Frequency Therapeutics — Hearing Loss Regeneration

[Diesel]

Nice to see directors directly buying shares of the company...

https://investors.frequencytx.com/static-files/bffee4e3-9d04-40d8-b1c6-c7c30c4362c5

 

[Tezcatlipoca]

Nice to see directors directly buying shares of the company...

https://investors.frequencytx.com/static-files/bffee4e3-9d04-40d8-b1c6-c7c30c4362c5

But I thought all they did was sell and this is all a scam to make money?

Maybe they didn't tell this "Chief Manufacturing Officer", sounds like a low level guy.

 

[F-u-T]

Nice to see directors directly buying shares of the company...

https://investors.frequencytx.com/static-files/bffee4e3-9d04-40d8-b1c6-c7c30c4362c5

That's interesting. Maybe it's time to double down Lost my ass once already. What's the worst that could happen.

 

[Flamberg]

Hey guys,

Can someone give me a brief summary of what to expect in the following months regarding Frequency Therapeutics?

Thanks in advance!

 

[Street Novelist]

Hey guys,

Can someone give me a brief summary of what to expect in the following months regarding Frequency Therapeutics?

Thanks in advance!

Frequency Therapeutics will be releasing their full readout from the Phase 2A trial next month. We are anxiously awaiting the results of the severe hearing loss trial, which is also supposed to end next month; at least, that's what it says on ClinicalTrials.gov. However, they said they will be releasing the results of that trial in quarter 3. So, that probably means August or September.

If those results are positive, we are hoping for anotherPphase 2A trial later this year, but only 1 shot of either the drug or the placebo. Hopefully, they will accept more people this time as the last trial was extremely small.

 

[Kam75]

what to expect in the following months regarding Frequency Therapeutics?

Nothing...

 

[ThomasRobert]

Can someone give me a brief summary of what to expect in the following months regarding Frequency Therapeutics?

The whole company depends on this:

 

[Kleiner]

Anyone know if there will be more information about Study FX-322-111 in June? The details will be interesting to compare with Phase 1.

 

[Chad Lawton]

The whole company depends on this:

View attachment 45074

No, it doesn't. How many times do we have to say, they already have TWO single dose trials showing it works. Every other study is just figuring out who else it MIGHT work on. If FX-322-113 fails, it means it doesn't work for severe SNHL but it still works for mild to moderate SNHL.

 

[Diesel]

The whole company depends on this:

View attachment 45074

It actually doesn't.

The Severe trial having a positive outcome means they would add patients with severe hearing loss to the New Phase 2. If not, they'll just go with Moderate - Moderately Severe hearing loss in the Phase 2.

This is why these trials were setup after the original Phase 2A. The original strategy was probably to add these groups (if successful) to a final phase. Now it's just buildup for a single-dose redo Phase 2.

 

[Zugzug]

No, it doesn't. How many times do we have to say, they already have TWO single dose trials showing it works. Every other study is just figuring out who else it MIGHT work on. If FX-322-113 fails, it means it doesn't work for severe SNHL but it still works for mild to moderate SNHL.

It actually doesn't.

The Severe trial having a positive outcome means they would add patients with severe hearing loss to the New Phase 2. If not, they'll just go with Moderate - Moderately Severe hearing loss in the Phase 2.

This is why these trials were setup after the original Phase 2A. The original strategy was probably to add these groups (if successful) to a final phase. Now it's just buildup for a single-dose redo Phase 2.

Yes and no. Firstly, the open-label trial wasn't placebo controlled so I don't count it as a full trial -- more like something that makes me smile for a few seconds. Moreover, the results from Phase 1/2 weren't like out of this world for the moderate-moderately severe group. A lot of the curiosity and optimism stemmed from the responder data, particularly the three super responders. Even amongst the responders, they all regressed a weird amount at long-term follow up.

I don't think trial 113 is "make or break" for the drug, but if there are placebo super responders and a lack of results, then much of the encouragement from Phase 1/2 is diminished, on top of incomplete info on the ideal patient.

Ultimately, they have the money so the drug won't be dead until the next Phase 2 fails again, but weird placebo data would kill a serious amount of hope (that's already lost).

 

[Diesel]

Firstly, the open-label trial wasn't placebo controlled so I don't count it as a full trial -- more like something that makes me smile for a few seconds.

