Otonomy OTO-413 — Treatment of Hidden Hearing Loss

When you say they are still researching it, are there plans for testing it longer than 6 months duration?

 

Yes.

"Next steps for program:

o Complete analysis and submit for presentation at a future medical conference
o Consider higher dose and/or retreatment with OTO-313 (Day 30) to increase % of responders
o Design Phase 2 that considers expanded tinnitus population (e.g., bilateral patients; > 6 months)"

https://investors.otonomy.com/static-files/5d9cb779-996b-49b3-b162-8285d00b6e71

 

Make it 81k shares . Couldn't help but be impressed with Weber at the conference today combined with the market weakness. Could still go lower, but we'll see.

 

I think that they might try, though the thing is that there would be a high apathy towards them if they do. This is because there will be no justification for doing so.

I also believe that this will be a risk for hearing aid companies because this might actually turn people against buying new ones and looking to alternative options. These alternative options include things like the cheaper devices which you can get over the internet and also second hand ones too.

Why spend money on getting the latest inclusions and technology when the benefit is probably very minimal at best, especially when it is going to become much less likely that the extra features like the ones which assist with noisy places like a restaurant are actually needed, and when you can get something slightly older or more basic which fulfills the purpose you want to use it for?

From where I sit, if synapse medicine was available and also if hair cell medicine was possibly going to come out too, hearing aid companies clearly should be doing everything they can to retain customers while the demand for their products is still available. Therefore hearing aid companies would want to get all the sales while they still can.

This is correct and there are two reasons for price hikes. These are that the hearing aid companies and also audiology companies can claim that their overheads will actually increase with a lower demand for devices. Thus they will use this to justify raising prices, although they will likely encompass an additional 'profit' component in this price increase as well because they can take advantage of things this way.

 

Market weakness is not a good thing from the perspective that people might be less likely to invest in these companies engaging in this excellent work and research.

However, the positives of this market weakness are that it is cheaper per share to buy and also secondly that this weakness is affecting the market as a whole and not just solely Otonomy. This is positive because it indicates that this stock price decrease has nothing to do with the performance of Otonomy.

 

In today's Oppenheimer webcast, they did state they wanted to look into cases of tinnitus with longer duration for their phase 2 trial. I believe they said 9 and possibly 12 months from onset.

 

Are they saying the "acute" period may be up to a year in regards to this drug or they feel it may help with chronic tinnitus also (or did they say?)?

 

All valid points my friend and unless someone has some insider knowledge on something negative, I'll continue to chalk it up to overall market weakness.

 

I rewatched the portion of the presentation that covers this (33:30 if you'd like to check it out yourself) and they don't really define acute and chronic tinnitus. Just that the results were so good for those with tinnitus duration of 3-6 months that it's driving them to look at those who have had tinnitus for 9-12 months.

 

The markets simply seem flat at the moment. Many indicators in Australia suggest that the markets will be weak and interest in investment will be seriously subdued until things stabilise from the COVID-19 closures and downturns and people have some direction about what is happening within the economy and markets.

I assume that the same sort of situation is happening in America. I also think that the interest in biotech stock would have been further dampened by the regulation around prescription pricing that Trump has implemented (no matter how good or promising a medicine looks).

To show how fickle the markets are and how down things are right now, we were told that the economists predict property prices to increase between 10-15% over the next two years once things stabilise . Thus I think that if you have the means to invest in things then now might actually be a good time, as I don't see there being a further giant downturn.

 

That's some investment in 1 company with high risk. Be careful.

 

This is the thing with biotechs. Very, very, very high risk. Trading biotechs comes with huge risk, but huge rewards for a few. FREQ is trading low again, seems a lot of biotechnology stocks were hit hard over the last 2 days.

