Frequency Therapeutics — Hearing Loss Regeneration

Carl LeBel said that they didn't believe that was a factor for their drug.

 

Off the top of my head:

1) they have other untreated pathology that is more significant and possibly even undiagnosed (e.g. Hydrops, third window syndromes both are notorious for being hard to diagnose).

2) they didn't follow instructions and moved too much and/or swallowed after injection.

3) their injury is closer to the apex than where FX-322 reached.

4) they have an untreated immune or autoimmune pathology that makes the ear less conducive (this is theoretical but inflammation impairs that process in the intestine, so it makes sense).

5) they have a problem outside of their cochlear or one not addressed by hair cell regeneration (e.g. Neurotransmitter dysfunction after anti depressants, TMJ, ETD).

 

When Frequency Therapeutics did their perilymph analysis study earlier this year, they stated that anatomical factors did not affect drug delivery: "The presence of round window membrane mucosal folds in certain subjects did not prevent the entry of FX-322 into the cochlea"

https://hearinghealthmatters.org/hearingnewswatch/2020/frequency-therapeutics-fx-322-inner-ear/

 

I actually think that your point about taking doctor's views as fact being a thing of the past is rather relevant, especially when you look at the way things are going in the medical field. From what I can see, the biomedical researchers actually seem to be much further ahead in the treatment space than the vast majority of doctors. Furthermore those working in the research field have far more knowledge around treatment options, what treatments would work and how to look at developing new treatments than the doctors do. It actually amazes me how clueless some doctors are when it comes to either knowing what treatments to prescribe people, how to look at developing treatments and also what is being worked on for future treatments.

I have been prescribed medicine by a GP which has then turned out to be no longer the best medicine choice when I have ended up going to the pharmacist to get this. Therefore the pharmacist has even contacted the doctor to suggest/ask if they would approve the alternative and better medicine. Furthermore the way which we see treatments dismissed by some doctors for some conditions, even though there is evidence supporting that they will work actually demonstrates that they mightn't be the ultimate source in all situations for medical opinions.

I actually find that when a new medicine treatment is either coming onto the market or when new medicine is getting researched, doctors can be quite willing to dismiss it/criticise it/question it and often not have sufficient basis to do so.

A good example would be medicines like heart medicines which effectively eliminated the need for surgeries. Someone in my family had a heart condition around the time that these new medicines came onto the market and they were initially told by one doctor a whole lot of stuff about how the medicine wouldn't work because they are too hit and miss and the surgery is probably going to be much more reliable etc. They visited a second doctor who also happened to work in the research field too. They said that the medicine probably would work as they had already seen this happen and secondly it is better to try the medicine first as it would be much less invasive and risky option. The second doctor was actually quite confused and also interested in the lack of merit and knowledge demonstrated by the first doctor in his reasoning.

Apparently the specialist told him that he had found doctors were not providing it because they hadn't actually done the required research and learning about what this medicine does. Thus I think that this very clearly demonstrates that if you get a doctor who is not on top of what is happening within their field you might get an inferior/adverse research outcome. Furthermore this shows me how out of date and clueless doctors can be, especially when it comes to medicine treatments.

I also strongly believe that the biomedical experts are far better versed in the medicine and treatment field because they have actually got an understanding of why treatments work, what makes treatments work and how to make treatments work. They work with the biological components which tell them how the body functions and why the body will or will not react to certain treatments. Furthermore researchers also work with the research technology which has come along so far in the past 10 years and improved the research quality immensely. Doctors have no clue about this.

FX-322 is a good example of this theory. Just look at how research workers have proven medicine can get in the ear and also actually provide treatment benefit. This is all the while we still see doctors claiming that you aren't able to get treatment in the ear even though the evidence tells us otherwise.

I think that this high level of analysis is going to continue every time information is released from any of these hearing medicine companies.

Consequently I think that high levels of analysis and discussion are beneficial and prudent. This ensures that people not only share their thoughts about what is going on but also we can also find out why something is actually being said and what is happening. Having the ability to analyse this information is also going to mean more of us are informed.