One thing that I think we're overlooking, is that subjects with Severe Hearing Loss were included in the Open-Label trial. This was not the case with the Phase 1/2. So, they may already have an idea of how the drug works with Severe Hearing Loss.

Unfortunately, they haven't provided any patient-level data; and perhaps they won't with the severe trial already in progress.

 

[kiki]

One thing that I think we're overlooking, is that subjects with Severe Hearing Loss were included in the Open-Label trial. This was not the case with the Phase 1/2. So, they may already have an idea of how the drug works with Severe Hearing Loss.

Unfortunately, they haven't provided any patient-level data; and perhaps they won't with the severe trial already in progress.

Take a look at slide 20.

Phase1b-111 had an interim read out in March.

Those marked with "*" have had interim read outs.

Perhaps Phase 1b-112 will also have an interim read out.

https://investors.frequencytx.com/static-files/4a540e6b-b160-4e35-b487-5c82d264103b

 

[ThomasRobert]

It actually doesn't.

The Severe trial having a positive outcome means they would add patients with severe hearing loss to the New Phase 2. If not, they'll just go with Moderate - Moderately Severe hearing loss in the Phase 2.

This is why these trials were setup after the original Phase 2A. The original strategy was probably to add these groups (if successful) to a final phase. Now it's just buildup for a single-dose redo Phase 2.

Could you list at least one factor that a moderate hearing loss patient has, that a severe hearing loss patient doesn't have? When in a similar environment.

 

[Diesel]

Could you list at least one factor that a moderate hearing loss patient has, that a severe hearing loss patient doesn't have? When in a similar environment.

Better word recognition in quiet. Better word in noise metrics. Better pure tone average.

 

[ThomasRobert]

Better word recognition in quiet. Better word in noise metrics. Better pure tone average.

I apologize as my question was not very clear.

I meant if you could list a factor which a moderate hearing loss patient has, but the severe hearing loss patient doesn't have inside the ear?

Both have support cells, hair cells, synapses, etc.

To be more clear, why would FX-322 work better on moderate hearing loss patients than severe hearing loss patients?

 

[Pero1234]

I assume it will be easier to clearly determine results with people who suffer from severe hearing loss as opposed to people with moderate hearing loss.

I don't say you can fake a word test or speech in noise tests... but I do believe that, if you desperately want a treatment to work, you are inclined to concentrate harder and put more effort to make a guess... with speech in noise that can be enough to get better results.

I think with severe hearing loss, you either hear something or nothing...

What are your thoughts on this?

 

[Diesel]

I meant if you could list a factor which a moderate hearing loss patient has, but the severe hearing loss patient doesn't have inside the ear?

My crude understanding is likely more hair cells/synapses in general or in better condition.

 

[Chad Lawton]

To be more clear, why would FX-322 work better on moderate hearing loss patients than severe hearing loss patients?

Will McLean postulated on this a few years ago. He said something along the lines of that severe patients may not benefit as much as moderate patients because you need healthy progenitor cells in place in order for the drug to work on and often when a patient has reached severe hearing loss through noise trauma, the progenitor cells are damaged as well.

 

[Zugzug]

I apologize as my question was not very clear.

I meant if you could list a factor which a moderate hearing loss patient has, but the severe hearing loss patient doesn't have inside the ear?

Both have support cells, hair cells, synapses, etc.

To be more clear, why would FX-322 work better on moderate hearing loss patients than severe hearing loss patients?

IMO:

If trial design was theoretically perfect, the drug should be better for moderate sufferers for a variety of reasons.

• Higher likelihood of more in tact support cells
• Hearing loss usually disperses over time from high to low frequency from noise-induced (most common cause) hearing loss. FX-322 can really only hit 6-8 kHz at the very max.
• Correlative factors: People with severe hearing loss are more likely to have multi-factorial problems such as synapse damage, genetic factors, viral or autoimmune factors, stria and/or vascular problems. They are also more likely to be older.

Optically speaking, there's a nice sell for the moderate group, which is that if the drug worked, they may be able to avoid the hassle of hearing aids. On the other hand, even if FX-322 worked as intended, there's no way it's replacing the role of hearing aids in people who have severe or profound losses.

