Thank you everybody for joining us for this Citizens JMP Life Science Conference. We're happy to have Enanta Pharmaceuticals, our next company. We have Jay Luly, he's Chief Executive Officer, and Tara Kieffer here with us, Chief Product Strategy Officer. So thank you, Jay and Tara, for joining us. Maybe just quickly give us a background of Enanta, what you guys do, what you're good at.
So before I begin, I want to remind you, 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. Enanta is a drug discovery and development company. We focus on small molecules. We've spent a lot of time in infectious disease. Starting in the early days in antibacterials, we moved into virology. We helped discover a few cures for hepatitis C, the AbbVie sells, and we have moved on to other viruses, respiratory viruses. We were doing RSV before the pandemic and got involved in the pandemic virus, of course. And more recently, we've announced sort of a broadening of our mandate into immunology as a sort of allied field with virology.
So we're excited to be branching out and, you know, pushing forward our antivirals, but also moving into interesting areas in immunology.
Okay, great. All right. And you're focused on small molecule, oral drugs, that's really what you do, that's your-
Yep
... sweet spot, right?
Yep.
All right. Well, let's kick it off first to get with the virology bit. That's the most advanced in the clinic, RSV, zelicapavir, your lead candidate, EDP-938. So you've got a couple of Phase II's ongoing-
One is gonna read out this year. So maybe just talk to us about that trial, the one that's gonna read out this year in pediatric patients. What do you consider a win there? And I'm gonna... Most likely, it's gonna be in 4Q, I'm guessing, 'cause it was 3Q, and now it's in second half. Is that a fair assumption?
It's in second half. That's what we've guided as recently as last week on earnings, so.
Right.
Yeah, and we also... we'll get to the other RSV drug, I'm sure.
Yep
... EDP-323, that's easier to define because of the way it's recruiting, but we plan that one for Q3. But zelicapavir, so we're in two high-risk patient trials, one's in high-risk adults. High-risk adult population includes... I mean, RSV tends to hit younger and older people more severely, right? So the high-risk adult, you have a population that's elderly, that's at high risk, but you also have other adults that have high risk for poor outcomes, and those include people with asthma, people with COPD, people with congestive heart failure, and so on. So that's one study that's cruising along. The one that we expect to read out in the second half is the pediatrics study. And there, it's at the complete opposite end of the age spectrum.
In each case, you're dealing sort of with people who may have compromised immune systems, some because you're becoming more elderly, your immunity wanes. But, newborns and children in their first few years of life are also at risk because they haven't yet been exposed to RSV multiple different times, and you need to be exposed in order to build up a certain level of immunity. So we have focused on children from a very young age of only 28 days of age, up to 3-year-olds. That's sort of the zone where a lot of children are getting exposed and infected with RSV, some for the first time, some for multiple different times. So that's the strata that we're focused on there.
Okay, all right. You updated enrollment on the last earnings call. There's two age cohorts, right? 28 days to six months, and then six months to three years. So, maybe just walk us through the enrollment there and what you're doing in terms of Northern Hemisphere, Southern Hemisphere.
Sure. So there are two parts to the study. The first part, which is completed, was looking at safety and tolerability, doing a little bit of dose escalation, you know, starting to explore some doses to pick the optimal dose, and so you do that, obviously, very carefully. So we had those two age groups in part one, and we wrapped that up, moved into part two, where we do much the same thing, but we also take a much... Well, we take a look at virology. We're actually looking at virology in both parts, but in part two, we're taking, you know, the sort of go-forward dose into the second part of the study.
So the older children in that second part of the study, those from sort of six months to three years, that's fully enrolled, and we're now down into the final cohort, which is the 28-day to 6-month-olds. That's a cohort of about 20 patients, and you know, that's partially enrolled. We're at a situation right now where it's a little bit of the changing of the guard. The Northern Hemisphere RSV season, although we still see a little bit in the Northern Hemisphere, even in the U.S. It's substantially now shifting to the Southern Hemisphere.
And so we have sites in places like South Africa, Brazil, Argentina, New Zealand, Australia, and so their season now is starting to rise, and then that'll go on for a few months, and it'll careen back to the Northern Hemisphere in the fall.
