Frequency Therapeutics — Hearing Loss Regeneration

[GlennS]

Yes. It only needs to provide a clinically significant improvement for it to be viable which is a pretty low bar.

No kidding. The term "clinically significant" has become meaningless to me thanks to Neuromod.

 

[Zugzug]

I agree they can't have it both ways, but that doesn't mean there isn't a scenario where they can't. TFI was experimental and not a criterion (to my understanding), so if Frequency Therapeutics are saying the unconscious bias is about WR scores and audiograms because they specifically communicated that with regards to those tests, there is a world where they can come back and say "hey, look at these improved TFI scores - we never communicated anything about some kind of minimum suffering here to get into the trial". That's assuming of course we even get a positive readout for TFI, which seems highly unlikely, even in the face of the patient I've spoken to who said their tinnitus is practically gone.

Kindly, I disagree. This is having it both ways. So we can literally assume that a human being lied about hearing a word or not, without proof, but we're supposed to say their TFI change is believable? The minute they said "unconscious bias" they were dying on the trial design sword.

I guarantee you, if the TFI results are horrible, we will say "oh, well the trial design was bad anyways." Any meaningful result has to come from a supposition that if the results were bad, we would own it in total shame.

Nothing is salvageable from Phase 2 other than on an emotional level. I also like to read about people seeing their tinnitus go away, but if someone had a worsening, we would probably say it was from the injections themselves or something.

Is there any chance at all that this goes to pivotal? Technically, yes. But it's so little that the benefit of holding out for false hope is strongly trumped by the importance of developing new coping strategies.

 

[Piney]

A lot of stock talk on here.

I'll buy the stock when someone comes out of the trial and says it cured their tinnitus and hearing loss.

 

[Zugzug]

Well put. From a business standpoint, it makes sense to scrap Phase 2A and move on with a clearer/simpler path to an FDA-Approved product in the short-term.

Right now, they're working purely on initial investment and cash, no real revenue stream. And now, a stock price that is half of its IPO value. So, they need to be extremely smart with how to allocate limited resources, and show continuous iterative successes that de-risk the development of FX-322.

A single dose drug route eliminates the need to again retry 1 or more multi-dose trials, which would further push out any potential pivotal trial, and continue to muddy the likelihood of FDA-Approval. Imagine if they re-did another Phase 2A, but with 4x monthly doses, and that didn't work? Would there be any trust that the drug worked? Would any investors be willing to come back to the table for a third Phase 2A? Or to pick up all the sunk-costs to THEN go to a single-dose route? Would there be money left in the tank to get the delivery method trials updated?

Simplifying to a single dose enables them to identify a specific population of patients where the drug is most consistently effective. Some consensus here is that the severe trial may be the most reliable beachhead for a first-generation product. If approved for these smaller, specific populations, they can then begin to generate cashflow to fund more multi-dose trials, upgrades to delivery methods, and other reformulations. Plus, the stockholders will certainly like a company with a product-driven revenue.

I have a question that you would understand better than I would. What do you think are the chances that some of these companies start buying each other out?

Just as a layman, what I am seeing is OTIVIDEX and FX-322, both hyped drugs, run into trial design problems (we can assert this and say the drug failed, it's not an excuse). I know Carl LeBel used to work for Otonomy. Didn't someone say that Otonomy has the delivery technology?

I have no idea what I'm talking about. I'm just wondering if some of these companies should merge. They all have mountains to clear in every way: safety, efficacy, outdated hearing metrics, lack of education on hidden hearing loss, etc.

 

[Aaron91]

But it's so little that the benefit of holding out for false hope is strongly trumped by the importance of developing new coping strategies.

Agreed, which is why I intend on taking a break from here for a bit. I intended to do so immediately after the results but couldn't help myself in trying to track down some patients. Make no mistake: I'm not clinging on to hope with FX-322. I think our best case scenario is the whole thing gets pushed back 18 months, if we're lucky. I previously said to myself I could cope knowing I'd be out of this hole within the next 3 years (how naive that was), but it now looks like that might be 5 years at best and most likely never, at least as far as hyperacusis is concerned. I think I speak for many here, yourself included, when I say I had a lot of hope, plans and goals for my life. I worked really hard to get to where I was. That's all gone now, and all I can think about is surviving and finding the mental fortitude to be able to suffer through each day.

