Frequency Therapeutics — Hearing Loss Regeneration

[Lucifer]

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.

I wish we had better diagnostics of knowing what's regrown with FX-322. This is basically a cat and mouse game.

 

[Diesel]

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."

I always took you for more of an Ian Malcolm:

 

[Gb3]

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.

New guy here! Just joined to say there will never be a cure!

 

[Diesel]

New guy here! Just joined to say there will never be a cure!

There is a cure: TRT.

 

[RB2014]

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.

The stock could go up between now and then, but agreed with your assessment. At this point its just best to sit back and see what it goes.

 

[Lucifer]

The stock could go up between now and then, but agreed with your assessment. At this point its just best to sit back and see what it goes.

I mean it depends how much money you put in. I would definitely not buy a lot but if you willing to spend max around $250-$500 then go for it. If you buy now and it goes up to $20 before they release the results, then sell if you don't have confidence that FX-322 works. If it was, me I'd continue holding.

 

[Tezcatlipoca]

New guy here! Just joined to say there will never be a cure!

Sorry but half a dozen guys already beat you to it.

 

[Jrblovsky]

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.

The odds of losing at the casino and on this stock are not in favor of the house. Hang it up dude. The stuff doesn't work.

 

[Matchbox]

There is a cure: TRT.

Best April Fool's I heard today.

 

[HootOwl]

 

[RingingBrother]

The stuff doesn't work.

It does though.

 

[WickedCarnival]

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.

See my other post. The problem is the delivery, not the drug itself. Otomagnetics delivery system is the answer to getting it working! But no, I guess I'm not loud enough to catch people's attention with it.

 

[Gabriel5050]

This thread is just going in circles lol.

 

[Matchbox]

See my other post. The problem is the delivery, not the drug itself. Otomagnetics delivery system is the answer to getting it working! But no, I guess I'm not loud enough to catch people's attention with it.

How the hell are magnets going to do anything? There isn't exactly precise control when it comes to any external magnetic field. This makes zero sense.

 

[Aleksandar]

See my other post. The problem is the delivery, not the drug itself. Otomagnetics delivery system is the answer to getting it working! But no, I guess I'm not loud enough to catch people's attention with it.

I hope Frequency Therapeutics is aware of Otomagnetics because their delivery method looks very interesting. I think with this system FX-322 might go down to 3-4 kHz.

 

[kiki]

Change of pace.
I will try wishful thinking.

If FREQ does not fail the two Phase 1Bs it is currently working on, what would it do next?

1 Without improving the current FX-322 as it is, proceed to Phase 2a of a single injection for a large number of people by collecting the three types of subjects so far.

2 Without improving the current FX-322 as it is, proceed to Phase 2a of multiple injections at long intervals for a large number of people collecting the three types of subjects so far.

3 Make some improvements to the current FX-322, and perform Phase 1b by collecting the three types of targets so far. Then proceed to Phase 2a for a single injection for a large number of people by collecting the three types of subjects so far.

4 Make some improvements to the current FX-322, and perform Phase 1b by collecting the three types of targets so far. Then proceed to Phase 2a of multiple injections at long intervals for a large number of people collecting the three types of subjects so far.

4 Other... Collaboration with other companies, etc.

What do you think?

 

[Auricle]

I saw the diagram, but it didn't make sense. How would they deliver it through the Eustachian tube?

According to this literature review paper from 2013, it's possible using endoscopy but not easy:

"Both of these techniques, endonasal and transtympanic endoscopy, require an anesthetic due to their invasiveness and require considerable skill in an anesthetized
patient, as well as technical support. They are not in widespread use and due to technical restraints are unlikely to increase in utilization."

Drug delivery to the ear

 

[Rb86]

This thread is just going in circles lol.

No shit.

Anyhow, do I remember correctly that it was mentioned Frequency Therapeutics was going to measure and comment on tinnitus levels?

 

[Zugzug]

This thread is just going in circles lol.

Everyone's just using their own coping mechanisms lol. For some, it's to talk about it. For others, it's to reject the whole thing. None of it really matters.

 

[GlennS]

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

And this is where the thread goes south. Love that use of royal we. I'm hardly the only pessimist in this thread. If you want to tone-police this thread down to just a safe-zone for optimists you're going to have to do more than just attack me.

