Q3 2020 DURECT Corp Earnings Call
Oh presentation, if anyone should require operator assistance during the conference. Please press star zero on your telephone keypad.
As a reminder, this conference is being recorded I would now like to turn this conference over to your host Mr., Mike Aaron Berg Chief Financial Officer. Please go ahead Sir.
Good afternoon, and welcome to our third quarter 2020 earnings Conference call.
This is Mike Herring Burke, Chief Financial Officer of direct Corporation.
I'll provide a brief review of our financial results and then Jim Brown, our president and CEO Ivan.
Our program we.
We will then open up the call for a question and answer session.
Before beginning I would like to remind you of our safe Harbor statement during.
During the course of this call we may make forward looking statements regarding direct products in development expenses.
Benefit.
My plans future clinical trial.
<unk> financial results.
Forward looking statements involve risks and uncertainties that could cause actual results could differ materially from those in such forward looking statements.
Further information regarding these and other risks.
Our SEC filings, including our 10-K and 10-Q under the heading risk factors.
Let me now turn to our financials.
Total revenue in Q3, 20 22.7 million tons.
10.8 million in Q3 2019.
Q3, 2019 included the recognition of 6.2 million and deferred revenue from an upfront fee and milestone payments.
So excluding that scarcity to 2.7 million versus 4.6 million.
Product revenue largely from the sale of pumps and LACTEL.
The 2.4 million for Q3, 2020 compared to 3.0 million.
320 19.
Gross margin for these combined.
55% in Q3 2020, these product lines continue to be strong cash flow positive.
R&D expense was 7.0 million for Q3 2020 compared to 7.9 billion Q3 29 <unk>.
Primarily due to lower expenses and partner funded R&D programs and lower partner related expenses.
<unk> expenses were 3.5 million for Q3, 2020 as compared to 3.8 million.
Q3 2090.
Our underlying burn rate during the quarter with 7.6 million.
In Q3, we raised 6.1 million <unk> expenses by selling about 2.7 million shares through our ATM facility at an average price of $2 or 32 cents.
At September 32020, we had cash and investments right now.
Millions as compared to 51.3 million at June 32020 at 64.8 million, that's a separate 31 2019.
With that thanks again for joining our call and I will now turn the call over to Jim for an update on certain of our progress.
Thank you, Mike and Hello, everyone.
You for joining us today, I hope, you're all doing well during the quarter, we made exciting progress on a number of fronts.
We announced the design of a from the Dior nitrate seems to.
The alcoholic hepatitis trial, we're now initiating clinical sites and expect to begin dosing patients very soon.
We started dosing in the phase two trial for do you want to have to wait and hospitalized COVID-19 patients with acute liver.
Kidney injury.
Actual reported positive top line data from the phase one be Nash study with you or nine to eight we announced that additional data from this trial will be presented at the upcoming eight S.L.D. liver meeting.
We continue to work with the FDA on the positive our NDS.
And today I'm pleased to announce our hiring of Dr. enormous assessment as our Chief Medical Officer.
Do you want to actuate is it epigenetic regulator the modulation the expression of multiple clusters. The master G that are involved in many important cell signaling pathway.
Do you want to actuate up and down regulates more than a thousand g. and Bobby functions that include stabilizing the mitochondria, reducing the toxicity regulation of inflammatory or stress responses and promoting cell survival.
I'll begin with an overview of the opportunity for do you are not you wait and alcoholic hepatitis or age.
They are 122000 hospitalizations per year in United States for age.
There are no approved therapies for age.
We demonstrated 100% survival at day, 28, and our phase two A.H. trial.
The historic 28 day mortality rate great age is 26%.
Currently we are initiating sites and they're on the customer starting patient dosing in a firm there.
The night to eight phase two be H. safety and efficacy trial.
Oh from the 300 patient the feeble controlled double blind multinational study the primary endpoint will be 90 day survival.
Based on the results from the phase two A.H. trial, and the fact that survival is the primary end point for us and we are optimistic that if we are able to demonstrate a robust survival benefit in this trial. It may support an anda filing.
Approval based on a single trial is not uncommon in fact, 37% new drug approvals between 2005 in 2012, the based on a single pivotal trial.
And 42% new drugs most of the United States in 2018 Board approved based on single trial.
H is an acute form of alcoholic liver disease or a LT.
It is characterized by long term heavy alcohol intake.
A recent period increased alcohol consumption or binge drinking.
As well as jaundice fever, fatigue weakness nausea, vomiting loss of appetite and a depressed or negative mental state.
D.A.S.L.D. guidelines provide the following criteria for the diagnosis of the age and.
An onset of John it's been in the past eight weeks.
Ongoing consumption for at least six months or more than 40 grams of alcohol a day for a woman or 60 grams rock holiday for a man.
To put this type of alcohol consumption into perspective.
This means approximately three standard drinks per day for a woman and for for a man for the last six months.
A 12 ounce beer glass of wine or one and a half ounces the spirits. It's considered one standard drink.
Oh, so less than 60 days of assets before the onset of John This.
Sure and Bill <unk> levels greater than 3.0 milligrams per deciliter and these patients also typically have elevated liver and.
If you think this disease did not affect people you know you're wrong well.
