Enanta Pharmaceuticals at Baird’s Biotech: Strategic Virology and Immunology Shift

On Tuesday, 22 July 2025, Enanta Pharmaceuticals (NASDAQ:ENTA) presented at Baird’s Biotech Discovery Series, outlining its strategic shift from a virology focus to a broader portfolio that includes immunology. The company highlighted its financial stability and upcoming data readouts, but also acknowledged challenges in differentiating its RSV therapeutics in a competitive market.

Key Takeaways

• Enanta is transitioning from a virology focus to include immunology, emphasizing its RSV and immunology programs.
• The company maintains financial stability with a cash runway into fiscal year 2028, supported by royalties from AbbVie’s hepatitis C drug, MAVERIT.
• Upcoming data readouts for the RSV HR study and a third immunology program announcement are anticipated later this year.
• Enanta’s RSV therapeutics aim to address unmet needs with replication inhibitors offering high resistance barriers.
• The company is exploring partnerships for its RSV assets and is open to strategic collaborations.

Financial Results

• Enanta’s financial position is bolstered by royalties from AbbVie’s MAVERIT, which significantly contribute to operating expenses.
• The company closed the last quarter with over $193 million in cash and received a $33 million tax refund in April.
• Royalties from MAVERIT will continue until 2032, after which Enanta will receive 100% of the royalties.

Operational Updates

• Enanta is advancing its RSV programs, zelicapavir and EDP-323, both designed as replication inhibitors with high barriers to resistance.
• The zelicapavir program has completed several phase two studies, with a phase 2 readout for high-risk adults expected this quarter.
• EDP-323 has shown robust antiviral effects in challenge studies.
• The immunology program includes a KIT inhibitor, EDP-1421, targeting urticaria, and a STAT6 inhibitor positioned as an alternative to Dupixent.

Future Outlook

• Enanta plans to pursue phase 3 studies with zelicapavir and phase 2 studies with EDP-323.
• The company is open to potential partnerships for its RSV assets but has not factored these into cash runway projections.
• A third immunology program announcement is expected later this year.

Q&A Highlights

• Analysts expressed interest in Enanta’s RSV strategy, focusing on treatments due to unmet needs and differentiating through replication inhibitors.
• The company emphasized its pursuit of oral small molecules in immunology for better tolerability and selectivity.

Readers can refer to the full transcript for more detailed insights.

Full transcript - Baird’s Biotech Discovery Series:

Mike Perrone, Baird’s healthcare specialist, Baird: And thank you for joining Baird’s Biotech Discovery Series. I’m Mike Perrone, Baird’s healthcare specialist, and I’m pleased to be joined by Enanta Pharmaceutical CEO Jay Lulli and senior vice president of product strategy and development, Tara Kiefer, as well as my colleague, Baird’s senior biotech analyst Brian Skorney, who will be moderating the discussion today. As a reminder, Baird’s biotech discovery series is an opportunity for investors to hear directly from interesting and innovative biotech companies in a fireside chat format. A few quick logistics. If you would like to submit a question, you can do so via the webcast portal or you can email brian at bskorney@rwbaird.com.

And finally, before we begin, I’m required to remind attendees to please refer to the event calendar, publish research or Baird’s website for important disclosures regarding the companies discussed during this event. I’ll now hand it over to Brian to kick off the discussion.

Brian Skorney, Senior biotech analyst, Baird: Great. Thanks a lot, Mike. And, hello, everyone online. Thanks for joining us today. Like Mike said, I’m Brian Skorney, senior biotech Analyst here at Baird.

I’m really glad, to have with us today, management team from Nantes Pharmaceuticals. I’ve been following them, I mean, probably more than a decade at this point. I’ll let, Jay and Tariq give a little bit of an intro to themselves and their company before we get into into the q and a session. So to start, Jay, would you mind providing a little bit of background on Enanta, including, you know, maybe a brief history of the company’s focus and how that plays into today’s company strategy?

Jay Lulli, CEO, Enanta Pharmaceutical: Sure. Thanks, Brian. But before I begin, I wanna remind you that I’ll be making some forward looking statements. For a summary of the risks associated with these statements, please see our filings, on sec.gov and on our website. So Enanta, maybe we could pull a slide up here.

Enanta, as you are I I know, Brian, well aware, we started several years ago in virology and, brought forward, a couple of, drugs for hepatitis c with AbbVie. We’ve also, focused on other liver viruses and respiratory viruses, a big focus in RSV right now, which I’m sure we’ll get into in in some detail. We’re involved in COVID, and suffice it to say that over time, have migrated our sort of our portfolio into immunology. We found that, you know, over time, some of the the main viruses that we were focused on targeting, we had accomplished, and we wanted to move into another area that’s has certain adjacencies to virology and would allow us to to broaden our reach into many other indications. So we moved into immunology a a few years ago.

