Hough Ear Institute's Hair Cell Regeneration Project

[Mentos]

What I understood from the podcast the pill managed to restore synaptic connections and suppress tinnitus 4 weeks after acoustic trauma - tested on rodents.

@Justin De Moss, is there any indication about therapeutic window, can this be effective also years after synapse damage? Or is it just speculation?

Another question is about criteria for phase 2 clinical trial, do you plan to invite chronic tinnitus sufferers as well (years of tinnitus) or only acute cases i.e. up to 3 months from the trauma?

 

[Lucifer]

They need $735k specifically for it to be potentially labeled as a tinnitus treatment, for insurance access.

Without it you'd be able to get it prescribed but would have to pay out of pocket.

Thanks for the clarification.

 

[Buzzy1]

Hey, can Hough Ear Institute's pill help age-related hearing loss?

I'm not sure about all the facts, but I'm really hoping it will. If they need any volunteers for testing my hand is up and staying up After 38 years of gradually worsening t and hearing loss I think I'd sell my house to pay for the medication!

 

[Tweedleman]

I'm not sure about all the facts, but I'm really hoping it will. If they need any volunteers for testing my hand is up and staying up After 38 years of gradually worsening t and hearing loss I think I'd sell my house to pay for the medication!

Here here! My hand also way up! I'm practically still in the acute phase, Hough! Pill me up already!

 

[UKBloke]

What I understood from the podcast the pill managed to restore synaptic connections and suppress tinnitus 4 weeks after acoustic trauma - tested on rodents.

This point prompted my main question as well. What does 4 weeks in a rodent equate to in humans?

 

[Rb86]

Yeah, I'm angry about this.

I was led to believe Hough Ear Institute already had proof of concept in animal models for tinnitus, and that's how it acquired the new partnership for the next phase. That's why I invested at all in the first place.

Now, this exciting top secret partner is a 5-year-old Korean subsidiary that has virtually no profile online, and is owned by GtreeBNT, whose stock went up in 2018 due to its acquisition of a possible brain cancer drug, and now has fallen back down to levels prior to that acquisition (presumably because they're not showing any progress).

Now it's OUR burden to raise money, to prove to "Oblato" that it's worth studying as effective for tinnitus?

Number one, don't waste your time or anyone's money. If you get it approved by the FDA to treat cochlear implant damage, the tinnitus community will quickly get their hands on the pill and tell the world it either works or doesn't. That's provided it's affordable for everyone, not just some, like you've said it would be.

Number two, you get any kind of real proof of concept and you'll have your choice of pharma companies with REAL money knocking on your door.

This drug was developed ten years ago now. It took 5 years to say it was safe. It's now taken another 5 years to be picked up by "Oblato" who's testing it for something else. Damnit.

I'm over it. I need to learn to live my life with this and not wait on magic or waste money I don't have on it.

I appreciate what Hough Ear Institute is doing, and I know it's hard to get funding, but lying isn't going to help you. Don't tell me you have evidence it's effective for tinnitus in animal models, and then your new partner needs you to prove it before they'll invest. What kind of BS is that?

And yeah, I was up all night with loud ringing, and I came here for some good news.

 

[Justin De Moss]

Thanks so much for answering our questions.

Does this mean that tinnitus would included in a potential phase 2b after the cochlear implant injury study if you can raise funds for a proof of concept study?

Or will the aim be to release this drug with the indication of protecting against injury due to CI insertion so it can be released faster with off label studies being done later?

We are trying to get tinnitus as an indication for Phase II trials. That will get it in people's hands quicker and more cost-effective than waiting until it's approved by the FDA.

I'll answer the CI trauma (?) in another post from another contributor.

 

[Justin De Moss]

I wouldn't wish this on my worst enemy, let alone someone who is so proactive and engaging in our community. Ear-infection-induced/exacerbated tinnitus looks like it has close to the best recovery outcomes (coming from someone whose obsessively read the success stories at least three times over in efforts to cope). Hopefully this will be just a blip on the radar few months from now. Are you on any antibiotics? Some are more destructive than others. @FGG might be able to shed some light on that.

Good luck man. We appreciate you.

edit: one thing that's interesting about this $735k proof of concept study for tinnitus is that the sole reason for this would be so that those with tinnitus could have this prescribed with approval by insurance. I inquired about the same application for insurance approval in the FX-322 thread since they are currently able to do so in a separate experimental arm, although it seemed like the consensus was that even if it showed considerable efficacy for tinnitus in the experimental arm, that it would have to be prescribed off-label for tinnitus and thus unlikely to be approved by insurance. Any thoughts?

If we can show efficacy during the clinical trials - that makes it likely to be covered by insurance. If we don't, then it would not be covered by insurance for the indication of tinnitus.

