Q1 2021 Enanta Pharmaceuticals Inc Earnings Call

Good afternoon, and welcome to enhance of Pharmaceuticals first quarter 'twenty 'twenty, one financial results conference call. At this time all participants are in a listen only mode. There will be a question and answer session at the end of the prepared remarks. Please be advised the this call is being recorded.

Operator: Good afternoon, and welcome to Enanta Pharmaceuticals' first quarter 2021 financial results conference call. At this time, all participants are in a listen-only mode.

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 conference over to Jennifer Viera, Investor Relations.

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

Jennifer Viera: Thank you, Operator, and thank you to everyone for joining us this afternoon. The news release with our fiscal first quarter financial results was issued this afternoon and is available on our website. On the call today is 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 and results to differ materially from those statements.

Thank you operator, and thank you to everyone for joining us. This afternoon. The news release with our fiscal first quarter financial results was issued this afternoon and is available on our website.

On the call today is Dr. Jay Lullay, President and Chief Executive Officer, Paul Mellett, Our Chief Financial Officer, and other members of Anantha 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.

And results to differ materially from those statements.

Jennifer Viera: 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?

A description of these risks is in our most recent form 10-Q and other periodic reports filed with the SEC 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 <unk>, President and CEO Jay.

Thank you Jennifer and good afternoon, everyone.

Jay R. Luly: Thank you, Jennifer, and good afternoon, everyone. Our fiscal first quarter was an exciting and productive time for Enanta as we continue to advance our robust, wholly owned pipeline. We currently have six ongoing clinical trials, to and respiratory syncytial virus, and Hepatitis B, and non-alcoholic steatohepatitis, as well as three respiratory virus discovery initiatives, including a recently announced RSV-L inhibitor. Complementer HMPV and COVID-19 Program We also recently introduced a new selective oral HPV RNA destabilizer that is advancing toward the clinic mid-year. I'd like to take a moment and acknowledge the commitment and dedication of our employees who continue to go above and beyond, contributing to the significant pipeline progress we have made across our business.

For fiscal first quarter was an exciting and productive time for NAV as we continue to advance our robust wholly owned pipeline.

Currently have six ongoing clinical trials two in respiratory syncytial virus.

Hepatitis B.

And two of non alcoholic stay out of the hepatitis as well as three respiratory virus discovery initiatives, including our recently announced RSV L inhibitor.

The complement or each MPV and COVID-19 programs.

We also recently introduced our new selective oral HBV RNA destabilizer it is advancing.

Towards the clinic.

Mid year.

I'd like to take a moment and acknowledge the commitment and dedication of our employees, who continue to go above and beyond contributing to the significant pipeline progress we've made across our business.

We continue to build out of our team with talented individuals not just this quarter made three significant new hires who will contribute to the company's growth.

Jay R. Luly: We continue to build out our team with talented individuals and, just this quarter, made three significant new hires who will contribute to the company's growth. We look forward to their contributions over the coming months as we approach several significant milestones. In December, Dr. Tara Kieffer joined us from Vertex as Senior Vice President of New Product Strategy and Development.

We look forward to their contributions over the coming months as we approach several significant milestones in December of Doctor Cherokee for joined US from vertex as senior Vice President of new product strategy and development.

Jay R. Luly: Tara brings over 20 years of scientific expertise in infectious diseases and product development. In January, we announced Dr. John DiVincenzo, one of the most highly regarded investigators in respiratory syncytial virus, would be joining the Enanta team. For the past 30 years, John has played a significant role in many of the major RSV clinical trials. Most recently, we were pleased to announce Brendan Liu as our Senior Vice President of Business Development, a role to which he brings 20-plus years of diversified business development and sales and marketing experience in the pharmaceutical and technology industries, most recently at Merck KGAA.

Tara brings over 20 years of scientific expertise in infectious diseases and product development.

In January we announced Doctor John deepened Chun so one of the most highly regarded investigators in respiratory syncytial virus will be joining the internet to the team for the past 30 years. John has played a significant role of many of the major RSV clinical trials.

Most recently, we were pleased to announce Brendan Lou sort of senior Vice President of business development role to which he brings 20 plus years of diversified business development and sales and marketing experience in the pharmaceutical and technology industries. Most recently at Merck kg.

Jay R. Luly: Turning to our pipeline, I'm excited to review the progress of the past quarter in more detail and share our plans for multiple catalysts throughout 2021. I'll start with RSV, where we are advancing a robust clinical development program consisting of two ongoing studies and one planned study of EDP938, the only RSVN inhibitor in clinical development today. 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.

Turning to our pipeline I'm excited to review the progress of the past quarter in more detail and share of plans for multiple catalysts throughout 2021.

I'll start with RSV, where we are advancing a robust clinical development program consisting of two ongoing studies and one planned study of Edp nine create the only RSV <unk> inhibitor in clinical development today.

RSV is the severe respiratory infection associated with significant morbidity and mortality in N. The.

The elderly and immune compromised adults and the condition for which there is currently no safe and effective therapy.

Jay R. Luly: Globally, there are an estimated 33 million cases of RSV annually in children less than 5 years of age, with about 3 million hospitalized and approximately 118,000 dying each year from complications associated with the infection. The first of our ongoing studies is RSVP, a Phase 2b, double-blind, placebo-controlled study of EDP938 designed to enroll approximately 70 subjects who are randomized to receive either EDP938 or placebo for five days. Currently, the RSV season in the Northern Hemisphere has not begun due to the continuing COVID-19 mitigation measures.

Globally. There are an estimated 33 million cases of RSV annually and children less of five years of age with about 3 million hospitalized and approximately 118000 dying each year from complications associated with the infection.

The first of our ongoing studies as RSVP the phase two the double blind placebo controlled study of Edp 938 designed to enroll approximately 70 subjects were randomized to receive either edp 938 or placebo for five days.

Currently the RSV season in the northern Hemisphere is not the gun due to the continuing COVID-19 mitigation measures. We believe the when these measures subside RSV will reemerge.

Jay R. Luly: We believe that when these measures subside, RSV will reemerge, and recent modeling is even predicting large future outbreaks of respiratory viruses, especially influenza and RSV. In fact, this has already occurred in New South Wales, Australia's most populated state, where a recent government surveillance report showed a steep increase in RSV rates that experts believe was due to relaxed social distancing measures. Furthermore, the RSV rates were even higher than the usual average peak in the last five years. Despite being delayed by several months, this peak occurred in Australia's summer season, when these cases are usually low.

In recent modeling is even predicting large future outbreaks of respiratory viruses, especially influenza and RSV and for.

This has already occurred in new South Wales, Australia as most populated state for a recent government surveillance report showed a steep increase in RSV rates that experts believe was due to relax social distancing measures.

Further the RSV rates were even higher than the usual average peak in the last five years.

Fight being delayed by several months and this piece of occurred in Australia as summer season. When these cases are usually low.

Also the scarcity of RSV cases during the pandemic is breaking the chain of immunity in children.

Jay R. Luly: Also, the scarcity of RSV cases during the pandemic is breaking the chain of immunity in children, who normally get repeated exposures to RSV and build resistance in the first few years of life. This has allowed for a larger vulnerable patient population, which experts believe may result in higher than average levels of RSV when the virus reemerges. That said, we believe RSV will reemerge, and our strategy is to be ready across the globe with clinical trial sites ready to go when the hotspots emerge.

Normally get repeated exposures of RSV and build resistance from the first few years of life.

This has allowed for a larger vulnerable patient population with experts believe may result in higher than average levels of RSV one of the virus re emerges.

That said, we believe RSP will reemerge and our strategy is to be ready across the globe with clinical trial sites ready to go when the hotspots emerge for.

For example, we are setting up trial operations for RSVP not only in North America, but also in Europe, The Pan Asia territory, and the southern hemisphere, aiming to more than double the number of sites globally.

Jay R. Luly: For example, we are setting up trial operations for RSVP not only in North America but also in Europe, the Pan-Asia Territory, and the Southern Hemisphere, aiming to more than double the number of sites globally and provide updated guidance on RSVP timelines as RSV becomes prevalent again. Turning to our other RSV clinical trials, in December, we initiated RSV-TX, a global multicenter Phase IIb randomized double-blind placebo-controlled study evaluating the efficacy and safety of EDP938 in adult hematopoietic cell transplant recipients with acute RSV infection of the upper respiratory tract.

We'll provide updated guidance on RSVP timelines as RSV becomes prevalent again.

Turning to our other RSV clinical trials in December we initiated RSV, TX a global multicenter phase <unk> randomized double blind placebo controlled study evaluating the efficacy and safety of Edp 938, adult hematopoietic cell transplant recipients with acute ours.

The infection of the upper respiratory tract.

The study is designed to enroll approximately 200 adult subjects with the primary objective of evaluating the effect of Edp 938 on development of the lower respiratory tract complications in the east transplant patients, who will receive edp 938 or placebo for 21 days and then be followed for 28 days.

Were also currently planning to initiate our third of RSV Phase II study RSV Peds later this quarter. This is the global multicenter phase two double blind placebo controlled dose ranging study of Edp 938, and children, aged 28 days to 24 months.

Jay R. Luly: The study is designed to enroll approximately 200 adult subjects with the primary objective of evaluating the effect of EDP-938 on the development of lower respiratory tract complications in these transplant patients who will receive EDP-938 or placebo for 21 days and then be followed for 28. We're also planning to initiate our third RSV Phase 2 study, RSV-PEDS, later this quarter. This is a global, multi-center, Phase 2, double-blind, placebo-controlled, dose-ranging study of EDP938 in children aged 28 days to 24 months.

Designed to enroll approximately 90 hospitalized for non hospitalized and from some children with RSV.

The study will have two parts and part one the primary objective.

Objective is to evaluate the safety and pharmacokinetics of Edp 938 in multiple ascending doses and for age cohorts oldest to youngest while the objective and part two is two sets of the antiviral effects of ours against RSV.

And each part subjects will be dosed for five days and then solid for 23 days.

Beyond these three trials, we are excited about the expansion of our RSV program with the introduction of RSV L protein inhibitor discovery initiatives that includes potent animal or leads against both the RSV a and rspb.

Jay R. Luly: It is designed to enroll approximately 90 hospitalized or non-hospitalized infants and children with RSV. This study will have two parts; in part one, the primary objective is to evaluate the safety and pharmacokinetics of EDP938 in multiple ascending doses in four age cohorts, oldest to youngest, while the objective in Part 2 is to assess the antiviral effects against RSV. In each part, subjects will be dosed for 5 days and then followed for 23 days.

Similar to 93 eight we are for.

Focusing on replication inhibitors is this non fusion approach directly targets viral replication as opposed to viral entry.

<unk> inhibitors are not expected to have cross resistance to other classes of inhibitors and therefore, it can potentially be used alone or in combination with agents targeting different car of speed mechanisms such as Edp 938, the possibly broaden the treatment window for the eligible patient population.