We’ve announced a program focused on kid inhibition, program focused on coming up with an oral stat inhibitor, and we’re also planning on, you know, announcing a third program later this year. So, again, an initial strong focus in virology, building into immunology. We have good balance sheet. We have we closed last quarter with just over a 193,000,000 in cash. That does not include the over $33,000,000 tax refund we received, in in April, which, by the way, came in the form of paper checks.

So, anyway, I think, maybe we flip to the next slide. We can show our, pipeline at at large, and then, we can dive in anywhere you want, Brian. I think we

Tara Kiefer, Senior vice president of product strategy and development, Enanta Pharmaceutical: You’re on mute.

Brian Skorney, Senior biotech analyst, Baird: Sorry, I had to unmute. Yes, maybe focusing on RSV to start, think you have a pretty near term catalyst coming up there. But maybe tell us a little bit about your view of the opportunity here. How does this virus work, and where do you see the opportunity for an effective antiviral? And maybe what are the current options for preventing or treating RSV, and how are they used today?

Jay Lulli, CEO, Enanta Pharmaceutical: Sure. So, you know, RSV has been around for a long time. I mean, a lot of people really only heard about it in connection with the pandemic. You know, COVID was running around. Everybody learned SARS CoV two.

And then RSPs, you know, was repressed during the pandemic, but then it came out afterwards. So was flu. It was repressed during the pandemic and then kinda unfurled. And so now people talk about the triple demic of of COVID, RSV, and flu and so on. But in reality, RSV has been around.

I think it was first characterized in 1956. But in spite of that and in spite of people trying for a real long time to come up with prophylactic approaches, then we can talk about those. There have been some recent developments there. But nobody has successfully brought forward to completion a therapeutic. And so our focus is on therapeutics.

We wanna try to bring forward the first ever treatment for RSV. The way we’re differentiated, I think, from most approaches that have been used in the past, in the past, most people really focused on viral entry. So they took an approach where they targeted the fusion protein, the so called f protein. This is what the antibodies target. It’s what vaccines all vaccines can target more than that.

But fundamentally, it’s the f protein and prophylaxis that people have used. And so small molecules were developed by others in that approach. And what was found was a a couple of things. It’s easy to get really potent molecules, but it was also very easy to generate resistance against those molecules. And so it has super low barrier to resistance.

The other thing is we reason that when people present with an RSV infection, they’ve been infected for a few days. The virus has already entered a lot of cells. It’s set up replication machinery, and now you have sort of unbridled replication going on. And so we reasoned rather than trying to block viral entry at a stage when people are already symptomatic and undergoing viral expansion. It was better to try to focus on, you know, sort of tried and true mechanisms of, direct acting antivirals that would shut down viral replication.

And so to that end, we set about working on, a couple of different programs. The first one is our n protein inhibitor, known as zelicapavir. We also have, an l protein inhibitor, called, EDP three two three. The l protein is the polymerase. So many people have heard of polymerase inhibitors in connection with, antivirals.

And so I think what we’ve chosen here are two very logical replication inhibitor approaches that, again, will target viral viral replication rather than viral entry. We also know that we have high barriers to resistance. So combination of replication, high barrier is where we are where we are focused. With regards to the prophylactic options that you asked about, there are really two approaches. One is monoclonal antibodies.

You may remember years ago, was a monoclonal antibody called Synagis, which was the first sort of targeted antibody. It worked to some degree prophylactically in high risk premature babies, but it did not work therapeutically. And it was very expensive, and so, you know, it wasn’t widely used. There’s a follow on to Synagis called Nirsevimab. It’s a longer acting and and I think has been more widely adopted.

But, you know, the problem is that the these antibodies just still don’t provide lasting immunity. It’s only a passive immunity that you get, and you really can only use them in the the first season RSV season. If you’re born into an RSV season, you might get it. After that, you’re kind of on your own. The antibody, will be gone in a few months, and you won’t have any lasting or any immunity to the virus until you actually get it.

So you’re you’re destined to have multiple RSV infections just like you, you ordinarily, would. There’s been a couple of vaccines that have approved and approved. Pfizer has one that’s used in high risk adults. It’s also used in maternal vaccination where you vaccinate the mother right before she’s due to give birth. Antibodies are generated, transferred transplacently into the into the fetus, and then ultimately, the the child is born with, again, some short term immunity but has the same problem as the others.

GSK also has an adult vaccination, but it’s only used in adults, not in peds. And, you know, these vaccines, the uptake has actually been sort of suboptimal in, you know, and there are you know, it’s basically, not a lot of uptake with that vaccine. So punch line is, whether people get vaccinated or not, there’s still breakthrough infections. Most people aren’t vaccinated, and, none of it’s long lasting. So what we wanna do is, again, come up with a treatment because there’s that’s where the huge unmet need is out there.

