Q4 2019 Earnings Call
Please be advised so today's conference is being recorded if your part or any further assistance. Please press star zero I would now like to hand, the conference over to your speaker today girls in Philly. Thank you. Please go ahead.
Operator: I would now like to hand the conference over to your speaker today, Carolyn Kershaw.
Sally: Thank you, Sally. Thank you.
Chantel: Thank you. Please go ahead.
Carolyn Kershaw: Thank you, Chantel, and thanks for joining us this afternoon. The news release with our financial results was issued and is available on our website. On the call today are Dr. Jay Luly, President and Chief Executive Officer, Paul Mellett, our Chief Financial Officer, and other members of Enanta's senior management team. 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 and expectations with respect to our research and development pipeline and financial projections, all of which involve certain assumptions and risks beyond our control that could cause our actual developments A description of these risks is in our most recent Form 10-Q and other periodic reports filed with the SEC. Enanta 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. Jay Luly, President and CEO of Enanta Pharmaceuticals Inc.
Thank you Shannon tell and thanks for joining us. This afternoon. The news release with our financial results was issued and is available on our website on the call today's Dr., Jay life, President and Chief Executive Officer, Paul Miller, Our Chief Financial Officer, and other members of it into senior management team.
Before we begin but our formal remarks, we want to remind you that we will be making forward looking statements, which may include our plans and expectations with respect to our research and development pipeline and financial projections, all of which involves certain assumptions and risks beyond our control that could cause our actual development results to differ materially from those.
Statements a description of these risks in our most recent Form 10-Q , another periodic reports filed with the FCC and it does not undertake any obligation to update any forward looking statements made during this call.
I'd now like to call the turnover called the <unk> turn the call over Dr., Jay we like President and CEO .
Jay R. Luly: Thank you, Carol, and good afternoon, everyone.
You Carol good afternoon, everyone.
Jay R. Luly: We made great progress at Enanta this year, and I'm excited to share with you the plans we have for the year ahead. In our clinical development programs, we announced positive Phase IIa data for our RSV and NASH compounds. We are advancing our first HBB core inhibitor through a Phase 1a, 1b study, and our research continues to discover world-class molecules. This afternoon, we announced our newest drug candidate, ADP297, which is our follow-on FXR agonist development candidate for NASH. We are also working on follow-on compounds for RSV and HPV as well as new compounds in the early stages of discovery that are targeting other mechanisms of action and, in some cases, other disease areas. We continue to receive substantial royalties from our HCV collaboration with AbbVie, and this, coupled with our strong cash balance of $400 million, is sufficient to fund our business, including our growing clinical development programs for the foreseeable future. In fact, since our March 2013 IPO, we have not needed to raise, nor have we raised, any additional capital. Before I begin with a review of our development program, I wanted to thank our talented and dedicated employees.
We made great progress at an end to this year and I'm excited to share with you. The plans we have for the year ahead.
From our clinical development programs, we announced positive phase two a data for RSV and Nash compound.
We are advancing our first H.B.B. core inhibitor through phase one a one be study and our research continues to discover world class molecules.
So for now when we announced our newest drug candidate ATP to nine seven which is our follow on FX, our agonist development candidate for now.
We're also working on follow on compounds for RSV and HBV as well as new compounds in the early stages of discovery that are targeting other mechanisms of action and in some cases other disease areas.
We continue to receive substantial royalties from our HCV collaboration with Abbvie and this coupled with our strong cash balance of $400 million is sufficient to fund our business, including our growing clinical development programs for the foreseeable future.
In fact, some sort of March 2013, IPO, we have not needed to raise nor have we raised any additional capital.
Before I begin with a review of our development programs I wanted to think are talented and dedicated employees.
Jay R. Luly: who have worked tirelessly to bring forward what we believe are some of the most promising compounds for RSV, NASH, and HPV in development today. I'll now begin my review with our most advanced program, EDP938, our end-protein inhibitor for respiratory syncytial virus, known as RSV. As a reminder, RSV is a severe respiratory infection associated with significant morbidity and mortality in infants, the elderly, and immune-compromised adults, and a condition for which there is currently no safe and effective therapy.
Worked tirelessly to bring forward, what we believe or some of the most promising compounds for RSV.
In HPV and development today.
Well now begin my review with our most advanced programs 80, peering three eight or in protein inhibitor for respiratory syncytial virus known as RSV.
As a reminder, RSV is a severe respiratory infection associated with civic significant morbidity and mortality and influence the elderly and immune compromised adults the condition for which there is currently no safe and effective therapy.
Jay R. Luly: In June, we announced positive top-line results from our Phase 2a Human Challenge Study of EDP938 in healthy adults infected with RSV. This study yields some of the most promising data to date from an RSV challenge study. EDP 938 demonstrated highly statistically significant reductions in RSV viral load as measured by RT-PCR assay and by plaque assay, as well as in total symptom score and mucus weight. Given these results, we are pleased to announce that we have initiated a Phase 2B study of ADP 938. This study, which we have named RSVP, will focus on adult outpatients with community acquired RSV.
In June we announced positive top line results from our phase two a human challenge study of PDP 938, and healthy adults infected with RSV.
This study yield somewhat of the most promising data to date from an RSV Challenge study.
D. P 938 demonstrated highly statistically significant reductions in RSV viral load.
As measured by RT, PCR assay and by plaque assay as well as in total symptom score and mucus weight.
Given these results were pleased to announce that we've initiated a phase twob study of ATP 938.
The study, which we have named RSVP well focus on adult patients with community acquired RSV.
Jay R. Luly: The RSVP study is designed to provide further information about EDP938 in a community-acquired RSV adult population and to better understand the feasibility of DAA therapy in an outpatient setting. We are preparing to conduct further studies in targeted patient populations such as the immune-compromised, the elderly, and pediatric populations. The RSVP study is a randomized, double-blind, placebo-controlled study that is designed to enroll approximately 70 subjects up to the age of 75 years, randomized to receive either 800 milligrams of EDP-938 or placebo for five days. The primary objective of this study is to evaluate the effect of EDP-938 on progression of RSV infection by assessment of clinical symptoms measured over the course of the 14-day study observation period. Any viral activity will be evaluated as the key secondary endpoint.
Our SPP is designed to provide further information about 80.938, and a community acquired RSV adult population and to better understand the feasibility of D.A. therapy, and an outpatient setting.
We are preparing to conduct further studies and targeted patient populations such as the immune compromised the elderly and pediatric population.
The RSVP study is a randomized double blind placebo controlled study that is designed to enroll approximately 70 subjects up to the age of 75 years randomized to receive either 800 milligrams of GDP 938 or placebo for five days.
The primary objective of this study is to evaluate the effect of GDP 938 on progression of RSV infection by assessment of clinical symptoms measured over the course.
Of the 14 days study observation period.
Any viral activity will be evaluated as a key secondary endpoint.
Jay R. Luly: Depending upon the severity of the RSV season in North America and the rate of enrollment, our goals to complete the RSV-P study in one season and top-line data could be announced in the third quarter of calendar 2020. If needed, however, we have plans to continue the study in the Southern Hemisphere, where RSV infection occurs later in the year. Given our promising Phase 2a results in RSV and the non-fusion mechanism of EDP938, we believe it represents the best chance for success in a therapeutic area that, to date, has been challenging. Our next most advanced program is for NASH.
Depending upon the severity of the our ski season in North America, and the rate of because of enrollment our goals to complete RSVP study in one season and topline data could be announced in the third quarter of calendar 2020.
If needed. However, we have plans to continue this study in the southern Hemisphere, where RSV infection occurs later in the year.
Given our promising phase two able results and RSP and the non fusion mechanism of ATP 938.
We believe it represents the best chance for success in a therapeutic area that today has been challenging.
Our next most advanced programs for Nash and September an anti announced topline data from the phase two a argon one study a nash subjects.
