Enanta Pharmaceuticals Q3 2023 Earnings Call Transcript

Quartr
Provided by Quartr
August 7, 2023

There are 12 speakers on the call.

Operator

Afternoon, and welcome to Enanta Pharmaceuticals Fiscal Third Quarter 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.

Operator

Please go ahead.

Speaker 1

Thank you, operator, and thanks to everyone for joining us this afternoon. The news release with our fiscal Q3 2023 financial results was issued this afternoon and is available on our website. Making formal remarks on today's call are Doctor. Jay Luly, President and Chief and Paul Mellett, our Chief Financial Officer. Doctor.

Speaker 1

Scott Roddinghouse, our Chief Medical Officer And Doctor. Tara Kiefer, our Senior Vice President of New Product Strategy and Development will be available during the Q and A portion of the call. 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. 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.

Speaker 1

I'd now like to turn the call over to Doctor. Jay Luly, President and CEO. Jay?

Speaker 2

Thank you, Jennifer, and good afternoon, everyone. At Enanta, we are committed to our mission of being a leader in the development of groundbreaking therapeutics for viral infections. In this quarter, we made important strides to bring us closer to impactful inflection points and ultimately our goals. I'm proud of the work our team has accomplished this quarter and throughout the year so far across our pipeline and business, most notably in our respiratory syncytial virus or RSV program and our COVID-nineteen program. We're in a strong position to continue to advance our pipeline and I am confident in our team's efforts to progress antiviral small molecule medicines to treat life threatening viral infections.

Speaker 2

Today, I'll provide an overview of our progress during the Q3, beginning with our RSV program, and then I'll comment on our COVID-nineteen program and the rest of our pipeline. RSV is a severe respiratory infection associated with significant morbidity and mortality that can cause serious for patients infected with RSV. Starting with our most current update, we recently announced positive data from the Phase 1 trial of for EDP-three twenty three and healthy volunteers. As a reminder, EDP-three twenty three is our L protein inhibitor in development as a once daily oral treatment for RSV with fast track designation from the FDA. This Phase 1 study enrolled healthy volunteers to evaluate the safety, tolerability and pharmacokinetics of oral EDP-three twenty three and single ascending doses and multiple ascending doses for 7 days along with the effect of food.

Speaker 2

The THAAD phase enrolled a total of 6 cohorts ranging in dose from 50 to 800 milligrams and the MAD phase enrolled 4 cohorts with doses ranging from 200 to 800 milligrams. EDP-three twenty three was Most adverse events were mild and there were no serious or severe adverse events. There was one study discontinuation due to syncope, which was deemed unlikely to be related to EDP-three twenty three. EDP-three twenty three Exposure increased with increasing single and multiple dosing up to 600 milligrams with a half life ranging from 11 to 17 hours supporting once daily dosing. EDP-three twenty three doses ranging from 200 to 800 milligrams once daily resulted in strong EC90 multiples against both RSV A and B strains and when administered for 7 days were found to result in C24 concentrations at steady state of 11 to 44 fold over protein adjusted EC90 of 0.3 nanomolar against both RSV A and B string.

Speaker 2

Additionally, no food effect was observed with the highly fat meal suggesting that EDP-three twenty three can be administered without regard to food. We are pleased with this encouraging safety and pharmacokinetic data. In virology, when a potent antiviral such as EDP-three twenty three achieves high multiples of EC90 safely, It is a very positive signal and an important de risking step for the program. These data enhance our belief in EDP-three twenty three as a potential therapeutic and give us the confidence to continue to progress the program. We believe EDP-three twenty three could serve as a standalone treatment or be used in combination with other agents such as EDP-nine thirty eight to broaden the treatment window or addressable patient population for RSV.

