Q4 2020 Enanta Pharmaceuticals Inc Earnings Call

Good afternoon, and welcome T. and anti Pharmaceuticals fiscal fourth quarter and year and 2020 financial results call on.

Operator: Good afternoon, and welcome to Enanta Pharmaceuticals' fiscal fourth quarter and year-end 2020 financial results call. At this time, all participants are in a listen-only mode.

At this time all participants on a listen only mode. There will be a question and answer session at the end of the prepared remarks. Please be advised that this call is being recorded.

Operator: There will be a question and answer session at the end of the prepared remarks. Please be advised that this call is being recorded. I would now like to turn the call over to Jennifer Viera, Senior Director, Investor Relations. Please go ahead. Thank you, Operator, and thanks to everyone for joining us this afternoon. The news release with our fiscal fourth quarter and 2020 year-end financial results was issued this afternoon 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. Jay?

I would now like to turn the call over to Jennifer Viera Senior Director Investor Relations. Please go ahead.

Thank you operator, and thanks to everyone for joining us. This afternoon. The news release with our fiscal fourth quarter and 2020 year and financial results was issued this afternoon and is available on our website on the call today is Dr., Jay Lou line, President and Chief Executive Officer, Paul Mellett, our chief.

Financial Officer, and other members of an interest 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 on all of which.

Involve certain assumptions and risks beyond our control that could cause our actual developments and results to differ materially from those statements.

Description of these risks is in our most recent form 10-Q and other periodic reports filed with the FCC and answer 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 Lou line, President and CEO Jay.

Okay, and Jennifer and good afternoon, everyone.

Jennifer Viera: Thank you, Jennifer, and good afternoon, everyone. Throughout 2020, we made meaningful advances across our pipeline. Today, I'm excited to review this progress and to share our plans for multiple catalysts in 2021. Looking ahead, we believe that we are in a unique position to leverage our years of drug discovery experience to deliver new medicines to patients. Not only do we have a robust and growing internal portfolio, which I'll review momentarily, but our efforts are informed by our previous successes, including the discovery of two products which are currently marketed by AbbVie as part of its leading treatment for chronic HCV infections. At the beginning of the year, we announced our program for human metapneumovirus, or HMPV. And in March, we began working to find a treatment for COVID-19.

Reported 20, we made meaningful advances across our pipeline and today I'm excited to review this progress and to share plans for multiple catalysts and 2021.

Looking ahead, and we believe that we are in a unique position to leverage our years of drug discovery experience to deliver new medicines to patients and.

We do have a robust and growing internal portfolio, which I'll review momentarily and our efforts here and foreign buyer previous successes, including the discovery of two products, which are currently marketed by Abbvie as part of its leading treatment for chronic HBV infection.

And the beginning of the year, we announced our program for human met and human virus or H.M.P.V. and in March we began working and find the treatment took over 19.

Jennifer Viera: I'm proud and appreciative of my colleagues for their efforts in rapidly responding to the pandemic and for the nimble and creative thinking they applied to translate our extensive experience in virology, notably respiratory virology, to fight this global challenge, taking a step back by focusing on these two respiratory viruses. Combined with our work in respiratory syncytial virus, we are establishing our position as one of only a few biotechnology companies explicitly developing a broad portfolio of respiratory virus treatments. We also advanced our hepatitis B compound, EDP514, a novel core inhibitor that displays potent anti-HPV activity in vitro at multiple steps in the HPV life cycle.

I'm proud and appreciative of my colleagues for their efforts and rapidly responding to the pandemic and for the nimble and creative thinking and they applied to translate our extensive experience in biology, notably respiratory biology to fight this global channel and.

Taking a step back by focusing on needs to respiratory viruses combined with our work and respiratory syncytial virus, we're establishing our position as one of only a few.

Biotechnology companies explicitly developing and a broad portfolio and respiratory virus treatments.

We also advanced our hepatitis B compound and GDP five one for a novel core inhibitor and the displays potent anti HPV activity and be true and multiple shots on HBV lifecycle.

Jay R. Luly: In February, we announced positive results from Part 1 of our Phase 1A-1B clinical study of BDP-514 in healthy subjects, which supported further evaluation of once-daily dosing in Part 2 of the study in chronic HPV patients treated with marketed nucleoside reverse transcriptase inhibitors, which we refer to as nuke-suppressed patients, as well as in chronic HPV-infected patients with high viral load not currently on Moving to our NASH programs, the past quarter was also marked by the initiation of two clinical studies. Argon 2, our Phase 2B study evaluating our first FXR agonist, EDP 305, in subjects with liver biopsy proven NASH, and a first in human study of EDP-297, a highly potent and targeted FXR agonist, but is there a follow-on FXR candidate?

On February we announced positive results from part one of our phase one day, one be clinical study and BDP 514, and healthy subjects, which supported further evaluation and once daily dosing and part two and the study and chronic HBV patients treated with marketed newt besides adverse trends.

Script piece and others.

Which we refer to as new.

Suppressed patients as well and and chronic HBV infected patients with five and viral load not currently on treatment, which we refer to as my roommate patients.

Moving to our Nash program for the past quarter was also marked by the initiation of two clinical studies are going on to our phase Twob study evaluating and our first FXR agonist, GDP, three or five and subjects with liver biopsy proven Nash.

And he first and human study of GDP to 97, highly potent and targeted affects our agonists, but is there a follow on that that's our candidate.

Jay R. Luly: As we move forward toward the remainder of 2020 and the beginning of 2021, we look forward to initiating two new phase two trials for our program in respiratory syncytial virus, or RSV. Now, let's look at our portfolio programs in a bit more detail. I'll begin with our virology-focused programs, more specifically our respiratory virus programs, RSV, HMPV, and SARS-CoV-2. I'll start with RSV, where we are developing EDP938, a potent non-fusion inhibitor of RSV-A and RSV-B. RSV is a severe respiratory infection associated with significant morbidity and mortality in infants, the elderly, and immune-compromised adults, a condition for which there is currently no safe and effective therapy.

As we move forward and toward the remainder of the 20 Twond and beginning of 2021, we look forward to initiating two new phase two trials and program and respiratory syncytial virus or RSV.

Net until it could on portfolio programs and a bit more detail on.

Beginning with our biology focus programs more specifically, our respiratory virus programs are a speed H.M.P.V. and Sars Coke too.

I'll start with RSV, where we are developing and GBP nine free a potent non fusion inhibitor of ours from me and Rspb.

RSV is a severe respiratory infection and associated with significant morbidity and mortality and and fence the elderly and immune compromised adults and the condition for which there is currently and no safe and effective therapy and.

Jay R. Luly: In an average year in the U.S., RSV infections lead to around 2 million outpatient visits among children younger than 5 years old and hospitalizations of more than 57,000 children under age 5 and about 177,000 older adults. Our Phase IIb double-blind placebo-controlled study of ADP938 is designed to enroll approximately 70 subjects up to the age of 75 years, randomized to receive either 800mg of ADP938 or placebo for 5 days. Starting in the southern hemisphere, recruitment in this study has been affected by the ongoing COVID-19 pandemic and related shutdown and social distancing measures which have reduced the incidence of flu and RSV. Thus, as we've previously said, we are hopeful that the 2021 Northern Hemisphere RSV season will allow us to finish enrollment in RSVP, but that will be dependent on RSV being as prevalent as in a normal season.

On an average year and the U.S. RSV infection lead to around 2 million outpatient visits among children younger than five years old and hospitalizations and more than 57000 children under age five and about 177000 older adults.

Our phase to be double blind placebo controlled study and PDP nine create is designed to enroll approximately 70 subjects up to the age and 75 years randomized to receive either 800 milligrams of PDP nine free aid or placebo for five days.

Starting on the hub and southern Hemisphere recruitment and the study and spend affected by the ongoing COVID-19, pandemic and related shutdown and social distance and measures, which have reduced the incidence of flu and RSV.

So since we've previously said we are hopeful that the 2021 and northern Hemisphere RSV season will allow us to finish enrollment and RSVP because that will be dependent on RSP and as prevalent as on a normal season to.

Did that and we are reactivating close to 50 of our existing RSVP clinical sites and North America and use sites are prepared with RT PCR and machines to diagnose patients RSV and to rule on flu and cobot and the same day, which should make and enrollment as efficient as possible.

Jay R. Luly: To that end, we are reactivating close to 50 of our existing RSVP clinical sites in North America. These sites are prepared with RT-PCR machines to diagnose patients' RSV and rule out flu and COVID in the same day, which should make enrollment as efficient as possible. In addition, we're working to set up about an equal number of sites in six different European countries by year end and are also planning to add sites in select Asia Pacific territories in 2021.

In addition, we're working to set up about an equal number of sites and six different European countries by year end and we're also planning to add sites and select Asia Pacific territories and 2021.

As we know today, but 19 is unpredictable and the rate of enrollment in this trial will continue to depend on the prevalence of RSV infection and the precautions that people are taking for COVID-19, and its a winner progressing and the northern hemisphere.

Considering that respiratory viruses off and have hot spots, we're prepared with many geographically dispersed sites to identify and under on his many patients as possible and that's RSV season.

Jay R. Luly: As we know, COVID-19 is unpredictable, and the rate of enrollment in this trial will continue to depend on the prevalence of ROC infection and the precautions that people are taking for COVID-19 as the winter progresses in the Northern Hemisphere. Considering that respiratory viruses often have hotspots, we are prepared with many geographically dispersed sites to identify and enroll as many patients as possible in this RSVC. Assuming we can complete enrollment in the second quarter of 2021, our goal remains to report data in the third quarter of 2021. We also plan to initiate two additional Phase II studies with ADP938, one in adult transplant patients by the end of 2020, and another in pediatric patients in the first quarter of 2021. The adult transplant study, named RSV-TX, is a Phase IIb randomized, double-blind, placebo-controlled study to evaluate the effect of EDP938 in adult hematopoietic cell transplant recipients and acute RSV infection of the upper respiratory tract

Let's say, maybe we can complete enrollment and the second quarter of 2021, our goal remains to report data and the third quarter 2021.