Jay R. Luly: In September, Enanta announced top-line data from the Phase IIa Argon I study in NASH subgroups. The primary endpoint, ALT reduction at week 12, and a key secondary endpoint, reduction in liver fat content as measured by MRI-PDFF at week 12, were met in the 2.5 milligram dosing group at the one milligram dose. Also showed, I'm sorry, the one milligram dose showed non-statistical numerical trends on several efficacy. Given this overall profile, we plan to further evaluate EDP-305 in Argon 2, a Phase 2B study that we plan to initiate in the second quarter of calendar 2020. Argon 2 will be a randomized, double-blind, placebo-controlled, 72-week study in approximately 340 subjects with biopsy-proven necks The primary endpoint of the study will be improvement of fibrosis without worsening of NASH or NASH resolution without worsening of fibrosis.
The primary endpoint LT reduction at week, 12, and a key secondary endpoint reduction in liver fat content as measured by MRI Pdfs at week 12 were masked in the 2.5 milligram dose in group.
At the one milligram dose.
Also showed.
I'm, sorry, though the one milligram dose showed non statistical numerical trends on several efficacy markers.
Given this overall profile we plan to further evaluate.
GDP Threeo five in Oregon too.
Phase Twob study that we plan to initiate in the second quarter of calendar 2020.
Argon two will be a randomized double blind placebo controlled 72 week study and approximately 340 subjects with biopsy proven Nash.
The primary endpoint of this study will be improvement of fibrosis without worsening of Nash and or Nash resolution without worsening of fibrosis.
Jay R. Luly: Two doses of EDP-305 have been selected to provide strong target engagement and a balanced profile in terms of efficacy and tolerability. We plan to use doses of 1.5 mg and 2 mg with the aim of demonstrating stronger biomarker signals of efficacy than seen at 1 mg and less pruritus than seen at 2.5 mg, which were the doses investigated in Argon 1. This study will include a 12-week interim analysis designed to enhance our ability to seek opportunities more quickly for the development of EDP-305 in combination with other mechanisms in that. Also, in our NASH program, Enanta has identified EDP-297 as its follow-on FXR candidate. Preclinical data on ADP297 reveal a differentiated profile that delivers high target tissue distribution, along with potency greater than that published on any FXR agonist in clinical development today. In preclinical models, CDP-297 delivered the drug preferentially to tissues with FXR receptors, namely liver and intestine, while minimizing drug levels in plasma and skin. We believe that having a highly potent and highly targeted FXR agonist like ADP-297 may allow for lower doses and reduce drug levels in non-targeted tissues, thereby potentially reducing pruritus if it's an off-target effect.
Two doses of BDP, three or five had been selected to provide strong target engagement and a balanced profile in terms of efficacy and tolerability.
We plan to use doses of 1.5 milligrams and two milligrams with the aim of demonstrating stronger biomarkers signals of efficacy than seen at one milligram and less per write us than seen a 2.5 milligrams, which were the doses investigated in Oregon one.
The study will include a 12 week interim analysis designed to enhance our ability to seek opportunities more quickly for development of BDP, three or five and combinations with other mechanisms in there.
Also in our Nash program and anticipate Densified MDP to nine seven.
And as its follow on FX our candidate.
Preclinical data on ATP to nine seven reveal a differentiated profile that delivers high target tissue distribution, along with potency greater than that published on any FX or agonist and clinical development today.
And preclinical models CDP to nine seven delivered the drug preferentially tissues, with FX, Saar receptors, namely liver and intestine, while minimizing drug levels and plasma and skin.
We believe that having a highly potent and highly targeted FXR agonists like GDP to nine seven may allow for a lower doses and reduce drug levels at non targeted tissues, thereby potentially reducing pruritis, if it's an off target effect.
We expect to initiate a phase one study of GDP to nine seven.
In mid calendar 2020, and plan to have data in the first half of 2021.
Finally, the Intrepid study in PBC is continuing and we expect to have topline data in the second quarter of calendar 2020.
Jay R. Luly: We expect to initiate a phase one study of EDP-297 in mid-calendar 2020 and plan to have data in the first half of 2021. Finally, the intrepid study in PBC is continuing, and we expect to have top-line data in the second quarter of calendar 2020. Our HPV program is also progressing well. Earlier this year, we 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 aims to evaluate the safety, tolerability, and pharmacokinetics of single ascending doses and multiple ascending doses of EDP-514 in healthy subjects, while Part 2 will assess the safety and antiviral activity of EDP-514 in nuke-suppressed patients with chronic HPV infections. Nuke-suppressed refers to chronic HPV patients who are We have completed the SAD portion or are well along in the MAD portion of Healthy Volunteers. We plan to have that data in the first quarter of calendar 2020.
Our HBV program is also progressing well earlier this year, we initiated a phase one a one be clinical study with our novel class two HPV core inhibitor ATP five one for.
Part one of this randomized double blind placebo controlled study aims to evaluate the safety tolerability and pharmacokinetics of single ascending doses and multiple ascending doses of GDP five one for in healthy subjects, while part II will assess the safety and anti viral activity of GDP five one for now.
New suppressed patients with chronic HBV infection.
Nuke suppressed refers to chronic HBV patients, who are being treated with nuclear side analog therapies, which are the current standard of care.
We have completed the sandy portion or well on long in the M- portion in healthy volunteers, we plan to have that data in the first quarter of calendar 2020.
We then plan to proceed to study ATP five one for nuke suppressed HBV patients in calendar Q1, followed by a separate study and by Uremic HBV patients in calendar Q2.
It would be five one for was selected from our lead series of HPV compounds that are characterized by potent antiviral activity.
Our promising preclinical data support our excitement for this mechanism.
Finally, it's important to mentioned that drug discovery remains a core strength of this company, we continue to invest substantial resources and research programs to discover backup compounds as well as new compounds targeting different mechanisms of action both in our core areas and in other areas.
Reviewing the broad range of our R&D portfolio makes me very excited about the coming here and I look forward to addressing any questions may have about it.
First, though I will turn the call over to Paul to discuss our financials for the quarter Paul Thank you Jay.
I'd like to remind everyone that an annual reports on September thirtyth fiscal year schedule.
Today, we are reporting results for our fourth fiscal quarter in fiscal year end ended September Thirtyth 2019.
Paul J. Mellett: We then plan to proceed to study EDP514 in nuke-suppressed HPV patients in calendar Q1, followed by a separate study in viremic HPV patients in calendar Q2. 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 metric. Finally, it's important to mention that drug discovery remains a core strength of this company. We continue to invest substantial resources and research programs to discover backup compounds as well as new compounds targeting different mechanisms of action, both in our core areas and in other areas. Reviewing the broad range of our R&D portfolio makes me very excited about the coming year, and I look forward to addressing any questions you may have about it. First, though, I will turn the call over to Paul to discuss our financials for the quarter. Paul. Thank you, Jay.
For the quarter total revenue was 51.3 million and consisted entirely of royalty revenue earned on Abbvies Global HCV product sales of 698 million. This compares to total revenue of 67.2 million for the same period in 2018.
The decrease in our royalty revenue quarter over quarter was due to lower global HCV product sales reported by Abbvie.
Well to revenue is calculated on 50% of Maverick sales at a blended royalty rate for the quarter of 15% in on approximately 30% of secure a sales at a royalty rate of 10% after adjustments for certain contractual discounts and rebates, which historically have approximated 1.5%.
These total reported HCV product sales.
During our fourth fiscal quarter, our royalty rates, a maverick was a blend of our third and fourth royalty tiers of 14% in 17% respectively.
Our royalties are calculated on a calendar year basis, therefore royalties for our fiscal first quarter ending December 31 will be calculated at the highest royalty rate and royalties for our fiscal quarter ending March 31st will be calculated at 10% our lowest royalty rate tier in our fiscal year.
You can review our royalty tier schedule in our 2018 Form 10-K .