So maybe I’ll maybe I’ll pause.

Brian Skorney, Senior biotech analyst, Baird: No. No. That’s a that’s a great intro to it. So so the zelacaprevir program focusing on that, specifically, it’s seen results in in several phase two studies, including a challenge study, seasonal RSV infection study and a pediatrics study. Can you walk us through the learnings that you have from those results?

Jay Lulli, CEO, Enanta Pharmaceutical: Yes. So zelicapavir, formerly known as EDP nine three eight, if you remember that number, it targets the the nucleoprotein. This is the only n protein inhibitor in clinical development today, currently in phase two. We had, you know, great phase one healthy data, safe, well tolerated, good blood levels. And then the rite of passage in RSV is then to move into a human challenge study.

So we did that. We got very strong results in that both from viral load suppression and also symptom suppression. And now where we are is we’re currently focused on high risk patients. These are patients that are at one end of the age spectrum or the other. So obviously, very young children are immune naive until they’ve been infected.

Then, you know, again, they keep having repeated infections as a child. So they’re at one level Elderly people at the other end of the age spectrum start to have that immunity that they built up during their adulthood starts to wane. So there’s immune senescence that, jumps in and suddenly they become more vulnerable. There are also adult populations that have high risk, people with respiratory difficulties, asthmatics, people with COPD.

Also congestive heart failure predisposes you for a poor experience in terms of an RSV ex infection. So these are the other high risk patient categories that we’re that we’re currently studying. In terms of that, you know, taking them in order, the challenge study, again, we saw highly statistically significant reductions in viral load. Symptoms were also very well suppressed over time. It was, you know, safe, well tolerated, and it the onset was pretty actually pretty quick in terms of that because, again, timing is of the essence when you’re dealing with acute respiratory infections.

We went from there into a translational study before we got into the high risks. And we we took people from sort of a similar patient population as the challenge study. These were otherwise healthy adults. And we asked the question, well, what if we caught these people, you know, in the real world with community infection? You know, could we get to them in time?

You know, did they need to be treated? These were the kinds of questions we asked about a so called standard risk population. That was a study called RSVP. And unfortunately, you know, what we learned was these patients don’t need to be treated. And in fact, I would submit that they can’t really be effectively treated because even though we recruited patients within forty eight hours of symptom onset, which is about as soon as you can possibly do it.

And we got, by the time we got drug on board at forty eight hours, viral loads had already peaked and were coming down. Symptoms had already peaked and were coming down. So it was just impossible to capture them soon enough. Their immune systems were very much intact. And for that population, the so called standard risk, it’s it’s just sort of like a little bit of a bad cold.

So not something that needs to be treated nor can be treated. The next study that we did was in a high risk patient population. And that was our first in peds study. And there are the primary endpoints that we were looking for safety and tolerability. Again, we’re we’re dosing babies down to as young as 28 of age.

And so safety is just super, super paramount. We wanted to also look at PK. You know, we had a good handle on our adult dose, but dosing peds, you know, at various weights and ages is a is a different matter. So we had to carefully do some dose ranging. And then the other plan was to demonstrate an antiviral effect and and then also symptoms.

It would be hard to get a lot of good symptom data in this study, but we wanted to try to capture as much as we could using this proprietary observer reported outcome tool. And so anyway, the good news was it was safe and well tolerated in peds. We saw very good blood levels. Even at our low dose, we deemed it to to be an effective dose based on what we knew from our challenge study in terms of what we needed. And, we demonstrated an a good antiviral effect, as well.

So all of those things were the primary measures of the study. We executed, on them. And and then we even you know, this proprietary tool that we’re building ultimately for registration studies called resolve p. Again, the babies can’t self report. Although they do in certain ways.

It’s hard to have a a good tool, you know, for crying and other kinds of things, but you have to rely on the observers in order to capture this information. So we’ve been working with physicians, caregivers, FDA, European, regulators, etcetera, to build a an observer reported outcome tool that would ultimately be used, in registration, studies. So we got a little bit of that data. I think it was on about a dozen or 15, babies. There was a a trend, from a symptom improvement, but, we need to get more data on that in a in a bigger study.

Yeah. So those are the studies that have been completed to date, and we’ve got one more coming obviously.

Brian Skorney, Senior biotech analyst, Baird: Great. So so maybe moving on to that phase two readout that I think we’re expecting this quarter in high risk adults. Can you can you discuss this study design, and what in particular we we should be looking for on the readout to have confidence in in the ability to move forward?