I must say that had others not analysed that article about FX-322, then we wouldn't have known that those two doctors interviewed in it actually have competing vested interests. Also we wouldn't be able to try and work out or to try and interpret the suggestive and/or cryptic comments being made about FX-322 by Frequency Therapeutics. The thing that we do know is that Frequency Therapeutics are releasing their information updates infrequently because they are not going to comment much while a trial is ongoing because they are very good at and focused at complying with the FDA rules. Furthermore Frequency Therapeutics is holding their cards close to them to not give away information to outsiders and more importantly competitors. I actually think that trying to limit and/or withhold information is a good sign because it suggests to me that Frequency Therapeutics thinks FX-322 is on the right track and so they do not need to say anything.

 

Is number 5 just related to tinnitus? I presume it is. Lucky, my hearing loss is just as big a concern, if not more so, than my tinnitus at present.

In relation to 4, would it then be a good idea to lower inflammation as much as possible before trying FX-322, i.e. using Astaxanthin etc?

 

Even then most of these potential treatment barriers do not seem as if they are that difficult for people to overcome.

For example if you swallowed at the incorrect time, it would just mean that you would require a redose. Or if the area actually needing repair was further in the ear then theoretically this could be overcome with better drug delivery methods.

My opinion is that this supports Frequency Therapeutics' belief that they could offer FX-322 to a good number of people.

 

Re: number 4, I wasn't thinking of run of the mill inflammation here. I wouldn't think this would be necessary for most people without autoimmune conditions (and they might be fine too but I could see it being a potential hypothetical factor in terms of maximum efficacy).

Re: number 5. You can get hearing loss or I should say hearing interference which can show up on an audiogram with TMJ (which improves with treatment):

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117795/

 

I agree with the TMJ issue. I have had conductive issues/short bouts of tinnitus on the left side that directly stemmed from moving the mouth.

 

Tommyd87 what is your background? You seem to be very knowledgeable?

 

When we talk about drug delivery, this is a project I read about years ago.


So anybody know if this device made it to the clinic?

https://www.draper.com/news-release...-ear-disorders-heads-preclinical-test-prompts

(But I guess, Frequency Therapeutics would knew about this device if it was ready)

 

In terms of work and/or study, I have nothing to do with this area at all.

Most of my learning relating to the hearing medicine are has been:

- through my own experiences

- being able to read and analyse the relevant information and learn about things in the hearing medicine area

and

- being able to logically work out what is happening based off of the data/information

I would say that learning broadly about the hearing medicine area has helped a lot, as it has meant I not only have learnt more about this area as a whole but also that I now understand the different purposes of the different medicines.

However, I'd argue that the ability to interpret the relevant information and also the logic are the most important. It is more important to be able to filter out and also dissect the various bits of information about what is actually happening broadly from various bodies. I feel that I have got a good ability to analyse information, check the claims made by a particular party about something and also interpret the reason and also the purpose of what is being said.

I don't find it too hard to look at the comments made by someone about the trial process or about the medicine and actually check the legitimacy of the claim if it sounds funny. For exampl,e the clinical trial processes and requirements are clearly available for people to see and thus I can check these out and weigh these up against the claim an organisation is making and check its validity and comment accordingly.

I'd also say I have a fairly good ability to evaluate things from a real world perspective too, so this means things like the practicality behind getting practices to take up offering treatments and the like.

Thus I might come across as fairly knowledgeable, however I would say I am probably not that knowledgeable. I am definitely not as knowledgeable as @FGG is for example when it comes to the drug info. However I'd say most of the stuff I write is based off of just my learning and also my ability to practically apply things too

 

I wonder how anyone who's had the Silverstein surgery fits into this. I know it's apparently reversible but even if the reinforcement can be removed, could it leave the round window in a non-permeable state? (Scar tissue etc.?)

 

The comparison of the advent of LASIK and the eye care industry at the time with what we are likely to see with the potential success of FX-322 and the hearing aid industry, I believe, is limited to similarities in economics only and it stops there. Hearing loss and tinnitus, unlike poor vision, carries with it a rather latent prognosis for mental depression, dementia, and social isolation for many people - despair leads to suicide when there is no hope in sight.