Speaker 2

We plan to initiate a human RSV challenge study evaluating EDP-three twenty three early in the 4th quarter, and we anticipate having results in the Q2 of 2024. Our broad RSV program also includes CEP-nine thirty eight, The only N protein inhibitor in clinical development, which we are currently evaluating in multiple Phase 2 studies as a potential treatment in high risk patient populations. These studies include RSVPEDS, a Phase 2 randomized double blind placebo controlled study in hospitalized and non hospitalized pediatric RSV patients RSV HR, A Phase 2b randomized double blind placebo controlled study in adults with RSV infection who are at high risk of complications, including the elderly and individuals with congestive heart failure, chronic obstructive pulmonary disease or asthma and RSVTS, The Phase 2b randomized double blind placebo controlled study in adult hematopoietic cell transplant recipients with RSV and symptoms of upper respiratory tract infection. Enrollment for RSV Peds, RSB HR and RSB TX is ongoing and we're utilizing sites in both the Northern and Southern Hemispheres to optimize our coverage to potential RSV surges. If there is a return to a normal pre pandemic type of RSV season in the Northern Hemisphere, We expect to complete enrollment in 1 or more of these studies in the upcoming Northern Hemisphere season and to have data in fiscal year 2024.

Speaker 2

Turning to COVID-nineteen, we announced additional analyses from the Phase 2 SARS CoV-two SPRINT study, which built upon our positive top line results that we announced in May of this year. EDP-two thirty five is our clinical stage once daily orally dosed inhibitor of coronavirus 3CL protease that was evaluated in SPRINT, A randomized double blind placebo controlled Phase 2 clinical trial in 231 adults with mild or moderate COVID-nineteen who did not have risk factors for progression to severe disease. Patients received 200 or 400 milligrams of EDP-two thirty five or placebo orally once daily for 5 days. In the Phase 2 study, EDP-two thirty five was found to be generally safe and well tolerated. A statistically significant dose improvement in symptoms was observed in the 400 milligram cohort starting as early as one day following the first dose.

Speaker 2

In a predefined subset of patients enrolled within 3 days of symptom onset, The statistically significant dose dependent improvement in symptoms was observed at all time points and a 2 day shorter time to improvement was observed and a subset of 6 symptoms in the 400 milligram cohort compared to placebo. Additional analyses announced in June demonstrated a virologic effect of EDP-two thirty five in the subset of patients who had not recently been infected as measured by lack of antibodies to the SARS CoV-two nucleocapsid, whom we refer to as nucleocapsid negative patients. Specifically, in nucleocapsid negative patients, a 0.8 log decline in viral load was observed at day 5 with 400 milligrams of EDP-two thirty compared to placebo and a one log viral load decline at day 5 in the subset of nucleocapsid negative patients who were treated within 3 days after symptom onset. Looking ahead, our current plan is to conduct all future COVID-nineteen work in the context of a collaboration. In particular, we continue to focus on progressing EDP-two thirty five into Phase 3 trials with a partner and gaining regulatory feedback to further enable a partnership.

Speaker 2

Moving on to our dual inhibitor research program targeting hmpv and RSV, we plan to select a clinical candidate in the Q4 of this year. In preclinical studies, our prototype dual inhibitor potently inhibited both hMPV and RSV replication in a dose dependent manner, demonstrating a significant reduction in viral load of each virus and maintains nanomolar activity against Multiple genotypes and strains of hMPV and RSV in a range of cell types. Our dual inhibitor is Broader spectrum antiviral that would allow respiratory infections diagnosed as either HMPV or RSV, both of which are significant causes of respiratory tract infections globally to be treated with a single agent, aiding populations such as children and the elderly who are at greatest risk. In hepatitis B, we We continue to monitor the field for compounds to develop in combination with EDP-five fourteen, our potent core inhibitor with FDA fast TRACK designation and a nucleoside reverse transcriptase inhibitor. We believe the core inhibitors such as EDP-five fourteen will ultimately be an important component of a successful combination regimen and that can potentially help us address the high level of unmet need in HPV.

Speaker 2

Finally, looking beyond virology, we are piloting new programs that leverage our core strength and small molecule drug discovery and look forward to sharing more details on these growth areas with you in the coming months. I'd like to wrap up by highlighting our near term milestones. Dan, we are thrilled with the progress of EDP-three twenty three and the positive results from our Phase 1 study, and we plan to advance EP-three twenty three into a human challenge study early in Q4. We anticipate having results in the Q2 of 2024. We plan to announce the selection of a dual inhibitor clinical candidate targeting both hMPV and RSV in the Q4 of this year.

