Q2 2023 Altimmune Inc Earnings Call
Good day, ladies and gentlemen, and welcome to the Ulta Beauty, Inc. Second quarter 2023 financial results Conference call. At this time all participants are in a listen only mode. Later, we will conduct a question and answer session and instructions will follow at that time.
To ask a question during the session you will need to press star one one on your telephone.
As a reminder, this call is being recorded.
I would now like to introduce your host for today's conference call Rich Eisenstadt, Chief Financial Officer of Alta meal Rich you may begin.
Thank you J J and good morning, everyone. Thank you for participating in the afternoon second quarter 2023 financial results and business update conference call members of the ultimate team and joining me on the call today are Vipin Garg, Chief Executive Officer, Scott Roberts, our Chief Scientific Officer, and Scott Harris, our Chief Medical.
Officers.
Following the prepared remarks, we will hold a question and answer session.
A press release with our second quarter 2023 financial results was issued this morning and can be found on the Investor Relations section of the company's website.
Before we begin I'd like to remind everyone that remarks about future expectations plans and prospects constitute forward looking statements for purposes of Safe Harbor provisions under the private Securities Litigation Reform Act of 1995 autonomy and cautions that these forward looking statements are subject to risks and uncertainties.
Cause actual results.
Really from those indicated for a discussion of some of the risks and factors that could affect the company's future results of operations. Please see the risk factors and other cautionary statements contained in the company's filings with the SEC.
I would also direct you to read the forward looking statement disclosure in our press release issued this morning, and now available on our website.
Statements made on this call conference call speak only as of today's date Thursday August 10, 2023, and the company does not undertake any obligation to update any of these forward looking statements to reflect events or circumstances that occur on or after today's date.
As a reminder, this conference call is being recorded and will be available for audio replay on all screens website with that I will now turn the call over to Dr. Craig <unk>, our Chief Executive Officer.
Thank you rich and good morning, everyone.
We appreciate you joining us today for a discussion of our second quarter 2020 financial results and business update.
We are excited about the progress of our lead product candidate <unk> do died a G. L. P. One glucagon dual receptor agonist in development for both obesity and Nash.
We recently announced the initiation of our phase two b impact biopsy driven trial to evaluate the efficacy and safety of family do died in Nash.
Given the compelling 12, and 24 week data from our phase one b trial in subjects with national deep.
We expect to achieve significant rates of Nash resolution.
And fibrosis improvement at data readout from the impact trial.
As anticipated in Q1 2025.
The data from our Nashville, deep trial demonstrated a greater than 75% relative reduction in liver fat at 24 weeks.
With over 50% of subjects, achieving the high bar of normalization of liver fat in the one eight milligram dose group.
Subjects also had a mean weight loss of up to seven 2% at 24 weeks in the one eight milligram dose group.
With weight loss continuing at the end of treatment.
We also achieved significant reduction in seat EMEA, LT and MRI based corrected one imaging.
Both are important markers of Nash improvement.
We believe that a robust reduction in Nash activity combined with fibrosis improvement.
And meaningful weight loss will be essential for a competitive product in the Nash marketplace.
With regards to obesity, we look forward to reporting topline 48 week data from our phase III momentum trial in the fourth quarter of this year.
The momentum interim results of 160 subjects reported earlier this year.
Showed weight loss of 10, 7% at the two four milligram dose and nine 4% at the one eight milligram dose compared to a 1% weight loss in subjects receiving placebo.
After only 24 weeks of treatment.
These robust reductions in body weight together with the effects of Perm, who died on serum lipids and blood pressure.
Without cardiovascular safety signals suggest that if approved and we do that can be an important treatment option for patients with obesity.
Especially those with Nashville, the Dyslipidemia.
It is important to point out that these two co morbidities.
Haviland and 60% to 75% of the obesity population.
Finally, we have to have a data readout from our phase II clinical trial of <unk> T cell in chronic hepatitis b in the first quarter of 2024.
Recall that this trial is designed to show evidence of anti viral effects against hepatitis B virus and.
And establish the rollout have T cell in combination therapy for the treatment of this unmet need.
We're excited about the progress of pending just I didn't have a T cell.
And the upcoming results of these ongoing trials with that.
I'll now turn the call over to our Chief Medical Officer, Dr. Scott Harris to discuss our clinical plans Scott.
Thank you vipin and good morning, everyone.