Hope plays huge in our world with much more stealth than vision problems whereby contact lenses and glasses are still today the choice by the wide majority. I believe the hearing aid industry including every audiologist should seriously consider the hidden suffering that we endure and to waver on any thought of downplaying the joy that is at hand if FX-322 proves beyond a doubt that it will help heal so many.

 

So FX-322 hasn't done anything to people's tinnitus yet?

 

What’s the reason only 4/13 participants saw significant improvements? Makes me a bit worried...

 

Obviously we all want that this drug will work for everyone, whether it be for hearing loss or/and tinnitus. That isn't going to happen.

What will people be happy with when/if this drug hits the market, e.g., 30% seeing significant gains, 30% seeing some gains, 40% seeing no gains? What would be considered good for you? I'm looking more at its potential to restore hearing as that is what's it's designed to do but hoping that it has the same potential rate for at least some causes of tinnitus.

 

Ok, this thread constantly does this. It is optimistic and excited and then people who haven't bothered to read, paratrooper in and throw cynicism all over the place, even though the vast majority of cynicism can be essentially debunked if they read previous posts. This requires usually only looking back at max 2 pages.

Why did only 4 of the 13 patients who received FX-322 see "significant improvements"? Well because they were the ones who had larger loss of hearing, meaning they were the ones who had enough room to improve to the extent that qualified for "significant improvement". Think about how someone who saw a 70 percent improvement in word scores still did not get classified as a "statistically significant improvement." The classification of what constitutes "statistical improvement" basically eliminated the majority of trial patients from being put in this category since their damage up to 8,000 Hz was on the mild side.

This brings me to another point. The argument that a "10 dB improvement at 8,000 Hz is not significant". As stated 10000 times by various well informed people such as @FGG who is so generous with their time and knowledge for always sharing it here, the drug starts high and works it's way low, meaning it would hit 16,000 Hz etc first. Not the other way around which some people seem to think.

Due to this fact and the word score improvements, it is quite likely that everything above 8,000 Hz improved by at least 10 dB, likely more. These are the frequencies believed to have a big role in sound clarification. If there was only a 10 dB improvement at only 8,000 Hz, you would not see such dramatic word score improvements. Clearly, everything above 8,000 Hz likely improved by a noticeable amount.

So now tie this in with the complementary studies done with FX-322. It fixed hearing in deaf mice. Well, their cochleas are smaller, so less of a physically long route to shoot the drug into. So it's probably easier to cover all the frequencies with the drug. Just a thought.

Also, they watched the drug regrow hair cells in a petri dish. They literally watched it work.

The issue isn't the drugs, it's the delivery method. This has been stated countless times. This is something that can be fixed with multiple dosages or a reformulated delivery method.

But remember, even with a single dose there is a good chance this drug can right now fix or improve your high pitch tinnitus by regenerating hearing 8,000 Hz and above. Typically, your outer hair cells are the first to get fried because they are on the outside and more exposed to the loud noises. This is why some people say they have a relatively normal audiogram yet also have tinnitus. Assuming the reason lies in the nerves in your ears, it's very likely you have damage done at the higher frequencies, which in our noisy day to day environment, should kind of be expected. The phantom damage is very likely to be improved with the minimal phase 1 dosing. That is actually incredible. Yes, at this point, there is no evidence that suggests lower frequency damage and corresponding tinnitus will be fixed with one dose but there is only evidence to be optimistic that with a few tweaks, the drug will be able to improve the sub 8,000 Hz.

Also, people need to stop hitting the panic button everytime the stock price takes a hit. Almost everytime it does, it's often a day that plenty of stocks went down. As well, remember that people who buy stocks sometimes have to sell in order to make money to spend. This stock is not a short term one lucrative one. It's not going to shoot up 10 times the value anytime soon. This makes it a good stock to buy at 18 and sell at 22 and rebuy later down the road.

Also keep in mind what Phase 1 testing is for. It is for safety, not efficacy. The results they observed over a safety dose is significant and only justifies optimism.

