Enanta Pharmaceuticals Inc. Q2 2023 Earnings Call

Okay.

Good afternoon, and welcome to Atlanta Pharmaceuticals First school second quarter ended March 31st 2023 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 that.

This call is being recorded I would now like to turn the call over to Jennifer Viera Investor Relations. Please go ahead.

Thank you operator, and thanks to everyone for joining us. This afternoon. The news release with our fiscal second quarter 2023 financial results was issued this afternoon and is available on our website a news release with top line data from our sprint clinical trial was also issued this afternoon and can be found on our website as well.

Slides for today's webcast will be available on our website after the call ends.

On the call today are Dr. J, Lullay, our president and Chief Executive Officer, Dr. Scott.

Our Chief Medical Officer, Paul Mellett, our Chief Financial Officer, and Doctor, Turkey for our senior Vice President strategy and development.

Before we begin with our formal remarks, we do 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.

A description of these risks is in our most recent Form 10-K and other periodic reports filed with the SEC and you have to 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. Lu I Jay.

Thank you Jennifer.

And good afternoon, everyone.

Our goal has always been to develop curative therapies for patients in need and that effort continues today with our announcement of the topline data from our phase two sprint study of Edp 235, or three C. L protease inhibitor in development as an oral once daily treatment for COVID-19.

I'll, let doctor Scott Rottinghaus, our Chief Medical Officer present, the data in a minute.

I will highlight a few key points, which support our belief that edp 235 to play an important role in the treatment of COVID-19.

First the trial met its primary endpoint, demonstrating a favorable safety and Tolerability profile. In addition, we are excited that the sprint data show that Edp three five had an impact on clinically meaningful end points.

Scott's presentation, we'll go through this in detail with that I'll turn the call over to Scott Scott. Thank you James.

As Jay stated Edp 335 met the primary endpoint and was generally safe and well tolerated we saw a dose dependent symptom improvement with edp three five treatment compared to placebo. However, we did not see an effect on biologic endpoints likely because of the rapid viral declining.

Placebo arm this immunologically experienced standard risk population.

As a reminder, this slide shows the study design of sprint, which was a randomized double blind placebo controlled phase II clinical trial of Edp three five at approximately 200 adults with mild or moderate COVID-19, who did not have risk factors for.

Progression to severe disease.

Patients were treated with Edp two to three five at doses of 200 milligrams 400 milligrams or placebo once daily for five days.

We randomized 231 patients in a one to one to one fashion. The safety population included all patients randomized.

We followed the patients out to day 33, and as you can see 95% to 97% of the patients completed the study.

The ITT C population of 190 patients is a modified intention to treat population that constitutes our primary efficacy analysis population.

It includes all patients who were confirmed to have a positive PCR for Sars COVID-19 two at baseline.

Demographics and baseline characteristics were well balanced between the arms, we had a young patient population with a median age of about 45 years, most patients were white and Hispanic three.

Three quarters were enrolled within three days of symptom onset based.

Baseline viral load was about five logs across arms the.

The majority of patients had been vaccinated against Covid and about 95% were seropositive, indicating a high degree of baseline immunity against Covid.

This is consistent with recent estimates from the CDC showing a high degree of Cerro positivity in the U S population.

The next slide summarizes the adverse events that we saw in this study.

Among our 231 patients only 10 adverse events were reported while there were numerically more adverse events reported on 400 milligrams, but on the other arms. The frequency was still low at six 4% compared to placebo at two 6%.

There were no serious adverse events or discontinuation due to adverse events most adverse events were mild in severity.

The adverse event that was graded as severe in this table was a fall and resulting arthralgia. There was judged by the investigator not to be related to study drug.

This slide shows the specific adverse events as you can see no specific pattern of adverse events was identified the two hepatic toxicities were asymptomatic transient elevations of transaminase is the one and 200 milligrams with a mild grade one elevation and the other in 400.

Milligrams I will discuss more on the next slide.

Laboratory values were generally unremarkable, but there are two specific callouts the patient I just mentioned who is receiving edp 235 at the 400 milligram dose reported concomitant use of alcohol and acetaminophen.

He had a L T at the upper limit of normal at baseline and experienced asymptomatic Alt elevation up to 12 times, the upper limit of normal and steady day six as ASP was five times the upper limit of normal GTT was elevated at baseline and increased further to four times the upper limit of normal.

Even in alkaline phosphatase were normal.

The patient remained asymptomatic and all labs returned to normal and follow up except for GTT, which remained mildly elevated but consistent with baseline.

The second laboratory observation is a transient and dose dependent elevation in total cholesterol and triglycerides with Edp three five.

Both total cholesterol and triglycerides, then trended toward normal after treatment.