Jay R. Luly: Beyond these three trials, we are excited about the expansion of our RSV program with the introduction of the RSV-L protein inhibitor discovery initiative. It includes potent animal or leads against both RSV A and RSV B, similar to 938. We are focusing on replication inhibitors as this non-fusion approach directly targets viral replication as opposed to viral entry. RSV-L inhibitors are not expected to have cross-resistance to other classes of inhibitors and therefore can potentially be used alone or in combination with agents targeting different RSV mechanisms, such as EDP938, to possibly broaden the treatment window or the eligible patient population.

Our respiratory virology discovery efforts are also urgently focused on developing targeted antiviral therapeutics for Sars Covid two.

Recently, several new variance of the original virus had been identified initially emerging in the U K, South Africa, and Brazil, which may have some impact on the activity of current monoclonal antibodies and vaccines.

The variance have mutations in the spike protein the potentially allow the virus the spread more readily or evade the immune system.

Our antiviral discovery program targets conserved regions and enzymes central for viral replication. So mutations in the spike protein are not expected to affect the activity of our inhibitors. We expect the emerging variance to retain full sensitivity to our inhibitors and are currently in the process of confirming the.

Pre clinically.

Among our respiratory virology discovery programs, which include RSP L protein Sars Covid, two and human Metapneumovirus, we have an animal or inhibitors undergoing lead optimization and each and our plan is to nominate clinical candidates and two of these three programs in 2021.

Jay R. Luly: Our respiratory virology discovery efforts are also urgently focused on developing targeted antiviral therapeutics for SARS-CoV-2. Recently, several new variants of the original virus have been identified, initially emerging in the UK, South Africa, and Brazil, which may have some impact on the activity of current monoclonal antibodies and vaccines.

One.

Let's move on to our hepatitis B program, where we are evaluating edp five one for our lead core inhibitor in chronic HBV patients treated with a nucleoside reverse transcriptase inhibitor referred to as nuc suppressed patients as well as in chronic HBV infected patients with high viral.

Jay R. Luly: These variants have mutations in the spike protein that potentially allow the virus to spread more readily or evade the immune system. However, our antiviral discovery program targets conserved regions and enzymes essential for viral replication, so mutations in the spike protein are not expected to affect the activity of our inhibitors. We expect the emerging variants to retain full sensitivity to our inhibitors and are currently in the process of confirming this preclinically. Among our respiratory virology discovery programs, which include RSVL protein, SARS-CoV-2, and human metapneumovirus, we have nanomolar inhibitors undergoing lead optimization in each, and our plan is to nominate clinical candidates in two of these three programs in 2021.

Loads not currently on treatment, which we referred to as by remake of patients.

Each trial is a randomized double blind placebo controlled study designed to evaluate the safety Tolerability pharmacokinetics antiviral activity of one of three orally administered multiple ascending doses of Edp five one for compared to placebo over a 28 day period and up to 24.

For randomized patients we plan to have preliminary data from both trials next quarter.

Last month, we were excited to announce the expansion of our HBV program to include our newest clinical candidate Edp 721 of potent and selective oral HBV RNA destabilizer. It has the potential to reduce production of multiple HBV proteins, which we believe could be key component in it.

Jay R. Luly: Let's move on to our Hepatitis B program, where we are evaluating EDP514, our lead core inhibitor, and chronic HPV patients treated with a nucleoside reverse transcriptase inhibitor, referred to as nuke-suppressed patients, as well as chronic HPV-infected patients with high viral loads not currently on treatment, which we refer to as viremic patients. Each trial is a randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of one of three orally administered multiple ascending doses of VDP514 compared to placebo over a 28-day period in up to 24 randomized patients.

<unk> of functional cure for chronic HBV.

We recognize this may take a multi drug approach involving mechanisms to stop viral replication and inhibits surface antigen also referred to as S antigen.

Nukes are the current standard of care and they are a reasonably effective but suppressing the HBV replication edp five one for our core inhibitor. The fact, several stages of HBV replication from uncoated and nuclear imported the virus to capsid Assembly and recycling.

And our new oral agent ADP 721 that can destabilize HBV Rnas leads to a reduction in viral proteins, including S antigen.

Last month, we shared compelling data demonstrating the three log reduction in S antigen levels with Edp seven to one in a mouse model, which demonstrated equal or superior efficacy to S. I RNA based and antisense Oligos based agents tested in the same model.

Jay R. Luly: We plan to have preliminary data from both trials next quarter. Last month, we were excited to announce the expansion of our HPV program to include our newest clinical candidate, EDP721, a potent and selective oral HPV RNA destabilizer that has the potential to reduce production of multiple HPV proteins, which we believe could be a key component in achieving a functional cure for chronic HPV. We recognize that this may take a multidrug approach, involving mechanisms to stop viral replication and inhibit the surface antigen, also referred to as S-antigen.

With Edp 721, now in our portfolio.

We see the opportunity for an all oral functional cure and we look forward to initiating the phase one clinical study of this exciting new candidate by mid year.

Moving onto our work in non alcoholic stay out of hepatitis or Nash, our first FX or agonist Edp three of five is in an ongoing argon two phase <unk> randomized double blind placebo controlled 72 week study in approximately 340 subjects with bi.

Jay R. Luly: Nukes are the current standard of care, and they are reasonably effective at suppressing HPV replicates. EDP514, our core inhibitor, affects several stages of HPV replication, from uncoating and nuclear import of the virus to capsid assembly and recycling.

<unk> see proof of Nash with fibrosis. The primary endpoint of argon two is improvement of fibrosis without worsening of Nash <unk> Nash resolution without worsening of fibrosis.

For a good target engagement and Tolerability were observed with the one milligram dose in Oregon, one with argon two we're exploring doses of one five and 2.0 milligrams to determine what additional dose or doses may also favorably balanced target engagement with tolerability.

Jay R. Luly: And our new oral agent, ADP 721 that can destabilize HPV RNAs, leads to a reduction in viral proteins, including S-anadrine. Last month, we shared compelling data demonstrating a 3-log reduction in S-antigen levels with EDP721 in a mouse model, which demonstrated equal or superior efficacy to siRNA-based and antisense-oligo-based agents tested in the same model, with A We see the opportunity for an all oral functional cure, and we look forward to initiating a phase one clinical study of this exciting new candidate by midyear.

In mid 2021.

We will have an internal interim analysis of 12 weeks of treatment in a subset of patients at which point, we expect to have more information to determine what dose or doses, we moved forward for potential combinations through partnering.

We are also developing edp 297 are oral follow on FX or agonist for Nash with potentially best in class potency and tissue targeted effects.

Currently being studied in a phase one randomized double blind placebo controlled first in human trial designed to assess the safety Tolerability and pharmacokinetics in approximately 70 for healthy adult subjects, we look forward to reporting clinical data in mid 2021.

Jay R. Luly: Moving on to our work in non-alcoholic steatohepatitis, or NASH, our first FXR agonist, EDP305, is in an ongoing Argon2 Phase IIb randomized double-blind placebo-controlled 72-week study in approximately 340 subjects with biopsy-proven NASH with fibrosis. The primary endpoint of Argon 2 is improvement of fibrosis without worsening of NASH or NASH resolution without worsening of fibrosis.

So in mid 2021, we expect to have important insights for both Edp 305, and Edp 297 will be positioned to prioritize these assets and define the optimal go forward strategy.

I'd like to conclude my remarks by emphasizing the key few points.

And especially active time for <unk> as we continue to progress and expand our wholly owned pipeline.

Over 'twenty and 'twenty, one we look forward to several catalysts, including the initiation of the phase one clinical study of Edp 721, our HBV RNA Destabilizer by mid 2021, and preliminary data for both phase one studies of Edp five one for in HBV patients in the second quarter of 2021.

Jay R. Luly: While good target engagement and tolerability were observed with the one milligram dose in Argon 1, with Argon 2, we are exploring doses of 1.5 and 2.0 milligrams to determine what additional dose or doses may also favorably balance target engagement with tolerability in mid-2021. We will have an internal interim analysis of 12 weeks of treatment in a subset of patients, at which point we expect to have more information to determine what dose or doses we move forward for potential combinations through partners.

Further one looking toward our respiratory virology discovery efforts, we anticipate nominating two new clinical candidates. This year among our H M. P V. Sars cov, two and RSV programs finally of Nash with the argon two trial of Edp three of five in the Phase one study of Edp 290 <unk>.

Seven we look forward to having valuable insights mid year to inform next steps.

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

Thank you Jay I.

Jay R. Luly: We are also developing EDP-297, our oral follow-on FXR agonist for NASH, with potentially best-in-class potency and tissue-targeted effects. It is currently being studied in a Phase I, randomized, double-blind, placebo-controlled, first-in-human trial designed to assess the safety, tolerability, and pharmacokinetics in approximately 74 healthy adult subjects.

I would like to remind everyone that the natural reports on a September 30 fiscal year schedule.

Today, we are reporting results for our first fiscal quarter ended December 31 2020.

For the quarter total revenue was $31 7 million and consisted entirely of royalty revenue earned on <unk> Global HC Peel HCV product sales of $481 million.

This compares to total revenue of $52 6 million for the same period in 2019.

The decrease in royalty revenue quarter over quarter was driven by lower HCV product sales as treated patient volumes have remained below pre COVID-19 levels as reported by Abbvie.

Jay R. Luly: We look forward to reporting clinical data in mid-2021. By mid-2021, we expect to have important insights for both EDP-305 and EDP-297. We'll be positioned to prioritize these assets and define the optimal go-forward strategy.

Royalty revenue was calculated on 50% of Maverick sales at a blended royalty rate for the quarter of 13% and an approximately 30% of the care of sales at a royalty rate of 10% after adjustments for certain contractual discounts rebates and set offs, which now are approximately two 7% of <unk>.

Jay R. Luly: I'd like to conclude my remarks by emphasizing a key viewpoint. It's been an especially active time for Enanta as we continue to progress and expand our wholly owned pipeline. In 2021, we look forward to several catalysts, including the initiation of a Phase I clinical study of ADP721, our HPV RNA destabilizer, by mid-2021, and preliminary data for both Phase I studies of ADP514 and HPV patients in the second quarter of 2021. Further, looking toward our respiratory virology discovery efforts, we anticipate nominating two new clinical candidates this year among our HMPV, SARS-CoV-2, and RSV programs.

<unk> total reported HCV product sales as.

As a reminder of royalties are calculated on a calendar year basis, therefore royalties for our fiscal first quarter ending December 31 will be calculated at the highest royalty rates for the year and royalties for our fiscal quarter ending March 31 will be calculated of 10% of lowest royalty rate tier.

In our fiscal year.

You can review our royalty tier schedule in our 2020 form 10-K.

Recently Abbvie reported that the global HCV sales were $1 3 billion in 2020 and guided to 2 billion for global HCV sales in 2021.

Moving onto our expenses for the three months ended December 31, 2020 research and development expenses totaled $36 7 million.

Jay R. Luly: Finally, in NASH, with the Argon 2 trial of EDP-305 and the Phase 1 study of EDP-297, we look forward to having valuable insights mid-year to inform next steps. I'll stop here and turn the call over to Paul to discuss our financials for the quarter.

For 32 8 million for the same period in 2019.

The increase was primarily due to the timing of activity of our clinical trials year over year.