 

I found the most interesting part of the presentation at 18:25, when Dr. Weber seems to contrast his company with Frequency Therapeutics without naming them. He again stresses their drug delivery system and how it's more efficacious than getting multiple injections. It seems to be his company's secret sauce. His use of "all of the target tissue" was also interesting. However, it's not clear to me if they've done any studies (like Frequency Therapeutics has) to show that their drug is actually hitting where they think it's hitting. Before Frequency Therapeutics did their study, they thought they were getting down to the 4500 Hz range, but afterwards they realized they were really only getting their drug to just below the 8000 Hz range.

We'll know soon enough though. If the OTO-413 study shows any hearing improvement (even if it's minor) in the 250 Hz-8 kHz range, Otonomy will have a winner on their hands. Worst case they could license their gel to Frequency Therapeutics, best case OTO-413 and OTO-6XX work and wind up dominating the market.

 

Not trying to be argumentative, but I think that Otonomy has never indicated the treatment is for acute cases only. Rather, cases of short to medium term duration were part of the trial inclusion criteria, which caused people to “assume” the treatment is for “acute” only. Someone please correct me if i am mistaken.

 

People are under that assumption because of the MoA (Mechanism of Action) and the comparison with Auris Medical's Keyzilen (AM-101).

Also, looking into Josef Rauschecker's theories of gates and all that in the brain, established long lasting tinnitus goes beyond the MoA deep into the brain. That's why tinnitus is so difficult to treat.

 

Yes, i picked up on that part of the presentation as well, and not needing multiple injections is wonderful.

 

Yes, entire markets have been red this month.

 

Otonomy has jumped pre-market. Looks like that investor conference has attracted some interest.

 

That's my understanding as well.

 

Just out of interest, hasn't this Rauschecker guy's work been questioned recently and also hasn't he made admissions that he has engaged in an unconscionable way with tinnitus?

 

I'm not sure but where tinnitus is involved, it's all theories and all that. Nobody really knows. It's never been proved anyway regarding his work.

 

Some interesting divergence between FREQ and OTIC over the past 5 days:



https://www.google.com/search?tbm=fin&q=NASDAQ: OTIC#scso=_bSB2X9HdCpK5tQbs86C4CA7:0&smids=/g/11fnmy4kwk&wptab=COMPARE

It's probably nothing, but with so little news to go on, it's interesting to see one climb and one drift down. It's kind of strange, I can find almost nothing on OTO-413. For FX-322, there is a lot of news and a lot of talk in various Facebook groups and forums.

Re-reading the Otonomy Q2 release, it notes this about the OTO-413 study:

I wonder why the first 3 dose cohorts were just 8 people? Also, when the study is done, 30 people will have taken OTO-413, so we'll have a pretty good idea of how it works.

I'm also very curious about when we'll learn more about OTO-6XX. It's been listed on their website for ages, and they've been partnered with Kyorin (whom they're licensing it from) since at least 2016. I wonder how much additional preclinical work is needed before they enter into a Phase I/II study?

 

Otonomy has a near term product that will go on sale to the general public next year (OTO-104) that makes it more attractive near term.

 

I think you have answered this fantastically FGG. From what I have observed, Otonomy has appreciated as the treatment is near release, while Frequency Therapeutics tends to totally be fluctuating just like the rest of the biotechs have been presently.

I would wisely suggest that the reason Otonomy might have delayed the work surrounding other treatments such as OTO-6XX would be partially put down to the fact that they currently have gotten other treatments proceeding through the trials. Furthermore, I wonder whether Otonomy would even contemplate proceeding with this if FX-322 was successful with their trials? I say this because there would be little to no benefit in them investing in the trial procedures for a treatment that may end up being inferior to a competing medicine. I also wouldn't be surprised that if OTO-413 has gotten appropriate results from the phase 1/2 trials that Otonomy might focus on getting this released as soon as they can. This is due to the fact that while it is indicative that FX-322 is ahead at the current time when it comes to regenerative hearing medicine, Otonomy could consequently be ahead with synapse treatments.