While the majority of age patients are between 40, and 60 years old and have liver cirrhosis apart.
Approximately 20% of the age population or in a 20 to 30 and may not have cirrhosis at all.
89% of hospitalized each patients have insurance.
Unfortunately during this pandemic alcohol consumption in the United States has increased.
According to a September publication in the Journal of American Medical Association network on average alcohol can still consume one more day per month by three or four adults in the United States.
For women.
It was the most significant increase of 0.18 days of heavy drinking, but the 95% comp that's available.
From a baseline and 2019 0.44 days.
This represents an increase of 41% over the baseline and equates to an increase of one day well.
Well one in five women.
In my conversations with physicians, who treat the study they have told me the answer to the H has also increased according to many of these doctors. They are also seeing a larger number of younger age patient.
There is no approved treatment for age.
What physicians have available throughout today, primarily involved after that's as supportive care, which includes nutrition and hydration.
And analysis of 77 study published between 1971 in 2016, which includes data from more than 8000 patients showed the overall mortality from H was 20.6% in 28 days.
29% at 90 days and 44% at 180 days.
Hi, one more mortality rate from the time of diagnosis is similar to the ferocious cancers, such as M L and advanced breast or pancreatic cancers.
According to the A.O.L.D. guidance Stuart maybe used in certain patients with severe age.
However, steroids have shown only minimal benefit and they increased the infection rates and age patients.
And the stop a trial a study of more than a thousand age patient. She writes significantly increased the infection rate.
Stop H. trial also convincingly demonstrated that steroids did not improve survival rate over placebo at 90 days or one year.
And many age patients are not eligible for steroids in fact, according to one recent study less than half a severe age patients were eligible for steroid use.
The hospitalization costs for age or more than $50000 per patient in the first year.
Alcoholic liver disease is becoming a leading cause of liver transplant in the United States the cost of the liver transplant exceed $800000.
Regarding hospital stays and age the average hospital stay for an age patient was approximately seven days with many staying significantly longer than.
In our do you weren't actuate phase two A.H. trial 14 of the 19 patients were discharged in less than four days after receiving only one.
Infusion of de wired back to it.
All of the 19 patients in this study survived through the 28 day follow up period of the trial 12 of these 90 patients were classified as severe based on their meld scores also 15 to 19 were classified as severe based on the scoring system that is specific to age called my base discriminate function score.
Dior nitrate was well tolerated by all of the patients and at all doses evaluated and study, including in all of the severe age patients.
There were no serious drug related adverse events reported in this trial.
Age patients have greatly elevated believe it or.
The minimum dealing with them level to be diagnosed with A.H. Street, which is about two and a half times the upper limit of normal patient.
Patients in our phase two a trial had an average quarterly revenue of over 14.
Significant early that is day, seven reductions ability levels from baseline or a critical factor in determining a patient's prognosis age.
H. patients treated the Dior nights a week in our study I sit near good day, seven reductions and believe it.
Well, ignostic scores, including legal and mill as well as Sam Kraton, even ever and I in our we're also improved in this trial.
To summarize the deal on Actuate H. program.
During the quarter, we announced the design of the affirmed trial for patients with severe H.
Affirms the 300 patient double blind randomized placebo controlled multi national trial.
Affirmed valuate three treatment arms 30 milligrams 90 milligrams of de Oro, 90 weight and a placebo arm.
As with the phase two a trial patients in the affinity trial will receive an infusion of the viewer nitrate or placebo on day, one and if they're in the hospital on day four they will receive a second infusion.
The primary endpoint for a firm will be 90 day survival.
We are currently initiating clinical sites and expect to dose the first patient said.
We expect that if we achieve a robust survival benefit. This study may support the N.D.A. <unk>.
Next I will update on the do you want to actuate phase two trial in hospitalized, hoping 19 patients with acute liver or kidney injury.
You weren't actuate is not an anti viral agent its a naturally occurring epigenetic regulator that has tremendous potential to treat acute organ injury, including the systemic inflammation such.
Such as is the case that stretches.
Phase two a clinical evidence in patients with acute alcoholic hepatitis and preclinical evidence in a number of multi organ injury model, which demonstrate protection of the lungs liver and kidney.
Well as demonstrated safety at age patients in our phase two a study suggests that the U.S. actuate, maybe able to help cover 90 patients.
In addition to lung injury patients with severe cold at night, he can't develop multi organ injury, including acute kidney liver and cardiac injury, resulting from direct viral infections, well complications from the viral infection.
These may contribute to poor outcomes of patients with over 90.
From a safety perspective, do you watch weight has been well tolerated nearly 300 subjects, both healthy volunteers and patients in multiple phase one and two study.
Most relevant to cover 90 are the results from our phase two study do you aren't actuating age patients.
Described earlier, all 90 patients treated with your nitrate survived the 28 day study, while one month mortality and age clinical trials is on average 26%.
Besides multi organ injury, one of the main complications associated with the death of age patients similar to those patients with a couple of my team it's sepsis.
Therefore, if acute organ injury could be effectively treated or prevented in hospitalized patients who cover my team I could be potentially shade.