 

[Zugzug]

Agreed, which is why I intend on taking a break from here for a bit. I intended to do so immediately after the results but couldn't help myself in trying to track down some patients. Make no mistake: I'm not clinging on to hope with FX-322. I think our best case scenario is the whole thing gets pushed back 18 months, if we're lucky. I previously said to myself I could cope knowing I'd be out of this hole within the next 3 years (how naive that was), but it now looks like that might be 5 years at best and most likely never, at least as far as hyperacusis is concerned. I think I speak for many here, yourself included, when I say I had a lot of hope, plans and goals for my life. I worked really hard to get to where I was. That's all gone now, and all I can think about is surviving and finding the mental fortitude to be able to suffer through each day.

I'm so sorry. I never thought FX-322 would make or break my situation (good chance it does nothing).

One reason why I think I can adjust to the "long-term" approach more is because it's always been long-term for me. I really wanted FX-322 to succeed because it would clear an important barrier, allowing for more cash flow and further advancements. I need a cure for autoimmunity and probably a host of regeneration type of drugs to try to see what sticks.

What I'm the most shaken by is just how hard it is for these things to succeed. I read the papers; this thing was (and really still is) legit. I share your sentiment about all of the calculations. If the best case scenario is 5 years, it's probably more like 10-20. So depressing.

If I believed this drug was picture perfect for my problems, I would be so much more devastated. Really sad stuff. Sorry everyone.

 

[FGG]

Agreed, which is why I intend on taking a break from here for a bit. I intended to do so immediately after the results but couldn't help myself in trying to track down some patients. Make no mistake: I'm not clinging on to hope with FX-322. I think our best case scenario is the whole thing gets pushed back 18 months, if we're lucky. I previously said to myself I could cope knowing I'd be out of this hole within the next 3 years (how naive that was), but it now looks like that might be 5 years at best and most likely never, at least as far as hyperacusis is concerned. I think I speak for many here, yourself included, when I say I had a lot of hope, plans and goals for my life. I worked really hard to get to where I was. That's all gone now, and all I can think about is surviving and finding the mental fortitude to be able to suffer through each day.

Re: noxacusis. I personally think it depends on what's causing your ear pain. We discussed this together on another thread while ago but I never saw FX-322 as a cureall for noxacusis for a few reasons:

1) the ATP leaks from gap junctions as well as damaged OHCs. So, at minimum, you would need to deal with that inflammation, too. Ebselen may be part of that equation, however.

2) the unknown time desensitization would occur.

For loudness hyperacusis, however, IHCs may be a big part of why this occurs. So if pain was more secondary to loudness --> increased sensitivity of tensor tympani --> TTTS type pain this would have more effect.

I still think multi dosing is the way to go for OHCs but they haven't shown clinically how that has to happen and at what intervals.

 

[Paulmanlike]

The term "clinically significant" has become meaningless to me thanks to Neuromod.

Did they ever get their results peer reviewed? I don't think they did. Total failure.

 

[dd314]

I want to say something about the curiosity with TFI from Phase 2:

I'm out of the loop, what's the curiosity? I thought we don't get to see that data until April?

 

[Diesel]

I have a question that you would understand better than I would. What do you think are the chances that some of these companies start buying each other out?

Just as a layman, what I am seeing is OTIVIDEX and FX-322, both hyped drugs, run into trial design problems (we can assert this and say the drug failed, it's not an excuse). I know Carl LeBel used to work for Otonomy. Didn't someone say that Otonomy has the delivery technology?

I have no idea what I'm talking about. I'm just wondering if some of these companies should merge. They all have mountains to clear in every way: safety, efficacy, outdated hearing metrics, lack of education on hidden hearing loss, etc.

When it comes to merger/acquisition, the goals (usually) are to either expand the business vertically (acquire a supplier, or consumer of your product), or expand the business horizontally (acquire a similar firm to gain access to a specific market). Sometimes it's for both, but most often it's horizontal or vertical specifically.

To look at JUST mergers, where two companies of a similar size/market position merge to become a "new entity", it is almost always a horizontal move to get more market share and better compete against either many dominant players, or establish dominance amongst a market full of many small players. With mergers, as mentioned above, they're typically similar firms.

So, when looking at the potential for a merger of two firms like Otonomy and Frequency Therapeutics, it doesn't make sense. Frequency Therapeutics strategy is to expand its PCA platform into other diseases that are non-hearing related. Otonomy is specifically focusing on hearing. The other issue is that many of their products do not have well defined patient populations, since most are in Phase 1. The other problem with let's say other combinations of firms merging besides Otonomy and Frequency Therapeutics, let's say Pipeline Therapeutics and Otonomy, or Pipeline Therapeutics and Sound Pharmaceuticals; is that there's a high likelihood of some type of cannibalization of their pipeline. Which would mean the mergers would start with sunk costs.

