Frequency Therapeutics — Hearing Loss Regeneration

The Hough pill delay really didn't seem to have anything to do with the FDA or the clinical process as a general concept.

Hough had a previous biotech partner (Otologic Pharmaceutics--a very small player local to Oklahoma and in fact Kopke from Hough is on their board) who didn't push it forward or at least not in the same way. In fact, the drug at some point was tried for other indications like stroke. Oblato, as a multi-national biotech, at least know what they are doing in this regard and if they had partnered with Oblato first, I think the drug could be close to market by now.

It was interesting to listen to the latest Tinnitus Talk Podcast and hear Dr. Thanos describe how he has literally no idea how the process of getting investors/fundraising works and had to hire veterans to figure that out. He didn't even seem to know the basic ideas of it. Which, i suppose makes sense since he's a scientist and not a fundraiser but it seems like the scientists themselves would make the best advocates for funding.

Personally, I think if you wanted to make a difference in this regard, more accessible consultants to small cap biotechs would be a game changer.

 

If FX-322 doesn’t help with the majority of us I believe that by combining it with a synapse drug such as OTO-413 it should solve all of our issues.

Unless there is something else in the ear that needs restoring other than IHC’s, OHC’s and synapses this should be the key to our problems.

 

It is very frustrating not to be able to help research go faster.

(If I worked at Frequency I think I would sleep directly there to work).

I also wonder if among their researchers some have hearing loss / tinnitus.

I so hope that the FX-322 is the key to get us out of this prison.

I admit that even if I did not follow the research with Audion, the fact that it did not work for phase 2 gives me a little spike in the heart.

Besides, how do you know if hearing loss is caused by hair cells or synapses?

Courage to you guys!
(Sorry for English I use a translator)

 

I understand you clearly.

I don’t think Audion Therapeutics drug failed at all. They just didn’t think the improvement was enough to warrant a Phase 3 clinical trial.

I still think they could have gone into Phase 3 trials but they might have realised that if FX-322 were to come out then Audion Therapeutics would have lost a lot of money due to FX-322 being superior and it wouldn’t be worth it to continue making the drug if another company made something superior.

 

The entire reason the delay happened was because Hough didn't have the funding to get their drug through FDA trials, no?

Yeah, that's really what I mean. Scientists aren't necessarily going to be the best salespeople or have great minds for business. To me it seems like they have a vast amount of knowledge, but most of that knowledge is often limited to the field they have dedicated their lives to.

Asking a small biotech or team of researchers to create relationships & gather the financial resources to come up with tens/hundreds of millions of dollars to push their drug through FDA trials is like asking an electrician to build a bridge across the Golden Gate.

I've stated before that I'm a big fan of how Astellas is working with Frequency Therapeutics. They provided the money upfront (I assume this is based on how promising the given therapy seems to be) and give more with each milestone achieved during clinical trials. I think if there was more proactive action such as this taking place, either through consulting or by representatives of such companies, we wouldn't have as many therapies 'slipping through the net' and losing lives because of it.

Just my opinion though! I definitely have a ton of research to do. The more I learn about this the more passionate I am about the subject...

 

It's a shame that it all comes down to money in this world.
(I am not saying that money is not important but just that it is not always spent in the right way)

Now that I have tinnitus I understand how important it is to know how the human body works.
I may be wrong but I have the impression that we know more about animals than about ourselves.
(Surely a question of ethics and money)

(Sorry it's a bit of anxiety taking control tonight )

 

I'm currently drafting an email to Paul Fuchs from Johns Hopkins (one of the researchers who uncovered the role of the type 2 nerve fibers being pain fibers in the ear) to ask whether he's aware of anything in the pipeline that would benefit hyperacusis patients specifically and if regeneration drugs or the new Retigabine could help us. He gave an interview back in 2016 and said that he'd had like 3-4 contacts from the pharma/biotech sectors who are expressing interest in tackling this stuff.

