Frequency Therapeutics — Hearing Loss Regeneration

Just listened to the JP Morgan webinar. Nothing new to report I think. Just a re-iteration of the report that came out a couple of days ago. There were like 5-6 question in the end from listeners, but Frequency Therapeutics seemed very secretive about giving out any additional information beyond the already posted report.

 

FDA gave FX-322 Fast Track status with data on 15 dosed patients in 2019. FDA cleared FX-322 for three concurrent trials in 2021 with multi-location support. And they're having an end-of-Phase 2 meeting in Q4 of 2021. Hardly seems like foot dragging to me...

 

Hey guys, what are your thoughts on the webcast?

I think they didn't release any new information. I guess we will have to wait for the results from the clinical trial.

The only thing I got out of the webcast is that they are planning further trials which would mean that we might have to be patient for even a longer time.

 

Hi everyone!

I wasn't able to join the investor company unfortunately, and the recording is not available yet. Anyone on this forum had a chance to attend it live? Any highlights from the presentation and the Q&A?

Thanks!

 

I have one basket and it’s full of FX-322 eggs.

 

39th Annual J.P. Morgan Healthcare Conference

On-Demand Webcast in Process

The presentation has ended. We are currently preparing a recording of this session.​

I missed the presentation, looks like there will be a recording posted at some point though. Did anyone watch it? Was there any new news?

 

I just realised something. Since Frequency Therapeutics are doing multiple clinical trials this year, what I have come to realise is that they could release FX-322 out into the market once they finish their multiple trials in the current phase.

@Danad posted a WSJ article that said most drugs that receive Fast Track status come out after Phase 2. Frequency Therapeutics hasn’t got Breakthrough Therapy status, but once they do, I see 2022 a real possibility for us to get FX-322 treatment.

 

Frequency Therapeutics seem to be excited to see that 90-day data, and confident. The "group" level data will be split into dose cohorts. They consider a success to be a measurable improvement over baseline that is clear between each cohort, improved QoL measures.

Carl LeBel also implied what @FGG has suggested: There will likely be a Phase 2b/3 pivotal. He mentioned that Phase 2A dosing would be the driver for future Phases involving patient designations from the two Phase 1b trials (Age-Related & Severe). So, one might conclude that they are making the case for combining all designations into a single final trial.

 

The JP discussion disagrees with this theory, unfortunately. They spoke about a future trial after those in 2021 complete. So, it's likely that there will be a 2022 Pivotal trial with the product probably available in 2023.

 

Attached below is an MP3 of today's webcast (Q&A only since the initial part was just a review of company's online presentation). I learned that they were unable to multi-dose in their animal studies due to membrane vulnerabilities. The tone was rather zip-lipped though; as it should be given their adherence to forward looking statements.

 

What is the likelihood that the mention of a pivotal trial was a conservative estimate? They may not need to do a pivotal trial if the multiple trials show positive effects.

Remember they still haven’t received Breakthrough Therapy designation which could help skip the pivotal trial.

 

I'm just going off other info from this thread. Hopefully by adjusting the dosing they can have more than 10 decibel gains @ 8 kHz.

Maybe I missed something but were there gains in other frequencies?

 

Is this something that is a concern for human trials? I thought they were doing multi-dose trials on humans right now.

Why would that matter for animal studies but not human? Or is it a concern?

 

We'll know more at the end of the Phase 2A in probably June if there are specific audiogram improvements.

FWIW - The audiogram shouldn't be seen as the "gold standard" for hearing performance in this trial. All it does is measure loudness at narrow, specific frequencies.

The improvements in word score recognition in both quiet and in noise in the 90-day assessment in the Phase 1/2 is much more impressive. As understanding language really requires more of the cochlea to function in tandem to specification.

The 90-day analysis won't show any information on the audiogram improving, as that will be at the individual level. It will show improvements in word score recognition outcomes and tinnitus.