Jay Lulli, CEO, Enanta Pharmaceutical: Yep. Well, maybe we can there we go. Let’s put up a slide. So, yeah, that’s the ped studies. So let’s see.

I think we will go on to the high risk. Here we are. Yeah. So the RSV HR study is a proof of concept study. We have about a 180 adults in this study, so it’s it’s about twice the size of our ped study.

And, these again are all patients that are at high risk for severe outcomes. So the populations I just mentioned, elderly, COPD, asthma, and CHF. And also, just so that we didn’t, you know, enrich a study with, otherwise healthy asthmatics or people who are, you know, quote, in our elderly bucket, but are 65 to 74. You know, they’re, quote, elderly, but not elderly. We took those 65 to 74 year olds along with the asthmatics and said they can’t be more than twenty percent of the study.

So eighty percent are 75 or older or COPD or c and or COPD or CHF. So it’s a larger study. It’s enriched for high risk patients, as I just mentioned. And we also have a tight window on recruitment. So the recruitment window is patients are enrolled within seventy two hours of symptom onset.

So it’s really a three day window cut. You know, it’s a little tighter than we had up to five days in our ped study mainly because we were trying to recruit h RSV positive children so that we could do PK and and and that sort of thing, and it didn’t the day from symptom onset didn’t matter quite as much. We did see that, you know, that within three days seems to be about the sweet spot in that study, and we’re using it in a go forward way here too. So larger study, tighter window, and the, the primary endpoint for reduction here is, symptoms. So, you know, unlike the ped study where we only had the pediatric tool toward the end of the study, to try to capture some information on symptoms, We have a tool called the RIIQ that where it’s been used previously in in studies.

So we have sort of a an understood tool to use, and we have we’ll have data on every patient. So we’ll have, you know, a good symptom dataset, which is which is our primary endpoint. So I think the next slide this is how we’re kind of thinking about what what to expect. So there’s not a lot of data, symptom wise in terms of looking and again, what we’re looking at is, time to symptom resolution. Okay?

So a shortening of the time to resolution, and we want something that’s clinically meaningful. So, since there aren’t any, registration studies that have been done in RSV for for this age population. What we wanted to do was at least look at other acute respiratory infections. And so I’ve got flu here on the left and SARS CoV-two on the right. And if you look at, Tamiflu, which going from left to right are the first two sets of, data points, what you can see was in the Tamiflu phase three study, was 65 and above, they saw about a day shortening and time to resolution of symptoms.

And again, this is a phase three study. As you can see at the very bottom, there’s an n there. It’s around, well, just under 500 patients. And that proved to be stat sig for one day. The next panel is also Tamiflu.

It’s sort of a meta analysis across a lot of different studies. But what you can see is it’s also about a day shortening the time to resolution. The next the third set of data is Baloxavir, which is Shionogi’s flu drug. And there, it was a registration study looking at adults, well, age 12 to 64. Again, a little bit all of these are are bigger studies, but showed about a day shortening in time to resolution of symptoms.

And then switching viruses now and drugs. This is SARS CoV two. This is a phase three that was run-in Japan for a Japanese approval on Encitralvir. Larger study just under 700 patients. And again, the the clinically meaningful result was, you know, about a day in each of these instances.

So it’s sort of uncanny across influenza, across two different drugs for influenza, across SARS CoV two. You know, the message seems to be, you know, about a day would be a clinically meaningful input. So I think it’s even on the next slide. We say, you know, for this proof of concept study, RSV HR has a smaller n. You know, we’re only at a 180, but I think that’s still a decent size proof of concept study.

We’re looking for about a day shortening and time to resolution. And we’ll be capturing lots of other secondary endpoints, which you can see, you know, sort of highlighted below. So we’ll look at the, you know, the totality of the shortening and resolution, some of these other secondary endpoints to provide confidence for moving into a larger phase three study, which, you know, would be sized in a way to to confirm with statistical significance the the findings from this study. So, that’s the dataset. Again, as you mentioned, it’s due to come late this quarter.

Brian Skorney, Senior biotech analyst, Baird: Great. So we look forward to those results. I know you have a second program in Phase two development for RSV EDP-three twenty three. Can you talk about how you see, the development of this asset in the context of zelacaprevir development? Do you see different or overlapping opportunities here given the different mechanisms?

Jay Lulli, CEO, Enanta Pharmaceutical: Yeah. So as I mentioned earlier, three twenty three is an L protein inhibitor, which is the RNA dependent RNA polymerase. And as I also mentioned, it was zelicapavir. After a successful phase one, which we had in healthy volunteers, the the next rite of passage is to go through the the challenge study. And, you know, when we were we got that data in September, I think, of last year.

