Q4 2020 Otonomy Inc Earnings Call
Good afternoon, ladies and gentlemen, and welcome to the Q for 2020 financial results and business update conference call. At this time all participants are in listen only mode. Later, we will conduct a question and answer session and instructions will follow at that time, if anyone should require assistance during the conference.
Please press Star then zero on your Touchtone telephone I would now like to turn the conference over to your host Mr. Robert Oh. Thank you Sir Please go ahead.
Thank you good afternoon, and welcome to Autonomies fourth quarter, and full year 2020 financial results and business update conference call.
Joining me on the call from autonomy are Dr. David Weber, President and Chief Executive Officer, and Paul Cayer, Chief financial and business Officer.
Before I turn the call over to Dr. Weber I would like to remind you that.
Pardon me todays call will include forward looking statements based on current expectations such statements represent managements judgment as of today and may involve risks and uncertainties that could cause actual results to differ materially from expected results.
Such statements include but are not limited to statements relating to the timing of results and activity for ongoing clinical trials statements relating to the use of and expectations regarding the negative binomial model for the phase III clinical trial of <unk>.
Plans to submit a new drug application and regarding launch preparation.
Expectations regarding design patient enrollment initiation and timing of results for planned clinical trials expectations regarding preclinical programs, including statements regarding development studies and activities data presentations and development timelines statements relating to the potential benefits of and activities.
Under the license agreement between Otani me and Kieran expectations regarding Autonomies business plans and market opportunity and expectations regarding cash runway and autonomy as ability and resources to support its product pipeline and development activities.
These refer to Autonomies filings with the SEC, which are available from the SEC or on the autonomy website for information concerning the risk factors that could affect the company I'll now turn the call over to Dave Weber, President and CEO of autonomy.
Yeah.
Thank you Robert Good afternoon, everyone and thank you for joining us on this call to discuss Autonomies business updates as well as financial results for the fourth quarter and full year.
'twenty 'twenty was both a productive and successful year for autonomy key accomplishments included the following.
We completed patient enrollment in the phase III trial of <unk> and veneers disease and are on track to announce results by the end of February.
We announced positive clinical results for OTO 313 in tinnitus and are working to initiate a phase two trial this quarter.
We announced positive clinical results for auto for 13, and hearing loss and plan to start an expansion of the trial in the second quarter.
We expect that result from both the OTO 313 phase two trial and OTO for 13 extension study will be available mid 'twenty 'twenty two.
We also advanced our multiple preclinical programs, including a gene therapy program for the most common cause congenital hearing loss.
To help fund this broad and rich pipeline, we completed a successful financing debt attracted new top tier biotech investors to the company and significantly significantly extended our cash runway.
Overall, I am very proud of our accomplishments during 2020 and excited to continue our progress this year beginning with the <unk> phase III readout later this month.
During this call I'll provide a brief update on our programs and then ask Paul to summarize the financial results. We can then open up the line for any questions.
Beginning with the <unk> phase III trial them in years disease, we enrolled a total of 149 patients from the United States and Europe exceeding our target of 142 patient.
In November we announced that a review of the revised statistical analysis plan by the F. D. A confirmed you for the negative binomial model for analysis of the primary endpoint for this trial.
We proposed use of the negative binomial model because we believe it provides the best fit of the <unk> clinical data based on the phase II B trial, the averts two trial and the integrated data set from both trials.
The final patients in the trial completed their last visit just before the end of December enabling us to announce results by the end of February.
Assuming positive results, we plan to submit a new drug application to the FDA in the third quarter of 'twenty 'twenty one.
Turning to other 313 for tinnitus, we have completed our planning for the phase II trial, which is based on the positive phase one two results, we announced last year.
This trial will enroll a total of 140 patients with unilateral tinnitus or at least moderate severity as measured by the tinnitus functional index or T F I.
As in the prior trial, where we observed a high correlation between the various metrics in responders. We will also attract tinnitus loudness and annoyance and patient global impression of change.
To enrich the study population the trial will exclude patients with severe hearing loss, who we believe are less likely to respond to treatment.