General and administrative expense for the quarter was $7 4 million compared to $6 9 million for the same period in 2019.

This increase was primarily due to increased head count the compensation expense.

Paul J. Mellett: Thank you, Jay. I would like to remind everyone that Enanta reports on a September 30th fiscal year schedule. Today we are reporting results for our first fiscal quarter ended December 31, 2020. Total revenue was $31.7 million and consisted entirely of royalty revenue earned on AbbVie's global HCV product sales of $481 million. This compares to total revenue of $52.6 million for the same period in 2019. The decrease in royalty revenue quarter over quarter was driven by lower HCV product sales as treated patient volumes have remained below pre-COVID levels, as reported by Abbott.

And the recorded an income tax benefit of $3 3 million for the three months ended December 31, 2020 compared to income tax expense of $1 5 million for the same period in 2019.

This income tax benefit was due to the companys pretax loss from the period, which can be carried back under the cares Act of 2020.

Net loss. The three months ended December 31, 2020 was $8 3 million or a loss of 41 cents per diluted common share.

<unk> to net income of $13 4 million for 65 per diluted common share for the corresponding periods of 2019.

And at the ended the quarter with $404 7 million of cash and marketable securities.

And then the expects that its current cash cash equivalents and marketable securities as well as its continuing the royalty revenue will be sufficient to meet the anticipated cash requirements of it.

Paul J. Mellett: Royalty revenue is calculated on 50% of Maverick sales at a blended royalty rate for the quarter of 13% and on approximately 30% of the CARES sales at a royalty rate of 10% after adjustments for certain contractual discounts, rebates, and setoffs, which are now approximately 2.7% of AbbVie's total reported HCV product sales. As a reminder, royalties are calculated on a calendar year basis. Therefore, royalties for our fiscal first quarter ending December 31 will be calculated at the highest royalty rate for the year, and royalties for our fiscal quarter ending March 31 will be calculated at 10%, our lowest royalty rate tier for the fiscal year.

The existing businesses and development programs for the foreseeable future.

For the financial details are available in our press release and will be available quarterly report on form 10-Q when filed.

I'd now like to turn the call back to the operator and open up the line for questions operator.

We will now open the call up for questions, we ask that you.

Please limit yourself to one or two questions before going back into the queue.

Many people as possible an opportunity to participate you ask a question you will need the press star one on your telephone.

Kind of your question press the pound key.

The standby, while we compile the Q&A roster.

Your first question is from Lori Buchanan with JMP Securities.

Hi, great nice quarter, thanks for taking the question.

So I guess wanted to start on Edp seven Q1, that's kind.

Struck with the debt.

Terrible activity I guess two weeks after the end of dosing you still five.

Paul J. Mellett: You can review our royalty tier schedule in our 2020 Form 10-K. Recently, Avri reported that their global HCV sales were $1.83 billion in 2020 and guided to $2 billion for global HCV sales in 2021. Moving on to our expenses, for the three months ended December 31, 2020, research and development expenses totaled $36.7 million, compared to $32.8 million for the same period in 2019. The increase was primarily due to the timing and activity of our clinical trials year over year. General and administrative expense for the quarter was $7.4 million, compared to $6.9 million for the same period in 2019.

Robust reductions in S antigen, I guess I'm curious if you know of any other small molecules that have shown.

Kind of durable effect of them in the mouse model and maybe if you could give any comments on what maybe explain the durable effect is it something to do with drug half life for the mechanism.

And then I'm wondering if you could give us any details about how.

You guys are approaching the potential for off target activity.

From this agent potentially on the host transcripts. Thanks.

Hi, Hi, Roy this is Jay so.

The the durability question I think.

I think I need to.

Hope you understand.

It wasn't a single dose and then monitor two weeks later it was dosed over a two week period.

The small molecule side.

The mix.

It makes more sense to you in terms of.

The responses that we've seen with the small molecule. So it has daily dosing.

Paul J. Mellett: This increase was primarily due to increased headcount and compensation expense. Enanta recorded an income tax benefit of $3.3 million for the three months ended December 31, 2020, compared to an income tax expense of $1.5 million for the same period in 2019. This income tax benefit is due to the company's pre-tax loss in the period, which can be carried back under the CARES Act of 2020. The net loss for the three months ended December 31, 2020 was $8.3 million, or a loss of $0.41 per diluted common share compared to net income of $13.4 million or $0.65 per diluted common share for the corresponding period in 2019, and at the end of the quarter, with $404.7 million in cash and marketable security.

All of its daily dosing that was over a 14 day period than it was compared to other People's 14 day data regardless of how they dosed.

So that's the first thing.

And.

You know comparing it to.

The other agents. So I think you may have seen the some of the data that we've shown it with regards to some of the <unk> is.

Out there or antisense oligos.

And.

71 performed very very well.

Stacked up quite well neither being.

As efficacious by law.

Log drop as.

Any of the agents and the more efficacious than almost all of them. So.

From that vantage point.

We are.

We're very excited about the the efficacy that we've seen so far and look forward to carrying it into the clinic.

There hasnt been of an extensive amount of preclinical work done.

Barbara logically mechanistically and looking at.

For all sorts of things from a field activity perspective and.

Paul J. Mellett: Enanta expects that its current cash, cash equivalents, and marketable securities, as well as its continuing royalty revenue, will be sufficient to meet the anticipated cash requirements of its existing businesses and development programs for the foreseeable future. Further financial details are available in our press release and will be available in our quarterly report on Form 10-Q when filed. I'd now like to turn the call back to the operator and open up the lines for questions. Operator?

We're quite pleased with the profile in terms of its specific targeting HBV.

<unk> versus others and.

And also with regards to its.

Safety profile pre clinically so.

Very very nice virology and very good pre.

Preclinical package.

And we're just sort of wrapping up.

The readiness to get ourselves into the clinic.

At year.

Okay, Great I'll hop back into queue. Thanks.

Thank you.

Your next question is from Yasmin Rahimi with Piper Sandler.

Operator: We will now open the call up for questions. We ask that you please limit yourself to one or two questions before going back into the queue so that as many people as possible have an opportunity to participate. To ask a question, you will need to press star 1 on your telephone.

Hi team. This is Rachel octane gasoline and thanks very much for taking your question.

So we have one question and then a follow up.

First can you provide us from color on the process and what you're looking for in the clinical candidate for your <unk> you Peter.

Unknown Speaker: Have a great weekend, pal. Hi, great. Nice quarter. Thanks for taking the question. So I guess I wanted to start on EDP721. I was kind of struck by the durable activity; I guess two weeks after the end of dosing, you still saw robust reductions in S-antigens. I guess I'm curious if you know of any other small molecules that have shown a kind of durable effect in the mouse model, and maybe if you could give any comments on what maybe explains the durable effect; is it something to do with drug half-life or the mechanism?

What's the significance of enhancing the elk advancing the al protein inhibitor and what advantages to the half over.

Thank you.

Yes, so the.

The process for identification is one that we're very familiar with.

Across lots of different viruses.

We we zeroed in on the polymerase the so called the al protein and <unk>.

<unk> got a drug discovery program.

Going in earnest actually quite some time ago.

Jay R. Luly: And then, I wonder if you could give us any details about how you guys are approaching the potential for off-target activity from this agent, potentially on the host transcripts. Thanks. Hi Roy, this is Jay.

And we we sort of weighted until we came up with.

Some very highly potent compounds that we thought were within striking distance of.

For the candidate and and then therefore announced the program this year and January of Jpmorgan.

I'd say, where we're sort of finishing the the.

Jay R. Luly: The durability question, I think I need to... Hope you understand. It wasn't a single dose and then monitored two weeks later. It was dosed over a two week period, you know, as a small molecule. So that probably makes more sense to you in terms of the responses that we've seen with a small molecule. So it is a daily dose. It's daily dosing. It was taken over a 14-day period.

The sort of final lead optimization looking at all of the different characteristics that make the drug candidate.

More than just the potent molecule for a lot of D. M. P K.

Work.

And the other viral logic work.

But we're getting we're getting reasonably close and I think it is one of the ones that we can add to our list of <unk>.

Ones that could hit this year.

With regards to advantage.

Jay R. Luly: It was compared to other people's 14-day data, you know, regardless of how they dosed. So that's the first thing, you know, comparing it to Now to other agents. I think you may have seen some of the data that we've shown with regard to some of the SIRNAs out there or antithetologos, and 721 performed very, very well. Transcripts provided by Transcription Outsourcing, LLC. Any of the agents and is more efficacious than almost all of them.

Not certain that there is an advantage of an L inhibitor over in the end I mean, we're very very pleased with the profile of 938 from the mechanism of <unk>.

The in protein targeting debt, we have with nine create has super high barrier to resistance and good activity across the.

You know the different types of the virus.

Performed exceptionally well clinically.

And so this is more about.

US looking at the.

The different and potentially complementary mechanisms.

Jay R. Luly: So from that vantage point, we're very excited about the efficacy that we've seen so far and look forward to carrying it into the clinic. I mean, there has been an extensive amount of preclinical work done, you know, virologically and mechanistically, looking at all sorts of things from a selectivity perspective, and we're quite pleased with the profile in terms of its specific targeting to HPV, RNAs versus others, and also with regard to its safety profile pre-clinically.

Just to you know again to be defining hopefully the.

The the best best.

The best in class across any different mechanism.

Some of it was the Atlanta can continue to sort of build a leadership position in not only RSV, but human respiratory virus right.

The Tories viral therapeutics.

More completely we also wonder and we've done preclinical studies looking at these different combinations of mechanisms and.

Jay R. Luly: Very, very nice virology and a very good preclinical package. And we're just sort of wrapping up, ready to get ourselves into the clinic mid-year. Okay, great. I'll hop back into queue.

It's clear that you know are.

N inhibitor plays well with other mechanisms and other mechanisms play well with inhibitors so whereas.

We may never need to do a combination.

Ah trial to demonstrate.

Unknown Speaker: Hi team, this is Rachel, Dr. Yasmeen, and thanks very much for taking our questions. So, we have one question and then a follow-up. First, can you provide us some color on the process and what you're looking for in the clinical candidate for your L-protein inhibitor? What's the significance of advancing the L-protein inhibitor and what advantages do they have over N-protein inhibitors?

Great.

More than adequate.

You can see we may want to.

And as much as it could.

Extend the treatment window, perhaps again, we don't know that for certain but each of the kinds of things that we'll be able to explore.

Extending the treatment window for opportunity to use therapeutics and maybe even.

Get a sense too.

Maybe even more challenging to treat patient populations of patients who are further along we may be able to reel them back in if we.

Jay R. Luly: Thank you. Yeah, so the process for identification is one that we're, you know, we're very familiar with across lots of different viruses. You know, we zeroed in on the polymerase, the so-called L protein, and got a drug discovery program going in earnest actually quite some time ago. And we, you know, we sort of waited until we came up with some very highly potent compounds that we thought were within striking distance of a candidate and then, therefore, announced the program this year in January at J.P. Morgan.

If we hit the virus with more than one mechanism. So these are the kinds of things that we're thinking about it.