Okay. But it seems like you can wrap up the-
Yeah, no, we're, we're desperate. You know, unfortunately, you know, when you're looking at kids, if you break it into six-month chunks, there are six, you know, sort of six-month age groups between 28 days and three years, and we're focused—we've—we're done with five-sixths of that, so we can only recruit in that one-sixth of the eligible age population right now to wrap that study. So it's a smaller, group, but, you know, we'll, we'll pull those last, few children in and then, wrap the study.
Okay. And the older cohort was all enrolled in the Northern Hemisphere, or was it a mix of...?
I would have to check on that. I can't rule out... Probably it was all in the Northern Hemisphere. Occasionally, you'll get, you know, South Africa popping in, an occasional child or two. They tend to be one of the earliest countries in the Southern Hemisphere to kick in-
Okay.
- RSV.
It, I mean, it's small numbers, so the concluding things on efficacy front is-
Mm-hmm
... gonna be difficult, but what are you hoping to see in terms of virological responses or?
Yep. So there's not a ton of natural history data in this patient population, although there is some, and there's not a lot of therapeutic precedent in this area, although there is some. Maybe, Tara, you can talk a little bit about-
Sure
... what's out there and what we expect to see.
Yeah, and I think, as Jay mentioned, you know, in order to expedite development, we designed this as an efficient study, to just give us some preliminary data on antiviral activity without, you know, powering on a specific virology endpoint. We'll also look at harder clinical endpoints, we'll look at symptoms and look at the totality of the data to really look for trends in that activity and give us confidence to move into a larger, powered phase III study. And, you know, it's hard to give a specific bar because, as Jay mentioned, there's little data out there. The one study we do know of was a phase III trial that was run in China from a company called ArkBio, the pediatric study.
A little bit larger, about 400 patients, I think, and they saw a statistically significant antiviral effect of about 0.6 log drop. That also then correlated to an effect on... a statistically significant effect on symptoms as well. So that's the only piece of data that's out there, but again, you know, we'll look at the totality of the data that we get in our study and look for those directional datas to give us confidence to move forward.
Okay, great. And I'm not sure you said anything about this, but just in determining the dose, anything you can say about how you found the dose to go into Part II? But obviously, no safety issues have stopped the study, so that's good, but any tolerability or anything that of note?
Yeah. So we, obviously, the study's not complete, you know, there's a dose escalation committee that looks at all the totality of the information with an outside drug safety monitoring board and so forth. So it's, yeah, you know, it's one of those things where no news is good news in that way.
Yeah.
You know, zelicapavir has been dosed in hundreds and hundreds of adults, and we have a, you know, a good-sized safety database, and it's had to... You know, and every study has been, you know, safe and well-tolerated. So, so far, so good.
Okay. All right, and I will get to EDP-235, the polymerase.
Mm-hmm
... inhibitor. But first, I wanna ask a general question first, so I don't forget it. Any changes to your strategy thinking from the RSV vaccines, the antibody that's been pretty successful to?
So no change in strategy. I mean, we're a therapeutics company. You know, we've since RSV was first characterized, I guess, in 1956, you know, people have been focused on trying to come up with a vaccine time and time and time and time again, monoclonal antibodies, too. There's been fits and starts, some antibodies that sort of blew up because of a mutational strain difference in the fusion protein at which they're targeted. Vaccines have finally come, but we've always assumed that there would be a backdrop of vaccines, you know, someday. But we're, you know, we're focused on therapeutics. The vaccination's never 100%, certainly in a I don't want to say a post-COVID world, but in a COVID world, we know that there's a lot of vaccine hesitancy and struggles with that.
But so it's never 100%, and efficacy is never 100%. People still get infected, and so that's the part of the population which is substantial that we focus on. The other thing about RSV, especially as you're thinking about it with pediatrics, is you rely on getting multiple different infections during childhood, in order to build durable immunity, somewhat durable immunity, that carries you through the rest of childhood. And these passive immune approaches, whether it's maternal vaccination, which is very short-lived, vaccinating pregnant mothers, you know, it's an approach that's been contemplated and is out there. But that's not durable in any way, nor are obviously the monoclonal antibodies that are given.
They can be given and provide some protection for a certain period of time, but the children are still gonna get infected. So if anything, it pushes the age a little bit to the right in terms of when they're gonna get their first infection, and their second, and their third, and that's what, you know, we wanna be there for. The other thing is these strategies are still vulnerable to potential mutations in the F protein.