First let me tell you about the initiation of our impact phase III Nash trial.
Despite C driven trial is being conducted at approximately 60 sites in the United States with Dr. Stephen Harrison Medical Director clinical research and adjunct Professor of Medicine, Oxford University.
Serving as the principal investigator.
We are planning for approximately 190 subjects, both with and without diabetes to be enrolled.
Subjects will be randomized to <unk>, one two milligrams.
Panther do tied one eight milligrams or placebo.
One to two to two ratio it will be status stratified for fibrosis stage and the presence or absence of diabetes.
Therefore, approximately 38 subjects are expected to receive Panther do type one two milligrams seven.
76 subjects Perm to do tied one eight milligrams.
76 subjects placebo.
To be eligible for our study participation subjects will be required to have a BMI of at least 27 kilograms per meter squared or.
Our liver fat content by MRI P DFS.
At least 8% and the natural the activity score of at least four on a pre treatment liver biopsy.
We also expect to have either <unk>, two or three fibrosis with at least 50% of subjects required to have F. Three fibrosis.
The primary end points of the impact trial will be the dual endpoints of achieving either.
Nash resolution with no worsening of fibrosis or fibrosis improvement with no worsening of Nash with the primary treatment comparison being the one eight milligram dose versus placebo.
Secondary endpoints will treat will include achievement of both Nash resolution and fibrosis improvement.
Liver fat reduction by MRI <unk>.
Correct T one or CET, one response rate serum lipids and noninvasive biomarkers of disease activity.
Importantly weight loss will also be assessed as a key endpoint.
All endpoints will be evaluated at week 24 week treatment in subjects will continue to be dosed and followed for an additional 24 weeks to a total of 48 weeks for safety and additional biomarker responses.
We plan to employ a consensus read between two pathologists with a third who will do judicate. If consensus is not reached.
Our plan has also been developed correlate noninvasive tests with Nash resolution and fibrosis improvement the biopsy endpoints and have commenced discussions with FDA regarding the use of these biomarkers as primary endpoints in phase III.
We anticipate reporting top line results of 24 weeks in the first quarter of 2025.
Now, let me talk about the phase III momentum trial of Perm to do tie in obesity.
The trial was designed to enroll approximately 320 subjects without diabetes, but with obesity.
Or overweight with at least one obesity associated kormos comorbidity Dr.
Dr. Lu of Rooney from Weill Cornell Medical School, a leading authority in obesity and obesity clinical trials is serving as the principal investigators subjects were randomized one to one to one to one dependent to do tied one two milligrams Panther do tied one eight milligrams.
Panther do tie two four milligrams or placebo administered weekly for 48 weeks in conjunction with diet and exercise.
Pre specified interim analysis was performed on a 160 subjects completed 24 weeks of treatment.
Weight loss of 10, 7% at the two four milligram dose of nine 4% at the one eight milligram dose was achieved compared to a weight loss of 1% in subjects receiving placebo.
Approximately 50% of subjects achieved at least 10% weight loss and approximately 20% of subjects achieved at least 15% weight loss by week 24 at the two four and one eight milligram doses.
Significant improvements are positive trends in cardio metabolic risk factors were observed.
Importantly, these effects were achieved without a risk without arrhythmia is clinically meaningful heart rate increases or other safety signals.
We look forward to the topline 48 week results for a moment the momentum trial in the fourth quarter of this year.
We expect to see continued weight loss beyond the double digit levels noted in our 24 week interim analysis other.
Other top line readout parameters will include subject disposition adverse events vital signs serum lipids and glucose control.
Also as we have previously announced we have completed enrollment in our phase II multicenter clinical trial of <unk> in patients with chronic hepatitis b.
Chronic hepatitis B continues to represent a serious unmet need in the United States and worldwide and represents a significant commercial opportunity.
<unk> is an immuno therapeutic designed to activate T cells to fight the hepatitis B virus infection.
The Hep T cell trial was designed to enroll approximately 80 subjects with an active chronic hepatitis b and low hepatitis b surface antigen the.
The primary endpoint of the trial is a one log reduction or clearance of the hepatitis b surface antigen.
We expect to announce the results of this trial in the first quarter of 2024 once all subjects complete the six month treatment period.
As general believe that an effective therapy for chronic hepatitis b infection will require both direct acting antivirals in immunotherapy and.