Over time.

As we develop the sudden agents against several other viruses that we're targeting.

Yeah, we're really pleased to have.

John Devon Shinzo, joining the team at Atlanta.

He is the world.

Expert on lots of the stuff.

And he'll.

He'll be able to to fit in with a very accomplished team of investigators that we already have or really broaden and expand our thinking on how we go about this so.

Uh huh.

Hopefully that gets your question was that the follow up here or yeah yeah.

Yeah, I don't think of it does incredibly helpful.

Follow up is about the COVID-19 program.

Can you comment on which targets youre evaluating that you believe.

Jay R. Luly: I'd say we're, you know, sort of finishing the sort of final lead optimization, you know, looking at all the different characteristics that make a drug candidate more than just a potent molecule. So a lot of DMPK work and other, you know, virologic work. But, you know, we're getting reasonably close, and I think it is one of the ones that we can add to our list of ones that could hit this year.

Well prevent infection by.

Moving to protect us against like putting Marion Thank you.

Sure. Thanks for the question so we're.

So we said you know.

Pretty early going into this thing we.

We think about direct acting antivirals sensor.

The sort of go too.

Jay R. Luly: With regard to advantages, I'm not certain that there is an advantage of an L-inhibitor over an N. I mean, we're very, very pleased with the profile of 938 and the mechanism of the N-protein targeting that we have with 938.

Approach on a lot of these things, particularly with regards to human respiratory viruses.

You can look at entry of inhibitors, but.

We're just wondering if the entry inhibitors of entry of inhibitors alone.

We'll offer enough either of horsepower or flexibility to have the longer treatment duration. So instead, we're going after replication inhibitors.

Jay R. Luly: It has a super high barrier to resistance and good activity across the different types of the virus, and performed exceptionally well clinically. And so this is more about us looking at different and potentially complementary mechanisms. Just to, you know, again, to be defining the best in class across any different mechanism. So Enanta can continue to sort of build a leadership position, and not only for RSV but human respiratory viral therapeutics more completely. We also wonder, and we've done preclinical studies, you know, looking at these different combinations of mechanisms and it's clear that our N-inhibitor plays well with other mechanisms, and other mechanisms play well with N-inhibitors. So, we may never need to do a combination.

I think we're we're sort of taking the same sort of approach not only to RSV, but we're carrying the end too.

Sars Covid two so.

With that in mind.

We've stated publicly that the among the things we're thinking about.

Our protease inhibitors in preliminaries inhibitors. So that's a fair share of assumption of what we're targeting there and we think they are good.

Good approaches.

As of the the variance the spike protein variants that are starting to emerge.

Yeah and the.

We are in the community today.

Okay. That's really helpful. Thank you so much and congrats on the progress.

Thank you.

Your next question is from Brian <unk> with Baird.

Hey, good afternoon, guys. Thanks for taking the question Jay we talked before about sort of the almost esoteric nature of nucleoside chemistry and.

Jay R. Luly: Transcribed by https://otter.ai, extend the treatment window, perhaps, again, we don't know that for certain, but these are the kinds of things that we'll be able to explore. Extending the treatment window for opportunity to use therapeutics and maybe even getting us into, you know, maybe even more challenging-to-treat patient populations or patients who are, you know, further along, we may be able to reel them back in if we hit the virus with more than one mechanism.

I've kind of always thought of that small molecule RNA destabilization seems like an almost equally if not more complex chemistry. So so I guess can you help us think through the way in which you develop the small molecule as opposed to a target at all ago debt that can result in specific destabilization of HBV RNA without interrupting the arnie that might be critical for normal cellular.

Jay R. Luly: So, these are the kinds of things that we're thinking about over time. As we develop these and agents against several other viruses that we're targeting, you know, we're really pleased to have John DiVincenzo joining the team at Enanta. You know, he's a world expert on lots of this stuff, and, you know, he'll be able to fit in with a very accomplished team of investigators that we already have, will really broaden and expand our thinking on how we go about this. So, I think Hopefully, that answers your question. We've got the follow-up, too, or, yeah. Yeah, no, thank you.

Our processes and of person like did you actually know the end target or targets of this chemistry now was the primarily been an evolution of high throughput screening for chemicals that wind up the <unk>.

<unk> got the antigen and primary human hepatocytes.

Yes.

No. Thanks, Brian So we know the targets and the specific molecular targets that were going.

Going after.

For once there their specific enzymes that are focused on stable of stabilizing HBV Rnas.

And.

We've come up with very specific.

Unknown Speaker: That's incredibly helpful. So our follow-up question is about the COVID-19 program. Can you comment on which targets you're evaluating that you believe will be protected against spike protein variants? Thank you.

Inhibitors of the east.

Times for the debt or not only good at inhibiting.

The enzymes, but inhibiting the enzyme in the context of hepatitis b infection. So.

Jay R. Luly: Thanks for the question. So we said, you know, pretty early going into this thing, we think about direct-acting antivirals as our sort of go-to approach on a lot of these things, particularly with regard to human respiratory viruses. You can look at entry inhibitors, but, you know, we're just wondering if entry inhibitors or entry inhibitors alone will offer enough either horsepower or flexibility to have a longer treatment duration.

It was not through a high throughput screen.

Great. Thanks for that that's really helpful.

You're welcome.

Your next question is from Brian Abrahams with RBC capital markets.

Hey, guys. Thank you for taking my questions and congrats on all of the progress I guess, one on Nash and just the then just a quick follow up.

I'm curious if you can speak to.

On your views.

Following the Fda's recent workshop on Nash drug development in the context of the specifics for the most advanced.

Jay R. Luly: So instead, we're going after replication inhibitors, and I think we're sort of taking the same sort of approach, not only to RSV, but we're carrying it into SARS-CoV-2. So with that in mind, we've stated publicly that among the things we're thinking about are protease inhibitors and polymerase. So that's a fair assumption of what we're targeting there. And we think they'

<unk> just wondering how that how that may shape, your plans and what you might be looking for a mid year from the three of five and 297.

The studies and then just as a follow up separately on the.

The Sars.

Sars Covid two inhibitor just wonder if you could talk a little bit more about potential timelines there for both the preclinical variant data and clinical entry and I guess would be would it be fair to say that once that gets into the clinic there could be of potential expedited regulatory path.

Jay R. Luly: Good approaches vis-a-vis the spike protein variants that are starting to emerge, you know, in the in the community today. Great, that's really helpful. Thank you so much and congrats on your progress.

Unknown Speaker: Hey, good afternoon, guys. Thanks for taking the question. Jay, we've talked before about the sort of almost esoteric nature of nucleoside chemistry. And, you know, I've kind of always thought that small molecule RNA destabilization seems like an almost equally, if not more complex, chemistry.

Yes so.

Starting with the Sars Covid two.

The first.

The again, where.

We're working with very very potent molecules right now that we're sort of the Apple polishing into.

Candidates.

Unfortunately with that process sort of can't legislate.

When you get to the finish line.

Unknown Speaker: So, I guess, you know, can you help us think through the way in which you develop a small molecule as opposed to a targeted oligo that can result in specific destabilization of HPV RNA without interrupting RNA that might be critical for normal cellular processes in a person? Like, do you actually know the end target or targets of this chemistry now, or has this primarily been an evolution of high throughput screening for chemicals that wind up? Stabilizing S Antigen in Primary Human Hepatocytes

Iterative and sometimes it's two steps forward, one step back but I I.

Appeal.

Confident enough.

When you line up.

The three programs you know the L inhibitor for RSP, the human met of Pneumo virus.

And also the.

The targets for Sars Covid, two they're all contenders for.

Candidates are this.

This year and hopefully we will harvest.

Harvests two of them in <unk>.

Of my list would actually be the Sars COVID-19 two so.

Jay R. Luly: Thanks. Yeah, we know... Thanks, Brian. So, we know the targets, and there are specific molecular targets that we're going after. There are ones, there are specific enzymes that are focused on stabilizing HPV RNAs. And we've come up with very specific inhibitors of these enzymes that are not only good at inhibiting the enzymes, but inhibiting the enzymes in the context of hepatitis B infection. So it was not through a high-throughput screen.

Depending upon when we get that.

We'll have to finish certain other R&D, enabling studies before we can get at the end of the clinic.

So the sooner that we can make the final candidate selection and nomination.

Probably be three quarters or so before we could go out of the clinic I think theres every.

Since the <unk>.

New administration is.

Looking at.

Covid is being more than just a vaccination sort of.

Unknown Speaker: Great. Thanks, Jay. That's really helpful. Hey guys.

Approach you know I think therapeutics are getting.

Unknown Speaker: Thank you for taking my questions and congrats on all the progress. I guess one on NASH and then just a quick follow-up. I'm curious if you could speak to your views following the FDA's recent workshop on NASH drug development in the context of the setbacks for the most advanced FXR. Just wondering how that may shape your plans and what you might be looking for mid-year from the 305 and 297 studies. And then, separately on the SARS-CoV-2 inhibitor, just wondering if you could talk a little bit more about potential timelines there for both the preclinical variant data and clinical entry. And I guess would it be fair to say that once that gets into the clinic, there could be a potential expedited regulatory path? Thanks.

Highlighted extensively and.

Could there be.

Some are very constructive dialog with regulators I think the answer could be yes, obviously you know.

You need to get there and pull pull the age of forward and get it into the clinic, but I I.

I would be very hopeful that the.

The.

You would get a lot of receptivity.

The interaction with the FDA to.

You know it helped design studies that could could.

Good things to patients as soon as possible.

With regards to.

To Nash I think Theres no impact.

Sort of on our progress in how were thinking around our current phase two <unk> study or a study design elements.

The FDA highlighted the importance of histology readout.

As an endpoint.

Until.

Jay R. Luly: Yeah, so, you know, starting with the SARS-CoV-2 virus, First, you know, the again, we're working with very, very potent molecules right now that we're sort of polishing into candidates. Unfortunately, with that process, you sort of can't legislate when you get to the finish line. It's iterative, and sometimes it's two steps forward and one step back. But I feel, you know, confident enough that when you line up the three programs, you know, the L-inhibitor for RSV, the human metapneumovirus, and also the targets for SARS-CoV-2, they're all contenders for candidates this year, and hopefully, we'll harvest them.

Non invasive biomarkers are.

Further validated I think that was one of the key points.

And the safety is also a key and chronic treatment.

So therefore, the need for long term follow up post conditional approval sort of thing.

But at this point, we don't really feel that there's any modification to our current plan.

Plan is two two.

To get.

Key information and data set in.

In mid 'twenty, one and.

How all of the day to hang together prioritize our Nash.

Portfolio and as we've said all along ideally identify.

Potential doses ex.

The dishes the.

Around three of five that could be.

Utilized in combinations.

Jay R. Luly: [inaudible] You know, so the sooner that we can make that final candidate selection and nomination, probably three quarters or so before you could go out of the clinic. I think there's every sense that, you know, the new administration is looking at COVID as being more than just a vaccination sort of approach. You know, I think therapeutics are getting highlighted extensively, and there could be some very constructive dialogue with regulators. I think the answer, you know, could be yes. Obviously, you need to get there and pull the agent forward and get him into the clinic. But I...