So overall, there is no justification to be pessimistic about FX-322. Even the science of how it works is amazing and theoretically will provide stable, long lasting hair cells. The "theoretical" part has been partially backed up recently by test results. I honestly think that had Frequency Therapeutics implemented an extended audiogram in the phase 1 testing, they would have had way more concrete evidence to show clearly how well it works, as opposed to having to connect the dots. This is why people get cynical quickly, they see the Coles Notes and don't dig into the studies and therefore conclude it's far less significant than it actually is.

The phase 2 trials ongoing right now are pivotal. I think they will show that FX-322 works better with more dosages. Sure, anything can happen and it can fail just like a meteor could suddenly hit the Earth and end all life but as of now, there is no evidence to be worried about such negative events.

Anyway, that's my rant.

 

Why does this worry you? It was a trial primarily designed for safety. Phase 2a will allow them to see what effect multiple dosing has.

 

Carl LeBel reported that some patients involved in the trial had mentioned improvements in their tinnitus.

 

And alas there will be little else to hang our hats on until their testing proceeds.

I mean, I do follow this thread because of the collapse of hope surrounding Lenire but it's still too early to develop any conclusions.

When things will really heat up is if/when someone who claims to have been through the treatment reports in here and subjects him/herself to interrogation. But that is pretty far away.

What I can say is that Frequency Therapeutics seems professional and doesn't have the same baggage of failure that Neuromod does. And while they haven't initially targeted tinnitus with this, they seem to be angling to make it a #2 priority. I'm just not picking up any red flags.

 

That would be crazy. I wonder if anyone in the trial lurks on this thread but can't comment because of the NDA. There already exists a yes or no to the million-dollar question, but for now, it's Schrodinger's cure.

 

Except we already know from Phase I/II that it does work in humans. The questions are: how will repeated doses help, how tinnitus will be affected, and if study adjustments will lead to a better outcome (everyone getting the high dose, everyone having moderate to moderately severe hearing loss, extended audiogram, etc).

Some people are pretty negative about FX-322, I have a feeling it's going to be a real shocker for some if they post good results (which I think they will).

One wild card that I could see shaking things up: Otonomy will release the top-line results of OTO-413 in the final quarter of this year. After reading up on their drug, I think there's a good chance they could post results similar to FX-322's Phase I/II study if it turns out their hydro-gel really is better (I think their drug is ultimately inferior based on what I read, but it could act as a nice compliment to hair cell regeneration drugs). That will put a lot of pressure on Frequency Therapeutics.

If OTO-413 shows that it improves hearing in the lower frequencies, I wonder if Frequency Therapeutics will attempt to license their hydro-gel - and if Otonomy would even be open to the idea, since they're developing their own hair cell regeneration drug.

 

In the group of 13 participants, does it also include those who received placebo?

 

Right, I meant with regards to tinnitus rather than hearing loss.

 

Right now they need to keep testing and see if they can achieve better results than what they currently have. They need to use extended audiograms to see how much it helped in frequencies above 8 kHz. People have speculated in previous threads with more information but right now if your tinnitus is located right within 8 kHz-16 kHz and your hearing only dropped 10 dB to 20db, I'd say your chances are pretty good of FX-322 being a cure. For everyone else they need to keep testing...

 

Maybe Otonomy would be open to the idea, since Otonomy was founded by Jay Lichter who has Meniere's & hearing loss with the aim to develop therapies for the inner ear. So maybe he would welcome any advance in the field.

Here's the story:
https://xconomy.com/san-diego/2017/04/11/the-otonomy-story-and-the-human-impact-of-innovation/

 

There are three things I would say in relation to your post:

1. It is too early to reach conclusions, however there is quite useful information available about whether FX-322 will provide benefit and will work from what was largely a safety trial.

This includes:

- The fact that it was safe
- The fact that it caused improvement in people
- The fact that it does what it is supposed to do

I think that the information to date tells us that FX-322 has a lot of upside to it and also that we can feel fairly confident that it will help benefit patients.

2. The information on tinnitus is limited because there is no data which Frequency Therapeutics can report. Tinnitus was not a subject of the inaugural trial and therefore Frequency Therapeutics cannot comment on it without getting blasted by the FDA. This is unsurprising considering how good Frequency Therapeutics has been at complying with the reporting and also the FDA requirements at all times.