Not sure whether to just sit on it for now until COVID-19's blown over or just send it although I'm worried I'll sound like an idiot. I might just do it and it's a bonus if I get a response.

 

Partly yes and partly no. I suspect they chose Otologic Pharmaceutics first because Kopke is a founder and on the board. Not that I blame him but a bigger partner could have got them funding right away. None of the other hearing biotechs ran into the funding problem for this reason imo. They were willing to allow a partner to have some financial stake from the get go. I think this is an absolute requirement in getting biotech funding either through larger biotech partners (Frequency) or venture capital/private equity (Pipeline).

 

Please do, I would be happy to look at a draft if you want feedback. Tinnitus made me miserable but I fear hyperacusis will make me a cripple.

 

I think you should send it. This is a great idea.

 

I still believe in the Audion anecdote that the musician was able to go on tour again due to his tinnitus and hyperacusis getting better.

I still wonder what type of hyperacusis he had. If it was pain hyperacusis then surely FX-322 will be able to solve our issues.

I really hope that the reason why pain hyperacusis occurs is due to the damage in the OHC’s which leaks ATP causing the type 2 nerve fibres to cause us pain. I feel like it’s all relative that restoring the hair cells in the ear should stop us from causing pain.

 

Roll on results time!! All this conjecture is getting us nowhere fast!!

It does keep hope alive, though.

 

This is what I keep saying. There is a finite amount of things within the ear than can cause tinnitus.

 

FX-322 restores the OHC, IHC and the underlying/attached synapses as I have understood. It won't restore a broken synapse if the OHC, IHC are still intact.

But do we have an idea if broken synapses or damaged OHC/IHC cause tinnitus? Or what damage would make sense for causing tinnitus?

 

It does seem plausible that repopulating with functioning IHC/OHCs will increase signal gain, thereby inhibiting tinnitus. We shall find out more when phase 2a results are released.

 

Just sent it! Will post my reply if/when I get one.

 

If it does indeed restore hearing and increase signal gain, what do you think the likelihood is that FX-322 can help hyperacusis/a reactive form of tinnitus?

Would it make sense that hearing restoration could lead to a normalized auditory system in regard to sound sensitivity?

 

@Jaysterk

Personally, I think there are more than we think. FX-322 repairs the inner ear. There may be damage to the middle ear for example. Many after hearing trauma suffer from TTTS and may have tinnitus related to this: pulsatile tinnitus or normal tinnitus. At that time, even if you correct the inner ear, you will continue to suffer from tinnitus.

 

I fear this drug doesn’t work... I was optimistic at start but is it possible that no one that took this medicine has posted any improvements??? You claim that it is forbidden by company policy but I would think that friends or some relative would have posted something! If I were a trial patient I would post with another account in some internet center. No way they catch you.

This drug doesn’t work. Sorry to say.

 

Sorry if I missed something here but are the current trials for FX-322 already using an enhanced delivery method different than the previous trial or is that something they plan on looking into in the future? I'm hoping to be accepted into the study in my area. I will know after they receive my audiogram.

 

NDAs keep everything under lock and key, unfortunately. We will know more when Phase 2a wraps up at the end of September.

From Phase 1, we know there were improvements in key measures of hearing function. One would think hearing regeneration should have a positive impact on the reduction of tinnitus at least to some degree. Of course, the type of hearing damage matters (hair cell vs. synapse). The latter may require OTO-413 or the Hough Pill. A mix of these medicines may even be required for some.

Tinnitus is being assessed as a secondary outcome measure in Phase 2a (part of the experimental arm). The fact that it’s being measured is a good sign as Frequency must feel there is a correlation between regenerated hair cells and tinnitus. While nothing regarding tinnitus improvement is certain at this point, there are lots of reasons to be optimistic.