And we are increasing the minimum T F I score required for entry to improve prove our ability to see a treatment benefit.
We will also expand the patient population eligible for enrollment by increasing the time from tinnitus onset from six months to one year.
Finally, while we will continue to use responsive both months wanted to following a single treatment for primary efficacy. We will also extend the total observation period out to for months to assess the durability of the treatment effect.
Our clinical team is working to finalize the operational aspects of this trial in order to initiate the study by the end of this quarter and we expect to have top line results in mid 'twenty 'twenty two.
Our third clinical stage program is OTO 413, a sustained exposure formulation of brain derived neurotrophic factor or bdnf that we are developing for hearing loss due to cochlear snap top iffy.
Recent research has identified damage to synaptic connections as an underlying pathology in noise and age related hearing loss that manifests as speech in noise hearing deficit.
Neurotrophic factors, including Bdnf have potential therapeutic effects in the cochlea by promoting the survival of spiral ganglion neurons, increasing neurite outgrowth and reconnecting neurons with cochlear hair cells after damage.
In December we announced positive topline results from our phase one two trial that provides clinical validation of this therapeutic approach for hearing loss.
Ascending dose trial demonstrated.
Demonstrated that a single interest tympanic injection of OTO for 13 was well tolerated across all dose cohorts.
Furthermore, the therapeutic activity of OTO for 13 versus placebo with demonstrated for multiple clinically validated speech in noise hearing tests at consecutive time points of day, 57, and 85 compared to placebo.
Beginning in the second quarter of 'twenty 'twenty, one we plan to enroll additional hearing loss patients in an expansion trial to evaluate a refined study protocol in preparation for phase two.
This expansion study will randomize subjects to a single treatment with OTO for 13, or placebo and evaluate a reduced number of endpoints focusing on the three speech in noise hearing tef assessed in the initial patient cohorts.
These are the digits annoys words, and noise and American English matrix tests that uses phrases.
Enrollment criteria, Syria will continue to target a broad hearing loss population to support the design of a phase two trial, we expect topline results from the expansion study to be available in mid 'twenty 'twenty two.
Yeah.
Finally, a brief update about our three preclinical programs that are focused on additional hearing loss paths allergies and patient populations.
The first of these is auto 825 hour gene therapy collaboration with a G. T C that targets G. J b two the most common cause of congenital hearing loss.
Patients born with this mutation can have severe to profound deafness in both ears that is identified in screening tests now performed routinely in newborns.
We presented preclinical results from the past year, demonstrating that a gene of interest can be expressed and support cells of the cochlea.
Which are the relevant target cells for treating G. J b two deficiency.
Using novel and proprietary AAV capsid.
Also consistent X gene expression was observed for at least 12 weeks following a single local administration in nonhuman primates.
These results supported selection of OTO 825 for advancement into I N D enabling studies.
We have recently generated some very exciting preclinical results for this program that we look forward to presenting at an upcoming conference.
We also presented data during 'twenty 'twenty related to our our OTO 510 program targeting other protection for patients at risk for cisplatin induced hearing loss or C. I H L.
Cisplatin is a potent chemotherapeutic agent that is widely used to treat a variety of cancers in adults and children.
Unfortunately, it is also commonly associated with severe adverse effects, including cisplatin induced hearing loss net of the progressive bilateral and irreversible.
We have identified a novel class of agents that potentially bind to cisplatin and provide greater OTO protection in preclinical models, the known anti oxidant anti apoptotic molecules and increased potency relative to relative to other cisplatin binding molecules currently in clinic.
<unk> development.
These results highlight the therapeutic potential of our locally delivered OTO 510 product candidate to provide superior other protection without tumor protection.
Our third preclinical program Boto, six X X targets per cell repair and regeneration as an approach to treating patients with severe hearing loss.
It is well established that damage to cochlear hair cells through aging excessive noise or exposure to ototoxic chemicals leads to hearing loss and that these sales do not regenerate naturally.
In a similar way that we are repairing Toronto connections to herself with BD and F. We believe it is possible to repair and regenerate the hair cells themselves through drug treatment.
