Episode 16: The Sound of Science — Otonomy

[Tinnitus Talk]

Hey there!

Very few commercial drug companies focus on hearing disorders. Even fewer focus on tinnitus. Otonomy does both. In this episode of the Tinnitus Talk Podcast, we spoke with David Weber (PhD), President and CEO, and Alan Foster (PhD), Chief Scientific Officer.

They shared their views on what they see as the "renaissance" of hearing research and how there is currently more investor appetite to address hearing issues. We discussed why Otonomy is not only seeking solutions for different kinds of hearing loss, but also tinnitus specifically. The interview covers each of the company's drugs in-depth, from its mechanism of action to commercialization plans.

For our Patrons, we also have a video version of this interview. Support our work!



​

Listen on:

• Tinnitus Talk Podcast (incl. timestamps and transcript)
  
• SoundCloud
  
• Apple Podcasts
  
• Spotify

We welcome any discussion, but please keep the following in mind when commenting:

• Off-topic comments, i.e. not directly responding to the content of the podcast, will be removed. So please do listen before commenting!
• While we welcome constructive criticism on ideas or policies, we do not tolerate direct attacks on individuals.

This episode was produced by @Markku and @Hazel, with the support from the following volunteers: @FGG, @Andrea Rings, and @AfroSnowman. Do you want to volunteer as well? Let us know!

We thank our Patreon supporters for making this podcast possible.

Don't forget to:

• Send Ideas and Suggestions for Future Podcast Episodes

Sharing Is Caring
Share the podcast on your social media and with your tinnitus friends!

 

[Óscar PP]

Very interesting, thank you! Hopefully something good comes out soon.

 

[Paulmanlike]

A bit devastating when they talk about OTO-313 and chronic tinnitus becoming central, as opposed to peripheral. Wasn't this what Rauschecker was talking about?

I would also have liked to hear their thoughts about OTO-413 and hearing regeneration resolving tinnitus.

Nevertheless, thank you for putting this out!!!

 

[Hazel]

A bit devastating when they talk about OTO-313 and chronic tinnitus becoming central, as opposed to peripheral. Wasn't this what Rauschecker was talking about?

Yeah. I must say this is in line with my personal theory, i.e. that tinnitus gets "centralised" in the brain over time, which would mean that resolving the original cause no longer helps. But I try not to let my personal views shine through too much during the interviews . Indeed, Rauschecker, and for that matter most neuroscientists, tend to believe the same. But on the other hand, it's not scientific consensus per se...

I would also have liked to hear their thoughts about OTO-413 and hearing regeneration resolving tinnitus.

We did talk about OTO-413 and I asked whether they had any anecdotal reports of it affecting tinnitus (no). I did not explicitly ask whether they believe it could help tinnitus, but considering their theory of centralisation I'm guessing the answer would at best be "maybe." (Which is anyway what almost all the experts say.) I guess there's always some questions you inevitably miss out on

Nevertheless, thank you for putting this out!!!

Thanks! It was a lot of work, so always nice to be appreciated

 

[Paulmanlike]

Yeah. I must say this is in line with my personal theory, i.e. that tinnitus gets "centralised" in the brain over time, which would mean that resolving the original cause no longer helps. But I try not to let my personal views shine through too much during the interviews . Indeed, Rauschecker, and for that matter most neuroscientists, tend to believe the same. But on the other hand, it's not scientific consensus per se...

We did talk about OTO-413 and I asked whether they had any anecdotal reports of it affecting tinnitus (no). I did not explicitly ask whether they believe it could help tinnitus, but considering their theory of centralisation I'm guessing the answer would at best be "maybe." (Which is anyway what almost all the experts say.) I guess there's always some questions you inevitably miss out on

Thanks! It was a lot of work, so always nice to be appreciated

You are very much appreciated @Hazel and I thank you and the other guys who do the work.

I've only had a chance to skim over it but I will tune in for a proper listen.

I'm starting to think avenues affecting the brain may be the way to go for a treatment for tinnitus. We will see how these companies investigating that pathway get on... the search continues!

 

[Kleiner]

Yeah. I must say this is in line with my personal theory, i.e. that tinnitus gets "centralised" in the brain over time, which would mean that resolving the original cause no longer helps. But I try not to let my personal views shine through too much during the interviews . Indeed, Rauschecker, and for that matter most neuroscientists, tend to believe the same. But on the other hand, it's not scientific consensus per se...

We did talk about OTO-413 and I asked whether they had any anecdotal reports of it affecting tinnitus (no). I did not explicitly ask whether they believe it could help tinnitus, but considering their theory of centralisation I'm guessing the answer would at best be "maybe." (Which is anyway what almost all the experts say.) I guess there's always some questions you inevitably miss out on

Thanks! It was a lot of work, so always nice to be appreciated

According to the various theories and studies on the subject, the majority of tinnitus is central (DCN, auditory cortex), you are right.

But that doesn't mean they're "stuck" in the brains.