 

[Justin De Moss]

I hope you recover quickly, sounds bad. Thanks for all the work you are doing.

I would love to know approximately what the full price of the drug would be. Here's hoping you can get it onto the market as soon as possible.

It's hard to say, but the models that we have worked with show that, after the first two years from the initial release it should cost less than the price of a single hearing aid.

 

[Justin De Moss]

Hey, can Hough Ear Institute's pill help age-related hearing loss?

Doubtful, but the hearing loss injection we are working on will!

 

[Justin De Moss]

I found that shocking.

I thought with the new partnership with Oblato they have the funds for the clinical trials.

Do they actually need more funding?

Oblato is funding Phase II and Phase III clinical studies. They pick which indication they want to pursue based on many factors.

1) Which is the most likely to demonstrate success?
2) How can we test for efficacy objectively?
3) How expensive is each indication to bring through the trials?
4) What is the size of the target demographic?
5) and many others

The reason we need to raise more money for a proof-of-concept study is to show 1) tinnitus can be tested objectively, demonstrate the cost of doing so, show that it can be successful, and illuminate the target demographic of those who suffer from tinnitus.

We already have a model that has shown this several times with promising results. We now need to increase the size of the experiment and get outside validation of results to show justification for the additional Phase II and III expenses.

The good news is that they have expressed an interest in helping pay for some of this new study! I'll have to wait and see but I believe we are looking at them matching half the cost.

 

[Justin De Moss]

I read that a little differently.

My understanding is that by limiting the initial Phase II trial, and making it easier to earn FDA approval, there is a greater likelihood of bringing the drug to market as soon as possible.

Then, once approved, it can be prescribed off-label so tinnitus-sufferers will at least have access while waiting for a mop-up trial to potentially enable insurance reimbursement - if it works.

The alternative, that the clinical trial is overly broad means that even if the drug is successful for some indications, it can stall out and get delayed by years or worse.

Not quite. We aren't limiting the Phase II trials, it just that CI trauma has the best path toward success. This does help get the drug quicker to market.

By adding additional indications, we don't stall or delay approval, it just means that the drug can be FDA approved for more than one indication and insurance is more likely to cover.

I believe insurance would have a healthy interest in covering the drug because tinnitus leads to a whole host of other issues like anxiety, depression, etc.

 

[Justin De Moss]

What I understood from the podcast the pill managed to restore synaptic connections and suppress tinnitus 4 weeks after acoustic trauma - tested on rodents.

@Justin De Moss, is there any indication about therapeutic window, can this be effective also years after synapse damage? Or is it just speculation?

Another question is about criteria for phase 2 clinical trial, do you plan to invite chronic tinnitus sufferers as well (years of tinnitus) or only acute cases i.e. up to 3 months from the trauma?

Aside from the insurance angle and indications that the pill can be approved for - this is exactly why we want the larger proof of concept study. Every indication of the data shows that it would be effective in chronic tinnitus sufferers. Now, we need to demonstrate that, while also having the results validated by an outside organization.

As far as the criteria for the trials - that will be up to Oblato since they will be running the trials.

 

[Justin De Moss]

This point prompted my main question as well. What does 4 weeks in a rodent equate to in humans?

It's hard to say, hence the reason we want to do the proof-of-concept study. In humans, the damage generally starts 24 hours after the trauma and goes on for about a week. The pill has already been demonstrated to prevent damage if given within 24 hours of trauma AND has show recovery from damage when given much later, weeks later.

These are all great questions. They help to illuminate the complexity of drug development and all its challenges.

 

[Justin De Moss]

Yeah, I'm angry about this.

I was led to believe Hough Ear Institute already had proof of concept in animal models for tinnitus, and that's how it acquired the new partnership for the next phase. That's why I invested at all in the first place.

Now, this exciting top secret partner is a 5-year-old Korean subsidiary that has virtually no profile online, and is owned by GtreeBNT, whose stock went up in 2018 due to its acquisition of a possible brain cancer drug, and now has fallen back down to levels prior to that acquisition (presumably because they're not showing any progress).

Now it's OUR burden to raise money, to prove to "Oblato" that it's worth studying as effective for tinnitus?

Number one, don't waste your time or anyone's money. If you get it approved by the FDA to treat cochlear implant damage, the tinnitus community will quickly get their hands on the pill and tell the world it either works or doesn't. That's provided it's affordable for everyone, not just some, like you've said it would be.

Number two, you get any kind of real proof of concept and you'll have your choice of pharma companies with REAL money knocking on your door.

This drug was developed ten years ago now. It took 5 years to say it was safe. It's now taken another 5 years to be picked up by "Oblato" who's testing it for something else. Damnit.