We also plan to initiate two additional phase two studies with PDP 9381, and adult transplant patients by the end of 2020 and another in pediatric patients and the first quarter of 2021.

The adult transplant study named our EPS to be TX is that seems to be randomized double blind placebo controlled study to evaluate the effect of PDP 938, and adult and meadow poetic cell transplant recipients and acute RSV infection of the upper respiratory tract.

Right.

The pediatric trial named RSVP.

We'll be a phase two randomized double blind placebo dose ranging study.

Evaluate 80, P. nine threeg regimens and hospitalized or non hospitalized infants and children age 28 days to 24 months, who test positive for RSV based on and approved diagnostic assay.

Our goal for both of these studies to enroll during 2021 and 2022 subjected to the potential impact and COVID-19 on the and on the incidence of RSV infections and activities and trial size.

Turning into our other two respiratory virus treatments and development, each and MPV and virus that causes respiratory infection with something simple similar to ours speed and Sars Coke too we have discovered several potent molecule.

Jay R. Luly: The pediatric trial, named RSVP, will be a Phase II randomized double-blind placebo dose-ranging study to evaluate EDP938 regimens in hospitalized or non-hospitalized infants and children aged 28 days to 24 months who test positive for RSV based on an approved diagnostic assay. Our goal for both of these studies is to enroll during 2021 and 2022, subject to the potential impact of COVID-19 on the incidence of RSV infections and Turning to our other two respiratory virus treatments in development, HMPV, a virus that causes respiratory infection with symptoms similar to RSV, and SARS-CoV-2, we have discovered several potent molecules. For SARS-CoV-2, we are leveraging our expertise in direct acting antiviral mechanisms to discover new compounds to treat COVID-19 using a combination of drug target screening and drug design.

For starters Scoop, two we are leveraging our expertise and direct acting antiviral mechanisms to.

To discover new compounds to treat COVID-19, using a combination of drug targets screening and drug design.

The advantage of this discovery approach and so you can make a potent purpose built inhibitors against multiple different targets.

While we are encouraged that the vaccine could be available soon we still see a need for an oral treatment for those and various patient populations, where none the less and talk to the code and 19.

Regarding h. and PV since announcing our new drug discovery effort and January we've been optimizing nanomolar inhibitor leads against this virus, we're hoping to finalize and clinical candidate selection for each program next year.

Let's move on to our hepatitis B program with GDP five one for our lead core inhibitor currently being tested and chronic HBV patients, who are new to suppress and and by remake HBV patients.

On February we announced positive results from part one of the phase one a one b clinical study and GDP 514, and healthy subjects, which allowed us to initiate part two and chronic nuke suppressed HBV patients.

Jay R. Luly: The advantage of this discovery approach is that you can make potent purpose-built inhibitors against multiple different targets. While we are encouraged that the vaccine could be available soon, we still see a need for an oral treatment for those in various patient populations who are nonetheless infected with COVID-19. Regarding HMPV, since announcing our new drug discovery effort in January, we've been optimizing nanomolar inhibitor leads against this virus. We are hoping to finalize clinical candidate selection for each program next year. Let's move on to our Hepatitis B program with EDP-514, our lead core inhibitor currently being tested in chronic HPV patients who are nuke-suppressed and in viremic HPV patients. In February, we announced positive results from Part 1 of the Phase 1A-1B clinical study of EDP-514 in healthy subjects, which allowed us to initiate Part 2 in chronic nuke-suppressed HPV patients. These encouraging data, which highlighted positive safety and tolerability, as well as pharmacokinetics suitable for once-daily dosing, were presented in a poster presentation in August at the Digital International Liver Congress, sponsored by the European Association for the Study of the Liver, or EASL.

These encouraging data, which highlight and positive safety and tolerability as well as far and it cool kinetics suitable for once daily dosing and were presented and a poster presentation and August at the digital international and liver Conkers sponsored by the European Association for the study of liver or EASL.

Part two of the Phase one day, one B study, which is now and going is designed to evaluate the safety tolerability pharmacokinetics and any viral activity and orally administered multiple ascending dose and so we need to be five on core versus placebo and up to 24 randomized nuke suppressed patients over it.

28 day period.

Or on any further significant COVID-19 disruptions, we plan to have preliminary data from part two and the second quarter of 2021.

Also on our HPV program and July we initiated a phase one b clinical trial and by remake HBV patients.

This randomized double blind placebo controlled phase one b study and by remake chronic HBV patients.

Currently on therapy, as and similar design to the one and nuke suppressed HBV patients. We plan to enroll 24 subjects that are clinical trial sites, and Hong Kong, and Taiwan, which are both areas with large unmet need for HCV treatment.

We expect preliminary data from this trial and the second quarter of 2021.

And finally, we continue our HPV efforts in search of a novel oral agent against a different HBV mechanism that could be combined with GDP 514, and a new to create an all oral triple regimen.

Jay R. Luly: Part 2 of the Phase 1A-1B study, which is now ongoing, is designed to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of orally administered multiple ascending doses of EDP514 versus placebo in up to 24 randomized nuke-suppressed patients over a 28-day period. If there are any further significant COVID-19 disruptions, we plan to have preliminary data from Part 2 in the Also, in our HPV program, in July, we initiated a Phase 1b clinical trial in viremic HPV patients. This randomized, double-blind, placebo-controlled Phase 1b study in viremic chronic HPV patients not currently on therapy has a similar design to the one in nuke-suppressed HPV patients.

Progress against that and strong this year as well.

And we'll have further details around this new program and our oral HPV Triple strategy early next year.

Shifting gears to our work and non viral liver disease.

We are currently focused on Nash, where we are conducting clinical trials on GDP three or five our first FX our agonists based on data from Oregon, One, which was highlighted and an oral presentation and easily in August we initiated recruitment and Oregon two in July.

On to as a phase to be randomized double blind placebo controlled 72 weeks study and approximately 340 subjects with biopsy proven Nash with fibrosis.

Primary endpoint of Oregon, too is improvement of fibrosis with without worsening of Nash and or Nash resolution without worsening and fibrosis.

Are you seeing any p., three or five debt issuance of 1.5 milligrams and 2.0 and milligrams, which we believe will favorably balance strong efficacious target engagement with Tolerability.

Jay R. Luly: We plan to enroll 24 subjects at our clinical trial sites in Hong Kong and Taiwan, which are both areas with a large unmet need for HPV treatment. We expect preliminary data from this trial in the second quarter of 2021. And finally, we continue our HPV efforts in search of a novel oral agent against a different HPV mechanism that could be combined with ADP-514 and a nuke to create an all-oral triple reg. Progress against that has been strong this year.

Whereas additionally, developing and ATP to nine seven or follow on FX are candidates for Nash with potentially best in class potency and targeted effects.

And easily presented two posters, which demonstrated the treatment with GDP to nine seven demonstrated significantly reduced fibrosis progression and improved and liver function and a rat model Nash.

We are encouraged by ATP to nine seven preclinical profile, which shows high target tissue distribution, and the liver and and test and versus plasma and skin.

Jay R. Luly: We'll have further details around this new program and our oral HPV triple strategy early next year. Shifting gears to our work in non-viral liver disease, we are currently focused on NASH, where we are conducting clinical trials on EDP305, our first FXR agonist. Based on data from Argon1, which was highlighted in an oral presentation at ESL in August, we initiated recruitment for Argon2, a phase 2b randomized, double-blind, placebo-controlled, 72-week study in approximately 340 subjects with biopsy-proven NASH with fibrosis. The primary endpoint of Argon2 is improvement of fibrosis without worsening of NASH or NASH resolution without worsening of fibrosis.

And September we announced the initiation of a phase one randomized double blind placebo controlled first in human study designed to assess the safety tolerability and pharmacokinetics, excluding the effect and food and take.

Of orally administered meaty piece can be nine seven and approximately 74 healthy adult subjects.

The study includes two phases.

Single ascending dose phase and rolling six cohorts, including a two part food effect cohort and and multiple ascending dose phase and rolling three cohorts, we look forward to reporting and clinical data and the second quarter of 2021.

By mid year 2021, we expect to have important new and side for both PDP, three and five and PDP to nine seven which will inform next steps across our Nash program.

Jay R. Luly: We're using EDP-305 doses of 1.5 milligrams and 2.0 milligrams, which we believe will favorably balance strong efficacious target engagement with tolerability. We're additionally developing EDP-297, our follow-on FXR candidate for NASH, with potentially best-in-class potency and targeted effects. At EASL, we presented two posters that demonstrated that treatment with EDP-297 significantly reduced fibrosis progression and improved liver function in a rat model of MAC.

We will know whether that tissue targeting and potency design elements, we introduced and 297 will allow us to better leverage FX, our agonists without encountering tolerability challenges.

And at approximately the same time, we had.

Factors that are going on to will provide us an interim analysis at 12 weeks of treatment on a subset of patients to enhance our ability to prioritize our FX, our AG and its compounds and seek opportunities more quickly for development of one or both of them and combinations with other mechanisms for Nash.

We are encouraged by the efficacy demonstrated by FX, our agonist for Nash with fibrosis and disease with high unmet need and believe that this mechanism has promise and as a potential therapeutic.

Jay R. Luly: We are encouraged by ADP297's preclinical profile, which shows high target tissue distribution in the liver and intestine versus plasma in the skin. In September, we announced the initiation of a Phase I, randomized, double-blind, placebo-controlled first-in-human study designed to assess the safety, tolerability, and pharmacokinetics, including the effect of food intake, of orally administered ADP-297 in approximately The study includes two phases: a single ascending dose phase enrolling six cohorts, including a two-part food effect cohort, and a multiple ascending dose phase enrolling three cohorts. We look forward to reporting clinical data in the second quarter of 2021. By mid-year 2021, we expect to have important new insights for both EDP 305 and EDP 297, which will inform next steps across our NASH program.

We've accomplished all of this while we still managing the impact of COVID-19 on our lives and business.