Wrapping up safety there was a low frequency of adverse events and most were mild in severity. There were no serious adverse events or discontinuation due to adverse events laboratory values were generally unremarkable apart from the patient with transaminase elevations in the lipid trends that I just discussed.

<unk>.

Moving to PK Edp 235 achieved target exposures and the results were consistent with what we saw in phase one.

Plasma drug levels were 7% and 12 times higher than the EC 90 of Omicron for the 200 milligram and 400 milligram dosing levels.

Mean, and median pre dose concentrations of Edp 235 on day five are shown in the table.

Yeah.

Now for efficacy.

Let's start with the total symptom score and the full efficacy analysis population the ITT seed.

As a reminder, the total symptom score comprises all 14 symptoms as defined by the FDA for evaluating drugs to treat COVID-19. They are listed on the right hand side of the slide.

You can see here that there is a dose dependent trend favoring edp three five with statistical significance being achieved at multiple time points as indicated by the Astral <unk> with a P value of less than 0.05.

Statistical significance was observed as early as the first time points evaluated which was one day after the first dose.

While the baseline total symptom score at the 400 milligram dose was slightly higher than the others are rapid early and sustained improvement in symptoms was observed compared to placebo.

For Contextually station. This slide shows our Edp 305 data that I. Just showed you next to data from another protease inhibitor and central here.

We chose in central Veer for contextual information because it's the only antiviral with a sufficiently robust data symptom data set in the public domain.

Our phase II study looked at the 14 symptoms I, just discussed and 190 patients and the change from baseline in total symptom score is graph here out to 10 days.

In Central <unk> Phase <unk> study of 341 patients looked at the same symptoms, except for taste and smell and these data are graphed out today's six.

As you can see.

Dose dependent trends and symptomatic improvement were observed for both Antivirals.

As you May remember the protocol stratified patients at randomization into two groups those with less than three days of symptoms and those with greater than three days of symptoms.

We pre specified analysis of the patients who are randomized within three days of symptom onset.

You will recall from the demographics slide that this population includes about three quarters of the patients in this study.

And this population Edp 235 at 400 milligrams showed statistically significant reductions in total symptom score compared to baseline at all time points after treatment.

We interrogated our dataset with the goal of identifying a subset of the FDA specified 14 symptoms that better reflect the clinical manifestations of the current COVID-19 variants and the treatment effect on these symptoms.

Shionogi performed a similar analysis identifying five symptoms from their phase <unk> study, which were subsequently used as a primary endpoint in their phase III.

As shown here, we identified a subset of six symptoms, including shortness of breath sore throat, stuffy or runny nose chose our shivering, fearing hotter feverish and headache.

This figure shows an analysis of these six symptoms in the pre specified population of patients enrolled within three days of symptom onset.

Two to three five at the 400 milligram dose demonstrated an even greater improvement in symptom score at all time points.

Now, let's move to looking at time to symptom improvement.

While our pre specified endpoint of time to improvement for all of 2014 symptoms did not show a difference between the active and placebo arms analysis of the six symptoms from the last slide showed a statistically significant difference in the ITT population.

Furthermore, as shown on this slide this difference was even greater among patients who are enrolled within three days of symptom onset.

You can see that the hazard ratio for the difference of Edp three five at the 400 milligram dose versus placebo.

One nine.

With a P value of 0.006.

Median time to improvement for these six symptoms with shortened by two days, specifically patients receiving placebo improved in five days, while patients receiving 400 milligrams of Edp three five improved in three.

Three days.

Moving to viral logic and points. This graph shows change from baseline in viral RNA as measured by nasopharyngeal swabs.

No difference was demonstrated between patients treated with edp, three five and placebo likely due to the rapid viral decline observed in the placebo arm.

The main baseline viral load in this study population was approximately five logs and a precipitous decrease in viral RNA was observed in all study arms, indicating that this hiring immune population rapidly cleared virus from the nose.

To understand this further we performed an additional analysis of patients with a baseline viral load greater than five logs.

And this represented about half of the study population.

We saw a viral load decline of 0.4 logs at day, three and both tooth Edp three five treatment groups compared to placebo.

This 0.4 log decline with sustained.

Five and the 400 milligram arm.

For more contextual realization. This slide compares the viral RNA change from baseline in the placebo arms of other direct acting antiviral Covid studies.

You can see here that the decline seen in the placebo arm of the sprint study was more rapid than in any other study.

This may not be surprising given the highly immune population in which the study was conducted as evidenced by recent CDC data from a nationwide zero prevalence study showing the high prevalence of natural and hybrid immunity, which continues to grow over time.

Details of these data can be found in the appendix of the slides posted to our website.

Yeah.

In summary.