Paul J. Mellett: Thank you, Jay. I'd like to remind everyone that Enanta reports on a September 30th fiscal year schedule. Today we are reporting results for our fourth fiscal quarter and fiscal year-end ended September 30th, 2019. For the quarter, total revenue was $51.3 million and consisted entirely of royalty revenue earned on AVI's global HCV product sales of $698 million. This compares to total revenue of $67.2 million for the same period in 2018. The decrease in our royalty revenue quarter over quarter was due to lower global HCV product sales reported by AbbVie. Royalty revenue is calculated on 50% of Maverick sales at a blended royalty rate for the quarter of 15% and on approximately 30% of Viqueira sales at a royalty rate of 10%, after adjustments for certain contractual discounts and rebates, which historically have approximated 1.5% of AVI's total reported HCV product sales.
Moving onto our expenses for the three months ended September Thirtyth 2019 research and development expenses totaled 38.7 million compared to 26.9 million for the same period in 2018.
Increase was primarily due to greater clinical costs associated associated with the progression of our wholly owned clinical programs and RSV Nash PBC in HBV, including a three phase two clinical trials.
General and administrative expense for the quarter was 6.2 million a slight increase to the comparable quarter in 2018.
An into recorded an income tax benefit over half million dollars for the three months ended September Thirtyth 2019, compared to income tax expense of 8.5 million for the same period in 2018.
For the 12 months ended September Thirtyth, 2019, and answers effective tax rate benefit was approximately 2% compared to an effective tax rate of approximately 23% for the 12 months ended September Thirtyth 2018.
I'd like to note that the drivers of the decrease in the effective tax rate I covered in the press release.
Paul J. Mellett: During our fourth fiscal quarter, our royalty rate for Maverick was a blend of our third and fourth royalty tiers of 14% and 17%, respectively. Our royalties are calculated on a calendar year basis. Therefore, royalties for our fiscal first quarter ending December 31 will be calculated at the highest royalty rate, and royalties for our fiscal quarter ending March 31 will be calculated at 10%, our lowest royalty rate tier in our fiscal year.
And then come from the three months ended September Thirtyth, 2019 was 9.2 million or 44 cents per diluted common share compared to net income of 27.4 million or $1.30 cents per diluted common share for the corresponding period in 2018.
And then to ended the quarter with approximately 400 million in cash and marketable securities an increase of 75 million for my 2018 fiscal yearend balance of 325 million.
In terms of guidance for fiscal 2020, we expect our research and development expense to be between 155 in 175 billion and our general and administrative expense to be between 27 and $33 million.
Paul J. Mellett: You can review our royalty tier schedule in our 2018 Form 10-K. Moving on to our expenses, for the three months ended September 30, 2019, research and development expenses totaled $38.7 million, compared to $26.9 million 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 in RSV, NASH, PBC, and HBV, including our three phase two clinical trials.
Further financial details are available in our press release and will be available in our current report on Form 10-K when filed.
I'd now like to turn the call back to the operator and open up the lines for questions operator.
As a reminder to ask a question you will need to press star one on your telephone to withdraw your question press the pound or hash key please limit your questions to one question and one follow up to allow other participants time for questions. Please standby compiled acuity roster.
Paul J. Mellett: General and Administrative Expense for the quarter was $6.2 million, a slight increase over the comparable quarter in 2018. Enanta recorded an income tax benefit of $500,000 for the three months ended September 30, 2019, compared to income tax expense of $8.5 million for the same period in 2018. For the 12 months ended September 30th, 2019, Enanta's effective tax rate benefit was approximately 2% compared to an effective tax rate of approximately 23% for the 12 months ended September 30th, 2018. I'd like to note that the drivers of the decrease in the effective tax rate are covered in the press release. Net income for the three months ended September 30, 2019 was $9.2 million, or $0.44 per diluted common share, compared to net income of $27.4 million, or $1.30 per diluted common share, for the corresponding period in 2018.
Your first question comes from Brian Abrahams with RBC capital markets. Your line is open.
Hi, there thanks for taking my questions.
Congrats on all the continued progress.
I guess first on.
On the on the Nash program and argon too.
Can you talk a little bit more about how you guys selected those those doses and maybe some of the.
The data analyses that you did to find.
You believe could be a sweet spot there and I guess Im also wondering if you could also talk more about the.
Interim analysis, when that might when you might expect to see that and.
How you would think about positioning this in combination are you thinking about internal combinations or external combinations what might be the optimal mechanisms and then I had a quick follow up on RC. Thanks.
Sure.
Thanks for the questions, Brian So on argon too.
We.
Yes, it was actually reasonably straightforward as we as we indicated on the no the Oregon, one data call.
We saw a very strong target engagement at 2.5 milligrams, whether you looked at.
Paul J. Mellett: And then, at the end of the quarter, with approximately $400 million in cash and marketable securities, an increase of $75 million from our 2018 fiscal year-end balance of $325 million. In terms of guidance for fiscal 2020, we expect our research and development expenses to be between $155 million and $175 million, and our general and administrative expenses to be between $27 million and $33 million. Further financial details are available in our press release and will be available in our new report on Form 10-K when it is filed. I'd now like to turn the call back to the operator and open up the lines for questions. Operator?
[noise] LT reductions fat reductions either on an absolute or on a rough relative scale TGT reductions.
Looking at Al Phos see for up to you have 19.
Whole profile lined up to show very very strong target engagement.
One milligram, we saw some reasonable signs of that.
But certainly not as strong as.
2.5, so we.
We looked at those.
Those two sort of doses as sort of goalpost.
And then started asking ourselves.
What would we like to ultimately achieve number one obviously, we saw a fair amount to provide us two and a half milligrams.
Not much at all at one milligram.
And so I think the key is.
Really driving to a dose that is higher.
Then one in terms of giving better Bart biomarker indications of efficacy.
Operator: As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound or hash key. Please limit your questions to one and one follow-up to allow other participants time for questions. Please stand by while we compile the Q&A roster. Your first question comes from Brian Abrahams with RBC Capital Markets. Your line is open.
And dose lower than 2.5.
In relations to having.
A better tolerability profile than than 2.5, so we.
Ultimately aims to.
Two we came down on on 1.5, and two is that reasonable.
So those will be going.
Ahead and from a timing.
Perspective that will.
You know depend on accrual will share.
Brian Corey Abrahams: Hi there. Thanks for taking the time to answer my questions. Congratulations on all the continued progress. I guess, first, on the NASH program and Argonne 2. Can you talk a little bit more about how you guys selected those doses and maybe some of the data analyses that you did to find what you believe could be a sweet spot there? And I guess I'm also wondering if you could also talk more about the interim analysis, when you might expect to see that, and how you would think about positioning this in combination, whether you're thinking about internal combinations or external combinations, what might be the optimal mechanisms? And then I had a quick follow-up on RSV. Thanks.
The results with those as the as the study.
Gets up and and going.
What will do is.
Take information you ultimately from those intermediate doses.
Which we think might be.
One or both I guess in theory might be interesting to explore.
In relation to.
Combinations.
And with regards to ideal combination partners.
We're not.
Likely to have an internal molecule that will be at that stage two.
Jay R. Luly: Sure. Thanks for the questions, Brian.
Jay R. Luly: So on Argonne 2, we... You know, it was actually reasonably straightforward, as we indicated on the Argonne one data call. We saw a very strong target engagement at 2.5 milligrams, you know, whether you looked at ALT reductions, fat reductions, either on an absolute or on a relative scale, GGT reductions, looking at ALKFAST, C4, FGF19. I mean, the whole profile lined up to show very, very strong target engagement.
To do those combinations with at the time other than in FX. Our agent. So we'll be looking at other non FX are.
Mechanisms.
Out there are two to do those combinations so stay tuned on that front.
Yes.
Question.
Yes, and then just on the on the RSVP.
Study.
