Hough Ear Institute's Hair Cell Regeneration Project

It might work out if Hough Ear Institute agreed to offer the treatment to donors at a discounted rate upon market release. I definitely would donate $100 if it meant that I got $500 off the cost of the pill.

 

At this point, I would say even a smaller phase 2 study going over effectiveness would help their cause.

Their reasoning for donations from the public doesn't add up in my book.

Oblato has already given them $300k for the trial as far as I know, this extra amount of $65k wouldn't be much more.

Also, that 20M people that suffer from tinnitus? Most of those have a low sine wave in the background. They're not going to donate, nor are they looking up tinnitus.

It would be one thing if they had data on human subjects showing improvement, but with just animal models and making such bold claims, it feels sketchy.

 

Often there is correlating data between rats or mice and humans. I have happened to see a lot of these connections, so I would not simply rule out that there is not a link at all just because there is no information on humans yet.

While it is only $65k required right now to supposedly proceed with the proof of concept study, it is really $135k when considering the fact that the donations get matched by a third party organisation.

What I've understood about a proof of concept study in the phase 2 trial is that this means that they need to show that the treatment achieves its intended outcomes obviously not just in its intended area of research but also actually in associated areas to be indicated for the wider benefit it may provide.

Below is from: Proof of Principle Studies - PubMed

Thus taking this summary of what a proof of concept study is, it seems that it is not really that unnecessary or far-fetched that this needs now to get done.

What we don't understand is why Hough Ear Institute hasn't got the means money wise to fund this either through obtaining a loan or acquiring complete funding through their own sources.

Simply put, it would be best if Hough Ear Institute could just come out and give solid statements, for example that they cannot fund it internally due to not having the funds available.

Or that if they got a loan or further funding from another party like the pharma organisation then they would need to give up or lose rights to be able to sell this in the United States as a commercial treatment. Given this, they would then lose the revenue source that they would need in order to fund their other treatments such as the injections.

This would clear things up significantly for patients and as a result really would work in their favour as it would alleviate most patients' confusion, hesitance and reservedness in donating diligently.

 

I haven’t heard much more on this in the last week or so however I am actually more and more questioning their process.

Hough provides positive info when they released the FDA video, however since then there has been little detail provided to inform us of important pieces of information.

This includes details on the pill’s need to be taken through the Proof of Concept study and also why they cannot obtain funding for it through the pharmaceutical company, Oblato.

I genuinely believe that their methodology and products may be sound, however the vagueness in answering relevant and specific questions leaves me confused.

It just seems somewhat interesting that they have not moved on with the treatment process promptly. Especially when we consider that other firms with similar treatments have done so.

Hough are doing themselves a slight disservice by not directly indicating why there are certain delays with the process. Not to mention going by the evidence a lot of people here are also simply annoyed with their responses around the required funding such as that people are spending several hundreds dollars on potions rather than donating to real science.

 

Hough's stance on their efforts were quite confusing initially. They are advertising much efforts in the Hough Pill but then are repeatedly talking about cochlear regeneration. However, these two concepts are completely separate target treatment. The Hough Pill is an anti-oxidant cocktail, which is primarily targeting preventative measure of hearing damage. The other one has a focus on cochlear hair cell regeneration via some specific gene therapy delivery method.

It is very confusing how they are emphasizing their pill concoction and then talking about their excitement with their cochlear regeneration study without a very demarcated distinction because they are not the same treatment. Their communication does not inspire confidence.

And let's be honest, we've all tried various anti-oxidant supplements, including the infamous NAC molecule that's already known to have positive preventative effects on hearing damage. I just can't seem to get excited on another NAC concoction with another molecule, especially since their studies have indicated it's primarily on prevention... And our hope that it will help chronic sufferers is just that: patient bias and hope. If it would help chronic sufferers, then I think they would have already done animal studies on chronic cochlear damage.

Did anyone listen to the Tinnitus Talk Podcast, the Hough Ear Institute episode? Is it just me or did the explanation on how the pill works seem very mumbled and incoherent?

 

To be fair to Hough, even if they haven't been as transparent about their financial arrangement with their partner(s), it doesn't mean their drug doesn't work.

HPN-07 was an antioxidant/potent free radical trapping agent that they happen to discover regrow synapses in their pre-clinical studies. It seems to be a unique drug in that regard.

Though, it seems logical to say "why would this antioxidant work when others don't?" Since presumably they have a similar mechanism of action but in medicine it doesn't always work that way. Unexpected off target effects (and side effects too) happen all the time.

