Q3 2019 Earnings Call
Operator: Good afternoon. My name is Catherine, and I will be your conference operator today. At this time, I would like to welcome everyone to the Enanta Pharmaceuticals third quarter financial results conference call. All lines have been placed on mute to prevent any background noise.
At this time I'd like to welcome everyone to the N. and I must say to close third quarter financial results Conference call.
Oh lanes hasn't seen some mute to prevent any background noise.
After the speakers remarks, there will be a question and answer session.
Operator: After the speaker's remarks, there will be a question and answer session. If you'd like to ask a question at that time, please press the star and then the number one on your telephone keypad. If you would like to withdraw your question, press the pound key.
If you ask a question at that time. Please press Star then the number one on your telephone keypad.
If he would like to withdraw your question. Okay. Thanks to today's conference is being recorded I'd now like to turn the call. It affect your host Ms. Carol Miceli director of Investor Relations Ma'am you may begin your conference.
Operator: Please note that today's conference is being recorded. I'd now like to turn the call over to your host, Ms. Carol Macelli, Director of Investor Relations. Ma'am, you may begin your conference. Thank you, Katherine, and thanks for joining us this afternoon.
Thank you Catherine and thanks for joining us.
A news release with our financial results for the recent order was issued this afternoon is available on our website.
Carol Macelli: The news release with our financial results for the recent quarter was issued this afternoon and is available on our website. On the call today is Dr. Jay Luly, President and CEO. Financial Officer and other members of Enanta's board. Before we begin with our formal remarks, we want to remind you that we will be making forward-looking statements, which may include our plans in a. All of which involve certain assumptions and risks beyond our control that could cause our actual development. The Bulletproof Executive 2013, and other periodic reports filed by the U.S. Department of Health and Human Services. Enanta does not undertake any obligation to update any forward-looking statements made during this meeting.
On the call today is Dr., Jay Mcknight, President and CEO .
And our Chief Financial Officer, and other members of any interest senior management team.
Before we begin with our formal remarks, we want to remind you that we will be making me.
These statements, which may include our plans and expectations.
Electronics and financial projections.
All of which involve certain assumptions that are beyond our control that could cause our actual results to differ materially from those statements.
A description of these risks.
Our most recent form check here and other periodic reports filed with the <unk>.
And the answer that does not undertake any obligation to update any forward looking statements made during this call.
I'd now like to turn the call over to Dr. James.
Carol Macelli: And now, I'd like to turn the call over to you.
Jay R. Luly: Thank you, Carol. Good afternoon, everyone, and thank you for joining us today. At the end of Enanta's fiscal third quarter, our clinical development programs to treat viral infections and liver diseases had progressed well. Our pipeline is maturing, and we have clinical studies ongoing with three different compounds, all of which have fast-track designations. Our most recent achievements were the initiation of a Phase I study of EDP514, our lead candidate for HPV, and the announcement of highly statistically significant top-line data from our RSV program. In addition, we at AbbVie, our HCV partner, recently announced that the European Commission has granted marketing authorization to AbbVie Permaverate to shorten the once-daily treatment duration from 12 to 8 weeks for treatment-naive chronic HCV patients with compensated cirrhosis and genotype 1, 2, 4, 5, or 6 infections.
Thank you Carol good afternoon, everyone and thank you for joining us today.
At the end of announces fiscal third quarter, our clinical development programs to treat viral infections and liver diseases has progressed well.
Our pipeline is maturing and we have clinical studies ongoing with three different compounds all of which have fast track designation.
Our most recent achievements for the initiation of a phase one study of GDP five one for our lead candidate for HPV.
The announcement of highly statistically significant topline data from our RSV program.
In addition, we announced the or you see the partner recently announced that the European Commission.
As granted marketing authorization to Abbvie for Maverick.
Shorten the once daily treatment duration from 12 to eight weeks for treatment naive chronic HCV patients with compensated cirrhosis genotype, one two or five or six.
I'll begin my review of our clinical development programs, our most advanced program.
Jay R. Luly: I'll begin my review of our clinical development program with our most advanced program, EDP-938, a respiratory syncytial virus known as RSV. In June, we announced that successful completion of this trial was a very exciting milestone for Enanta and yielded some of the most promising data from an RSV challenge study. Specifically, data from this study demonstrated that EDP-98 achieved a highly statistically significant reduction both in viral load and in resolution of clinical symptoms compared to placebo. And remember that highly statistically significant means that the p-value is less than 0.001.
Three a respiratory syncytial virus or RSV.
In June we are now.
The successful completion of this trial was a very exciting milestone for Atlanta and yielded some of the most promising data from an RSV challenge study.
Specifically data from this study demonstrated that ETP.
We achieved a highly statistically significant reduction both in viral load and in resolution of clinical symptoms compared to placebo.
And remember that highly statistically significant means that the P value is less than 1.001.
The data on the viral load that we previously reported namely the number of copies of viral our M&A from quantitative RT PCR is consistent with additional data. We now have from cell based infectivity assays using high virus.
Jay R. Luly: The data on the viral load that we previously reported, namely the number of copies of viral RNA from quantitative RT-PCR, is consistent with additional data we now have from cell-based infectivity assays using live virus. The cell-based data show an approximately 80% reduction in live RSV virus across subjects in both treatment groups compared to the placebo group. This result was also highly statistically significant.
The cell based data showing approximately 80% reduction in live RSV virus across subjects in both treatment groups compared to the placebo group. This result was also highly statistically significant.
Jay R. Luly: In addition, ADP 938 demonstrated good pharmacokinetics. Mean trough levels of drug, namely the levels of drug in plasma just before the next dose, were maintained at approximately 20 to 40 times above the in vitro EC90 or RSV-infected human cells. This means that the drug levels achieved in humans were dramatically higher than the amount of drug needed to reduce 90% of the viral RNA in RSV-infected cells. Overall, ADP 938 was generally well tolerated and demonstrated a favorable safety profile that was comparable to placebo over five days of dosing through day 28 of follow-up. There were no serious adverse events and no discontinuations of the study.
In addition, 80 938 demonstrated good pharmacokinetics mean trough levels of drug, namely the levels of drug in plasma just before the next dose were maintained at approximately 20 to 40 times about the in vitro DC 90.
For RSV infected human cells.
This means that the drug levels achieved in humans, we are dramatically higher than the amount of drug needed to reduce 90% of the viral are in a and RSV infected cells.
Overall, GDP 938 was generally well tolerated and demonstrated a favorable safety profile that was comparable to placebo over five days of dosing through day 28, the follow up.
There were no serious adverse events and no discontinuations of study drug.
Jay R. Luly: We expect to present additional details of the challenge study at an upcoming conference. In summary, the challenge study has shown that we can safely deliver high trough blood levels and get the drug to the target site of infection at concentrations that effectively halt the progression of infection. Also, over 250 subjects have now been exposed to ADP 938 for up to seven days, and the drug has generally been very well tolerated and has demonstrated favorable safety profiles similar to. We are very pleased with this safety program.
We expect to present additional details of the challenge study.
At an upcoming conference.
In summary, the challenge study has shown that we can safely deliver high trough blood levels and get the drug to the target site of infection. The concentrations of effectively halt the progression of infection.
