Master Spreadsheet of Hearing Pipeline

Hi everyone,

For a long time, I've had a desire for a progress-oriented master spreadsheet with all of the relevant medications being explored. The idea is for something that's highly visual and easy to look at without opening up a million tabs and having to think about each drug out there.

Over the course of the day, I have made such a spreadsheet. It is likely not the finished product, but I wanted to share it now in order to get feedback. Even if someone else has something like this out there, I made this for myself, so no issue if we don't use it.

It took me a lot of time to work through the details, dates, clinical trials (successes and failures). The way it's generally formatted is that other than a couple of big names (e.g. FX-322 and SPI-1005), I mostly just list the clinical trial that's the furthest along.

The only thing needed to understand this is what the colors mean. Very simple: green means it succeeded, yellow means we are awaiting the result, and red means it was a bad result. Note the clinical trial and press links.

I surely have made mistakes from all of the copy pasting and formatting. If this idea is popular, my next idea is to throw the idea out there of making this sharable so that others can edit it. There's a lot of drugs on here and depending on when my hyperacusis flares up, I don't know if I can really keep up with it in this manner forever.

Enjoy!

Zugzug

EDIT: How this thread will work: From time to time, I will update the file. I will update the date both in the file name and in the line below.

Updated version: December 11, 2022

How can you help:

• Accuracy: Number one thing is to look for mistakes. The biggest areas that mistakes could have been made is from the copy/pasting. The other area that could be prone to mistakes is the number of times that a trial failed/succeeded. If I didn't see negative press, I generally assumed it hadn't failed that phase before, but it's possible that some of the drugs (that I follow less closely) have failed before and I didn't realize it. This kind of thing matters with respect to the number of failures that a company can endure financially.
• Updates: The technical aspect of updating this is super easy. The hard part is keeping up with all of the news. Please do not hesitate to quote me or somehow get my attention with an update that I may not be aware of.

 

This is awesome. Only thing I would maybe include is that Hough Ear Institute claims their pill also treats synaptopathy.

Why the Vertex stuff out of curiosity?

 

This is a great post, thank you. Hopefully we'll be seeing a lot more green in the years to come.

 

Thanks Zugzug for the spreadsheet. You are doing good work for this community.

 

Thanks for the suggestion. I just changed it on mine. BTW, I had a difficult time tracking down the official clinical trial that cleared Phase 1 for the Bomb Blast Pill. Not sure why.

Vertex made its way on there from following rabbit holes. I actually resisted the urge to add more; I kept thinking about everyone's medical problems on here, but I had to use some degree of discipline to keep it to hearing -- otherwise, it would be too cumbersome.

I did add the CRISPR stuff because it's very general and a huge way of the future, IMO. Besides, @serendipity1996 was dropping gold over some of this stuff so I thought to include it. I also have an interest in gene editing for my own problems, so there's some bias there.

I don't have noxacusis (at least not yet), but I wanted to include stuff on NaV1.7 and NaV1.8. Actually, this whole process was super educational. I reread the Professor Tzounopoulos Tinnitus Talk Podcast transcript and saw a connection between the idea of opening potassium channels in neurons in the DCN and blocking sodium channels in nociceptor neurons.

Another thing to note:

Sometimes it's unclear, the line between "discovery" and "preclinical." Most people probably view them similarly like me, but I wasn't super precise on this. If they advertised it as preclinical, that's what I put. If I wasn't sure, I put discovery.

Also, some other stuff:

Obviously, there's overlap between hair cells and tinnitus and hair cells and synapses, etc. I tried to keep it simple by sticking to main actions.

 

Can the CRISPR stuff help with tinnitus?

Also, you may want to add the QurAlis drug, they have eliminated a ton of Retigabine's side effects. However it's in pre-clinical.

 

Thanks @Zugzug, this is marvellous and will help a lot of people. I am thinking of a friend who is not often on the forum, as he is very debilitated, and I think this could lift his morale considerably. I will send him a link to this thread.

A few possible additions (but I understand if you don't want to include them as they are more indirect): the Xenon Pharmaceuticals drugs and the Huperzine A study by Fudan University.

The XENON drugs are not targeting tinnitus specifically but they might help given the past success of Retigabine and the potassium channel opener features. There is no clinical data for tinnitus, though, only many anecdotes, so I understand it is hard to include in a scientific spirit. Just in case:

Xenon Pharmaceuticals
XEN-496 (Ezogabine, similar to Retigabine)
XEN-1101 (Not clear it targets the right potassium channels)

Fudan University has a trial that is at a good point for tinnitus, signalled by @FGG, trialling Huperzine A. This is officially for tinnitus and is a trial, so it might be worth listing.

Apologies if you already listed these and I missed them, my floaters and visual snow are acting up today.

 

I share your interest in the Xenon drugs for epilepsy, which could help tinnitus off-label. Huperzine A is definitely worth adding to the tinnitus section — I simply missed it.

When things start to settle after receiving suggestions, I will post an updated version.

To anyone reading this, don't be offended if I don't include everything. This list is an attempt to toe the line between exhaustive and somewhat succinct.

 

Wow, just wow. Absolutely phenomenal. Thank you for this. I wish something like this would be available in ENT offices.

Also might I suggest an addition? PIPE-505 also regenerates OHCs in small, but not completely insignificant amounts (at least per their preclinicals). It was enough for them to mention it on one of their old presentation slides.

Maybe we can throw them a line in the hair cell regeneration category as well.

One more from me. I would prefer having Cisplatin Protection as its own separate category. Three different companies (Decibel Therapeutics, Hough Ear Institute, and Otonomy) are working on it and I think partitioning it out would be helpful.