Speaker 3

And if there is

Speaker 2

a return to a normal pre pandemic type of RSV season in the Northern Hemisphere, we expect to complete enrollment in 1 or more of for Phase 2 studies of EDP-nine thirty eight in the upcoming Northern Hemisphere season and have data in fiscal year 2024. With that, I'll turn the call over to Paul to discuss our financials. Paul?

Speaker 4

Thank you, Jay. For the quarter, total revenue was $18,900,000 and consisted of royalty revenue earned on AbbVie's global MAVERID net product sales. This compares to total revenue of $19,500,000 for the same period in 2022. In April 2023, We sold 54.5 percent of our ongoing Maverick royalties from AbbVie for an upfront payment of $200,000,000 from OMERS, one of Canada's largest defined benefit pension plans. For financial reporting purposes, the transaction will be treated as debt With the upfront purchase payment of $200,000,000 paid to us being recorded as a liability, Enanta will continue to record 100% future royalty payments as revenue and will then amortize the debt liability proportionately as royalties are paid to Olmos until a cap of 1.42x the purchase payment is met.

Speaker 4

Interest expense will be recorded in our consolidated statement of operations as and other expense based on an imputed interest rate. Moving on to our expenses. For the 3 months ended June 30, 2023, Research and development expense totaled $43,000,000 compared to $39,100,000 for the same period in 2022. The increase was due to the timing of clinical trial expenses in our virology programs. General and administrative expense for the quarter was 12 point $6,000,000 compared to $12,900,000 for the same period in 2022.

Speaker 4

Enanta recorded income tax expense of $4,200,000 for the 3 months ended June 30, 2023, driven by the receipt of the $200,000,000 from the royalty sale agreement, which is taxable for federal and state purposes. Enanta was able to utilize federal net operating loss and research and development tax credit carry forwards as well as the deduction for foreign derived intangible income to substantially offset the taxable effect of the royalty sale agreement. For the 3 months ended June 30, 2022, Enanta recorded an income tax benefit of $400,000 which was due to the release of the state tax reserve during the period. Net loss for the 3 months ended June 30, 2023 was $39,100,000 or a loss of $1.86 per diluted common share compared to a net loss of $31,700,000 or a loss of $1.53 per diluted common share for the corresponding period in 2022. Ananta ended the quarter with approximately $392,500,000 in cash and marketable securities.

Speaker 4

We expect that our current cash, cash equivalents and short term and long term marketable securities as well as our ongoing royalty revenue should be sufficient to meet the anticipated cash requirements of our existing business and development programs into the second half of fiscal twenty twenty seven. Driven by changes to our COVID clinical development plans, we are reducing external spending. To that end, we've updated our guidance for fiscal 2023. We now expect our research and development expense to be between $165,000,000 $175,000,000 and our general and administrative expense to be between $50,000,000 $55,000,000 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 the lines up for questions.

Operator

Thank you. Our first question will come from Brian Abrahams with RBC Capital Markets. Your line is open.

Speaker 5

Hi, there. Thanks so much for taking my questions. Just a couple of questions for me. First off, On the RSV program in NKTR-three twenty three, given the CK data that used and the safety data that you saw with 323 in healthy volunteers. I'm curious if you could maybe elaborate A little bit more on your latest views on the combinability and complementarity between 3 23 and 938?

Speaker 5

And then I had a follow-up. Thanks.

Speaker 2

Thanks, Brian. This is Jay. The 323 and 938, We've studied them preclinically to look at their combinability and preclinically they behave very well together. One is an inhibitor, that's 938. One is an L inhibitor, that's 3 23.

Speaker 2

So we don't expect any issues with combinability from an interaction standpoint. I think the real question is, will we need to combine them or will we ultimately want to combine them in And those are kinds of things that are going to take a little bit longer to sort out. Number We believe that 938 as a standalone could well have all the horsepower We need in garden variety RSV. 323 could also perform very well as a single agent. We'll get more insights And to that as we get data from the upcoming human challenge study.