Also over 250 subjects have now been exposed to.
Threeeight for up to seven days and the drug has generally been very well tolerated Ms demonstrated favorable safety profile similar to placebo. We are very pleased with the safety profile.
Challenge study is excellent safety and efficacy data give us confidence to advance CDP nine create into further trials, particularly since we have known for some time that he ninth create this differentiated from fusion inhibitors currently in development.
Jay R. Luly: The excellent safety and efficacy data from the challenge study give us confidence to advance EDP938 into further trials, particularly since we have known for some time that EDP938 is differentiated from fusion inhibitors currently in development because it directly targets the viral replication process of RSV and has demonstrated a high barrier to resistance in VTB. We now aim to show that EDP938 can demonstrate efficacy in adult outpatients with community-acquired Our goal is to initiate our first phase 2b study before the end of calendar 2019, and we then anticipate conducting additional studies in pediatric patients and other at-risk populations. Let's move now to our next most advanced program, which is Frenet.
Because GDP 938 directly targets the viral replication process of RSV and has demonstrated a high barrier to resistance in vitro.
We now aim to show that GDP nine create can demonstrate efficacy in adult patients with community acquired RSV infection.
Our goal is to initiate our first phase Twob study before the end of calendar 2019.
And we then anticipate conducting additional studies in pediatric patients and other at risk populations.
Let's move now to our most next most advanced program, which is for Nash.
NIH Edp 305, our lead FXR agonist is being investigated in two ongoing phase two studies, one for Nash and one for PVC.
Jay R. Luly: EDP-305, our lead FXR agonist, is being investigated in two ongoing Phase II studies, one for NASH and one for... Argon 1, our NASH study, is a 12-week, randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of EDP-305. Enrollment is complete in the NASH study, and we anticipate sharing top line Directionally, we want to see positive improvements in ALT, C4, and FTF-19, among other criteria. Assuming the aggregate data support it, we plan to initiate a Phase 2B study in the first quarter of calendar 2020 and look to partner the asset prior to Phase 3. This will allow us time both to gain more data on ADP305 and to explore which combination of assets and partners would be preferred.
Argon one our Nash study as a 12 week randomized double blind placebo controlled study designed to evaluate the safety Tolerability pharmacokinetics and efficacy of Edp 305.
Enrollment is complete in the Nash study and we anticipate sharing top line data by the end of this quarter.
Directionally, we want to see positive improvements in LTV C and Fts 19, among other criteria.
Assuming the aggregate data support it we plan to initiate a phase Twob study in the first quarter of calendar 2020.
And look to partner the asset prior to phase three.
This will allow us time, both to gain more data on GDP, breo, five and to explore which combination assets some partners would be preferred.
We continue to believe that FSR as one of the most promising mechanisms in development today for Nash.
In addition to GDP three five we've made good progress with our follow on program from which we expect to announce a development candidate later this year.
Regarding the Intrepid study of GDP, Breo, five and PVC.
We continue to enroll patients and we'll provide further updates as the study proceeds.
Beyond FX are we also continue our research into other mechanisms for Nash.
Jay R. Luly: We continue to believe that FXR is one of the most promising mechanisms in development today. In addition to EDP 305, we've made good progress with our follow-on program, from which we expect to announce a development candidate later this year. Regarding the intrepid studies of EDP-305 and PBC, we continue to enroll patients and will provide further updates as the study progresses. Beyond FXR, we also continue our research into other mechanisms for NAT.
Let's shift to HPV.
We recently initiated a phase one a one b clinical study with our novel class to HPV core inhibitor Edp 514.
Part one of this randomized double blind placebo controlled study is designed to evaluate the safety tolerability and pharmacokinetics of single ascending doses and multiple ascending doses of CTP 514 in healthy subjects, while part two will explore the antiviral activity of GDP 514 in new suppressed patients with chronic HBV infection.
So the plan is to enroll approximately 98 subjects and to evaluate up to six dose cohorts with ETP 504 administered orally once daily.
Jay R. Luly: Let's shift to HPV. We recently initiated a Phase 1a, 1b clinical study with our novel Class 2 HPV Core Inhibitor EDP514. Part 1 of this randomized, double-blind, placebo-controlled study is designed to evaluate the safety, tolerability, and pharmacokinetics of single ascending doses and multiple ascending doses of UDP514 in healthy subjects, while Part 2 will explore the antiviral activity of UDP-514 in nuke-suppressed patients with chronic HPV inflammation. The study plan is to enroll approximately 98 subjects and to evaluate up to 6 dose cohorts of ADP 514 administered orally once daily.
We plan to share data from the healthy volunteer portion and initiate part two of the study dosing nuke suppressed HBV patients in the first quarter of calendar 2020.
In addition, we are planning to initiate another phase one study in HBV patients this time and by a remake chronic hepatitis b patients not currently on treatment.
GDP five one form of selected from our leads series of HBV compounds that are characterized by potent antiviral activity.
And our promising preclinical data support our excitement for this mechanism.
Preclinical data demonstrate that ebfive, one for as a potent inhibitor of HPV replication and prevents the de Novo formation of new Cccdna and primary human hepatic sites when given early during each.
Section.
In vitro data also show that GDP 500, fours pinching, a terrific and that combinations of GDP 514, with nucleoside reverse transcriptase inhibitors, which are the current antiviral therapies for HBV.
Jay R. Luly: We plan to share data from the Healthy Volunteer portion and initiate Part 2 of the study dosing nuke-suppressed HPV patients in the first quarter of calendar 2020. In addition, we are planning to initiate another Phase 1b study in HPV patients, this time in Viremic Chronic Hepatitis B patients not currently on treatment.
Or with a class one core inhibitor resulted an additive to synergistic anti viral effects.
In vivo models of GDP 504 demonstrate excellent efficacy with greater than four log viral load reduction in HBV infected PXP mice.
Based on our preclinical data we believe GDP 514 may have best in class potential for the core inhibitor mechanism.
Jay R. Luly: EDP514 was selected from our lead series of HPV compounds that are characterized by potent antiviral activity, and our promising preclinical data support our excitement for this approach. Preclinical data demonstrate that EDP514 is a potent inhibitor of HPV replication and prevents the de novo formation of new CCC DNA in primary human hepatocytes when given early during, In vitro data also show that EDP514 is pangenotypic and that combinations of EDP514 with nucleoside reverse transcriptase, which are the current antiviral therapies for HPV, or with a class one In vivo models, BDP514 demonstrated excellent efficacy with greater than four log viral load reduction in HPV-infected PXP mice. Based on our preclinical data, we believe UDP514 may have best-in-class potential for its core inhibitor mechanism.
Now I'd like to conclude my remarks by reminding you that we look forward to communicating our progress on all our clinical programs starting with Argonne, One phase two Nash data by the end of this quarter and then additional updates on our other programs later this year.
I'll stop here and turn the call over to Paul to discuss our financials for the quarter. Paul. Thank you Jay I'd like to remind everyone that answer reports on September thirtyth fiscal year schedule.
Today, we are reporting results for our third fiscal quarter ended June Thirtyth 2019.
For the quarter total revenue was $44.4 million and consisted entirely of royalty revenue earned on Abbvies Global HCV net sales of $784 million.