To consider JUST acquisitions, where typically a larger company acquires a supplier or consumer; this I could see happening for any of these hearing loss firms. In the case of these dinky pharmaceutical development firms, any number of major drug manufacturer might have an interest in acquiring them for their tech; especially after their stock price nose dives, and they look like a bargain as they trend towards bankruptcy. They may even have an interest in acquiring 1 or more at a discount, throwing away the IP/development that's a flop, and keeping what works in production. This would make the funds available to make the mountain easier to climb; and they'd have the resources/influence to fund education/marketing/provider access/etc.

 

[FGG]

When it comes to merger/acquisition, the goals (usually) are to either expand the business vertically (acquire a supplier, or consumer of your product), or expand the business horizontally (acquire a similar firm to gain access to a specific market). Sometimes it's for both, but most often it's horizontal or vertical specifically.

To look at JUST mergers, where two companies of a similar size/market position merge to become a "new entity", it is almost always a horizontal move to get more market share and better compete against either many dominant players, or establish dominance amongst a market full of many small players. With mergers, as mentioned above, they're typically similar firms.

So, when looking at the potential for a merger of two firms like Otonomy and Frequency Therapeutics, it doesn't make sense. Frequency Therapeutics strategy is to expand its PCA platform into other diseases that are non-hearing related. Otonomy is specifically focusing on hearing. The other issue is that many of their products do not have well defined patient populations, since most are in Phase 1. The other problem with let's say other combinations of firms merging besides Otonomy and Frequency Therapeutics, let's say Pipeline Therapeutics and Otonomy, or Pipeline Therapeutics and Sound Pharmaceuticals; is that there's a high likelihood of some type of cannibalization of their pipeline. Which would mean the mergers would start with sunk costs.

To consider JUST acquisitions, where typically a larger company acquires a supplier or consumer; this I could see happening for any of these hearing loss firms. In the case of these dinky pharmaceutical development firms, any number of major drug manufacturer might have an interest in acquiring them for their tech; especially after their stock price nose dives, and they look like a bargain as they trend towards bankruptcy. They may even have an interest in acquiring 1 or more at a discount, throwing away the IP/development that's a flop, and keeping what works in production. This would make the funds available to make the mountain easier to climb; and they'd have the resources/influence to fund education/marketing/provider access/etc.

On top of that, Otonomy has their own hair cell regeneration drug in pre-clinical that they are developing. A merger makes no sense on Otonomy's side.

 

[FGG]

Did they ever get their results peer reviewed? I don't think they did. Total failure.

They have and they have been published, yes.

 

[Zugzug]

When it comes to merger/acquisition, the goals (usually) are to either expand the business vertically (acquire a supplier, or consumer of your product), or expand the business horizontally (acquire a similar firm to gain access to a specific market). Sometimes it's for both, but most often it's horizontal or vertical specifically.

To look at JUST mergers, where two companies of a similar size/market position merge to become a "new entity", it is almost always a horizontal move to get more market share and better compete against either many dominant players, or establish dominance amongst a market full of many small players. With mergers, as mentioned above, they're typically similar firms.

So, when looking at the potential for a merger of two firms like Otonomy and Frequency Therapeutics, it doesn't make sense. Frequency Therapeutics strategy is to expand its PCA platform into other diseases that are non-hearing related. Otonomy is specifically focusing on hearing. The other issue is that many of their products do not have well defined patient populations, since most are in Phase 1. The other problem with let's say other combinations of firms merging besides Otonomy and Frequency Therapeutics, let's say Pipeline Therapeutics and Otonomy, or Pipeline Therapeutics and Sound Pharmaceuticals; is that there's a high likelihood of some type of cannibalization of their pipeline. Which would mean the mergers would start with sunk costs.

To consider JUST acquisitions, where typically a larger company acquires a supplier or consumer; this I could see happening for any of these hearing loss firms. In the case of these dinky pharmaceutical development firms, any number of major drug manufacturer might have an interest in acquiring them for their tech; especially after their stock price nose dives, and they look like a bargain as they trend towards bankruptcy. They may even have an interest in acquiring 1 or more at a discount, throwing away the IP/development that's a flop, and keeping what works in production. This would make the funds available to make the mountain easier to climb; and they'd have the resources/influence to fund education/marketing/provider access/etc.