For instance, they (researchers, not Hough) happened to recently discover synapse regrowth with Bisphosphonates (an osteoporosis drug which inhibit osteoclasts), something that should not have an effect on cochlear synapses.

Hough might not even know why it works (but maybe they do) even as they observed synapse regrowth as a pleasant surprise pre-clinically (Justin has described it exactly as a pleasant surprise). Hence, the vague scientific explanation.

Financial transparency would inspire more confidence in their drugs but maybe they don't feel that they can disclose that sort of info for whatever reason.

 

I think that Hough just needs to state that they cannot disclose this information. To date all that they have said when they have been pressed on it are things like that’s just a part of research or that’s how these things work. Both comments are vague and do not do much in the way of alleviating the concern and confusion many have.

Just come out and say that you cannot disclose the funding agreement and that way you will put all the concerns to bed.

 

Interesting update regarding the pill.

Question:

Answer:

There was a follow up question asked which was:

The above has not been answered at present.

I would be interested in seeing whether Hough Ear Institute can provide a clearer indication on the time frame and process regarding the pill study and trial(s).

The question of why the study needs to be completed first is still not answered. Furthermore, my understanding is that if a treatment is approved by the FDA for one indication (such as damage caused by ototoxic drugs), then there is no limitations in prescribing it off-label for other indications such as tinnitus.

 

The link below explains that proof of concept vs traditional clinical trials pathway. I found it quite interesting and answers some of the questions you posed. Quite an interesting read.

https://www.lifescienceleader.com/doc/benefiting-from-accelerated-proof-of-concept-programs-0001

Tldr; The proof of concept combines phase 1 and 2 for both safety and efficacy to see if it will be a waste of time or not.

 

That’s the type of answer Hough hopefully will give/should have given if accurate from their end. However this should have been done at a much earlier time.

This essentially explains what I thought about the reason for doing both together. It still does not, however, explain the reasons regarding why it will take so long to complete the trials.

I think that the pill trial is actually up to phase 2, although not sure if it is a requirement to retest for safety with the tinnitus aspect.

 

Further update from Hough Ear Institute:

This answer still simply makes so little sense.

On the one hand, we are told that the drug is ready to get trialled and furthermore that there are seemingly no delays impacting the process.

Then on the other hand, we are told that we need to get this study funded so we can continue moving forward with it.

Something simply doesn't add up here, especially after we were previously informed that Oblato wanted the pill tested for tinnitus prior to the commencement of phase 2. I am also certain that the tinnitus study is not required as a part of FDA requirements either.

Thus I am now keen to ask why funding through Hough Ear Institute is needed to conduct this study if it is now firstly not a FDA trials requirement and secondly being apparently run by Oblato.

 

After reading Hough's paper on HPN-07 a second time (in regards to the Hough Pill), I can not agree that it is regenerative and thus not significant for us chronic sufferers.

"Surprisingly, the observation that HPN-07 treatment initiated within four hours after noise exposure and continued for 2 days has long-lasting effects, some of which only become evident 21–180 days later, is not readily explained from our evaluations but could be interpreted to suggest that HPN-07 may have the capacity to initiate repair mechanisms or a regenerative response among one or more components of the cellular architecture of the cochlea."​

After reading their data, I can not see how they are suggesting it is regenerative.

Figure 8 (page 16-17) shows data on day 3, 10, 21, 180d of 6 animals each and all of which shows significantly less hair cell loss but more importantly the percentage hair cell loss was relatively the same on ALL days from day 3 group to day 180 group. This indicates that hair cell loss was already prevented early on by using the treatment 4 hours after acoustic shock to the animals. However, to conclude hair cell regeneration, the graphs would need to show a higher percentage hair cell loss early on and a lower percentage of hair cell loss at a later date. The fact that percentage of hair cell loss did not change much for all days of 3, 10, 21, 180 do not reflect hair cell regeneration but rather hair cell lost prevention early on.

However, their research does show it is an effective preventative measure and that is great.

 

Their pill (HPN-07) reportedly regenerates synapses, not hair cells.

Their pre-clinical intratympanic injection drug (totally different drug) addresses hair cells.

 

Further follow up from Hough Ear Institute - Much clearer now:

This is a lot more clearer compared to the previously provided details.

So it seems significant to know that the FDA approved clinical trials for hearing loss as an indication and the other study for tinnitus as an indication are totally independent from one another and although Hough Ear Institute wants to get the tinnitus study done ASAP, the FDA approved clinical trial for hearing loss will commence this year.