And we believe that Hep T cell, it's hybrid highly differentiated highly differentiated and may provide for a functional cure of chronic hepatitis b infection with combined with novel direct acting Antivirals.
I'll now turn the call over to Ritch Allison start to give an update on our third quarter financial results rich. Thank you Scott and good morning, again for today's call I'll be providing a brief update on <unk> second quarter 2023 financial and operating results more comprehensive information will be available on our Form 10-Q to be filed with the SEC.
Today.
<unk> ended the second quarter of 2023 with approximately $160 million of cash cash equivalents and short term investments compared to $184 $9 million at the end of 2022.
Research and development expenses were $13 $3 million in the second quarter of 2023 compared to $16 million in the same period in 2022.
Approximately $7 $4 million of this total for the second quarter of 2023 were direct expenses for the conduct of our clinical programs, including $5 $6 million and direct costs related to development activities for <unk> and $1 $8 million in direct costs related to the development activities for <unk>.
General and administrative expenses were $4 $8 million for the three months ended June 32023, compared to $4 $4 million in the same period in 2022.
The change was primarily attributable to increased stock compensation and other labor related expenses approximately $3 million of our quarterly operating expenses noncash expense primarily stock compensation.
Interest income was $1 $8 million in the second quarter of 2023 compared to $300000 in the same period of 2022.
Net loss for the three months ended June 32023 was $16 1 million or <unk> 32, net loss per share compared to net loss of $21 million or <unk> 42, net loss per share for the second quarter of 2022.
We estimate that our existing cash funds us through the 24 week biopsy results from our impact phase III.
Nash trial expected in the first quarter of 2025, our financing also funds completion of a 48 week momentum trial and the hefty cell trial.
Now I'll turn it back over to <unk> for his closing remarks.
Operator that concludes our formal remarks, and we would like to open the lines to take questions.
Could you please instruct the audience on the Q&A procedure.
Yes.
Thank you as a reminder to ask a question. Please press star one one on your telephone and wait for your name to be announced.
Draw. Your question. Please press star one one again.
Please standby, while we compile the Q&A roster.
Our first question comes from the line of Seamus Fernandez from Guggenheim.
Hi, there this is Amanda on.
Christine next from Guggenheim. Thanks for taking our question. We were just I'm curious as far as your expectations for weight loss at 48 weeks and are you still targeting mid to upper teens and secondly.
Any thoughts on what Merck presented with respect to you there.
Our net Eagle recently, thank you.
Sure Atlanta and good morning.
Scott do you want to take that.
Yes. Thank you for the question, yes, we still are expecting weight loss in the mid to upper teams. We think that in view of the select readouts, which showed that to be associated with a significant reduction in cardiovascular risk.
Significant point to achieve but with regards to select I would point out that that was achieved.
With <unk> monotherapy alone.
And with the glucagon effects, we believe that with the reduction in serum lipids and also hepatic fat that we can achieve even better results than those achieved.
Some are glued tied on that trial.
With regards to Merck we believe.
I'm.
Findings validate.
Our.
Our continued hypothesis and results on this.
Extremely important for reducing liver fat.
So we were happy to see confirmation of the information with several things I would point out about that trial was number one that had to go through a significant titration period.
We're not doing that we have no titration at the two doses that we're employing.
Our upcoming.
Trial <unk> trial and the second is our compound has also been associated with significant heart rate increases.
Which as I mentioned in my opening remarks, those have not been seen in our program.
Great. Thank you.
Okay.
Thank you one moment for our next question.
Our next question comes from the line of Yasmin Rahimi from Piper Sandler.
Yes.
Good morning team and thank you so much for all the great update.
I think this morning.
Now that the select data.
That's neat cause really emphasized.
How the demand for new novel therapies for obesity continue to increase I think we saw also this morning another acquisition by Knowable. So this raises the question sort of you could just kind of give us an update on how the M&A interest.
Evolving I think we have seen in the last month two acquisitions of therapies.
Where they bring broad of novelty and that it's not just about weight loss. So I would love to get an update on how M&A interested.
It is growing and what do you expect the impact on select will be in your discussions with potential partners around obesity.
And then secondly, there are two additional key readouts.
Upcoming in the first half of 2024.
<unk> T data from tourists appetite.
Well.
The glib glucagon compound from <unk> Zealand, So would love to hear your thoughts on how you're thinking about how those resolved could provide color or detail or translation or anything around that I think a lot of our clients may not be may not realizing that those julie.