And before that, about a year ago, people were asking, you know, well, what would would make you happy? You know, what’s what would be the signs of success in this study? At that point, we were just focused on, you know, sort of recapitulating the data that we saw, with Zelie Capavir. It’s a very good Zelie was a great challenge study. We published it in the New England Journal.

And so that was sort of the bar for excitement, if you will, on data. And what we were pleased to see was there are even some aspects, I think, that are that are even maybe more exciting with this molecule. So we saw very strong viral loads in the, you know, 85 to 87, percent range in terms of reduction of viral load AUC. We saw very good symptom, reduction too in terms of a c reduction of symptoms in the, you know, sort of 66 to 78 range. But where I think this really jumped out was if we can pull up the slides on first the viral load by PCR.

Let’s see. There we go. This is the PCR one. And so there it is, eighty five to eighty seven percent, you know, reduction. And what we did was a high dose and a low dose we explored, and they were basically exactly the same because even the low dose gives massive multiples of the protein adjusted EC 90.

So you can see that on day zero, which is defined as when the first drug is administered, if you look at the y axis, the the viral loads are, you know, between two to three logs. And what you also see is after the first dose, first little tick mark there is twelve hours time point, it has already altered the course of the infection. Placebo in green, viral loads keep going higher, drug treatment, the lines separate. When you look at this, this is a PCR measurement. So you’re looking at, you know, amplifying live virus, dead virus, viral particles, etcetera, etcetera.

But if you look at the the viral loads by culture, which is on this slide, you can see just how just how robust this antiviral effect is. And so here you see a 97 to 98% reduction in in viral load. In fact, twelve hours after the first daily dose, the viral loads have are down and and then basically just flatlined. So this is a very, fast acting drug. Again, as I mentioned, when you’re dealing with acute respiratory viruses, time is of the essence, and you need to get a drug on board as quickly as possible.

The only thing better than getting a drug on board as fast as possible is to have a drug that works really quickly. So 03/23, I think, may well eclipse zelicapavir slightly by just the speed of onset. You asked about combinations and positioning. I think, you know, we know preclinically these two drugs play well in combinations. We’ve explored that.

We’ve looked at the virology of that. There’s nothing in the profile of the drug either drug that would suggest any DDIs that would be problematic. And so I think the the combinability is is very good. The question, real question is, do you need to combine them? And if so, in what patient population?

And our current thinking is that with a standard patient, sort of a typical RSV patient at either end of the spectrum, monotherapy is probably gonna be adequate for an acute virus. It has a high barrier. They’re both potent. They’re both, pretty quick acting, and, you might not need to do combinations, which is is great in my opinion. I mean, spent a lot of time in the combination world of hepatitis c and hepatitis b, combination drug development.

If you don’t have to do it, it’s, you know, it’s always simpler to not have combinations. And so but that said, you know, could there be populations, highly immune suppressed population? So this in this patient population, if somebody gets infected with RSV, it doesn’t behave like an acute respiratory virus because they can’t clear it. And that’s a situation where you need to dose certainly, you probably need to dose longer than just five days. And you might also benefit from having, you know, orthogonal approaches going after the virus in a more heavy handed way, with two different mechanisms.

So that’s something that we’re thinking about. The other is just, you know, when we charted out RSV several years ago, it was with the goal of not only having the first RSV drug to the market, but also having, you know, sort of the best portfolio for the long term. And to that end, you know, one might imagine Zelle has been potentially the first market following it with three two three, you know, in a longer term scenario for life cycle management, either as monotherapy or, used in combination. So that’s that’s our current thinking about it.

Brian Skorney, Senior biotech analyst, Baird: Got it. Great. So on your slide deck, you list RSV programs under BD opportunities for partnership. Pharma has kind of been in and out of antivirals over the years. Can you discuss the level of interest you’re seeing on partnerships for the RSV assets, appetite for antivirals in general?

And any question just on the level of confidence and timeline for a partnership?

Jay Lulli, CEO, Enanta Pharmaceutical: Yes. Well, I won’t I think let us get our data. We’ve got some data coming. And I probably won’t I probably won’t comment too much on sort of detailed business development discussions. But suffice it to say, I think there are pharma companies out there that are interested in in RSV antivirals.

And it’s a a strong there’s just no there’s no there’s no approved therapeutic, really. Right? So you have a a market that’s just laying there open. Many of the fusion inhibitors, as I’ve mentioned, have faded away. You know, Gilead had one, and it, you know, went away.

G and J ultimately shut down their program that had a fusion inhibitor in it. Roche had one that they ultimately handed off to ArcBio. They’re developing it. Well, mostly has been developed in in China. Pfizer had a a fusion entry inhibitor from Reviral.

