deficit. We will however, be on a beach, in a forest or overlooking a serene lake with nothing to accompany us but the sweet sound of silence. Fact.

 

[Philip83]

Just a reminder to those who are not experienced in trading stocks but might be getting excited about this one.

Most promising drugs fail, sometimes in Phase 3. When they fail the stock price can drop more than 90% almost instantly. I'm long on this as well but for stocks like this I don't put in more than I can afford to lose.

On the other hand how cool would it be to get your tinnitus fixed and make a bundle in one fell swoop?

Also, no matter what the stock or state of the company, buying at or near all-time-highs is always high risk.

 

[Diesel]

I was going to ask you about this earlier. What happened to the other 10 people that were in the trial? Did they show no gains or what was the deal with that?

They had mild hearing loss, and did not have measurable word score deficits. One older presentation said 45+ word scores. In January of 2020, Chris Loose answered that exact question at the JP Morgan conference. He said, "All patients that received FX-322 saw an improvement. All of them."

We have to keep in mind that this study was primarily for safety. The fact remains, an extremely tiny 15 person sample set created significantly significant results in word score.

 

[Diesel]

Not going to sugar coat this, but the talking heads on the webinar today didn't seem to think FX-322 to be much more than an early stepping stone towards further tinnitus research.

We are putting a lot of stock into a statement of "there were some anecdotes" from the previous trial.

In a way, it's correct. The only tinnitus that may see improvement from FX-322 is a symptom acquired SNHL. That's one of many causes of tinnitus.

We also see many get fixated on "CURES"... FX-322 isn't a cure for anything. It's a treatment.

 

[Diesel]

I'm thinking nothing but positivity for the outcome of FX-322, it will be regarded as a clinical breakthrough for the hearing impaired and for those who suffer from relentless tinnitus.

A few years from now many of us will not reside on this forum in search of hope, we will no longer be bound by our sensory deficit. We will however, be on a beach, in a forest or overlooking a serene lake with nothing to accompany us but the sweet sound of silence. Fact.

We actually need to be more specific than just making broad strokes about OVERALL success rate of a drug from Phase 1 -> Launch. The odds improve for each successive trial where the primary outcomes are positive.

Let's first keep in mind that FX-322 will have been through FIVE trials by the end of 2021:

Phase 1, Phase 1/2, Phase 2A, Phase 1B, Phase 1B.

Also, FX-322 has been given Fast Track status; and drugs with that designation have a higher success rate when the safety profile is favorable. FX-322 seems to have a favorable safety profile. But for this example, we'll ignore the Fast Track status, since there aren't good stats on the exact benefit.

A drug that is starting Phase 1 has a 7% likelihood of making it all the way to approval.

FX-322 has already passed a Phase 1, and Phase 1/2, with primary outcomes and secondary outcomes being overall positive. So, it's already beaten the initial odds to get to Phase 2.

Drugs in Phase 2 have a 15% likelihood of making it all the way to approval.

We're in Phase 2 right now. If the 90-Day results look generally positive; it's 75% likely to proceed to Phase 3. There aren't clear calculations for the additional Phase 1B trials, but I suppose positive outcomes for those will improve that likelihood.

62% of drugs that make it through Phase III with overall positive outcomes make it to market.

So, with the math outlined above (and excluding the benefit that Fast Track might give on the odds), one might argue there is a 46% - 62% chance TODAY in Phase 2A + Phase 1B + Phase 1B that the drug makes it to market.

 

[reggie green]

In a way, it's correct. The only tinnitus that may see improvement from FX-322 is a symptom acquired SNHL. That's one of many causes of tinnitus.

We also see many get fixated on "CURES"... FX-322 isn't a cure for anything. It's a treatment.

Well a treatment is better than nothing. It's a step towards the right direction. More companies will follow with better results.

 

[FGG]

In a way, it's correct. The only tinnitus that may see improvement from FX-322 is a symptom acquired SNHL. That's one of many causes of tinnitus.

We also see many get fixated on "CURES"... FX-322 isn't a cure for anything. It's a treatment.

Right, if you have a cause other than hair cell loss, this ain't your drug.

 

[Lucifer]

Well a treatment is better than nothing. It's a step towards the right direction. More companies will follow with better results.

At least we will know more about which drugs will help with different conditions in the ear such as tinnitus, hyperacusis and hearing loss.

 

[Gb3]

Right, if you have a cause other than hair cell loss, this ain't your drug.

Do you think sudden hearing loss is one of the causes that FX-322 will help?

 

[FGG]

Do you think sudden hearing loss is one of the causes that FX-322 will help?

If you have audiogram changes (and it's not from conductive losses), then you at least have OHC loss so yes, this should help.

 

[FGG]

We actually need to be more specific than just making broad strokes about OVERALL success rate of a drug from Phase 1 -> Launch. The odds improve for each successive trial where the primary outcomes are positive.

Let's first keep in mind that FX-322 will have been through FIVE trials by the end of 2021:

Phase 1, Phase 1/2, Phase 2A, Phase 1B, Phase 1B.

