Frequency Therapeutics — Hearing Loss Regeneration

[tommyd87]

Are there any experiences or concepts of FX-322 or OTO-413 passing or bypassing a surgically sealed round window membrane (connective tissue added during tympanotomy) to enter the cochlea in a somehow promising concentration?

Anyway, would love to experiment one day to find out.

I don't know how your ear would stay sealed since the injection makes a hole in it.

 

[FGG]

Are there any experiences or concepts of FX-322 or OTO-413 passing or bypassing a surgically sealed round window membrane (connective tissue added during tympanotomy) to enter the cochlea in a somehow promising concentration?

Anyway, would love to experiment one day to find out.

Did you have round window reinforcement surgery?

 

[Stenk]

There will be if they can show positive results in their current Phase 2a clinical trial. It will be easier to prove that FX-322 works as improved hearing is not a placebo.

Phase 3 is usually a longer study. Do we have any information how long the Phase 3 would take since, as already mentioned, they won't have other medication to compare it to?

 

[Princebeyel]

Phase 3 is usually a longer study. Do we have any information how long the Phase 3 would take since, as already mentioned, they won't have other medication to compare it to?

I don't think there's any way of knowing the answer to your question as of now. If someone knew, I'm sure we all would by now.

 

[Lucifer]

Phase 3 is usually a longer study. Do we have any information how long the Phase 3 would take since, as already mentioned, they won't have other medication to compare it to?

Phase 3 may be quicker depending on how many days they have to review their patients. In Phase 2a they had to review patients up to Day 210 and we are hoping that for Phase 3 they would only need to review patients up to Day 90.

 

[Philip83]

Is it known when the NDA is possibly lifted on the Phase 2 participants? Just contemplating when we could potentially have some anecdotal stories on the forum.

 

[Diesel]

Is it known when the NDA is possibly lifted on the Phase 2 participants? Just contemplating when we could potentially have some anecdotal stories on the forum.

Normally NDAs have a term (i.e. are upheld for 1 year from execution) and include a provision for a written letter from the executing party (in this case, Frequency Therapeutics), that the NDA is terminated sooner than the term ends.

It possible that for a clinical trial, they can make them like 5-year terms and include some language that once the trial completes, the NDA expires x days after. This way, the NDAs aren't termed out while the trial is still active, especially since delays are common.

This is all speculation.

 

[uissnhl]

Did you have round window reinforcement surgery?

Yes. Done after suffering profound ISSHL to rule out round window membrane rupture.

So the question arises if this reinforcement might have a negative impact and thus needs to be undone first (if even possible) or requires some special form of direct inner ear delivery of FX-322 (like this) or higher concentration.

Anyhow, even natural round window membranes seem to come in different anatomic variations with presumed effect on permeability.

 

[FGG]

Yes. Done after suffering profound ISSHL to rule out round window membrane rupture.

So the question arises if this reinforcement might have a negative impact and thus needs to be undone first (if even possible) or requires some special form of direct inner ear delivery of FX-322 (like this) or higher concentration.

Anyhow, even natural round window membranes seem to come in different anatomic variations with presumed effect on permeability.

Frequency Therapeutics was asked about the anatomic variations and said it was not a factor.

I would think a membrane surgically placed over the round window might be, however.

They aren't likely to trial it before release in cases like yours so if I were in your position, I would try it first (because it won't hurt to do that) and if I didn't achieve results, I would schedule the reversal surgery.

 

[Diesel]

In their January 2021 investor presentation, Frequency Therapeutics provided a little more insight on the 90-day readout.

Time to set expectations...

 

[Philip83]

In their January 2021 investor presentation, Frequency Therapeutics provided a little more insight on the 90-day readout.

Time to set expectations...

View attachment 42728

Yeeeeah, let's gooo!

 

[AfroSnowman]

In their January 2021 investor presentation, Frequency Therapeutics provided a little more insight on the 90-day readout.

Time to set expectations...

View attachment 42728

You just made me very happy. I have been trying to keep my expectation in check, I was concerned that tinnitus wasn't going to make the March review at all.

On top of that it looks like we are going to have scraps and tidbits of news to shift through over the next two weeks. On the 13th the CEO is doing a presentation and Q&A at the JP Morgan Healthcare conference and then on the 19th an investor conference focused on FX-322 with lots of speakers.

 

[Diesel]

You just made me very happy. I have been trying to keep my expectation in check, I was concerned that tinnitus wasn't going to make the March review at all.

On top of that it looks like we are going to have scraps and tidbits of news to shift through over the next two weeks. On the 13th the CEO is doing a presentation and Q&A at the JP Morgan Healthcare conference and then on the 19th an investor conference focused on FX-322 with lots of speakers.

Yeah hopefully by "group" level they read out at the dose level, so: 1x, 2x, 4x, Placebo.

Otherwise it will be FX-322 or Placebo.

Either way should show meaningful results, but I will be interested in the dosage effect at the group level.

 

[Philip83]

Yeah hopefully by "group" level they read out at the dose level, so: 1x, 2x, 4x, Placebo.

Otherwise it will be FX-322 or Placebo.

Either way should show meaningful results, but I will be interested in the dosage effect at the group level.

Hopefully dose results are 4>2>1>placebo, since it would mean there's a good chance more than four shots could improve things even further.

 

[NewLionel]

Maybe Phase 3 includes hyperacusis or maybe some anecdotal evidence from Phase 2?