Edp 235 was generally safe and well tolerated.

There was a low frequency of adverse events and most were mild in severity.

There were no serious adverse events or discontinuation due to adverse events.

Edp three five showed a dose dependent improvement in total symptom score.

Among patients enrolled within three days of symptom onset there was a statistically significant improvement in the total symptom score for Edp three five at 400 milligrams at all time points, starting at one day after dosing.

There was no difference between treatment arms and placebo for viral RNA decline in this highly immune population that was able to rapidly clear Sars COVID-19 two from the nose.

However, an additional analysis of patients with a baseline viral load greater than five logs showed a viral RNA decline of 0.4 logs at day, three and both Edp 305 treatment groups compared to placebo.

In conclusion, we're excited to see the Edp three five to 400 milligram dose had a significant effect on symptoms in this sprint study, suggesting that we have the potential to affect clinically meaningful endpoints moving forward in development.

That concludes my presentation of the data with that I will turn the call back to J J.

Based on the positive spread data, we are focusing on partnership opportunities for phase three and on the potential for a phase III study in acute or long COVID-19 that could further demonstrate the efficacy of edp three five we look forward to providing an update on our plans in the coming months.

I also want to note we continue to progress our research program to develop Sars Covid, two <unk> like protease or appeal pro inhibitors.

Beyond COVID-19, our patient centric approach continues with our industry, leading respiratory virology treatment.

Portfolio.

With RSP, specifically, we are advancing a broad program, which includes Edp 938, the most advanced and protein inhibitor in clinical development as well as ADP <unk> three our novel oral therapeutic targeting RSV L protein RNA polymerase.

We are monitoring RSV epidemiology to evaluate the impact on trial enrollment and timing for data Readouts and our ongoing phase III studies of Edp 938.

We expect enrollment to continue throughout 2023.

While we are wrapping up our ongoing phase one study of Edp three to three and we look forward to reporting topline data for Edp 323 next month.

This quarter, we also announced that the FDA granted fast track designation to ADP <unk> three underscoring its potential as a once daily oral therapeutic for the treatment of RSV.

As a reminder of the phase one study is a double blind placebo controlled first in human study that will enroll approximately 80 healthy subjects and is evaluating the safety tolerability and pharmacokinetics of orally administered single and multiple doses of Edp 323.

Beyond our clinical RSV programs, we are particularly excited by the potential of our novel broader spectrum Antiviral research program targeting both RSV and human Metapneumovirus or <unk> TV with a single agent.

Both of these viruses have a severe impact on several vulnerable patient population such as children. The elderly adults with underlying cardio pulmonary disease, and those who are immune compromised.

Our preclinical data in support of this program showed that our prototype dual inhibitor demonstrated potent in animal or activity against multiple genotype constraints of both viruses in a range of cell types.

We're making progress in the optimization of our potent dual inhibitors and aimed to select a clinical candidate in the fourth quarter of 2023.

Before I turn the call over to Paul to provide an update on our financials I want to comment on the $200 million royalty sale transaction, we closed two weeks ago.

The additional non dilutive funding has increased our financial flexibility and extended our cash runway.

With that I'll turn the call over to Paul.

Thank you Jay.

Before I provide details on our second quarter financial results I also want to take a moment to comment on our royalty sales transaction, which we announced in April .

This transaction involved the sale of 54, 5% of our future global royalties, we earn on net sales of Maverick beginning in July 2023 through June 2032, with total payments capped at 142 times the purchase price.

In exchange the purchase up purchaser <unk> paid us $200 million upfront. We are excited to partner with <unk>, which is one of Canada's largest defined benefit pension plans.

This sale not only secure additional non dilutive funding, but also gives us increased financial flexibility and retained economics.

Please note that our naphtha retain 45, 5% of all royalties until the cap is hit at which point, 100% of all further royalties referred to an AD tech.

Now, let's turn to our quarterly results.

For the quarter total revenue was $17 8 million and consisted of royalty revenue earned on <unk> Global Maverick net product sales.

This compares to total revenue was $18 7 million for the same period in 2022. The decrease was due to lower patient volumes in 2023 compared to 2022.

Moving onto our expenses for the three months ended March 31, 2023 research and development expenses totaled $43 5 million compared to $42 1 million for the same period in 2022.

The slight increase was primarily due to the timing of clinical trial expenses and a virology programs.

General and administrative expense for the quarter was $13 8 million compared to $10 5 million for the same period in 2022.

The increase was due to increased stock related compensation expense and legal fees associated with our patent infringement suit against Pfizer.

Net loss for the three months ended March 31, 2023 was $37 7 million or a loss of $1 79 per diluted common share compared to a net loss of $33 6 million or a loss of $1 63 per diluted common share for the corresponding period in 2022.