I'm over it. I need to learn to live my life with this and not wait on magic or waste money I don't have on it.

I appreciate what Hough Ear Institute is doing, and I know it's hard to get funding, but lying isn't going to help you. Don't tell me you have evidence it's effective for tinnitus in animal models, and then your new partner needs you to prove it before they'll invest. What kind of BS is that?

And yeah, I was up all night with loud ringing, and I came here for some good news.

I'm sorry you feel that way.

First, we do have a model that has been tested multiple times with great results. That is what got us excited about the possibility of the drug treating tinnitus. It was originally developed to prevent hearing loss and or help restore hearing. The studies are limiting though. They didn't check for efficacy for long-term tinnitus and they need to be larger in scope and validated by outside researchers.

As far as Oblato is concerned, I think you assume too much in your analysis of them. We know of the investment with the brain cancer drug. That partner is who introduced us to them and they are very pleased thus far with Oblato. We all need to be careful about relying too much on our own understanding, especially when we are not "in the field". It is one thing to ask the question - perfectly reasonable. It another thing to state as fact something we do not know to be true.

I get your frustration. But this is really good news. The fact that Oblato is considering paying for half of this study says a lot!

Lastly, no one ever lied to you. I'm very good at raising money and I'm going to do just that because of people like you. Your suffering, frustration, all of what you and so many others are going through - that is why I do what I do.

 

[mrbrightside614]

Hey, can Hough Ear Institute's pill help age-related hearing loss?

Look up pramipexole. Several people with presbycusis have had success after using it, it's a D2 blocker.

If we can show efficacy during the clinical trials - that makes it likely to be covered by insurance. If we don't, then it would not be covered by insurance for the indication of tinnitus.

So if you show efficacy for hearing loss, it would be covered by insurance for hearing loss-related claims only though, correct?

What I'm saying is FX-322 has the experimental arm that would cost you guys $735k for testing specifically for tinnitus—this would suggest that a separate arm is required to have insurance approval for only tinnitus-related claims, right?

 

[Capstan]

They need $735k specifically for it to be potentially labeled as a tinnitus treatment, for insurance access.

<rant>Its beyond frustrating that filthy rich tech-billionaires are spending their fortunes racing for Space rather than investing in bio-tech firms that could directly improve the quality of lives of millions.</rant>

Doubtful, but the hearing loss injection we are working on will!

I hope you receive all the needed funds to get this into the hands of people to help soon. It would be devastating lack of funding could have a cure sitting on a shelf.

 

[mrbrightside614]

I hope you receive all the needed funds to get this into the hands of people to help soon. It would be devastating lack of funding could have a cure sitting on a shelf.

This injection tech seems most similar to Regain, and somewhat similar to FX-322 except the latter actually duplicates the support cell in addition to creating an active hair cell. Both of these drugs are in phase 2 and, with FX-322 being fast tracked, will reach the market much quicker than even the pill will.

 

[Artemis2K]

Doubtful, but the hearing loss injection we are working on will!

Sorry, I meant to ask whether or not it can stop/reduce progression.

 

[Buzzy1]

Doubtful, but the hearing loss injection we are working on will!

Hi @Justin De Moss

My t started with an ear infection, but it is getting worse now due to hearing loss.

Is there any information you can give me about the injection? I thought the pill was for age related hearing loss as well. It's all very confusing, is there a link I can go to for more information?

Thank you

 

[brokensoul]

@Hazel and @Markku,

Tinnitus Talk provides better content than the American Tinnitus Association and British Tinnitus Association combined!

Wonderful work and highly appreciated.

Thanks to @Justin De Moss and Dr Kopke (HEI) for agreeing with the interview. Hope to see good results in the future!

 

[Lucifer]

@Justin De Moss

When you said they will fund half the cost is that to include tinnitus as an indication?

Also is the $750k what you need to raise, or do you need to raise $375k?

 

[mrbrightside614]

@Justin De Moss

When you said they will fund half the cost is that to include tinnitus as an indication?

Also is the $750k what you need to raise, or do you need to raise $375k?

It's $735k. I don't think Oblato is funding half of that.

 

[Mentos]

It's hard to say, hence the reason we want to do the proof-of-concept study. In humans, the damage generally starts 24 hours after the trauma and goes on for about a week. The pill has already been demonstrated to prevent damage if given within 24 hours of trauma AND has show recovery from damage when given much later, weeks later.

These are all great questions. They help to illuminate the complexity of drug development and all its challenges.

You believe the pill can restore damaged nerve endings and synapses in a cochlea in humans which basically means it could treat cochlear synaptopathy. Did HEI develop a method to diagnose cochlear synaptopathy in alive humans? Are you able using your diagnostic methods to say that certain individual has damaged synapses?