Continually impressed by the team, we have built and their ability to maneuver around the challenges with which we have been presented.

I want to thank our very talented and committed employees, who have worked tirelessly during the pandemic. Their dedication is evidenced by the progress we have been able to make this year.

I'd like to conclude my remarks plant and emphasizing a few key points.

We made significant progress during our fiscal year. Despite the multitude of the challenges presented by the cobot pandemic, including the initiation and four new clinical trials.

Two for our HBV program and two for our Nash program concurrent with conducting our ongoing phase two b program for RSV.

Further we are on schedule to initiate RSV, TX and adult transplant patients later, this quarter and RSVP and pediatric patients and the first quarter of 2021.

We were also successful and moving on our HBV trial and by remix patience forward as well and it's and progressing our phase one b trial on HBV patients, who are new to suppress with preliminary data expected profit, but these studies and the second quarter of 2021.

Jay R. Luly: We will know whether the tissue targeting and potency design elements we introduced in 297 will allow us to better leverage FXR agonists without encountering tolerability challenges. And at approximately the same time, we expect that Argon2 will provide us with an interim analysis at 12 weeks of treatment in a subset of patients to enhance our ability to prioritize our FXR agonist compounds and seek opportunities more quickly for the development of one or both of them in combination with other mechanisms for that. We are encouraged by the efficacy demonstrated by FXR agonists for NASH with fibrosis, a disease with high unmet need, and believe that this mechanism has promise as a potential therapeutic.

And finally, we look forward to advancing our candidates and Nash with the Oregon, two trial BDC free of five and the phase one study of 80% to 97.

Looking toward 2021, we are poised for an exciting year with multiple data readouts anticipated across our pipeline.

I'll stop here and turn the call over to Paul to discuss and financials for the quarter Paul.

Thank you Jay I'd like to remind everyone that and annual reports on a September thirtyth fiscal year schedule.

Today, we are reporting results from fourth quarter and fiscal year ended September Thirtyth 2020.

For the quarter total revenue was 23.6 million and consisted entirely of royalty revenue earned on and these global HCV product sales and 414 million.

This compares to total revenue was 51.3 million from the same period and 2019.

The decrease in our royalty revenue was due to lower global HCV product sales as reported by Abbvie.

Jay R. Luly: We've accomplished all of this while we are still managing the impact of COVID-19 on our lives and business. I'm continually impressed by the team we have built and their ability to maneuver around the challenges with which we have been presented. I want to thank our very talented and committed employees who have worked tirelessly during the pandemic. Their dedication is evidenced by the progress we've been able to make this year. I'd like to conclude my remarks by emphasizing a few key points. We made significant progress during our fiscal year despite the multitude of challenges presented by the COVID pandemic, including the initiation of four new clinical trials, two for our HPV program and two for our NASH program, concurrent with conducting our ongoing Phase IIb program for RSV.

Treated patient volumes have remained below pre covance levels.

And we now expect total HCV sales of approximately 1.9 billion.

For the calendar 2020 as treatment to remain below pre cold and levels.

A royalty revenue was calculated on 50% of the average sales and a blend of our first and second royalty tiers of 10 and 12% respectively.

And on approximately 30% of the kerosene and.

On a royalty rate of 10% after adjustments for certain contractual discounts rebates and set on US which are now just over 2% of at least total reported HCV sales.

Royalties on calculated on a calendar year basis, therefore, royalties and a fiscal first quarter ending December 31, and will be calculated at the highest royalty rate.

And royalties for our fiscal quarter, ending March 31st will be calculated at 10%.

Jay R. Luly: Furthermore, we are on schedule to initiate RSV-TX in adult transplant patients later this quarter and RSV-PEDS in pediatric patients in the first quarter of 2021. We were also successful in moving our HPV trial and viremic patients forward, as well as in progressing our Phase 1B trial in HPV patients who are NUCC suppressed, with preliminary data expected for both these studies in the second quarter of 2021. And finally, we look forward to advancing our candidates in NASH with the Argon 2 trial of EDP-305 and the Phase 1 study of EDP-297. Looking toward 2021, we are poised for an exciting year with multiple data readouts anticipated across our pipeline. I'll stop here and turn the call over to Paul to discuss your financials for the quarter. Thank you, Jay.

Most royalty rate here and our fiscal year.

You can review, our royalty tier schedule and our 2019 form 10-K.

Moving on to our expenses.

Three months ended September Thirtyth, 2020 research and development and expenses totaled $36.7 million compared to 38.7 million from the same period and 29.

This decrease was primarily due to the timing of on clinical studies year over year, and COVID-19 related delays and two clinical studies that are now on going.

General and administrative expense for the quarter was $6.7 million compared to 6.2 million from the same period and 2019.

And and recorded income tax expense was 10.7 million for the three months ended September Thirtyth 2020, compared to an income tax benefit from 25 million for the same period in 2019.

The income tax expense and 2020 was driven by and non cash valuation allowance recorded against our deferred tax assets of approximately $18 million.

Which was partially offset by 7.3 million event or well carry backs and R&D tax credits.

For the 12 months ended September Thirtyth, 2020, and and as effective tax benefit was approximately 3% compared to an effective tax rate of approximately 2% for the 12 months ended September Thirtyth 2019.

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 fourth quarter and fiscal year ended September 30, 2020. For the quarter, total revenue was $23.6 million and consisted entirely of royalty revenue earned on AbbVie's global HCV product sales of $414 million.

I'd like to note that the drivers of the decrease in the effective tax rate are covered in the press release.

Net loss for the three months ended September Thirtyth, 2020 was $29.3 million or a loss of $1.46 per diluted common share growth.

Compared to net income of $9.2 million or 44 cents per diluted common share for the corresponding period and 2019.

The net loss for 2020 was due to the decrease in HCV royalties earned under our heavy agreement.

Paul J. Mellett: This compares to total revenue of $51.3 million for the same period in 2019. The decrease in our royalty revenue was due to lower global HCV product sales as reported by Abbott, as treated patient volumes have remained below pre-COVID levels. Abby now expects total HEV sales of approximately 1.9 billion for the calendar 2020 as treatments remain below pre-COVID levels. Royalty revenue was calculated on 50% of maverick sales at a blend of our first and second royalty tiers of 10 and 12%, and on approximately 30% of Vaquera sales at a royalty rate of 10% after adjustments for certain contractual discounts, rebates, and set-offs, which are now just over Our royalties are calculated on a calendar year basis. Therefore, royalties in our fiscal first quarter, ending December 31, will be calculated at the highest royalty rate.

Which were adversely affected by the cold and 19 pandemic.

And then to ended the quarter with approximately 419 billion and cash and marketable securities.

An increase of approximately 19 million from our 2019 fiscal yearend balance of 400 million.

Notwithstanding our current level of operating losses are existing cash balances together with our ongoing royalties are expected to be sufficient to fund our operations for the foreseeable future.

Regarding guidance for fiscal 2021, we expect our research and development expense to be between 145 and $165 million.

And our general and administrative expense to be between 27 and 33 million.

For the financial details are available in our press release and will be available on our annual 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.

And at this time I would like to inform everyone in order to ask a question and you will need to press star one on your telephone to withdraw your question press the pound or hash key.

Please standby and we compiled acuity roster.

Your first question comes from the line of Roy Buchanan from JMP Securities. Please go ahead.

Hi, great. Thanks for taking the questions.

Paul J. Mellett: 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 2019 Form 10-K. Moving on to our expenses, for the three months ended September 30, 2020, research and development expenses totaled $36.7 million, compared to $38.7 million for the same period in 2019. This decrease was primarily due to the timing of our clinical studies year over year and COVID-19-related delays in two clinical studies that are now ongoing. General and administrative expense for the quarter was $6.7 million compared to $6.2 million for the same period in 2019.

And at a few on the RSV program, so far RSVP it sounds like your.

More sat versus the last quarter in terms of adding Asian sites and 2021.

It does it does and northern agencies, and largely mimic that and in North America and can you provide any specifics on the potential age and size is China included.

Okay.

Hi, This is Jay Jay.

So in terms of Asia and different countries.

And you.

Slightly gifts line.

Season, former actually.

Almost year round and.

So.

In the broader perspective, you know on the local.

And northern Hemisphere, and the new Us and Canada, and we look with Europe.

I think if we can build on Asia.

And we'll we'll be getting more and more.

Coverage and.

At least somewhere and for you know maybe.

Paul J. Mellett: An unrecorded income tax expense of $10.7 million for the three months ended September 30, 2020 compared to an income tax benefit of $0.5 million for the same period in 2019. The income tax expense in 2020 was driven by a non-cash valuation allowance recorded against our deferred tax assets of approximately $18 million, which was partially offset by $7.3 million of NOL carrybacks in R&D tax credit for the 12 months ended September 30th, 2020. Enanta's effective tax benefit was approximately 3%, compared to an effective tax rate of approximately 2% for the 12 months ended September 30, 2019.

Thanks, so much for your.

Well I think.

And I will specifically will it will come back later will flow on other Asian.

Asian countries and.

And what were looking on but that's the plan is to continue on the go.

On the.

On 2021 timeframe.

Of course in the meantime, we'll have.

Lots of North American sites on onboard and recall, we were poised with the flow dozens of them.

Previously so well how approaching.

What's the North American clouds on on hopefully, we've all that many more on the E U line.

Moving on to work so.

Really trying to.

On pulled the south fault.

One of them as loans.

So on any of the North American sales yet open do you have any feedback from those sites.

And timing.

And just coming up and you know, but what we what we can tell as you know and you'll recall last year, the Ses and became.

Paul J. Mellett: I'd like to note that the drivers of the decrease in the effective tax rate are covered in the press release. The net loss for the three months ended September 30, 2020 was $29.3 million, or a loss of $1.46 per diluted carbon share, compared to net income of $9.2 million, or $0.44 per diluted common share, for the corresponding period in 2019. The net loss for 2020 was due to the decrease in HCV royalties earned under our AVIA grant, which was adversely affected by the COVID-19 pandemic. At the end of the quarter, we had approximately $419 million in cash and marketable security, an increase of approximately $19 million from our 2019 fiscal year-end dollars of $400 million. Notwithstanding our current level of operating losses, our existing cash balances, together with our ongoing royalties, are expected to be sufficient to fund our operations for the foreseeable future.

