Frequency Therapeutics — Hearing Loss Regeneration

[RB2014]

It didn't catch my excitement until now for some reason aha, but yeah that's really soon!

I know. I was expecting something like 5 years from now... I'm excited as well.

Alright chaps, ponder this:

They are starting their Phase 2 very shortly. From the time they finish dosing until the time that they will measure hearing improvement, AND TINNITUS, it will be 3 months. BUT we will have to wait an entire year to know what the results were. That's 9 months that we will all be sitting here going insane and killing ourselves without being allowed to know if this helps with tinnitus.

If it helps with hearing loss, it will help with tinnitus for most people. I am the textbook example of put hearing aides in tinnitus goes from a 5 to a 1 even in a quiet room. Take them out and tinnitus goes from a 1 to a 5. Sometimes minutes, sometimes seconds, but the result is the same. Our brains are plastic and I like to experiment on myself enough to know that it is going to help. Please everyone keep faith.

I also created this thread so we could post, discuss, vent, argue... whatever. We are all on the same team!

 

[Phendran]

"Please be aware that it is important that you not discuss your condition with anyone at our organization. "

So, uh... Is it important to keep ailments secret now? If I break my leg, should I try to hide that?

In any case that response was hellawack. Dodging the question with a wall of text isn't the right way.

 

[Jurger]

I don't think so. Well, depending on how thick the gel gets. When you swallow, fluids flush down the eustachian tubes and the best thing you can do is not swallow or talk when medicine is in the middle ear. When you're asleep and or sedated, swallowing is involuntary. I have probably had more intratympanic injections than anyone else in North America, possibly all of the western world. If not then I'm certainly up there. When the ear drum is numbed correctly, it isn't that bad. It is a little intense but kids can hold still. One thing that happens is that as the middle ear fills with a substance that is a different temperature than the body is that you get transient vertigo for a minute or so.

I also know very well what it is like to have the injections when the lidocaine wears off. It is really painful and intense. There is the pain, the noise of the needle going into you eardrum, the vertigo, etc. BUT as soon as the needle come out all is well and it only takes a second. Some kids probably could not handle that. A better option than sedating them would be to immobilize them.

So what do you think about better delivery methods? Columbia University is working on a needle that can get drugs directly inside the cochlea by infiltrating the round window membrane instead of drugs permeating through it. The same needle can be used to extract perilymph, possibly allowing us to get a better picture of what's going on in the inner ear.

There's also Otomagnetics that recently partnered with a company that specializes in getting drugs and medical devices on the market.

 

[FGG]

So, uh... Is it important to keep ailments secret now? If I break my leg, should I try to hide that?

In any case that response was hellawack. Dodging the question with a wall of text isn't the right way.

It came off like a form letter type response to be honest. They didn't even ask about any symptoms/conditions.

 

[JohnAdams]

Columbia University is working on a needle that can get drugs directly inside the cochlea by infiltrating the round window membrane instead of drugs permeating through it. The same needle can be used to extract perilymph, possibly allowing us to get a better picture of what's going on in the inner ear.

That's bad ass.

There's also Otomagnetics that recently partnered with a company that specializes in getting drugs and medical devices on the market.

That is the dumbest idea I have ever seen. For that to work then the drug would have to be mixed with ferrous nano particles. Do we really want nano sized pieces of metal in our cochlea? Also, if you watch the video, they clearly have no idea how magnets work. You cannot just make a magnetic field to hold stuff in space a certain distance from the magnet, magnets attract. The only way to do that is by using super conductors and cryogenics.

 

[Fabrikat]

I'm wondering if the delivery method isn't part of the reason most patients didn't improve below or at 8000 Hz in this trial. In other words, I have my doubts about the efficacy of intratympanic injections. Frequency itself basically said the same thing by pointing to their previous findings that the highest concentration of the drug is found in the base of the cochlea (high frequencies). A better delivery method would ensure not only that the drug reaches the apex of the cochlea, but also higher concentrations of the drug overall and possibly for a longer period of time. Intratympanic injections have downsides because, among other reasons, not all round window membranes are created equal

I agree with you on this. Delivery of the drug into the cochlea will be the crucial issue and I wonder if Frequency's hydrogel will be enough to do the job.

If the results of the FX-322 experiment on the cochlea removed from a patient were deemed successful, but not necessarily as robust as they'd desired and this was an easily accessible cochlea on a tray in a lab, then how much improvement can be expected in a live ear which must deal with all the issues of access and permeability.

No matter how effective FX-322 may be, it's not much use if it can't get into where it needs to go.

 

[JohnAdams]

It came off like a form letter type response to be honest. They didn't even ask about any symptoms/conditions.

Yes, it is boiler plate.