It does seem, though, like "proof of concept" in vivo could be easier to demonstrate in the severe group (particularly patients with mostly just standard hair cell loss) because it's not the same random chance of the drug properly targeting the right lucky patch of inner hair cell loss before it gets diffused away.

I think it was smart of them to cast a wide net in order to make sense of these considerations.

 

[tommyd87]

IMO:

If trial design was theoretically perfect, the drug should be better for moderate sufferers for a variety of reasons.

• Higher likelihood of more in tact support cells
• Hearing loss usually disperses over time from high to low frequency from noise-induced (most common cause) hearing loss. FX-322 can really only hit 6-8 kHz at the very max.
• Correlative factors: People with severe hearing loss are more likely to have multi-factorial problems such as synapse damage, genetic factors, viral or autoimmune factors, stria and/or vascular problems. They are also more likely to be older.

Optically speaking, there's a nice sell for the moderate group, which is that if the drug worked, they may be able to avoid the hassle of hearing aids. On the other hand, even if FX-322 worked as intended, there's no way it's replacing the role of hearing aids in people who have severe or profound losses.

It does seem, though, like "proof of concept" in vivo could be easier to demonstrate in the severe group (particularly patients with mostly just standard hair cell loss) because it's not the same random chance of the drug properly targeting the right lucky patch of inner hair cell loss before it gets diffused away.

I think it was smart of them to cast a wide net in order to make sense of these considerations.

The claim that FX-322 can only hit 6 kHz-8 kHz at the very max is still not definitive.

To date the trial results have shown this is the maximum reach with the current dosing mechanism/methods, however lab work has shown it can work more deeply as well. We know for a fact that Frequency Therapeutics are working on and investigating new and improved dosing methods to get the treatment working more deeply and much more effectively.

Essentially the current dosing method of regular intratympanic injections has been the problem when it comes to obtaining the best results possible.

 

[kiki]

To date the trial results have shown this is the maximum reach with the current dosing mechanism/methods, however lab work has shown it can work more deeply as well. We know for a fact that Frequency Therapeutics are working on and investigating new and improved dosing methods to get the treatment working more deeply and much more effectively.

I also speculate that they must be studying improvements in delivery methods.

If what you know is true, it is great hope.

Where did the information come from?

What kind of dosing methods are they investigating?

 

[Tezcatlipoca]

Where did the information come from?

They hired an expert on delivery.

What kind of dosing methods are they investigating?

Most likely that's a corporate secret.

 

[GlennS]

they already have TWO single dose trials showing it works.

The chatter and stock movement doesn't suggest FX-322 can function effectively solely on its existing test results. That might be enough to impress you but not necessarily Wall Street.

 

[OptimusPrimed]

I also speculate that they must be studying improvements in delivery methods.

If what you know is true, it is great hope.

Where did the information come from?

What kind of dosing methods are they investigating?

Drug distribution along the cochlea is strongly enhanced by low-frequency round window micro vibrations

Likely it's something like that for the delivery method. This literally solves their drug application problem.

This drug isn't dead… yet. It's just finding its niche. There will be better drugs coming, and worse ones. From other companies and this one.

 

[Billy_Shears]

FX-322 is not getting a fair trial and FREQ knows it.

 

[ThomasRobert]

Not sure if this has been posted earlier, but I found it to be an interesting article.

Progenitor Cells from the Adult Human Inner Ear

"...we demonstrate that sphere-forming progenitor cells can be harvested from adult human inner ears. We further show that the spheres grown from these progenitor cells can be propagated, albeit with limited potential, and that spheres grown from utricle-derived progenitors gave rise to hair cell-like cells and neuronal or glial cell types. Based on this finding, we conclude that the adult human utricle harbors multipotent progenitor cells..."

 

[Chad Lawton]

The chatter and stock movement doesn't suggest FX-322 can function effectively solely on its existing test results. That might be enough to impress you but not necessarily Wall Street.

Wall Street is treating it as if it doesn't work because FREQ shot themselves in the foot by switching from single dose to multi dose when they went from Stage 1 to Stage 2.

 

[GlennS]

FREQ shot themselves in the foot by switching from single dose to multi dose when they went from Stage 1 to Stage 2.

While that's their excuse, it has yet to be confirmed, and should not be cited as if it has. That's where the beating a dead horse stuff comes in.

 

[Street Novelist]

I wish they would try cochlear pumping.