Early.

And.

And so this year versus last year, its a little quiet so far this year.

And we'll just have to keep an eye on that and we started the screen.

But.

In general the the rates.

And you know loans and stuff like that and see or are you know.

Pretty quiet right now well just have to wait and see and <unk>.

This is and progressive and that the backdrop of Kobe and central dispensing and and the like you know what what the.

This is more.

On the.

The loans.

Okay, great and on how to couple on the on the new Phase two trials, if you don't mind so.

For RSV P.D. pad, how many on patients are you planning on the endpoint is progression to lower respiratory tract infection, and then from that probably have investigators line up I guess.

And he kind of similar to the last question just.

How are they view and the current situation and the feasibility starting the trial.

And sorry are you talking about the the PK study, yeah, right RC pad Pete.

Yep Yep.

Yes, so the and.

Speeds from you know we're aiming to.

Start.

And next quarter were and.

I mean for about a 90 patients total.

And.

Yeah, So I think the uncertainty.

The the main points and turns of the PD study itself.

And one is going to be safety and PK.

And then we'll have a part two where we will be looking at the actual virus soul change change and ours from shutting.

Paul J. Mellett: Regarding guidance for fiscal 2021, we expect our research and development expense to be between $145 and $165 million, and our general and administrative expense to be between $27 and $33 million. Further financial details are available in our press release and will be available in our annual report on Form 10-K when filed.

On the things that we look at and so we need to be given.

Nine threed or placebo on.

Four or five days.

And we'll be looking at cohorts.

Up to on 24 months of age.

Okay, Great and then one last one on the transplant traffic on line. So how many sites you planning for that one.

I also including Europe, and he is there any information on that.

Current RSV race, and the transplant setting either on the U.S. or elsewhere. Thanks.

And think.

On the sites and I will come on line will not get numerous sites.

Operator: And at this time, I would like to inform everyone that in order to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound or hash. Please stand by while we compile the Q&A roster. Your first question comes from the line of Roy Buchanan from J&P Securities. Please go ahead. Hi, great. Thanks for taking the questions. I had a few on the RSV program. So for RSVP, it sounds like you're more set versus the last quarter in terms of adding Asian sites in 2021. Does the northern Asian season largely mimic that in North America?

And we'll be on a global.

All studies, and we'll have more on sites and and all though.

Obvious.

Sure.

Her Tories there.

We'll be looking at 938.

Versus placebo.

From 21 days and.

And.

And we are doing so a little bit longer because.

Patients are you know, obviously immune compromised and there aren't you.

There aren't a lot of statistics on.

And it's a specific patient population. So we just get some of them and a lot of the center and streamline the normal season and.

On the crude as they come.

Your next question comes from the line of Brian Skorney from Baird. Please go ahead.

Jay R. Luly: And can you provide any specifics on a potential Asian site? Is China included? Hi Jay, this is Ben from Asia. So in terms of Asia and different countries, they have, you know, slightly different seasons. Some are actually almost year-round. So, in the broader perspective, you know, when we look at the Northern Hemisphere, the U.S. and Canada, and we look at Europe, we think if we can build on Asia, that will be getting coverage, at least somewhere for, you know, maybe nine or so months a year. Um, so I think, specifically, we'll come back later with, you know, other Asian countries in particular that we're picking up, but that's the plan is to continue to add some of those in the 2021 time frame.

Hi. Thank you. This is on Jack dialing in for Brian. Thanks for taking our questions. We'd have one quick one.

We're wondering about if you had any updated thoughts with regard to the HPV opportunity for core inhibitors in light of on the disappointing news from assembly and their core plus new graduation, and the sustained viral response and we saw there I know you're looking at the Triple a cash.

Combination internally as well, but were just wondering what your thoughts were in line lendings. Thank you.

Yeah, So and interesting data set and you know.

When I heard from kind of korlym or for doing on study.

The study of Woods I was looking at the core inhibitor plus a new close on sort of question.

Could a core plus a new cost time.

You too and functional cure.

And.

And again nobody knew the answer to that question.

Jay R. Luly: Of course, in the meantime, we'll have lots of North American sites on board. You recall we were poised with dozens of them previously. So we'll have approaching 50 North American sites and hopefully at least that many more in the EU by the end of the year. So, really trying to, you know, pull the stops back for many, many. So are any of the North American sites yet open? Do you have any feedback from those sites?

Well it looks like your current time coin.

Over the course of the theirs.

There's been no investigations free months and six months from here and so forth.

And you know what else.

The results.

Were produced on the.

And this initial study werent, particularly.

Positive.

And it could be on a lot of different reasons I mean, it's either a nuke plus a core plus more time, you know, although they want for.

Jay R. Luly: It's just coming up, you know, but what we can tell is, you know, if you recall last year, the season came early. And so this year versus last year, it's a little quiet so far this year. You know, we'll just have to keep an eye on that. We've started the screen. But in general, the rates, you know, as trapped by CDC or, or, you know, pretty quiet right now. We'll just have to wait and see as the season progresses and the backdrop of COVID and social distancing and, and the like, you know, what the season will provide. Okay, great.

12 to 18 months on to do so it's a good chunk of time.

It's possible that we reported first generation core inhibitor.

Once and you know.

Potent Tonight I think that's among the reasons why they are working on other generations.

DDP five one for ours.

Our core inhibitor and.

And as roughly 10 times more potent and.

And the one that you're referring to and that when that study.

And then another possibility of courses and the core plus and new.

Gross.

A 30 day joint going.

And actually.

You know be though the one and strategy to get you. There you know just decline enough price.

Jay R. Luly: And I had a couple on the new phase two trials, if you don't mind. So, for RSV-PED-PED, how many patients are you planning? And the endpoint is progression to lower respiratory tract infection. And then for that trial, do you have investigators lined up? And I guess maybe kind of similar to the last question, just how are they viewing the current situation and the feasibility of starting the trial? I'm sorry, are you talking about the PEED study? Yeah, right. RSV-PED. PEED.

Pressure on the virus and from different angles and from different stages of.

A mechanistic intervention and so.

And you know all along we've been working on.

Multiple different mechanisms and so it would have something.

In addition to and Nuke, plus the core and harbor.

And we're making pretty good progress on that front so.

On the.

You know earlier next year, we'll have more to sort of and.

And Scott surround our.

Progress on that front and cleaned up and also on our strategy of coming up with.

But the clinical triple and think for for Us.

Jay R. Luly: Yep. Yeah, so on the peds front, you know, we're aiming to start next quarter; we're aiming for about 90 patients total. Yeah, so I think those are the, you know, the main points in terms of the PED study itself. Part one is going to be safety and PK, and then we'll have part two where we'll be looking at the actual virus. So change in RSV shedding will be one of the things that we look at. So patients need to be given 938 or placebo for five days.

We're highly focused on.

All oral treatments as you know.

Some of the well historically people have use and server interfere on us and injectable.

With or without a new credits and so.

Sort of a poorly tolerated treatment that leads to very very low cure rates.

Other folks have done on using.

Some R&D approaches to.

And on Injectables to oral agents on.

And.

You know that's a that's an interest in an approach that some others are taking we're we're highly focused and committed to if we can come up with an all oral drugs from and we think we'll need and the and having all oral therapies.

Jay R. Luly: And, you know, we'll be looking at cohorts up to 24 months of age. Okay, great. Then one last one on the transplant trial, if you don't mind. So how many sites are you planning for that one? Are you also including Europe?

And so we could be.

Put together.

Dose combination.

And that could be.

Disseminated to you know to the millions of people hundreds and millions of people globally and that suffer from some folks on this.

Jay R. Luly: And is there any information on the current RSV rates in the transplant setting, either in the US or elsewhere? Thanks. I don't think so.

That would offer.

Significant.

The advantages overall, so highly focused on.

Jay R. Luly: The sites, you know, will come online. We'll, you know, get numerous sites. There'll be a global study that will have, you know, sites and all the obvious sort of territories. They'll be looking at 938 versus placebo for 21 days. And, you know, a dose a little bit longer because the patients are, you know, obviously immunocompromised. There aren't...

All oral agents and and hopefully with the addition of the new England all oil cyclical.

Your next question comes from the line a cash to line from Wolfe Research. Please go ahead.

Hi, this is anybody on free cash. Thanks, so much for taking a question we get from Gabriele on RFP and then one on HBV.

[music].

So I hear from here, it's starting with your pay TV and stem cell transplant and you have any data supporting the safety of longer term dosing with GDP nine 380, and then why did you stephie symptom onset cut off to be three day instead of two day like you did for outpatient adult.

Jay R. Luly: There aren't a lot of statistics on this specific patient population, so we'll just get set up in a lot of centers during the, you know, the normal season, and recruiters. It's very common. And your next question comes from the line of Brian Skorney from Barrett. Please go ahead. Hi, thank you. This is Jack Downing for Bryan.

And then on the RFP out patient trial and how many patients are currently involved in this trial and is there any way to modify it into a phase three registrational trial. Additionally, how are you ensuring that patients will be dosed with and the right time window and then one last one on HPV, one hypothesis why assemblies core inhibitor.

Jay R. Luly: Thanks for taking our questions. We just have one quick one. We're wondering if you have any updated thoughts with regard to the HPV opportunity for core inhibitors in light of the disappointing news from Assembly and their core plus nuke regimen and the sustained viral response data we saw there. I know you're looking at the triple combination internally as well, but we're just wondering what your thoughts are in light of that news. Thank you.

And is that the drug doesn't completely stopped the formation of new Cccdna and we were just wondering what the and depot or in vitro potency of ATP five on for it to specifically and hibbett Cccdna formulation. Thank you.

Well.

Let's start with the first one.

So three days versus two day.