This phase two trial is a double blind placebo controlled multi center study to evaluate the safety and efficacy of do you aren't actuate in hospitalized severe of critically ill cover 90 patients with acute liver or kidney injury.
This study is an 80 patient trial with a three to one ratio of actually to placebo.
The dose of the overnight rate was 150 milligrams by intravenous infusion on day, one and day for.
The primary efficacy endpoint is a composite of survival and being free of acute organ failure at day 28.
It is our hope that youre and lightweight in combination with the standard of care will be able to help cover 90 patients with acute liver or kidney injury, which if successful ultimately could save lives. Some of these patients.
We go start first patient in this trial in September we now have drug at multiple sites and we are in the process of adding more sites.
Next I will update on the deal or how much weight Nashville right.
In May of 2020, we reported positive topline results from our phase one B trial do you want actuate in Nash patients with stage one to three fibrosis.
This was a randomized open label multi center study of do you aren't lightweight and Nash patients conducted in the United States.
Your nitrate was dosed orally for 28 consecutive days at 15 milligrams or 150 milligrams once a day or 300 milligrams twice a day I followed up for an additional 28 days.
A total of 65 patients completed the study and there were at least 20 patients per dose group.
She endpoints include safety, and pharmacokinetic clinical chemistry, and Biomarkers as well as liver fat content and liver stiffness by imaging that includes both MRI pdfs and fibers.
Do you want to write you a treatment in this trial resulted in a global reduction from baseline of liver enzymes liver fat stiffness as measured by imaging and serum look at many of these reductions were statistically significant.
A statistically significant 24% reduction of plasma triglyceride was seen in the 60 patients who had baseline triglyceride levels above 200 milligrams per deciliter.
What are your 3% of the patients in this trial had at least a 10% reduction in liver fat as measured by M or IP that pdfs.
In this group of patients there was that we were sticking with liver enzymes and serum that they were statistically significantly reduced from baseline.
You are nitrate was well tolerated at all three doses evaluated.
There were no serious adverse events reported during the study pharmacokinetic parameters. After repeated dosing were comparable to those after a single dose from a prior study, indicating Nokia in relation after repeat dosing.
Also drug exposure was dose dependent.
We believe having multiple important parameters all moving in the desirable direction are particularly impressive when you consider the patients will only dosed for one month.
Additional results will be presented in a poster at the upcoming eight SVB.
Which is gonna be between November 15th and 16th.
These results achieved over one month course of treatment together with the continued safety profile or do you want to actuate a promising indicators do you watch weights potential in Nash.
Next to the possible program.
Positive or is our investigational post operative pain relief people that uses our patented sabre technology and is designed to deliver be typically to provide up to three days of pain relief after surgery.
Since our last earnings call. We have continued to communicate with the FDA regarding their review of the polymer NDS and believe they are making progress with every deal.
If approved we plan to license Pos much with partners for commercialization in the United States. We expect that this deal will include an upfront license fee and royalties based on product. So.
Hey, it's my pleasure to welcome Dr. enormous assessment as our new Chief Medical Officer Don.
Dr Assessment is a renowned hepatologists with a proven track record in clinical research of liver disease.
He will provide critical support in advancing our clinical programs and we look forward to his contributions.
Dr Assessment has extensive clinical experience and expertise in the liver disease field. He brings over 30 years of clinical research and development experience in academia and industry.
He joins direct from Baylor College of Medicine.
Where he was an associate professor of medicine and surgery.
Dr Assessment has been a faculty mentoring member at Baylor College of Medicine intermittently since 1985.
During this time he has served as a principal investigator for research focused on assessment and management of acute liver failure and artificial liver support.
Dr. Assessment has also had leadership experience and industry as the founder and Vice President of both you Paddocks Inc. from 1993 to 90 95.
And antioxidant cell technologies and 1995 to 2003.
Most recently he has served in senior leadership roles as a member of the Baylor Faculty Senate and EPS Director of project Echo The Telehealth program at Baylor St Luke's Medical Tech.
Dr. Stuthman received hit EM BBC age from the University of Vic waters, Rad, and you'll have a spoke south Africa.
Good day, ladies his residency at St. Louis University Hospital, and its post doctoral fellowship at Washington University.
He is board certified in internal medicine, Gastroenterology and transplant hepatology.
Dr. Assessment is also a fellow of the American Association of the study of liver disease.
Which is a designation that recognizes its superior level of professional achievement in the field and hepatology.
He is a thought leader in the field of hepatology and excellent condition and communicator. We're excited to have him with us as a member of our senior team.
We are planning a virtue that later this month to introduce Dr. assessment to our investors. We then went out the details of this event in the near future.
In summary, we are excited about the progress on deal and I have to wait the flagship of our epigenetic regulator program.
We have begun clinical site initiation visits and are nearing first patient dosing in a for our phase two D. Do you aren't actually trial in severe age patient.
Based on the results from the phase two A.H. trial, and the fact that survival is the primary endpoint for fun. We are optimistic that if we are able to demonstrate a robust survival benefit in this trial it may support NDS filing.
We initiated patient dosing and are adding clinical sites into the do you aren't actuate phase two trial in COVID-19 patients with acute liver or kidney injury.
In addition to the positive top line results, we've already announced from our phase one B trial, a deal why not to wait a nash patients.