How important is reductions and hospitalization I guess, what I'm trying again kind of getting at is it do you view. This initial population youre going to be testing.
The age antennas.
Jay R. Luly: One milligram, we saw some reasonable signs of that, but certainly not as strong as 2.5. So we looked at those two doses as sort of goalposts and then started asking ourselves, you know, what would we like to, you know, ultimately achieve? Number one, obviously, we saw a fair amount of pruritus at two and a half milligrams, not much at all at one milligram. And so I think the key is You know, really driving to a dose that's higher in relation to having, you know, a better tolerability profile than 2.5. So we ultimately aimed to, We came down on 1.5 and 2 as the reasonable doses, and so those will be going ahead. And, you know, from a timing perspective, that'll, you know, depend on accrual.
A population that you may potentially move forward with for registration or is this just more of a way to get quick proof of concept with.
Real World infection that I guess I'm wondering when we see the data how translatable well the results be onto some of the high unmet need groups like pediatrics, just given the differences in immune system and viral kinetics there.
As well as to.
Immune compromised patients. Thanks.
Yeah, why would I would certainly put it into the category of it. So it's a really good proof of concept study and community acquired RSV.
You know I don't know that.
Ultimately is the largest patient population, but there's still a lot of adults that do get.
Our as fee and patients. So it's also it's and it's a it's further it's a way to us.
It to look at conducting a trial and an outpatient setting which.
Jay R. Luly: We'll share, you know, results with those as the study gets up and going. What we'll do is, take information, you know, ultimately from those intermediate doses, which we think might be One or both. I guess, in theory, it might be interesting to explore in relation to combinations. And with regard to, you know, ideal combination partners, we're not likely to have an internal molecule that will be at that stage to do those combinations with at the time other than an FXR agent. So we'll be looking at other non-FXR mechanisms out there to do those combinations. So stay tuned on that. Yeah, an RSD question.
It is interesting all by itself so I'd say it's a.
No a good.
Good and logical step in the progression.
You know it's.
Our ability to.
Kind of get at the feasibility to of.
Of rapid treatment.
After a rapid diagnostic.
That could.
Prevent hospitalizations ultimately, but so yeah, it'll it'll give us a whole bunch of.
Information.
And the and the broad spectrum again, we're trying to learn as much about this drug in different patient populations as we can.
Makes sense. Thanks, so much Jay.
Youre welcome.
Your next question comes from Jay Olson with Oppenheimer. Your line is open.
Brian Corey Abrahams: Yes, and then just on the RSVP study, I guess how important is reduction in hospitalization? I guess what I'm kind of getting at is, do you view this initial population you're going to be testing the agent in as a population that you may potentially move forward with for registration, or is this just more of a way to get quick proof-of-concept with real-world infection? I guess I'm wondering when we see the data, how translatable would the results be to some of the high unmet need groups like pediatrics, just given the differences in immune system and viral kinetics there, as well as to immune compromised patients. Thanks.
Alright, congrats on the progress and thanks for taking the questions.
My first question did you want anything at A.S. held the that changes your view of the opportunity for an FX art in Nash and specifically with regards to the potential to improve upon efficacy safety or tolerability over other FXR agonists and then I have a follow on if I may.
Learn anything it up and Esselte I mean I think the.
One thing that we saw esselte was.
Trope effects or.
Jay R. Luly: Yeah, well, I would certainly put it into the category of it's a really good proof of concept study in community acquired RSV. But you know, I don't know that it
Had prior to us I mean that was.
An interesting.
I guess observation that comes from a.
Sort of a different chemical plants and so forth.
Jay R. Luly: So, you know, ultimately, this is the largest patient population, but, you know, there's still a lot of adults that do get RSV in patients. So it's also, and it's further, it's a way for us to look at conducting a trial in an outpatient setting, which, you know, is interesting all by itself. So I'd say it's a good and logical step in the progression. Um, you know, it's our ability to kind of get at the feasibility of Rapid Treatment after Rapid Diagnostic. Page PAGE of NUMPAGES www.verbalink.com Page PAGE of NUMPAGES
And they had reported too much until they did their dose escalation up into the range, where they started seeing.
Significant.
Efficacy marker movement, and then that came in so.
That was.
That was one.
Aspect to it.
The.
I think the other.
I guess, maybe that's a good segue to thinking about ATP to nine seven.
In terms of our our new candidate we've been working on a follow on molecule.
For quite some time as I think everybody sort of listening and is probably aware and we're trying to fine tune a profile nobody fundamentally understands exactly what's causing.
The tolerability issue with.
Brian Corey Abrahams: That makes sense. Thanks so much, Jay.
Next ours has there been seen today.
Jay R. Luly: You're welcome.
So we felt one of the absence of discrete mechanism.
Jay Olson: Your next question comes from Jay Olson with Oppenheimer. Your line is open.
One could.
Jay R. Luly: Oh, hi. Congratulations on the progress and thanks for taking the questions. My first question is, did you learn anything at ASLD that changes your view of the opportunity for an FXR in NASH, and specifically with regard to the potential to improve efficacy, safety, or tolerability over other FXR agonists? And then I had a follow-on question, if I may.
Fully understand.
The best next best thing you can do is ratchet down the potency against your intended target.
Super Super well and.
We certainly did this discovery team at an end to deserves.
A lot of congratulations in terms of being able to.
Fine tune. The goal is if you can push harder and harder on.
FX are.
Generally speaking.
Jay R. Luly: Um, learn anything at FASLD. I mean, I think the one thing that we saw at ASLD was tropifexor had pruritus. I mean, that was... An interesting, I guess, observation that that comes from a sort of a different chemical class and so forth. And they hadn't reported too much until they did their dose escalation up into the range where they started seeing, you know, significant efficacy marker movement.
At least you have a chance of improving selectivity over other.
Receptors.
We then came up with a targeting approach which.
Is aimed at.
So the intestine FX our receptors in the intestine and also in the liver both sites of which have have shown.
Places, where you can FX are agonist can modulate pathways that are important and the pathogenesis of Nash patients. So.
Jay R. Luly: So that was, that was one aspect of it. The other, I guess, you know, maybe that's a good segue to thinking about, you know, EDP297. In terms of our new candidate, we've been working on a follow-on molecule for quite some time, as I think everybody sort of listening in is probably aware, and we're trying to fine-tune a profile. Nobody fundamentally understands exactly what's causing the tolerability issues with FXRs that have been seen to date.
We have a very high degree of targeting.
Those tissues with FX arbor sectors, and we dialed down.
Dramatically.
Associated plasma levels that you would run into so that'll help contained or contain things outside in the periphery and then other tissues.
You know such as skin.
Where we again, we're focusing on.
Getting drug levels, so we down so.
Well that.
Jay R. Luly: So we felt one of the, you know, absent a discrete mechanism, that one could fully understand. The next best thing you can do is ratchet down the potency against your intended target super super well and we certainly did this. The discovery team at Enanta deserves credit. You know, a lot of congratulations in terms of being able to, you know, fine tune that the goal is, you know, if you can push harder and harder on FXR, generally speaking, you know, at least you have a chance of improving selectivity over, you know, other receptors. We then came up with a targeting approach, which is aimed at the intestine, FXR receptors in the intestine and also in the liver, both sites of which have shown places where you can, FXR agonists can modulate pathways that are important in the pathogenesis of NASH So we have a very high degree of targeting, in those tissues with FXR receptors, and we dialed down dramatically the associated plasma levels that you would run into.
Play out.
It will remain to be seen but.
We think it's very.
Interesting approach and worthy of exploration and our next studies. So again, we're aiming to have GDP to nine seven.
In the clinic and mid 20.
Okay, Great and then if I could ask a quick question on GDP 514.
Could you just talk about your treatment objectives for.
The two populations you mentioned nuke suppressed HBV patients and viremia HBV patients what are the goals in those two different patient populations.