According to my last year discussion with Massachusetts Eye & Ear Infirmary researcher till now there was no reliable method to diagnose cochlear synaptopathy in alive humans, it was possible only post mortem. If you managed to find one it means a big step forward in our understanding of inner ear dysfunctions.

 

[Rb86]

I'm sorry you feel that way.

First, we do have a model that has been tested multiple times with great results. That is what got us excited about the possibility of the drug treating tinnitus. It was originally developed to prevent hearing loss and or help restore hearing. The studies are limiting though. They didn't check for efficacy for long-term tinnitus and they need to be larger in scope and validated by outside researchers.

As far as Oblato is concerned, I think you assume too much in your analysis of them. We know of the investment with the brain cancer drug. That partner is who introduced us to them and they are very pleased thus far with Oblato. We all need to be careful about relying too much on our own understanding, especially when we are not "in the field". It is one thing to ask the question - perfectly reasonable. It another thing to state as fact something we do not know to be true.

I get your frustration. But this is really good news. The fact that Oblato is considering paying for half of this study says a lot!

Lastly, no one ever lied to you. I'm very good at raising money and I'm going to do just that because of people like you. Your suffering, frustration, all of what you and so many others are going through - that is why I do what I do.

I stated nothing as fact. I used the word presumably. If I'm wrong about Oblato then so be it. That does not change Oblato, the new partner, requiring a proof of concept for it to study the pill against tinnitus.

"The reason we need to raise more money for a proof-of-concept study is to show 1) tinnitus can be tested objectively, demonstrate the cost of doing so, show that it can be successful, and illuminate the target demographic of those who suffer from tinnitus."

To show tinnitus can be tested objectively means you need bio-markers. Something to physically identify tinnitus. Nobody has that. That's the single hardest part in tackling this condition. You get that and it's simply a matter of time until this is cracked. You get a true biomarker and you will have your golden ticket. Yes, word scores for speech in noise and general hearing tests, but not all who have tinnitus have hearing loss. The target demographic is already illuminated.

As far as I'm concerned you're still at square one, and this partner is a side avenue.

Like I say, if you get FDA approval for the cochlear implant trauma, you will very quickly have the tinnitus community buying this pill and letting you know if it works or not.

Bottom line, I was rooting for Hough Ear Institute in a big way. But setback after setback and then some kind of false excitement really sours it.

I don't mean to be a jerk about it. I respect you for fighting the good fight. But I'm pissed. I'm suffering and I'm fresh out of patience.

 

[Mentos]

To show tinnitus can be tested objectively means you need bio-markers. Something to physically identify tinnitus. Nobody has that. That's the single hardest part in tackling this condition. You get that and it's simply a matter of time until this is cracked. You get a true biomarker and you will have your golden ticket. Yes, word scores for speech in noise and general hearing tests, but not all who have tinnitus have hearing loss. The target demographic is already illuminated.

You can have qEEG brain mapping, it shows level of neuronal activity in the auditory cortex. The ones with tinnitus have it hyperactive. My qEEG shows hyperactivity and it's the only marker that shows I have tinnitus; hearing tests, otoemissions, ABR all are ok.

 

[Joly]

@Mentos

When you say the treatment repairs nerve endings, are you talking about the auditory nerve?

 

[all to gain]

Off topic a little, but how can one tell if the auditory nerve has been damaged? An ENT said mine probably was and that the hair cells probably hadn't been affected. No idea how she 'knows' this though.

 

[brokensoul]

You can have qEEG brain mapping, it shows level of neuronal activity in the auditory cortex. The ones with tinnitus have it hyperactive. My qEEG shows hyperactivity and it's the only marker that shows I have tinnitus; hearing tests, otoemissions, ABR all are ok.

Just confirming that my Loretta qEEG indeed also demonstrated hyperactivity in my auditory cortices. It's a strong indicator of tinnitus.

Researchers say that we need objective biomarkers, but there must be something that can already be used today to demonstrate efficacy during clinical trials.

If the solution works, this should be visible on some types of scans that reveal reduced hyperactivity along the auditory pathway. Is it not possible also to verify hyperactivity in the cochlear nucleus?

 

[FGG]

Just confirming that my Loretta qEEG indeed also demonstrated hyperactivity in my auditory cortices. It's a strong indicator of tinnitus.

Researchers say that we need objective biomarkers, but there must be something that can already be used today to demonstrate efficacy during clinical trials.

If the solution works, this should be visible on some types of scans that reveal reduced hyperactivity along the auditory pathway. Is it not possible also to verify hyperactivity in the cochlear nucleus?

What is the sensitivity and specificity of that test or is that unknown?