Liver enzymes that the fat and liver stiffness as well as plasma lipid all moving in the right direction.
We will be presenting biomarker data from this Nash trial at the A.S. I'll be meeting this month.
When you combine these results with the safety profile Dior nitrate, we believe it has a chance to play an important role in the treatment of Nash.
Today, we welcome Dr. enormous sussman Darex, new Chief Medical Officer is experiencing patient focus will be critically important for the development of deal in actuated H and for other indications.
And during the quarter, we continued correspondence with the FDA regarding deposit Miranda I believe they're making progress on their review.
With that we'd now like to take any questions you may have.
Hi, I'm sure we'll be conducting a question answer session.
I would like to ask a question. Please press star one.
Hey confirmation indicate your line is in the question queue. You may probably start show if you would like sort of overfishing from dish for participants using speaker equipment. It may be necessary for you to pick up your handset before passing the Starkey one moment, while we poll for questions.
Our first question comes from the line of Chris.
With Cantor Fitzgerald, you May proceed with <unk>.
Her question.
Hi, good afternoon, everybody and thank you for taking my questions. My first question is in regards to the fees to be affirmed study for alcoholic hepatitis. So based off the three month mortality probability correlated with meld scores and the literature around the hospitalizations and mortality I wanted to.
Ask what you might assume the mortality rate could be for the placebo group what these understanding.
Well, we did make a number of assumptions with regard to that as we laid out our patient numbers and we were very conservative in our estimates that's how we arrived.
Arrived at 300, but we haven't given the actual breakdown I don't know weight cheap what are your thoughts on that.
Yeah, I think that that Oh, when we calculate tens of placebo mortality and William on 'em, We absolutely look at 'em multiple publications Oh. They are and then based on the school pump patients at though honestly months' mortality so in general.
Patients how lots have three mobs mortality as a 20% to 30% so we actually make up.
Oh.
Well a lot like all come till the modeling and then maybe from a host of scale off the mortality as compared with nine to eight Oh caused you on October eight we haven't had the sway monks mortality data base on a level we do have.
Hi, the eighth day mortality kobe's, so assume we have a similar inquiries from the second month told so Bob intends I'll start writing.
Writing off mortality I saw published that they tell them, we run a model like calculate Oh power.
Yes mortality.
Yes that was kind of the basis and then we took a very conservative view on all that as we did the computer modeling yeah.
We spend a lot more placebo patients would live in a lot more lightweight patients would die with our basic assumption.
Okay. Thank you for that the next question is on the COVID-19 study for acute liver kidney injury. So it appeared on clinical trials Dot Gov that you have sites opened in Chicago, Detroit and new work, where unfortunately, we have seen an increase in terms of the number of Cove in 19 cases there.
I know in your prepared remarks, you did mentioned that you are looking to open more sites. So I wanted to ask what are the key metrics you're looking at at this time and then also in a situation where you know perhaps Chicago work more cases really are unfortunately sky Rocketing would you look to kind of try to balance it out in the sites or so for example, theres.
One where you know there's a lot of patients you might look to balance it more across the sites.
Well you always try to have balance in any clinical trial for sure.
And unfortunately, it if it does come in and scripts as you said and it's horrible when it does it get a center and then and then it would go away and never come up someplace else. So yeah. We always tried to be mindful about whenever we oh, we're conducting any clinical trial and as far as the new centers that that we looked at it.
And those are generally in the south and the west and we've been working on this for a while and expect that there will be ups and so.
I hope that gives you some sense of it.
Yes. Thank you and then the last question also related to this program. It's just that since some of these organ injuries may appear during the hospitalization and now that you know there's been more cases off more literature to kind of support the different organs that are being damage as a result of ONIVYDE.
Chris how often are these patients getting their liver enzymes and the other key measurements checked a you know kind of look for this now that it's more known.
Well, it's all part of the their screening so they they get those it's all part of the normal panel.
And it's been unfortunate because we have seen of late that these monoclonal antibodies on semi to help the more seriously ill. The most seriously ill patients and they're looking to try and get those earlier, obviously had a couple of major programs.
Stop there.
Critical patient dosing and look to try to pay those patients who are less less damage, but but they but we do they are they do the blood chemistries on a regular basis. So we would go and the conditions would know what was going on what she would you add anything to that.
Yeah. So I think an odd they do test I mean, all these patient I guess no.
Soccer that are these patients oh, so the thought Oh hospitals physicians and then ER Doc has demos they usually they do care for them. They they buy them the samples they do the only checked a lot I'm typically once daily So every day.
Got that out safety panels chat.
So what they thought that was a ends on level never ends on levels as they tend to they can follow them carefully Wednesday NATO criteria. So I'll additions and our study called the Nato's now following alpha and the monitoring these patients that would close life and one out.
Some patients may be did not quite meet our criteria, but they actually mom and baby.
Oh.
Okay. Thanks, that's very helpful looking forward to the updates at the liver meeting.
Good thank you.
Our next question comes from.
Oh Boy with Oppenheimer. You May proceed with your question.