Also, FX-322 has been given Fast Track status; and drugs with that designation have a higher success rate when the safety profile is favorable. FX-322 seems to have a favorable safety profile. But for this example, we'll ignore the Fast Track status, since there aren't good stats on the exact benefit.

A drug that is starting Phase 1 has a 7% likelihood of making it all the way to approval.

FX-322 has already passed a Phase 1, and Phase 1/2, with primary outcomes and secondary outcomes being overall positive. So, it's already beaten the initial odds to get to Phase 2.

Drugs in Phase 2 have a 15% likelihood of making it all the way to approval.

We're in Phase 2 right now. If the 90-Day results look generally positive; it's 75% likely to proceed to Phase 3. There aren't clear calculations for the additional Phase 1B trials, but I suppose positive outcomes for those will improve that likelihood.

62% of drugs that make it through Phase III with overall positive outcomes make it to market.

So, with the math outlined above (and excluding the benefit that Fast Track might give on the odds), one might argue there is a 46% - 62% chance TODAY in Phase 2A + Phase 1B + Phase 1B that the drug makes it to market.

I hate the overall market metric because it's meaningless and misleading because it's spread across the whole market. For instance, Alzheimer's drugs have an extremely high failure rate. Only a handful of drugs in 10 years were approved. Same with certain kinds of cancers.

We don't know what the success rate of cochlear regeneration drugs is because it's never been done before but so far the data shows that this drug does work.

 

[Street Novelist]

Not going to sugar coat this, but the talking heads on the webinar today didn't seem to think FX-322 to be much more than an early stepping stone towards further tinnitus research.

We are putting a lot of stock into a statement of "there were some anecdotes" from the previous trial.

Maybe because the whole point of FX-322 is restoring hearing, not curing tinnitus. If your tinnitus is not a result of hearing loss, I don't even know why you would be in this thread.

 

[serendipity1996]

Well a treatment is better than nothing. It's a step towards the right direction. More companies will follow with better results.

I think "cure" is a word that's easy to get hung up on. However, at the end of the day there are many conditions which can't be cured, but can be effectively treated so that you can live a normal and happy life.

 

[Diesel]

I think "cure" is a word that's easy to get hung up on. However, at the end of the day there are many conditions which can't be cured, but can be effectively treated so that you can live a normal and happy life.

"Cure" sets the wrong expectations for this drug and any hearing loss drug. A cure for hearing loss / tinnitus would mean that once taken, one's hearing would be restored to a Day-Zero condition, and their tinnitus would go to zero as well. It also implies that one would never be able to experience such a condition, and that is what many will expect will happen if cure keeps getting thrown around.

The reality is, that hearing looks like it will be restored to a reasonable extent, but not back to the way it was at Day-Zero of our lives; same with tinnitus as a symptom. All the brand new hair cells that are created are still subject to the same wear-and-tear as the original hair cells. So, hearing loss will still progress naturally, and if the patient has their tinnitus resolved, they're likely to experience it again some day.

Also, let's not forget that FX-322 doesn't touch hair cells that aren't damaged/dead.

So, after FX-322 treatment, a patients cochlea is probably going to be scattered with a mixture of spanking-new hair cells and hair cells aged/worn to their current age. Those worn cells are still going to wear at a faster rate than the new ones.

This is my problem with "Cure."

 

[Keith Handy]

All the brand new hair cells that are created are still subject to the same wear-and-tear as the original hair cells. So, hearing loss will still progress naturally, and if the patient has their tinnitus resolved, they're likely to experience it again some day.

I wouldn't worry too much about the death of the new hair cells, if it took this long for them to die in the first place, and you have most likely learned a little basic caution. That said, if you need a second run someday, at least the treatment will have already been invented and approved (and maybe surpassed by something even better).

I do realize though that we're only really talking about the word "cure," and of course, you're correct.

 

[AfroSnowman]

which can't be cured, but can be effectively treated so that you can live a normal and happy life.

We need to remember that for more than 98% of people with tinnitus it's such an inconsequential deal that it isn't even worth a shrug. An effective treatment is the one that brings us from being sufferers to shruggers.

 

[Diesel]

I wouldn't worry too much about the death of the new hair cells, if it took this long for them to die in the first place, and you have most likely learned a little basic caution. That said, if you need a second run someday, at least the treatment will have already been invented and approved (and maybe surpassed by something even better).

I do realize though that we're only really talking about the word "cure," and of course, you're correct.

I agree that it will be reassuring at that future state, the availability of treatment will make regenerating those "original stock" hair cells a lot less of an issue. The fact remains, recent research shows that hearing/hair cells with a history of early noise exposure/acoustic traumas degrade at a faster rate than those that do not.

I suspect we'll see a "cohort" of patients that think their hearing is cured. But in reality, they'll face a series of returns when they got back to daily life and start wiping out those "original equipment" cells that didn't get treated that are already compromised.

 

[Jrblovsky]

We need to remember that for more than 98% of people with tinnitus it's such an inconsequential deal that it isn't even worth a shrug. An effective treatment is the one that brings us from being sufferers to shruggers.

I think more people than what you realize find tinnitus a nuisance, but you're right, most aren't debilitated. I wish it was just a nuisance.

