Otonomy OTO-413 — Treatment of Hidden Hearing Loss

From what I have read, their Meniere’s drug could treat the very low frequencies, however I am wondering whether they have stayed silent on this because they don’t want to get in trouble with the FDA for making false assertions and claims about their drug delivery which is unproven officially at this stage.

I think Otonomy and Frequency Therapeutics will be able to treat lower frequencies, however it is going to be a matter of time. Thus Otonomy will need to show it when they commence their clinical trials, though they seem to have implied that they can treat all areas in the ear. Frequency Therapeutics' FX-322 results tend to depend on what happens with the current trial and as I think has been said before multiple times, I think it will be a matter of waiting and seeing what happens with the current trial before they contemplate revising or redoing their dosing. I definitely think that if FX-322 is successful but doesn’t just say work below 5000 Hz then they will revise its dosing due to wanting to provide proper and comprehensive treatment.

 

Their Meniere's drug isn't for hearing loss so it would be weird and inappropriate to report anything about penetrance for hearing.

However, they are using the same extended release for other drugs (presumably OTO-6xx). Your conference call summary said their technology penetrates the whole cochlea.

You wrote:

I'm not disputing this at all (because i think their drug delivery technology is excellent), but did they say how they confirmed that? That would probably put a lot of people's minds at ease. What was their exact wording?

 

I haven’t got a transcript, sorry, but the president said that the thing that makes them stand out is the fact that they can deliver a broad treatment from a single intratympanic injection which will avoid the need to patients to have retreatment or redosing later. The president then referred to the fact that you can look at the outcomes from the medicines trialled up to now such as OTO-313 and Otividex to demonstrate these outcomes.

Obviously I cannot see in the transcript post where I wrote cochlea, when I searched for this, sorry.

 

You can get a transcript here:

https://seekingalpha.com/article/43...r-on-q3-2020-results-earnings-call-transcript

You'll need to turn off JavaScript in your browser to read it. In Firefox this can be done like so:

1: Type "about:config" in the URL bar of your browser.
2. Search for "JavaScript", and disable it.

I use Firefox as my no-JavaScript browser. It's good for reading articles on news sites that bug you. This works for a surprisingly large number of sites (ex: New York Times).

 

"That delivery technology and the ability to deliver high concentrations of drug for an extended period, the hallmark of that, why that is so important to us is the ability to drive efficacy that you're getting enough drug in. And I think this is one of the things you're seeing about our program that compares differently to other companies in the field. And I mean, multiple companies that have been working in the otology space, the need to retreat and undergo multiple re-treatments as opposed to our practice of doing a single intratympanic injection to cover a broad patch of time is inherent to our technology and strong IP position around drug delivery to the ear. And that really we believe drives efficacy. So while it's very convenient for the physician and for the patient and will aid in the commercialization of a product, importantly, we think it's an important determinant of efficacy, and so I think that's probably the most important."

 

Any word on when phase 1 results will be out?

 

They haven't specified other than Q4/2020, according to their November corporate presentation, so by the end of this year. Hopefully sooner rather than later.

 

Otonomy is to participate in two upcoming investor conferences; webcasts will be available on their website after the events, on December 1 and December 2.

https://www.globenewswire.com/news-...ate-in-Two-Upcoming-Investor-Conferences.html

 

Potentially big news?

 

Investor conferences are pretty run of the mill events, but hoping for something

 

They actually announced them at the end of their Q3 financial results call, so they've been planned for a while. The soonest possible they could have gotten the results is Oct 27 (if they filled the study the same day they said they were almost full). But I think it's more likely it took another week or 2 after they posted their "almost full" message for the study to be filled. If processing the results takes 3 weeks (like it did for OTO-313), then we should expect results pretty soon - maybe the first or second week of December.

I suppose there's still a chance they could say something about the results this coming week. If they did, it'd be pretty exciting. However, it's also the week of Thanksgiving, which isn't a good week to put out big news.

 

One of the conferences has a pre-recorded "Fireside chat" which can be listened to:

https://investors.otonomy.com/events/event-details/piper-sandler-healthcare-conference

Talk on OTO-413 starts at 2:30. However, nothing new is discussed. The CEO mentions that the read-out will come "at the end of the year", so I'm thinking they'll release the top-line data sometime after mid-December.

 

Otonomy Provides Update on OTIVIDEX® and OTO-313 Programs

"Otonomy intends to evaluate the same dose for OTO-313 in a Phase 2 trial that will enroll an enriched unilateral tinnitus patient population. To enrich the study population, Otonomy intends to exclude patients with severe hearing loss and increase the minimum TFI score required for entry. The company will also expand the unilateral patient population eligible for enrollment by increasing the time from tinnitus onset, and will extend the observation period to assess durability of the treatment effect."

 

Sounds promising.

 

I noticed yesterday (December 1st) that they didn't post anything about the Evercore ISI 3rd Annual HealthCONx Conference. I watched the Events page at 3:05 but nothing ever showed up, and no stream was ever posted:

https://investors.otonomy.com/news-...rticipate-two-upcoming-investor-conferences-1

Today they have the Piper Sandler 32nd Annual Healthcare Conference, but that is listed as a 1-on-1 meeting, with no video (the only video is a pre-recorded session from the 16th).