Yeah, So maybe I'll hand to this question over to not only just to make a couple of quick comments on those studies hi. Thank you for inclusion so I think at that stage.
Obviously, we are looking at the phase one a b.
Steady for new surprised and Viremia basin.
And therefore, you know we have to go a step wise as we are looking to have become pony in this population. So we we'd be looking good safety and Tolerability, mainly for 28 days of treatment as well as have you seen of some of the new biomarker getting a sense main devoting patient.
Jay R. Luly: So that'll help contain things outside in the periphery and in other tissues, you know, such as skin, where we, again, are focusing on getting drug levels, you know, way down. But will that, you know, work? You know, it'll remain to be seen, but we think it's a very interesting approach and worthy of exploration in our next studies. So, again, we're aiming to have ADP297 in the clinic by mid-20.
For the activity of the trend so thats the plan for the early stage.
Okay, great. Thanks for taking the questions.
Good thank you.
Your next question comes from Yasmeen Rahimi with Roth Capital. Your line is open.
Jay R. Luly: Okay, great. And then, if I could ask a quick question on EDP 514, could you just talk about your treatment objectives for the two populations you mentioned, nuke-suppressed HBV patients and viremic HBV patients? What are the goals in those two different patient populations?
Poultry as me I'd seen congrats on the progress this quarter. So because of two question today first could you just help walk us through the powering.
Endpoint RSVP.
And also we just wondering could give us your thoughts on moving through five into phase be given the competitive mashed landscape.
Natalie: Yeah, so maybe I'll hand this question over to Natalie just to make a couple of quick comments on those studies.
So maybe I'll start with the the second question first and all that not only a work on the first question for you the.
Natalie: Hi, thank you for your question. So, I think at that stage, obviously, we are looking at a phase 1 AB study for a nucleoprase and viremic patient. And therefore, as you know, we have to go stepwise as we are looking to have a B compound in this population. So, we will be looking at safety and tolerability, mainly for 28 days of treatment, as well as, obviously, some of the new biomarkers giving us a sense, mainly in the viremic patient, of the activity of the drug. So, that's the plan for the early stage.
Second question is the Nash landscape has anything but understood right now we're at a an early stage and this whole disease area I would sort of call. It a 1.0.
Stage, where.
Only now are we beginning to understand what are the most promising.
Mechanisms and Nash and we barely know much about that yet.
In patients.
Actually when you're looking at.
Later stage studies with.
Natalie: Okay, great. Thank you for taking the question. Good, thank you.
Good patient numbers and good read outs.
Paul: Your next question comes from Yasmeen Rahimi with Roth Capital. Your line is open.
So we're at the very early stages of understanding what are the most important mechanisms and then we have even further to go before people will know for sure what are the very best.
Paul: Paul on behalf of Yasmeen. Hi team, congrats on the progress this quarter.
Paul: So we just have two questions today. First, could you just help walk us through the powering for the primary endpoint on RSVP? And also, we just were wondering, could you give us your thoughts on moving 305 into Phase B given the competitive NASH landscape?
Single agents against those single mechanisms and then only then can we really begin to move on to 2.0 and beyond which will be.
Likely involving combinations of agents so I.
Jay R. Luly: So maybe I'll start with the second question first and I'll let Natalie work on the first question for you. Second question is that the Nash landscape is anything but understood, you know, right now, we're at a, an early stage in this whole disease area, I would sort of call it a 1.0, stage where, you know, only now are we beginning to understand what are the most promising mechanisms in NASH and we we barely know much about that yet in patient especially when you're looking at, you know, later stage studies with.., you know, good patient numbers and good readouts. So, we're at the very early stages of understanding what are the most important mechanisms, and then we have even further to go before people will know for sure what are the very best, single agents against those single mechanisms, and then only then can we really begin to move on to 2.0 and beyond, which will be likely involving combinations of agents. So, I think, you know, what we continue to see is ZDP 305 does have a very strong, Profile is an FXR agonist. It's generally safe.
I think what we continue to see as GDP three or five.
Does have a very strong.
Profiles and FX are agonist, it's a generally a safe.
The Tolerability profile, we know.
That profiles not.
Dissimilar from some others were trying to see if we can improve upon it. We've also at least in the Oregon, One study appear to have seen.
You know a good profile of GDP, three or five on lipids and so we're we're going to again pressed to the next question just like in phase one when we made the phase one.
Migration into argon one study we had to change our doses.
To lower doses, where we still saw a target engagement, but avoided.
Right as none in Nash patients, we were surprised that everything became more sensitive with.
Our FX our agonist in terms of efficacy and Tolerability. So we're just frame shifting things a bit but it's very strong.
Jay R. Luly: The tolerability profile we know. We're going to keep that one moving forward. Again, if we can get some information ultimately to aid us in peeling that off into combinations sooner, we're going to do that. And meanwhile, in parallel, we'll have a follow-on that has a very differentiated profile versus any other FXR agonist in development today. In terms of number one, at least on preclinical data, being the most potent one that's out there, it eclipses tropifexor by a bit.
Candidate and.
We're going to keep that one.
Moving ahead again, if we can get some information ultimately to aid us in peeling that often to combination sooner.
We're going to do that and Meanwhile, in parallel will have.
A follow on that has a very differentiated profile versus any other FXR agonist and development today.
In terms of number one at least on preclinical data being the most potent one that's out there.
Eclipsing trope effects or by a bit.
Jay R. Luly: And number two, having this tissue targeting component, which again, we think is, is very attractive compared to other molecules that we've looked at. So I think now, you know, we, you know, back to the question I think was asked. Unknown Speaker 0. Okay. Unknown Speaker 0. Okay. FxR does appear to be one of the mechanisms that can meaningfully move the needle on a fibrosis endpoint, and I think that's going to continue to be an important thing to try to do, and we're obviously heavily engaged in that with both of our molecules. On the RSVP study, I'll let Natalie just make a few remarks about that.
Number two having this tissue targeting.
Component, which again, we think is.
Is very attractive versus other molecules that we've looked at so.
I think now we back to the question I think was asked.
FX, our does appear to be one of the mechanisms. The can meaningfully moves the needle with the fibrosis endpoint and I think thats going to continue to be an important thing too.
It to try to do and and we're obviously, having heavily engaged in that with our with now both of our molecules.
On the RSVP study.
Oh, it not only just make a few remarks about that okay. So just to make sure I completely understand you question. So bad justification of the polar the always GDP.
Natalie: Okay, so just to make sure I completely understand your question, is it about the justification for the power of the RSVP?
Operator: Yeah, just the power for the primary endpoint for RSVP.
Yes, just the the power for the primary endpoint for deferral.
Natalie: Yeah, it's obviously a good question, given that it may not be completely intuitive. So I mean, obviously, you know that we haven't yet used EDP938 in patients in real life. And so the experience that we had was based on our challenge study. The nice thing about the challenge study is that you have a placebo arm. And therefore, we are looking at the treatment effect and comparing that to the placebo arm. And as you know, the primary endpoint that will be looked at in the RSVP is the total symptom score. So we powered our study by looking at the effect in comparison to the placebo arm in the challenge study.
Yes, it's obviously a good question given that.
Made and be competing treaty. So I mean, obviously you know that we haven't yet.
Yeah, Thanks, waiting patiently movie alive, and so the expense that was based on our challenge study.
The nice thing could lead to generate studies that you have a placebo arm and therefore, we are looking at the treatment effect.
And compare that to the placebo and as you know deployment, we endpoint that we'd be Luke that can you obviously be totally symptom score so we borrow steady.
Looking at defect in comparison to the placebo on independence day.
Natalie: Okay, great. Thanks again for taking our questions.
Okay, great. Thanks, again for taking my questions.
Huh.
Your next question comes from Lisa Bayko JMP Securities. Your line is open.