Jay R. Luly: Yeah, so it's an interesting data set, you know. You might have to hand it to them for doing that study. The study was looking at a core inhibitor plus a nuke plus time. So the question is, could a core plus a nuke plus time get you to a functional cure? Again, nobody knew the answer to that question. They looked at different time points over the course of their investigations, three months, six months, a year, and so forth. And, you know, whereas the results that were produced in this initial study weren't particularly, [inaudible] you know, there could be a lot of different reasons. I mean, it's either, you know, a nuke plus a core plus more time, you know, although they went for, you know, 12 to 18 months, so it is a, it's a good chunk of time. It's possible that their first generation core inhibitor wasn't, you know, potent enough. I think that's among the reasons why they're working on other generations.

In terms of the.

And plan on.

Thank you and.

Okay and then include the range we're looking on.

A $40 was the inclusion criteria or.

RSVP.

There was nothing special about that I'll build on we believe that.

You know.

And on as always likely to be better.

You know who drugs are often within.

Two days or three days, and so 48 72 hours and there.

[music].

Our or probably pretty reasonable.

Time frames to be looking on a.

We certainly have all the talks and.

Last you know to support.

Most likely study.

And progressing well forwards so.

And what were some rather and question and.

Couldn't write them down cost and all.

Good day.

If you go off line.

Hello can you hear me.

Ah I cant and.

Okay, great I apologize for that on yet so.

So for the on the out.

I don't know time.

[laughter] for sure [laughter], yes, so outpatient trial, how many patients are currently and rolled and is there a potential to modify into some sort of a phase two three registrational trial.

Jay R. Luly: EDP514, our core inhibitor, is roughly 10 times more potent than the one that you're referring to in that study. And then another possibility, of course, is the core plus a new plus a third agent, which actually could be the winning strategy to get you there, you know, just applying enough pressure on the virus and from different angles and from different stages of mechanistic intervention. And so, you know, all along, we've been working on multiple different mechanisms, so we'd have something in addition to a nuc plus a core inhibitor. And we're making pretty good progress on that front. So,

Well I think this is and stuff.

Really a phase two and.

And study you know that were.

Using too.

Captured the initial.

Data in that and that based on population and so our plan is where it could be it is true. We don't really discuss you know recruitment on ongoing trials, others and its targets for where we are.

And our.

You know, where we expect to have data.

So, it's all but and again to be clear RSVP is not a registrational study, but will instead to be supportive of the entire on program overall.

And so the better sales the feasibility and the window and cetera, and so are we.

Jay R. Luly: [inaudible] you know, early next year, we'll have more to sort of discuss around our progress on that front and also on our strategy of coming up with a potential triple. I think for us, we're highly focused on all oral treatments. As you know, some of the, well, historically, people have used interferon as an injectable, you know, with or without a nuke, but there are some RNA approaches to add injectables to oral agents.

And again are able to get.

People, who arrived with symptoms within the 48 hour long time line and.

So.

On on cool.

And the you know the bigger wildcard is what will the scenes and be on.

The the presence and.

What cobot and social discounts on them on potential locked on Sept, something on the you know.

No one has on Lucky and we'll just have to go into on.

Jay R. Luly: And, you know, that's an interesting approach that some others are taking. We're highly focused and committed to coming up with an all-oral regimen, if we can. We think, in the end, having all-oral therapies that, you know, potentially could be put together as a fixed-dose combination and that could be, you know, disseminated to, you know, the millions of people, hundreds of millions of people globally that suffer from this infection, that that would offer, you know, significant advantages overall. So, highly focused on all-oral agents and, hopefully, with the addition of a NUCC and all- Your next question comes from the line of Akash Tiwari from Wolf Research. Please go ahead. Hi, this is Amy Lian for Akash.

Sort on.

Okay, great. Thank you and then last question on on Hepatitis B I just wanted to know what the in vitro and in vivo potency Abili T trial. When four is specifically on inhibiting cccdna from on the rate for information.

And turns and PCC and DNA formation as I recall its and the.

It's on the Nanomolar range.

Range and want to say it was around.

30, and animal or so.

Again this is said.

And something that you.

The term and and you true.

You know at the time is from infection. So.

30, 30 nanometer and sticks and some online.

Great. Thank you so much.

Welcome.

Your next question comes from the line.

Yes, and <unk> from Piper Sandler. Please go ahead.

Hi team I have two questions, maybe the first question and [noise] whatever.

Operator: Thanks so much for taking our questions. We just had several on RSV and then one on HPV. So starting with your phase 2b in stem cell transplant, do you have any data supporting the safety of longer-term dosing with EDP938? And then why did you set the symptom onset cutoff to be three days instead of two days like you did for outpatient adults? And then, on the RSV outpatient trial, how many patients are currently enrolled in this trial, and is there any way to modify it into a phase 2, 3, registrational trial? Additionally, how are you ensuring that patients will be dosed within the right time window? And then one last one on HPV. One hypothesis why assembly's core inhibitor failed is that the drug didn't completely stop the formation of new CCCDNA. And we were just wondering what the in vitro potency of EDP514 is to specifically inhibit CCCDNA.

Why do we know about the viral kinetics, obviously on RSV is different between you know.

Hospitalized peak share said pediatric patients Burgess immuno compromised and how do we really capture is its efficacy and the next stage of development I think commenting on that would be helpful. And then the second one question and recently at that meeting we saw on data from another FX are I get asked that had.

Very encouraging biomarker data on that failed to achieve a technological benefits show how do we think about sort of the mix of correlation and especially as we think about you know on data from the first generation and second generation XR agonist and you for taking our question.

Jay R. Luly: Thank you. Well, let's start with the first one. So three days versus two days in terms of transplant, I think it's in the range we're looking at. And, you know, 48 hours was the inclusion criteria for RSVP. There was nothing special about that other than we believe that, you know... Cleaner is always likely to be better. You know, flu drugs are often effective within two days or three days, and so 48, 72 hours in there are probably pretty reasonable timeframes to be looking at.

Yes.

Sure So starting with the second question first I think.

Triple caps or so we'll stay with us and we're referring to.

Correct.

It was in a 48.

Yeah, and study and we wait and see a lot of the markets moving on.

A lot of the right directions.

The Biblically pruritis.

Buckley.

But they didnt see.

Don't think people and Scott said on fibrosis improvement.

And.

I think one of the key.

Differences you know people generally view.

And are subsumed results as.

Being the sort.

And it will benchmark ones to be looking backwards and us.

Jay R. Luly: We certainly have all the talks, as you asked, to support this type of study progressing forward. So, um. What were some of your other questions? Couldn't write them down fast enough. Did you go off the line?

Leadership on the class.

And I think one of the big differences loans. They didn't they didn't go 72 weeks so.

And bump obviously, what we've built into our Oregon and two study.

And you get and many people you know hold looked and shorter duration loans from.

Operator: Hello, can you hear me? I can now. Okay, great. I apologize for that.

Various levels of success in terms of trying to demonstrate.

Operator: Um, yeah. So for the RSV outpatient trial, how many patients are currently enrolled, and is there a potential to modify it into some sort of a Phase II-III registrational trial? Yeah, I think this is it's really a phase two, Transcripts provided by Transcription Outsourcing, LLC. to capture the initial data in that patient population.

On effect on fibrosis. So we just won.

And the intercepts fund studies and phase three work.

And.

And design work on two core.

Accordingly, so I think the other thing is and Novartis study.

You know once on <unk>.

And I don't believe it was.

Hugely powered and terms and members and subjects also so.

Jay R. Luly: So our plan is for it to be phase two. We don't really discuss recruitment in ongoing trials other than to set targets for where we are or, you know, where we expect to have data. So it's, but then again, to be clear, RSVP is not a registration study, but instead, to be supportive of the entire program overall to better assess the feasibility, the window, etc. And so we are again able to get people to arrive with symptoms within the 48 hour timeline. And, So, again, I think we'll... I think the, you know, the bigger wildcard is, you know, what will the season be like?

Good question I guess.

You know the the powering in order to get a difference from Cibolo and also the all the shorter duration mobile and this study that they do and I think some of these fibrosis improvement one points and just so that will be once a one and two more patients on.

Yeah on Pete's.

You know Pete usually please and now with upper airway infection, and they have a high viral load and Yahoo.

And with three trial initially and the.

The key.

Other income in.

Compromised or or non tools to make sure try to prevent try to catch the infection moments and upper or weighed on inception.

On presented from the virus from sort of going down the elevator shaft and to the lower Airways, which.

Which is where.

Jay R. Luly: And the presence of COVID and social discontent and potential lockdowns, that's something that, you know, no one has any idea about, we'll just have to go into and sort out. Great, thank you. And then our last question on hepatitis B, just wanted to know what the in vitro and in vivo potency of EDP514 is specifically in inhibiting CCCDNA formation. In terms of CCC DNA formation, as I recall, it's in the... It's in the nanomolar range. I want to say it was around 30 nanomolar or so.

You become start to have some extra them inflammatory.

Disease going on and so you do.

And viral disease.

I think.

Symptoms can be and sex normal specific outcomes scale.

And transplant.

You'll we'll be looking for patients at home.

Initially upper or wait and see some on price too.

I don't have the prevention and we'll see a.

Lower airway publications.

And it's.

It's a.

I'm not specifically.

Able to point to at least right now anyway and I'm not.

Jay R. Luly: Again, this is something that you know at the time of the infection, so. 30, 30 nanomolars. Great. Thank you so much. You're welcome. Your next question comes from the line of Yasmeen Rahimi on Piper Sandler. Please go ahead.

On team Ken.

On the on the differences on terms of how the viral course plays out and compromise one.

They do believe.

You know longer treatment groups on <unk>.

As warranted and on patient population.

Thank you so much Jay scratching my questions.