During 2020, we entered an exclusive license agreement with Kieran pharmaceutical company, providing us with worldwide rights to develop and commercialize one other novel compounds for the treatment of hearing loss.
This program is complementary to auto for 13 and expands our targeted patient population to include those with severe hearing loss.
In summary, Twenty-twenty was a very successful year for autonomy as we made significant advancements across our broad pipeline.
The positive clinical results for OTO 313, and OTO for 13 provided validation for these programs and position us as the only company in the neuro otology field with clinical stage programs for both tinnitus and hearing loss to large patient populations with significant unmet.
Medical need.
Furthermore, we are excited to be approaching the highly anticipated completion of our <unk> phase III trial in many years disease and following positive data look forward to shifting our focus to the NDA submission and launch preparation.
And finally, our low our gene therapy, and other preclinical assets received little attention because of the focus on our clinical assets. These programs address important indications and we plan to share compelling preclinical data and information about development timelines in the coming months.
With that I'll turn the call over to Paul Kerr, our Chief financial and business Officer, who will provide a summary of our financial results and plan.
Thank you, Dave and good afternoon, everyone.
Overall, our expenses for 2020 were in line with our financial guidance and our cash balance reflects the successful financing we completed in July.
Now let me briefly recap the financial results from 2020 that are more fully described in today's earnings release and 10-K filings.
In the fourth quarter of 2020, we reported total non-GAAP operating expenses of $8 5 million with GAAP operating expenses totaling $10 1 million.
The primary adjustment for non-GAAP expenses is exclusion of stock based compensation.
So this is the financial metric that best approximates our spending level.
For the full year 2020, total non-GAAP operating expenses were $36 5 million with GAAP operating expenses totaling $42 6 million.
These expense levels were in line with our financial guidance.
And demonstrate our ongoing commitment to carefully manage our spend.
As of December 31, 2020, we held a cash balance, including cash cash equivalents and short term investments totaling $86 3 million.
This compares to $60 7 million for the prior year.
It reflects the financing we completed in mid 2020 that raised gross proceeds totaling approximately $69 million.
The importance of this financing was twofold first we were able to strengthen our shareholder base with a number of top tier biotech investors.
And second the additional funds extend our cash runway through the next set of clinical catalysts for OTO 313 in a row for 13.
Putting us in a solid financial position going into the data readout for <unk>.
With that I'll turn the call back over to Dave.
Yeah.
Thank you Paul operator, we are now ready for questions.
Thank you, Sir ladies and gentlemen, if you have a question at this time please press the star.
And one key on your Touchtone telephone. Thank for your question has been answered or you wish to read.
From the queue. Please press the pound key.
Our first question is from Ken Cacciatore from Cowen <unk> Company. Your line is open.
Hey, guys good afternoon.
And congratulations on really broadening out the company and all the progress on all of the different plans that it's really starting to show all the work that's been done. That's my first question is on many years I know, we're getting close now to the data right around the corner I thought it would be good to just take an opportunity to step back and talk about the disorder itself. The.
For the commercial opportunity is kind of best you can frame it at.
And to what extent in terms of sales force size, you think would be appropriate to approach. It. So just trying to get some.
We use a kind of early views or thoughts on or around the commercial opportunity and then maybe also just a discussion and you went into and obviously with the change of the statistical plan, but maybe some other nuance differences.
With this study or the steps that you took in this study to try to ensure I'm a.
A little bit of a different outcome as you tried to control for the kind of the patients that were entered into the study and I'll leave it at that for right now. Thank you sure. Thanks, Ken appreciate you participating today and why don't I take the second question first and then let Paul address the market opportunity and our commercial.
Fanning.
So with regards to the differences of this study to the prior studies clearly what we've been able to do here.
Is really learn from the prior work.
And identify what we think were key.
Drivers in the prior failure of the Averts, one trial, but the success of the averts two trial and that was really around careful patient selection.
Ensuring high quality veneers patients.
That were well known to the clinicians.
Really choosing high quality clinical centers.
Primarily these are academically associated are academically, what I'll call academically inclined clinical investigators.
So that's important because they understand really the importance of careful patient selection as well as the criticality of communication with patients.