Operator: Your next question comes from JMP Securities. Your line is, Hi, thanks for taking the question. Just wanted to understand a little bit more about the study design. How are you thinking about the assumptions behind the powering for the endpoint? And then also, how quickly patients come into the study? Obviously, it's important to try to get them in as soon as possible. Is there any way you can try to augment that? And do you have a cutoff where we only accept patients with symptoms for this, you know, period of time prior to entry? So there are two questions there.
Hi, Thanks for taking my question just wanted to understand a little bit more about the study design. How are you thinking about the assumptions behind the powering for the endpoint.
And then also.
Where where are you thinking about like how quickly patients come in into the study.
This is important to try to get them and as soon as possible. So anyway, you can try to augment that and you have a cut off on you know we only will accept patients with sometimes for this period of time prior to entry so two questions there.
Operator: Yeah, so I think Natalie just answered that question. You know, so the idea came as a result of studying our challenge study............ Do you have the...
Yes, so I think not only just answered that question.
So the powering came as a result of studying our.
Our challenge study.
Natalie: Yeah, we can touch base with you later on that if you want to. If you want to... Unknown Speaker But the other part is we're going to try to catch patients in the first 48 hours in the study.
And so we can do you have both yes.
Yes, we can.
You later on that if you want to.
If you want to.
Sure It again, but the the other part is we're going to.
Try to catch patients in the first 48 hours.
In the study.
Operator: Okay, and is that I mean, how do you sort of get patients in that early have a window of time? Are you doing any specific targeting or
Okay and is that I mean, how do you.
How do you sort of get patients in that early of a window of time.
Are you.
Natalie: I love being enrolled in it.
Doing any specific targeting or.
So the enrolling patients.
Natalie: I love being a role model. Yeah, I can take that question and maybe just briefly say that, you know, obviously, we are using a certain number of sites that have had experience not only with RSV infection but also with the flu. And so there are diverse types of sites. They could be research sites, academic sites, or family practitioner sites. They have been selected mainly on their experience of dealing with RSV infection or flu infection. We will obviously also conduct a big campaign of education and information about our study. Therefore, we hope to link patients with symptoms and bring them to the clinic within the appropriate window.
I can think that question and maybe just Wifi say that.
We are using a certain number of side that expands the timing RSV infection, but also in the flu and so they are diverse type of site. They could be research side getting me title. So many petition aside they did they have been selected mainly on do expand suites.
Leading with always be infection of screen protection, we will be obviously also.
King beat campaign of education, and information, but steady.
Therefore, we hope.
To link.
Patient, we symptoms and bring them to clinique, we deemed appropriate window.
Okay.
Operator: Okay. And then for your new NASH compound, can you maybe give us a little bit more information on how it's differentiated from 305 and also just wanted to better understand the PK. Is it linear, or does it have a similar profile to 305?
And then for your new Nash compound can you maybe.
Give us a little bit more information on how its differentiated from trail five and also just wanted to better understand the PK is it linear parts that has a similar.
Profile to 305, thank you.
Well, it's a it's certainly.
Jay R. Luly: Well, it's certainly more potent than 305 and more potent than all the other FXR agonists. [inaudible] with regard to other key differentiations, you know, we talked about the tissue targeting. We've enhanced that over 305. We've enhanced it over, you know, other FXRs that we've benchmarked against.
Certainly more potent than three or 510, more potent and all the other FX our agonists.
The other.
With regards to.
Other key differentiations.
Yeah, we talked about the the tissue targeting.
Weve enhance that over three or five we've enhanced it over.
Other FX ours that Weve benchmarked against.
Jay R. Luly: And so from that perspective, and again, we need to test 297 to see how that translates, but there's at least an opportunity to drive a wedge in the tolerability signal. The PK, I think what you might have been referring to was the clinical, the human clinical PK dose-ranging study that we did on EDP-305 in healthy people, which was very linear through the whole range until we got to, I think it was going from 10 to 20 milligrams is where the non-linearity in the PK curve crept in, but that was in a dose-ranging study in human clinical studies where you're Preclinical profile The preclinical PK profile of 297 is very strong. I mean, we typically don't put any molecules into the clinic unless we've past that hurdle and a number of different preclinical species. So,
And so from that perspective, and again, we we need to test to nine seven to see how that translates but theres at least an opportunity to to drive a wedge.
In the Tolerability signal.
The PK I think.
What you might have been referring to.
Was the clinical as the human clinical PK.
Dose ranging study that we did on ATP threeo five and Healthys.
Which was was very linear.
Through the whole range until we got to I think it was going from 10 to 20 milligrams is where the non linearity in the PK curve.
Crept in but that was I want to dose ranging study in human clinical studies, where you're looking at.
Very low doses, all the way up very high doses and we havent, obviously gotten that far yet with 297 preclinical profile preclinical PK profile on.
297 is very strong I mean, we.
Typically don't put any molecules into the clinic unless weve.
Yes that hurdle in a number of different preclinical spcs. So.
Jay R. Luly: It's... It's...
It's a it's a fairly polished candidate at this point.
Jay R. Luly: It's a fairly polished candidate at this point.
Okay is it the same kind of scaffolding gases as maybe pizzeria five.
Jay R. Luly: Okay, is it the same kind of scaffold, I guess, as EDP-305?
Jay R. Luly: We'll say more about the structural components of the molecule at a future meeting.
I will say more about the the structural components of the molecule in the future at a future time.
Okay. Thank you.
Jay R. Luly: Okay, thank you. You're welcome.
Operator: [inaudible]
You're welcome.
Your next question comes from Eric Joseph with Jpmorgan. Your line is open.
Eric William Joseph: Your next question comes from Eric Joseph with J.P. Morgan. Your line is open.
Operator: Hey, good afternoon. This is Turner on behalf of Eric.
Hey, good afternoon. This is churn on for Eric Thanks for taking the question I'm just hoping you can help set expectations for the phase one GDP five one for readout in healthy volunteers as it relates to safety Tolerability are there any specific ease that you anticipate and what are deemed acceptable rates, particularly within the broader a core inhibitor class.
Turner: Thanks for taking the question. I'm just hoping you can help set expectations for the Phase 1 EDP514 readout in healthy volunteers. As it relates to safety tolerability, are there any specific AEs that you anticipate? And what are deemed acceptable rates, particularly within the broader core inhibitor class? And lastly, what plasma concentrations correlate with EC90s observed in vitro? Thank you.
And lastly, what plasma concentrations correlate with easy Ninetys observed in vitro. Thank you.
In preclinical models rather thank you.
Jay R. Luly: Thank you.
So.
Jay R. Luly: So, you know, we obviously will report the results when we have them, but, you know, we're not in, you know. We don't anticipate anything a priori. It's a...
Obviously, we will report the results when we have them, but we're not in.
We don't anticipate anything apriori its a.
Jay R. Luly: The study that we've had up and going, as I said, the FAD component is done, the MED is well along the way, and we'll have the data set in Q1. So there's nothing a priori that we're expecting out of that study. I think you asked what blood levels were correlated. Say that again. What's your question?
The study that Weve had up and Guardians of said the.
The CD.
On it is done in the immediate as well along the way and well have the dataset in Q1 so.
There's nothing apriori that we're expecting that study.
Hi, Doug I think you asked what blood levels correlated say that again, what's your question.
Turner: Just curious, what plasma levels correlate with the EC90 observed in preclinical models?
Just curious what plasma levels correlate with the Cninety observed in preclinical models.
I'd have to get back to you on that.
Jay R. Luly: I'd have to get back to you on that. I'm not sure that that's a Yes. I'd have to get back to you on that.
Im not sure that that's a.
Yes, I'd have to get back to you on that.
Okay, great. Thanks.
Turner: Okay, great, thanks.
Your next question comes from Patrick Trucchio with varying bird capital markets. Your line is open.
Operator: Your next question comes from Patrick Truccio with Berenberg Capital Markets. Your line is open.
Patrick Truccio: Thanks. Good afternoon.