Through the partnership so.

That's still a plan a and one that we're continuing to execute very well in line.

Got it that's really helpful. Thanks for all of the color Jay.

Oh, you're welcome.

Again, ladies and gentlemen that of Star one of you would like to ask a question at this time.

Your next question is from Jay Olson with Oppenheimer.

Oh, Hey, thanks for taking the question.

For your Sars Covid two program once you move that.

Small molecule direct acting anti viral into the clinic.

Do you plan to seek out of partner to expedite the clinical development and ultimately manufacturing and distribution and commercialization of that drug or is that something you envision doing independently and then I guess more broadly.

Jay R. Luly: I would be very hopeful that you would get a lot of receptivity and interaction with the FDA to help design studies that could, could, you know, get things to patients as soon as possible. With regard to Nash, I think there's no impact on our progress and how we're thinking around our current phase 2, 2B study or study design elements. The FDA highlighted the importance of histology readout as an endpoint until non-invasive biomarkers are further validated. I think that was one of the key points.

On the business development front now that you have.

The increased your teams.

The team's capabilities and business development and given your cash position.

What do you plan.

Or where do you envision this year in terms of your business development objectives. Thank you.

Yes so.

With regards to Sars Covid, two I I think atlanta's pretty.

Pretty well situated as a small company.

Again this isn't the car first respiratory virus.

And one of the ways that we're thinking about this from the way to be really successful with the Sars Covid two therapeutic.

Jay R. Luly: And safety is also key in chronic treatment, you know, so there is the need for long-term follow-up post-conditional approval sort of thing. But at this point, we don't really feel that there's any modification to our current plan. You know, our plan is to get key information and data sets in mid-21 and look at how all the data hang together, prioritize our NASH portfolio, and as we've said all along, ideally, identify potential doses expeditiously, around 305 that could be utilized in combinations, likely through partnerships. So that's still plan A and one that we're continuing to execute very well. Got it. That's really helpful. Thanks for all the color, Jay.

In the in the longer term.

Is to have something that's very safe and very oral.

Or was it safe in the Laurel.

You know of such that you could you could almost think about it in the context of.

I'd like an RSVP study, where you have otherwise healthy.

Patient shows up.

To the Doctor's office with respiratory sometimes hopefully not terribly far advanced get.

<unk> are probably coming with the policy you know positive test results. The maybe it's the nascent symptomatic person who just as it was.

Unknown Speaker: Welcome. Oh hey, thanks for taking the question. For your SARS-CoV-2 program, once you move that small molecule, direct-acting antiviral, into the clinic... Do you plan to seek out a partner to expedite the clinical development and ultimately manufacturing, distribution, and commercialization of that drug, or is that something you anticipate doing independently? And then, I guess, more broadly on the business development front, now that you've increased your team's capabilities in business development, and given your cash position, what do you plan to do?

Part of some employee protocol or other wise gets task of test positive and they may be asymptomatic user of perfect candidates too.

To receive.

Direct acting anti viral hopefully jump on the virus quickly with several days of dosing of knocked that viral load down stop the shutting of the Scott.

The break the chain of Transmissibility.

Well you get the person recovering at home.

Quickly and being tested negative.

Very quickly in an otherwise back to gainful employment or school or whatever the case may be so.

Jay R. Luly: What do you envisage this year in terms of your business development objectives? Yeah, so, with regard to SARS-CoV-2, I think Enanta is pretty well situated as a small company. Again, this isn't our first respiratory virus. And, you know, one of the ways that we're thinking about this and the way to be, you know, really successful with SARS-CoV-2 therapeutics in the longer term is to have something that's very safe and very oral, or very safe and oral, such that you could, you could almost think about it in the context of like an RSVP study, you know, where otherwise healthy outpatients But maybe it's an asymptomatic person who just is part of some employee protocol or otherwise gets tested, tests positive, and may be asymptomatic.

We're no stranger to this.

Setting up that kind of of study running that study in fact, a lot of the sites that we have around the globe could be candidates to run those kinds of studies. So I think were you know.

We will have good insights in terms of how to how the jump in.

Ultimately.

If we have a very.

The very big product candidate of course, we'll have to look and think about.

You know can we maximize it.

Completely ourselves or do we need to seek a partner I think we've got a while to.

The sort of sort that out well, we'll be watching to see.

What gaps in vaccinations there are.

And.

And look at that.

Longer term as we would with any of our.

Programs, but it's just it's very nice to.

To tuck that in.

Into our broader portfolio, where we have multiple different RSP assets, but not of pneumo of another.

The significant one and then Sars COVID-19 two dovetails perfectly in terms of the building.

Very comprehensive.

Human respiratory virus therapeutics.

Jay R. Luly: These are perfect candidates to receive, you know, a direct acting antiviral, hopefully, jump on the virus quickly with just several days of dosing and knock that viral load down, stop the shedding, stop the, you know, break the chain of transmissibility, get the person recovering at home quickly and being tested negative, you know, very quickly, and otherwise back to gainful employment or school or whatever the case may be. So, you know, we're no stranger to... [inaudible] a very big product candidate, of course, we'll have to look at and think about, you know, can we maximize it? And, you know, I think, you know, we're not going to be completely ourselves, or do we need to seek a partner?

The franchise, if you will so.

Yeah.

First things first we'll get the candidate and demonstrate what we need to demonstrate but.

I think we've got a pretty clear.

Instead of a of.

Thoughts and an approach that we would take.

On the BD front, we did hire.

Brendan Lou you know we've.

Get asked on almost every one of these calls.

You know what are you thinking about the business development.

How are you thinking about RSV or HBV or for Nash.

And you know, we've always said debt.

You know Nash falls into that category of probably being bigger.

Bigger than we are ultimately on a global basis, particularly in as much as the combinations are going to end up being.

Jay R. Luly: I think we've got a while to sort that out. We'll be watching to see, you know, what gaps in vaccinations there are. And look at that, you know, longer term, as we would with any of our programs. But it's just, it's very nice to, to tuck that in into a broader portfolio where we have, you know, multiple different RSV assets, human metanumo, another significant one, and then SARS-CoV-2 dovetails perfectly in terms of building. You know, a very comprehensive Unknown Speaker... Human Respiratory Virus Therapeutics Franchise, if you will. So, first things first, we'll get the candidate and demonstrate what we need to demonstrate.

Very very important so.

I think.

As we've guided along the way of.

Oregon to a big piece of that was understanding what 12 week data look like.

The connection with argon one.

Data to allow for potential combinations more quickly and again, we're looking toward.

Yeah mid year to get that understanding.

You know already we know from argon one that the one milligram dose.

It looks pretty interesting are two and a half milligrams gave us intercept like pruritus.

The Oregon to we'll look at a couple of other doses to see if there's the dose above of milligram.

You know the kids gives good.

A good balance there in terms of targeting.

Jay R. Luly: But I think we've got a pretty clear set of... [inaudible] NASH falls into that category of probably being, you know, bigger than we are, ultimately, on a global basis, particularly in as much as combinations are going to end up being, you know, very, very important. So I think, you know, as we've guided along the way, ARGON2, a big piece of that is understanding what 12-week data look like in connection with ARGON1 data to allow for potential combinations more quickly.

Target engagement and Tolerability of the use of the things that will readily be able to to sort of understand the move on sorry, I would say.

Nothing's changed in that regard.

The Nash is an important one probably nearer term and that we would aim to try to team up prior to.

In the phase III work and maybe.

Sooner.

And and then the other things are on the sort of of spectrum I think HPV.

We've got a portfolio of.

Kind of said.

You know the starting to build and we had we started well everyone sort of has a nuke because of the background therapy out there that patients are on is the standard of their standard of care in there or the.

There are becoming cheap and ultimately generic here soon so.

Jay R. Luly: And again, we're looking toward, you know, mid-year to get that understanding. You know, already we know from ARGON1 that the one milligram dose looks pretty interesting. So Argonne 2, we'll look at a couple of other doses to see if there's a dose above a milligram that gives a good balance there in terms of target engagement and tolerability. These are the things that we'll readily be able to sort of understand and move on.

You have that is of great sort of the base.

Your line of therapy that you can start adding other agents on sort of five one for.

Obviously as our first combination study with the Nuc and we'll have data on that next quarter, but were hopeful that 721 could be you know of <unk>.

The piece in the missing link of creating on the all oral.

The triple.

Coming up with something that does affect.

Pension and.

Jay R. Luly: So I would say nothing's changed in that regard. You know, NASH is an important one, probably in the near term, and we would aim to try to team up prior to, you know, any phase three work and maybe, you know, sooner. And then the other things are on sort of a spectrum.

In addition to a couple of.

Things that knocked down DNA, and RNA and and do other things Mechanistically, adding 721 now could allow us to create an all oral triple now how far we progressed that remains to be seen I think we want to try to.

Jay R. Luly: I think HPV, you know, we've got a portfolio of... [inaudible] Lyme Therapy that you can start adding other agents to. So 514 obviously is our first combination study with Anouk, and we'll update on that next quarter. But we're hopeful that 721 could be a key piece in the missing link of creating an all oral triple, coming up with something that does affect SNN. And in addition to a couple of..., youtube.com, To put that forward as an all-world triple combination, you know, maybe we seek other things that we might ultimately add to that or, you know, so that would be among the possibilities.

To put that forward as the ethanol world Triple combination you know maybe we.

We seek other things that we might ultimately add to that or.

So that would be among the possibilities, but if you if you run it further out.

I think hep b ultimately it will be like Hep C.

Where.

If you really want to maximize the and you want to you know.

Cure millions of millions of people.

On a global basis, especially we're happy is.

Predominantly ex U S. When you look at it.

I think we would definitely have a global partner now would we.

Some point tried to.

<unk> retained the the possibility of a co commercialization, we have that option with abbvie, even in the Hep C days, we didn't exercise of the at the time, we needed the exercise of the because it didn't make sense for us as the company, but so we would think about that.

Jay R. Luly: But if you run it further out, I think hep B ultimately will be like hep C where if you really want to maximize it and you want to, you know, cure millions and millions of people on a global basis, especially where hep B is predominantly ex-U.S. when you look at it. I think we would definitely have a global partner.

You know as the the time kind of came.

Where are we in terms of thinking about the commercial.

The infrastructure around Hep B, we've got a while too.

Sort that out but in the meantime, we're I think I'm asking a very nice.

Jay R. Luly: Now, would we, you know, at some point try to..., you know, retain the possibility of co-commercialization? We had that option with AbbVie even in the Hep-C days. We didn't exercise it at the time we needed to exercise it because it didn't make sense for us as a company.

Set of assets, one that we can control.

One that may lead to a functional cure that's all oral.

And then you know RSV is the broader you know human respiratory viruses is something that we're not looking to do a.

Jay R. Luly: But, you know, so we would think about that. You know, as the time came, where were we in terms of thinking about a commercial infrastructure around hep B? We had a while, you know, to sort that out.

Our global <unk>.

<unk> ship on any any time soon maybe if ever will.