They dropped that one. So I think I think it’s time for replication inhibitors. As I said at the outset, we were very focused on that from day one. We only made fusion inhibitors to benchmark and to demonstrate to ourselves that they had very low barriers to resistance, etcetera, etcetera. So, you know, we’ll see.

But I it’s time for people to have a therapeutic opportunity for RSV.

Brian Skorney, Senior biotech analyst, Baird: Great. So so maybe shifting gears a little bit. You you’ve started to deploy your medicinal chemistry expertise in into the I and I space. Maybe talk through a little bit this pursuit, and and how you you think about strategically per pursuing targets.

Jay Lulli, CEO, Enanta Pharmaceutical: Yeah. So, as I mentioned, you know, we we targeted most of the viruses we set out to target and, you know, looked in fact, until the pandemic came along, we thought we were ready to move to some other things. Pandemic probably deferred that a little bit. But even during the pandemic, we started building for the future in terms of other areas that we could pick, and immunology just surfaced. Some of our virologists had actually trained in immunology and, you know, became virologists.

And so, you know, we had the skill sets we thought inside to be able to go after some of this. We just wanted to make careful selections in terms of targets and unmet need and so forth. So we un I think at the beginning of last year, we unfurled our first program, which is in KIT inhibition, again, going after wild type KIT, going after small molecule approaches. I think the antibodies had sort of paved an interesting path for wild type KIT small molecules to to come in. We also said at the beginning of last year, you know, our goal would be to have a second program by the end of the year announced, we now know that to be stat six.

We’ve been working on stat six actually for for some time now. Didn’t announce it till the end of last year. Similarly, now we we have an another program announcement that we’re aiming for later this year on a third program. So we’re trying to bring these out with a certain cadence, with a certain critical mass of having explored the targets, explored the markets, looked thought through clinical trials, thinking for things where there’s either clinical validation or good biomarkers or human genetics, looking for things where there’s very significant markets, but maybe an opportunity for a small molecule modality to, to fit in. And, yeah, so this is how we’ve, how we’ve largely, selected these things.

We’re also trying to, you know, at the time of announcement, you know, have assays and models in hand, chemical matter built up, intellectual property, know, underway, etcetera, etcetera, so that there’s a certain level of maturity of these programs when we pull them out.

Brian Skorney, Senior biotech analyst, Baird: Great. So maybe turning to the the first half of the the KIT inhibitor, I I think you’ve nominated a drug now, EPS fourteen twenty one, I’m if I’m not mistaken. How do you sort of think about the validity so far of KIT as a target and how your approach might be differentiated?

Jay Lulli, CEO, Enanta Pharmaceutical: Yeah. I’ve been talking a lot. I think I’ll hand this one to Tara. I’ll let her chat for a little bit.

Tara Kiefer, Senior vice president of product strategy and development, Enanta Pharmaceutical: Sure. Yeah, so I think with our KIT inhibitor, in terms of the first indication we would look at would be urticaria, so either chronic inducible urticaria or chronic spontaneous urticaria. And what we know about that disease is that mast cell activation is actually a primary driver of that inflammation in the skin, and it’s also implicated in a number of other multiple other allergic disease areas. And so what we’re doing with KIT is inhibition of this is directly reducing the quantity of mast cells that are available to cause that pathology by apoptosis and depletion. And so it’s really targeting and addressing a key driver of the disease.

The current therapies that are out there are really reducing just the level of activation of mast cells, but KIT inhibitors will directly reduce the quantity of mast cells. We also like to target because there’s good clinical validation, as Jay mentioned, with an antibody against this target. They this is from Feldex, and they’ve now shown long term 52 data with a phase two study. And that efficacy that has been established is is, you know, some of that in disease efficacy that we’ve seen. So we’re hoping to replicate that with an oral molecule.

And, you know, the nice thing about this target as well in this disease is that there’s really good biomarkers that are available in, for example, serum tryptase that you can get early signs of efficacy in the clinic even in healthy volunteers. So you’d asked about differentiation, and I think for that, we’re obviously targeting, as we always do, a best in disease efficacy with an oral option, optimizing around things like potency, selectivity, and then DMPK properties as well. The other thing we’re thinking a lot about is dosing strategies for this molecule that may enable a more favorable tolerability profile.

Brian Skorney, Senior biotech analyst, Baird: Great. So maybe just talking a little bit more about development strategy and how you kind of think about the monoclonals out there. Do you see fourteen twenty one? Really just on the oral bioavailability and the oral option that you see as an improvement over the monoclonal? Or do you sort of see a chance in any of the characteristics for actual outperformance on efficacy?

Tara Kiefer, Senior vice president of product strategy and development, Enanta Pharmaceutical: Absolutely. I mean, certainly oral is an advantage. Many patients will prefer to have an oral option in terms of route of administration. But certainly we’re thinking about other differentiation factors as well. I hinted a little bit about that the end of my last comment, talking about different dosing strategies.