This compares to total revenue of $57.3 million for the same period in 2018.
The decrease in royalty revenue is a result of Abbvies lower net sales, mainly driven by lower treated patient volumes in select international markets.
Royalty revenue was calculated on 50% of Maverick sales at a blended royalty rate of 12% and approximately 30% of securus sales royalty rate of 10% after adjustments for certain contractual discounts and rebates, which is historically have been approximately 1.5% of Abbvies total reported HCV sales.
Paul J. Mellett: I'd like to conclude my remarks by reminding you that we look forward to communicating our progress on all our clinical programs, starting with Argonne I Phase II NASH data by the end of this quarter, and then additional updates on our other programs later this year. I'll stop here and turn the call over to Paul to discuss our financials for the quarter.
During our third fiscal quarter, our blended royalty rate from Maverick encompasses our first three royalty tiers of 10%, 12% and 14%.
Paul J. Mellett: I'd like to remind everyone that Enanta reports on a September 30th fiscal year schedule. Today, we are reporting results for our third fiscal quarter ending June 30, 2019. The quarter's total revenue was $44.4 million and consisted entirely of loyalty revenue earned on AbbVie's global HCP net sales of $784 million. This compares to total revenue of $57.3 million for the same period in 2018. The decrease in royalty revenue is a result of AbbVie's lower net sales, mainly driven by lower treated patient volumes in select international markets. Royalty revenue is calculated on 50% of Maverick sales at a blended royalty rate of 12% and approximately 30% of Kira sales at a royalty rate of 10%. After adjustments for certain contractual discounts and rebates, which historically have been approximately one and a half percent of Abbey's total reported HCBC.
I will remind everyone that our royalties, which are calculated separately for each product are determined on a calendar year basis to a tiered schedule rising royalty rates.
The royalty schedule restarted at our lowest royalty rate of 10% in our quarter ending March 31.
This means that the quarter ending March 31, we will be at the lowest royalty rate of 10% and our royalties for the quarter ended December 31st we'll have the highest royalty rates in our fiscal year.
You can review our royalty tier schedule on our 2018 Form 10-K .
Moving onto our expenses for the three months ended June Thirtyth, 2019 research and development expenses totaled $34.5 million compared to $28.5 billion for the same period in 2018.
The increase was primarily due to greater clinical costs associated with the progression of our wholly owned clinical programs and RSV Nash PBC in HBP, including our three phase two clinical trials.
General and administrative expense for the quarter was 6.2 million, which was consistent with the comparable quarter in 2018.
Financial recorded an income tax benefit of $5.9 million for the three months ended June Thirtyth 2019, compared to income tax expense of $3.7 million for the same period in 2018.
The income tax benefit for the quarter was driven by a federal tax benefit associated with foreign derive royalty income from our Abbvie collaboration agreement.
Paul J. Mellett: During our third fiscal quarter, our blended royalty rate for Maverick encompassed our first three royalty tiers of 10%, 12%, and 14%. I will remind everyone that our royalties, which are calculated separately for each product, are determined on a calendar year basis through a tiered schedule of rising royalty rates. The royalty schedule restarted at our lowest royalty rate of 10% in our quarter ending March 31. This means that the quarter ending March 31 will be at the lowest royalty rate of 10%, and our royalties for the quarter ending December 31st will have the highest royalty rates in our fiscal year. You can review our Royalty Tier Schedule and our 2018 Form 10-K. Moving on to our expenses, for the three months ended June 30, 2019, research and development expenses totaled $34.5 million, compared to $28.5 million for the same period in 2018.
And the answer is effective tax rate for the nine months ended June Thirtyth 2019 was less than 1% compared to approximately 22% from the same period in 2018.
We expect our effective effective tax rate for fiscal 2019 to be approximately 1%, which reflects the impact of the foreign derive royalty income tax benefit R&D tax credits as well as tax benefits from stock awards activity.
Net income for the three months ended June Thirtyth, 2019 was $7 million or 33 cents per diluted common share.
Compared to net income of $20.3 million or 97 cents per diluted common share for the corresponding period in 2018.
And then the ended the quarter with approximately 389 million in cash and marketable securities an increase of approximately $64 million from our 2018 fiscal year end balance of $325 million.
We expect that these cash resources as well as our continuing the royalty revenue will be sufficient to meet our anticipated cash requirements for the foreseeable future.
Further financial details are available in our press release and will be available in our Form 10-Q for the quarter when filed.
Paul J. Mellett: The increase was primarily due to greater clinical costs associated with the progression of our wholly-owned clinical programs at RSV, NASH, PBC, and HBB, including our three Phase II clinical trials. General and Administrative Expense for the quarter was $6.2 million, which was consistent with the comparable quarter in 2018. Enanta recorded an income tax benefit of $0.9 million for the three months ended June 30, 2019, compared to income tax expense of $3.7 million for the same period in 2018. The income tax benefit for the quarter was driven by a federal tax benefit.
I'd now like to turn the call back to the operator and open up the lines for questions operator.
Yes, Sir ladies and gentlemen, just as a reminder, if you like.
Question. Please press Star then the number one on your telephone keypad once again that is star and the number one.
Our first question comes from the line of Brian Abrams with RBC.
Hi, Thank you for taking my question.
I guess first question on 938, it sounds like you've been able to do some additional.
Analyses on the data from the challenge in the pocket talent study.
I'm wondering if you have we're able to.
Again any data with respect to.
Our resistance variance.
As well as the efficacy of the agent relative to when post confection.
Paul J. Mellett: Enanta's effective tax rate for the nine months ended June 30, 2019, was less than 1%, compared to approximately 22% for the same period of 2018. We expect our effective tax rate for fiscal 2019 to be approximately, which reflects the impact of the foreign derived royalty income tax. R&D Tax Credits, as well as tax benefits from stock avoidance activities. Net income for the three months ended June 30, 2019 was $7 million, or $0.33 per diluted common share, compared to net income of $20.3 million, or $0.97 per diluted common share, for the corresponding period in 2018. Enanta ended the quarter with approximately $389 million in cash and marketable securities, an increase of approximately $64 million from our 2018 fiscal year ending balance of $325 million.
It was it was given and then I had a follow up.
So no we don't have data on resistance.
Variants.
We haven't identified.
Really any patients with them.
So it's it's challenging I think one of the things to to point out as you know with that nine create has an incredibly high barrier.
To resistance and.
We've been even laboratory settings, where we've tried to force the conditions to allow it we havent.
Yes, we've been able to.
It's really do that so we have not identified any patient with a breakthrough yet.
Okay, that's really helpful.
And then you mentioned in addition to the community acquired study that's about to start.
Down the line you'd be also looking at potential pediatric study and I was just curious what if any additional work would need to be done be done with respect to dose mapping formulation tox et cetera.
Before moving into a pediatric population and what might that study look like and hop back in the queue. Thanks.
Operator: We expect that these cash resources... as well as our continuing royalty revenue, will be sufficient to meet our anticipated cash requirements for the foreseeable future. Further financial details are available in our press release and will be available in our Form 10-Q for the quarter when filed. I'd now like to turn the call back to the operator and open up the lines for questions. Operator? Yes, sir. Ladies and gentlemen, just as a reminder, if you'd like to ask a question, please press star and then the number one on your telephone keypad. Once again, that is the star and the number one.