Because obviously the communication with patients can't drive placebo response, and so not only in terms of selection of the clinical sites are was that important but also then in training. So we undertook extensive training of both investigators and their staff on proper communication too.
The subjects as well as San even training for patients regarding the nature of clinical trials, we don't know if the drug works or not and the importance of reporting their symptoms as they experience.
The final things that are really key here was really tightening up on our inclusion exclusion criteria to ensure that we were really excluding patients who may have.
Syndromes or conditions that are highly <unk>.
Similar to many years, but that are not many years things for example, like for stipulate or migraine and so we worked with kols to tighten up those criteria. So these were all very key steps to our approach that we think will show great benefit in the the present study that will soon readout.
Yeah, Hi, Ken it's Paul jump in about the marketing and some initial comments about how we're thinking about the commercial build.
So it's a very attractive market that has yet to be developed having said that we believe there are over 850000 patients in the U S debt have the diagnosis based on health.
Health claims data about a third of them seek treatment each year, that's clearly an opportunity by getting out to patients and let them know that there is an effective and approved therapy available. We think that that number will grow on time and expand the market, but even if you just take the third or so that are seeking treatment each year, but have half of them are already treated with steroids whether.
It's high dose oral steroids or repeat injections with the off label steroid solutions. So we will clearly focus on converting in TS who are the target audience for this from using <unk>.
<unk> label steroids to using <unk>.
We actually based on the market research believe that many of them will start to offer that to their patients is that a first line treatment, whereas steroids are currently second line behind diabetics and low salt diet.
So increase the usage of a.
Steroids by providing a pivot acts as a single administration approved product with robust clinical data and then starting to sort of expand the market from a commercial build out. The nice thing is this is a specialist audience about 10000, Ian teas and within that.
It's actually a smaller set that are the.
<unk> and Otologist that are the real specialists, who will be the focus of our.
Initial efforts so we'll provide more.
Guidance around how we see the commercial build but we think it can be a very targeted focused launch really focusing on those high volume existing users.
Get some good.
Usage and ramp going and then expand from there and clearly a lot of what we're going to be working on is on the buy and bill side to get the J code to establish.
Good history of reimbursement and two to really support providers that way.
Thanks, so much and good luck going into the data.
Thank you Ken.
Thanks, Ken.
Your next question is from Tyler Van Buren from Piper Sandler Your line is open.
Hey, there good afternoon, and congratulations on all the progress I had a follow up on the commercial discussion.
And the things that you just mentioned I guess.
Can you talk about how easy it is to access. These neurotoxin just from apologists as you look to potentially rollout O to EBITDAX and for those who are familiar I guess with the tip REO experience. It would be helpful to maybe compare and contrast AR.
How how this might be different from <unk> and then secondarily to that just wanted to hear the latest on CMC and manufacturing in terms of the scale that you guys could potentially have for <unk> prior to a launch at the end of next year.
Yeah. So David you want I can take the first part and then I'll throw it back to you for the kind of the second part.
So with respect to identifying and targeting Tyler I mean that is the nice thing about this it's not abroad.
Set of clinicians that we'd have to go after it is not only the.
And Ts as I mentioned, but within the E&P those otologist from no autologous. Those are if you look at the data, which we obviously have.
Those are the routine users of interest in panic injections for treating the nearest patients now what's interesting that the the market research suggests is that.
The sort of more generally in tea.
Is I'm interested in and.
And wants to use that kind of treatment approach, but you know frankly.
Frankly, the off label use of a liquid.
Liquid storage solutions is not very amenable to broad utilization. They don't know what formulation to use they don't know how much did deliver they don't know how often to bring the patient back none of that has been standardized and obviously with single administration of pivot X. We've kind of taken all of that uncertainty away and provided not only an approved product.
But with that we will provide a lot of support so we actually think it'll be very straightforward to identify that a subset of of clinicians that not only are routinely using <unk> injections today, but those that are seeing.
Good volume of many years disease patients center are ready for a product like <unk>.
So we're kind of anxious to get out naturally start to kind of build that awareness.