 

I feel you being worried... I am too. If this fails, we are going to have to wait a long time! The first phase is only about safety. In the second phase they will measure hearing improvements over 4 doses. They already saw hearing improvements after 90 days with one dose. They said the drug reached only up to 8 kHz. They did not tell us about any improvements above that. What I fear the most is the drug will only reach up to 6 kHz and people like me will have to wait longer. People with high frequency hearing loss should be fine.

I just called them about the clinical trials and left a message asking them if they are still taking patients and also if they expect any delays due to COVID-19. I also thanked them for the awesome work they do!

 

I think this is unfounded pessimism tbh. I think it's natural to sort of guard against crazily high expectations etc but we already have encouraging evidence pointing to the efficacy of this drug.

Statistically meaningful improvement was observed with a safety dose, human explant data has shown that hair cells were successful regenerated and the recent news from their German study demonstrated that the drug reached its destination in the cochlea.

Clinical trial participants will have had to sign an NDA.

 

I’m not so sure it’s entirely unfounded to be a bit reserved. Let’s not forget that Frequency started out with Bob Langer saying they’re aiming to make this into a one or two injection treatment. Now they’re testing 4 injections. Drug delivery into the inner ear, more specifically the apex of the cochlea, is one of the biggest challenges in the hearing field right now. I wouldn’t be surprised if this drug does well with regards to word recognition, and only modestly for pure tone averages in the 250-8000 Hz range. And I would be pretty happy with that.

Let’s also not forget this is a first generation drug. How many diseases were cured with the first drug that came out?

 

It's very hard to wait for something so long when it's so important, but there's no basis to say that at this time. Hang in there.

 

I agree in that I think reservation is fine but claiming: "This drug doesn't work. Sorry to say" as in the post I quoted seems a bit premature to me.

 

Yeah I agree. At the end of the day all that matters are the Phase 2a results. If they don’t deliver they’ve got a real problem on their hands. If it meets our expectations we probably have a winner, barring any long term side effects that haven’t come to light yet. It either restores hearing or it does not. We’ll know more at the end of the year.

 

Delivery to sub 100Hz has actually already been done successfully by Otonomy and Pipeline in preclinicals for their drugs. Frequency probably initially formulated without a poloxamer (if anyone has access to their patent info we could check to see, I’d be curious) and will hopefully remedy this with a second re-formulation.

It’s not really a question of “can” they do it, but “will” they do it. But I would think the full range of frequencies within the speech banana is still very much their ultimate goal.

 

Preclinical as in not in a live human being? As far as I know it’s pretty darn hard to get a drug into the apex when delivered intratympanically. You’ll probably need something better. As for Frequency’s gel, this is what it said in their prospectus:

FX-322 is our proprietary thermoreversible polymer formulation that is administered through the eardrum, or intratympanically, into the middle ear in a procedure that takes approximately 10 to 15 minutes.

 

They will. It makes perfect business sense to do what they are doing. Right now they have a drug that shows evidence of restoring at high frequencies, and have already invested heavily in getting it to the market. It makes good business sense to get that first-generation in the market and begin turning a profit from it. That is why their messaging is so focused on clarity and what is gained by hearing restored at high-frequencies. There's also no real competition addressing high-frequency space.

Once they have this initial product turning a profit just by restoring at the high frequencies, they'll see higher levels of investment and market interest in a drug that reaches deeper into the cochlea and restores lower frequencies.

This is a very typical approach for nearly any novel product in any industry. Get a "Minimum Viable Product" into the market to prove that demand exists; then iterate and corner the market.

The MVP is high frequency restoration, plus the benefits that come along with it.
The cash-cow iteration is a full hearing restoration.

Everyone reading this should SAVE this comment. As more is learned through each phase and each new iteration of drug, Frequency will shift their messaging from clarity to deeper restoration. It will all be driven on the (hopefully) promising data from each phase.

Note: As a publicly traded firm, they can't make any claims about a product until there is evidence/data to back it up. So, right now, we're seeing claims based on the Phase 1/2 and the perilymph measurement study.