Readouts are really key so we'd love to hear you could tackle M&A tackle.
What do you expect to see in these two biopsy readouts with two anchor tenants in the first half of 2024, and I will jump back into the queue. Thank you.
Thank you yes. Thank you for the questions. Let me take the M&A question, and then I'll turn it over to Scott Harris to talk about the data coming out.
In the first half of next year.
So as you know we've been saying all along that obesity is going the whole market is going to segment.
Going to be multiple mechanisms that that people would want the physicians want the patients want and they would benefit from it and Thats basically what we are starting to see now that this is not game over with just the first generation of <unk>.
Obesity drugs, but we are going to need additional mechanisms and thats exactly what we bring to the table.
By adding glucagon to DLP, one we think that really gift set.
To provide some additional differentiation from <unk> alone.
That we are seeing profound improvement in serum lipids.
<unk> class, leading liver fat reduction.
If you look at this patient population.
First wave of diabetes treatment is really designed for.
Obesity treatment is designed for patients with obesity and diabetes, but there's many more patients that don't have diabetes, but have other comorbidities such as set of Dyslipidemia and high liver fat content. So we think we fit really nicely there and we've been very encouraged there is lots of interest as you have seen already.
From two recent acquisitions.
In novel obesity mechanisms and compounds and glucagon is going to have a seat at the table. We are seeing that from large pharma from their internal programs. The data coming out on glucagon. So we are very encouraged with our ongoing discussions and the data from momentum upcoming data from momentum.
And the fact that we have initiated impact is.
Going to further capitalize those those discussions so we're very excited about the prospects of having a partner on board before restock phase III development in obesity.
Time next year.
Yeah, Ashwin and I'll take your second question about the tours appetite in the Boehringer Ingelheim Zealand Readouts in the first half of next year.
I think it's important to point out that tourist appetite hasnt gone activity.
And the <unk>.
Activity in the Boehringer Ingelheim Zealand compound is pretty minimal its the compound is highly biased to <unk>. The ratio was eight to one.
And as evidence of that Theyre, not seeing meaningful effects on serum lipids and for that matter <unk> appetite and that tracks directly to the absence of having glucagon. In contrast, we have glucagon were nominally seeing.
Very significant reduction in serum lipids, but also liver fat as well.
And Theyre Noninvasive study two separate tied at the 15 milligram dose there top dose only achieved a reduction in liver fat content at the end of an entire year.
39% and we think that we think that reflects what I just said about glucagon.
Zealand has not come forward with any noninvasive data about the liver fat, but we think it would follow the same pattern. So.
We still believe the glucagon is key.
Two the rapid reduction of liver fat, we think the rapid reduction of liver fat is important for retrieving not only Nash resolution and fibrosis improvement on the biopsies and we think that.
The results that we get from our impact trial will significantly exceed those from either of those two compounds in the first half of next year.
Thank you so much team and really excited on the continued progress I'll jump back into the queue.
Thank you one moment far next question.
Our next question comes from the line of Roger song from Jefferies.
Great.
We're at four one.
A lot of progress as well and thank you for taking the question maybe a couple of questions mostly related to the obesity first of all maybe can you comment on you.
Our readiness for the phase III for the obesity trial in terms of the.
Dosing and there may be some of that consideration after you've seen the phase <unk> 24 week data.
At a minimum and are you still waiting for that 48 week, but just curious.
The preparation for the phase III.
Conjunction with partnership discussion.
Number one number two very interesting.
And you mentioned this comorbidity with.
Oh, PCT, a pretty high percentage just curious given the very differentiated Glucagon addition to the mechanism.
How likely you think your you can do some.
Creative design for the trial, maybe enrich those comorbidity patients to demonstrate even bigger.
She may in fact, all of the benefit for those patients with the comorbidity. Thank you.
Absolutely Scott do you want to take the Comorbidity question first yes, Roger Thanks for the question. So obviously, we're deeply in preparations for phase III.
And we have not been public about what those specific plans would be but we have talked about the fact that based on the prior programs. We think the safety database would be about 5000 subjects with about three quarters of those receiving active drug and about one quarter receiving placebo. It appears that it's the size.
So the safety database that matters.
The agency appears so we wanted to study in non diabetics in diabetics beyond that theres been some options about looking at for example, osteoarthritis looking at co morbidity and the like and we're in active discussions right now.