Sorry was there a second part of the marketing question before going to CMC.
Well it was I think it was.
Sorry go ahead, no temporary O experience, yeah, sorry, Yeah, I mean, it's obviously very different I mean, as you remember with the chip Rio.
The kind of the challenge with its initial indication was.
Not with Emts, who really like the profile and.
And wanted to actually use the product.
And I'm, just sort of broadly but.
In order to do that they'd have to have the formulary at the hospital approve its use and that's what it.
It took quite a bit of time, when we had the sales force in place.
Yeah, the challenge with a temporary O leased with its initial indication was not with E&P was with that access in those facilities. So we bypass that entirely with the pivot X because the primary side of care for many of those patients in the office.
And the great thing about.
The kind of the setup from an access standpoint is the interest of panic injection already is reimbursed under an existing CPT code, it's very straightforward to get the unique J code for <unk>.
And we will clearly be providing a lot of access support services not only for those providers, but also for the patients. So we think it's it's a.
It's a very different situation for me.
For HBO, just because of the access.
Yeah, and then Tyler to address your questions about CMC manufacturing as we've said, we will be prepared to and anticipate submitting the NDA based on successful results from this.
Clinical trial in the third quarter of this year and in that it really is only the clinical data from this clinical trial as well as the integrated efficacy in summary that we need to put together, we already have our CMC information and in fact have been preparing for the NDA and we have completed.
<unk> lots. So I think it's important that people remember we've already had one successful approval with the <unk> and commercial support there.
And obviously I know how to do this.
So with regards to scale I think again this is something that we expect no issues with regard to.
The need to support the product in the market in terms of.
Entities, because it's a very small dose that we're giving to individual patients for our batch sizes very similar to retinal drugs are very small and so with one batch we can make a large large amount of materials and we have a a very nice.
Expiration dating program for this product.
So I think all in all we're.
We're well positioned.
Thoughtful Faye we've completed all of our safety work as well with the repeat dosing of <unk> X to support the every three month dosing regimen and so.
We look forward to taking the clinical data and submitting the NDA on success in the third quarter.
Wonderful thanks for the thoughts.
Thank you Tyler.
Your next question is from Aryan.
<unk> <unk> from H C. Wainwright your line is open.
Thanks, guys that actually have a few can.
Can you just remind us are in this third phase III, where how much room for error or you're leaving yourself out with the powertrain with regards to the day to you saw in the prior phase two be at Novartis to and assuming that's positive.
You mentioned that <unk> NDA filing I don't remember, if you've ever spoken about hopes or expectations for a potential priority review given fast track designation and I have a follow up thanks.
Okay. Thanks, Lauren Yeah first in terms of the error and and what we've allowed ourselves I think you know we have taken a conservative approach here.
So when we say that we're 90% powered we did not hit the you know.
Basically try to keep that close to the 90% and then Furthermore, we over enrolled so we enrolled 149 subjects.
Over the target of $1 42, So we think we're in a very good position power wise.
And we also think this is also one of the strength of the negative binomial as we've shown the data comparing the negative binomial to the pathology not only is it highly sensitive.
But also it has it's a very robust.
Statistical test, even even over per song. So we think that those coupled together give us a lot of power and a lot of ability to handle this very unique dataset.
With regards to priority review obviously.
Obviously, it is something that F. D. A looks at following a review and acceptance of the NDA, but we clearly have experience with submitting NDA successfully so.
So we think we're in a very good position to that and we've been working on the NDA, we're not waiting to we did not wait to start that work. We were had been working on the NDA.
Submission, while this third trial was going on.
Furthermore, I'll just remind people that we have a fast track designation so that.
That should be favorable.
For priority review, but again we.
We will need to submit and wait for the F. D. A to see if they will accept our request.
I will point out that with priority review in third quarter that would put us into the first part of 'twenty 'twenty two for commercialization.
Right. So I guess on that front, if you do get priority review or I guess in case, you need to prepare for that positive development too low you know when do you think you'll released assuming positive phase three when do you think are going to start really ramping up that commercial investment.
Well I think we'd start working quickly on that we've already started thinking about our preliminary steps of our he started about our.