Speaker 2

But I guess the question is, is mightn't you Want or need to combine them in a certain very difficult to treat patient population and that's something that we can certainly explore down the road or might you want to combine them to see if you could open up a treatment window that would be wider than either agent alone. Again, that's something that we can look at down the line as we're optimizing You know the category. So, those are the initial thoughts right now.

Speaker 5

Got it. That makes a lot of sense. Thanks, Jay. And then, on the COVID program, can you help us understand the implications of The data you recently reported showing those viral load reductions in the nucleocapsid negative patients. Should we think about that as Potentially speaking to a subpopulation that could down the line be uniquely targetable or just more as in further evidence or biological evidence of the mechanism here.

Speaker 5

And I guess where do you stand in terms of the regulatory path forward? Can you maybe speak to Some of the paths you're exploring, is it might this still involve additional Phase 2 work moving right into Phase 3, perhaps exploring long COVID as well. Thanks. I'll hop back in the queue.

Speaker 2

Yes. So the patient population that you're referring I think it's the nucleocapsid negative patient population. These are people who haven't had A recent COVID infection or haven't had one at all. That's sort of a unique Antigen that you can look at to determine whether or not someone's again had the virus somewhat recently. I think one of the takeaways that we gleaned from our further analysis of the data is, It's hard to measure viral load changes in the nose of people who have more recently been infected.

Speaker 2

And when you look at the patient population who hadn't been most recently affected, you could measure Viral load changes in the nose. As time goes on, probably Everybody who hasn't been infected is going to be infected. And so variously, that's going to sort of challenge the ability to look at that measurement of viral load change in the nose, But that doesn't tell you anything close to the whole story, because what really matters is The viral load changes that are happening elsewhere in the body where sites of infection can set up shop in the respiratory tract and in other tissues. So We feel that that's the more important thing overall. This is why FDA has not Sort of embraced using viral load endpoints as a path to approval, but rather to focus on Symptoms and outcomes as it relates to COVID infection.

Speaker 2

So looking at symptoms where As you know, in the SPRINT data, we had very nice data set on symptoms. And then ultimately, that endpoint Probably changes to hospitalization and death and certain patient populations that are at high risk. So I think that's sort of our takeaway from that data set. And as I look forward, It really doesn't change, I think, how you progress a drug through registration Again, that's all going to be based on symptoms and other kinds of endpoints. With regards to Registration, we are in communication with the regulators And this is not just in the U.

Speaker 2

S. But elsewhere. Really getting the latest thinking on pathways to approval and different kinds of trial designs. So, those discussions are in progress. And then as we said before, any next study is our plan to be conducting that study in the context of a partnership.

Speaker 2

So That's ultimately is our plan is to identify that Phase 3 and commercialization partner and do so hopefully with greater insights from the latest thinkings of the regulators in terms of pathways to approval.

Speaker 5

Makes sense. Thanks so much, Jay.

Speaker 2

You're welcome.

Operator

Thank you. Our next question comes from Jay Olson with Oppenheimer. Your line is open.

Speaker 6

Hey, thanks for taking the questions. We're curious about the 3 RSV Phase 2 studies currently enrolling for 938. Can you talk about the enrollment speed, interest level and Which one is gaining the most attention? And then for 2024 updates, do you expect to provide each Phase 2 readout 1 by 1 as the results become available? Or will you wait until they're all complete and disclose all the results together?

Speaker 6

And if you do choose to read them out sequentially, what would be the read across from one trial to another? And then I have a follow-up if I could.

Speaker 2

Sure. Thanks, Jay. This is Jay. We have The 3 Phase 2s for EDP-nine thirty eight, up and running. We've kind of Double down on the footprint of trial sites.

Speaker 2

It's not a robust RSV season Exactly now. We're sort of between seasons, although that we're still seeing activity in the Southern Hemisphere. We have sites down in Brazil and Argentina, New Zealand, Australia, South Africa And then in the Northern Hemisphere, we're in another 10 countries waiting for The virus to come north. So, big footprint, it's hard to Exactly, because they're very different patient populations. So peds is sort of one set of Circumstances and trial size, the adult high risk is a different one yet.