Therefore, there is a possibility that the treatment could be available before the tinnitus part of the study is completed.

Clearly we can only hope that the hearing loss trial is successful so we can have actual access to the treatment off-label within a couple of years rather than potentially six years or so for the tinnitus study to complete.

 

If that's the case, then it seems quite redundant to do the tinnitus study. If the pill passes clinical trials for hearing loss issues, then I'm sure many of us will jump to buy it and see if it works for tinnitus! By that point, we'll know for ourselves if it works for tinnitus or not. And if many of us report that it doesn't work or have some relief, then the ongoing tinnitus study is moot. And it's also moot if many of us report that it has helped them through word of mouth. Speaking on the consumer side of things...

 

According to Hough Ear Institute, the only benefit from conducting the PoC (Proof of Concept) study is to receive coverage from insurance if the pill’s prescribed solely for tinnitus.

Hence if the pill is FDA approved for treating damage caused by ototoxicity, there is nothing stopping a specialist from prescribing the pill off-label to treat tinnitus.

I am certain that many wouldn’t care about paying full price for the pill if their PoC study isn’t done for tinnitus prior to its release. That’s assuming it’s a successful treatment.

Thus while the PoC study is necessary and beneficial to obtain cheaper access to the treatment, it isn’t necessarily as urgent as Hough Ear Institute has claimed. The treatment can be made available off-label simply after completing the FDA trial(s).

 

It's not moot though. What Hough is hoping is that it becomes covered by insurance, which if it does, saves a lot of money for the sufferer.

 

I agree, however most patients (especially those outside America) actually aren’t eligible to get the treatment through the insurance anyway. Thus while I would wholly agree that doing the study is not moot it isn’t as beneficial for many as you may think.

For example, I would need to pay the actual full retail amount if I obtained it in America. Alternatively in Australia I’d need to do the same, unless they subsidise this through the pharmaceutical benefits scheme. This is where our government pays for or covers a significant portion of a number of medications.

Thus the pill’s release is possibly a bigger priority for majority of candidates than it being covered by insurance.

 

Further follow up and further clarification from Hough Ear Institute:

QUESTION:

ANSWER:

So at this stage it is evident that they want to push the treatment through a phase 2 trial for tinnitus. Despite Oblato being very interested in treating tinnitus, they were not able to fully fund the trial.

It is also evident that Hough Ear Institute has come out with different and seemingly contradictory claims about the status of the phase 2 trial.

First they said that the phase 2 trials will be starting this year and that according to what others like @FGG have claimed is that they will be testing for cochlear implant trauma as it is the quickest method for approval. Now they are saying that the trial will be delayed until the proof of concept study for tinnitus is finished.

I am actually somewhat glad that we know now exactly where Hough Ear Institute stands regarding the pill, however I am not actually thrilled about their miscommunication/contradictory information in relation to the planned progress and testing methodology.

Is anyone interested in having a discussion with them and/or doing a Q and A follow-up to discuss the pill? This was put forward as an option.

 

Just ask Justin De Moss to come back to Tinnitus Talk, he had already answered many questions here before.

He really needs to clear the waters, Hough is appearing like a scam almost now... all the contradictory information and miscommunications is really hard to swallow.

 

It’s possibly not the case but I feel like Oblato and Hough have confidence it works for the hearing loss side but don’t have confidence that it works for tinnitus. Thus the burning question is why won’t Oblato fund this on their own or at least the rest of it if they are absolutely keen to investigate tinnitus.

@Hazel would you be interested in setting up another discussion with Hough.

 

So seeming we haven’t heard back from @Hazel, what sort of questions would people want to ask Hough in the event that we don’t get another talk done through @Hazel?

 

Once Hough collects money for the proof of concept study, how much time is needed to start the phase 2 for tinnitus?

 

Justin was happy doing a call/interview/chat/whatever, although at this point I am thinking a text Q&A seems better.

Why don't we wait a week or so and see what gets asked. As it stands I got many questions I want answered, although I will leave these for the time being as others have actually probably got the same questions. I will ask them though at a later time if they haven't been put up.

 

@Justin De Moss,

@ajc and @tommyd87 did misinterpret the answer regarding the off label use.