We've been getting feedback from partners about that as well as what their preferences would be.
As soon as we have additional information about that we'll share that with investors.
<unk> to do a couple of things first of all in terms of being phase III ready and our plan is to be phase III ready.
The second half of next year. So obviously, we have to wait for the 48 week data before.
Requesting a meeting with the FDA, which we plan to do so we are putting all the plans in place for that and.
Our goal is to have a partner lined up before destock phase III, so from a timing perspective that kind of fits nicely.
It gives us the first half of next year to both lineup at partner as well as as well as to have the phase III ready program as soon as the as soon as we have the end of phase II meeting with the FDA.
In terms of enriching patients for co morbidity.
<unk> as Scott mentioned, it's going to be a fairly large phase III campaign anyway. So we really don't have to go looking for these patients. These patients out of that I mean that the prevalence of these two comorbidities is even higher than diabetes. So it's not hard to find these patients. So so we were.
In a good shape in terms of having access to those patients.
In the obesity subpopulation, if you want to think of it that way Scott Yeah, Roger what I wanted to add in I was waiting for Clifton two finishes comments.
Was that the best place to look at those that enrich populations as an an outcomes trial because actually that's the endpoint right and you want to make sure that decided quickly powered.
So as I mentioned in the opening remarks, the select trial is extremely important for showing that obesity.
Improves the outcomes of patients at risk.
Also mentioned in the opening remarks, we think that with comparable weight loss, we will do better than that because of glucagon effects on serum lipids in the paddock fat content.
So that trial will be enriched with those patients we think thats, probably the best place to analyze those results because of the number of subjects in the power and the trial and what the outcome actually is.
That's great. Thanks for all the comments I really I really appreciate it that's it from us.
Thank you one moment far next question.
Our next question comes from the line of Corin Jenkins from Goldman Sachs.
Good morning, this is Craig on for Karen.
So I wanted to build on a point that you just highlighted specifically that about finding a partner to develop and video tied and I guess, what I'm wondering is can you describe what your ideal partner would look like and specifically are you looking for someone to contribute to the development of Nash and obesity or just individual.
Indications.
Absolutely.
Good morning, and thank you for the question. So I mean, the best thing the best.
The way I can describe it that we're talking to fairly large universe of companies all of the companies that you would expect us to be talking to and then some.
In terms of looking at the indications.
We don't believe that a partner would want to split indications given that it's the same molecule and its the same drug for both Nash and obesity. So yes, our ideal partner would be somebody who is interested in both of these indications and the good news is that they are both metabolic diseases.
We are finding that people are interested in both indications and even additional indications.
Four.
<unk> and <unk> based compounds so overall.
We have flexibility we can we constructed the deal and maybe its ways, but I think both of these indications perhaps all indications would be included in that partnership the key for US is to really get the full value for the assets. So we are very encouraged with conversations and we'll keep moving forward.
Got it thank you very much.
Thank you one moment for our next question.
Okay.
Our next question comes from the line of my Young Moms, Johnny from B Riley Securities.
Good morning, Thanks for taking our questions a few from us.
Staying on this theme of new Gabon based therapeutics being complementary.
Number of go.
Programs out there.
I was curious if there's any work underway regarding combinability with chemo.
Large face to be us.
As even some side of background data.
Diabetes obesity level.
Not sure if you can comment on what those rate side. So you haven't been able to dig out of the clinical trial design yet on <unk> Gov.
That's close.
And then I have a couple of follow ups.
Yeah, Mike we believe.
<unk>.
<unk> would be saved on top of existing <unk> one therapy.
It's something that we've certainly looked at as potentially studying at some point in the future, but our current feeling as though there would be no problem.
Physician wanted to combine those therapies using them concomitantly and.
And more importantly, we should see additional benefit of putting family do died above over and above any of the baseline diabetes treatments again because of the glucagon component and having.
Direct effective direct hepatic.
Effect on hepatic fat.
Thank you Christine <unk> activity should only be helpful. Given does and then momentum quickly.
Baseline characteristics there for the full patient cohort relative to be embedding analysis population cohort that unit quoted out in March.
Any any insight you have bid on defensive and I was also curious about it there are certain sites that may have contributed to a higher.
Discontinuation rate so it was there.
Was there like a ratio that you can share what the.