 

[Sironketchup]

If this thread was about a stock or a coin, I would say it's time to buy. Very low sentiment.

 

[Street Novelist]

FX-322 works. People need to stop with the pessimism. If you get the drug, have your hearing restored, and fuck up all over again and lose your hearing, then you're an idiot.

 

[Lucifer]

FX-322 works. People need to stop with the pessimism. If you get the drug, have your hearing restored, and fuck up all over again and lose your hearing, then you're an idiot.

I agree that FX-322 works. Only problem is that we don't know whether additional doses of FX-322 go deeper in the round window. If it doesn't, FX-322 will need to use a different delivery method to get it deeper in the round window.

 

[Gb3]

FX-322 works. People need to stop with the pessimism. If you get the drug, have your hearing restored, and fuck up all over again and lose your hearing, then you're an idiot.

I hope it works, but to say it works for sure, is a little premature.

 

[Diesel]

I hope it works, but to say it works for sure, is a little premature.

I feel like we're going to keep reading this quote until after the 90-day results, the Phase 2A end results, both Phase 1B results, and the end of the Phase 3 results... "We still don't know it works for sure until... xyz"

 

[Gb3]

I feel like we're going to keep reading this quote until after the 90-day results, the Phase 2A end results, both Phase 1B results, and the end of the Phase 3 results... "We still don't know it works for sure until... xyz"

Well yes, that's why they are doing trials.

 

[Street Novelist]

If the drug didn't work, it would not have made it out of Phase 1. Does everyone remember the trial in San Antonio in 2018? People were given the drug then. If it didn't work then, we wouldn't have a Phase 2.

 

[Bill Arsenault]

In a way, it's correct. The only tinnitus that may see improvement from FX-322 is a symptom acquired SNHL. That's one of many causes of tinnitus.

We also see many get fixated on "CURES"... FX-322 isn't a cure for anything. It's a treatment.

For some of us older people - our ears are so abused and messed-up in so many different ways that I am thinking if the treatment is effective we will get some relief or benefits in one way or the other.
I would be happy with that for now.

As of right now I am extremely fearful of completely losing my ability to hear anything over 8 kHz and only hearing tinnitus.

Since my tinnitus became intrusive several years ago, I have gradually lost from 14 kHz down to 9 kHz and the tinnitus gets louder as this continues to happen.

I can no longer hear some of warning beeps that trucks make when they're backing up.
I used to have plenty of warning when my boss was arriving and now he just pops up and I'm like where the hell did you come from.

Anyway - I don't want to go deaf and only hear tinnitus - so that's my positive spin on my expectations for FX-322.

My heart often goes out to the younger folks with this affliction who are trying to go to school, make careers, have relationships, raise children, buy property etc... and with all of the amazing stuff going on right now I rest easier knowing they will be getting real help instead of all the BS and lies that previous generations were sold or had no choice but to buy into.

 

[Koz]

I had some bad news yesterday. It would seem my bad ear is in the severe to profound range now. Hopefully FX-322 shows efficacy for severe hearing loss. Which I think would probably mean FX-322 might be partially effective to not effective at all for me. Fingers crossed its the former and not the latter.

At least if this stuff works I can always use it if anything happened to my good (right) ear I suppose. Looking forward to some hope from the Phase 2A/1B readouts.

 

[Pero1234]

If the drug didn't work, it would not have made it out of Phase 1. Does everyone remember the trial in San Antonio in 2018? People were given the drug then. If it didn't work then, we wouldn't have a Phase 2.

Not quite... That phase is just to make sure the drug does not kill you.

(Exaggeration but you know what I mean).

 

[Gb3]

If the drug didn't work, it would not have made it out of Phase 1. Does everyone remember the trial in San Antonio in 2018? People were given the drug then. If it didn't work then, we wouldn't have a Phase 2.

The first trial was just for safety.

 

[Aaron91]

If the drug didn't work, it would not have made it out of Phase 1. Does everyone remember the trial in San Antonio in 2018? People were given the drug then. If it didn't work then, we wouldn't have a Phase 2.

This is misleading. Phase 1 trials have in the past been known as "first-in-humans" trials with the intention of gathering some data as to how the drug's safety profile translates from animals to humans. This is also why the cohorts in Phase 1 trials are so small. If 8 people die, at least they're facing only 8 potential lawsuits.

It's true Frequency Therapeutics carried out efficacy results as well, which usually happens only in later phases, and they observed positive results, but even if their results were not so positive this would not mean they would not have carried on. Part of Phase 1 testing is about also determining the right dosage, but translating dosage models from animals to humans isn't an exact science. If it were, Frequency Therapeutics wouldn't be now experimenting with four different dosages. In other words, it's possible that one can observe positive effects with a drug but only at the right doses. For many of us here who take other medication this is hardly news at all. There can be a certain threshold of dosage that a drug needs to pass for one to observe a benefit. It just so happened that in the case of FX-322 that threshold was clearly surpassed in the initial phase, albeit not at statistically significant levels in all patients.

With all this said, you are right when you say that this drug works, or at least does something. The pertinent question is, which all of us have had now for a while is: how high is the ceiling?