What we do know however is that tinnitus improvement has been reported anecdotally. This is obviously unverified information, however it is a pretty good indication that there has been a positive benefit for tinnitus.

It should also be noted that FX-322 may not actually ever be the sole treatment which people need in order to treat their tinnitus. There is evidence to suggest that some people may need other treatments like synapse treatments to resolve their tinnitus, though I think that FX-322 will work in many instances.

3. I would also suggest another good sign is when Frequency Therapeutics says something anecdotally or hints something cryptically to allow them to convey a specific message or some specific information. Frequency Therapeutics has not only done this with tinnitus information but also a few other things too. This indicates that something is worth telling, however it needs to be done in the most loose and most unofficial way also to ensure compliance with the FDA rules.

I would overall say that the Neuromod management or their Lenire treatment is nowhere near that of Frequency Therapeutics. Frequency Therapeutics has been much more robust, transparent and also amazingly realistic in the information that they have provided when compared to Neuromod. Furthermore Neuromod isn't even in the same ballpark as Frequency Therapeutics is with its treatment. Frequency Therapeutics is working on a medicine which will treat the underlying causes and has shown some promising success with doing this thus far. Neuromod made a bimodal stimulation device which will never be anywhere near as effective as FX-322 could or would be.

No this is only those who were dosed with FX-322.

However of these 13, half got the low dose and half got the high dose. The reason that Frequency Therapeutics has now chosen to use the high dose in the later trials is because it is much more effective than the low dose. The dosing size was another thing that was determined out of the phase 1 safety trial.

 

There's two things that I would point out about this post from a factual benefit.

1. There is still much debate about tinnitus being caused by very high frequency hearing loss. Many experts have actually identified that the tinnitus is much more likely to have been caused by hearing deficiency in the 250 Hz-8000 Hz range solely because this is where the vast majority of day to day sounds are located.

Furthermore, there is evidence which supports this such as the fact that the tinnitus can quite often be eliminated while using a hearing aid. At this stage most hearing aids do not go above 8000 Hz.

Also there are suggestions that tinnitus might be caused by damaged synapses and not hair cells.

There are three facts which support synapses being a potential cause of tinnitus:

- FX-322 is believed to restore synapse connections in conjunction with hair cells. There are also anecdotal accounts that FX-322 helped with tinnitus.

- The tinnitus treating Hough Ear Institute Pill is also assisting with synapse repair as well as supposedly being able to also treat tinnitus.

- There are people who have hearing loss but no tinnitus. This tends to be a fairly plausible indication that the synapses may play a bigger role in causing tinnitus than what people think they actually do.

Thus I am actually reckoning that while we might see benefit with tinnitus from using FX-322, we might actually see bigger benefit from treatments that target primarily synapses. This is because FX-322 is believed to not target synapses as effectively as a specific synapse treatment would.

2. Your theory about FX-322 being a cure for a 20 dB drop in 8000 Hz-16000 Hz is relatively realistic, even if it is not proven as of yet. However I don't necessarily agree that better testing is necessarily the answer to seeing if Frequency Therapeutics can get better results, but rather a better delivery method for FX-322 is.

There is already evidence that FX-322 works within the full range of hearing in the lab setting and thus it is just a matter of getting FX-322 much deeper in the ear to make it work more effectively.

 

Enrollment of FX-322 Phase 2a Complete:

Frequency Therapeutics Completes Enrollment of FX-322 Phase 2a Study for Sensorineural Hearing Loss

 

I frequently see a need on here to localize tinnitus to one structure in the cochlea. This is wrong. If it was just synapses, hydrops alone would not cause fluctuating tinnitus depending on severity (and it does). Same with middle ear disease, ETD etc etc.

Tinnitus is phantom cochlea. *Anything* that causes hearing interference can cause this. Regenerating synapses will help those whose cause was synapses. If it was hair cell, you need a hair cell drug. The underlying cause for each individual is what causes the brain to respond with tinnitus.