Thinking about the pieces that we need to put in place.
And we would start implementing that based on the positive data.
From this trial. So I think importantly here is if as Paul.
<unk> indicated in his discussion about the market and our approach this will be very much of a ramp a launch it is not something where we need to bring in.
Because a large number of people immediately.
Both because.
We already know our target audience of what we're going to target first it's a very limited number of targets initially to build out that reimbursement data and support for the product among kols, which we can then expand upon I think also our work with a tip Rio has given us on all of the knowledge and capabilities that are already either.
They're in house or that we have through working with other vendors and partners. So I think we have a lot of potential here too to ramp very quickly and it's not something that we're concerned about we think we have a very capable of doing that.
Alright, I appreciate it I'll get back in the queue.
Thanks for it.
Your next question is from Charles Duncan from Cantor Fitzgerald. Your line is open.
Super.
Afternoon, David and Paul Thanks for taking my question and should should you live in interesting times hope things go well.
Wanted to ask a question on many other study.
First first of which is call it timing of data and I know that day.
Weeks.
Not months, but what is really kind of driver to the COVID-19.
David timing and more substantively this may.
<unk> seem like a silly question, but you mentioned a positive result.
And I guess the question is.
What do you consider positive results beyond the stat Sig.
When you when you think about response rates versus reduced number of nears events or days, what kind of effect size are you looking for based on Dod leader discussions would be meaningful to to the community.
Yeah. Thanks, Thanks, Charles for those questions. So with regard to timing I mean.
As with all studies for registration Theres been a carefully orchestrated process.
Of going through a data query and resolution.
During that all documentation is verified and signed off by the investigator appropriately bringing down materials at the clinical sites and closing out the clinical sites and then of course ultimately getting to database lock.
Analysis by the statisticians and then obviously at that point then.
Looking at the results. So that's been the the you know the process that we're going through and why are we have through the excellent work of the investigators the site staff across.
The world as well as our own CRO and clinical team we've been successful in doing all of that despite the challenges with COVID-19. So quite impressive work that allows us to to meet that goal of by the end of February that we've announced now.
So with regards to the.
Positive will clearly from an FDA standpoint that stat FIC, we already have one successful phase III trial, we need one more and that requirement is typically significant outcome at point O five or less.
With regards to the markets.
And what clinicians and patients are looking for it really comes from them as we've talked with both patients and clinicians what we routinely hear it.
Is that if we can just save them one day of definitive Vertigo.
Really really helps them a lot. So while these patients may be experiencing a lot more it really is any day that you can save them as the day, they get back and so the hurdle here is really low in.
In terms of our ability to have a positive treatment effect that said however, what we've seen from our work as we've shown for both the averts two trial M has been also very consistent with the phase two b as we see much more than that what we're seeing on average is 2.5 days of definitive.
Burger Vertigo spear, but more importantly, I think even more is that it's a reduction of the vertigo episodes in total and reduction of the severity. So all those things taken together really provide a robust benefit to these patients and then I'll just remind you that you know as we look at the responder analysis.
40% of the patients.
Treated with <unk> across the averts, two and the phase two B trial demonstrated no definitive vertigo episodes in the third month following treatment. So that's obviously quite profound in terms of that population and even when we look at the ability to.
We reduced the number of episodes by 50% or even 75% is quite pronounced. So I think we're very confident in the ability of <unk> to to help these patients and that it's a robust.
And in effect and again with that positive result on the statistical outcome I think the product will will fare very well in the marketplace.
That's helpful added color Dave.
Let me just ask you for a qualitative.
No.
Steel or per person.
<unk>.
The breakdown of this study and terms of investigators adhering to protocol.
Sure.
And capturing all the data needed working with characterize patients how do you feel maybe even relative to the for its one experience or maybe debt that's not an easy comparison.
Well I think in terms of.
With regards to this trial and the work for the team has done the investigators site staff even patients has been exemplary it is.
I'm totally confident in the the.
City of the study.
And the breakdown of this study we had extremely high compliance throughout even through the Covid times. When we were initially going into the Covid epidemic, we saw a very high <unk>.