Jay R. Luly: Hi team, I have two questions. Maybe the first question is, What do we know about viral kinetics? Obviously, if RSC is different between, you know, hospitalized patients versus pediatric patients versus immunocompromised patients, and how do we really capture its efficacy in the next stage of development? So I think commenting on that would be helpful. And then the second question is, recently at the meeting, we saw data from another FXR agonist that had very encouraging biomarker data but failed to achieve histological benefits. So how do we think about the sort of the myth of correlation, especially as we think about, you know, data for the first generation and second generation of FXR agonists? And you were taking our question. Sure, so starting with the second question first, I think tropofexor is the effector you're referring to, correct? It was in a 48-hour study, and they did see a lot of the markets moving in a lot of the right directions. They did see pruritus.

Your next question can on those from on the line.

Your next question comes from the line of Sacred John from Roth Capital Partners. Please go ahead.

Hi, Thanks for taking my question I have two quick ones for you I think on the first one I assume that you've been really busy with multiple studies and I'm just curious about that and I see study do you think that day.

Okay on putting Rome, and up the ongoing and JCP study also what estimates and rest.

That you see on chip Paucek and lever studies as Paul mentioned increased costs associated with some studies and slowed on trade. He can talk about.

So what was the first part of your question.

Competing for one and other the studies yeah, just competing for Anvil net why do you need.

I'd expect that to be a top line.

Among our studies are between our studies and other studies that's on your studies.

Yeah, No I think there.

Jay R. Luly: Unknown Speaker, But they didn't see, I don't think they had stats on fibrosis improvement. I think one of the key differences, you know, people generally view Intersteps results as being the sort of the benchmark ones to be looking at for leadership in the class. And I think one of the big differences was they didn't go 72 weeks.

They they each requires significant and turnover source, but they they're very different.

And diverse patient population, so I don't.

And expect.

And any real challenges there all the question on Clover, though is there was a question and I mean.

We do know.

People have done this.

As we were setting up for the southern hemisphere.

Jay R. Luly: That's obviously what we've built into our Argon2 study. Again, many people, you know, have looked at shorter-duration ones and various levels of success in terms of trying to demonstrate an effect on fibrosis. So, we just looked... [inaudible] you know, work on, I don't believe it was, Unknown Speaker We're hugely powered in terms of numbers of subjects also, so I would question, I guess. The powering in order to get a difference from a placebo and also the shorter duration of the study that they did. I think some of these fibrosis improvement endpoints are just necessarily going to be when one needs to be more patient. I'm, you know, and Peds. PEDs usually present with an upper airway infection. They have a high viral load in the upper respiratory tract initially.

You know and though he and the late spring no one really knew what the one through time wouldn't look like on the southern hemisphere and it turns out.

Due to a lot of the mitigation strategies that places like from New Zealand on.

Were right on top of.

You know they were able to stem.

Stem the tide of Cove, and significantly, but with that due to travel bans and lock towns and social distancing and close and comes up.

They did a pretty much presents and many other respiratory.

Viruses from from really occurring and and to that and.

And to look at who is one of the major cycles for that and RSV and as well. So there was very little with regards to the <unk> and we have some of the other respiratory infections.

Due to covert mitigation strategies on and now were rolling into what looks like a pretty nasty and co good situation and emerging on and the northern hemisphere, particularly and move on the U.S. and do you.

Jay R. Luly: And, you know, the key, whether it's immune compromised or not, is to, you know, make sure, try to prevent, try to catch the infection when it's an upper airway infection; you start to have as much of an inflammatory disease going on as you do a viral disease. I think symptoms can be assessed on a specific outcome scale, and transplant. You know, we'll be looking for patients that initially have upper airway disease and try to, you know, prevent lower airway complications. I'm, It's a, um...

And so we'll just have to work just have to see the most we can do is have sites set up everywhere and we'll have.

Approximately 100 sites.

Oh, and the U.S. he knew on ultimately and quotes and usual.

And I just try to try to capture the total and 17.

On patients and but but it is going to be and some those are covert are dependent on a phone call.

Hopefully, we won't have some of the and that specific trial on impacts.

And that we had and the earlier covert way and.

Latin America.

But no one from rural those sorts of things.

Jay R. Luly: I'm not specifically, [inaudible] Able to point to, at least right now anyway, the differences in terms of how that viral course plays out in an immunocompromised one. But I do believe..., you know, longer treatment duration is, Thank you so much, Jay, for answering my questions. Your next question comes from the line of Zeke Vajala from Roth Capital Partners. Please go ahead. Hi, thanks for taking my question. I have two quick ones for you.

And we'll just have to see what some of the on social distance and them and other sorts of things plays out in terms of rates of.

And diagnosed starts on RSV and flu and other kinds of loans. So.

On to.

Ladies and.

We're rolling into but we'll just have to watch.

Next and things stand out and just a quick follow up here about the Nash data expected and turn the turn your line how much data and with that I would actually like to have at the time it out and then and just on they were on there that you're from and now our carbon and argue that you'll be able to achieve that.

So you are you talking about three or five or non.

Jay R. Luly: I think the first one is, I've seen that you've been really busy with multiple studies, and I'm just curious about the planned RSV study. Do you think that it could hamper the enrollment of the ongoing Phase IIb study? Also, what are some of the risks that you think could, you know, pause or delay the study since Paul did mention increased costs associated with some studies being slowed or delayed due to COVID? So what was the first part of the question? Were they competing for one another, the studies? Yeah, just competing for enrollment, or did you not expect that to be a problem? Among our studies or between our studies and other studies? Between your studies.

When I was on to <unk>.

I prefer to put them on the real class interest at some cohort.

Yep, Okay, yes, so well you know we're on track that mean.

And.

The guidance that we gave 'em, we have to build some and Nash talk to you and we have a lot of countless coming and sort of the the first half of the.

On the year.

Two and HBV and on the second quarter were.

We're also expecting to have data from our follow on effects, our 297 and.

On the second quarter and.

And our claims to be study or NP, three or five and so called on to study, we're hoping to have enough.

Jay R. Luly: Yeah, no, I think they're, You know, they each require, you know, significant internal resources, but you know, they're a very different and diverse patient population. So I don't expect I'm not going to go into any real challenges there. The question on COVID, though, is a question. I mean, you know, people have been, as we know, As we were setting up for the Southern Hemisphere, you know, in the late spring, no one really knew what winter time would look like in the Southern Hemisphere. And it turns out, due to a lot of the mitigation strategies that places like New Zealand were right on top of, they were able to stem the tide of COVID significantly. But with that, due to travel bans and lockdowns and social distancing and closing things up, they did pretty much prevent many other respiratory viruses from really occurring.

Police and hit the.

On the target or the.

And analysis threshold, but we can.

And you know them and have that and form decision, making around the whole hold on Nash program. So again, we'll have.

All kinds of of data.

You know to look at and when that timeframe right.

Right now things are running and along and and going generally smoothly. So.

Anything can happen on the middle of next year with regard to the code, but it would be something that we're not currently seeing so we're on track for those.

[noise] targets that we guided to put on.

Looking forward to them off topic.

Well thank you.

Your next question comes from the line Eric Joseph from JP Morgan. Please go ahead.

Hi, good evening, thanks for taking the questions.

Jay R. Luly: And to that end, you can look at flu, it's one of the major signals for that, and RSV as well. So there was very little with regard to that, and other respiratory infections due to COVID mitigation strategies. And now we're, you know, rolling into what looks like a pretty nasty COVID situation emerging in the northern hemisphere, particularly in the US and EU. And so we'll just have to, we'll just have to see, you know, the most we can do is have sites set up everywhere. Again, we'll have approximately 100 sites. (Inaudible) That makes sense. Thanks, Jen. Just a quick follow-up here about the NASH data expected in mid-2021. How much data do you expect or would you actually like to have at the time of readout?

From our recent interactions with care wells.

A lot of interest and pursuing and FX started as a combination regimen and.

And you talked about exploring some non to ethics are.

Modalities and Nash just what's your latest thinking on the what would be an attractive.

Mechanism to partner with either three or five and United Seven and do you have a sense of whether development of a combo regimen of two novel agents and would be feasible and initial registration strategy.

Thanks.

No. Thanks, Eric So I you know I think.

I thought Saar combos are really interesting and you know because there was some elements of FX or I mean, that's that's always a little bit of a sort of and utility whether I mean it.

And it goes after some of the pro fiberoptic met.

Mechanisms, it's got some anti inflammatory.

Components and.

And it's also.

Correct.

Metabolic leave and so these are some of the.

The hallmarks of the.

On the disease.

Jay R. Luly: And then, based on the enrollment that you're seeing now, I'll call it an RU that you'll be able to achieve that. So you're, are you talking about 305 or Argonne too? I suppose both, but I'm more 305 since you said some cohorts. Yeah, okay. Yeah. So, well, you know, we're on track. I mean, today's guidance that we gave, we have two bits in NASH. In fact, we have a lot of catalysts coming in sort of the first half of the year.

So as such it could really talking on with.

You know from many of the different mechanisms that are.

You know on their study and you know.

There were a bunch of on out there so I.

I think.

You know there was a reasonably solid rationale to talk on and off XR and with Oh.

Virtually or any of the other classes.

You know ultimately in terms of combination strategies and.

I think.

And clearly some people or.

Thinking of fixed dose combinations and there are some people are thinking of maybe clicking on single agents forward. So that they can be mixed and matched.

Jay R. Luly: We'll have two in HPV in the second quarter. We're also expecting to have data from our follow-up on FXR-297 in the second quarter. And in our phase 2B study of EDP-305, the so-called Argonne 2 study, now we're hoping to have enough patients hit the target for the interim analysis threshold so that we can, you know, then have that informed decision making around the whole NASH program. So again, we'll have all kinds of data, you know, to look at in that time frame. Right now, things are running along and going generally smoothly, so anything can happen between now and the middle of next year with regard to COVID, but it would be something that we're not currently seeing, so we're on track for those, you know, targets that we guided to tonight. Looking forward to the multiple updates. Yeah, thank you. Your next question comes from the line of Eric Joseph from J.P. Morgan. Please go ahead. Hi, good evening.

I think I think both of those are are possibilities, but in the and you know you're going to need likely to have a have a combination so.