Speaker 2

And Bone marrow transplant recipients are very different patient population. So, each is going to Proceed at its own pace. I think the only thing that I would say is transplant is probably the hardest because you're again asking for a few different Not that common things to happen. 1 is to have a bone marrow transplant and another is to get RSV in a very Careful lockdown world for bone marrow transplant recipients where they're extremely cautious. So I think If I were, again, you can't truly predict, but I would predict that transplant will be Lagging behind the other 2.

Speaker 2

With the other 2, again, we've got we're in 15 countries. In peds, I think we have over 70 sites now active in the adult transplant or I'm sorry, in the adult high risk. We've got over a 100 sites active and we're just waiting for the virus to come back this fall and hopefully have a really For the sake of the trials anyway, a really robust sort of standard North American or Northern Hemisphere, I should say, season because we're throughout Europe, we're in the Middle East, we're in Asia And obviously all across North America. When it comes to reporting out, we're not going to wait. We're not going to harvest all three at once.

Speaker 2

So We'll read them out as they come.

Speaker 6

Okay, great. I guess as you look ahead to the Phase 3 studies for 938, How will the adoption of the RSV vaccine play a role in your Phase 3 strategy?

Speaker 2

Yes, sure. Yes, there's vaccines and monoclonal antibodies. Maybe I'll let Tara Kiefer Speak to that one.

Speaker 7

Sure. Hi, Jay. This is Tara. So in terms of the vaccines that have been recently approved in adults, We don't anticipate that having much of an impact. Both GSK and Pfizer have guided toward minimal uptake of their vaccines, at least initially in the first season.

Speaker 7

So just by way of example, GSK has sort of guided to expectations to be less than what they saw with Shingrix in the 1st year. So that was, So we don't expect that to have too much of an impact.

Speaker 6

Okay, great. Thanks for taking the questions.

Speaker 2

You're welcome.

Operator

Thank you. One moment for our next question. We have a question from Ed Arce with H. C. Wainwright.

Operator

Your line is open.

Speaker 6

Hi, Jade and Tay Tara. Thanks for taking our questions. Wanted to start with The RSV program, 3/23, and the recent Results from your Phase 1, including the PK, supportive of once daily. I missed the EC90 multiples that you stated as well as the nanomolar potency. And then beyond that, I just wanted to ask if you could opine on how We should think about benchmarking those relative to potential other Agents in development or indeed how to handicap the probability of success.

Speaker 2

So thanks, Ed. This is Jay. So the potency Of EDP-three twenty three, again, this is the L inhibitor. It's extremely potent. It's 0.3 nanomolar, so 300 Pikomolar in terms of an inhibitor, that's good, but it's Good, but not necessarily sufficient.

Speaker 2

What you want to see is obviously good PK and safety. So those were the 2 other things that we clicked off in the Phase 1 study. So we in the MAD Doses, we looked at 200, 400, 600, 800, so a range of 200 to 800 milligrams. And when we looked at the 24 hour trough time point after a single dose, At the low dose, we saw multiples that were 11x the EC90. And at the high dose, we saw multiples that were 44x the EC90.

Speaker 2

So just Whopping multiples of that very potent TC90 and we were able to do that In a manner that was very safe and well tolerated. So, I know, Ed, you've focused on Infectious disease for a long time, when you have an agent where you know the potency it takes To sort of tick out the bug and you can deliver those concentrations or high multiples of those EC90s safely With either antibacterials or antivirals, it's usually a very significant de risking step along the way. So I think It bodes well. The next proof in the pudding, I guess, goes to when we Get inside that human challenge study, which again will be starting early next quarter. And with that, we'll actually be able to look at antiviral effects at various doses.

Speaker 2

So stay tuned for that. Hopefully that will enroll fairly Straightforwardly because the human challenge study recall is in healthy volunteers that we Then in fact with RSV. So it's not a question of seasonality, it's really just a question of bringing in cohort after So that will be the next Steph, where we actually show hopefully some very solid, antiviral activity.