We'll have to see how that goes that may be the one that we can prosecute ourselves.

Yeah on the RFP front, where single agent 93, eight maybe all you need and.

Jay R. Luly: But in the meantime, we're amassing a very nice set of assets, one that we can control, and one that may lead to a functional cure that's all oral. And then, you know, RSV is a broader, you know, human respiratory virus. This is something that we're not looking to do a... You know, a global partnership on any time soon, maybe if ever, you know, we'll have to see how that goes.

We have the opportunity to.

To be the first or one of the early.

Drugs to market and that in that indication the first.

The first ever treatment, if you will.

So I believe him down kind of in the net order of priority and then what the.

The start to explore.

Thank you for the Super helpful. I appreciate the details.

Youre welcome.

Yeah.

Your next question is from Lisa.

Jay R. Luly: That may be one that we can prosecute ourselves, especially on the RSV front, where single agent 938 may be all you need. And we have the opportunity to, you know, be the first or one of the early drugs to market in that indication, the first ever treatment, if you will. So I'd lay them down kind of in that order of priority, and then we'll just start to explore. Thank you, that's super helpful.

For our core ISI.

Hi, Thanks for taking my question.

The RNA Destabilizer can you talk about.

One of the preclinical tox workup that you've done so far I know, it's a really interesting and exciting molecule and I agree it can be a really important.

Contributed here to getting towards that goal.

You know an all oral functional cure for happy at the same time, we've seen another a number of companies.

The they've had some issues with their program. So hopefully the trend at the middle there. So just curious about your preclinical Tox Inc.

Unknown Speaker: I appreciate the details. You're welcome. Hi, thanks for taking the question. About your RNA destabilizer, can you talk about sort of the preclinical trial workup that you've done so far? I know it's a really interesting and exciting molecule, and I agree it can be a really important contributor to getting towards that goal of, you know, an all-oral functional cure for Hep B. But at the same time, we've seen another number of companies that have had some issues with their programs. So hopefully, you've threaded the needle there.

Sure Yes, so thanks for the question Lisa.

The others have.

Tried to do this and haven't always been able to progress there the programs.

And so you know as we.

No we were working on this program actually for years.

You know optimizing the molecules coming up with ones that were exquisitely potent had.

Very very nice drug like properties and importantly safe.

Safety I mean, we usually don't.

Talk a lot about preclinical safety, because it's an enabler to get you to the the <unk>.

Jay R. Luly: So just curious about your preclinical talk. Sure. Yeah, so thanks for the question. I mean, others have tried to do this and haven't always been able to progress their programs.

The clinical data, but.

We've done a very extensive work up and have gone through.

13 week talks and the multiple species so.

Jay R. Luly: And so, you know, as we have been working on this program for years. [inaudible] by every measure that we've looked at it from a virologic perspective, from a DMPK, and also from a safety perspective. A very, very nice small one.

The the molecule looks incredibly good.

By every measure that we've looked at it from of Virological perspective from us from.

The D M PK and also from a safety perspective.

The very very nice molecule.

Unknown Speaker: Can you talk about your preclinical talks, sort of species and duration, how much coverage you have now in terms of moving into clinical development? Can you dose for? You know, a month, three months, what's your coverage?

Can you talk about how many of you pretty kind of other types of species and duration of how much coverage do you have now in terms of moving into.

And also the development can you dose for.

You know.

The three months, let's share coverage at this point.

Jay R. Luly: Oh, we have 13 weeks. So we've got three months of coverage with regard to that. Okay, great. I mean, obviously, we're going to go into a shorter term phase one won't be three months of study and healthy volunteers, but we've got ample talk coverage. Great. Okay, good. And do you mind saying what species you've presented?

Oh, we have 13 weeks so we've got three months.

Coverage with regards to that.

Okay, Great I mean, obviously, we're going to go into a shorter term you know phase one will be phase one won't be three of three months study in healthy volunteers, but we've got amp.

Ample tox coverage.

Right Okay. Good.

And do you mind, the saying that species means the battle.

Again typically these are details that we just don't.

Jay R. Luly: Again, typically, these are details that we just don't, you know, get into, but they're You have to line them up with your metabolites, and you have to line them up with where you make sure you cover all your metabolites. Any metabolites have to be covered in your toxicology program as well. So those selections were made by a combination of, you know, the DMPK and the safety team at Enanta, but they were the appropriate ones for this molecule to go safely into. Okay. And then you were a little vague on the expectations for the RSVP. Are you still targeting some kind of goal this year? Or do you think that's something, you know, that you think is more likely next year?

Get into but.

There.

You have to line them up with your metabolites in the App and the line them up with where.

Where you are.

Make sure you cover all your any of any metabolites have to be covered in your of your toxicology program as well so those selections for me.

Made by a combination of.

The D in PK and safety team kind of an answer but it's the appropriate ones that were for this molecule to go safely into the human.

Okay and then.

For the big on expectations for our SVP of you're still targeting kind of this year or do you think thats something.

On the E. You think it's more likely next year I'm just trying to.

Jay R. Luly: I'm just trying to set expectations for myself. No, it's not. We're not expecting it this year.

That expect kind of <unk> and myself no it's not at the we're.

We're not expecting it this year and as we.

Jay R. Luly: And as we pointed out a few weeks ago at J.P. Morgan, and people can, you know, you can go look at this, and there's articles in the papers all the time, you know, there's been no influenza this year. And I mean, normally, that's a good thing unless you're trying to recruit for a study like RSVP, but I don't want to wish RSV on anyone, but if anyone gets it, I'm happy to treat them.

As we pointed out a few.

Few weeks ago of J P. Morgan and people can you know you can go look at the news articles from the papers all the time you know theres been no influenza this year.

And the.

And I mean, I guess normally that's the good thing unless you're trying to recruit for a study like ours the P. But.

I don't want a wish.

RSV on anyone but if anyone gets it I'm happy to treat them.

Jay R. Luly: So they, and RSV is pretty much, Parallel in Flu. If you look at the map on the CDC website for flu, it's basically all green. There's not even a light shade of green, except for in four states, I think.

So they are and of our.

RSV is pretty much.

It's paralleling the flu. It's if you look at the map on the CDC website for flu, it's basically all green it's not even.

A light shade of green, except for in four states I think so it's.

Jay R. Luly: So it's, But it's basically a flatlined case. So it's, it's not something I mean, again, pandemic not withstanding, I think we were on a good trajectory based on, you know, our readiness. But, but that part's, you know, not likely to happen, or at least not likely to happen in a normal season. I think one of the things that was really interesting was that report we saw a few weeks ago out of Australia, where, you know, they let their guard down for just a little bit, you know, because it's summer down there, and all of a sudden, they saw this massive spike in RSV infections, and it Unknown Speaker Bigger than most spikes, and it happened in their summer, which is out of phase.

But it's basically flatlined cases, so it's a it's not something I mean again pandemic notwithstanding I think we were on the on a good trajectory based on you know of.

Our readiness, but but.

But that parts.

No.

Not likely to happen or at least not likely to happen and then and the normal season I think one of the things that was really interesting was that a.

Net report, we saw a few weeks ago out of Australia.

Were.

They they let the guard down for just a little bit you know because its summer down there and all of the suddenly saw this massive spike in RSV infections and it was a big spike.

Bigger than most spikes and it happened in the summertime, which is out of state. So it's sort of pie out of phase with the the normal season and.

Jay R. Luly: So it's sort of out of phase with the normal season. And so when you think about those kinds of considerations, I'm not sure there's a real clear rulebook for what happens when COVID mitigation strategies start to subside. And I think one thing that I can tell you that people are beginning to worry about is whether there could be, on the other side of the COVID pandemic, epidemic levels of influenza and RSV.

So when you think about those kinds of considerations I'm not sure there's a real clear rulebook.

For what happens when when Covid mitigation strategies start to.

Subside and.

One thing that I can tell you that people are beginning to worry about is could there be on the other side of the COVID-19 pandemic could there be epidemic levels of influenza and RSV. When people are worrying about the particularly in children, where you rely on.

Jay R. Luly: And people are worrying about that, particularly in children where you rely on the first year of birth to build up a little bit of immunity by exposure once or more than once. And then your second year of life, you build it up a little more. And then your third year, you have a little more.

<unk>.

The first year of birth to build up of a little bit of of immunity by you know.

What the exposures once for more than once and then your second year of life you build it up a little more of the third year you have a little more eventually kids start to shake These RSV infections for a little while and then they're they're protected for a day.

Jay R. Luly: Eventually, kids start to shake these RSV infections for a little while, and then they're protected for a bit of time. But now, you know, last year and into this year, every kid that was, you know, less than one year old probably didn't get an RSV infection. And the kids who were between one and two years old didn't get them either.

Out of time.

But now you know last year and into this year every kid that was less than one year old probably you didn't get an RSV infection. The the the kids who were between one and two years old didn't get them in the the people of the kids who were two to three didn't get them and so your break.

This chain of the immunity.

And.

Jay R. Luly: And the kids who were two to three didn't get them, and so you're breaking this chain of immunity. And, you know, ultimately, that can lead to, you know, some really unexpected, unprecedented levels. So we'll have to see how that all shakes out. But it could be a very different season on the other side of some of this. So we'll just, you know, as we said on today's call, we're just, We'll just update our guidance when we see the RSV prevalence kick up again. Okay, but it won't be this year. It's unlikely to be this year.

Ultimately that can lead to.

Some of some really unexpected unprecedented.

The level, so we'll have to see how that all shakes down but.

But the it could be a very different season on the on the other side of some of this so we're just you know.

As we said.

On today's call we're just.

We will just update our guidance when when we see the RSV prevalent kicking up again.

Okay, but it wont be this year.

It's unlikely to be this year.

Alright, okay. Thanks, a lot.

Yep you're welcome.

Your next question is from Eric Joseph with JP Morgan.

Hi, good evening, Thanks for taking the question just a couple of Nash.

You alluded a little bit to it earlier, but I'm just wondering if you could clarify which endpoints will be of.

Unknown Speaker: All right. Okay. Thanks a lot. Yep, you're welcome. Hi, good evening. Thanks for taking the question. There are just a couple in Nash.

The reporting out in the 12 week interim analysis for the argon two.

We're looking at.

ALC in fat fraction as well as the safety of particular pruritus and then as we think about the phase one data with 297.

Unknown Speaker: You alluded a little bit to it earlier, but I'm just wondering if you could clarify which endpoints you'll be reporting out in the 12-week interim analysis for Argon 2. We'll be looking at ALT and fat fraction as well as safety, particularly arthritis. And then as we think about the Phase 1 data for 297, we know that safety and healthy volunteers have been a little under-informative in the past. Is there a particular data point or a couple of data points that you'd be newly focused on that might better characterize or de-risk the safety profile of NASH subjects compared with the 305 experience? Thanks.

We know that.

The safety of healthy volunteers has been a little under formative in the past is there a particular data point as couple of the appointment of UV.

The newly focused on that might better characterize as the rest of the safety profile of the Nash subjects compared with the three of five experience. Thanks.

So.

I'll answer the first question hopefully very clearly because the you know of 10 of our slide deck and and.