This thread is just going in circles lol.

Everything turns into lord of the flies once there's no news left.

The odds of losing at the casino and on this stock are not in favor of the house. Hang it up dude. The stuff doesn't work.

Incoming attack from Street Novelist in 3, 2, 1...

 

[Momme]

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

What does words in noise mean?

 

[WickedCarnival]

How the hell are magnets going to do anything? There isn't exactly precise control when it comes to any external magnetic field. This makes zero sense.

Watch this video about the system's concept:

 

[RB2014]

What does words in noise mean?

This is when they test understanding words mixed in with a background noise. This would be similar to talking in a loud bar. When you start to lose high frequency hearing, usually this can be found in the words in noise test. Some people hear "ok" in quiet environments and not good in noisy ones.

To give you an idea, with my hearing aids and lip reading, I get like 90 percent accuracy on a word score. Without lip reading and just hearing aids, I get 30 or so. My word in noise is pretty much 0. Keep in mind these are really bad scores, but my hearing is almost gone.

 

[FGG]

Change of pace.
I will try wishful thinking.

If FREQ does not fail the two Phase 1Bs it is currently working on, what would it do next?

1 Without improving the current FX-322 as it is, proceed to Phase 2a of a single injection for a large number of people by collecting the three types of subjects so far.

2 Without improving the current FX-322 as it is, proceed to Phase 2a of multiple injections at long intervals for a large number of people collecting the three types of subjects so far.

3 Make some improvements to the current FX-322, and perform Phase 1b by collecting the three types of targets so far. Then proceed to Phase 2a for a single injection for a large number of people by collecting the three types of subjects so far.

4 Make some improvements to the current FX-322, and perform Phase 1b by collecting the three types of targets so far. Then proceed to Phase 2a of multiple injections at long intervals for a large number of people collecting the three types of subjects so far.

4 Other... Collaboration with other companies, etc.

What do you think?

They have indicated they plan to proceed with single dosing. Their patient selection and trial design will depend on results.

 

[FGG]

According to this literature review paper from 2013, it's possible using endoscopy but not easy:
Drug delivery to the ear

The endoscopy approach just gets it to the middle ear. I don't see that as an advantage over IT injections for most patients but it's clearly an advantage for certain conditions like delivering drugs for chronic untreated middle ear infections where the ear drum might be too friable to inject.

It might be useful in cases where the eustachian tube is open and you want less drug to drain out, too.

 

[Keith Handy]

Watch this video about the system's concept:

I am not opposed to giving this consideration. Right now we can't afford to dismiss any delivery system. The problem here is that it seems to deliver to the round window but not help distribute through the cochlea; it's the bus dropping the child off at school, but they still need to find their homeroom after entering the building, which is the stumbling point for FX-322.

 

[Zugzug]

I was looking at some of the details of the Severe SNHL trial.

The bad news (and more of a reason why Phase 1 results can be less trustworthy) is that the sample is split into 30=24+6 into treatment versus placebo. There are several reasons why people should understand that these results are less meaningful than Phase 2 trials.

Firstly, because safety is the main concern, they have no problem making it 4:1. The reason is that they simply want as many people as possible taking the drug to look for adverse effects.

Secondly, it helps recruiting because people are more interested in joining a clinical trial with a higher probability of receiving the treatment. This is precisely why Phase 2a had poor design; it was a 3:1 design of some treatment versus placebo. When the ratios are this skewed, the sample sizes have to be much larger to demonstrate statistical power.

The thing I'm saddened by is that even if 0/6 of the placebos in the severe trial have massive word score gains, it's still only 6 people -- still not out of the realm of possibility that it's from chance. Basically, the treatment arm has to crush the placebos for there to be some real encouragement.

BTW, this is pretty standard. For example, OTO-413 also had 3:1 recruitment for Phase 1/2. Safety, safety, safety.

If in the next Phase 2 trial, Frequency Therapeutics makes the ratio closer to 1:1, they will have greater recruitment problems (50% chance of receiving 1 dose). Recruitment is going to be longer and more expensive, in all likelihood.

 

[FGG]

I am not opposed to giving this consideration. Right now we can't afford to dismiss any delivery system. The problem here is that it seems to deliver to the round window but not help distribute through the cochlea; it's the bus dropping the child off at school, but they still need to find their homeroom after entering the building, which is the stumbling point for FX-322.