<unk> versus being debt about analysis population looks like in those sites.
Yes, Mike we announced when we completed enrollment in momentum and I believe that was in the.
September of 2022, we announced that we had done a comparison of the full population versus the interim analysis population.
And that.
We have made have made public statements that the demographics were comparable in terms of age BMI.
Body weight gender ratio.
And the like.
So there's been no additional information that was really a snapshot we took when the trial completed enrollment.
Regarding the discontinuation rates of trials, yes, there has been.
Some sites that had.
Out of place.
<unk>.
Rates of discontinuation that clearly were higher than other sites for example, doctor erroneous sites had no discontinuation at all and it showed that the careful management of patients really.
Controlled or mitigated the discontinuation rate.
So yes that is something we've taken a look at those sites and whether they would really be sites that we would consider for future trials.
Okay got it and how to ask a quick some legacy Vod drive question, obviously, we have to see the quoted out there, but since this was a non type two diabetes.
<unk> population and everyone's trying to understand the SBA loans the independent mechanisms at work there I was curious about the CRP biomarker.
As we know the inflammatory underlying Steve that can help them outcomes is that marker youre.
Youre looking at.
India now study that is standing out or even in the obesity studies would report on that.
We hope to have that information in the future. We don't have information to share at this point.
Okay and last one for rich quickly on the R&D spend coming down quarter over quarter obviously.
Ramp up with this nice steady scaling up and we should.
I had that sort of trend back up.
Curious, if any new manufacturing capacity related investments.
That also kind of feed into that.
Obviously, you are probably making sure that you are making investments with a key supplier.
Supply of the drug.
Yes.
All of that is true Mike.
Spend did come down as some of the other trials the Napa Charles we ran last year for diabetes drug drug interaction trial rolled off so Q2 is pretty much just.
Momentum.
Trial expense, a little bit of investment into the impact trial looking at the second half of this year the impact travel expenditures should increase and as you point out. We also will have some manufacturing expenses.
To get the phase III materials ready.
All of that will probably lead to some increase or.
Rebound back to the old R&D expenditure rates, but that should be just temporary or a tap role as momentum completion of patients are rolling off that trial now so as we complete that there's always a big expenditure towards the end of the trial as we do the data analyses and such for us, but that will end up.
Rolling back out and.
In 2025.
Our 2024 I'm sorry.
Understood. Thanks for taking our question.
Thank you one moment for our next question.
Okay.
Our next question comes from the line of Joe John Welborn from JMP.
Hey, good morning, and thanks for the update and taking the questions two for me.
You mentioned expectations for weight loss after 48 weeks, but I was hoping you could talk about what you think you will see in terms of Tolerability Gi adverse events, especially within the context of the trial design and then also Scott you mentioned heart rate a couple of times I'm wondering what you view as that threshold between acceptable and unacceptable heartburn.
Rate increases for the class.
Yeah. Thanks, Jonathan regarding the first we're still blinded to.
So the data we certainly are not seeing any thing that would indicate that.
We would have.
Any worsening of any adverse events.
We think theres only the <unk> prospect of this continuing to get better, but we'll have the data at 48 weeks.
One thing to point out as we go into phase III.
There's learnings in phase two we have seen that with all of the companies. We saw 20% adverse event discontinuation rates with the oral <unk> one program, but Lily program, we saw it with the tourist appetite excuse me we saw it with the Red II tried program and it was also as we've mentioned in prior calls <unk> seen another phase III.
Programs. So we think that these companies have clearly address this and we think that our dose reduction strategy.
It's something that will really bring this down over the course of time, especially in phase III.
Regarding the heart rate increases.
It's not really known what the actual threshold is.
But one of the things I would point out is the concern.
In the Red II tried trial that heart rate increase was also associated with <unk> and the two could be linked.
In the ready to tried.
Phase one studies they were seeing heart rate increases that were quite high as much as 30 beats per minute early on the data that we're reporting out is really at the end of the trial.
So there's a lot more to learn as that data comes out, but I would flip to the positive and say that we're not seeing that with our data we're not seeing any heart rate increases, we're not seeing any imbalances arrhythmia, and we really think that that distinguishes us from.
From Red to tried and other compounds in the field.
And Mechanistically you would expect that to happen early on in treatment for opioid after 24 weeks on unlikely to see a 48.
That's a difficult question, but there does appear to be higher heart rate increases early on there appears to be adaptation over the course of time.