And we are.

Some of our call and we sort of.

Starting this year.

At the at the at the J P. Morgan conference. The argon two interim analysis is an internal read only.

It will not be reported out.

It will not be reported out.

So this is something that the.

There's somebody of the DSM b and and.

Jay R. Luly: Yeah, so, I'll answer the first question, hopefully, very clearly because, you know, it's on our slide deck and it's on our call, and we started this year at the J.P. Morgan Conference. The Argonne II interim analysis is an internal read only, so it will not be reported out. So, this is something that only the DSMB and key people who are not involved in the conduct of the study will be able to, you know, take a peek at some of the information again in order to make dose selection determinations for potential combinations and compare that to Argon 1 data.

A key people who are not involved in the conduct of the study.

We will be able to take.

Take a peek at some of the information.

Again in order to make.

Dose selection determinations for potential combinations and comparing that to argon one data, it's really for that purpose.

And if.

We'd have to power the study in a different way if we were gonna be reporting that data out because we would be spending alpha and that's something we certainly don't want to do on the Oregon toothpaste, So that'll be informational will get the information.

Asian as it relates to prioritization of the assets in the doses.

And really defining for US you know the go forward strategy for.

Jay R. Luly: It's really for that purpose, and if, you know, we'd have to power the study in a different way if we were going to be reporting that data out, because we would be spending alpha, and that's something we certainly don't want to do on the Argon 2 study, so it'll be informational. We'll get information as it relates to prioritization of assets and doses and really define for us, you know, the go forward strategy for Nash, quote at large, at Enanta, so that's what it is.

For Nash quote at large.

So that's what it is but we will you know I'm just so you know it'll be looking we'll be looking at things.

Like Oh target engagement.

You know things like see for in F 2019, our fat.

Fat.

These are the kinds of things that we looked at and the.

Argon, one and we have a you know a.

Very clear dataset at one milligram of <unk>, two and half of milligrams. All we're gonna be doing I'm, just trying to understand on a subset of argon two patients out of.

The parameters look at two new doses of 1.5 and two milligrams.

Jay R. Luly: But we will, you know, just so you know, we'll be looking at things like, you know, target engagement, things like C4 and FGF19, FAT. These are the kinds of things that we looked at in Argon1.

Pure and simple.

The 297 trial on the other hand is the.

The study in healthy <unk> and.

It's.

One of the things that we also know well by having studied three of five in healthy So and you may recall you know we looked at.

Jay R. Luly: And we have a, you know, a very clear data set at one milligram and two and a half milligrams. All we're going to be doing is trying to understand, in a subset of Argon2 patients, how those parameters look at two new doses, 1.5 and 2. The 297 trial, on the other hand, is a study in healthy people, and, um, It's, it's one of the things that we also know well by having studied 305 and healthy. So, and you may recall, you know, we looked at SAD, single sending dose, and we looked at multiple sending doses in healthies. And then we redid the MAD alongside in presumed NAFLD subjects.

S.

The single ascending dose and we looked at multiple ascending dose in healthy and then we rebid the M. A D alongside.

The presumed in applebee's subjects.

Just so we can try to get a bead on what a bona fide Nash patient might look like to see does the drug do anything different to that patient population or does that patient population do anything different to the drug.

And it turned out it was on the one hand uninformative or no there wasn't.

So I'd say that the.

The presumed applebee's behave very similar to the healthy volunteers.

Jay R. Luly: Just so we could try to get a bead on, you know, what a bona fide NASH patient might look like to see if the drug does anything different in that patient population, or does that patient population do anything different to the drug? And it turned out it was, on the one hand, uninformative, or it wasn't.

And so but what we did learn was when you dose two we're watching the dose escalation. So as we went from what.

Remember.

All of the dose that you go from five to one to two and a half of the five to 10 to 20 milligrams.

As we as we doubled the dose.

Jay R. Luly: The presumed NAPLDs behave very similar to the healthy volunteers. And so, but what we did learn was when you dose to, we were watching, you know, dose escalation. So as we went from, I remember, all the doses, you go from 0.5 to 1 to 2.5 to 5 to 10 to 20 milligrams.

Escalating we saw.

You know these type of target biomarker changes and so forth.

With or without pruritus, all the way up until we got to 20 milligrams in healthy is where we saw a lot of pruritus unexpectedly, but we saw it and so we knew kind of how to how to handicap that you know we can figure out the dose of the exposures.

Jay R. Luly: As we doubled the dose escalating, we saw, you know, these target biomarker changes and so forth, with or without pruritus, all the way up until we got to 20 milligrams in healthyies, where we saw a lot of pruritus, unexpectedly, but we saw it. And so we knew kind of how to handicap that. You know, we could figure out the dose and the exposures that caused caritis, and we could go backward, downward from that to find the doses that gave us, you know, target engagement.

Debt caused chloride us and we could we could go backwards downward from that defined the doses that gave US you know targeting.

Target engagement and I'm, sorry, I think one of the the things here when we overlay of new dataset like on the 297, which has some other design elements Senate and three of five did.

But when we lay that data set over the three of five dataset.

Have basically you know of.

Good a good level of information to understand you know did we do something different.

Jay R. Luly: And so I think one of the things here, when we overlay a new data set, like on 297, which has some other design elements in it than 305 did, but when we lay that data set over the 305 data set, you know, we'll have basically, you know, a good level of information to understand, you know, did we do something different? You know, is this a product?

Is this the product.

The opportunity that has differentiation.

And beyond the three of five or is it just like a super Super potent three of five.

We hope it will be.

Differentiated we designed it to have certain elements of that could lead to that but the reality is you Gotta go in there and run that study and when we get that data set.

Think we will be able to compare it to.

Two.

Jay R. Luly: Uh, opportunity that has differentiation, you know, above and beyond 305 or is it just like a super, super potent 305? We hope it will be differentiated. We designed it to have certain elements that could lead to that. But the reality is you gotta go in there and run that study. And when we get that data set, I think we'll be able to compare it to our 305 data set and really understand how it..., how it all hangs together. So I think we will recognize improvement if it's there. Okay. Okay. Thanks for taking the question. You're welcome.

Two or three of five dataset and really understand you know how.

Howard.

Howard.

How it all hangs together so.

I think we will recognize improvement if it's there.

Okay. Okay. Thanks for taking the questions.

Youre welcome.

Your next question is from Zacks.

Roth capital partners.

Okay. Thanks for taking my question it looks like you have multiple.

And in 'twenty and 'twenty, one for that I just wanted some additional clarity on the HBV that out that's fine and then the second point.

Yeah.

What we've seen with assembly of just kind of line even know how you are setting up occasionally that day.

Yeah. So.

The data set so we're expecting to two datasets.

No one will come from.

Unknown Speaker: Right guys, thanks for taking my question. Looks like you have multiple milestones in 2021. So that's good. Just wanted some additional clarity on the HPV data that's going to come out in the second quarter of this year. You know, with what we've seen with assembly, just kind of wanted to know, how are you setting expectations as we head into that? Yeah, so the data sets. We're expecting two data sets. You know, one will come from 514 that's added on top of a NUC, and the other one will be 514 on the backdrop of patients that haven't received any nuke therapy. So they're more viremic at that higher viral load. So one population will have very low viral loads, and the other one will have higher viral loads.

Five one for that's added on top of the.

Of a nuke.

And the other one will be five one for in the backdrop of of patients that.

I haven't received any any nuc therapy. So there I remember they've got higher of viral load. So one one population will have a.

Very low viral loads. The other one will have higher viral loads. So.

And the study you know with regards to the nuke, it's gonna be a lot of it's going to be about safety and tolerability and how the two molecules play well together over a 28 day period, you're not likely to get a lot of information about.

You know virology.

And the patient population over that time period, because theyre already reasonably suppressing some of the 28 day. So you wouldn't expect to see some of the viral antigens, if they were to ever move.

Jay R. Luly: So in the study with regard to the nuke, a lot of it's gonna be about safety and tolerability and how the two molecules play well together over a 28-day period. You're not likely to get a lot of information about virology in that patient population over that time period because they're already reasonably suppressed, and it's only 28 days. So you wouldn't expect to see some of the viral antigens if they were to ever move on that.

To be typically the moving on that so it's it's a it's one kind of a study of the necessary study because of you'd started the standard.

The health care.

And then ultimately.

You know, we're gonna be looking at the the by remake study data, which will be one in which we can get a little bit more.

Information over that 28 day period.

We should be able to see a.

We should be able to see a good solid D N a drop.

Jay R. Luly: So it's one kind of study. It's a necessary study because nukes are the standard of care. And then ultimately, we're going to be looking at the Viremic study data, which will be one in which we can get a little bit more. Unknown Speaker Okay, information over that 28-day period. We should be able to see a good, solid DNA drop, and those in those subjects, over a 28-day period.

And those.

In those subjects.

Over the 28 day period.

Probably a multi log.

Drop would be encouraging something say more than two logs or so.

And you should also be able to see.

You know in effect on on the RNA.

As well.

RNA effects of usually not as.

Jay R. Luly: Probably a multi-log drop would be encouraging something, you know, say more than two logs or so. And you should also be able to see an effect on RNA as well. Probably RNA effects are usually not as pronounced as DNA effects, but you should still be able to see something in that over a 28-day timeframe.

Pronounced as the DNA effects, but you should still be able to see.

Something in that over a 28 day timeframe. So those are the kinds of data that we'll be reporting them to give us key information in terms of.

You know PK and PD and safety.

And help us really understand dose ranging for.

Jay R. Luly: So those are the kinds of data that we'll be reporting. And they give us key information in terms of P.K. and P.D. safety and help us really understand dose ranging for future studies. Thanks, Shane.

Future future studies.

Okay, and just a follow up on that line as well.

Good day that the data do you anticipate just going with the combo of going forward. How do you think you'll wait for the triple.

I will go forward yeah, what's the.

Unknown Speaker: Just to follow up on that one as well, when you do get the data, do you anticipate just going with the combo going forward, or do you think you'll wait for the triple? Oh, we'll go forward. Yeah. You know, we'll have the, We'll have the, The triple will catch up, shall we?

The company will have the one of the well.

I have the.

The triple will catch up shall we say.

Sounds good and then the last when he was just about the recent hires and the and get as you know I Beg your pardon me thing.

For me and yet we're just wondering how these new Hyatt kind of flattening of approach are you know our strategic accounts to like the business.

Jay R. Luly: And then the last one here is just about the recent hires. I'm viewing them as, you know, very promising for the company. And so I was just wondering how these new hires kind of reflect your approach, you know, or strategic approach to the business. And, you know, what can we kind of expect?

And that you know what can really kind of ex backpack and we talked briefly about the business is about in the athlete's back yeah.

My Broccoli.

Yeah well.

As you know Atlanta, we've got a very experienced team, it's it's very well rounded.

You may remember, we used to have a.

The person in the company, that's probably before you started before you.

The picked up initiation on us, but we had a person in that new.