I guess I'm thinking about it mostly from the perspective of combining scientific minds. You're right that Otonomy and Frequency Therapeutics have different scientific goals, and from the consumer's standpoint, there's not really an element of one choosing Otonomy or Frequency Therapeutics exclusively since their drugs do different things.

Actually, all of the main players pretty much fit this bill.

I just wonder if clearing the finish line is so hard that they would be willing to make sacrifices. For example, Otonomy won't help them with their MS program, but maybe they could with delivery. Similarly, Pipeline Therapeutics has a huge remyelination/neuroinflammation/axonal repair program, which uses different technology than PCA, but I have to believe there's an overlap in scientific minds.

I'm wondering how much Frequency Therapeutics is kicking themselves over the aggressive weekly doses versus having genuine internal concerns about failing. Surely, Otonomy is dealing with the same issue.

From an "expand horizontally" perspective, there could be a doubling up of education on hidden hearing loss, a really hidden (no pun intended) part of this. By better education, pressure to obtain a rock star product goes down. Otonomy targets synapses and tinnitus, whereas Frequency Therapeutics targets hearing loss and hidden hearing loss. While synapse and IHC loss target different hearing problems, we are so far in the dark ages that they seem like the same thing to the average person -- not to mention the fact that FX-322 also targets synapses.

To me, I see Frequency Therapeutics shooting out tweets about hidden hearing loss, seemingly into the abyss. It would be awesome to see these companies find a way to push hidden hearing loss mainstream. It would help a lot of hearing problems, from tinnitus to hyperacusis to speech problems.

I'm playing an armchair business expert; obviously they have smarter and more experienced people than me performing the analysis so it probably makes sense how it currently stands.

 

[Street Novelist]

I understand all the negativity, but before everyone declares FX-322 dead, do you think you could wait for the next trial where they only administer 1 dose at a time, spread out over lengthy intervals? If that doesn't work, then bury it.

 

[Keith Handy]

Maybe not merging, but licensing?

 

[Zugzug]

On top of that, Otonomy has their own hair cell regeneration drug in pre-clinical that they are developing. A merger makes no sense on Otonomy's side.

I guess there's a sunk cost for both companies getting to their respective points with different technology (FX-322 vs OTO-6XX). But if both drugs eventually work, isn't there a shared market based on which drug is slightly better? In other words, if one has a better reputation, a person would probably choose that consistently.

I guess these companies really believe in themselves, and it would take a lot of humility (and possibly stupidity for all I know) to scrap the technology and admit that the other company has a better chance of succeeding.

 

[Zugzug]

I understand all the negativity, but before everyone declares FX-322 dead, do you think you could wait for the next trial where they only administer 1 dose at a time, spread out over lengthy intervals? If that doesn't work, then bury it.

Only the emotional negative people are burying the whole thing. The negativity concerning Phase 2a is 100% justified. It's not like the whole thing is a failure, unless you are willing to be a conspiracy theorist. Hell, I'd even go as far as say that even if Frequency Therapeutics tanks, it still doesn't mean the whole thing was a failure towards the eventual goal of hair cell regeneration.

 

[FGG]

I understand all the negativity, but before everyone declares FX-322 dead, do you think you could wait for the next trial where they only administer 1 dose at a time, spread out over lengthy intervals? If that doesn't work, then bury it.

Totally agree. They got a hearing signal in Phase 1 that wasn't chance or placebo. They have been published and peer reviewed.

They have come up with an explanation why Phase 2a might have failed despite a working drug (multi dose in rapid succession is detrimental plus they saw historical vs trial word score mismatch).

So unless the company is full of it (which I have a hard time believing since it is made up of long time veterans), there isn't yet a reason to doubt them.

I'm watching the severe arm closely.

 

[GlennS]

So unless the company is full of it (which I have a hard time believing since it is made up of long time veterans), there isn't yet a reason to doubt them.

Sure there is, on the basis of extraordinary claims require extraordinary proof.

I have no doubt they're trying and they're qualified but what they are attempting is indeed extraordinary and the burden of proof is on them.

 

[Diesel]

I guess there's a sunk cost for both companies getting to their respective points with different technology (FX-322 vs OTO-6XX). But if both drugs eventually work, isn't there a shared market based on which drug is slightly better? In other words, if one has a better reputation, a person would probably choose that consistently.

I guess these companies really believe in themselves, and it would take a lot of humility (and possibly stupidity for all I know) to scrap the technology and admit that the other company has a better chance of succeeding.

This is a complex question, and the speculation could go a hundred different ways on why one might be adopted/consumed differently based on doctor/patient preference factors.