So what's important to understand with regards to say Theres a rhythm, yes, it's not that they occurred but when they occurred during the course of the trial now.
Charles that are being conducted in phase two or.
Alrighty clinical development standards relatively small they are supposed to be in phase two.
But these are the kind of events that come out and outcomes trials when you're studying 15000 subjects, we feel very comfortable with our cardiovascular safety profile, but you know as you start.
Any drug with any kind of signal in expanding the population you may be seeing something.
And a large outcomes trial, especially one that's a risk enriched with patients at risk.
That's helpful. Scott, Thanks, again for taking the questions.
Thank you one moment for our next question.
Our next question comes from the line of Patrick <unk> from H C. Wainwright.
Hi, Good morning, Luis here on for Patrick Thanks for taking our questions.
One question regarding the Nash program ends.
Our.
24 weeks and efficacy benefits on Nash resolution and fibrosis improvements.
And do.
Do you think you can already have some.
Data preclinical data that could predict that.
And then I have another question on the Hep C.
Program.
Alright, Thanks for the question Louise So we do have preclinical data.
Animal models of Nash, showing fibrosis improvement and that's been accompanied also by gene expression studies, showing a reduction in those drivers of satellite so activity in fibrosis.
Regarding the 24 week end point several companies have shown the ability to achieve Nash resolution and fibrosis improvement at 24 weeks and we believe that with our class leading liver fat reduction effects.
With the link between liver fat reduction and the factors that you just mentioned, we think we have a very high likelihood of achieving.
Success in those end points at 24 weeks.
Yes, it's important to point out that is not just the magnitude of the effect. It's also how fast you can get there so.
So not only these class leading in terms of overall reduction in liver fat, but.
Speed of it very fast reduction in liver fat, we believe gives us plenty of time for them for the liver to shield in 'twenty four.
Thank you that's helpful.
Can you discuss the antiviral mechanisms that you believe will be most complementary to the Hep T cell and.
What do you need to see in the T cell data to do you have more confidence to move the program forward to a larger trial.
Scott.
I'm going to combination trials potentially.
Sure Robert do you want take that absolutely.
Yes, so the mechanism of hefty cell itself, which is an immuno therapeutic is to stimulate T cells that are able to recognize them.
HBV virus and in that way how clear the virus from the infected cells as you know the recent anti virals.
<unk> monoclonal antibodies against surface antigen have been very effective at dropping the surface antigen level, but the removal of those agents causes a rebound and the and the level of that surface antigen immune tolerance state that results from that.
That's why it's generally believes that the combination of a direct acting antiviral too low with the surface antigen levels and take the pressure of the immune suppression of Siemens system together with an immunotherapy.
To wrap up that the now released immune system could.
It could be an effective way to treat this disease and so we believe that <unk> with its ability to stimulate.
Responses against very conserved portions of the HBV preliminaries and core antigen will be an effective immunotherapy that when combined with a with an effective anti direct acting antiviral.
Could yield very interesting.
Effective therapy as far as what we're expecting in the phase II <unk> study.
Study.
Efficacy endpoint.
Is set at a one log reduction in surface antigen.
We believe that thats readily achievable.
Really any.
Sort of convincing effect.
<unk> therapy with a hefty cell would then align us and prepare us for four or.
A follow on study with a direct economic barrel.
Great just a just a quick follow up on that would you have any other types of analysis on E antigen presenting cell.
Sure.
The potential if I could have not.
Not just a stronger response, but a broader response with the type of CDA T cells that are required to to clear those infected cells.
Well, especially with respect to breath.
Really one of the differentiating aspects of hefty sell it's the epitopes that we've selected to include.
And the peptides that constitute happy so.
So with respect to breath, because these epitopes are in largely and hydrophobic regions and are highly conserved between the different genotypes, we feel that the immune response, which we've demonstrated pre clinically to be brought against.
At June <unk> would extend through all of the known genotypes right now with the bioinformatics would suggest and we do have the preclinical data showing a very broad response.
Great. Thank you.
Thank you at this time I would now like to turn the conference back over to Vipin Garg for closing remarks.
Thank you. Thank you everyone for participating today, we appreciate the opportunity to share our results and outlook with you and thank you for your continued interest have a nice day.
This concludes today's conference call. Thank you for participating you may now disconnect.
Okay.
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