To declare tinnitus as "stuck" is to deny cerebral plasticity. And we know that cerebral plasticity is at the origin of tinnitus.

Solving the initial problem should improve symptoms, perhaps the neuromodulation / Kv7 2.3 modulator could help this process.

 

[Hazel]

According to the various theories and studies on the subject, the majority of tinnitus is central (DCN, auditory cortex), you are right.

But that doesn't mean they're "stuck" in the brains.

To declare tinnitus as "stuck" is to deny cerebral plasticity. And we know that cerebral plasticity is at the origin of tinnitus.

Solving the initial problem should improve symptoms, perhaps the neuromodulation / Kv7 2.3 modulator could help this process.

To be clear, I never said that tinnitus gets "stuck" in the brain, only that it gets centralised, which is not the same thing. I also never said that it therefore cannot be resolved, nor did I deny neural plasticity. In other words, I think you completely misinterpreted my point.

 

[Kleiner]

To be clear, I never said that tinnitus gets "stuck" in the brain, only that it gets centralised, which is not the same thing. I also never said that it therefore cannot be resolved, nor did I deny neural plasticity. In other words, I think you completely misinterpreted my point.

I quote you: "which would mean that resolving the original cause no longer helps"

For me that means: "treating hearing loss (if there is one) will not cure your tinnitus"

If I misinterpreted your words, I apologize. But there are still too many people talking about this 'it's stuck in the head' theory, destroying any hope of seeing a cure one day.

 

[Hazel]

I quote you: "which would mean that resolving the original cause no longer helps"

I should have worded that more carefully, i.e. it "could" mean that resolving the original cause no longer helps. The fact is no one knows for sure. But plenty of experts, including the Otonomy folks, believe that curing tinnitus would likely require more than only fixing the original cause for chronic cases, and I tend to believe them. I did not however mean to insinuate that fixing the original cause would not help in any way.

But there are still too many people talking about this 'it's stuck in the head' theory, destroying any hope of seeing a cure one day.

I fail to see how a belief in the centralisation theory "destroys any hope for a cure." It only means that to find a cure we should not only look at the ears, but also at the brain. I believe that's a very sensible approach, and supported by a lot of the science.

 

[csaaphill]

Yeah, the brain is what creates this crap. Why not look at ways to short out the electrical pulses the brain creates, then sends to the eardrum and cochlea to be translated back as music or words etc...

Technically speaking it's not hallucinogenic, since it is created by the brain, it's physical, just not heard by anyone else but us.

So yeah, why not treat the brain with something that can short this stuff out?

Since I can't hear well, I am reading the transcript of this Tinnitus Talk Podcast. Very interesting.

I've always had trouble hearing in crowded places. I've never been able to tune out the background noise and that may be part of my problems now? I've had not chemotherapy so to speak, but I've had cancer treatments and those may have contributed to my hearing loss and MES (Musical Ear Syndrome) that I have?

I wish I could put a wire in my brain and hook it up to a listening device and let people hear what I hear. They'd freak out! Seriously mine's so weird, paranormal and supernatural are what would come to people's minds if they could hear this stuff I hear 24/7.

CT and MRI scans show nothing so the only other option I have now is an EEG. I truly hope it finds something for if it doesn't, I'm left with paranormal activity since I am not crazy not schizophrenic!

The thing that gets me is MES is not psychotic in any way but the main treatment is antidepressants that I believe started mine to begin.

But reading the transcript, OTO-313 and the rest of Otonomy's work seem promising!

 

[tommyd87]

I should have worded that more carefully, i.e. it "could" mean that resolving the original cause no longer helps. The fact is no one knows for sure. But plenty of experts, including the Otonomy folks, believe that curing tinnitus would likely require more than only fixing the original cause for chronic cases, and I tend to believe them. I did not however mean to insinuate that fixing the original cause would not help in any way.

I fail to see how a belief in the centralisation theory "destroys any hope for a cure." It only means that to find a cure we should not only look at the ears, but also at the brain. I believe that's a very sensible approach, and supported by a lot of the science.

Yeah, the brain is what creates this crap. Why not look at ways to short out the electrical pulses the brain creates, then sends to the eardrum and cochlea to be translated back as music or words etc...

Technically speaking it's not hallucinogenic, since it is created by the brain, it's physical, just not heard by anyone else but us.

So yeah, why not treat the brain with something that can short this stuff out?

Since I can't hear well, I am reading the transcript of this Tinnitus Talk Podcast. Very interesting.

I've always had trouble hearing in crowded places. I've never been able to tune out the background noise and that may be part of my problems now? I've had not chemotherapy so to speak, but I've had cancer treatments and those may have contributed to my hearing loss and MES (Musical Ear Syndrome) that I have?

I wish I could put a wire in my brain and hook it up to a listening device and let people hear what I hear. They'd freak out! Seriously mine's so weird, paranormal and supernatural are what would come to people's minds if they could hear this stuff I hear 24/7.