The second comment might come down more to investor influence than anything else. Investors, especially those institutional backers, put money into companies like Frequency Therapeutics because they believe there is a potential in the science to generate a return. It would be pretty unlikely to see a firm + investors just stop development because "the other guys is better."

 

[Jurger]

I have a question that you would understand better than I would. What do you think are the chances that some of these companies start buying each other out?

Just as a layman, what I am seeing is OTIVIDEX and FX-322, both hyped drugs, run into trial design problems (we can assert this and say the drug failed, it's not an excuse). I know Carl LeBel used to work for Otonomy. Didn't someone say that Otonomy has the delivery technology?

I have no idea what I'm talking about. I'm just wondering if some of these companies should merge. They all have mountains to clear in every way: safety, efficacy, outdated hearing metrics, lack of education on hidden hearing loss, etc.

I don't think any type of technology can take away the fundamental drawbacks of intratympanic drug delivery. Those drawbacks have been well documented. It's unreliable, unpredictable and has a very hard time getting drugs beyond the ultra high frequencies. The major reason most otologic companies utilize it, is because ENTs perform them on a regular basis for steroid delivery, which, by the way, has not been demonstrated to be more effective than oral steroid treatment. It's all a hail Mary.

 

[Sunshine007]

Another thing I want to address from a mathematical point of view is the following idea: (Using fake numbers) - Does four successful Phase 1b trials with n=25 each equate or override one unsuccessful Phase 2 with n=100?

No. There are many reasons for this, but here's a simple reason. In Phase 1 trials, the primary thing being tested is safety. This means the recruiting approach is to choose smaller sample sizes with the understanding that the absolute worst thing here is safety violations. Efficacy could be a pleasant accident, but it's not the main benchmark.

Trial design and statistical inferences planned in advance are also more experimental. Don't believe me? Here's a quote from the published Phase 1/2 paper:

A sample size of approximately 24 subjects was considered adequate for an initial assessment of safety and tolerability and was not based on formal statistical considerations. Prespecified statistical analyses were exclusively descriptive and included 95% confidence intervals (CIs) as appropriate. Audiometric analyses were considered exploratory and conducted without multiplicity adjustments.
​

What they are basically saying is "we're not trying to prove anything about efficacy." The problem is, to do science properly, this trial can't be used as an efficacy proof just because they like the results. Why? If the results were bad, they would say "Oh, well we were focused on safety." They will use the same excuse if the remaining Phase 1b trials fail.

On the other hand, a Phase 2 efficacy study -- even if it's a Phase 2a so slightly more experimental -- is largely putting yourself out there on display. If they results are a boom, you get to celebrate. If they are not, you have to save face.

There are also technical reasons why a bunch of Phase 1 studies don't equate to a Phase 2. For example, four Phase 1 studies introduce four sets of recruiting standards, and therefore, four sets of fixed effects.

If they somehow get this to pivotal on the backs of a bunch of successful Phase 1 studies (probability is so low that it shouldn't invoke any emotional investment), it will have everything to do with a current lack of other drugs. It has nothing to do with finagling the science in a convenient way.

If we ignore the phase monikers, essentially the reported Phase 2 trials and Phase 1 trials differ in n and probably the randomization criteria. If we are talking about the same dose, I am totally with you on the above, however here we have a situation where the higher n was the wrong therapeutic dose (taking the lawn effect at face value), wouldn't it be fair to say we are not comparing the same thing?

The argument to go to Phase 3 maybe:

We conducted three different trials with three different populations and saw an effect, we tried the higher dose it did not work, therefore in the Phase 3 trial we will prove our effect at single dose in the target population they zone in on.

While it's not yet been proven that the drug works in a large population, we have not yet seen any argument to say the drug will not do so as a single dose even with the Phase 2 data (taking lawn effect at face value). The various single dose trials, if they readout well, will prove the drug does something and prove the Phase 2 dose/lawn effect was indeed the culprit.

 

[FGG]

I don't think any type of technology can take away the fundamental drawbacks of intratympanic drug delivery. Those drawbacks have been well documented. It's unreliable, unpredictable and has a very hard time getting drugs beyond the ultra high frequencies. The major reason most otologic companies utilize it, is because ENTs perform them on a regular basis for steroid delivery, which, by the way, has not been demonstrated to be more effective than oral steroid treatment. It's all a hail Mary.

What's interesting to me is how AAV therapies are working to get around this. Viral vectored genetic therapies have to be directly locally injected, and can't go through the middle ear.