 

When are the OTO-413 results going to be released? Otonomy should have released their results last month. This better not be another Audion Therapeutics failure.

 

No, they shouldn't have had the results released last month. Many comments were made in their chats etc that they were going to end up releasing them in December.

 

I'm assuming Otonomy is performing these trials in San Diego? That's their contact address on their website. Man... that's right down the road from me.

 

Looks like yesterday's stream is now up:

https://investors.otonomy.com/events/event-details/evercore-isi-3rd-annual-healthconx-conference

I'll update if there's anything new / interesting (though I expect there won't be).

 

Talk focused on OTIVIDEX and OTO-313. I took these notes:

• OTIVIDEX treatment lasts around 3 months. They expect some patients to get treated every 3 months, while others will only come in when needed. On average they expect patients to get 2 doses a year. Though it wasn't said, I think they're planning the same type of model for OTO-313... and maybe the other drugs in their pipeline too? When I was researching BDNF / synapses repair, in one of the studies I read it stated that the synapses created by BDNF in pigs weren't that durable. After a certain period of time (I can't remember - maybe 6 months?), many of the new ones died off. If the same is true in humans, I bet the plan will be to just have people continuously be re-treated.
• Interviewer: What causes tinnitus? Answer: (paraphrased) Tinnitus is triggered by cochlear injury. Injury is causing a looping of signaling from hair cells, leading to release of Glutamate. OTO-313 attempts to break this looping.
• Though it wasn't said, Dr. Weber has previously stated that he wanted to up the dosage of OTO-313 for Phase 2 and was hoping the FDA would approve that idea without making them re-do Phase I. They're not upping the dosage, so I'm assuming the FDA denied their request. Kind of a bummer.

 

Are we getting Phase 1 results for both drugs?

 

OTO-313 Phase 1/2 results were released earlier this year, if that's what you're referring to.

 

What's the point of having two separate drugs for chronic and acute tinnitus?

 

OTO-413 is a synaptopathy drug so it's aimed more broadly at hidden hearing loss and repairing the lost synaptic connections. The hypothesis is that this will help with tinnitus and possibly some forms of hyperacusis, as Liberman says. I'm honestly not too clued up on OTO-313 - according to Otonomy's website it's "a sustained-exposure formulation of gacyclidine, a potent and selective NMDA receptor antagonist."

I do think that most of us here would benefit more from OTO-413.

 

Just a another example of the useless bureaucracy of the Failed Drug Administration or FDA (have to sound professional). If OTO-313 works better in higher dosages, why not just let them do it. This is just another reason the FDA should be abolished and reformed with 100% new staff from the top down. How many other drugs for anything would likely have worked better and been approved if they were just allowed to up the dosage a little as long as it's the same drug and they're not changing mid way through a phase like 20 mg one week and then switching to 50 mg the next.

I hope OTO-313 works regardless of the FDA trying to hinder its potential.

 

Otonomy has a lot of drugs in the works:

https://www.otonomy.com/pipeline/

The most important are:

• OTO-313: Tinnitus. Passed Phase I/II with positive results earlier this year.
• OTO-413: Hidden Hearing Loss (i.e., understanding words when there's background noise). However, many people on this forum suspect that this will help tinnitus. Bad tinnitus was part of the exclusion criteria for the study, but I'd be surprised if there wasn't at least 1 person with tinnitus in the study.
• OTO-6XX: Hair cell regeneration. Little is known about this drug.
• OTIVIDEX: Vertigo / Ménière's disease. This is the most important drug in their arsenal (from a financial stand point). It's Dexamethasone + Otonomy's extended delivery gel. It famously failed its US Phase 3 trial back in 2017 and caused its stock to crash ~85%. However, a second Phase 3 trial they were doing in Europe passed (this came a month or two after the first Phase 3 trial results). They believe their US Phase 3 trial failed due to higher than expected placebo effect. They've done a bunch of stuff to prevent the same thing from happening and are wrapping up a new Phase 3 trial soon. If it passes, Otonomy will have a lot of success, if it fails, the company will be in a lot of trouble financially.

 

I think that it is very likely that most of us will benefit from a synapse medicine whether it is PIPE-505 or this.

If people need to get redosed every 6 months or so hypothetically with OTO-413 then consequently, I can see this medicine as having to be very cheap in order to enable people to use it and also make them want to use it.

In regards to OTO-313, I wonder whether they will use multi dosing instead to get around this or whether they will simply aim to release the medicine first in the current dose if they can do so and then look at upping the dose later on after approval. At this stage I think they have learnt the benefits of getting the dosing right early on in the Phase 1/2 trial, hence why they did multiple dosing with OTO-413.

 

I'm curious as to which drug would be preferable - PIPE-505 or OTO-413?

 

Why would OTO-413 have to be redosed every 6 months? Are you confusing it with Otividex?

 

I’m going off of what @patorjk posted in the post of theirs I quoted when he makes references to a pig and states BDNF synapses aren’t that durable.

Pretty much my comment was a direct reply to what he had posted.