 

Yes they are doing multiple dosing on humans. I do not think this is a concern. It only explains why they didn't maybe do multiple dosing on animals before humans? Either way, a tiny mouse ear is likely more physically fragile than a human ear, so maybe they determined that. In my opinion, it's a non issue.

 

Animal models apparently could not withstand multidosing (presume anatomical differences) but human subjects can. Good news if multiple injections yields proportionately better results.

 

Well hopefully they will figure it out. It would be amazing to move on with life.

 

It would be certainly great if they got Breakthrough Therapy designation and could skip the pivotal trial. The more data they can compile that FX-322 is safe for multiple hearing loss designations, and if multiple dosing shows to be effective, obviously the more convincing it will be to skip the pivotal trial.

However, it's much more likely that the data will convince the FDA to "lower the bar" on the pivotal trial, requiring less participants while allowing them to recruit for the most common hearing loss designations in a single pivotal trial.

In my opinion, in this likely scenario, it still puts Frequency Therapeutics ahead of the typical 7-year timeline for a Fast-Tracked drug. We should expect that the drug be released in 2025. But considering the progress through 2021, and a potential pivotal trial in 2022; a 2023 product launch is looking more likely.

 

I tend toward predicting a product launch late 2022 if endpoint results are met in the the three currently running trials with no adverse effects. That does put some faith in the FDA to do their job in a timely fashion and award Breakthrough Therapy designation. If tinnitus results are also statistically promising and the VA gets involved (Veterans' #1 disability) then maybe some external pressure would accelerate the process. The media blitz following Phase 2a could prove helpful. Really the difference between @Diesel's opinion and mine on the timeline is but months.

 

If FX-322 comes out in 2023, would it be in the beginning, middle, or at the end of the 2023?

 

So, realistically, we probably won't get the Phase 3 trial this year. This year, just like 2020, will be a wash.

 

No. But we will learn a lot that we don’t know, and have burned hundreds of pages on this forum discussing:

1. Do multiple doses of FX-322 penetrate deeper in the cochlea and restore more hearing?

2. Does FX-322 improve high frequency hearing?

3. Does FX-322 treat tinnitus when it is a symptom of SNHL? And if so, how well does it treat tinnitus?

4. How “bad” of hearing can FX-322 restore?

5. Is FX-322 safe at multiple doses?

The fact that we’re even this far along in discussing a drug, where nothing existed 5 years ago is enough to put up with a couple years of final trials.

 

We will know more about the answers to those questions as soon as March and then we can stop speculating .

The answer to number 3 will be a little more complicated because of bilateral tinnitus and the contribution of synaptopathy but there should be at least a significant difference between control and treated cohorts. This difference would be much more magnified if those factors were controlled for but we should still see a difference between the two groups.

 

It's not a concern. Other drugs in humans like Dexamethasone are given in multi doses without issue.

 

Number 4 as well though, no? I'm excited about the March results but more so for the other trial for severe hearing loss patients as that's where my damaged ear is at. (Moderately Severe to Severe).

 

I don’t think we’ll truly know the answer to this question as they are only giving the participants 1 dose of FX-322 in the severe hearing loss trial.

 

Interesting enough, LeBel did mention on the J.P. Morgan presentation that they had internal filtering criteria to ensure a specific "benchmark" for all Phase 2A participants. I suppose it stands to reason that all 95 reporting having SNHL-related tinnitus. I wonder if they could get as specific as to recruit unilateral cases only?

It would be great to back that up with some data. However, there doesn't seem to be great population data on the prevalence of tinnitus as hearing conditions worsen, or the prevalence of unilateral shifting to bilateral, etc.

 

Yes this is true but if the Phase 2a show positive results following on from the the 1 injection in the initial trial, then I think it's reasonable to assume any improvements, even if very minor (for the severe hearing loss population), in Phase 1b is something to be optimistic about for when they do their pivotal trial.

 

That's a good point.

 

Thank goodness then for OTO-6XX that is also on the horizon.