But the one thing about the antibodies has been some on target tolerability in the form of decline in neutrophils and some hair color changes. They seem fairly manageable, and many of them are just tolerability issues and not really safety effects, but we are thinking a lot about having different dosing strategies that might be able to better thread that needle between efficacy and safety to improve that profile. And and so what I mean specifically about that is, are we able to dose enough to drive down the population of mast cells that would allow for the the same clinical efficacy? But that may that PD effect may outlive the PK in that once you deplete those mast cells, it will take some time for them to repopulate. And if you take the drug pressure off, you may be able to see a repopulation of other cell types like neutrophils blood cells that have a more rapid turnover rate.

And so we’re thinking a lot about how we might interrogate this in the clinic and optimize further around a better tolerability profile.

Brian Skorney, Senior biotech analyst, Baird: Got it. And then moving on to STAT6, which is your second announced INI target. Maybe tell us a little bit about the validation of this target in INI. Think STAT6 inhibitors have been called the oral Dupixent.

Tara Kiefer, Senior vice president of product strategy and development, Enanta Pharmaceutical: How does stat six

Brian Skorney, Senior biotech analyst, Baird: fit in pathway versus IL-thirteen?

Jay Lulli, CEO, Enanta Pharmaceutical: Yes. So basically, you’re dealing with the same sort of signaling pathway. When you look at IL four, IL 13 signaling upon receptor engagement, you get JAK activation, JAK’s phosphorylates STAT6. And then when you get the phosphorylated STAT6, you get dimerization of STAT6 and translocation into the nucleus. And then subsequently transactivation of a number of pro inflammatory cytokines, basically.

So it’s the same signaling pathway coming through stat six. We like we like it because stat six is sort of specific to that pathway, whereas JAKs, people who have entered know, JAK kinases inhibitors work well as well, but they’re involved in the signaling of a lot of other receptors. So you don’t get quite the same level of selectivity as you do with with stat six. So we like it for the validation that it has mainly through I mean, there’s there’s genetic gain of function and loss of function types of studies that you can look at mechanistically. But, you know, the ultimate validation of that pathway, I think, is Dupixent, which has obviously been approved in many different indications.

And so that’s that’s kinda how we’re thinking about it. If we can come up with an oral Dupixent, you would, you know, I think have a broad opportunity to hit a number of different indications with a single drug, assuming that you can get, you know, very good selectivity. So we’ve demonstrated high levels of potency, high levels of selectivity, not just not just with, you know, stat six, but, you know, across the whole stat stat family. We’ve demonstrated good target engagement in in vitro and in vivo models. So our prototypes are looking very, very good.

We’re we’ve got good PK. So it’s really a little bit of apple polishing that we’re doing right now, zeroing in on the, the exact, finalist, which we expect to, announce here in the second half.

Brian Skorney, Senior biotech analyst, Baird: Got it. And maybe can you compare and contrast your efforts at targeting Stat6 with some of the other small molecule efforts? In particular, how we should think about sort of direct binding of Stat6 versus degrading Stat6?

Jay Lulli, CEO, Enanta Pharmaceutical: Terry, you wanna take that one?

Tara Kiefer, Senior vice president of product strategy and development, Enanta Pharmaceutical: Sure. Yeah. So we’re we’re taking the approach of targeting stat six with a small molecule inhibitor. And to your point, Brian, there’s other companies, Chimera, for example, that is protein degradation, which can remove the target and protein entirely. You know, so we we obviously like small molecule inhibitors.

They’re very well understood modality with long term, you know, robust preclinical and clinical data. We’ll have to see as more clinical data come out on these degrader modalities. There aren’t any approved to date, so the data is certainly more limited. But from a small molecule perspective, you know, have a lot of learnings that have generally been able to guide a good translation from preclinical models into the clinic. So predictable PKPD relationships for dose selection, good understanding of the metabolic metabolism profile.

So I think we’ll ultimately have to see as the clinical data comes out. But certainly, as Jay said, we’re targeting a best in class molecule. And certainly, as we’ve seen with other targets and with other indications, if you can get a small molecule inhibitor that can achieve exposure levels that are above your EC90 or your measure of preclinical potency, they should be able to completely inhibit the protein without removing it. And we’ve shown this actually preclinically with our prototype.

Brian Skorney, Senior biotech analyst, Baird: Great. And then as you look at additional immunology programs, and I know you’re saying there’s probably an announcement before the end of the year on a third program, what sort of informs your decision making process here? Do you select a target and try to design chemistry around it? How does biological validation and competition come into play when you’re determining where to go next?

