Welcome to the Cantor Global Healthcare Conference. I'm Pete Stavropoulos , a Biotech Analyst with Cantor. With us, we have Enanta Pharmaceuticals , a company that's developing drugs in viral antivirals and immunology indications. I'm pleased to introduce Jay Luly , CEO , and Tara Kieffer , Chief Product Strategy Officer. We'd like to welcome you, but also my condolences for Paul.
Thank you. Am I in?
Sure.
I have two mics going.
Okay, thank you.
Okay, so before I begin, I want to point out that we released some news this morning that our Chief Financial Officer, Paul Mellett , who's been our CFO for over 20 years, sadly passed away over the weekend. Many of the people here at the conference know Paul, many people on the webcast, and let's just say he was a great guy, consummate professional, and he will be dearly missed. Before I begin my formal remarks, I want to 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. For those of you who are a little less familiar with Enanta , we're a virology and I&I company. Our roots are heavily in virology.
In fact, for the last 20 years, we've been doing work against various viruses, starting with hepatitis C, where we discovered two drugs that made it to market, and AbbVie has done late-stage development and commercialization for. The first one, Viekira Pak, was replaced by the second one, MAVYRET, and today it's the only eight-week cure for chronic and acute hepatitis C . We've worked on other liver viruses, hepatitis B, but our more recent focus in the last several years has been in respiratory viruses. We became involved in this before the pandemic, starting with respiratory syncytial virus, or RSV. We have two approaches to taking out the virus. They're both replication inhibitors. The N protein, known as zelicapavir, and the L protein target, which is the viral polymerase of a drug called EDP-323. They are both at the phase II stage of development.
Probably for today, we'll spend some extra time talking about the high-risk adult study for zelicapavir , which is due to report out later this month. The pandemic came along. We were working on respiratory viruses and clinical trials in that area and knew protease inhibition very well. We've worked in COVID, have a phase II asset there with good proof of concept data. We started to make the migration several years ago into immunology. We made the first formal announcement about that early last year with the introduction of our KIP program. We have a molecule that's advancing toward the clinic. We hope to have it in the clinic as early next year as possible. We announced a second target at the end of last year, STAT6, where we're basically going for an oral Dupixent. We have other work ongoing that will ultimately be disclosed later in the year.
Okay, next slide. This slide's a little sticky here. Doesn't seem to be advancing. There it goes. Just an outline on the zelicapavir high-risk study. This is a high-risk adult study. By that, we're looking at people who are elderly, age greater than 65, those who have COPD, asthma, or CHF, which are predisposers of poor outcomes in RSV infections. Ultimately, it's a study that's skewed even to the higher of the high risk because we cap the people who are 65 - 74 years of age, who are otherwise pretty healthy. They're still at high risk, but not as high a risk as somebody who's 75 or older. Similarly, with asthmatics, if your asthma is fairly well controlled, not much else going on, you're not necessarily at the highest of the high-risk category. We cap those two patient populations together at 20% of the study.
The majority of the study is obviously in the other buckets. We enroll patients within 72 hours of symptom onset. That's important because time is always the enemy in infectious disease. Said another way, the sooner you treat, the better the result. You can see it's a five-day treatment followed by a follow-up. The ultimate primary endpoint here is symptom-based. It's using a tool called the RiiQ. It's a patient-reported outcome tool that looks at lower respiratory tract disease symptoms. That's the primary. We have a number of different secondaries. The question is, what sort of resolution improvement from a timing perspective should you expect? There haven't been any registration trials for RSV therapeutics. What we did was we looked toward the, there we go. We looked toward other respiratory viruses, namely influenza and SARS-CoV-2, where drugs have been approved based on symptom endpoints.
On the left-hand side of the slide, you'll see oseltamivir, which is Tamiflu, and baloxavir, which is XOFLUZA. Those are two commercialized flu drugs. In the registration studies that led to their approval based on symptoms, you can see in each case, it was about one day shortening of the time to resolution of symptoms. That was viewed to be clinically meaningful and ultimately approvable. You can see that there was also a study that led to an approval of a SARS-CoV-2 protease inhibitor. This is Shionogi's ensitrelvir that was approved in Japan based on a similar study. It's around, their phase III was about just under 700 patients. You can see that these phase IIIs were in the 500 - 650 or 700 patient range where they could demonstrate that effect. For us in RSV, if I can get this slide clicker to advance the slide.