Otonomy is a weird one for this because although they list their potential drug as being for “Cisplatin induced hearing loss”, when you read the description it is for acute application and prevention. So I would suggest at least moving OTO-510 into acute, until further information becomes available.

Last thing, I swear. @Hazel, could I propose we sticky this to the top of the Research category? It’s such a good primer for anyone looking to get their feet wet in hearing loss/disorder research.

 

Great stuff.

I'd like to see you include the neuromodulation treatments although these have lost their luster since Lenire.

 

Thank you so much for clearing that up for me, regarding PIPE-505. I remember some of us having a discussion about PIPE-505 and transdifferentiation so I was a little confused to see them talking about synapses.

Good point about ototoxicity. I debated making it a separate topic (I would include Cisplatin with antibiotic toxicity, for example). It's a good suggestion because the ototoxicity drugs are a mix of prevention and acute treatment. If someone was taking one for long-term chemo, presumably this is not an acute situation.

I will make a note of this.

I debated this one. Personally, they are not my thing. Maybe if Susan Shore's device is a success, I will add it and start tracking improvements.

 

Fantastic, high-quality post. Great to see the inclusion of potential pain treatments. On that subject, I also recently came across another potential avenue - Professor Peter McNaughton of King's College London is looking to target HCN2 protein - 2 years ago a collaboration and licensing was deal was signed by KCL and Merck to take this into the clinic. I haven't found further updates but I assume they would be in pre-clinical development.

Pioneering pain research leads to landmark deal

Also, interestingly his research was the subject of this article in The Economist a few years ago (you have to make an account to view the whole article although it's still free). It's scary how some of the pain psychiatrists interviewed here push back against the idea of improved medication for chronic pain and imply that patients want to remain ill.

Will there ever be a cure for chronic pain?

 

What about The Bionics Institute?

 

Real good shit man. Thank you! I might eventually forward this to my ENT (if that's ok).

 

I updated the file, taking some of the suggestions into account. See the original post.

 

I was curious about this too. CRISPR is a huge breakthrough for medicine, but I am really also curious on how and/or if it is possible that it can help tinnitus. Perhaps this is something that has gone under the radar that can help tinnitus?

 

Awesome work. Would you consider adding neuromodulation treatments (Dr. Shore, ABI, DBS, HIFU, etc.)?

 

The CRISPR drugs could help noxacusis, which many people on the forum suffer from along with tinnitus.

 

To Zugzug:

You should be very proud that such an assemblage and collation (which I have not encountered on any other independent web site) indicates a real basis for hope and may result in many desperate suffers neutralizing their rampant suicidal ideation. (Or, just reading how many projects are in the works may induce many not to kill themselves). I know that it gave me an entirely fresh perspective on the extent and range of the research.

 

Thanks, Dave. I've had horrible suffering and inability to concentrate over the past two years so I decided to make this during a window when I was able to. It's definitely nice for people to be able to calculate ranges of expectations for their future. Of course, sometimes conditions improve with time and dumb luck, but it's nice to track the pharmaceutical end.

In the immediate future, it's looking like the fast-tracking of SPI-1005 could be key to helping at least some people. I'm confident that the hair cell, synapses, and nerve regeneration drugs will pass over the next 10-20 years, but with little confidence in the timeline.

I also think the potassium channel opener drugs could be a game changer in terms of mental health breaks. CRISPR will eventually help a bunch of problems with due time.

 

I came across this tonight. I'm not sure if it should be added because I'm really not sure what it is exactly:

O-Ray Pharma

 

Looks interesting, from the website. I'll probably add it to the "Delivery" section.

It looks like they are trying to treat Meniere's disease in a parallel way to OTIVIDEX compared to intratympanic steroid shots.

I'm at least a little confused as to why their net is so big. It comes off as vague, just as a layman viewing the website. Maybe they designed the site with less technical details, but it seems confusing as to what they would actually do.

 

It reads to me like they are writing the page for a specific kind of layman (future investment partners). Even the "about us/management" page is about how friendly the founder is with the FDA.

Considering the authors on this publication, I think this is what they are looking to do (and it is delivery).

Candidate drug "OR-102" seems to be implantable Fluticasone polymer beads for cochlear implant trauma and autoimmune cochlear diseases.

I think the "age-related" and "otitis" beads would contain an established drug but I'm not sure what.

EDIT: This was the study I meant to include:

A Polymer-Based Extended Release System for Stable, Long-term Intracochlear Drug Delivery

 

@Zugzug, there are also the Sensorion drugs to add, potentially, as from this thread.

 

@Zugzug, very nice work!

There is another company that aims at reducing chronic tinnitus. They are preclinical, but claim that they will soon start human trials. They are called Cognosetta.

CS0022 (formerly called BMS-191011) is a next generation BK channel opener designed to lower tinnitus volume by regulating the abnormal neural excitability in the central auditory system (CAS)… thereby restoring the proper “balance of excitation and inhibition” necessary for silence.

I don't know what a BK channel opener is, but someone here probably does.

https://www.cognosetta.com/

EDIT:

BK is apparently a calcium-activated potassium channel opener.

That's a new one to me.

Is this another approach of tweaking Trobalt?

 

This is another otoprotection one. It's for protection from Cisplatin and its release is imminent (passed Phase 3, awaiting FDA re-inspection of facility). Their compound (Sodium Thiosulfate) is given IV. And it looks like Decibel Therapeutics is trialing the same compound intratympanically (DB-020). I wonder if OTI-510 is going to be the same thing but extended release.

https://fennecpharma.com/

 

Things are happening, not at the pace we want it to, but it is happening.

 

Good news everyone.

CRISPR Breakthrough: Scientists Can Now Turn Genes On and Off at Whim

 

What about RL-81?

 

Do you know what's unforgivable? When my spreadsheet looks better than some of the websites.