So theres always preparatory work for.
Pete Studies, I mean, you obviously need to switch off your formulation.
You need to.
We do a lot of.
Basically the PK work modeling.
Need to.
No, but basically.
A lot of it really results from.
Modeling.
Yes, the bio equivalence doses that you look at in adults.
You've got to translate into.
Our children and it's going to depend on what.
Hey for the children are into because some of them have still.
On developing.
No metabolic hardware if you will so there's always a few extra studies that you want to try to understand.
Brian Corey Abrahams: Your first question comes from the line of Brian Abrahams with RBC. Hi, thank you for taking my questions. I guess the first question on 938. It sounds like you've been able to do some additional analyses on the data from the positive challenge study. I'm wondering if you were able to get any data with respect to resistance variants, as well as the efficacy of the agent relative to when it was given post-infection, and then how
You know in advance that's all that will be going on in parallel with.
You know our adult studies, which.
Timing perspective is what we wanted it to do anywhere we do want to get.
You know as much information as we can.
Adult population.
Before we go into the feed study. So so you can go into it.
Most intelligently.
So yeah I think.
That's.
Where we're at.
Your next question comes from the line of ethylene Rahimi with Roth capital partners.
Jay R. Luly: So, no, we don't have data on resistance variants. We haven't actually identified, really any patients with them.
Hi team. Thank you for the update.
Two questions for you question. One is our theme question two is on that.
So can you.
On to it.
Jay R. Luly: So it's... I think one of the things, too, to point out is, you know, 938 has an incredibly high barrier. Transcribed by https://otter.ai, conditions to allow it. We haven't, Yeah, I've been able to
What lat tier tremendous success and Carolyn study.
Hi, you're infection rates with one of the highest.
And then second that leap into what elements of the fee to be talman study require really thoughtful manner.
Jay R. Luly: Okay, that's really helpful. And then you mentioned, in addition to the community acquired study that's about to start, down the line, you'd also be looking at potential pediatric studies. And I was just curious, you know, what if any additional work would need to be done with respect to dose mapping, formulation, talks, etc. before moving into a pediatric population? And what might that study look like?
And how do you plan on tackling at.
And then I have a follow up on that.
Well you know.
You.
We did have a very high.
Rate of infection.
In the study I mean.
That always helps.
Number one just because you can get more data and more patients more quickly.
I think wed.
The lesson learned.
And it's I think it's probably intuitive from even before we decide to do that.
And translation to phase two b.
We need to identify what is the allowable dosing window.
Brian Corey Abrahams: And I'll hop back in the queue. Thanks.
Jay R. Luly: So there's always preparatory work for PEAT studies. I mean, you obviously need to switch up your formulation, and you need to, you know, do a lot of, you know, basically DMPK work and modeling. You know, but basically, a lot of it really results from modeling. You know, the bioequivalence doses that you look at in adults. You've got to translate it into children. It's going to depend on what each group the children are in too because some of them have still Unknown Executive, Yasmeen Rahimi, Jay Olson, Jennifer Viera, Amy Luly, Scott Rottinghaus, You know, as much information as we can and the adult population before we go into the heat study. So, we can go into it, you know, most intelligently.
And we're going to have to be very thoughtful about how we approach that.
Just basically really trying to understand for this virus and for this mechanism against this virus what is the acceptable dosing window.
So, we'll we'll look at that.
Over.
You know a purely a time window breaking it down into parts so that we understand.
With that limits are.
Hopefully that broader the window that identified.
The better but for example with flu.
You really have like a 48 hour window in which you have to.
Identify.
The patients and get get drug on board so.
Well if you if we like what we see.
More forgiving in flu, we don't know that no one knows the answer to.
Question other than intuitively.
The earlier the tree that you treat the better the likelihood of more impactful.
Yasmeen Rahimi: So yeah, I think that's where we're at.
Yasmeen Rahimi: Your next question comes from the line of Yasmeen Rahimi with Roth Capital Partner. Hi team, thank you for the update.
Outcomes so.
This really every step of the way that from our phase Twob studies that were going to be looking at were going to be thinking about.
Jay R. Luly: Two questions for you. Question one is on RFC, and question two is on NASH. So, can you comment on sort of what led to your tremendous success in the CHALLENGE study? Your infection rates were one of the highest, and then second, that leads into what elements of the Phase 2b CHALLENGE study require thoughtfulness, and how do you plan to tackle it? And then I have a follow-up on Nash.
Looking at that.
Optimizing that dosing window opportunity and we'll learn more about the drug is.
As we go in terms of what that level one Joe is for again for this mechanism against this virus.
That's helpful.
Yes. Thank you Jay and then the question on assets I mean were very eagerly awaiting the arc on one data.
Jay R. Luly: Well, you know, you, uh... We did have a very high rate of infection in the study. That always helps.
Then you continuously remind us said you're going to.
Dan that's grown ethic clinical candidate, which sort of fear and bastards, which make one conclude that maybe tail five is not optimized and therefore, there is a need for a follow on so can you explain to me while were waiting for the data from why there is such a need for a 2.0 version.
Jay R. Luly: And number one, just because you can get more data on more patients more quickly. I think the lesson learned is, you know, and it's probably intuitive from even before we did this study that translation to Phase 2B. We need to identify what the allowable dosing window is, and we're going to have to be, you know, very thoughtful about how we approach that. Just basically, really trying to understand for this virus and for this mechanism against this virus, what is the Acceptable Dosing Window. So we'll, you know, we'll look at that over, you know, a period, a time window, you know, breaking it down into parts so that we understand, you know, what the limits are, you know, hopefully, the broader the window that's identified, the better, but, you know, for example, with flu, you really have like a 48 hour window in which you have to identify the patients and get the drug on Will it be more forgiving than the flu? We don't know.
So again just to back up a little bit we we had an answer I don't.
Work on any program without having.
Follow on molecules and backups.
Everything we do.
It's done that its very common and small molecule drug discovery.
So page right out of the the sort of standard playbook, So theres nothing.
I was curious about this program or any of our other programs. We we do this as a matter of course on everything we do.
You may remember.
In the Hep C. Previous days, we had lots of molecules thousands of them.
We picked her attacker here is the first candidate.
To move forward, but.
I was going along and clinical trials and you just have a lot of it.
Okay.
You know.
What should I say, just quiet periods, where you're waiting for data.
In the meantime.
You know, it's just prudent to have.
However, continuing.
Activities in a mechanism that you feel strongly about.
Yasmeen Rahimi: No one knows the answer to this question other than intuitively, the earlier that you treat, the better the likelihood of more impactful outcomes. So it's really every step of the way that from our phase 2b studies that we're going to be looking at, we're going to be thinking about, you know, optimizing that dosing window opportunity. And we'll learn more about the drug as we go in terms of what that allowable window is for again for this mechanism against this virus. Is that helpful?
Just it's just pipeline management and it also affords the opportunity that.
Even if you have a good molecule.
At the outset may still be able to come up with an even better one so thats the.
Thanks.
Were the ambition to have.
And it's just prudent practice and that's just the way an answer to this business, which isn't quite honestly that different than.
Many other companies to hard core.