Speaker 6

Great. Well, I agree that these early readouts Do give a lot of confidence in the correlations to actual patient results. The other question I had was around the COVID program. And I believe this is a new sort of decision to look for partnerships For Phase 3, once you've completed the ongoing study, I'm wondering If the rapid drop in COVID vaccine demand as described recently by both Pfizer and Moderna impact the potential of the program either for our licensing or otherwise?

Speaker 2

Well, a reduction in vaccination can only lead to an increase in Infection where you need an antiviral. So we've always believed this to be the case that ultimately Vaccines would never have 100% efficacy. I had 5 vaccinations and Still got COVID. So they're never 100% efficacious And compliance is never 100%. We've seen that compliance drop way, way off.

Speaker 2

Now meanwhile, COVID is the COVID levels right now are a little they're pretty low, It's starting to creep up a little bit here in Boston as we watch the wastewater every day, but it's They're still pretty low, but we'll see what happens in the fall as we get closer to the sort of the normal So I think ultimately, we all now believe that the virus It's not going away. It's going to go back into sort of being like a nasty flu and we need drugs for that. So I think it's actually not new news that our decision on The partner in front of me, we made that. I think it's pretty clear last quarter that and even before that, we've telegraphed for really since the beginning of the pandemic that our ultimate aim is to To find that commercial partner that would really handle the late stage work and give us a global footprint that we couldn't possibly Achieve as well alone were we to do it. So that's still our plan.

Speaker 2

We'll see what happens to The virus starting to fall.

Speaker 6

Appreciate your comments, Jay. Thank you.

Speaker 2

You're welcome.

Operator

Thank you. And our next question comes from Eric Joseph with JPMorgan. Your line is open.

Speaker 8

Thanks for taking the question. Just actually sticking with the point about benchmarking for EDP-three twenty three, I guess,

Speaker 2

What type of data readouts from

Speaker 8

the human challenge study would kind of give you an indication of the molecule is Differentiated perhaps from 938, would you perhaps be including 938 as an active comparator in the trial? And Maybe just more generally with respect to the trial design, are there any key differences in the design of This upcoming hematology study compared to that conducted in 2019 for 938? Thank you.

Speaker 2

Yes, I think I mean we're going to use the same outfit to conduct the study. I think you should be thinking of this study as being Very much the same design. And I think the one of The world's best benchmarks to look at is EDP-nine thirty eight. That was one of the most robust data sets Ever performed in a or achieved in a human challenge study. So 938 will be the standard that we'll compare it to.

Speaker 2

We're not going to do sort of a side by side in this study. That would only drag it out further and postpone the time for us to get into Later stage studies with the molecule. I think we've got such a good handle on that challenge data and how to look at that challenge data that we'll be able to get pretty much everything we need to know from just The drug versus placebo. And to remind you, 938, the kinds of data that we showed with that was an extremely robust antiviral effect. So pretty much within 12 hours Of dosing 938, it altered the course of the infection.

Speaker 2

So people who were on 938 Viral loads continued to rise and plateau and only after many days returned back toward normal. So It was a highly statistically significant antiviral effect that we achieved versus placebo. And the same was the exact result when you looked at it was achieved with symptom scores as well. So From a symptom standpoint, within a day of dosing, symptoms had stabilized and started to go down, whereas people on placebo symptoms continue to progress. They got worse And they plateaued at an elevated level and then only gradually resolved over time.

Speaker 2

So that's the kind of data that we're looking for. And again, we've got a very excellent benchmark comparator With EDP-nine thirty

Operator

eight. Thank you. One moment for our next question. We have a question from Roy Buchanan with JMP. Your line is open.

Speaker 3

Hey, thanks for taking the A couple on 235, any publications or presentations of details from the SPRINT data expected later this year?

Speaker 2

The timing on that is subject to getting Presentation is accepted at conferences. So we'll we are planning presentation of the data. So what I will say is stay tuned On that front with regards to timing and we'll certainly announce the time and place and the venue once we've been accepted for presentation.