It's just not, I don't know where to point it. There we go. I didn't double click it. We have RSVHR as a proof of concept study. It's about 180 patients. We actually over-enrolled it with 186. Our goal there, not surprisingly, is to show a clinically meaningful reduction of symptom duration of about a day. We'll be taking that information and coupling it with several other secondary endpoints that we're going to be trying to measure, all kinds of things to help best inform the registration study. Assuming the results are positive in that category, we would then aim to confirm that about a day or more improvement with statistical significance in a phase III. We're estimating that the phase III would be roughly in the size that the other phase IIIs were that I showed on the slide prior. I'm going to try again to advance the slide.
Next slide.
Now it's catching up. Can we go back to, okay, go forward to the next slide, slide seven. Here we are. We look forward to having the data readout later this month for the RSVHR study. Thank you. Shifting gears quickly to our KIP program. KIP is going after mast cell-driven diseases, things like CSU. We have a stable of molecules. The chemists have done a fantastic job. Here's the lead candidate, EPS-1421. It's potent, very potent in both in vivo and in vitro assays, highly selective, great ADME properties. We're looking forward to moving that into the clinic as early next year as we can. Currently, we're wrapping up scale-up activities and IND-enabling work. So far, everything's on track. The STAT6 program, again, we're going after basically an oral Dupixent.
We want to be able to go after all the indications ultimately that Dupixent can serve, but with an oral molecule. STATs were originally thought to be fairly undruggable, but we've made excellent progress honing in on lots of really good chemical matter. We have molecules that are very potent, orally available, highly selective for STAT6 and selective versus all kinds of other targets that we look at. We've demonstrated good target engagement in in vivo models. We're finalizing the last bits on the final candidate for development, which we expect to announce here in the second half of the year. Just to wrap up, key catalysts. We talked about KIP inhibition moving toward the clinic early next year, STAT6 inhibition. We have a candidate selection nomination that should occur in the second half. We're planning to announce a third immunology program.
Later this month, the data on RSVHR, the high-risk adult study. Our plan ultimately, now that we have, we didn't talk much about our polymerase inhibitor EDP-323, but it's a very, very strong molecule as well. It could be viewed as a next-gen for zelicapavir . Zeli's further along. There are some attributes of 323 that we really, really like. They're a really strong pair, which collectively create the strongest RSV portfolio in the industry. With that, we'll head into Q&A. Thank you.
Thank you for the introduction. Congratulations also on the recently approved MAVYRET for the first treatment for use in acute HCV. What's the importance of being able to treat the acute HCV infection?
Acute, it's interesting. People are acutely infected before they're chronically infected. That seems logical. Heretofore, the approvals for Hep C have been in chronic hepatitis C. The two leading drugs on the market today are MAVYRET that came from Enanta and AbbVie and Gilead's EPCLUSA. These two drugs are, again, they were approved for chronic Hep C. How do you diagnose that? That's a big part of the problem. You have to be tested first. You test positive for Hep C, then you have to confirm that you have the virus circulating. You have to wait for six months or a year and then confirm that you still have it. Then you're deemed to be chronic, and then you can be written a script for either of the two chronic drugs. With the acute label, now you can pretty much treat somebody when they're first diagnosed. That's a huge thing.
Not only just in terms of managing patients, it's always, you know, why not treat them as early as you possibly can if you know you have this infection? The other is that they're not waiting around to be determined chronic and infecting other people potentially. From a public health perspective, it manages that too. AbbVie has the only approved drug with that acute indication. It allows us to treat lots of patients as they become diagnosed and before they enter the chronic pool that we would ultimately share with Gilead.
Is Gilead actually conducting any clinical studies in the acute setting?
I believe they had.
They had?
Yeah.
Okay. Positive outcomes or?
I think you'd have to look.
All right. This is a partnered asset like you mentioned with AbbVie. How meaningful is this for Enanta in terms of royalties and long-term revenue impact?
We just got this label in June, and AbbVie reported Hep C sales. I mean, they were up a tick. It's too early to tell exactly how much of an impact there was in only a few weeks in June for their quarter. I think we'll need a few quarters to see what patterns emerge. Ultimately, it's just good because finding patients and keeping them in the cascade of care has always been a challenge in Hep C. The pandemic deeply disrupted that, and Hep C sales fell for both companies across the board. Now maybe it's a good opportunity to catch new patients very early.
Okay. All right. Switching gears to RSV, where indication-wise, there's been a lot of interest and activity in this space with approvals for mAbs and vaccines. How do you sort of view the landscape evolving and the need for a small molecule antiviral?