Post #966 and specifically at the quoted answer at part 6, which was talking about off-label use not covered by insurance and that it would put "medical license in jeopardy":

6) If prescribed off label and/or the insurance company doesn't cover it because the study wasn't objective, rather subjective for example, then a patient could take it - for any reason they wanted to assuming that a) their Dr. is willing to write a script for the drug for an indication that the drug has not been approved for (and thus potentially putting their medical license in jeopardy) b) they don't mind paying the full market value of the drug - which can be thousands if not tens of thousands of dollars.​

My interpretation is that it can be used off-label but doctors' might be not willing (due to the nature of off-label use jeopardizing medical license but is entirely dependent on the doctor's choice) and if the doctors are willing, then it concerns about insurance coverage.

I see that some people can misinterpret assumption "A" regarding off label use can put doctor's "medical license in jeopardy" as an interpretation that it can not be used off-label.

Expanding on the general confusion:
@tommyd87 main concern, and probably the general consensus, is that the extra tinnitus study is unnecessary when a clinical trial for hearing loss is being conducted because the general assumption is that curing hearing loss cure tinnitus (but that has not yet been proven so everyone's just banking on this assumption).

Personally, I would be in favor of a tinnitus study once the hearing loss trial show positive results in phase 2. If it does show positive results from the hearing loss study, then I think it would be necessary to do a tinnitus study. The issue is that it would be an entire waste of both money and time if the hearing loss study do not show positive results. Again, the assumption is the correlation between hearing loss and tinnitus. Based on that assumption, if it shows no efficacy regarding hearing loss, then it would be unlikely to help tinnitus and thus prematurely conducting hearing loss study and tinnitus study at the same time is jumping the gun.

@Justin De Moss Thank you for your interaction and discussion at Tinnitus Talk.

With that being said, I can understand everyone's frustration at the slow pace of things. As someone who had mild tinnitus developing into moderate tinnitus 3 months ago, I'm also desperate and impatient to push for fast results. We're all impatient that a tinnitus study is needed to be funded when a hearing loss study is already green lit.

 

@Justin De Moss I haven't read the others' apparently disrespectful posts but let it roll off your back.

I can tell you all I've had numerous emails with Justin and he gives a shit. Genuinely. I've also been the frustrated hopeless and angry guy on here too.

I honestly get both sides. We need a cure yesterday and it's hard to pull off. Really hard.

Continue to fight the good fight. Putting a dent in, if not curing tinnitus would be one of the most righteous feats for mankind the world over.

Anxiously waiting.

 

I got an email stating Hough were entering Phase 2 trials, not sure if it meant now or in the future.

 

Can you post the language from the email? Thanks.

 

You’re a hero – a hearing hero! You’ve implemented safer hearing practices with your family and already had or at least scheduled everyone’s annual hearing exam. WOW! I’m so grateful for your dedication to your children’s future and success.

Because you’re so invested in this beautiful gift of sound, I want to share with you the hope for hearing restoration. Some of you might suffer from hearing loss damage that you’ve been told can’t be fixed. Maybe your parents’ hearing is deteriorating. It’s possible that your child even has some form of hearing loss like Eloise, who I mentioned in my last email.

Hearing loss causes deteriorating relationships and adds more obstacles to life. But there is a hope dawning on the horizon! Hough Ear Institute has spent over two decades researching and creating medicines with the hope of restoring hearing. And today, I’m proud to tell you that we are closer than ever! Our proprietary hearing loss pill is entering phase 2 FDA clinical trials, and we have so much more in the works. This pill is the closest science has ever been to hearing restoration – apart from a device or expensive technology. Simply put, this pill works to regrow the nerve endings in the inner ear to restore hearing function and make it better. We are closing in on something that was once thought impossible!

And because you’re a hearing hero, I knew you’d want to be part of this amazing adventure into scientific breakthroughs! You have the opportunity to partner with this work and build a legacy of hearing restoration. How? Well I thought you’d never ask!

Put your money where your ears are – literally! Your donation of any amount keeps this research moving ahead, even during a pandemic. If you’re a new donor to HEI, or your gift is over $1000, it will be matched 100% (for a limited time). That means you can DOUBLE your impact with just one donation!!

Become an advocate at your child’s school for the hearing impaired. Let your voice be heard and show your local educators that you care about those kids who are struggling because of hearing loss. Rally behind your local officials to implement annual hearing testing in schools.
Continue to practice healthy hearing practices and get those annual tests scheduled for next year!

You and your kids are the reason why we are doing this work. You’re also the way we are able to do the work. Will you continue your heroic efforts in hearing health and give to Hough Ear Institute today? Will you give hope to kids just like Eloise?

Sincerely,

JUSTIN DE MOSS, M.A., CFRE
Chief Philanthropy Officer