Thanks, Good afternoon, Ive, a few follow ups on <unk>.
Patrick Truccio: I have had a few follow-ups on EDP305. Regarding the interim readout, we know that changes in liver histology can take some time. So, I'm interested in understanding what efficacy and or safety and tolerability measures will be evaluated in the interim analysis and how far into the study this analysis will be built in. And then, secondly, if you can, can you tell us if, in addition to accelerating the development in combinations with other mechanisms, there would also be an opportunity to accelerate the start of a pivotal program for 3-0-5 as a monotherapy treatment for NASH
Five.
Regarding the interim readout, we know that changes in liver histology can take some time.
So I'm interested in understanding what efficacy endorse safety and Tolerability measures will be evaluated in the interim analysis and how far into the study. This analysis will be built in and then secondly, if you can can you tell us if in addition to accelerating the development in combinations with other men.
And isms would there also be an opportunity to accelerate the start of the pivotal program for 305 as a monotherapy treatment for Nash.
Jay R. Luly: Yeah, so I'll answer the last question first: it wouldn't accelerate that. You know, the idea behind a 12 week Interim read is, again, it won't examine the primary endpoint. It's really going to be looking at secondary markers of efficacy, like what we did with Argon 1 in a 12-week study, and also tolerability. So by that point, we will have looked at 1, 1.5, 2, and 2.5 at 12 weeks, and we'll have good directional information, I think, in terms of knowing how we might proceed with that in a combined study.
Yes, I'll answer the last question first it wouldn't accelerate that.
The idea behind a 12 week.
Interim read is again.
I want.
Examine the primary endpoint.
It's really going to be looking at.
You know secondary markers of efficacy some like what we've done in argon, one and a 12 week study that also tolerability.
So by that point, we will have looked at one one of the half two and two and a half.
12 weeks and will have.
Good directional information I think in terms of knowing.
No how we might proceed with that in a in a combination study.
Okay and then on.
Jay R. Luly: Okay, and then on EDP 938, can you tell us what the incidence rate of community-acquired RSV infection is, what it is, and what additionally relevant inclusion or exclusion criteria should we be aware of for the trial?
Three eight.
Can you tell us what is the incidence rate of community acquired RSV infection, what is that.
What additionally, relevant inclusion or exclusion criteria should be should we be aware of for the trial.
Jay R. Luly: Well, the incidence is not quite flu-like, so forget the exact numbers, but it's a fraction of what [inaudible] with Morbidity and Hospitalizations.
Well the.
The incidence is not quite a flu.
So its a.
I forget the exact numbers, but it's it's a oh, it's a fraction of what.
Flu is but.
But still really.
You know significance. So there are a lot of.
Significant number of hospitalizations of elderly and.
Jay R. Luly: In terms of exclusion criteria, we obviously want to sample very carefully to make sure people don't have flu. We'll be doing that with an in-office RT-PCR diagnostic where we can rule out Flu A, we can rule out Flu B, and we can rule in RSV. So it's very impressive, actually. You can do this in about 20 minutes.
Children every year.
So there's a tremendous amount of morbidity associated.
With us morbidity and hospitalizations what.
In terms of.
Exclusion criteria, we obviously want to sample very carefully to make sure people don't have flu.
And we'll be doing out with a an art in office RT Pcr.
Diagnostic where we can.
Rule out.
Flu way, we can rule out flu b and we can rule in.
Rs fees so.
Very impressive actually you can do this and about 20 minutes.
Jay R. Luly: And so obviously, patients with asthma and COPD would be excluded, but they're, you know, apart from that, people with stable asthma and treated COPD or treated COPD could be allowed. [inaudible] So we're not bringing in people with really complicated underlying respiratory pathologies that aren't either stable or being treated. So we'll be on the lookout for that. We'll be on the lookout to exclude the flu. And, you know, again, the key to this and every other study is that you want to try to get to patients quickly. So that's what we're going to aim to do.
And so obviously a patients with asthma and C O PD.
Be excluded, but they're apart from that.
People with.
People with a stable asthma and treated CRPD were treated.
Oh PD could be allowed.
So we're not bringing in people are really complicated respiratory underline respiratory.
Solid shoes that aren't either stable or or being treated so.
We will be on the so look out for that.
It will be on the look out to exclude flu.
And you know again the key in this and in every other study.
I think among the lessons learned as you want to try to get to patients quickly. So thats, where can aimed to do.
Patrick Truccio: Helpful, thank you very much. You're welcome.
That's helpful. Thank you very much.
Jay R. Luly: You're welcome.
You're welcome.
Your next question comes from Brian Skorney with Baird. Your line is open.
Operator: Your next question comes from Brian Skorney with Baird. Your line is open.
Brian Peter Skorney: Hi, thank you for taking our questions. This is Jack Downing for Bryan.
Hi, Thank you for taking your questions. This is Jack dialing in for Brian .
Jack Downing: Many of my questions have already been asked, but I just want to ask one brief one on the follow-on FXR agonist. I know you spoke a bit about the pruritus side effects and how you're optimizing for, I guess, liver exposure as opposed to skin exposure. How would that play with respect to the lipid side effects that we've seen with some of the FXR agonists? Have you investigated that pre-clinically, and do you see any differences with this follow-on compared to your FXR that's already moved into the clinic or some of the competitors as well?
Many of my questions have already been asked but I just got five one brief one on the follow on FX our.
Agonists.
I know you spoke a bit about the per right of side effects and how you're optimizing for.
If liver exposure as opposed to skin exposure.
How about play with respect to the little bit side effects that we seem to some of the FXR agonists have you investigating that preclinically and do you see any differences with the follow on compared to your your.
Your next our that's already moved into the clinic or some of the competitors as well. Thank you.
Jay R. Luly: Yeah, well, I can speak more about, you know, 305. We, as by way of a backdrop, you know, with in terms of looking at lipids, you can see, mechanistically on paper, how one might get an increase in LDL levels by virtue of having reduced C4, because you're because you block the conversion. 2C4, you can have a backup of cholesterol in the system. What we saw, at least preclinically in the case of ADP-305 and, and other kinds of studies, you know, we'll ultimately be doing with 297 is that. You know, we saw what might be, I guess, a compensatory upregulation of the LDL receptor.........
Yeah like I can speak more about.
Threeo five we.
By way of backdrop with in terms of looking at lipids.
You can see on Mechanistically on paper, how one might get an increase.
In LDL.
Levels by virtue of having reduced.
C.
Because your because you block the conversion.
To see for you can have a backup of cholesterol and the system, what what we saw at least Preclinically and the case of ATP three or five and.
And other kinds of studies will ultimately be doing with 297.
Is that.
There was we saw it can.
What might be I guess, a compensatory upregulation of LDL receptor.
Jay R. Luly: So the biology is fascinating. And actually, that was a sort of a differential effect that we saw versus OCA when we looked at them side by side preclinically. So we'll be looking at that and other things preclinically as we continue to finalize all of our data on 297, and our aim will also be to start to put some of that data out next year.
And.
So the biology is.
It's fascinating and actually that was a.
That was a.
I have a differential effect that we saw versus CA.
When we looked at them side by side Preclinically. So we'll be looking at that and other things Preclinically as we continue to to finalize all of our data in 297.
Yeah.
Our aim will also be to to start to put some of that stayed out next year.
Jack Downing: Awesome, thank you so much for taking our questions.
[noise] awesome. Thank you so much for during our question.
Jay R. Luly: You're welcome.
You're welcome.
Operator: If you would like to ask a question, press star 1 on your telephone. Your next question comes from Liisa Bayko with JMP Securities. Hi, thanks for taking the follow-up. I actually forgot to ask one of my questions earlier. I was just curious, what are you looking for in the RSV study to move forward with either the elderly or the younger pediatric population? Is it more just to ensure safety? Do you definitively want to see some sort of benefit in this adult population? How are you thinking about the kind of hurdle to move forward into those other populations from this study? Thanks.