Right.
You know, whereas just like we saw with COVID, with antibodies, and in fact, it has been seen within RSV with antibodies, before, too.
Okay.
Mutations can take that out.
So you're still skeptical on the fusion protein?
Not, not skeptical. I think it's, you know, it's a viable approach. I mean-
Yeah
... it can work. Again, it's not an overall solution to the situation of RSV, though.
Right. Okay. Yeah.
You need therapeutics.
Okay, got it. Okay. All right, so yeah, let's talk about EDP-323. It's a polymerase inhibitor.
Yep.
It's non-nuc, I believe you guys have said.
Yep.
So yeah, maybe just talk about the challenge trial, that's coming up, results in the Q3. You know, you guys did a challenge trial with zelicapavir that looked really good. Is it pretty much the same trial and... Yeah.
Very similar. Very similar in design. We're running it at the same CRO over in the U.K. And basically, for those of you who don't know what this challenge study is: you take healthy volunteers, and you infect them with RSV. It's done in a hospital-like setting, and so, people are monitored, obviously, very, very closely. But the nice thing about it, and that's why timelines can be a tad more predictable, is, you can recruit these healthy volunteers and infect them. You know, you're not waiting for a season and a certain geography, you know, to happen. And so from that vantage point, you know, things are on track. And it's a very similar kind of a study. We look at both virology, and we look at symptoms.
Okay, great. And I, I, I mean, what do you expect from the... I know I've asked this question to you, like, eight times, but... I'm not gonna ask you whether you, it need to be better than-
Did you say 8 or 80?
Eighty, probably.
Okay.
Better than zelicapavir. But, do you expect lumicitabine had maybe a different curve appearance, small numbers. Do you expect something more like that?
You know, we're data-driven. We'll get the data and look. I-
Okay
... I
I knew that was gonna be your answer.
Yeah, well, it is. It's the way, it's the way, it's the way we operate. But I think you look at, you know, there's some interesting—I mean, it's a different mechanism, right? So you have an N protein, which is also a replication inhibitor in zelicapavir. With 323, it's a polymerase inhibitor, but they're both direct-acting antivirals. They both shut down replication of the virus instead of trying to block viral entry, right? So they're quite different from that standpoint, but they're, but they're slightly different mechanisms. 323 is a, is a more potent molecule. zelicapavir is quite potent itself, but, you know, this is one of the most potent molecules we've ever made in 323. It's a picomolar inhibitor of the polymerase. It has great PK, and we know that from phase 1 studies, where we...
It was safe, well-tolerated. We had massive multiples of the protein-adjusted EC90. So we've kind of set up the preclinical and early clinical development as well as we possibly could to, to be successful in the next stage. But you get the data, compare it. zelicapavir sets a high bar. It's probably one of the best challenge studies ever run in, in the whole field. But we would like to see something close to that, right? Something that's on par with that, I think.
Yeah. Okay, fair enough. All right, let's move to immunology. A new space for you guys, as far as I'm aware. So maybe just tell us why you went into immunology and why KIT as your first target?
Well, I'll go through the first part. So virology, you know, is something that we worked on for, you know, geez, more than, certainly more than 10 years. And, you know, we've looked at hepatitis C, came up with a couple of drugs for that. Cured well over 1 million patients with Enanta, you know, containing regimens for hepatitis C, so very proud of that. We've spent some time in hep B. I know you know that area well. It's a tough nut to crack. We still have our peripheral vision on it, but we're, you know, it's just hard for us to have conviction around certain knowable targets that we could put in combination with our existing asset to really get a functional cure.
So until we can have that confidence, we're not going to spend capital on that. And then we got into respiratory viruses because beyond Delta, there's probably no other interesting liver viruses. We've kind of mined those with RSV, took a look at human metapneumo, have done SARS-CoV-2. And beyond that, there are viruses that you could work on, but it starts to become a narrowing constellation of interesting things to do. And many of the scientists who are doing virology at Enanta were actually classically trained in immunology, and they're sort of allied fields in a certain way. So it made some sense for us as we were thinking about areas to grow beyond virology that immunology would be an interesting one.