Hi, Thanks for taking the question. The first one here just wanted to talk about the evolution of the primary endpoint, you're obviously, it's easier. It's a shorter time period seems like 90 days is it still a pretty short which is nice and then can you just talk about how that's evolved in terms of the length of survival rate with time.
Sure.
Well historically longer and in fact, when guilty or did the trial that didnt work with or ask you want to temper that was a six month trial.
But the FDA and the liver association both in the U.S. and Europe have been meeting Oh fairly frequently going over this in the last meeting where where we attended the <unk> where this was discussed was in October of last year in Chicago at that meeting. It was decided that 90 days would be an appropriate amount of time.
To be able to to to look at follow up in survival. Because this is an acute episode doesn't seem to be the best.
Duration and so based on that that I think the FDA made their decision, but that's what they wanted to see on this call.
Okay, great and in terms of the dosage.
Could you just talk about the difference between Windows and two doses here and how you know how that was decided for the phase to be and you know your confidence in that the second dose. It therefore could help.
Sure Yeah, we I'll, let you speak to that first cohort Ritchie.
Sure. Thank you agenda so.
So we actually in our phase two <unk> study Oh of course that study was designed to assess safety PK study. So we gave up first I was ever patient, let's see what's especially the first dose. However, we all the time, we made that decision we thought the if the patient is qualified to be it's challenged why should we keep.
These patients because our I saw Oh, the Oh Gee imagine these patients are relatively young and then they tend to call. The fight by themselves. If you can help them to the couple of from the acute episode so what.
They are Oh, no source does recover from that okay. The episode and then why should we keep them in the hospital. So that's why in the first place to eight study we made that decision only those patients. If they are still hospitalized, but then they want to receive the stuff and that was also that.
Also based though of course based on the mechanism of action offline drugs. So what that experience in mind and then we decide that when we moved towards a phase two beach, while we won't keep the same or something.
I don't think regimen. So only if those people are still pacing a skilled hospitalized then they want to see that happened out.
They after the first dose if they do we'll cover it and I'm not not cool I mean, they are on the trend of recovering so the chances on most of these patients and will that eventually.
Oh come down calm down there.
Inflammation.
Okay.
Okay understood and then is there a doctor assessment on the line or no.
For it and they know he he's not he's not on the line right now he's actually if it is actual first day, so who's going through orientation, and just kind of getting all the paperwork done and everything else. So [laughter] Oh boy I'd say he was he was on a call earlier this morning, Savi, but he was yeah.
The first day stuff today [noise].
Okay, great and it's actually it's it's actually been working with us helping us for upper one sorry go ahead [laughter] figure.
Figure yeah.
On the age side, obviously that would tobey there seems to be more and more of the drinking and the consumption as as you mentioned do you think that something you are you guys doing any color on the recruitment timing is is that something that you actually you know a lot of companies are struggling to enroll drink. So that and do you think this is something that can actually accelerate your enrollment.
You know its I don't know accelerates the right term, but I do think unfortunately, I know that that alcohol consumption is up the United States. We know that from the literature, we know that from the physicians, we talk to as we've been out talking to wait you know, they're talking to physicians that senators, whether it's with the cobot trials or no centers are sure age as of Sunday.
Besides they're all talking about the age patients that they have in there. So there are a lot more lot more alcohol consumption a lot more people in the hospital for H and Unfortunately, it seems as if a lot of them are younger and so.
[noise] yeah.
No I I don't want to make any projections right now we want to kind of see how the trial is going as far as enrollment. So we're going to give it some monks to try to get a sense of it all but.
It certainly is a different time and if you've got alcoholic hepatitis you don't have an option to stay home. If you stay home, you're probably gonna die and so they do end up having to go to the hospital and they do end up at the hospital and so I think it's different from that perspective versus other trials, where you know that the election limitation.
You know I've heard this for so many different diseases from my colleagues out there running of the company said that it can be a challenge.
During this this time to conduct clinical trials with that may not be the case, probably won't be the case for this.
Okay. Okay, and then just lastly here this is probably more for Mike or any color you can give on revenues kind of going forward is this something that we would expect your I'm thinking more on the collaboration R&D and other line.
306000, it was negative 30000 in the first quarter, just trying to get a gauge for going forward, what you can share there.
Yeah. Thanks first of all we don't really project our revenues <unk> like.
Like that but yeah, we do have a number of early stage collaborations that generate revenue and ER and then on the product revenue side. You know we are I would say that the Q3 was a little bit suppressed from the.
Due to the virus, but I think Q4 will look better.
Okay I'm just trying to you know if there's something that's changed in the business on that side versus the first quarter and second COVID-19, where it was more about 1.5 million on that one.
The biggest change on the on the collaborative R&D was gilliatt.
You know they were they were driving a fair amount of that in 2019, so that you take that away and but we still have a number of early stage small programs. So.
They kind of they're gonna kind of fluctuate from quarter to quarter.
Excellent all right that's it for me. Thank you guys.
Thank you.
Our next question comes from the line of my Young one tiny with B. Riley you May proceed with your question.
Hi, Good afternoon. This is all along for my own Scott Congrats on all the progress would be you are not great.
Dr. Sussman joined team or we look forward to working with him.