CT and MRI scans show nothing so the only other option I have now is an EEG. I truly hope it finds something for if it doesn't, I'm left with paranormal activity since I am not crazy not schizophrenic!

The thing that gets me is MES is not psychotic in any way but the main treatment is antidepressants that I believe started mine to begin.

But reading the transcript, OTO-313 and the rest of Otonomy's work seem promising!

It might be possible that you will need to fix more than the 'original/underlying' cause of tinnitus in order to overcome it.

I do however question why when we see other causes of issues relating to nerves etc in the body resolved, such as by treating burns or when you have hips replaced for example (both which have supported and verified research to back this), that the same scenario could not happen for tinnitus.

The thing that I think we are all going to agree on is the fact that at this stage we simply do not know one way or the other.

 

[Tezcatlipoca]

Yeah, the brain is what creates this crap. Why not look at ways to short out the electrical pulses the brain creates, then sends to the eardrum and cochlea to be translated back as music or words etc...

Technically speaking it's not hallucinogenic, since it is created by the brain, it's physical, just not heard by anyone else but us.

So yeah, why not treat the brain with something that can short this stuff out?

Since I can't hear well, I am reading the transcript of this Tinnitus Talk Podcast. Very interesting.

I've always had trouble hearing in crowded places. I've never been able to tune out the background noise and that may be part of my problems now? I've had not chemotherapy so to speak, but I've had cancer treatments and those may have contributed to my hearing loss and MES (Musical Ear Syndrome) that I have?

I wish I could put a wire in my brain and hook it up to a listening device and let people hear what I hear. They'd freak out! Seriously mine's so weird, paranormal and supernatural are what would come to people's minds if they could hear this stuff I hear 24/7.

CT and MRI scans show nothing so the only other option I have now is an EEG. I truly hope it finds something for if it doesn't, I'm left with paranormal activity since I am not crazy not schizophrenic!

The thing that gets me is MES is not psychotic in any way but the main treatment is antidepressants that I believe started mine to begin.

But reading the transcript, OTO-313 and the rest of Otonomy's work seem promising!

You have obvious hearing issues. How can you say this is a brain thing?

 

[csaaphill]

You have obvious hearing issues. How can you say this is a brain thing?

Have you not read up on MES i.e. Musical Ear Syndrome? If not, I recommend you research it, for it's the brain that causes the music and or other noise people hear. Yes, lack of hearing is the beginning but it's the brain with lack of hearing that causes this mess. The brain needs that feedback from hearing and when it's not getting it, it creates its own.

Plus I'm not saying it's a brain thing, but that the brain does create this mess. The brain is a powerful tool and weapon and can create all kinds of mess. Plus I believe mine wasn't totally due to hearing loss for I had lived with hearing loss for years until I began to take Gabapentin which is what I believe caused my MES. I've now been living with MES for almost a year.

Gabapentin in my own research is guilty of causing visual and auditory hallucinations. Its effect on my brain, along with my left ear's history of misinterpreting what I thought I heard helped cause the musical hallucinations I hear now.

Right now I need something to short this crap out which is the electrical impulses that are making this music crap I hear. Regeneration of the cochlear is a good idea but may not stop this crap I hear now and may make it worse if the brain isn't treated too!

I never said it wasn't a hearing issue but the effects of the hearing issue are brain-related. OR at least what I read on, so going off that.

 

[Greg Sacramento]

Otonomy patents may be second or third for value in biotech. Old retired MIT researcher friend is up to date on the research references in this article and added new references from those. He thinks that Otonomy will be the leader in helping those with hearing loss and tinnitus. I probably won't be around to know.

I expect the company to do an INT offering in the hundreds of millions within 2 years that will support price and get Wall Street attention.

It's the references that's important and new university study references from those can be requested.

Otic Drug Delivery Systems: Formulation Principles and Recent Developments

 

[AfroSnowman]

INT offering

Thanks Greg. I don't want to drag this thread into investor talk, but what does INT offering mean?

 

[Greg Sacramento]

what does INT offering mean?

When an institution such as ones holding shares below (partial holding list) buys an offering of shares at a fixed price to give company working capital.

Institution Name Shares Held % Outstanding - Otonomy
Baker Bros. Advisors LP 7,694,038 13.57 Increased holdings
Federated Hermes Global Investment Management Corp. 4,856,200 8.57
Adage Capital Management, L.P. 4,000,000 7.06 Increased holdings
RA Capital Management, LP 3,092,294 5.46 Increased holdings
The Vanguard Group, Inc. 2,442,617 4.31

Drug delivery will take time, but from article I posted above - lots of study going on as seen in the many article references. Most encouraging is that one can follow these references for updates, but it would involve emailing. I know one retired MIT researcher involved with this and he favors Otonomy over Frequency Therapeutics. All too much for me to tag as I have lots of physical problems, but last year, I did email a few selected references for updates. Not interested in stock prices. If you are young or middle age there's much hope. I literally pray for you.