Anantha ended the quarter with approximately $225 million in cash and marketable securities before giving effect to the royalty sale transaction.

We expect that our current cash cash equivalents and short term and long term marketable securities along with the $200 million in cash we received on the sale of a portion of Maverick royalties as well as our retained portion of royalty revenue will continue to be sufficient to meet the anticipated cash requirements of our existing business.

And development programs into calendar 2026.

Further financial details are available in our press release and will be available in our 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.

Thank you and as a reminder to ask a question you will need to press star one on your telephone and wait for your name to be announced to withdraw your question simply press Star One again, please standby, while we compile the Q&A roster.

Okay.

One moment for our first question that comes from Jasmine Rahimi with Piper Sandler. Please proceed.

Hi, Kim Thank you so much for all the detail from sprint.

I guess, maybe now with this data on him like what are what are the next steps right like how soon can you meet with the agency.

<unk>.

And tied in regards to the phase three design.

Maybe.

You know given that there.

Quite a bit of variability in the viral load and maybe maybe not different with the peg to them. The total symptom score like do you think those data points cut.

Impact may or may not impact the discussions with potential partners.

If you could maybe highlight why are they have a deep appreciation of their ability.

Alright.

This is Jay so.

Maybe I'll, let Scott fill in some of the.

A little bit of the details but.

I think we will be progressing our dataset taken it too.

The agency.

We will be also.

The viral load bed, which we can talk a lot more about it.

<unk>.

To prove any of the Covid drugs based on viral load. It's based on some other endpoints. So if youre looking at a standard risk patient population is going to be based on <unk>.

Sometimes if youre going to be looking at a high risk patient population is going to be on hospitalization and death.

And so I think in particular, that's why we were really pleased to see the statistically significant.

Improvements in the in their total symptom score and in that time too.

Improvement so those are both really important metrics that.

Could be viewed as clinically highly clinically relevant.

Yes, Jasmine thanks for that question I mean, just to reiterate we're so excited about the strong data and symptoms.

We do expect that.

To form the basis of a discussion with regulators to look at.

Next steps in terms of phase III design.

Well, while the virology data are are mixed as you say I do think we have an opportunity here given given the symptom data. So we are.

You know very excited and looking forward to moving this to next steps.

I think one of the other things that's clear is that.

The patient population over time since the beginning of the pandemic has changed dramatically as has the virus and so.

<unk>.

Good for the humans.

<unk> Cerro positivity that were building up over time.

Either through vaccination or through natural infection, or both giving your hybrid immunity.

This is only built and built and built over time and in every sort of consecutive study population that people are looking at.

And.

For that reason.

As you saw the data just even looking at the placebo.

Curves.

The slide deck.

This slide deck will be posted at the end of the call.

But when you when you look at all those placebos from all the various studies.

It becomes clear that over time.

The the fiber load drops have happened more quickly and more dramatically as time has gone on at least hence you can measure viral loads in the nose, which is obviously the compartment that can easily be interrogated what's happening.

The rest of the body and the rest of the tissues from a viral logic standpoint, much more difficult to assess but we know that our drug has great tissue penetration high potency good exposures high multiples of EC <unk>.

And.

Has had a very significant effect on symptoms, which.

Again, we think compares very well to it.

Any other study that's been done in this patient population so.

I think.

Bank.

And interesting.

Next study I think the.

The question I think you asked yes was.

Next plans will be thinking about.

Other kinds of studies, there's things you can think about and I'm talking about phase twos now.

It could conduct and long COVID-19 or in another patient population.

Thinking about.

The future with phase III.

Our plan has always been to engage a partner for late stage development.

Our commercialization strategy and ultimately the launch.

With this positive data, we see a broad opportunity for <unk> five in multiple different treatment paradigms for covered you can think of standard risk high risk prophylaxis long COVID-19, so really to.

In order to realize this vision, we feel our pharma partnership with better enable us.

Youre welcome.

One moment for our next question please.

Okay.

It comes from the line of Brian Abrahams with RBC capital markets. Please proceed.

I guess my first question is.

I guess, how confident are you that some of the symptomatic benefits that youre seeing R&D dose dependent versus maybe related to a slightly higher baseline.

For the 400 milligram arm I guess I'm curious.

At the end of day, five half 402 hundred milligram patients compared in terms of where they got to on an absolute basis on symptom score and how youre thinking about the go forward dose.

I think the go forward dose is going to be 400.

That stood out in so many.

So many ways.

There were slight differences in the baseline, but what what that what happened there.

Within the first.

Really in the first 24 hours.

The 400 milligram dose brought things.

Down very quickly.

And basically.

Lined up with the other patient population so.