Again, if you would like to ask a question press star one on your telephone.
Next question comes from Liisa Bayko with JMP Securities. Your line is open.
Hi, Thanks for taking the follow up I actually forgot to ask one of my questions earlier I was just curious what are you looking for and the RSP study to move forward into either the elderly or the high end or pediatric population is it is it more just to clarify safety do doesn't it.
I really want to see sort and some centered benefiting this adult population how are you thinking about [noise].
Kind of the hurdle to move forward into those other populations from this study thanks.
Liisa Ann Bayko: I would say we want to continue to see the very good safety and tolerability profiles we've seen in the past. And, you know, basic, basic efficacy, you know, these are fundamental things we're getting to this adult population. We hope in a... Transcripts provided by Transcription Outsourcing, LLC. Basically, duplicate what we've seen in the challenge set.
Yeah, I'd say, we want to see continue to see a very good safety and Tolerability profile as we've seen in the past and.
And.
Basic a basic efficacy these are fundamental things, we're getting to this adult population.
We opened a.
Timely way, so we want to be able to.
Yes, basically duplicate what we've seen in the challenge.
Jay R. Luly: With obviously with a community.
Okay, with obviously with a community acquired RSV a patient population the so called real World study.
Jay R. Luly: with obviously with a community-acquired RSC.
Jay R. Luly: RSV patient population, the so-called real-world study.
Akesh Tiwari: Your next question comes from Akesh Tiwari with Wolf Research. Your line is open.
Your next question comes from a cash.
Research Your line is open.
Akesh Tiwari: Hey guys, thanks so much. So we've seen Tamiflu get FDA approval by reducing the duration of symptoms by basically a day or a day and a half. Can you give us some color on your discussions with the FDA and kind of what you guys are looking for in terms of absolute symptom reduction in your adult outpatient study? And I guess some color on those endpoints.
Hey, guys. Thanks, so much so we've seen tamiflu get FDA approval by reducing the duration of symptoms by basically a day or a day and a half can you give us some color on your discussions with the FDA and kind of what you guys are looking for for your adult outpatient study in terms of absolute symptom reduction and I guess some color on those endpoint.
Jay R. Luly: And then also, you alluded today on the call that you're going to have kind of a 20 minute rapid acting test to detect RC in your outpatient trial. If we look at prior RSV studies and we think about baseline viral titer at the time of dose, it's about six logs. So, kind of right at the peak of the virus. When you think about your trial and you're trying to get these patients within this 48-hour window, what type of viral titer does that actually translate into? Thanks so much.
And then also you've kind of you alluded today on the call that you're gonna have kind of a 20 minute rapid acting test to detect artsy for your outpatient trial. If we look at prior RSV studies when do we and we think about baseline vial tighter at the time of dose it's about six log so kind of right at the peak of the virus.
When you think about your trial and you're trying to get these patients within 48 hour window, what type of viral tighter does that actually translate into thanks. So much.
Yes. So so first of all this you know in terms of discussions with ft et cetera et cetera. This is not a registrational study, it's a proof of concept study so.
Jay R. Luly: Yeah, so, first of all, this, you know, in terms of discussions with FDA, etc., etc., this is not a registrational study; it's a proof of concept study. So, further, you know, the ultimate registration studies, there's going to be obviously a very detailed set of discussions around those pinpoints, and And, you know, at the appropriate time, those discussions will be had.
And further.
Ultimate registration studies, there's going to be obviously, a very detailed set of discussions around.
Yeah, those endpoints and.
You know at the appropriate time, those discussions will be had so.
Akesh Tiwari: So it's important to realize what this study is and what it's not. The titers are likely to be, you know, a bit higher than what we've had in the past in the challenge study. But, you know, it's not clear by exactly how much some of the people, you know, some of the people in our challenge study were already starting to exhibit symptoms, right? So it's going to be really a spectrum of, you know, folks, depending upon where in that window they come, exactly where their viral loads are, and so forth, and so. But again, the goal is to get folks, Not only before the viral load has taken its toll over several days, but also, you know, to try to catch things if you can, while it's still an upper airway infection, at an earlier stage in the process So Yeah, so we'll be lined up with the diagnostics again that are readily available and rapid. Great! Thank you so much.
It's important to realize what this study is and what it's what it's not.
The titers are likely to be oh, a bit higher than.
What weve had in the past and the challenge study, but you know it's not.
Clear by you know exactly how much you know some of the people some of the people and our challenge study, we're already starting to exhibit sometimes right. So it's going to be really a spectrum of.
Folks, depending upon where in that window, they come exactly where their viral loads are and and and so forth.
And so.
You know the but again the goals to to get folks.
Not only before.
The you know the viral load has taken its a.
Total over several days, but also you know to try to catch things. If you can while it's still an upper airway infection, you know earlier stage and the.
And the process that can that can only.
You know it can only be a more positive.
Approach to treatment so.
Yes, so we'll be lined up with the diagnostics again that are.
At are readily available and and rapid.
Great. Thank you so much.
Jay R. Luly: Thank you so much.
You're welcome.
Your next question comes from.
Jay R. Luly: You're welcome.
Operator: Your next question comes from Yasmeen Rahimi with Roth Capital. Your line is open.
With Roth capital Your line is open.
I think I just have one follow up and maybe a little overlap I think you said for RSVP. The primary endpoint will be total symptom score and just wondering what how.
Yasmeen Rahimi: I just have one follow-up, and it may be a little late. I think you said for RSVP, the primary endpoint would be total symptom score, and I'm just wondering what, how... How does that translate to a hospitalization endpoint? Is it possible? I know it's only 14 days of observation, but is there any way to kind of get a granular sense of which way things are going? Thanks again for taking my
How does that translate to hospitalization point is it possible I know, it's only 14 days.
Of observation, but is there any way to indicate a granular sense of which which we things are going thanks again for taking my follow up.
Natalie: So I just want, this is Natalie. I just want to make sure I fully understand your question. You mentioned hospitalization. Can you just... clarify? Yes.
So just like.
I just wanted to make sure I fully understand your question you mentioned, let's be transition can you just clarify yes. Those are just hospitalization and then.
Yasmeen Rahimi: or just hospitalization, as in... That's the end point typically used in a phase three study.
That's the endpoint typically use.
In a phase threes, though.
Natalie: Okay, I see. So again, I think we have mentioned that, you know, it is more like a proof of concept study at that stage. We will not be assessing, you know, prevention of hospitalization. But Jay mentioned earlier that there will be patients with comorbidities that are stable, obviously, with asthma and COPD. And if we can learn from those patient populations about severity or even prevention of hospitalization, obviously, that information will be important together. But this is not an end point at that stage that we will be assessing. We will need a larger sample size than we can imagine.
Okay. So again I think we have mentioned that you know.
More like a proof of concept study showed that states, we will not be assessing you know prevention.
In addition, but Jim mentioned earlier than we'd be vision, we school morbidity that I'll stay, but obviously, we asked my into a PD and if we can run some does a patient population about CVD O even prevention.
Discontinuation, obviously those inflammation, we'd be in pong together, but he is not an endpoint that stays typically would be assessing we we need to now just simple ending.
Yasmeen Rahimi: Okay, thank you.
Okay. Thank you.
Okay.
There are no further questions at this time and I'll turn the call back over to Carol for closing remarks.
Carol: There are no further questions at this time. I will now turn the call back over to Carol for her closing remarks. Thank you, everyone, for joining us today.
Thank you everyone for joining us today, a new corporate presentation will be posted on <unk> on our website shortly and if you have any additional questions feel free to give us a call me office. Thank you.
Operator: A new corporate presentation will be posted on our website shortly. And if you have any additional questions, feel free to give us a call in the office. Thank you. This concludes today's conference call. You may now disconnect.
This concludes today's conference call you may now disconnect.