Novartis' surgery was very destructive, so obviously their approach needs some work but Akouous so far is reporting their surgery (still a general anesthesia open approach to visualize the inner ear but use oval window venting to get their drug across the whole cochlea instead) is much safer. Their AAV drug is for genetic hearing loss but I would love to see wider and esp clinical data on safety and am watching them as well.

 

[Cernuto]

I still wonder why it can't be combined with DMSO. Is DMSO otoxic?

Another thing I'm wondering is if they mixed placebo doses in with real doses for the same person in the study.

 

[Zugzug]

If we ignore the phase monikers, essentially the reported Phase 2 trials and Phase 1 trials differ in n and probably the randomization criteria. If we are talking about the same dose, I am totally with you on the above, however here we have a situation where the higher n was the wrong therapeutic dose (taking the lawn effect at face value), wouldn't it be fair to say we are not comparing the same thing?

The argument to go to Phase 3 maybe:

We conducted three different trials with three different populations and saw an effect, we tried the higher dose it did not work, therefore in the Phase 3 trial we will prove our effect at single dose in the target population they zone in on.

While it's not yet been proven that the drug works in a large population, we have not yet seen any argument to say the drug will not do so as a single dose even with the Phase 2 data (taking lawn effect at face value). The various single dose trials, if they readout well, will prove the drug does something and prove the Phase 2 dose/lawn effect was indeed the culprit.

I'm going to propose the same type of question I've asked before.

Say the safety studies were fine for all three placebo controlled Phase 1, but efficacy was minimal. Then Phase 2 was a huge success. Would we say, "well the lack of efficacy in the Phase 1 studies overrides the Phase 2?" No, we would say what really matters is the efficacy study.

I've learned my lesson with regards to pushing the drug deeper. The lawn effect doesn't exist until it is proven to exist. Successful trials with different designs is not a proof.

 

[FGG]

I still wonder why it can't be combined with DMSO. Is DMSO otoxic?

Another thing I'm wondering is if they mixed placebo doses in with real doses for the same person in the study.

The pharmacokinetic studies show the drug gets through the round window in appreciable amounts, it just doesn't diffuse far. A better approach imo would be something like extended release, nanoparticles/Otomagnetics, or a much safer surgical approach.

If the severe arm shows word score improvements, especially, this is something they don't have to tackle first, though, and could even piggy back off another technology.

 

[FGG]

I'm going to propose the same type of question I've asked before.

Say the safety studies were fine for all three placebo controlled Phase 1, but efficacy was minimal. Then Phase 2 was a huge success. Would we say, "well the lack of efficacy in the Phase 1 studies overrides the Phase 2?" No, we would say what really matters is the efficacy study.

I've learned my lesson with regards to pushing the drug deeper. The lawn effect doesn't exist until it is proven to exist. Successful trials with different designs is not a proof.

I see it as less a need to figure out the exact mechanism (for now) multi dosing has a worse outcome if they can repeatedly show that it does.

 

[Tezcatlipoca]

The pharmacokinetic studies show the drug gets through the round window in appreciable amounts, it just doesn't diffuse far. A better approach imo would be something like extended release, nanoparticles/Otomagnetics, or a much safer surgical approach.

If the severe arm shows word score improvements, especially, this is something they don't have to tackle first, though, and could even piggy back off another technology.

The Bionics Institute is doing nanotechnology.

 

[Zugzug]

I see it as less a need to figure out the exact mechanism (for now) multi dosing has a worse outcome if they can repeatedly show that it does.

I agree. None of this will truly be worked out for a long time, as they don't have the luxury of failing a bunch of times. By the time it is relevant, there could even be a great, sustained-release delivery that eliminates all of the complications of drugging the cochlea multiple times.

 

[Cernuto]

The pharmacokinetic studies show the drug gets through the round window in appreciable amounts, it just doesn't diffuse far. A better approach imo would be something like extended release, nanoparticles/Otomagnetics, or a much safer surgical approach.

If the severe arm shows word score improvements, especially, this is something they don't have to tackle first, though, and could even piggy back off another technology.

I see. I wonder if it could be agitated further down using existing structures and white noise audio with a high pass filter. Sweep the filter down, letting in more low frequencies over time and let FX-322 ride the wave, like a surfer. Maybe bone conduction audio would work better for this method?

Or lay the person's head on a platter that wobbles in the opposite direction of the spiral of the cochlea and let the effects of momentum do the work.

Can anyone answer my question about the same person getting placebo or the real thing randomly for their four injections?