There is there is.

Clear evidence that the 400 milligram.

Moved very quickly and efficacious slate in the right direction.

And I would point out.

Oh, sorry, Brian I was just going to say I would point out also that in addition to the decrease in total symptom score. If you look at those specific symptoms you see an improvement in time to two improvement and so we have.

Multiple different.

Avenues of evidence that that point to the fact that this is.

Really.

Rio dose dependent improvement in efficacy.

Yeah, we feel quite confident in it.

Got it.

To what do you attribute that to.

Symptoms signals that you're seeing here.

Given that there isn't a measurable antiviral effect.

Is this.

Is this related to maybe sort of a.

Second Unmeasured Bowl effect, that's going on in terms of final clearance and a different reservoir or some sort of.

Additional benefit on.

Anti inflammatory benefit.

Oh, Yes key key question, Brian . So we think it's the compartment that we're measuring right.

Everybody looks at to knows.

That's where we can.

Easily access.

Check, but we know that these patients have 95% zero positivity and you can look at some of the background information that we put in our in our deck as well the whole population is becoming really strong in terms of hybrid immunity.

And the ability to clear this virus now that having been said we do believe when you see these systemic symptoms in particular, there are clearly other reservoirs a virus throughout the body that.

We can't necessarily access to measure efficiently, but we do know that our drug has excellent tissue distribution excellent tissue penetration and we believe that that's what potentially sets it apart and that's what's allowing us to get a.

Rick effect on symptoms, whereas we don't see so much on virus in the nasopharynx.

That makes sense and if I could squeeze one more quick one in.

I was wondering if you could maybe talk a little bit more about the triglycerides total cholesterol effects that youre seeing in terms of I guess, how long he followed those patients and how close to.

Baselines did they return and does that imply anything in terms of how you might think about future studies and higher risk patients who may have concurrent hyperlipidemia at baseline.

Yeah, absolutely. So obviously, we will follow patients very closely in terms of lipid going forward, but we saw within 14 days. The triglycerides had returned entirely to normal and within 14 days. The total cholesterol was was well on its way.

It's a little bit delayed from a metabolic perspective of course. So we have every reason to believe that these cholesterol changes are mild and and.

Yes, we think that we can monitor them and manage them pretty effectively particularly given that this drug is for acute and not chronic use.

Great. Thanks, again, I think the other thing that's interesting on that front is.

You saw some of these findings as well.

So I guess it bakes in with a very sort of a different chemical class.

And so.

The question is that some exposure there is something that you will see with protease inhibitors.

Got it also reminded.

The.

Okay.

Looking at other mechanisms even.

That.

<unk>.

<unk>.

<unk> I mean early in earlier in the pandemic.

Gilead drug room that severe.

Failed to demonstrate viral load changes and the nose. Other people have demonstrated viral changes in the nose, but not something else. Other. So this is why the FDA doesn't want to use viral loads as a as a.

Approvable endpoint.

When we did look at.

A patient population that had viral loads higher than the five.

We did see about a half a log change in this.

Still experienced patient population so.

That's just getting I think it's just getting harder and harder to find that in this otherwise healthy standard risk.

Patient population with the current variance in the current state of immune education.

That patients have.

Thank you one moment for our next question.

Hey, great. Thanks for taking the questions. Most have been answered a couple of quick ones just noticed that drug drug interaction studies had completed.

They're not the most exciting but anything you can tell us about the drug drug interaction profile of 235.

And then just any.

Potential alternative explanation for the lack of viral load effect I guess, maybe you guys have gone through it already to tissue.

Distribution of the virus et cetera.

Just anything else you guys can think of and then.

Just really quickly on Edp 514.

What's the status of Sandy maybe well I'm sorry, Charlie will just focus on the first question first so.

Tell you about.

<unk> load in the nose today, I think we addressed that a couple of different times no further thoughts.

Right now certainly.

And then with regards to the DDI studies that are ongoing.

I'm sorry, you can go onto the next question. If you have one brief one. Thank you said 501 for if youre still on right.

If not maybe you'll come back on the queue.

Yes, sorry, 551 for just the status of searching for additional candidates to combine with that may be considered out licensing.

514 in addition to in licensing something else. Thanks.

I think we'd be open minded in any way to bring together a marriage of the right combination.

And.

To that end I think.

Theres more data readouts that are going to come out in the area of Hep B.

That's still a little tricky to know exactly what that right combination might be for us or anybody else. So in our plan.

As to.

Continue to watch other.

Datasets think about other mechanisms follow the literature closely.

And looking at external assets.

That could be combined and we're agnostic as to whether we export our asset or import another but we just want to make sure. It's the right combination.

Great. Thanks.

Thank you.

One moment for our next question.