Small molecule drug discovery and development.
So.
All that said you know we.
I look forward to Oregon, one data at the end of this quarter.
We have been working on our follow on program.
Jay R. Luly: Yeah, thank you, Jay. And then the question on NASH is, I mean, we're very eagerly awaiting the Argonne 1 data, but then you continuously remind us that you're going to advance a follow-on FXR clinical candidate, which sort of puts fear in investors, which makes one conclude that maybe 305 is not optimized, and therefore there's a need for a follow-on. So can you explain to me, while we're waiting for the data, why there is such a need for a 2.0 version?
Now for a while weve been just patiently going through.
Lots of potential.
Molecules and looking for.
Within the contenders as a follow on.
You know just basically we have the the beauty contests.
Sort of wrapping up and.
We always to safe to assume that no matter, what we do we're thinking about.
Optimizing potency selectivity safety.
Anything that we can try to next week.
We do and so.
Jay R. Luly: Um, so again, just to back up a little bit, we at Enanta don't work on any program without having, you know, follow-on molecules and backups; everything we do has done that. It's very common in small molecule drug discovery. It's a page right out of the, you know, the sort of standard playbook. So there's nothing, you know, mysterious about this program or any of our other programs. We do this as a matter of course in everything we do. You may remember in the hep C protease days, we had lots of molecules, you know, thousands of them. We picked parataprovir as the first candidate, you know, to move forward. But you know, when you're going along in clinical trials, you just have a lot of, you know, what should I say, just quiet periods where you're waiting for data. In the meantime, you know, it's just prudent to have an ever-continuing
Stay tuned on that front, but I think.
I think we've made some very good progress.
On that program and we'll have more to say later in the year.
Thank you Jay and are you able to comment at least what the follow on chemistry.
Greenberg scenario planning at this point.
Yes, I will we will roll out a lot of data.
At the appropriate time, but again is the assumption that as.
It's all about.
No, it's all about efficacy and safety and.
No DNP K considerations and other kinds of things.
Biodistribution, there's lots of things you can study here really.
Ill focus on.
Yes, what you would wouldn't look for in a follow on molecule.
So anyway I guess.
What I can say right now.
We'll have a lot more to say later in the year.
Thank you.
For taking my question.
Your next question comes from the line of Kashkari last Wolfe research.
Hi.
Jay R. Luly: activities in a mechanism that you feel strongly about. It's just pipeline management. And it also affords the opportunity that even if you have a good molecule at the outset, you may still be able to come up with an even better one. So that's a, I think that's a worthy ambition to have. And it's just prudent practice.
This is Joyce Shao on cash thank you for taking my question.
My first question is what's the cost of the potential phase should be for Nash.
And my follow up question will be what you were expecting on ASCII LTL reduction LDL increase and MRI Pdfs and curious rate we charge for your compound.
Jay R. Luly: And that's just the way Enanta does its business, which isn't, you know, quite honestly, that different from many other companies that do hardcore Small Molecule Drug Discovery and Development. All that said, you know, we look forward to Argonne One data at the end of this quarter. We have been working on our follow-on program. Now, for a while, we've been, you know, just patiently going through lots of potential molecules and looking for, you know, within the contenders as a follow-on. You know, basically, we have the beauty contest. You know, sort of wrapping up, and it's safe to assume that no matter what we do, we're thinking about optimizing potency, selectivity, safety, anything that we can try to tweak. And so stay tuned on that front. But I think we've made some very good progress on that program, and we'll have more to say later in the year.
The three all five.
Yes.
If I had all the data and I you know I would talk about it.
Let me.
The answer let me answer your first question first so.
The cost of the phase two b, we're still in the process of.
Mapping out the.
Protocol, what that looks like in terms of.
Powering the patient numbers duration et cetera, et cetera, so until we really finalized all those inputs.
It's hard for me to give you a.
Dollar reduction.
Wouldn't be.
Dissimilar from what other People's Similarly.
Structured pays to be.
Number two with regards to all of the.
Readouts from our trial.
There again, there are a lotta.
What were looking at in this trial.
And I will look at able to see of course, we'll look at it.
Before 19.
MRI as.
We've looked at MRI pdfs predominantly is an inclusion criteria.
If we wanted to since we were.
As we were bringing patients into the study.
Jay R. Luly: Thank you, Jay. And are you able to comment at least on how the follow-on chemistry is different versus 305 at this point?
Phenotypically, rather than necessarily having a biopsy proven Nash.
We wanted to make sure that patients receive a tight so we did just baseline MRI.
Jay R. Luly: Yeah, we'll, we'll roll out a lot of data at the appropriate time. But again, make the assumption that it's what it's all about. You know, it's all about efficacy and safety and, you know, DNPK considerations and other kinds of biodistribution. There are lots of things you can study here to really focus on, Yeah, what you wouldn't look for in a follow-on molecule. So anyway, that's about what I can say right now. We'll have a lot more to say later in the year.
PDF have sort of course, we'll get.
That on subjects that at end of study as well so we'll have that kind of data.
And.
So on other biochemical markers will have.
Elastography.
Cetera, but the but the punch line is.
What do you want to get from a study like this.
This is a 12 week study or mine.
You and others that this is a 12 week.
Non biopsy study.
As a means to do a few things we aim to learn what does the safety profile and Nash patients.
Now, we want to confirm activity with our drive.
In Nash patients.
And.
Also importantly, we want to affirm.
Joy Xiao: Thank you. Thank you for taking the time to answer my question. Your next question comes from the line of Akash Tiwari with Wolf Research. Hi. This is Joy Xiao on behalf of Akash. Thank you for taking my question. My first question is, what's the cost of potential phase 2B for NASH? And my follow-up question will be, what are you expecting in AST, ALT reduction, LDL increase, MRI, PDFF, and puritis rate at week 12 for your compound, EDP-305?
What our dose selection as for phase Twob.
So.
From this we're going to get directionality from a number of different.
Readout.
Among the ones that you that you just mentioned.
But.
For FX ours.
At 12 for 12 week endpoint, there's just not.
The time is comparable data out there.
Even for Ltd.
On the 12 week time point.
Thanks plant had.
Looking at placebo corrected.
Per cent change from baseline.
On LT Flint had about a 20% reduction.
Jay R. Luly: Yeah, so you know if I had all the data, I would talk about it, but let me answer your first question first.
And.
Intercepts phase three study regenerate.
Had about 15% to 18% reduction.
Jay R. Luly: So the cost of phase two B, you know, we're still in the process of, [inaudible] Number two, with regard to all of the readouts from our trial, again, there are a lot of things that we're looking at in this trial. We looked at MRI and PDF predominantly as an inclusion criteria. We wanted to, since we were bringing patients into the study phenotypically rather than necessarily having a biopsy-proven mesh. We wanted to make sure that patients were steatotic, so we did get baseline MRI, PDF set, PDFFs, and of course, we'll get that on subjects at the end of the study as well, so we'll have that kind of data, and so on. Other biochemical markers will have elastography, etc.
And really the only other comparison out there on 12 weeks. This novartis is.
Molecule.
This advancing.
And about 6% to 9% reduction.
So thats the sum total of 12 week.
Ill Tee data that you can look at you you look for a 12 week MRI PDF data you find even less.