First question from US is all about pausing here would be great. If you could provide a bit more granularity on some of the information request if any that are more recent than others and any incremental color you have on sort of the agencys thought process on how close the mere might fit in the post operative pain management paradigm and you know I'm thinking of some of the recent.
The A. reviews in the state one being kind of the CRL issued the Avenue therapeutics due to what their theoretical concern of opioid stocking, but also observed and some non opioid analgesic like I'd be milache. The cabin here on this program. So just any color you have there would be great.
Yeah, that's what we're trying to stay as neutral as we can on this so the you know we're just we want but we want our investors know what's going on as far as communication and we have been in active communications with the FDA. During this past quarter, which is what you know what we what we shared we haven't given details as to the types of Congress.
Stations.
You can your communications that we have had and I couldn't really speak to.
You know their thoughts on you.
You know the Postop space, certainly there have been a number of decisions and different no good with different products.
But no problem or has its own path and and we're working towards it. We don't we don't want to over pure overly optimistic we don't want to pick up as pessimistic, where I'm really trying to just communicate a neutral kinda position at this point in time, but just to let people know they're asking questions were giving answers very quickly I at this point don't want to give the types of questions are asking but.
[laughter] still going on.
Okay. No. That's fair I appreciate there's a lot of maybe switching gears to the alcoholic hepatitis program.
[noise] similar line of questioning on how you sort of see nine to a fitting in the context of the treatment paradigm I'm, particularly in the context of the watch and wait approach I'm looking at the recent you know gilliatt observational study that they'll present, a S.L.D., where sort of clearly earlier intervention, albeit with transplant.
Have resulted in better outcome and in that same line of thinking would help how you think about kind of accommodating a placebo response that patients are aggressively managed in a more well controlled clinical trial setting.
Well I think.
The nice thing about this.
Diseases, the patients do have an opportunity, but you know to have a liver transplant. There at the end of the line and there's no. There's no other help I know what I hope for them, so and they turned out to be.
Every bit as good stewards as the Hep C patients had been so that's nice to have that backstop. The unfortunate circumstances is that backstop is very expenses at a minimum kind of 800000 oftentimes goes well in excess of $1 million.
And so what we have with nitrate or something.
That.
You know, we hope can be out there to help these patients put them on the right track there's.
Physically and then allow them to to not to move forward with their lives in the right direction and you know save a tremendous amount of cost along with potentially saving lives and so we think there's a great opportunity to construct because as you know there is no therapy approved out there and steroids have been shown not to improve service.
I don't want to double the infection rate nearly so and so it's.
It's Uh huh.
We think it's a great opportunity for nitrate to be able to help patients and a nice are you setting and they will be the first of many indications, but certainly as very very important one probably one of the most important ones out there in the liver space today, It's one of the reasons why Dr. assessment is joining us.
And I look forward to when you guys get a chance to hear his experience because he just literally on Friday love to clinic and you know he was treating these patients you know for many many years. So I can give you his perspective as to why he's here and what do you think it's going to me.
Oh, absolutely I very much looking forward to that sort of virtual investor, but and just lastly, one question on the dash indication kind of given me benign safety profile that you guys observed in the phase one B study with oral candidate is there any plans to explore a pediatric Nash indication and.
So you know what sort of incremental talks work may be pending.
Oh that it would require additional talks and that is something the one always looks at but I think we would we would cut the pass through first in adults and then and then look for pediatric after but you are right in noting that the U.R. nitrate has a very nice safety profile.
To date, and we're quite happy that that that's the case.
And you know we're also very fortunate to have all of those parameters moving in the right direction. No for 28 day study, that's pretty impressive and look forward to sharing more data the biomarker data.
Yes, I'll be meeting coming up in another two weeks or so.
Great. Thanks for taking our questions and congrats on all the projects.
Thank you.
Our next question comes from the line of Michael Morabito would chart in capital markets. You May proceed with your question.
Hi, guys. Thanks for taking the questions just make sure that there are a couple of other states and so you mentioned that you have already opened a couple of sites so far.
But you haven't started dosing yet or do you have any indication of how many patients do you think that you make those young as early as this quarter in L. that will increase moving forward as you open that sites and could you also give us a.
And so how many of those sites will be in the U.S. versus at U.S.
Sure I'll, let wait she they speak to the the site.
Split between you and your projected projected I guess.
Yeah, Oh, what probably approximately one a one.
<unk> well be in.
Okay, and then two thirds also side well be.
In U.S. So that this is a death run from that that gets trial as a gen earlier mentioned, that's a one off the benchmark for the enrollment felt good about the most probably that's out there size was focused in Europe, but we decided to focus most on all sides.
In U.S., so that Oh, that's oh, well, we are currently well focusing on namely opening up at the U.S. side.
Okay. Yeah. Thank you, but you know I think that's good yeah, I think if we look at.
Using the the Gilead trial is the benchmark they took.
It was about 18 months for them to enroll 100 patients but that was.
Required six months my follow up and we will be doing all this treatment. So yes, it will be less.
Last time, there. They also required liver biopsy of all of their patients and that unfortunately tends to slow trials down and they required all the patients she takes stewards and that only this summer.
Were around 40% of serious patients are eligible to take Stuart So that was a substantial cut on the population as well when you add those together with the phase two data we have such a nice response and then yeah unfortunate fact that during the pandemic. This.