Regarding the OTO-413 safety trials/doses, I reckon right now that there is probably a high likelihood that Otonomy knows that the big dose will work better/provide a bigger benefit than the other doses. I think that the reason that they have had to instigate a dosing system with multiple sized dosing is to demonstrate that the treatment is safe, however they can also actually aim to see whether there is a different benefit from giving someone a different sized dose. Usually more is better, however sometimes strange things happen lol

 

I wonder if the BDNF treatment from OTO-413 is capable of healing the auditory nerve. Its intent is for synapses, but I wonder if the drug delivery would have any benefits. My understanding is that BDNF is required for peripheral nerve regeneration.

 

From what I have googled, yes, it does have positive impacts on nerve regrowth. Right now I am actually wondering whether many of us are going to need auditory nerve treatment though since it appears that the vast majority of us probably only need hair cell and synapse treatment?

This is a piece of research I have happened to find that explains this too:

BDNF gene therapy induces auditory nerve survival and fiber sprouting in deaf Pou4f3 mutant mice

There has also been research from over 20 years ago that indicates the nerve(s) can be redone with BDNF. As a result, I am wondering when we hear comments from organisations like Hough Ear Institute and Frequency Therapeutics that their treatments may have restored nerve ends, maybe these are the nerve ends they are actually referring to?

 

Otonomy has its "proprietary otic drug delivery technology" which will make or break its upcoming drugs. At this point it looks like FX-322 can't reach the lower frequencies. Even with repeated dosing it'd be kind of shocking if there were improvements at 4,000 Hz. If Otonomy really can reach the lower frequencies, then OTO-6XX could be a true hearing aid replacement. It'd blow FX-322 out of the water (though it'd be several years behind - at least 3).

It's one reason I'm kind of excited about the upcoming OTO-413 results. Even if OTO-413 only leads to modest hearing improvements (ex: 10dB), if it shows this at a lower frequency it means OTO-6XX will have incredible potential.

 

I don’t think that there is unequivocal proof that FX-322 cannot get to the lower frequencies or that Frequency Therapeutics is not going to try to make FX-322 reach the lower frequencies.

Frequency Therapeutics has hinted on multiple occasions that treatment of all frequencies is most certainly on the agenda. They have given clues like there are some very clever drug dosing people around so who knows what might happen, therefore implying that they’re trying to get FX-322 working better.

Furthermore when you link their comments about dosing with the fact that Frequency Therapeutics have been ultra conservative with their expectations about FX-322 and its outcomes to avoid FDA sanctioning, you can clearly see why Frequency Therapeutics won’t comment about FX-322 in anyway outside what they can safely comment on.

Finally Frequency Therapeutics have a model now which seemingly is to get FX-322 approved in the fastest way possible and then take it and play around with things like dosing after. This way Frequency Therapeutics can commence treatment ASAP and deal with the other things like dosing or reformulation later.

So while Otonomy’s OTO-6XX treatment may be able to reach the lower frequencies sooner than FX-322 if they have superior dosing method, I would not rule out FX-322 working on getting the treatment into the lower frequencies and also being able to achieve this.

 

Just a note on the partnership with Kyoto’s for OTO-6XX. There was actually an announcement about this in August. As a result of this announcement, I can reasonably assume that there is going to be something further happening with this treatment in the near future as it is incredibly unlikely that an official announcement like this would have been made otherwise.

Otonomy Announces Exclusive License Agreement with Kyorin for Novel Compound in OTO-6XX Hearing Loss Program

 

I'm not ruling out Frequency Therapeutics coming up with a better delivery method, but it clearly seems that it's a non-trivial thing to do, and they haven't given any sign that they have something for it in the works. In recent conferences they've stated that FX-322 was "designed" to target the higher frequencies. This is spin.

Don't get me wrong, I'll be thrilled if tomorrow they announce that they have a reformulation ready that can hit the lower frequencies, but I haven't seen any indication that that's what they have in store.