Clients being retained and have seen that throughout and so I think from the standpoint of the documentation from the standpoint of patient compliance from an investigator compliance I M. In the delighted with what I've seen.
I don't know that I'd want to try to compare across studies.
Clearly this study was much more.
<unk> not only in the U S, but in many countries in Europe.
During what is a very unusual.
Unusual time for all of us with Covid and I could not be more proud or impressed by what the group group of people involved here have done.
With this trial and the compliance that the patients have demonstrated I think speaks to the issue of their unmet need and how significant are there unmet need is in terms of looking for therapy that they have that kind of high compliance.
Okay very good and last question is regarding the filing of the NDA just to clarify.
Would you be filing for an indication of treating veneers generally or specifically with one dose or do you think that it won't be limited at all in terms of re dosing and and then I guess that brings up another question what would you like to do it in a.
Or would it include re dosing or do you think that's not going to be necessary in this setting.
Yeah.
Good question so.
With regards to the indication the indication will be for the treatment of Vertigo symptoms are vertigo associated with many years disease that is what we're treating as the vertigo.
And then in terms of the re dosing what we have done and this was in work with the FDA in agreement with them that we conducted our repeat dose safety work, which has all been completed successfully and is ready to be submitted with the NDA to support up to every three months of administration.
You'll recall that in phase two b, we conducted an additional months of observation and saw that the effect was starting to to where in some patients and so that was the purpose of designing that every three months of administration.
So that's what we expect in the label.
Single use for course of treatment with re treatment being available.
Available every three months, we think that patients will really kind of fall into two groups. There will be patients, who say I want to be seen every three months and receiving an administration. So I can minimize my vertigo symptoms.
And there will be some patients, who say hey, I'll I'll come back when I need to if if I'm doing well for a few months and I don't need. It I'll then come back when I have an attack and 90 yet.
So we think that will be the initial type of patient population. So we think about an average of two administrations per patient per year.
Now we do think as you bring up the kind of the future. We're very actually excited about the potential for this product.
To to be able to.
Spare the hearing loss at these patients suffer I think while these patients are really struggling because of the vertigo and that keeps them from going to work or are being with their families. One of the things that they talk about next is the impact on the hearing as you know these patients will typically ultimately become deaf.
In that affected ear for example, our founder is now depth in that ear, and so and there's always the risk that they can get bilateral veneer, which is very scary for them. So one other things that has been suggested from the literature is that it.
It may be possible that with continued treatment.
And maintaining that treatment that there may be ability to spare the hearing.
And obviously that would be a great way to support that every three month dosing and so this is something that we have.
Actively thought about.
That is something that we could do post approval is get into additional work to look at that ability to to spare the hearing over a long term.
Study.
Super look forward to the data and increased pipeline visibility yet this year. Thanks for taking my questions.
Thank you Charles.
Again to ask a question. Please press star one on your telephone keypad again Thats star one on your Touchtone telephone.
Your next question is from Yogi steamer of Oppenheimer. Your line is open.
Hey.
Thank you Youll JCR and it would be helpful. Thanks.
Thanks for taking my question.
Just a quick one here on clinical studies.
In OTC T O N T.
So I'm as you mean bad next day is to try it anyway.
Any patient who has mitten Kennedy's some fashion.
J J.
Kennedy's so how are you.
For Q I'm, making.
In order to minimize its typical flow of issue in this trial.
Yeah. So thanks Joseph for your question. So in the phase two what we are doing is taking some of our learnings from the phase one two trial.
And having looked at the state and its part of the data that you can see in our corporate deck is we have looked at.
The.
The impact of the incoming tinnitus functional index that is the measure of the severity of the tentative at baseline.
In the initial in the phase one two study patients had to have a 25 or higher score on the T. F. I that's out of the 100, which would indicate moderate and moderate to severe tentative.
Well, we're going to do is raise that T F I score for inclusion up.
And by doing that we're go to a little bit more it'll still be moderate, but I'll call. It more of the middle moderate.
To moderate severe type of patient in their tinnitus that will give us basically.