I think novartis.
It was around 6% to 7%.
Depending on the dose and Gilly ad.
It was around 8% to 15%.
Depending upon the dose.
So you know.
As I mentioned many times before.
In MRI Pdfs, it's not the predominant.
Probably read out for an FX are that's not the calling card necessarily as a Mac mechanism, particularly it.
At a 12 week time point, so people just need to think about it in the context. So.
Jay R. Luly: But the punchline is... Now, what do you want to get from a study like this? This is a 12 week study. I want to remind you and others that this is a 12 week non-biopsy study. It's aiming to do a few things. You know, we aim to learn what the safety profile of NASH patients is, and we want to confirm activity with our drug in NASH patients. And also importantly, we want to affirm what our dose selection is for phase 2b. So, you know, from this, we're going to get directionality from a number of different readouts among the ones that you just mentioned. But, you know, for FXRs, at 12 for 12 weekend points, there's just not a ton of comparable data out there. You know, even for ALT.
No.
What other people have seen in 12 week studies.
We're going to look at that again main goal here is to look at a number of different readout.
That.
Show.
Proper safety good target engagement.
And confirmation of what our phase two the dose.
It should be.
Progressing at the next step.
So when we have data will share and.
As we said in the prepared remarks.
And what we've said.
For many quarters now is.
We expect to have that at the end of this quarter.
Thank you very much.
You're welcome.
Your next question comes from the line of Jay Olson with Oppenheimer.
Oh, Hey, congrats on the progress and thank you for taking my questions I just wanted to follow up on GDP three or five.
Jay R. Luly: On the 12-week time point, I think Flint had, you're looking at placebo-corrected... First, let's change from baseline, on ALT, Flint had about a 20% reduction. Intercepts Phase 3 Study Regenerate had about a 15 to 18% reduction. And really, the only other comparison out there for 12 weeks is Novartis' molecule, that's advancing at about 6% to 9% reduction. So that's the sum total of 12-week ALT data that you can look at. If you look for 12-week MRI PDFF data, you find even less. Um, I think Novartis was around 67%. Depending upon the dose and Gilead, you know, it was around 8 to 15 percent, depending upon the dose.
There was a recent Nash phase two study that read out in our competitors study and it missed the primary endpoint of MRI PD Ff.
But it did hit on important secondary endpoints like LP reduction and you touched on this a little bit but I was wondering if that study had any impact on your plans for Q3 of five and the design of the Phase Twob study that you plan to initiate in the third quarter, especially with regards to use of anti PDGF as an endpoint.
Yes, I mean, we.
Again, I think you're referring to.
Par mechanism.
Alpha Delta.
We.
You know they sat at their primary.
They didnt see that activity. They did see I think they had some LT.
Jay R. Luly: So, you know, as I've mentioned many times before, MRI, PDFF, is not the predominant, probably readout for an FXR. That's not the calling card necessarily of the mechanism, particularly at a 12 week time point. So people just need to think about it in the context of what other people have seen in 12-week studies. We're going to look at that. Again, the main goal here is to look at a number of different readouts. Proper safety, good target engagement, and confirmation of what our phase 2B dose should be progressing to the next step. So when we have data, we'll share it. And, as we said in the prepared remark, And what we've said for many quarters now is that we expect to have that by the end of this quarter.
Productions in their study, but as I just mentioned.
Now fat reduction isn't necessarily especially.
You know in short time period not the.
The hallmark of a of an FX are so we're going to be.
Looking our next study is going to be as histology end point study.
Along the lines of.
Yes say for example, what types so.
We.
We'll be very cognizant of what everybody else is doing particularly focusing on efficacy readouts that are germane for the for the mechanism that you're.
That you're studying in this case FX or.
Okay, great. Thanks for that color and then I was wondering if you could provide any comments on the rationale behind your decision to partner you need be three or five prior to initiating phase three.
Jay Olson: Thank you very much. Your next question comes from the line of Jay Olson with Oppenheimer. Oh, hey, congrats on the progress and thank you for taking the time to answer my questions. I just wanted to follow up on EDP-305. There was a recent NASH Phase II study that read out in a competitor's study, and it missed the primary endpoint of MRI-PDFF, but it did hit on important secondary endpoints like ALT reduction. And you touched on this a little bit, but I was wondering if that study had any impact on your plans for EDP-305 and the design of the Phase IIb study that you plan to initiate in the third quarter, especially with regard to the use of MRI-PDFF as an endpoint.
Yes, we have.
We've spoken about that a little bit in that in the past again, I I think that.
We've got it.
A lot of things going on as an asset we've got Nash Weve got Hep B, we've got RSV.
And if I might add all those up.
At one end of the spectrum.
In our Nash is going to be likely in the end, it's going to be a combination therapy.
The phase threes are going to be big an expensive and global.
And importantly.
The commercial.
Enterprise that takes on.
This new.
She'll this new indication to the marketplace I think needs requires a certain degree of sophistication sophistication and.
And strength and this is where we've seen it before.
I would say the same thing you know if we were looking at Hep C. Today ourselves again were similarly, situated theres no question that having on Abbvie alongside us when they ran.
Jay R. Luly: Yeah, I mean, we Again, I think you're referring to a PPAR mechanism. Alpha Delta.
12, or 15 phase threes, I'm not suggesting that's what would be involved here, but it was a huge phase three program. It was a global required sophisticated.
Jay R. Luly: We, You know, they said status or primary. They didn't see that activity. But they did see, I think they had some ALT reductions in their study. But as I just mentioned, fat reduction isn't necessarily, especially in short time periods, it's not the hallmark of an FXR. So we're going to be looking, our next study is going to be a histology endpoint study, along the lines of, say, for example, what a Flint-type study was. So, we'll be very cognizant of what everybody else is doing, particularly focusing on efficacy readouts that are germane to the mechanism that you're thanking yourself for studying, in this case, FXR.
Commercial launch strategy.
There is no way that.
I think of a smaller company like Nantucket maximize.
The asset like we could if we were.
Teamed up with somebody who was powerful at that stage.
Not police to us is very expensive undertaking we know that the case.
So I think.
I think we would.
Aimed to do that the other part of this there's a strategic part of partnering too.
Because as I mentioned Theres combination therapy.
Jay R. Luly: Okay, great. Thanks for that color. And then I was wondering if you could provide any comments on the rationale behind your decision to partner EDP-305 prior to initiating Phase 3. Yeah, we have
Likelihood here and.
If you are thinking to the future.
About where the wind could ultimately be.
Perhaps with.
Other combination ingredients that we don't have today.
Jay R. Luly: Yeah, we've spoken about that a little bit in the past. Again, I think that you know, we've got a lot of things going on as an answer. We've got Nash, we've got Hep B, we've got RSV. And if I line all those up, they're all on one end of the spectrum.
You could you could team up in a way that would have.
Strategic value by partner, bringing one asset partner, bringing another asset.
And going after it that way as well so I think you just increase your.
Overall chances of success in this indication from from many different perspectives.
