Frequency Therapeutics — Hearing Loss Regeneration

Folks are just sharing ideas, speculating and passing time in a constructive way.

We are on standby till the end of the year, fingers crossed, for phase2 a trial results.

Stocks are an indicator that there is promise and is a very good thing that the company is soaking up money. Another Boston based company just soaked up 100 million... (Akouos).

There is supposedly a conference I believe in a couple months where we may get bits and pieces... but ultimately we are waiting for this trial to fill and complete.

We are waiting, coping with our afflictions and praying the drug is amazing.

 

There's probably no point checking in before December then. You won't hear anything worth hearing before the results are announced. The study finishes at the end of September. Going by the last study, they'll take their sweet time in releasing results. We may not hear anything until early next year.

 

We'll have the Audion Regain Phase 2 results to pore over at the start of May which will probably give us some food for thought re how well Frequency's drug might do but as others have said nothing substantive from Frequency until the 2nd half 2020 (end of probs).

 

I'm a bit worried that Audion has been too quiet. Frequency has cut deals, made the news, is regularly going to conferences, and is gearing up for what looks like a roll out of FX-322. If you google for Audion, there's almost no news stories or buzz about them. If they have a drug that works, why are they being so quiet? Additionally, in Frequency's Phase I results, they played up how 4 of the individuals treated saw statistically significant improvements. There was nothing about patient improvements in the Audion Phase I results. The only indication we have that LY3056480 works is a second hand story from someone on this forum (which admittely is good intel, though why would someone whose hearing improved go back on tour to wreck it again?).

I poked around a little on LinkedIn, where Audion has a small presence. I noticed the CEO of Audion is also the CEO of another company. I'm not sure how common that is, but that seemed odd. Of the 3 employees listed, I looked at the activity of 2 of them and didn't see anything that really shed any light on big news coming.

Anyway, this is just me trying to read the tealeaves. I'm starting to wonder if we should expect disappointing results from Audion. If it wasn't for the story on this forum about a musican recovering, I would say it looks bad for Audion, though that leak seems to make it sound like they have something real - but if they have something that works, I don't understand why they'd be acting the way they are.

 

For a few reasons (and you have touched on one of them, lack of phase 1 fanfare), I have more than a bit of reservation about Audion. I hope I am wrong though!

 

Audion does not need to make noise or self-promote to get money. They get their money from the EU right?

Perhaps they choose just not to waste any energy on communications until they have something to communicate. Results after each phase?

Our Consortium
An international consortium of 7 partners has been awarded a €5,8 million European Commission Horizon 2020 grant to develop and test a new drug to treat hearing loss caused by the loss of sensory hair cells.
The consortium’s unique combination of expertise in hearing loss biology and drug development and clinical expertise in treating hearing loss allows REGAIN to advance from proof-of-concept to the clinic.

 

Out of curiousity, I'm guessing one of the other major reasons was the research paper [1,2] you mentioned a while back? I took another look at it and this line jumped out at me:

these results suggest that while Notch inhibition is sufficient for promoting stereocilia bundle formation, it is insufficient to convert neonatal supporting cells to mature hair cells.​

The first time I tried reading the paper I had trouble making heads or tails of what they were talking about. This time through it made a little more sense, definitely a bit discouraging. Hopefully the cells FX-322 generates are more like real hair-cells and less like these HCLCs (hair-cell like cells).

[1] Frequency Therapeutics — Hearing Loss Regeneration
[2] https://www.frontiersin.org/articles/10.3389/fncel.2018.00073/full#F1

 

Good recall on that paper.

You are correct. My skepticism on Audion's method was greatly amplified with that paper. I think essentially retrofitting a mature support cell is very likely to be no one near as effective or functional as creating one from a progenitor.

It may actually mean Audion works better for tinnitus than hearing loss, though, because even a abnormal signal probably stops the fusiform hyperactivity in the DCN I would guess. It still suffers the problem of SC depletion though and the CEO not sounding very excited about it.

 

This sounds great. Mind explaining a bit more how this might happen?

 

A few things:

1. I’m absolutely psyched to do this and I pray COVID-19 doesn’t delay the recording and/or broadcast of this Tinnitus Talk Podcast episode.

2. I have my script of what I think are the most important questions. I can assure you @FGG and I left no stone unturned in regards to Tinnitus Talk’s broad and individualized concerns.

3. We ARE taking members’ questions into consideration and we have not submitted our script to Frequency Therapeutics for review yet. So if you have questions, bring ‘em.

 

We know when a new hair cell is formed it reattached to the type 1 SGN. Do they also reconnect to the type 2 afferent SGN? This is a very important consideration for the potential to impact pain hyperacusis.

Since these neurons are not used for hearing they didn’t get much mention (that I noticed) in Frequency’s previous presentations.

Thanks so much @FGG and @mrbrightside614 for your hard work!

(I’ll send this through SurveyMonkey as well, didn’t notice the link at first).

 

Thank you so much.

 

Isn’t Pipeline using a form of notch inhibition as well to generate a small amount of OHC?

What’s strange is that they claimed that all of their new hair cells had proper characteristics and alignment. I wonder why Audion might be struggling with this and Pipeline hasn’t. Perhaps the notch pathway they are utilizing is different? Can different notch pathways affect the effectiveness of turning a mature SC into a fully functional hair cell?

 

This is wonderful news!

You're going to be getting a lot of questions

 

Is it possible to speculate at what time period, years, after sudden hearing loss that this drug would be effective? Poorly worded... Do we still have a chance to benefit from this drug say 7,10, 15 years after our trauma, hearing loss?

 

Pipeline are also using a Gamma Secretase Inhibitor, like Audion but I don't think it's as aggressive. This may be a situation where a weaker inhibition is better. When I emailed Pipeline, they seemed confident their hair cells were normal (I even emailed them this exact paper).