Again it comes from the line of our cash to worry with Jefferies. Please proceed.

Hi, This is Andy on for <unk>. Thanks, so much for taking a question.

She also had a high prior vaccinated question positive patients in their phase two trials in the range of mid to high 80% range and believe they show to have a lot to one log benefit over on viral load over placebo what are the major differences between your phase two in prior Covid antivirals.

Tribute to a potentially more aggressive placebo.

I was going to say either one of us can take that.

Yeah.

This.

Study was run in Japanese patients Asian patients.

Clearly with at a time that they had less exposure to natural infection. So we would expect a much.

And I don't have these data for either population, yet, but we would expect a much lower.

Rates of nuclear capsid positive positivity among that population that among our population. So we can see here in the year 2023, again that populations have very high hybrid immunity. So it's challenging to find.

Any patients much less a population that has a baseline viral load of seven logs like shionogi did in order to show that big drop in viral load I don't know if Terry you had anything to add to that.

Yes.

I think.

The terminology of <unk> positivity is.

Somewhat heterogeneous in terms of what provides that Seo positivity, whether it's through vaccination or natural infection, and we're seeing data coming out of the CVC now that in the U S. The percentage of people with hybrid immunity, meaning they have had it through both vaccination.

<unk> natural infection.

Is increasing probably provide somewhat better immunity and thats, probably borne out in the difference in baseline viral load between the two studies, we know that that is a major factor in.

Seeing these viral load declines.

So yes.

She never study had a baseline viral load of seven which is too long is higher than what we had at sprint.

And we've got just as an appendix to the slide deck.

That we presented today, which again should be on our website soon if its not already there.

Has a little bit of supplemental information about.

Zero positivity and also <unk>.

<unk> of patients or percent of the population that have been.

Previously infected as measured by Nucleocapsid antibodies so.

I think those trends are pretty interesting.

So if you extrapolate them backward into Japan at that time in place I think you would you would get a sense.

That.

It's likely it was a bit of a different patient population.

Great. Thanks, so much.

Okay Youre welcome a moment for our next question.

It comes from the line of Lisa <unk> with Evercore ISI. Please proceed.

Hi, there how are you doing.

Good.

I guess first question.

Bank showing an RNA change is important in terms of partnering discussions like how important is that I know, you've got sometimes and that's going to be important for phase three but.

Just wondering how much of that how important that would be the potential partnering discussions.

Well I mean again you have to look at the totality of any dataset.

At the end of the day people want to make sure.

You have sort of signs of a registration path forward.

<unk> certainly help to provide that.

The.

The fiber alert the viral load data I mean again, it's the.

It's the.

It was never powered on.

Virology.

And it.

It was surprising to us when we saw the placebo, especially when we laid our placebo against every other placebo that's been done in a comparable study.

Just how disadvantaged or patient population our treatment arm was in terms of demonstrating that but it's I think it's.

A sign of the.

Okay and so.

Do you think if you were able to tap into some of these other viral reservoirs and I know that's not possible that David just theoretically you would see that.

Changer.

I guess I'm, just trying to get the linkage between like a change of symptoms and actual buyer viral reduction whether or not you can.

Yeah, that's a different client detect oh I'd like to understand what the different question.

No I mean I.

I suspect you would but again accessing those compartments whether it yeah.

The hard deliver.

<unk>.

Other tissues these are raw.

Reservoirs.

The virus has been found in the brain right. So I mean, there's all kinds of places you could go look.

But I think that that's.

It becomes a challenge.

Obviously.

Sorry, and long Covid for example, I mean, Ron covered.

Probably a subset maybe even a good subset of patients out there that still have.

Virus for maintain and various other tissues as it might not be the nose.

Folks continue to.

Swab negatively but when you look at some of the symptoms and the drivers of some of the symptoms that are exhibited in long COVID-19.

They are very likely patient populations that could have reservoirs of that and that's something we're thinking hard about.

Are there interesting ways to go interrogate that and.

Sort that out but too early.

To call whether or not.

We would too.

A smaller phase two.

<unk> study to explore and exploit some of those kinds of.

Of reservoirs of virus with 235.

Okay, and does I guess natural immunity or vaccination disproportionately reduce virus and the nasal passage or why would why would it be different I guess the other reservoirs.

At least I think that's a good question.

Certainly hybrid immunity, we think from at least from the data that's out there.

Provides better predict could provide additional protection.

The nose is where the virus first enters and.

<unk> continues to.

<unk> spread and replicated in other parts of the body and that just appeared to be where it is being cleared and patients had mucosal immunity built up that.

Can contribute to the clearance at least in the nasal comprehend.

That makes sense and maybe postponing to counter it.