Speaker 3

Okay, great. And then anything you can give us on the tone of the party discussions for 2 35? As you mentioned, cases are pretty low in the U. S. At least.

Speaker 3

Are people waiting to see how that plays out this winter? You also mentioned regulatory uncertainty maybe. Is that a gating factor? Anything you can tell us about that?

Speaker 2

Not in any degree of specificity, but you've hit Interesting bets that are not only on our minds, obviously partners think about these things too, trying to exactly size What the market is and understand as clearly as they can what that regulatory pathway is. We can't control the what the infection looks like in a given season, but what we can try to do is glean Clarity from regulators in terms of pathways. So we're working on the part that we can control right now.

Speaker 3

Okay, great. And then one last one on 514. Just mechanisms for combination, are you looking at things that are already out there and being tested like just TLR Random Choice, or are you pretty much through those already? And are you looking at something completely novel, maybe hasn't been in the clinic, maybe even from an academic lab?

Speaker 2

Thanks. We've looked at a lot of the usual suspects That are out there. I mean, obviously, the TLRs are out there. People have looked at various RNAi approaches and whatnot, we haven't grabbed on to What we think is necessarily the right mechanism, yes. And so we're still monitoring the field.

Speaker 2

It's a little bit frustrating that There aren't a lot of sort of profound new steps forward in this and this field of HBV. So right now, It's a little bit of a holding pattern. As I've said before, we're not going to throw other agents in to create the triple combo Until we have a great deal of confidence that it's a study worth funding. So in the meantime, We're hunting still.

Speaker 3

Okay. Thank you.

Speaker 8

You're welcome.

Operator

Thank you. Our next question comes from Akash Tewari from Jefferies, your line is open.

Speaker 7

Hey, this

Speaker 9

is Amy on for Akash. So the first question on EDP-three twenty three, what percent of the drug is bound to plasma protein in vivo. And additionally, do you expect any safety risk from targeting RNA polymerization? We've seen neutropenia with lumacitabine, but no, that's a new analog, which is a little different, but would love to hear your thoughts here.

Speaker 2

Yes, I don't recall the level of protein binding, but the ratio or the multiples

Speaker 4

of the

Speaker 2

EC90 that I quoted earlier, which are ranged between 1144 fold were already adjusted for that protein binding. So, whatever the protein binding is, this is multiples on top of that When you look at it from a free drug perspective. And you're correct, lumacitabine being a nuke, a lot of the nukes in the field had Issues, nukes not uncommonly Suffer or benefit from, I guess, depending upon how you look at it, broad Activity across other polymerases and so fuel activity can be a problem. But EDP-three twenty three is a non nuc polymerase inhibitor. And so far, Preclinical safety was excellent and human safety in terms of safety and tolerability at least from our Phase 1 study was also very, very strong.

Speaker 9

Great. And then on 235, Are there any additional data sets that a potential partner would be looking for to support our collaboration? And then when do you expect to get clarity from a regulatory perspective on path to registration?

Speaker 2

So I think right now we have the clinical data that we have With regards to the SPRINT study, again, we saw antiviral effect. We saw effect on symptom improvement. So those are the data that we have and the as I mentioned, the regulatory discussions are ongoing. When we'll finish those, they'll be done when we're done with the exchanges. So It's hard for me to put a time point on that right now, but we'll have further updates

Speaker 9

Great. And then finally, one last one on cash runway. Can you go over the main drivers for you

Speaker 4

Well, as we've indicated, this is Paul Nellet. We've made the decision to wait for a partnering situation to continue the Phase 3 work on 235 And that's a significant extension of our runway for the most part and that's the primary driver. And obviously, we've not discussed any potential revenue or anything like that from a partner arrangement. It's just simply the expense bearing of the Phase 3 trials.

Speaker 9

Got it. Thank you so much.

Operator

Thank you. Our next question comes from Brian Skorney from Baird. Your line is open.

Speaker 8

Hey, this is Luke on for Brian. Thanks for taking the questions. First on 3/23, any consideration with regard And then just a second one on And RSV, the dual inhibitor.