 

[WickedCarnival]

So, uh... Is it important to keep ailments secret now? If I break my leg, should I try to hide that?

In any case that response was hellawack. Dodging the question with a wall of text isn't the right way.

I think it's mostly for preventing data bias: https://en.wikipedia.org/wiki/Bias_(statistics)

I would also guess that they want to set boundaries between themselves and patients when it comes to the relationship/psychological aspect of treatment and trials.

 

[JohnAdams]

I agree with you on this. Delivery of the drug into the cochlea will be the crucial issue and I wonder if Frequency's hydrogel will be enough to do the job.

It will just take many doses.

 

[Jurger]

That is the dumbest idea I have ever seen. For that to work then the drug would have to be mixed with ferrous nano particles. Do we really want nano sized pieces of metal in our cochlea? Also, if you watch the video, they clearly have no idea how magnets work. You cannot just make a magnetic field to hold stuff in space a certain distance from the magnet, magnets attract. The only way to do that is by using super conductors and cryogenics.

I'm not a scientist so I can't debate you on this. All I know is that their recent work on rats said it's safe:

"The test arms of this preclinical study included single and multiple magnetic doses, and control arms included intra-tympanic saline and intra-tympanic prednisolone. It was found that there was no statistical difference in hearing between magnetically treated ears versus ears that received intra-tympanic steroid, both 2 and 30 days after treatment. There were no adverse histopathology findings for ear tissues. All ear inflammatory changes were very mild in severity and by 90 days after treatment there was ongoing and almost complete reversibility of all changes. No ear tissue scarring or hemorrhage trends were associated with magnetic delivery. Additionally, the systemic levels of drug and iron were low after magnetic delivery to the ear. Systemic drug levels were below mass-spectrometry detection limits, and systemic iron levels were no different in animals that received nanoparticles to their ears than in animals that did not. In summary, after conducting a rodent safety study for magnetic injection of therapy to the cochlea, no adverse safety findings were observed."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235712/

In the end clinical trials will have to prove this is safe and effective. Their CEO said they want to go from Phase 1 to Phase 3 immediately and have this on the market in 2021 at the latest.

 

[Rb86]

It came off like a form letter type response to be honest. They didn't even ask about any symptoms/conditions.

The point is, I wasn't talking about my condition or situation at all. I simply asked when they plan to release the results of their first study.

 

[Rb86]

Has frequency been approved to go public on the stock market?

My understanding is that's hard to achieve without evidence.

 

[JohnAdams]

I'm not a scientist so I can't debate you on this. All I know is that their recent work on rats said it's safe:

"The test arms of this preclinical study included single and multiple magnetic doses, and control arms included intra-tympanic saline and intra-tympanic prednisolone. It was found that there was no statistical difference in hearing between magnetically treated ears versus ears that received intra-tympanic steroid, both 2 and 30 days after treatment. There were no adverse histopathology findings for ear tissues. All ear inflammatory changes were very mild in severity and by 90 days after treatment there was ongoing and almost complete reversibility of all changes. No ear tissue scarring or hemorrhage trends were associated with magnetic delivery. Additionally, the systemic levels of drug and iron were low after magnetic delivery to the ear. Systemic drug levels were below mass-spectrometry detection limits, and systemic iron levels were no different in animals that received nanoparticles to their ears than in animals that did not. In summary, after conducting a rodent safety study for magnetic injection of therapy to the cochlea, no adverse safety findings were observed."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235712/

In the end clinical trials will have to prove this is safe and effective. Their CEO said they want to go from Phase 1 to Phase 3 immediately and have this on the market in 2021 at the latest.

I knew nothing about this. Wow. Great find.

 

[JohnAdams]

The point is, I wasn't talking about my condition or situation at all. I simply asked when they plan to release the results of their first study.

It's a boiler plate. I've gotten it too.

 

[Rb86]

https://www.wsj.com/articles/ipo-market-rewards-early-stage-biotechs-1540983601

A bit of general but interesting info with biotech companies in the stock market ....

Some of these companies have raised hundreds of millions with no drug on deck. Basically to me means nothing if frequency is allowed to go public...

Accelerated path to phase 2 though

 

[Jurger]

By the way, did anybody read this little snippet in their prospectus?

"We have submitted an application for Fast-Track Designation for FX-322 for the treatment of SNHL in adults to the FDA."

Was some speculation/indication they were gonna do that, now it's confirmed.

 

[JohnAdams]

"We have submitted an application for Fast-Track Designation for FX-322 for the treatment of SNHL in adults to the FDA."

@Jurger, welcome to the forum. I can tell you are going to be a positive contributor to the discussion. If you're insane, join My Posting Place. We are meme-ing our way to a cure.