Tara Kiefer, Senior vice president of product strategy and development, Enanta Pharmaceutical: Yeah. So we’re really focusing on areas where there’s a good understanding of the underlying biology, disease, pathology, and where the target has some level of validation, you know, whether that’s genetic or clinical validation, that’s ideal. And then we’re obviously looking for indications where there’s a clear development path, well defined populations, and ideally if there’s biomarkers available for those early signals of efficacy, that’s helpful as well to derisk the program early on. Looking for areas where there’s really large unmet medical need and a good opportunity there, and where, you know, maybe the target is either not currently drugged with a small molecule or sub optimally drugged. Those are ideal targets for us.

We have a really good preclinical drug discovery process in house and get expertise in that area.

Brian Skorney, Senior biotech analyst, Baird: Great. And maybe just last question I really have is you continue to receive royalties on the AbbVie hep C combo MAVERIT. Can you tell us a little bit about your view of the stability there, durability and what you currently get in terms of economics?

Jay Lulli, CEO, Enanta Pharmaceutical: Yes. So the we first got royalties on parataprevir, which was the first protease inhibitor. That was ultimately surpassed by glecaprevir, our second protease, which is best in best in class. And so that has been in Maverick now since, I guess, The US approval was in 2038. So we’ve been getting royalties, double digit royalties on glicaprevir, which is half of Maverick for several years now.

And I think AbbVie’s analysts have revenues going out into 2033 in their models. So we have, you know, been participating in that. Now it’s interesting that, you know, the RSV royalty well, the RSV market RSV HCV market changed during the pandemic. It was really strange, you know, for both Gilead and for AbbVie. They’re basically the two companies that sell hepatitis c drugs now.

You know, as the pandemic, as we came out on the other side of the tunnel, the the overall sales were down versus before pandemic, but it’s still, you know, Abby’s selling north of a billion dollars a year on on Maverick. And so we expect that to continue for a a good long while. We did a couple things that have come up. So we, just a few weeks ago, got the first ever label for acute hepatitis c. We had chronic, but we didn’t have acute.

And so what that is is gonna allow people to basically be treated just at the acute phase. So if you get a positive test for HCV, you don’t wait to wait around to for it to become chronic. You can treat early. And we we think that’s obviously an advantage. The earlier you can treat, always better.

Gilead and AbbVie both have the indication for chronic, but will, you know, hopefully pick up a lot of patients at the acute phase before they even have a chance to become chronic. So it’s nice to have that label and that’s also eight weeks. So we have the only eight week cure for now, acute and chronic hep C across all genotypes. We monetized a little over half the royalty two years ago for $200,000,000. So our royalties now are on the other 45.5 percent of that royalty, which will continue until 2032, after which point a 100% of the royalties will revert to us.

So, anyway, that’s it’s it’s been a good it’s been a good to have that cash flow through these years.

Brian Skorney, Senior biotech analyst, Baird: Great. And then, you know, I think you mentioned at the top, you you had a little less than 200,000,000 in cash at the close of March, 34,000,000 on top of that. How does that kind of look versus your burn? How much of your sort of operating expenses are covered by the AbbVie royalty right now?

Jay Lulli, CEO, Enanta Pharmaceutical: Yeah. So well, it contribute it certainly contributes to our operating expenses. But with the with the cash on hand, the the paper checks that we got from the IRS for 33,800,000.0, you know, we’ve got cash runway into fiscal twenty twenty eight. So reasonably good on on cash. That that allows phase one, phase two study in KED, getting our stat six into the clinic and progression of a third program into the clinic as well.

And that’s without any assumptions on RSV partnerships. So I think, overall, it’s pretty sound.

Brian Skorney, Senior biotech analyst, Baird: Great. With that, that’s basically all my questions, but I’d love to give you the opportunity if there’s something that you think I missed that that you’d like to mention about Ananta, please feel free.

Jay Lulli, CEO, Enanta Pharmaceutical: No, I think you hit everything on the head. Big data set coming and new catalysts emerging in immunology.

Brian Skorney, Senior biotech analyst, Baird: Great. Jay, Tara, always a pleasure to talk to the two of you. Hand it back to Mike to close.

Mike Perrone, Baird’s healthcare specialist, Baird: Yeah. Thank you so much, Jay and Tara. And just for the investors out there, I do know that Enanta is gonna be coming to That’s gonna be, Tuesday and Wednesday, September in New York. They’ll be there on the tenth.

So if you’d like to connect with them, we’d be happy to set it up there. Or if you’re more interested in catching up earlier, please, let us know. We’d happy to, make the connection. So thanks everybody for joining, and have a great day.

Jay Lulli, CEO, Enanta Pharmaceutical: Thank you.

Tara Kiefer, Senior vice president of product strategy and development, Enanta Pharmaceutical: Thank you. Bye now.

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