This condition seems to be a higher all of those things.
Have any color on the enrollment rate.
Okay, great. Thanks.
And as a follow up as you move there are there.
There are many begin enrolling and dosing patients what impact you expect that to have and the R&D cost moving forward over the next 12 to 18 months.
Well you know the <unk> trial. It Fortunately is not a particularly expensive trial and by pharma standards. It's it's you know probably about 25 million total.
External costs and so that will be divided up the cost you know the the duration of the trial so it though.
It's certainly something that we can afford to do and that and having our budget.
Okay.
And finally I'd just that you mentioned in your press release or the launches method or are they Orient pharma do you expect this to have any kind of meaningful.
Meaningful impact and then I've.
Credit derivatives with the board.
I'll, let Mike speak to right.
Yeah. So it's a you know whats the first country to see the launch so it's a Taiwan, which is a relatively small 80 HD market, so probably not right away.
Hopefully Orient, we'll be partnering it in additional countries. They have 14 countries and are in Asia. So.
Certainly would hope that they would be partnering in additional countries and that there would be a you know for growth there, but initially it will be pretty small we would expect.
Okay, great. Thanks for taking the questions.
Sure. Thank you.
Our next question comes from the line of Ed Arce with H.C. Wainwright you May proceed with your question.
Hi, Good afternoon, everyone. Since Thomas you are asking a couple of questions for.
Congratulations to our citizens apartment units directly.
My first question is about our appears to be a from trial.
Growing along that were or last couple of questions. The Berlin.
Roughly.
Okay, Okay that or.
Rough number of sites or so.
So far.
[noise] given a for us.
Parked in oney for severe.
Patients Onewest expenses pays open enrollment versus the phase two a proof of concept trial.
Well the interesting thing in the phase two trial, we enrolled severe patients much more rapidly we enrolled all 12 their patients before we had completed we had only <unk> and all seven of the moderate patients because the moderate patients don't typically they.
They sometimes go to the hospital, but if they do they don't stay very long and because they aren't as severely ill.
So the fact, when Boeing severe I think well actually unfortunately, you know they prefer because they're sick well you know about the physical presented in a much higher rate.
Hum the number of centers I don't know that we've ever broken that out weight she's.
Oh, no I don't think so I don't think we haven't broken it out it's going to be a good number it'll be in north of 40 centers total between North America and Europe.
Hi, Omar, Yes, Oh anymore yeah.
And then we have a number that weve already you know have site initiation visits and we have more planned almost you know whenever they come on a weekly basis, we added more and more and then.
And you know they they get shut drug and let me just start set up and getting ready to go. So we are just starting it up but very very excited about being able to help these patients.
Yes, definitely it sounds like ER progress so far.
And recording the affirms and Orange.
Especially I think the survival benefit or professional or for accuray or receivables or do you believe kirker April nine two rates are at the.
Yes, if we if we're able to show robust survival at 90 days, it's hard to argue against that right. Because survival is that's kind of the ultimate endpoint and.
Surrogate endpoint isn't endpoints are very important clinical and the most important one so yeah.
If we can show an improvement in survival over placebo when there's no therapy out there today that is approved and patients are dying at a rate that you know somebody the worst cancers out there one month to month and three month survival. Ah you know, we certainly believe that would merit I'm sure the merits.
Eric and accelerated review and potentially getting approval on a single trial.
Right.
Okay. There were some go forward to EUR one question regarding the NASA over.
Given.
Three doses that were tested and it's one of the.
Are the ones that they are.
Are there any work on going to are either narrow down for those or perhaps even a testing you know where they have a new dosage right away for phase two.
Well certainly the next trial that we would do would be some type of Oh.
Thanks to a trial would be my guess and ER and the dose will be further refined there, but I don't know what you're doing to speak to the dose.
Well people inside.
Yeah, I think that that Oh wait for this current study completed the study and we have all that well why a dose range on the cost of the from 50 to 600 milligrams a day. So that's quite a wide range of Oh said, well then you are not until.
Hi, I'm a sub Jim earlier mentioned that a week just to have received the outbound holiday topic has the often done like unto itself and that mix ups down the age and.
So right now we have all the data together, we get submitted that post though for the S.L.D., but at the same time why in the process all cost sharing all data and then talking to multiple I'll fall can't rule out until gather feedback well could be out next study HM.
Field.
Okay. Thanks, Brent Becker were working up they are up and.
Most of all that I think are what kind of questions and congratulations on her sensible core.
Thank you so much.
Our next question comes from the line of Elemer Piros with Roth Capital Partners. You May proceed with your question.
Yes, Hello, everyone.
[laughter].
Jim If I may just are in for a quick moment and Mike Mike Yeah, I was too slow to ride done how many shares you issued during the quarter, maybe if you could give me please the ending share count.
As of September Thirtyth, if you have it.
Yes.
203.2 million shares.
Two or 3.3.
Thank you.
And then in the Cobot study how many sites do you plan to add to the current three.
What is the plan you know, it's it's not going to be a huge number at this point right.
Right now, where we're looking to maybe go.
Well that and it will depend on how long it goes and how this virus goes and where it goes because if it's not a simple process do you find that the same city and then.