And now our plan is to generate.

And interesting.

And in the case of free or five into screening assays to.

Data center that would enable us and you know even through having checked at the interim analysis at 12 weeks next year.

Two then Ah think about peeling off.

A dose that could then be used in combination with.

With and other age and so from somewhere else. So that's the that's the plan there I think as the field matures. This is very likely to end up and combinations that it's their oral.

Could be potentially a six.

Those combinations I know that was one of the approaches and Bill you had was clearly quickly and at the beginning when they were looking and so there are multiple single mechanisms on doing combination and since it's almost.

Reminiscent of the day is of a of Hep C.

And.

And so that's following it down further on but if it's combination studies.

Jay R. Luly: Thanks for taking the questions. From our recent interactions with KOLs, there's a lot of interest in pursuing FXRs as a combination regimen. And you talked about exploring some non-FXR modalities in NASH. Just what's your latest thinking on what would be an attractive mechanism to partner with either 305 and 297? And do you have a sense of whether developing a combo regimen of two novel agents would be feasible as an initial registration strategy? Thanks. Um, no, thanks, Eric. So, you know, I think FxR combos are really interesting, you know, because there are some elements of FxR. I mean, FxR is a little bit of sort of a utility hitter.

So promise of one sort or another I would imagine that people will.

On a go forward with.

Combinations for approval.

Okay, Great and just a follow up on HBV, if I could.

And just picking up on your comments about the potential for and all oral triple regimen any what you can share on what the third leg of that stool might look like and I guess is there a a protease component to the HCV lifecycle that could be a lifecycle that could be adapted here and.

And.

I guess when we and.

When you're able to say more about what the mechanism might be and would you be surprised.

On its identity relative to some of the other.

Points and the lifecycle that are being pursued so bar for either HPV or HCV. Thanks.

Well thanks.

Thanks for the question.

Jay R. Luly: I mean, it goes after some of the pro-fibrotic molecules. [inaudible] So as such, it could really tuck in with many of the different mechanisms that are, you know, under study, and, you know, there are a bunch of them out there. So I think, You know, there's a reasonably solid rationale to tuck an FXR in with virtually any of the other classes. You know, ultimately, in terms of combination strategies, I think, you know, clearly some people are thinking of fixed dose combinations, and there are some people thinking of maybe taking single agents forward so that they can be mixed and mashed. I think both of those are possibilities, but in the end, you know you're gonna need, and probably will have, a combination.

Well, we're not quite ready Tonight to.

You know to sort of unfurl, but we expect that we will be by early next year.

So and on that front claws stay tuned, but we've been sort of.

Grinding away.

For a long time and the background on.

Other hubs and stuff and when we've we've sort of rentals and that Uh huh.

Overtime and on I think we're getting to the point now and some of this is.

So well hopefully getting getting getting pretty close so.

On a kind of early on our plan is to try to go for all oil but stay tuned.

Okay and tunnel.

Great. Thanks for taking the question.

Okay.

Your next question comes from the line of Brian Abrams from RBC capital markets. Please go ahead.

Jay R. Luly: So, now our plan is to generate, you know, interesting, in the case of 305, interesting phase two data sets that would enable us, you know, even through having checked at the interim analysis at 12 weeks next year, to then think about peeling off a dose that could then be used in combination with another agent from somewhere else. So, that's the plan there. I think as the field matures, this is very likely to end up in combinations that, if they're oral, could be potentially fixed-dose combinations. I know that was one of the approaches that Gilead was clearly taking at the beginning when they were looking at their multiple single mechanisms, You know, reminiscent of the days of Pepsi.

Hey, Jay Paul and his team thanks for taking my questions.

Starting on Nash I was wondering if could speak broadly about on your views on the evolving regulatory landscape there and on.

How you might incorporate that into the development program for instance are there addition.

Additional noninvasive tests, you may explore to ensure easily translate above methods for identification of patients where benefit risk of and FX optimal on do you have any views on.

What the accelerated approval and points are and whether those might evolve. Thanks.

Yeah.

Jay R. Luly: And so that's following it down further. But if combination studies are done, I would imagine that people will go forward with combinations for approval. Okay, great. And just a follow-up on HPV, if I could. I'm really just picking up on your comments about the potential for an all-oral triple regimen. Any light you can share on what the third leg of that stool might look like?

Great. Thanks for the question as you know were everybody is.

Focused on trying to get rid of biopsy is because not only.

You know and and and point.

Well, there's one that.

It's important for approval, but but.

But also in terms and more robustly.

I'm not looking for a noninvasive tests that could could stratify patients.

On a better way on.

And also you know.

Jay R. Luly: I guess, is there a protease component to the HCV life cycle that could be adapted here? And I guess, you know, when we... When you're able to say more about what that mechanism might be, we'd be surprised by its identity relative to some of the other points in the life cycle that are being pursued so far for either HPV or HCV.

Perhaps give you a more informed and reliable read outs and histologic wall and point so.

You know were will.

We'll be working on.

With the scientific community to explore this within our programs.

We hope that the landscape.

Well, we'll change before.

You know our registration study on on what is the chance that it could well, there's a chance that and that it may not on.

Jay R. Luly: Thanks. Yeah, thanks for the question. We're not quite ready tonight to, you know, to sort of unfurl that, but we expect that we will be by early next year. So, you know, on that front, stay tuned. But you know, we've been sort of, [inaudible] is hopefully getting pretty close. So, and again, our plan is to try to go for all oil, but stay tuned. Outside.

And by that none of them off the field is moving.

Moving very solidly in that direction and Theres a lot and.

Encouraging signs you know even coming out of India. So the.

On that front, it's probably not quite.

Right there but.

But for now and we're still including histologic read outs, obviously and Oh, it's funny because that is the.

No.

Yes.

At this time at least in terms of.

Jay R. Luly: Thanks for taking the question. Your next question comes from the line of Brian Abrahams from RBC Capital Markets; please go ahead. Hey, Jay. Hey, Paul.

Targeting.

You know approvable endpoint, but I suspect that way and sequel change and it could change for the time.

Jay R. Luly: Hey, team. Thanks for taking my questions. Starting with NASH, I was wondering if you could speak broadly about your views on the evolving regulatory landscape in that country and how you might incorporate that into the development program. For instance, are there additional non-invasive tests you may explore to ensure easily translatable methods for identification of patients where benefit-risk of an FXR is optimal? Do you have any views on what the accelerated approval endpoints are and whether those might evolve? Thanks for the question. As you know, we're, everybody is, focused on trying to get rid of biopsy. It is not only an end point, that is one that. [inaudible] I'm looking for a non-invasive test that could stratify patients, you know, in a better way.

You know one is ready for phase three.

Got it and then on the earlier stage respiratory programs.

Human men and women virus and and the source code to.

Yes, I was wondering if you could talk about the potential timelines for development. There once you select lead candidates and.

The and how does the recent success and vaccines for COVID-19 impact your prioritization of development. Among those early stage programs is there a rule you would still potentially see for a a COVID-19 therapy for instance, and stockpiling. Thanks.

Yeah. So absolutely I think you know were last few weeks and.

On including I guess and part today and there's been on the news on the vaccine front and and much of it. So you know quite encouraging and equals the sort of the things we know and the things we don't know.

Jay R. Luly: And also, you know, perhaps give you a more informed and reliable readout than histologic endpoints. Um, you know, we're working along with the scientific community to explore this within our program. We hope that the landscape, [inaudible] You know, encouraging signs, you know, even coming out of ASLD, you know, on that front, it's probably not quite right there. But for now, we're still including histologic readouts, obviously, in our study because that is the... You know, the best at this time, at least in terms of Targeting Approvable Endpoints. But I suspect that the landscape will change.

And well number one we don't know what the.

The efficacy rates are going to be you know broadly across all sorts of different.

The patient population and Thats number one.

Nor do we fully know yet although there are some encouraging signs of durability may be minimal on a good direction, but you know you just really nucleus need a lot more information to.

Understand.

How fully efficacious.

Vaccines or and and further you know how much they do or don't hobby and lead for a therapeutic.

Okay, and so I think.

You know these questions about even.

Jay R. Luly: And it could change by the time... You know, one is ready for phase three. Got it. And then on the earlier stage respiratory programs, human metapneumovirus, and SARS-CoV-2, I was wondering if you could talk about the potential timelines for developing them once you select lead candidates. What's the, how does the recent success of vaccines for COVID-19 impact your prioritization of development among those early stage programs? Is there a role you would still potentially see for a COVID-19 therapy, for instance, in stockpile? Yeah, so absolutely. I think, you know, in the last few weeks, including, I guess, in part today, there's been a lot of news on the vaccine front, and much of it's, you know, quite encouraging. I think there's the sort of things we know and the things we don't know. Number one, we don't know what the efficacy rates are going to be, you know, broadly across all sorts of different patient populations. That's number one.

Long term safety and questions about compliance in terms of getting vaccinated and so you know for the foreseeable future I think there are always going to be people for one reason on another who turn up.

Pets and positive score Covidien and clean and to that end I'm, particularly and people who are you symptomatic.

Or or otherwise fairly early in the stage of their.

Infections. This is where it makes sense and plastic sense, you know club a therapeutic so will you know we'll continue down.

On this path with it with the full expectation and that there will be good.

The need and some form of core therapeutics.

With regards to that and on women men and pneumonia.

Which is a virus for which there was no current vaccines on with ours.

But coming back to human met and Umo and and our Sars close to program I'd say, they're tracking you know pretty.

Pretty similar literally right now, even though we we I mean, we announced or human met and remote program and and.

January with some some early leads and then we announced the start of.

And just beginning to look good.

As far as Q2, and ER and the March timeframe, but the net.

Jay R. Luly: , , , , , , , , , , , , , , how fully efficacious [inaudible] You know, there's questions about even long term safety, there's questions about compliance in terms of getting vaccinated. And so, you know, for the foreseeable future, I think there are going to be people for one reason or another who turn up testing positive for COVID-19. And to that end, particularly in people who are asymptomatic, or otherwise fairly early in their stage of their infections.