Yeah, I was just going to say, Lisa, particularly associated with natural infection, you get mucosal immunity that you wouldn't necessarily get to the same degree with vaccination.

Okay that makes sense, yeah, I get that.

And then my.

My Associate Cmos is sitting with me here raised a good point about rebound, but I think that was something that you were going to be.

Exploring could you comment at all on.

Now if you seen a difference in rebounds and check for that ERP will be checking or what's the plan there.

Yes, no nothing yet so we have.

I have looked grocery and haven't seen differences between between arms and we're working on getting those analyses done properly.

Okay, and then just as we think about kind of next steps are those predicated on finding a partnership or is that something you'd be willing to take on yourself like how power. How are we thinking about the gating factors for them.

Perfect.

I don't think any phase two study would be gating you know in a different population like long COVID-19 or something like that that's not gated in fact is it built into the financial guidance.

Paul talked about we would be able to do that and still have cash into calendar 'twenty six but.

But I do believe that as it relates to phase three.

These are bigger much more expensive.

Trials that ultimately I think you do want to have a partner engaging on the trial design, how you would.

Set those up and then.

Importantly, gaining a launch partner we're not.

We're not we've never planned on commercializing <unk>.

<unk>, but rather to do we've said this since the beginning of time.

Our plan has always been to find a late stage partner and commercialization launch partner for that so I think that is.

Going to be our current plan for progressing phase III.

Okay.

Okay. Thanks, a lot.

Youre welcome.

Thank you for a moment for our next question. Please.

And it comes from the line of Brian Corny with Baird. Please proceed.

Hey, good afternoon, everyone. Thanks for taking my question a question on just the wording in the press release as it relates to sort of.

Just one protocol are you talking about total symptom score and then you talked about 14 targeted COVID-19 symptoms can you just help me understand are these different arrays of symptoms that youre evaluating here and.

The protocol that is posted on clinical trials Dot com number three and four are the ones that related symptoms. When they say proportion of COVID-19, <unk> unchanged from baseline in COVID-19 find sometimes is that the key SaaS or is that the <unk> targeted COVID-19 symptoms.

It's the same yes, so the way we get it is we have the 14 symptoms and each one is graded by the patient on a scale of 012 or three and then add up to score.

That's the score so total symptom score and all 14 symptoms, we mean to be the same thing.

Does that help.

I guess, I guess I'm, having trouble understanding the line, where you say well no difference was observed in time to improvement of 14 targeted COVID-19, sometimes does that basically there was no. There was no difference in observed time to improvement in the key SaaS.

I don't really understand that.

Okay.

Oh I see what you mean, so we have a.

A different.

A different evaluation for the time to improvement so for the time to improvement you have to.

You have to have all of your symptoms either absence or mild.

And anything that was present or anything that was absent at baseline needs to still be absent and that has to be the case for two days and that has to be the case with all 14 symptoms alright, So thats, what I mean by time to improvement of all 14 symptoms and then when I say.

Take a selected group of those symptoms then that's looking at just those symptoms specifically.

The selected symptoms have given us a greater degree of power to.

To detect a difference.

Okay. Thanks that makes sense.

Thank you for a moment for our next question. Please.

And he comes from the line of Ed Arce with H C. Wainwright. Please proceed.

All right good afternoon, everyone.

Just asking questions for us alright.

Alright, Thank you for taking our questions.

So just trying to figure out.

COVID-19, entering Anthemic base.

Sure.

What do you estimate could be big market opportunity.

U S and ex U S markets.

Especially.

Kevin.

Fair enough.

Latex performance.

The inventory write down.

That's important.

I'm, sorry could you repeat I mean, youre asking what the market opportunity is for Covid therapeutics.

Yes, because.

COVID-19.

Transaction.

From a pandemic.

Ed and Dennis face and also demand for.

Alright treatment as well.

How do you look at.

Corporate nights in a market.

Going forward.

Sure. So I think what we can look at is what the guidance has been provided in terms of revenue from the.

The jobs that are currently available.

Looking at <unk> I think combined it.

Around $10 billion.

The market size and so if you look at five years.

Yes.

Information that they just released on there.

Quarterly revenue they were they were guiding to 8 billion revenue 2012.

Three and they actually reported $4 billion just in Q1. So we do believe that there is.

A good market and still a lot of use for antivirals in this in this indication.

Okay. Thanks, Dan. Thank you for the attention on a commission.

Perhaps.

Two more questions from us.

You mention in the press release.

Our long coal that will be a possibility now how does that.

When we compare it to COVID-19.

Are there any.

Endpoints in the phase <unk> study of <unk>.

Suggests protection on Covid.

Okay.

Yes, well on Covid is very different than acute COVID-19 that has different clinical manifestations.