Unknown Speaker: I think we talked briefly about the business development efforts, but you know, just more broadly. Yeah, well, you know, as you know, Enanta, we've got a very experienced team. It's, it's very well-rounded. You may remember, we used to have a person in the company, probably before you started before you, Unknown Speaker, picked up initiation on us, but we had a person in that new product strategy and development role previously. He has retired.

The new product strategy and development role.

Previously he retired.

And so you know I I embarked upon a.

The search Ah and Nash.

Trying to and actually the prior person you know had a sort of of BD.

The role as well so it was sort of of combined role and now as the company has grown.

We built out.

The strategy in a more complete way and B D and a more complete.

The end alone our way as we.

Envision just you know the pipeline maturity and complexity of what we're prosecuting.

Jay R. Luly: And so, you know, I embarked upon a search in that regard, and actually, the prior person, you know, had a sort of a BD role as well. So it was sort of a combined role. And now, as the company has grown, we built out, [inaudible] you know, the pipeline maturity and complexity of what we're prosecuting. So, very, very good young talented hires from great companies. We've spoken about BD Brendan, who spent a lot of years at Merck KGAA, he headed up the oncology business development for them, which is a big chunk of their business, and Tara Kieffer is a card-carrying, you know, Hopkins-trained PhD virologist.

So Barry.

Very good.

Young talented hires from from great companies.

We've spoken about BD.

P D Brendan.

<unk> spent a lot of years of Merck T. G. A a he headed up the oncology business development for them, which is a big chunk of the business.

And.

Tara are key for as a card carrying a hopkins trained the Phd virologist, who spent a lot of years at vertex and in many different roles not just on the virology side. Although she was she of not only our CMO.

We're involved in ultimately the.

The approval of tilapia of ear and Tara.

Was presenting the F D a odd columns and.

Jay R. Luly: And then she went more into a role in the clinical area and then ultimately into business development. So she's a very experienced person as well, who's highly technically trained. And so those are the kinds of people we love to have on the team.

And then she went more into the role in the clinical area and then ultimately into the business development. So she's a very experienced.

Person as well from his highly technically trained and so those of the.

Trying to people, we love to have on the team.

Unknown Speaker: Thanks Jay, sounds exciting. And thanks for the great call. I think it was really helpful in terms of kind of setting expectations for the upcoming, Okay, good. Thank you. Hey, guys, thanks so much for taking my question. So you're expanding the RSV trial sites for RSVP. How are you ensuring that patients are getting the drug within two days of symptoms? Like, what what?

It sounds exciting and thanks for the great client think of is the only helpful. In terms of kind of setting expectations for at that point.

Kind of quiet.

Good good thank you.

Our next question is from a cash tomorrow.

The research.

Hey, guys. Thanks, so much for taking my question.

So you're expanding the RSV trial sites for RSVP, how are you ensuring that patients are getting debt.

The drug within two days of symptoms like what.

What what.

Unknown Speaker: What are you putting into place to make sure, as you're doubling the clinical trial size, that it's still going to be run properly? And as we think about Dr. G. Vincenzo and his recent hire, how do you think he's going to be contributing to running the trial design, specifically as we think about Phase 2B to go into phase 3? What's the path forward for that program?

What are you putting into place to make sure as the doubling of the clinical trial site.

It's still going to be run properly and as we think about Dr.

Dr. Vincenzo and has been from higher how do you think he's going to be contributing to running the cloud design.

Specifically as we think about pace of the to go into phase three.

At what.

What kind of the path forward for that program could the things could be potentially the pivotal.

Unknown Speaker: Could the Phase 2B potentially be pivotal? You're alluding to a polymerase inhibitor and then a protease inhibitor. I look at the Pfizer program, and there are issues, I think, with that being an IV drug. I look at the RIGSVAC Merck program, and I think there are probably issues with carcinogenicity or safety in general with that target. What are you optimizing right now when you think

And then finally on your Covid program you guys are really thoughtful about wherever you are putting into the clinic.

Youre alluding to a preliminary inhibitor and then of protease inhibitor I look at the Pfizer program and the issues I think with that being an IV drug I look at the back of our program and I'm thinking there's probably give me the lift carcinogenicity thinking in general what that target what are you optimizing right now when you're thinking about the target.

Unknown Speaker: And how do you think that your molecule could potentially be differentiated versus the other protease and RNA polymerase inhibitors that are in development for COVID? Thank you. Okay, so a bunch of questions, but I'll take them since we're getting, I think, on to the end of the call here. So with regard to RSVP, I mean, this is the way we always do the study, right? People show up, they show up at one of our sites, and just as part of the investigator questionnaire, you find out when people are symptomatic.

And how do you think that your your molecule could potentially be differentiated versus the other per year and RNA polymerase inhibitors that are in development for COVID-19. Thank you.

Yeah.

Okay, So a bunch of questions.

But I'll I'll take them out of it since we're getting I think on because at the end of the call here, but the the.

So with regards to RSVP I mean, the this is the way we always do the study right people show up the show up to one of our sites and you know just as part of the as part of the investigator questionnaire or you find out you know when when people were symptomatic and that's so it's the.

Unknown Speaker: And so it's either they're within the 48-hour window, or they're not. And so if they're outside of that window, they're just excluded from consideration. So it's a key inclusion criterion for our study. If they are in that window, they are tested on site.

The teaser there within the 48 hour window or they're not and so if they're outside of that window. There just excluded from <unk>.

Consideration so it's the key inclusion criteria for our study.

If they are in.

In that window.

They are tested on site we've got.

Jay R. Luly: We've got RT-PCR machines in every site that will give quick answers, and you find out basically while the subject's still in the office, and they can be dosed straight away. So, you know, that part of it, I think we're all set on. And I don't expect there to be any, you know, abnormalities or perturbations from the existing protocols that we've had in place at other sites.

RT PCR machines in every site that will give quick answers and and you find out basically while the subject still in the office and they can be they can.

They can be dosed straight away so.

You know that part of it I think where we're all set on and I don't expect there to be any.

Uh huh.

Abnormalities or of perturbations from the existing protocols that we've had in place that the other side. So I think it's it should all be fine.

Jay R. Luly: So I think it should all be fine. John DiVincenzo, Dr. DiVincenzo, who will be joining us, is an expert in this, as I know you know. He's a KOL extraordinaire in the RSV space.

So.

John do you have insurance out of doctors, even tens of who will be joining us as expert in the sense I know you know the.

These are K O L extraordinaire and the RSV space. He has been involved in many if not all of the the key sort of RSV studies and key RSV therapeutic approaches over the years and he spent his whole career, hoping that he could.

Jay R. Luly: He's been involved in many, if not all of the key, you know, sort of RSV studies and key RSV therapeutic approaches over the years, and he spent his whole career hoping that he could, you know, ultimately help deliver a treatment for, you know, the patients he sees. And so it's too early to say anything now about his impact on creative clinical trial design in the future, but what I would say is it's absolutely the reason why we have him on board.

You know ultimately helped deliver a therapeutic for you know the patients he sees and.

And so we're.

Too early to say anything now about is the does impact on the creative clinical trial design and the.

For the future, but what I would say is it's absolutely. The reason why we have them on board again, our goal is to build the leading.

Jay R. Luly: Again, our goal is to build the leading franchise in this space. We've got a very talented team of folks who have been in the industry for quite a while, and I think now marrying that with sort of academic medicine and also sort of a translational thinker already. I mean, he had a clinical virology lab in his lab, he saw patients, he's been working on trial designs, he's been an advisor to pretty much everybody.

Franchise in the space.

We've got a very talented team of folks who have been in the industry for quite a while and I think now of Marin.

That with the sort of academic medicine, and also sort of of translational thinker already I mean, you've got a translation. He had a clinical virology lab in his lab you saw of patients who've been working on trial designs have been advisors.

Pretty much everybody so I think.

Jay R. Luly: So I think we'll be thinking about it as hard as anybody can and hopefully trying to come up with the most expeditious pathway to commercialization as we possibly can. Then, with regard to COVID, you mentioned some of the pitfalls that have been with polymerase in the past, and Protease Inhibitor, I think you were referring to Pfizer's. Is that what you think? Yeah.

You know, we'll be thinking about it as hard as anybody can and hopefully trying to come up with the you know the most expeditious pathway to commercialization as we possibly can.

And then with regards to Covid you mentioned.

Some of the pitfalls that have been with preliminaries.

You know in the past.

And protease inhibitor I think you were referring to Pfizer's is that what you see I think the yeah. So their their agent is not an on the interesting one.

Jay R. Luly: So their agent is not an uninteresting one. But it's, but it says, you know, it's given IV. And we do not want to, we don't want to go that route.

But it's but it says you know it's given IV.

Do not want to.

We don't want to go that route I think by the time, you're administering one of these agents ivs you've.

Jay R. Luly: I think by the time you're administering one of these agents IVs, you've lost, or I shouldn't say it that way, you've lost the opportunity to make it much more usable. And to our way of thinking, again, it's an oral agent; you take it, and you get out, and you don't have to have other, you know, more complicated routes of administration that, you know, bring you into the proximity of other people, and either in healthcare settings or other settings that you otherwise wouldn't need to be.

You've lost or I shouldn't say it that way you've lost the opportunity to make a much more usable.

Usable and.

To our way of thinking again, it's the oral agent you take it and get out and you don't have to.

Have other more complicated routes of administration that brings you in to proximity of other people.

And health care settings for other studies that you otherwise wouldn't need to be so we're focused only on the oral agents. We've got some very again as I mentioned some very.

Jay R. Luly: So, we're focused only on oral agents. We've got some very, again, as I mentioned, some very good oral agents that are potent and have good oral PK. And so, we're, again, just fine-tuning and optimizing. With regard to... you know, polymerase inhibitors. You know, nukes have had issues in the past. And, you know, some are fine, and some are not. And so, you know, we'll be thinking broadly, we are not wedded to anytime we go after a polymerase; we're certainly [inaudible] So suffice it to say, anything that we look at there will have an extensive toxicology workup just like any of our other programs.

Good.

Oral agents that are potent and have good oral PK.

And so we're again, just kind of fine tuning and optimizing.

With regards to them.

<unk> polymerase inhibitors.

You know nukes have had issues over the past.

And you know summer some are fine and some are not fine and so you know we will.

I'll be thinking.

Broadly we are not wedded to.

Anytime we go after of preliminaries for certainly.

Not wedded or necessarily even focus on.

Nuke polymerase and so we won't ignore them, but we need not look too nukes only as the.

Way to skin that cat and.

So suffice it to say anything that we look at there we'll have them kind of expensive.

The toxicology.

Work up just like any of our other programs so I'm.

Right.

Jay R. Luly: I think I think I think all of our approaches are generally, Thanks so much. Thank you everyone for joining us today. If you have any additional questions, feel free to contact us directly and have a good evening. Thanks for watching!

Think of I think all of her approaches are generally.

Fine.

You know on that front, especially if you pay for them to be safe and the oral.

Thanks, so much.

Youre welcome.

And there are no further questions in queue at this time.

Over to management for any closing remarks.

Thank you everyone for joining us today, if you have any additional questions feel free to contact us directly and have a good evening.

Yeah.

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

Disconnect.

Yeah.

Yes.

Okay.

No.

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