 

[Diesel]

Maybe Phase 3 includes hyperacusis or maybe some anecdotal evidence from Phase 2?

I would rely on the QOL score to infer hyperacusis improvement. There may be anecdotes, but there is no clinically accepted way to quantify hyperacusis.

 

[Diesel]

Box 6 is helpful.

Maybe I'm optimistic but I interpret this as Frequency Therapeutics anticipating FX-322 pivotal ending sometime no later than the end of 2023.

 

[Philip83]

Box 6 is helpful.

Maybe I'm optimistic but I interpret this as Frequency Therapeutics anticipating FX-322 pivotal ending sometime no later than the end of 2023.

View attachment 42729

Couldn't into 2023 be understood as the beginning of that year?

 

[Diesel]

Couldn't into 2023 be understood as the beginning of that year?

Semantics!

I suppose the 'into' could be translated as the 'first half'.

 

[Street Novelist]

2023? WTF! Why would it take 2 more years to reach Phase 3? They've been doing 1 trial per year. 2018 was Phase 1 and 2019/2020 was Phase 2. Logically Phase 3 should be held in 2021.

 

[Lucifer]

2023? WTF! Why would it take 2 more years to reach Phase 3? They've been doing 1 trial per year. 2018 was Phase 1 and 2019/2020 was Phase 2. Logically Phase 3 should be held in 2021.

I agree. I thought Phase 3 would be quicker if they review patients up to Day 90. They would already know Day 210 Phase 2a results, why would they do up to Day 210 again for Phase 3?

Fuck, this is going to take forever to come out.

 

[Diesel]

2023? WTF! Why would it take 2 more years to reach Phase 3? They've been doing 1 trial per year. 2018 was Phase 1 and 2019/2020 was Phase 2. Logically Phase 3 should be held in 2021.

Phase 2 isn't ending until 2021. The other two Phase 1b FX-322 trials don't end until later in 2021.

So once all those end, they could do a single multi-diagnosis pivotal maybe as early as 2022. It's going to take at least a year to advance it... thus ending sometime in... 2023.

 

[Street Novelist]

The last person injected was in September. They already know the 90 Day results.

WTF are we waiting for?

Phase 3 should be held in the fall.

 

[Princebeyel]

I agree. I thought Phase 3 would be quicker if they review patients up to Day 90. They would already know Day 210 Phase 2a results, why would they do up to Day 210 again for Phase 3?

Fuck, this is going to take forever to come out.

I know the severe hearing loss trial ends at 90 days.

 

[Aaron91]

Phase 2 isn't ending until 2021. The other two Phase 1b FX-322 trials don't end until later in 2021.

So once all those end, they could do a single multi-diagnosis pivotal maybe as early as 2022. It's going to take at least a year to advance it... thus ending sometime in... 2023.

This pretty much answers it. Not to mention two other things as well:

1) The six-month lag (potentially) between market application and FDA approval.
2) The lag time between FDA approval and Frequency Therapeutics producing the stock required for market.

Those two things alone could easily add another year, but if one is an optimist, you can note that the FDA approval is within six months and Astellas, who are backing Frequency Therapeutics, will likely have the resources to manufacture the drug both quickly and at volume.

 

[Diesel]

I agree. I thought Phase 3 would be quicker if they review patients up to Day 90. They would already know Day 210 Phase 2a results, why would they do up to Day 210 again for Phase 3?

Fuck, this is going to take forever to come out.

Note in the presentation that they're validating durability up to 210 days in the Phase 2A. So, if the drug looks to produce durable results at 210 days, and if most of the benefit is received in 90 days, that may be enough to keep the patient cycle at 90 days in the pivotal.

The Phase 3 typically isn't about assessing durability of a drug.

 

[Christiaan]

Isn't 2023 a conservative estimate? I mean, Frequency Therapeutics hasn't received breakthrough designation yet, so it might look very differently if the FDA wants to help speed up the process.

Btw, the study for sensorineural hearing loss (2a) didn't start synchronously with the study in age-related hearing loss and severe SNHL (1b). So why would we expect that these different studies will start at the same moment in the next phase?

 

[Philip83]

Phase 2 isn't ending until 2021. The other two Phase 1b FX-322 trials don't end until later in 2021.

So once all those end, they could do a single multi-diagnosis pivotal maybe as early as 2022. It's going to take at least a year to advance it... thus ending sometime in... 2023.

Would they necessarily wait for all of them to finish before starting to prep and recruit for Phase 3, though? And Phase 2 was delayed because of COVID-19 too, right?

My completely uneducated and optimistic guess is that they start injecting people for Phase 3 in late Q3 2021, read out 200 days later, and then like you say, market release in 2023, hopefully early.

 

[Diesel]

Isn't 2023 a conservative estimate? I mean, Frequency Therapeutics hasn't received Breakthrough Therapy designation yet, so it might look very different if the FDA wants to help speed up the process.

Totally conservative.

 

[Street Novelist]

Would they necessarily wait for all of them to finish before starting to prep and recruit for Phase 3, though? And Phase 2 was delayed because of COVID-19 too, right?

My completely uneducated and optimistic guess is that they start injecting people for Phase 3 in late Q3 2021, read out 200 days later, and then like you say, market release in 2023, hopefully early.

This is what I am hoping for as well. What does the trial for old people have anything to do with ours? Phase 3 should start this year. People should start being injected this summer.