 

This is so exciting, I can't wait to hear the podcast!

With @mrbrightside614 and @FGG's knowledge and passion behind the questions, and @Hazel's podcast/interview experience guiding the way I couldn't imagine a better group of people for the job!

As far as questions/topics go, I want to hear EVERYTHING, haha

...But really, I would be very interested to hear what they have to say about the robustness or longevity of the improvements FX-322 might offer. As I brought up in my question to the forum a few days ago, I would be curious if they have any insights in regards to the strength of the regenerated hair cells/synapses, both generally, as well as compared to someone who's never had damages. Do they believe there would be any greater noise exposure risk for someone treated with FX-322 as opposed to someone who never had more significant losses/damages?

As a side note, I can't help but get the feeling that, much like how they've added the tinnitus measures to their phase 2 trials, Frequency's willingness to appear on a podcast focused specifically on tinnitus is not without good reason. Might hint at some exciting trends they've seen in their trials so far!

 

Good heads up, I didn't notice that at first either!

 

This is a good question. I’ll add it as one of my follow-ups.

I agree with you on your last point as well. Very heartening in- and of-itself.

 

Sounds very promising and will hopefully allay many concerns regarding timelines from clinical trials to commercialization, efficacy and safety, and the spectrum of scenarios where FX-322 will have application.

Thank you @FGG, @mrbrightside614, and @Hazel for offering your time and specialized knowledge of the subject matter in making this event a reality. Also. thank you @Markku for the notice.

 

Saw this the other day. Audiologist on FX-322.

The First CURE for Hearing Loss? | FX-322

 

I like this guy and respect his channel but he neglects the fact that it was only a small safety dosage administered and that there were actually 4 patients if I recall correctly who did have a 10 dB threshold improvement @ 8 kHz. And they didn't report what was likely OHC growth in the UHF's.

Hoping @FGG can ready a good response to him

 

@mrbrightside614 @FGG @HootOwl @Hazel @Markku

Hey all! I've been lurking on this thread with a watchful eye for a couple of months now.

Thank you for all that you do.

Seriously, one of the few good things my hearing loss/tinnitus has given me is a great sense of admiration and sympathy for those of us who endure these burdens! Especially those of you who put in what is obviously hours per day to simply help and inform others.

I believe this would give any sensible person hope for humanity if they didn't have any before, and I cannot state my fondness of you enough.

I've pitched the below questions through the survey for the upcoming podcast (totally missed that link before) but am reposting to get some discussion going if possible:

What can those of us who are aware of FX-322 do to ensure we get the treatment as soon as possible?

Elaboration incoming:

Once this drug is approved to hit the market (as I believe it will) and the press gets a whiff of it, there is bound to be a media storm and a presumably large backlog of appointments at every clinic that offers Intratympanic injections.

We know that for the clinical trials, participants had to have an audiogram going back at least 6 months to show that hearing loss was stable.

Would it be a good idea for those of us who haven't had a professional audiogram to get one done - could demonstrably stable hearing loss end up being a prerequisite in order to receive the actual treatment?

In addition, while we don't know exactly when it's hitting the market, it has crossed my mind to schedule an appointment with a qualified ENT as soon as the drug is approved.

For example, my provider lets me email doctors about issues before meeting them; I could potentially inform my ENT of choice that I want to make an appointment in advance to receive the FX-322 treatment, in turn 'reserving' my treatment in wake of the incoming frenzy.

If I could be so bold, I believe that all of us who care enough to follow the developments on FX-322 want our injections ASAP.

Due to our acute awareness, we'll likely know when it's approved for the market before the vast majority of the public does: even if it's only by a few hours or days.

At the risk of sounding selfish, I'd like to leverage that headstart in order to get the treatment without standing in line behind the 30 million or so other American hearing loss sufferers, if at all possible.

Again, thanks for all that you do, I am truly inspired by your kind actions. I'm looking forward to the upcoming podcast, and intend on becoming a patron!

 

I think it's possibly deliberately misleading because he plugs hearing aids at the end. And Audiologists' primary job is to fit and adjust hearing aids.

The reason I say that is he referenced the cochlear implant patient study but not the explant study which showed OHC growth and, as you said, he didn't make the obvious safety dose connection or describe Frequency's own explanation attributing at least some of the word score improvements to UHF changes in OHCs.

What I got from the video: this is exciting but still buy hearing aids and don't wait for it.

 

@serendipity1996

It's great that he's spreading awareness! I also feel like he missed at least one point in addition to what @Tweedleman pointed out:

They were only tested up to 8 kHz.

The human hearing range can extend all the way to 20 kHz.

Most people with tinnitus and noise-induced hearing loss tend to lose those upper frequencies before losing the lower ones (as I understand it the frequencies get lower as you go deeper into the Coachella, so this makes sense).

For example, I have pretty moderate tinnitus but I hear speech frequencies perfectly fine. The loss of frequencies that are > 8 kHz, and largely untested by audiologists, seem to be responsible for a ton of hearing-related issues.

So even if the current formula of FX-322 isn't helping much at lower frequencies, regenerating the higher ones would still be a godsend for people like me.

In addition, the higher frequencies are also what is thought to help with word clarity, so that explains the correlation where he mentioned an improvement in word clarity among phase 1 patients...

This is why I think all audiograms should include high frequencies. Only testing up to 8 kHz seems kind of primitive (even when testing for speech), because our ears aren't that simple.

 

That's still pretty good advice, don't you think? From a hearing loss perspective anyway. I generally respect Cliff's opinion.

 

It's totally fine advice. It will be a while since FX-322 comes out anyway.