Scientists and made really good progress I'd say, we've got.

Potent molecule degree put molecules from.

Against both of those viruses and more now.

Turning you know potent molecules and functional potent molecules and to the finalist candidate for clinical development. So we're targeting to have.

You know hopefully one from each of those programs.

The candidates and next year.

And then you know from the time I think you want and part of your question was from the time of your candidate selection and how long until you get it and the clinic.

Jay R. Luly: This is where it makes fantastic sense to have a therapeutic diet. So we'll continue down this path with the full expectation that there will be a need in some form for therapeutics. With regard to that and Human Meta-Pneumo, which is a virus for which there's no current vaccine, same with RSV, but coming back to Human Meta-Pneumo and our SARS-CoV-2 program, I'd say they're tracking pretty similarly right now, even though we announced our Human Meta-Pneumo program in January with some early leads, and then we announced the start of just beginning to look at SARS I'd say we've got potent molecules, very potent molecules, against both of those viruses, and we're now turning selection of potent molecules into finalist candidates for clinical development.

You know there are you just got to finish a lot of buying and be enabling a things, but you know typically yeah.

Line 910 months something like cloud is is.

It was off from achievable and just and I can spike the criteria that we use to you know nominate or candidate so and again were hopeful to to plan and harvest the candidates for each of those viruses and next year and.

It really began to round out.

You know as our goal really building ounces and leading to him and respiratory virus portfolio, you know with the flagship or.

The bar and speed.

And you know.

And just you know weeks, we expect that we'll have three different phase twos going on or just asked why we havent.

And staff working on RSV research, we're still exploring other other mechanisms there or to consider doing not because we don't have tremendous faith and line created but we just want to continue to establish leadership position, there and looking at and you know.

Jay R. Luly: So we're targeting to have one from each of those programs as a candidate for next year, and then from the time, I think part of your question was from the time of your candidate selection, how long until you get it in the clinic. There, you've just got to finish a lot of IND-enabling things, but typically, 9, 10 months, something like that, is often achievable, at least in our hands, by the criteria that we use to nominate our candidates.

Any any reasonable mechanism started.

On pairing on even looking and we don't think we need combination free so reason, but maybe there is a certain patient population and that would profit from having a combination and if that's the case, we would love to have that Ah poor far and off the shelf asset that we have.

Jay R. Luly: Again, we're hopeful to try to harvest the candidates for each of those viruses next year, which would really begin to round out. Transcription by Transcription Outsourcing, LLC, of RSV In just a few weeks, we expect that we'll have, you know, three different Phase IIs going on. Just FYI, we haven't stopped working on RSV research. We're still exploring other mechanisms there to consider. Again, not because we don't have tremendous faith in 938, but we just want to continue to establish a leadership position there looking at, you know, any reasonable mechanism, start comparing them. Even looking, we don't think we need combinations for any particular reason, but maybe there is a certain patient population that would profit from having a combination.

And then on hold 100% ownership and so.

That's going on and RSV and hopefully soon will be supplementing that with a human not on pneumo.

Age and human and other Pneumo second leading cause of pretty much everything RSV causes.

And then you know cobot therapeutics to we've got you know a watchful eye on how vaccines are going to play there.

But again I.

I think there is no one who wouldn't want to have and effective COVID-19.

Sorry, just quick to age and.

Available to them something that was safe and the oral.

And there could be administered at early stages, you know from the first sign of a positive test and without you know needing to head into an infusion center either for a monoclonal antibody on age and play that's injectables. So.

Jay R. Luly: And if that's the case, we would love to have that for an off-the-shelf aspect that we have and have 100% ownership of. So, that's what's going on in RSV. Again, hopefully soon, we'll be supplementing that with a human metanemo agent, human metanemo, the second leading cause of pretty much everything RSV causes. And then, you know, COVID therapeutics, too. We've got, you know, a watchful eye on how vaccines are going to play there. But again, I think there's no one who wouldn't want to have an effective COVID-19 SARS-CoV-2 agent available to them, something that was safe and oral and that could be administered at early stages, you know, from the first sign of a positive test and without, you know, needing to head into an infusion center, So, you know, this remains a strong goal, and I think, in the aggregate, it really builds out an interesting sort of portfolio of human vascular biology.

This remains a strong goal and I think in the aggregate it really builds out and interesting on sort of portfolio of human particularly by the losses.

Great. Thanks, so much.

You're welcome.

Your last question comes from the line of Jay Olson from Oppenheimer. Please go ahead.

Oh, Hey, guys. Thanks for taking on our questions. We have two of them. The first question is about GSK is RSV vaccine, which.

And they announced today was moving into a phase three study if that vaccines eventually successful what didnt have any long term impact on your view of the market opportunity for and all I see therapeutics and then we have another question about Nash.

Yeah, and you know maternal and.

And maternal vaccines that right.

Yes, that's correct.

Yeah I.

I mean that net approach and as has been tried before and then Ted and promising results from phase two only not to hold up and phase.

Jay R. Luly: Great, thanks so much. You're welcome. Your last question comes from the line of Jay Olson from Oppenheimer. Please go ahead. Oh, hey guys, thanks for taking our questions. We have two of them.

Phase three studies.

I think there is you know just a fair number of questions around.

Oh around that strategy, not least of which is.

Jay Olson: The first question is about GSK's RSV vaccine. Today, we were moving into a phase three study. If that vaccine is eventually successful, would it have any long-term impact on your view of the market opportunity for an RSC therapeutic? And then we have another question about that. Yeah, you know, maternal. This is a maternal vaccine, is that right?

You know the degree of.

Penetration on and on compliance in terms of doing no mandatory but not mandatory but doing real broad.

Vaccinations and.

And pregnant women and for.

Something that.

You know me.

They are not.

Jay R. Luly: Yes, that's correct. Yeah. I mean, that approach has been tried before and has had promising results in phase two, only for them to not hold up in phase three studies. I think there's, you know, just a fair number of questions around, you know, around that strategy, not least of which is penetration and compliance in terms of doing, you know, mandatory, not mandatory, but doing real broad, The End Transcription by Transcription Outsourcing, LLC, of Pregnant There's I think there's other questions that are, you know, reimbursement questions, pay, you know, how these things are getting paid, will people really reimburse for something that, Again, is a, Well, it's just a question of the..., of the dollar value per benefit.

Warmed up being.

You know.

On a big issue and settling Theres other questions that are.

You know reimbursement question loans paid and you know how these things are.

Getting paid you know will people.

Really reimburse for something.

[noise] again is a.

Well, it's just a question had to and.

The dollar value per benefit.

Garnered there because.

You know these some of these vaccines.

Maybe I'm not.

Not be that durable and you're you're ultimately.

Just maybe postponing the inevitable I mean children reliably good RSV infections.

And if they.

They they usually rely on a few years sales.

The success of RSV infections to sort of build up of certain immunity to it but yes. They are.

Jay R. Luly: You know, some of these vaccines may help, and you're ultimately just maybe postponing the inevitable. I mean, children reliably get RSV infections, and if they, They usually rely on a few years of successive RSV infections to sort of build up a certain immunity to it, but if there's a break in that, the immunity is not sort of a durable one, and they're going to be prone to getting these infections anyway.

Since the break and immunity smiled, when unfold and durable on that.

You're gonna be prone to getting news and.

Infection. So anyway, so I think there's been questions around the efficacy piece on that approach from on once again, one and which I think he would want and still have a.

Under any even under any ducs and scenario.

On a robust armamentarium of.

Jay R. Luly: So I think there are big questions around the efficacy piece. [inaudible] Small Molecule Therapeutics. So there are. I think there are big safety hurdles in that area.

And.

On a small molecule on therapeutics.

And there's I think there's been safety hurdles and on the other one.

Jay R. Luly: Okay, great. Thank you. And then our second question is about NASH. And we're wondering if the CRL that Intercept received and then the subsequent work they're doing to resubmit their NDA have any impact on your own development plans for an FXR agonist in NASH, and specifically, whether you would consider targeting a narrower NASH patient population with advanced fibrosis?

Okay, great. Thank you and then a second question is about Nash and we're wondering if the CRL that intercept received and then the subsequent work they're doing to resubmit, there and do you have any impact on your own development plans for NSX on.

And it's in Nash and specifically, if you would consider targeting a narrower.

Cash patient population with advanced fibrosis.

Jay R. Luly: I think we just need to fully understand the situation. I'm not sure anybody really knows. You know, all the details are in that CRL. For us and for our immediate next steps, they're on a certain path that we've outlined and defined again today. And they're not, You know, there's literally no impact.

I think we just need to fully understand the situation.

I'm not sure anybody really knows.

And all the details around the CRL.

You know for us and for our immediate next steps.

They're on a on a certain price.

Weve.

Outlined and defined again today and they're not.

You know there is others literally no impact on.

I think, you know, we as a NASH company, in part, and all other NASH companies, I think, you know, you should be watching, you know, what that CRL means, just to fully understand it. But until we have... A lot more granular detail around it, I'm hesitant to... recommend the course changes at this time. Okay, great. Thanks for taking the questions, and have a happy Thanksgiving. You too? Thank you. And I will now turn the call back over to Jennifer Viera for her closing remarks. Thank you, everyone, for joining us today. If you have any additional questions, please feel free to give us a call or send me an email. Thanks so much. Have a good night. Bye-bye. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.

Of that based on a day or on our client ongoing activities I think.

We as a day Nash company and cards and all other and as companies.

And should be watching you know what that CRL.

Matt and just to fully understand it but until we have from.

You know a lot more granular detail around around it on.

Has its and cool.

Oh, yeah sort of recommending question interest at this point.

Okay, great. Thanks for taking the questions and have a happy Thanksgiving.

You too thank you.

And I will now turn the call back over to Jennifer Viera for closing remarks.

Thank you everyone for joining us today, if you have any additional questions. Please feel free to give us the carson, meaning email. Thanks, so much have a good night.

Hi.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.

[music].