Maybe I'll just set it up and then let Tara talk about that. RSV was first diagnosed in 1956. Until the last handful of years, there hadn't been anything other than a prophylactic monoclonal antibody called SYNAGIS that wasn't widely used. It was expensive. It was relegated to high-risk premature births. Vaccines had had a big safety record issue, particularly in pedes that's impaired development, again for over 60 years. More recently, there has been some success on the prophylaxis side, but still nothing on the therapeutic side. Tara, do you want to?
Yeah, and I think certainly prophylaxis is part of the solution to RSV, but we ultimately will need a treatment for the infection as well, similar to other respiratory infections like flu and COVID, where you have both prophylaxis and treatment. In terms of the prophylaxis for adult populations, there are two vaccines out there, and unfortunately, the uptake has not been optimal. I think at the moment, we're around 20% of the eligible population that's receiving the vaccine. There's still a lot of people that are vulnerable. Even in those that are vaccinated, you can see breakthrough infections. On the pediatric side, as Jay mentioned, there's monoclonal antibodies, but these only provide a passive immunization. They're protected for the time that the antibody is in the children or the babies. Once that is cleared, then the infants and children are fully susceptible to RSV after that.
What this will likely do is just shift the first stage of infection a little bit later. Treatment will still be needed. Of course, you know, breakthrough infections can happen there as well. Still unmet need for treatment.
I guess one quick way to see if there's antiviral efficacy is to sort of use a human challenge study model, which you did do for zelicapavir . You know, can you just briefly touch on the design and what the outcomes were?
We've done the challenge model on both zeli and more recently with 323. I kind of view that model as sort of a rite of passage model. If you can't jump through that hoop and jump through it well, you probably shouldn't advance further in development. Just briefly, first step is you test the drug in healthy volunteers. You're looking for safety, tolerability, and good PK exposure. With antivirals, if you get really good exposures and you know what concentration you need to take out the virus, you're enhancing your chances for success. We passed with each of our drugs, zelicapavir and EDP-323, very, very strong phase I healthy data that showed strong exposure and then supportive of moving into a challenge. The challenge then takes it one step further. You take healthy volunteers and you infect them with the virus. You infect them actually with a clinical isolate.
It's the real virus. You give them a good inoculum. They're otherwise healthy, so they're not at super high risk. They'll probably develop a sort of a bad cold-like symptom and resolve it fairly quickly on their own since they're otherwise healthy. What it allows you to do is, the day you inoculated the person, huge advantage, they're hospitalized, and then you can watch them, things that you can't do in the real world. You're taking nasopharyngeal swabs and doing RT-PCR twice a day. You're taking symptom diaries three times a day, and you're just waiting for that virus to come. After a variable number of days, three days, three and a half, four, five, the virus pops its head up. Once the viral load reaches a certain threshold, that becomes t0 in the study, and you start dosing.
What you can see with either of our two drugs is, within hours, placebo patients, viral loads continue to climb, symptom loads continue to climb, and those who are on either drug immediately start to come down. It's just really amazing. I think that's probably the one point where our two drugs, the first zelicapavir , that study is in the New England Journal of Medicine, and it looks like EDP-323 can even knock down that front wave even faster. Twelve hours after the first dose, and the virus by culture has been just completely nailed. Speed is your friend when it comes to drug action and drug time into patients. Those studies both went extremely well.
In the case of zeli, which, and we reported that challenge study on 323 roughly about a year ago, we've been doing just some enablement work for phase II for the high-risk adults study that would be done next, probably in the context of a partner. Zelicapavir , which passed that challenge test a while ago, was then liberated and allowed to go into high-risk patient populations, which are the ones that one would ultimately use to gain regulatory approval.
Okay. We're going to discuss in a minute the phase II pediatric data, but before that, any chances of combining 323 with zelicapavir ?
Yes, absolutely. We've done that, and we've done it preclinically. They're additive to synergistic in their effects. You know, you have orthogonal mechanisms going after the virus. Much like in COVID, where you can take Paxlovid for five days and you're fine, or any of the flu drugs, they're monotherapies typically. I think for an acute virus, acute viral infection, monotherapy should be sufficient and probably in the majority of patients. I think where combinations might be really interesting are in, say, highly immune suppressed patient population, because that's another high-risk category. You basically don't have your immune system helping you at all to fight the infection, and going after it with two mechanisms might have merit, and probably two mechanisms and for a longer time period. We've thought about those possibilities as well.
I assume population like someone who just underwent stem cell transplant?