A better ability to not only see a larger treatment impact, but also separating it from placebo and actually you can look at our slide deck and look at the slide that we have for the T. F. Five for the total population and then a couple of slides later, we have that same graph now just for <unk>.
Patients with a T F I score of 40 and higher and it really illustrates the point I just mentioned of really giving you.
Very clear and increased response on the improvement and tentative for 313 as well as a very clear.
Differentiation from placebo and so we think that will help with the floor effect and we believe that that will also help minimize the placebo effect.
Perfect. That's super helpful. Thank you.
Thank you.
We do have a follow up question from all in net net.
H C. Wainwright your line is open.
Thanks, I just wanted to touch on the pipeline as well for 3014.
Can you just sure again I think I might have missed it in the script, you said you're going out to four months, but what is the primary observation endpoint.
Yeah. Thanks, So on the primary endpoint is the same as in the phase one two so we're going to hold it to are.
At the same time points that we used their day.
Mainly that is the.
I get confused between the for 13 and $3 13, sorry, it's much it's month, one and two.
Yeah month wanted too.
Okay, and I think at some point you were talking about doing bilateral patients maybe two phase twos and I'm. Just wondering is that still on the cards are you hoping to maybe elucidate the drug effect in this you know better different enriched patient population before you start pushing the envelope.
Yeah, I mean, I think first of all it's very clear on the unilateral side that we can see the the benefit and and follow it quite closely and so we wanted to get going with the unilateral properly we are still considering bilateral.
But we are trying to get learnings there I can tell you that kols do have.
There is a question of <unk>.
The impact your have across both years and so it is something that we wanted to do a little bit more work to really understand how best to design that trial.
We do think that there is opportunity and bilateral patients for sure for this product.
Really more is in regards to how to properly do this study.
And that's part of what we're working on.
With us.
Okay, and then just lastly on for 13, I'm still little confused how what.
What is the main difference in this new expanded cohort.
Versus what we saw before or is this a different dose the different treatment or is it really just focusing on the narrower set of endpoint then if it's the latter you know what what do you think you'll learn that you didn't already learned before.
Yeah, I think several things with.
With this additional expansion cohorts. So first of all you recall, we were doing a lot of additional measures we talked about all the different audio metric measures. We were doing things like middle ear muscle reflects additional audio metric measurements.
A lot of testing in addition to the speech in noise test and even there we had an extensive amount of testing with the speech in noise and so that was because we all have to remember this is the first of its kind study that we've that we've had.
The first in human and so we are working with our.
Key opinion leaders and an expert Audiologist, we're learning a lot that has never been because this has never been done in clinical research before and so what we're doing here is we're refining what we've learned about what to look at what really shows the ability to see a difference between treated and untreated and.
So one other things that you're you see that we will have done is narrow down the measurements that we're doing both in terms of audio metric measures, but also even in terms of the speech in noise testing that we're doing we will still continue with those three tests, but we were actually looking at different.
<unk> is in addition to those different tests. So we've now been able to refine that down.
The final thing and the reason for the expansion is is we did 16 patients as you know.
And in our comparison in the study with placebo versus treatment and what we wanted to do is get more patients as well so basically get down to more of exactly what we think we're going to be doing in phase two but also get a larger number of patients.
Patients that will do two things for US one it will further confirm the result that we saw so give us further confidence that we are seeing that treatment effect in that and the size of that treatment effect, but also now we have the ability to really power the phase two and that's really the most import.
One of why we're doing this is we just feel that it would be better to have a larger patient population in order to size. The phase two and ultimately then select which of the speech in noise tests, we think should be primary.
Okay. That's very helpful. I appreciate it.
Good luck.
Thank you Arne.
Yeah.
I'm showing no further questions at this time I would know that.
To turn the conference back to you Dr. <unk>.
Well. Thank you everyone for participating in our call today. Please note that we will be attending the Cowen the H C Wainwright and the Oppenheimer virtual health care conferences in March and hope to speak with many of you then.
Have a good evening everyone.
Ladies and gentlemen from for today's conference. Thank you for your participation have a wonderful day.
Good day.
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Yes.
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