And a diverse patient population.

That said there may be comment elements in a subset that could be.

A patient population that could benefit from an antiviral and so.

Again, as I mentioned, a minute ago, we're going to look and think about that and.

Any plans for any next study where we do one.

Anlong Covid.

<unk> designed our give further details around the design at that at that point. So it's premature for us to comment on that today.

Got it.

Just one last one from us.

Three Q3 is switching gears to Richard Murray.

With the phase <unk> data expected next month.

Can you remind us what is worth more than the next step is the choice study.

Steady and if so can you give us some preliminary thoughts on <unk>.

That study will look like.

Yeah. So.

323, again, our primary inhibitor super potent.

Great preclinical PK and safety.

Took it into phase one study in healthy is Mad Sad study.

The data that we will report out next month.

Top line would have safety tolerability.

And PK.

From that will allow us to derive.

What sorts of multiples we have.

Protein adjusted <unk>, 90, which are the hallmarks of efficacy surrogates that you can measure in a phase one study.

Study, even in healthy patient population, so I think the logical next step.

Assuming positive data there would be a.

Challenge study and from that standpoint.

We've had a very successful challenge study for Edp 938 in the past.

Again.

One could look at that to get insight as to how we might be thinking about.

Progressing 323, assuming positive data.

And we will have.

More details on data and next steps.

Or at least that.

Next month.

And thats it.

Thank you so much again for taking my questions.

Youre welcome.

Thank you one moment for our next question. Please.

Any color from the line of Ron or beliefs with SBB Securities. Please proceed.

Great. Thanks. So my question is already asked but maybe a quick one on Q3 five I was curious if your outlook on time to possible approval for that asset has changed at all and especially considering the phase III and possibly an additional phase two that you might run.

Well again, a phase two would be.

Supportive, perhaps have a different indication.

I think the wildcard there is in the context of a partner I mean, obviously one of the reasons we're seeking.

Our partner would be the.

Potentially the time to approval could be accelerated by the.

The strength in resource of a global pharma partner, helping us to execute.

So.

Yes, I think right now.

I would I would.

Assume that it's going to be a lot driven by our partner in terms of moving that time.

Either forward or backward.

Yes, understood and then last one from me I was curious.

And those individuals where you saw elevated cholesterol or triglycerides.

Was there any trends or commonalities among them that could help you identify them proactively and some of the data that you've seen so far.

Thanks, Ron Us so.

Nothing specifically.

We've gone through it a population basis, there werent any substantial outliers, who didnt already have really high with its at baseline.

So we haven't detected anything specific or any patterns and.

In terms of outliers it was just kind of.

A general population trend.

Got it helpful. Thanks again.

Thank you.

One moment for our next question please.

And it comes from the line of Hannah <unk> with J P. Morgan. Please proceed.

Hi, This is Anna on for Eric Joseph Thanks for taking the question. So just acknowledging that there are a number of details left to be finalized as it relates to a pivotal study design.

The fact that you have observed treatment benefit and non high risk.

Mild to moderate Covid patients how are you thinking about the target patient population for the therapy.

Secondly, with Pfizer announcing plans to develop on that.

John Covid antiviral to backfill that that wont be using we're talking of your boosting just wanted to get your sense of how youre thinking.

About the impact that might have an event might have any bearing on potential partnership discussions for edp Gs.

Five.

Yes.

We've always assume theyre going to be multiple players in the Covid space I mean, that's that's not different than.

So I think with regards to Pfizer's next molecule, we'll see we'll see what data they can achieve with that one I mean, we know what they have with <unk>.

What shionogi has.

And apart from.

Apart from Pfizer and shionogi.

I would say we've got the other ones. So at least right now the space I think is.

Is still favorable given the size of the market and what.

What a protease can add.

Add to the overall.

Treatment landscape in Covid.

So.

I'm sorry, what was the other part of your question.

Just your thoughts on targeted patient population for the therapy since this thing.

Okay.

Yes, no the patient population I mean again I think we're thinking broadly about it standard risk the high risk patient population.

Which fits a sort of a different risk profile.

Prophylaxis long Covid I mean, there is there is nothing that I would see that wouldn't necessarily be not.

To be considered in a broad development program.

Sure.

Okay. Thanks for taking the questions.

Youre welcome.

Thank you and with that I will turn the call back to Jennifer Viera for final comments.

Thank you everyone for joining us today. Please note that we will have these slides on our website as well as our updated corporate presentation. If you have any additional questions feel free to contact us by email or call. The office, thanks and have a great night.

Thank you, ladies and gentlemen for participating in today's conference you may now disconnect.

Okay.

[music].

Okay.

Okay.

[music].

Okay.

[music].