So we started mining that a few years ago, actually, and we brought it forward more formally with an announcement of our first program going after KIT. I'll let Tara talk about KIT for a second, but we're coming, you know, our plan is to come forward with another target later this year, and then over time, build what we did in virology, I think, somewhat successfully, in immunology. But you wanna talk about KIT? Why KIT, you said.
Yeah. So maybe I'll start with the disease we're looking at, which is CSU or chronic spontaneous urticaria. There's a high unmet need here. This is an inflammatory skin disease that causes hives and/or angioedema. And you know, outside of the sort of skin disruptions and itchiness of that, it causes sleep disturbances, can cause depression, anxiety, so really problematic for patients. And the treatment, the standard of care is really just antihistamines. You can go up to four times the standard dose, but unfortunately, it really isn't helpful to at least half of the patients. And there's only one available biologic that you know, many patients don't choose to go on.
I think there's an unmet need for a potentially oral good treatment option that's safe and effective in these patients. It's very prevalent. It's about 0.5%-1% of the population at any given time. And we're very interested in KIT for several reasons. So KIT is a tyrosine kinase receptor, where signaling through that is essential for mast cell survival. And we know that mast cells are a key driver in this disease of CSU. So by blocking KIT, you're essentially driving the cells towards apoptosis, reducing the quantity of mast cells that are available to drive pathology for this disease. We also like it because there is proof of concept, clinical proof of concept that's been demonstrated with the monoclonal antibody.
And this is from an antibody called Barzo from a company, Celldex, where their phase II data has shown some of the best in disease efficacy, that's out there. And so that's very exciting towards us, and if we can replicate that efficacy with an oral route of administration, we think that could be beneficial to patients. The other thing that's nice about this inhibitor and this disease is that you're actually able to look early on in clinical trials at some biomarkers that give you some indication of activity, so de-risking the program early on. And the last thing I'll just say is that mast cells are implicated in a number of immunology programs or immunology indications, excuse me. And so one could think about this type of inhibitor being useful in any number of those diseases.
chronic inducible urticaria is an example, EoE. You know, asthma is another potential one as well, so a lot of different things for us to think about.
Okay.
Expanding into.
Have you presented any preclinical data yet? Do you plan to present any later this year?
So we at J.P. Morgan introduced a prototype molecule just to show kind of the state of play, you know, with that sort of entrant. You know, we were busy, you know, building up, building up the biology, building up the, you know, the med chem, doing a lot of intellectual property, doing other kinds of things related to, you know, PK, DMPK, and biodistribution, getting all those things in order. So a lot of work has been done. I think the prototype that we showed back in January is a very strong one, and right now we just have a you know, trying to knock it off the mountain sort of approach going on right now with lots of drug discovery activities.
So our plan is, you know, to zero in, pick the finalist, probably in fourth quarter, and then to be in the clinic, very, you know, shortly thereafter.
Okay. Do you think a presentation goes along with that announcement in 4Q, or...?
We haven't formulated all that stuff, but usually, when we put a candidate out, it'll come with some additional color.
Okay. Now, what, what key aspects are you looking to? There are other small molecules out there in, in development. Just what-
Yeah.
Yeah.
Well, there's... You know, in kinase inhibition, it's you wanna have very, very good selectivity. You wanna optimize selectivity to minimize off-target kinase potential side effects and other kinds of actions. And so, highly focused on improving, maximizing potency against the target, selectivity against the target, and, you know, where we can, building in, you know, biodistribution advantages, other kinds of drug-drug interaction optimization. There's a ton of work, you know, behind the scenes that goes into one of these candidates that we're highly focused on.
Okay, great.
Yep.
And then the additional candidate, I get you said the second half, another non-KIT candidate, is that?
We didn't say candidate, we said program.
Program.
Yeah. But usually, you know, by the time we announce a program, it has a certain level of maturation and, suffice it to say that a lot of the things that we have up and running, for example, on KIT at the time of announcement, are... you know, will be in place. And we're looking at multiple different things right now. We're sort of triaging and figuring out what would be the, you know, the best next one. So stay tuned.
Okay. Last second, any indication overlap or totally separate, or?
It'll be immunology based.
Okay. All right, fair enough. All right, I think that is time. We'll, I guess we'll leave it there, unless there's any burning questions from the audience.