Speaker 10

As you finalize selection of that candidate, is there any consideration of

Speaker 2

Yes. So, 323 this is Jay. 323, the challenge study, again, it's the challenge study, Right. It's the sort of right of passage for RSV molecules. Everybody puts them through the challenge study and For the most part, everybody runs the challenge study in a very similar way so that you can cross trial comparisons are always never Perfect or ideal, but to the extent that you can compare data in this setup, It's helpful to run it in the same way.

Speaker 2

So, not every molecule that goes into a challenge study comes out successfully from a challenge study. So it's not a given, but we view it as a good next Step and one that again further de risks things because if you come out of the challenge study with really robust data, you Know that you have a good antiviral in a human setting. So, you put that in your back pocket. And then with regards to human metanumomoresvdual, I don't there's not really not sure I fully understand your question. I mean there we have Again, we put data out on a prototype.

Speaker 2

We're aiming to have our final candidate or our candidate finalized In Q4, you can never exactly balance potency. Well, I suspect you could try to do that maybe for the rest of your life trying to get everything Exactly balanced, but that doesn't kind of matter because you always whenever you have a broader spectrum drug, there's always a dose defining pathogen, Which is the one that you're the least potent against knowing that if you dose for that and account for that And you'll be good against the, in this case, the other pathogen, which has even greater potency. We're optimizing different characteristics of the molecule in that program, Settling down to finalists that we're just doing sort of final characterization on the profile. And then assuming that all goes well, again, we're targeting Q4 As the timing for that candidate selection final selection.

Speaker 8

Great. Thanks. I'll hop back in queue.

Speaker 2

You're welcome.

Operator

Thank you. We also have a question from Nick Gaskic with Leerink Partners. Your line is open.

Speaker 11

Hi, everybody. Good afternoon. This is Mick Gassick on the line for Roan Maybe first off on your RSV program, which 3 23 doses are you planning to evaluate and the upcoming challenge study. I don't know if you've mentioned that. And maybe also, I guess, what learnings from the development of 938 so far Could you apply that to possible future development of 323?

Speaker 11

And are you planning to go after similar patient populations for 323 or could you explore other populations as well.

Speaker 2

Yes. So, we haven't disclosed the final doses For that study, we're likely to do that in connection with the announcement of the initiation of the study. So Stay tuned for that. Again, we're aiming for early Q4. But Suffice it to say there will be doses within the ranges that we've studied.

Speaker 2

We're really trying to just figure out what optimal Doses for various exposures that we want to try to hit and look at the product profile overall. And then with regards to 938, I mean, we've learned a lot about RSV through the use of 938 and I can only imagine that we'll have a more targeted expedient Pathway for 323 based on our learnings, whether it was what we learned in the standard risk patient population, which is that patient population doesn't need a drug. And then through the recruitment of our 3 high risk patient populations. There's very interesting teachings In each of those patient populations that you can only sort of figure out once you get into them. And We've learned a lot along the way with 938.

Speaker 2

So exactly The trial after the human challenge study, that's something that we're thinking about Very diligently right now, but not ready to speak to today.

Speaker 11

Got it. And also are you planning to pursue or evaluate 323 in similar patient populations or Would you explore other types of patients as well?

Speaker 2

Well, those are the 3 high risk patient populations. Peds, probably the largest patient population from a market perspective, High risk adults and immune compromised patients Of different flavors. I mean, we've chosen from immune compromise, we at least in RSV TX With 938, we've zeroed in on hematopoietic stem cell transplant, but there's other immune patient populations, Immune suppressed patient populations that one could also consider. But anyway, you want to be in a high risk patient population of one flavor or another if you really want to get it over the finish line.

Speaker 11

Helpful. Thanks, Jay.

Speaker 2

You're welcome.

Operator

Thank you. And I'm showing no further questions at this time. I'd like to turn the call back over to Jennifer Fiera for any closing remarks.

Speaker 1

Thank you, operator, and thanks to everyone for joining us today. If you have additional questions, please feel free to contact us by email or call us at the office. Thanks so much and have a good night.

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Earnings Conference Call
Enanta Pharmaceuticals Q3 2023
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