Jay R. Luly: You know, NASH is going to be, likely in the end, a combination therapy. The phase threes are going to be big and expensive and global, and importantly, the commercial Enterprise that takes on this new field, this new indication to the marketplace, I think, needs, requires a certain degree of sophistication and strength, and this is where, you know, we've seen it before. I mean, I would put the same thing, you know, if we were looking at Hep-C today, ourselves, again, we're similarly situated, there's no question that having, you know, an AbbVie alongside us when they ran, you know, 12 or 15 phase 3s. I'm not suggesting that's what would be involved here, but it was a huge phase 3 program, it was global, it required a Not least, too, is that it's a very expensive undertaking. We know that to be the case.
I guess that could always change, but for now weve been that's way weve been thinking and the way weve been thinking about it for a number of quarters I would contrast that with RSV.
Where.
You know, we're hopeful that given our mechanism given the fact that we've got a super high barrier to resistance, we may not need to combine it with other anti viral from an efficacy efficacy perspective or to prevent.
Resistance.
We may be able to proceed with a single agent.
Into a.
Little bit more of a defined area of RSV infection, something thats very easily and readily.
Diagnose.
And you know and then.
A scenario where.
Practitioners, who have been looking.
Forever for a successful RSV therapeutic I think that would be an easy one for us to get.
Message out.
Ultimately to have the opportunity to.
You know to push forward with that one all the way our ourselves so we don't anticipate.
Jay R. Luly: So I think we would, you know, aim to do that. The other part of this, there's a strategic part to partnering too. Because, as I mentioned, there's combination therapy likelihood here. And, you know, if you're thinking to the future about where the wind could ultimately be, you know, perhaps with, You know, other combination ingredients that we don't have today, you could team up in a way that would have strategic value by, you know, partner A bringing one asset, partner B bringing another asset, and going after it that way as well. So I think you just increase your overall chances of success in this indication from many different perspectives. I guess that could always change, but, you know, for now, that's the way we've been thinking and the way we've been thinking about it for a number of quarters.
You know sort of a.
Global.
Type of.
Partnership on RSV like we might.
Well contemplate on a on a Nash program.
Well that's super helpful. Thank you so much for all the color.
You are welcome.
Your next question comes from the line of Eric Joseph with JP Morgan.
Hi, This is Turner on for Eric.
Thanks for taking the question just one on 514 and thinking about the phase one to be in potential viral load reduction I'm curious what would be viewed at the clinically differentiated from the other novel core inhibitors or.
Rather what parameters would you look to established differentiation to other core inhibitors in development and what would you need and what would be viewed as meaningful advantage on that front.
It's a little hard to hear you.
Basically what.
At this juncture.
What have we done we've we've created.
Jay R. Luly: I would contrast that with RSV, where we're hopeful that given our mechanism, given the fact that we've got a super high barrier to resistance, we may not need to combine it with other antivirals from an efficacy perspective or to prevent resistance. We may be able to proceed with a single agent. Transcribed by https://otter.ai, and and, you know, and and a scenario where, you know, practitioners who have been looking for a big, global type of partnership on RSV like we might well contemplate on a NASH program.
A molecule 514.
The.
As far as we can tell has one of the best preclinical profiles of any.
Core inhibitor this.
That's been reported.
Looking at the totality of the in vitro data that weve generated and the in vivo.
Data that we've done in some very very.
Challenging animal models so.
I think the preclinical profile.
Yes. It looks good we we've also done a lot of work on DMP Kay.
And.
And so the molecule by Onefour hundred swings to go into the clinic.
Jay R. Luly: Well, that's super helpful. Thank you so much for all the color.
Phase.
So the early studies were going to be.
Jay R. Luly: You're welcome.
Really looking at safety and PK confirmation and.
Turner: Your next question comes from the line of Eric Joseph with J.P. Morgan. Hi, this is Turner on behalf of Eric.
In Healthys that we've got.
Turner: Thanks for taking the question. Just one on 514 and thinking about phase 1b and potential viral load reduction. I'm curious what would be viewed as clinically differentiated to some of the other novel core inhibitors, or rather what parameters would you look to establish differentiation to other core inhibitors in development, and what would you be, and what would be viewed as a meaningful advantage on that front?
You know just like we've had with many other candidates where weve designed the molecules hopefully well taken them into phase one.
Hopefully we'll have a.
Nice safety profile.
We will give.
Yes, very good exposure is after acuity.
The administration.
That will rapidly be going into.
The one b.
A portion of that study part two.
And looking at.
The any.
Any viral activity of.
The molecule, especially once we get into.
Jay R. Luly: It's a little hard to hear you. But, you know, basically what I want at this juncture. Um, you know, what have we done? We've created molecule 514. That, as far as we can tell, has, you know, one of the best preclinical profiles of any core inhibitor that's been reported, you know, looking at the totality of the in vitro data that we've generated and the in vivo data that we've done in some very, very, challenging animal models. So I think its preclinical profile is very promising. It looks good.
The.
Treatment naive patients.
Hi remix patients.
We'll be the other phase lumpy. So we've got two phase one piece coming up.
To start next year.
The first one B study, which will be a new suppressed is.
Assuming phase one in Healthys finishes when we expect it to.
We would roll right into the new suppress and want to be and then.
That would be in the first quarter.
Jay R. Luly: We we've also done a lot of work on DMPK, and so, you know, the molecule 514 ergot swings to go into the clinic, the early studies were going to be, Really looking at safety and PK, confirmation, and healthies that we have. You know, just like we've had with many other candidates where we've designed the molecules, hopefully well, taking them into phase one. Hopefully, we'll have a... [inaudible] will be the other Phase 1B. So we have two Phase 1Bs coming up to start next year. You know, the first 1B study, which will be in new suppressed is, Assuming phase one and healthy finishes when we expect it to, we would roll right into the nuc suppress and 1b, and then that would be in the first quarter.
As 2020 calendar quarter, and then we would aim to.
I get into the.
And to the buy remake.
Patients sometime in the first half so.
Stay tuned on the fine tuning of that timing, but the goal is really to get the molecule as quickly as possible into a variety of HBV.
Patients and to.
You know start to confirm.
And in fact it.
Patients the very good results that weve seen pre clinically.
Got it thanks, sorry, if in this line better now.
Yes sounds a little better okay, yes, no sorry, I was asking specifically in thinking about the viral load reduction in the phase one b what would be viewed as clinically differentiated to some of the other.
Jay R. Luly: 2020 calendar quarter. And then we would aim to get the molecule into the Biremic patients sometime in the first half, so stay tuned on the fine-tuning of that timing. The goal is really to get the molecule as quickly as possible into a variety of HPV patients and to, you know, start to confirm the very good results that we've seen preclinically.
Novel core inhibitors that are currently in development. Thanks.
Yeah.
Again I'm.
I think we'll have to wait list where are we on that one until we see more data.
At A. Esselte, I think right now we've only seen.
A minimal amount of data in terms of what.
Cores can can do.
In that environment, and I think we'll have a more complete data set from a larger group of.
Turner: Got it, thanks. Sorry if, uh, is this line better now?
Potential competitors after esselte in November so.
Jay R. Luly: Yes, it sounds a little better.
Turner: Okay, yeah, no, sorry, I was asking specifically about the viral load reduction in Phase 1b; will it be viewed as clinically differentiated from some of the other novel core inhibitors that are currently in development?
I think we're still it's very early days to see.
What that log drop business not just the long drop of course, that's a.