Yep, we actually did during the pandemic. We had a study, a third high-risk study going on in hematopoietic stem cell transplant recipients, and they're highly immunosuppressed. The problem was it was during the pandemic, and they were such a, they're a cautious, cautious population by nature to avoid environments where they might get a respiratory infection or any other infection. They were very, very hard to recruit in the pandemic. Everybody was masked up and isolated, and we recruited 10 or 12 patients, but decided that it wasn't going to happen during the pandemic. We focused our energies on pedes and high-risk adults, and we can always come back to that later.
Okay. In terms of the pedes study that you conducted, just the overall study design and also efficacy.
Sure. The RSV pedes study was done in about 90 patients, aged 28 days all the way to three years. Because this was our first in pediatric study, it was done a little bit differently because we had to do some dose finding first. There were two parts to the study. The first part was multiple ascending doses in two different age cohorts. Primary objectives there were really safety. Obviously, that's of utmost importance in this population. We wanted to establish the safety and then PK to select a dose. Once that dose was selected for the two different age cohorts, it moved into part two, using that selected dose. The primary objective there was looking at virology. We looked at both outpatients as well as hospitalized patients. What we found was, in terms of the virology, we saw a really good effect on viral load.
Prior to the data, in terms of a benchmark that's out there, the one study we could point to was a phase III that was run by a company called ArkBio in China in pediatrics. They showed about a 0.6 log drop at the end of treatment at day five. That also correlated to a statistically significant impact on symptoms. Our study, we actually were able to show about a 1.2 log drop at the end of treatment. About double that benchmark, which we are excited to see. Really good virology in these pediatric patients. We also did look at symptoms as an exploratory endpoint. We didn't have the tool in place. We're developing our own tool as a caregiver, I guess, reported outcome, working with regulatory agencies, physicians, caregivers. That tool was ready to go into the study only at the end. I think we captured about 15 patients.
It's a small n, but there was a trend towards seeing improvement in symptoms with that tool. We did incorporate another tool called ResVinet because it was the only one available. It wasn't designed necessarily to look at symptoms longitudinally, but that did not show an effect. We're pursuing our own tool, which is called RESOLVE-P.
If I remember correctly, that was actually designed for adults?
Yeah, it was more for vaccine trials to look kind of like at baseline symptoms.
Okay. The tool that you're developing, RESOLVE-P , where is that? Are you complete, ready to go with that, or still working?
Yes, we've had good discussions with regulatory agencies. We're running an observational study to generate more data on that tool and would envision that would be used in the next study for pediatrics.
The phase II data that's coming up in the high-risk adults, you spoke about the design in your introduction. What are your expectations there? What would you consider a win?
Yeah, again, it was striking, you know, when we canvassed all the approvals for respiratory viral infection drugs, whether flu or RSV, that multiple drugs across different viruses, some slightly different age populations. You know, when you looked at it in the aggregate, every single study had showed about a day benefit. I think that's sort of the bogey that we would be aiming for to get. If we can do better than that, obviously, that's a huge win. You know, based on precedent of drug approvals, that seems to be the benchmark for what is deemed to be clinically meaningful. Everybody knows when you're suffering from one of these viral infections, if you can make it go away a day sooner, that's good. You can get back to work. You can, you know, respond to other needs in life. It would be just a great outcome.
Okay. We have about a minute and a half. Just if we're sitting here one year from now, what would you like to say that the company accomplished value creation for shareholders?
Yeah, we have the, you know, the first ever, the opportunity for the first ever RSV treatment. I mean, we're coming on the heels of having helped develop a couple of cures for hepatitis C that have cured more than a million people around the world. I can't think of a better interesting next thing to do than to come up with a drug that could potentially treat every baby who is suffering from an RSV infection, every elderly person who's being taken down. That's a big, a big win in my book. Hopefully the data support that. We've got multiple shots on goal there. We even have the opportunity to have the first to market and then a next gen. A lot of the competition has drifted to the side. They both focused on entry inhibitors for the most part, not replication inhibitors.
That would be, you know, just really a good outcome. Longer term, as we break into new areas, the INI space is an expanding universe of opportunities, relatively speaking, I think, compared to virology. It made just a great deal of sense for us to move into that. The scientists are hammering hard on those programs.
All right. Unfortunately, we didn't get to touch on the INI indications. I had a whole list of questions, but I do appreciate you attending the conference. Thank you very much. Nice to see you both.
Thank you.
Thank you.
Thank you very much.