 

[JohnAdams]

"We may seek a Breakthrough Therapy designation for FX-322 if future results support such designation. A Breakthrough Therapy is defined as a drug that is intended, alone or in combination with one or more other drugs, to treat a serious condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development."

https://sec.report/Document/0001193125-19-239976/

 

[Dizzyhead888]

Who is the king of this thread and can answer the following:

- Do we have any members here who participated in phase 1? Have they benefited in terms of hearing loss, tinnitus, hyperacusis?

 

[Fabrikat]

Their CEO said they want to go from Phase 1 to Phase 3 immediately and have this on the market in 2021 at the latest.

Frustrating that some trials can progress so quickly, whilst others just drag on and on.

 

[Dizzyhead888]

Being totally selfish here, I'd be thrilled if FX-322 can fix high frequency hair cells, as that's precisely where my tinnitus and hearing loss (thanks Stanford for living up to your reputation and actually going all the way up to 16 kHz without being asked!) is.

Any source mentioned that it works on low frequency hair cells only and not high frequency?

 

[Jurger]

Frustrating that some trials can progress so quickly, whilst others just drag on and on.

Think it has to do with a drug delivery method being a medical device, which doesn't have the same strict requirements for approval as drugs.

 

[JohnAdams]

@Deathtotinni

 

[Mathieulh]

Any source mentioned that it works on low frequency hair cells only and not high frequency?

Not to sound egoistical, but high frequencies are good enough for me.

 

[Jurger]

Any source mentioned that it works on low frequency hair cells only and not high frequency?

It's the other way around, it seems to do regrow more hair cells in the higher frequencies. Why? Because those hair cells are located at the base of your cochlea and that's the area the drugs reach first after permeating through your round window membrane (that's Frequency's own theory).

It's also the reason I think we need to focus more on better delivery methods (intracochlear delivery, nanoparticle delivery) than intratympanic injections.

1. Better chance of reaching the apex of the cochlea (lower frequencies)

2. Higher concentration of drugs in the cochlea (less leakage of drugs through the eustachian tube)

3. Longer duration of drugs in the cochlea (meaning less injections or whatever delivery method they will use)

The better these drugs work, the more patients they can help and the more commercially viable they become.

 

[JohnAdams]

It's the other way around, it seems to do regrow more hair cells in the higher frequencies. Why? Because those hair cells are located at the base of your cochlea and that's the area the drugs reach first after permeating through your round window membrane (that's Frequency's own theory).

It's also the reason I think we need to focus more on better delivery methods (intracochlear delivery, nanoparticle delivery) than intratympanic injections.

1. Better chance of reaching the apex of the cochlea (lower frequencies)

2. Higher concentration of drugs in the cochlea (less leakage of drugs through the eustachian tube)

3. Longer duration of drugs in the cochlea (meaning less injections or whatever delivery method they will use)

The better these drugs work, the more patients they can help and the more commercially viable they become.

When they increase the dose for this trial it may very well reach the apex.

 

[Daniel Lion]

Not to sound egoistical, but high frequencies are good enough for me.

Why preface by saying "not to sound", why not just say, I want my high frequencies back because they are damaged. And for those with profound or severe hearing loss, oh well... they got a shitty hand of cards, but it's not my problem.

 

[85dB T]

Would be great if we could target tinnitus frequencies like keys on a piano.

"Targeted drug delivery, sometimes called smart drug delivery, is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others."

https://en.m.wikipedia.org/wiki/Targeted_drug_delivery

 

[Jurger]

Not to sound egoistical, but high frequencies are good enough for me.

The commercial viability of this drug will depend in large part on its ability to substitute or at least complement hearing aids. That's why Frequency keeps mentioning the billions that are being spent on hearing aids every year. They - or whichever company ends up buying this - will want to go to governments and insurance companies and say: look, instead of spending 4000 bucks per patient on hearing aids every 5 years, try this. Not to mention lowering the risk of dementia, which costs societies bucketloads of money and will likely increase the coming decades. If all this drug ends up doing is fixing frequencies >8000 Hz, it will strongly evaporate the value of this drug. That's not to discount patients who are suffering of tinnitus because of >8000 Hz hearing loss, but that's simply not the biggest market.

And besides, if a patient like that ends up with low frequency hearing loss because of age and gets tinnitus (again), that patient is still screwed.

 

[Jurger]

When they increase the dose for this trial it may very well reach the apex.

Might be, but there's strong evidence of intratympanic delivered drugs barely reaching the apex. I've seen studies where they found out 2.5% of the drugs reached the cochlea.

Edit: that's why I thought it was a shame they didn't publish more of their Phase 1 data. Sure, there were no adverse effects and the bioavailability was there, but the question for me is: how much and after how long? That tells us a lot. Honestly, the crux might be in that study instead of the Phase 1/2 one.