Otonomy OTO-413 — Treatment of Hidden Hearing Loss

Hough has said they very much believe it is for chronic too. They just need to prove it with further testing.

 

Their Cowen presentation from today is up:

https://investors.otonomy.com/events/event-details/cowen-40th-annual-health-care-conference

 

When I saw this slide from Otonomy's presentation regarding OTO-413 a few questions came to mind...

On the first graph, it's impressive how there was a huge amount of synapses that were regenerated, but it doesn't seem to have a huge effect on practical hearing (displayed on the second graph). Are the new synapses not as effective? Perhaps hair cell death could be attributed to the lack of hearing restoration? What do you guys think is happening there on the second graph that explains the lack of full auditory function regeneration?



Link to full presentation: https://seekingalpha.com/article/4218731-otonomy-otic-updates-on-otominus-413-program-slideshow

 

It actually seems very good for 10 to 20 Hz but less so at 4Hz and 40Hz. No idea what this means as far as "practical hearing" since you can't do a speech in noise test on a rodent but yes, it could imply those areas were more prone to other non-synapse damage. The trial results later this year on humans will give us a much better idea. Especially in regards to "practical hearing."

 

You meant kHz right?

 

What does "vehicle" mean?

 

Yep. That's what I meant.

 

The delivery vehicle. Basically the gel it's put in.

 

OTO413 + FX-322 are supposed to come out with results by the end of the year.

2020 is quite something at the moment... let's hope it finishes with good news.

 

I think the Hough Pill is using some antioxidant compound. So I would guess that's more for the acute phase. They actually also say so in the title of their paper.

Does somebody know the approach of OTO-413? Has it more potential to also help us (chronic cases)?

Edit: I just read the trial page from OTO-413
https://clinicaltrials.gov/ct2/show/NCT04129775?term=oto+413&draw=2&rank=1
and see that they don't measure tinnitus as an outcome measure and they also exclude tinnitus sufferers from the trial. Why do they do that?

 

OTO-413 uses BDNF, which is a growth factor.

As to why they excluded any tinnitus measurement I suspect it’s because they are trialing OTO-313 for tinnitus at the same time and do not want to cannibalize their results. I personally would have chosen to do otherwise if I was on their research team, but I suspect that’s the case.

 

Thanks @Autumnly for the new report of Otonomy's products. It seems that they excluded the 0-4 kHz range or brought it in the entire range of 0-10 kHz region, making it more impressive than their previous report.

 

Otonomy's June 2020 (15 June) Corporate Presentation is now online.

https://investors.otonomy.com/static-files/01101f4e-d2d9-4104-91cc-af03ac7221fd

 

This is rodent data and rodent frequencies btw. They have different frequency ranges. So far, they haven't had to sacrifice human participants and count their synapses before and after thankfully .

 

Thanks for pointing that out @FGG True. But I don't understand why they put these two ranges together. From what I gather from the previous report, the relatively weak score in 0-4 kHz would normally lower the mean for the 4-10 range if you put them together, but it didn't. So it makes me wonder if they have new input that shows that the lower frequency range scored better than what they had found in initial results. It's still a guess game of how this will manifest in humans, but considering these current results, it is quite positive news.

 

OTO-313:
Buy-and-bill model; high disease burden supports premium pricing

Probably when they find out that some hearing regeneration drug silences tinnitus a few zeros will be appended to the price. I am totally fine with it. The one who solves this should get infinitely rich. I just hope this is still covered by our insurance.

 

Has anyone contacted Otonomy and asked when they might offer compassionate use for OTO-413? Do they have a similar compassionate use page like Frequency Therapeutics has?

Also what is the difference between OTO-413 and FX-322? I know that OTO-413 restores synapses and FX-322 restores IHCs, OHCs and synapses where there is hair cell loss. Is it true that synapses allow us to be able to hear conversations when there is noise in the background and that’s why it is different to FX-322?

 

What do you mean by compassionate use page? Is it on their website?