Jay R. Luly: Yeah, Again, I think we'll have to wait. Why don't we, you know, pause on that one until we see more data at AASLD? I think, you know, right now we've only seen a minimal amount of data in terms of what CORS can do in that environment, and I think we'll have a more complete data set from a larger group of potential competitors after the AASLD in November. So, you know, I think we're still in the very early days to see.
That's a that's one key to along the road.
You are really looking into other pieces of information.
In terms of getting too.
Functional cures.
So I mean core inhibitors, even with.
The poor core inhibitor some of the earliest ones that went into the clinic.
You know showed.
Some significant viral load reductions, but that's that's obviously necessary, but not sufficient so I would expect based on the high potency of five one for that we would see a very good drop.
Jay R. Luly: [inaudible] In terms of getting to functional cures, so, I mean, core inhibitors, even with a poor core inhibitor, some of the earliest ones that went into the clinic showed. But more importantly, it's going to be how it performs in combination with a nuke and how you get to a functional cure. Right now, we have no reason to think that 514 is a good option, you know, less than any other compound from a potential perspective out there. We just need to generate that data.
But more importantly, it's going to be how does it perform in combination with a new and how do you.
To get to a.
A functional cure right now we have no reason to think that 500 fours.
You know less than any other.
Compound from a potential perspective out there, we just need to generate that data.
Great. Thank you started off the line.
Turner: Great, thank you. Sorry about the line.
Your next question comes from the line of late.
John: Your next question comes from the line of Liisa Bayko with JMP Securities. Hi, John, on behalf of Liisa, thanks for taking the questions and for the updates. Just a quick one on NASH. Jay, when you're mentioning ASLD, I'm wondering if the goal is to have the NASH data late this quarter and then hopefully have some additional presentation on ASLD? Will that timing work out?
Back out with JMP Securities.
Hi, John on for LIFO, Thanks for taking the questions and for the update.
Just a quick one on Nash.
Jay when you're matching and they'll be I'm wondering is the goal to have the Nash data leap of core and then hopefully have.
Some additional presentation and will be will that timing work out do you think.
Yes.
Jay R. Luly: Yeah, I'd say that would be beyond, probably beyond likely. But who knows?
The.
Beyond.
Probably beyond likely.
But who knows I cant commit.
Jay R. Luly: I can't commit today on that. Let's get the data first, and then we'll roll out. Top-line data first, and then we'll look to ultimately get it into the soonest reasonable conference that we can get it into.
Today on than what's.
Let us get the data first and then we'll roll out.
Topline data first and then we'll look to ultimately get it into.
Jay R. Luly: Okay, and then just one last question on RSV. Can you remind us of the size and design of the Phase 2B you're expecting to kick off here? Thanks.
Yes, the soonest reasonable confidence that we can get it into.
Okay, and then just one last one on RSP care minus of this size and design of a phase to be you're expecting the kick off here. Thanks.
On the outpatient study the size so protocols.
Jay R. Luly: on the outpatient study to size. So protocols are being put together, you know, sort of as we speak, so we'll be discussing that soon enough, but we don't have the final end quote worked out, looking at powering and other considerations. I don't want to put a number out until the team's had a chance to finalize the protocols.
Being put together.
You know sort of as we speak so I.
We'll be discussing that.
No soon enough, but we don't have the.
You know it the final.
In scope worked out looking at powering and other considerations.
I want to put a number until the teams had a chance to finalize the protocols.
Your next question comes from the line of Patrick True Chico with Baron Bird capital.
Patrick Truccio: Your next question comes from the line of Patrick Truccio with Barenburg Capital. Hi, good afternoon.
Hi, good afternoon.
Jay R. Luly: I have a follow-up on 938 and also on 305. Just first on 938, Jay, you alluded earlier to determining an acceptable dosing window for 938 for RSV, and we know with the influenza drugs, this window is within 48 hours. That's the best case we can get with these drugs. So I'm wondering if, with RSV, assuming there is also this acceptable dosing window in the phase 2B study, is there a definitive way to understand whether or not a patient is actually in that optimal dosing window, or is it more based on how long the patient has demonstrated RSV symptoms, with that being perhaps just a key part of the inclusion criteria?
A follow up on nine three and also on three of five just first on 938, Jay you alluded earlier to determining acceptable dosing window for.
For nine three for RSV and we know.
The influence of drugs. This windows within 48 hours and that's the best case, we can get with these drugs. So.
I'm wondering if with RSV assuming there is also this acceptable dosing window in the phase Twob study is there a definitive way to understand whether or not a patient is actually in that optimal dosing window or is it is a more based on how how long the patients demonstrated RSV symptoms without being perhaps just a key part of the inclusion criteria.
Jay R. Luly: I think it's the latter. We'll be looking at time from symptoms. And, you know, we'll be able to analyze the data based on, you know, based on that. So, yeah, I think it's... It's the latter.
Yes, I think it's the latter and we'll be looking at.
Time for some time.
And.
Well to analyze the data.
Based on that.
So.
I think as.
It's the latter.
Patrick Truccio: And then, in ARGON1, specifically on safety and tolerability of 305 in this study, can you tell us what we should anticipate in terms of impact on LDL-C and paritis at each dose compared to placebo, if this data will be included in the data release that's expected at the end of the third quarter, or if it will be provided at a later date? And then finally, what would you want to see demonstrated by this data or other data to give you confidence?
And then in argon, one specifically on safety and Tolerability of 305 in this study can you tell us what we should anticipate in terms of impact on LDL C and provide us at each dose compared to placebo. If this data will be included in the data release, that's expected at the end of the third quarter or if it will be provided at a later date and then finally, what would you want to see demonstrated by this data or other data to give you confidence that three or five has best in class safety and Tolerability attributes.
Yes.
Jay R. Luly: So any data will be included in this analysis. And again, as I was sort of saying before, with all the efficacy parameters, I think we'll be looking at the safety parameters in the same way.
Any.
The data will be included in this.
Analysis, and again I think.
So that was sort of seen before with all the efficacy parameters.
I think we'll be looking at the safety parameters in the same way.
Jay R. Luly: [inaudible]
Good thing.
Jay R. Luly: and the GESTALT, what our doses do, and what that sort of quote therapeutic window defined is for a go-forward dose. So it's just going to be data that we put into context, just like all the efficacy parameters. We should have that included in the data set at the... End of the quarter.
So what are those do.
And with that.
You know sort of close therapeutic window.
Ill defined is for.
Hey go forward so.
It will be.
Do you do that we'll put into context.
Just like all the.
Patrick Truccio: That's helpful. Thank you very much. You're welcome.
We should have that.
Included in the news.
Carol Nacelle: And with no further questions, I'd like to turn the call back over to Carol Nacelle for any closing comments. Thank you everyone for joining us. If you have any additional questions, feel free to call us in the office. Thank you. Ladies and gentlemen, this concludes today's conference call. You may now disconnect.
The.
For.
That's helpful. Thank you very much.
You're welcome.
And with no further questions I'd like to turn the call back over to Carol Miceli for any closing comments.
Thank you very much.
No question.
Yeah.
Thank you.
[noise], ladies and gentlemen. This concludes today's conference call you may now disconnect.
[noise].