Agree, if there is an IHC preference and/or restoring one row of OHCs does not produce large audiogram changes (e.g., as in the study @Diesel posted), "delivery" is not the main issue, it's the need for multi dosing (at bigger intervals).

Delivery does not explain Frequency Therapeutics' results, though it is something they will eventually have to address to reach sub 6-8 kHz since rapid multi dosing is too problematic.

I'm not fully sold on the Otomagnetics idea but if it changes the diffusion speed, it could help, especially if you can get more drug in with the same volume of liquid.

No one likes the idea of surgery but once the genetic deafness AAV therapies can administer their drugs safely (which have to span the whole cochlea as well as be directly administered into the cochlea), then they have solved the inner ear drug delivery problem.

I find Akouous' approach of Stapes venting intriguing and if it proves as safe as they suggest, it could be viable for delivery of any inner ear drug

 

[Zugzug]

Agree, if there is an IHC preference and/or restoring one row of OHCs does not produce large audiogram changes (e.g., as in the study @Diesel posted), "delivery" is not the main issue, it's the need for multi dosing (at bigger intervals).

Delivery does not explain Frequency Therapeutics' results, though it is something they will eventually have to address to reach sub 6-8 kHz since rapid multi dosing is too problematic.

I'm not fully sold on the Otomagnetics idea but if it changes the diffusion speed, it could help, especially if you can get more drug in with the same volume of liquid.

No one likes the idea of surgery but once the genetic deafness AAV therapies can administer their drugs safely (which have to span the whole cochlea as well as be directly administered into the cochlea), then they have solved the inner ear drug delivery problem.

I find Akouous' approach of Stapes venting intriguing and if it proves as safe as they suggest, it could be viable for delivery of any inner ear drug

Delivery could still be a big problem beyond just pushing deeper, couldn't it? For example, maybe it needs to maintain itself in the cochlea for a certain amount of time in order for IHC to grow in large amounts or for OHC to grow in any amount. I realize the rebuttal is that if the IHC are all regrown after >=1 passes, then the drug could immediately start working on OHC at future passes. I'm not sold on this. Maybe it helps some IHC and due to quick decay (bad delivery), it's impossible for it to fully revitalize a full layer of hair cells. Is that possible?

 

[Diesel]

I was looking at some of the details of the Severe SNHL trial.

The bad news (and more of a reason why Phase 1 results can be less trustworthy) is that the sample is split into 30=24+6 into treatment versus placebo. There are several reasons why people should understand that these results are less meaningful than Phase 2 trials.

Firstly, because safety is the main concern, they have no problem making it 4:1. The reason is that they simply want as many people as possible taking the drug to look for adverse effects.

Secondly, it helps recruiting because people are more interested in joining a clinical trial with a higher probability of receiving the treatment. This is precisely why Phase 2a had poor design; it was a 3:1 design of some treatment versus placebo. When the ratios are this skewed, the sample sizes have to be much larger to demonstrate statistical power.

The thing I'm saddened by is that even if 0/6 of the placebos in the severe trial have massive word score gains, it's still only 6 people -- still not out of the realm of possibility that it's from chance. Basically, the treatment arm has to crush the placebos for there to be some real encouragement.

BTW, this is pretty standard. For example, OTO-413 also had 3:1 recruitment for Phase 1/2. Safety, safety, safety.

If in the next Phase 2 trial, Frequency Therapeutics makes the ratio closer to 1:1, they will have greater recruitment problems (50% chance of receiving 1 dose). Recruitment is going to be longer and more expensive, in all likelihood.

I'm not so sure "the bad news" is so bad. In the Phase 1/2, they observed a mixed batch of hearing loss levels based on audiogram. Mild -> Moderately Severe. Word score also varied dramatically at baseline as a result. And, as you pointed out numerous times, the randomization of different hearing classes just happening to end up in placebo vs drug raised some concerns.

With the severe trial, its a very specific population that must will fit a narrower window on both audiogram and word score. I would argue that at these levels, the audiogram and word score tests are actually more useful. So, we should expect there to be 30 "like" candidates; which minimizes the variability that caused a lot of debate from the Phase 1/2.

As far as the next two trials go - Que sera, sera.