Difficult, it's very difficult to go to a city that is.
The hotspot.
And to set up at that point in time, because the centers are just overwhelmed and.
And so one needs to be somewhat anticipatory anticipate a little bit or find a center that that is not yet burning so hot and work with them 'cause it takes quite a bit of time to get a sense of up and running with all the legal paper work that needs to be done.
So I think we'll just have to we're just kind of we're moving through the process is very dynamic.
As it grows so do you have an advantage or vis-a-vis some competing.
It's a great question yeah.
In terms of it.
Yeah.
Address the unique aspect.
I think so I don't know that there really is anyone else out there looking to treat patients that have other organs that are damaged actively certainly the steroids are out there and being used for that and we're happy to use lightweight with your right. So that's that's fine and with any idea about that.
Okay helpful and I guess.
But.
Ah you.
You know it is so that I think it's to our advantage. The the reality of it is there are huge number of trials out there most of them are trying to help patients who are less.
Less severely ill that younger ones, we know we're going for severe the critical so most of our patients there were looking at our.
Yes, you are just about to go into the as you look at the different group of patients that a lot of.
Agents are looking at and then the other you laid over the top is that these vaccine trials, which although we're not competing with them in some.
From the site of patients, we're competing with them. Unfortunately by virtue of just infrastructure within a given hospital system and having study coordinators and the like so we do have some companies are looking to enroll 30000 patients or 50000 those are a wave of.
Oh requirements from these facilities that are that are challenging for them to deal with at the same time. So all of these things kind of interplay. So it's a complex <unk> well.
Yeah. So.
Once you had a.
And to share the complete national day covered the K alone.
And do you think we might hear [noise].
About the next step.
Our phase three trial is described it.
I think it will probably be a next year event and B I guess I'm just based on that I mean, we have there so I'll be coming up very shortly.
And we're talking to people certainly be talking to more people.
During its will be opposed to sobi with.
Stock assessment being on board. He will also be involved in the process. So I.
I don't know what you'd want to try and give any more clarity or is that reasonable.
I think that's reasonable I don't have that thing out so yeah, yeah, yeah, because the end of years coming faster than we'd like Unfortunately, yeah, yeah yeah.
Well. Thank you so much I'm sure.
Our next question comes from the line upfront Quadras Boy with Oppenheimer. You May proceed with your question.
They are very quick last one here I'm just wondering any update on a potential publication related to the mechanism of action of their nine to eight or just any color there.
He is working on it I don't know what GE, but what would you say about the manuscript folks going on.
Yeah. The manuscript has been submitted it and I'm ready to from outside and we do hope it saying Oh I couldn't be published the valley. So.
Oh cost Oh people, who are familiar with the publication procedures, sometimes maybe it depends on the added to its all that with you as they may want though the author too.
By the time paragraph I, they have different quite class chains, and that's how you should all like all the back and forth I feel wrong. So by then the manuscript Happing outcome compiled and that's something that sells well well they hoping it can be oh.
Yeah. It represented a great number of years never years of hard work by that last let me tell you already had a good well understood I just I had had to ask that you sure no [laughter] yeah.
Our next question comes from the line up paying sign with Gannett Securities. You May proceed with your question.
Hi, good afternoon, Jim Congratulations.
Dr Assessment to your team.
I'm not sure that this will be a major addition, and hopefully move projects along the more rapidly over time most of my questions have been answered, but I did have one week.
To the A.H. study if you if I could.
[laughter] ours, the hospitals that were involved in the earlier studies participating in the current anticipated study 300 patients.
I'd say almost all of them are and a lot of different [laughter], which you've already said.
Yeah, I think the I would say the same thing yes, yeah I know there's always a lot of people are you know been calling and asking when it's coming because they have so many of these patients. It's it's really sad and a lot of young people and are in their late Twentys and Thirtys. If he does I'd I guess, there is just more binge drinking but.
O'neal then there was from my generation for sure so.
Well I I noted that.
Your your earlier comment was that one.
Third of the hospitals would be in Europe.
Is that because we can't get enough.
Hospitals here in the <unk> in the United States, why or why are we extending the program to where you are I think it but I think it's both because the the disease. The circumstances occur both places number throwing everything we can to try and then speed enrollment and so we're we're availing ourselves of all possible.
You know, there's there's a decent fight out there that that they can help and especially you know if you look at <unk>.
You know what's going on in the UK and in certain places in Europe there yeah.
Northern Europe, and the likelihood and eastern Europe, there's a lot of.
Problems with alcohol consumption.
All right got it okay fine. Thank you very much and consider the gearing congrats on not on on adding Dr. assessment to your team no.
Oh thanks.
Ladies and gentlemen, we have reached the end of today's question and answer session I would like to turn this call back over to Mr., Mike Aaron Berg <unk> closing remarks.
Well thanks, everyone for participating we're excited about the progress we're making on a number of fronts and look forward to keeping in touch with those of you that we'd like to reach out over the next few days and weeks and months and Ah. Thanks.
Thanks again for participating.
Thank you all again.
Thank you for joining US today. This concludes today's conference you may disconnect your lines at this time.
[laughter].
[noise].