 

PRETTY POSITIVE that you are accurate and the two treatments work in tandem with each other and are actually complementary to each other. Obviously we don't know how they are going to work individually in order to treat their targeted plan eg FX-322 might treat hidden hearing loss also although am predicting both will be very positive and very necessary treatment.

It also somewhat seems that this treatment is doing the same sort of thing that Hough's pill is proposing to treat regarding synapses.

 

That’s what I’m unsure of. Frequency Therapeutics has a page talking about compassionate use and I was wondering if Otonomy has a page like that on their website.

This is Frequency Therapeutics expanded access policy:
https://www.frequencytx.com/expanded-access-policy/

 

As per Dr. Liberman's research, yes. OTO-413 addresses cochlear synaptopathy with BDNF.

 

Ok I found it on Otonomy website similar to Frequency Therapeutics:

“Expanded access policy
Otonomy is a biopharmaceutical company dedicated to the development of innovative therapeutics for neurotology.
We conduct clinical trials to assess the safety and efficacy of our investigational drugs. The establishment of the safety and efficacy of these drug candidates helps us obtain approvals from regulatory agencies such as the FDA, which approvals are required before these drug candidates can be made generally available to patients. We encourage awareness of and participation in our clinical trials and believe that participating in clinical trials is the best way for patients to access investigational drugs prior to regulatory approval.

At this time, we do not have an expanded access program that allows patients to have access to our investigational products prior to FDA approval. Individuals interested in participating in clinical trials for our products may visit the “Pipeline” section of our website for information on our ongoing clinical trials. We will update this page if we reassess our approach to expanded access programs. If you have any questions, please contact medinfo@otonomy.com.

Otonomy may revise this expanded access policy at any time. Additionally, the posting of this policy by Otonomy shall not serve as a guarantee of access to any specific investigational drug by any individual patient.

https://www.otonomy.com/patient-resources/

 

Ok that’s good so it can still help with hearing loss and has a good chance at passing the clinical trials.

 

I still think you need both treatments but think of it as a puzzle. FX-322 is 2/3 of the puzzle since it restores IHCs and OHCs and OTO-413 is 1/3 of the puzzle since it restores synapses. You may still get a benefit in either of these treatments but to fully recover you need both.

 

Do you guys think OTO-413 has any hope in treating hyperacusis? Maybe FX-322 + OTO-413?

 

It’s certainly possible that a more normalized auditory system could positively impact hyperacusis, but not enough is known at this point. It’s probably safe to assume that some participants in both trials have some degree of hyperacusis. We will know a lot more when results are announced for each current trial (OTO-413 Phase 1/2: Q4 of 2020; FX-322 Phase 2a: likely Q4 of 2020 or Q1 of 2021).

Perhaps, improvements in Hearing Handicap Inventory or Hearing Screening Inventory could provide an indication as to whether or not hyperacusis improved for any participants. I hope a second wave of COVID-19 does not further delay Frequency’s Phase 2a trial.

 

Considering OTO-413 is BDNF, have any of you tried taking supplements containing it (like curcumin) noticing any improvement in hearing? Obviously not going to be nearly as efficient as IT injection, but is it possible to get a therapeutic amount of BDNF into the cochlea by any practical means? Or is the BLB once again our obstacle here?

I tried the aggressive @JohnAdams high dose curcumin program but I can't attribute any of the slight improvements I've had over the past 6 months to it specifically. I was taking anywhere from 1 to 5 grams per day.

 

@Paulmanlike,

What happened to Auris Medical? Did their SNHL drug treatment fail? If so, why do they state they are in phase 3 on their website?

 

AM-111 is their SNHL drug. It's a JNK inhibitor. It is designed to block some of the acute damage from becoming permanent. Since it is for very acute damage (given within 72 hours in the earlier trials), it doesn't apply to most people on this forum so it isn't discussed/followed much here. But it could be useful for re-injuries (like Sound Pharmaceuticals and even the Hough Pill since it was originally planned to be a post "Bomb Blast" pill).

They had another drug AM-101 for acute tinnitus of a few months duration that got discussed more here but they haven't had great results with it.

 

Hopefully this goes well enough that they run a trial with tinnitus patients too.