Okay, I think we're ready to get started here in the room. Thank you everyone for joining us for the second annual Guggenheim Healthcare Innovation Conference. I'm Vamil Divan, one of the bio-pharma analysts here, joining on the stage for the Guggenheim site. Evan Wang, also on the team here. Next up in this room, we have the Assembly Biosciences team. Thanks so much, all of you, for joining us. From my, you know, from left to right, from as I sit on it, Anuj Gaggar the CMO, Jason Okazaki, the CEO, Bill Delaney, the CSO. Obviously, it's been an exciting few months for the Assembly team. We're just talking heavily. Seem to talk to you guys all the time now because there's so much going on.
Maybe I'll turn first, Jason, if you want to just sort of kick things off for those maybe still not as familiar with the Assembly story, the background, how the company came to be, and then we'll talk about some of the recent developments and things coming to come.
Yeah, thanks, Vamil. And thanks for having us. Always a pleasure to speak with you. Obviously, it's been quite regular lately, so it's a good problem to have. Look, Assembly originally started as a capsid assembly modulator company focused on HBV. This team joined about five years ago, and it was most recently two years ago. Your two areas of business: one was to basically maximize the capsid assembly modulator for HBV cure, which Bill and Steven did. Second was expand the pipeline. That's really why we're here today and the success we've had most recently. Our pipeline now today is much further beyond just viral HBV cure. We are really a herpes virus company that our lead assets are two herpes virus compounds for high recurrent genital herpes. We've got 5366 and 1179, both in phase 1b trials.
We just announced very positive data for 5366. We'll talk a lot about that, I'm sure. 1179, which is also another molecule, HPI, which we'll talk about more. We'll have data on that later this year. We've got two great lead molecules for treatment of recurrent genital herpes. Beyond that, we also have a molecule in phase 1a that just finished phase 1a for Hep Delta. It's an oral small molecule entry inhibitor. We intend to move that into phase 2 next year. Last but not least, we've got an HBV, the CAM, what we referred to earlier, just finished the 1b trial, and that's set up for Gilead opt-in, right? We've got four assets in the clinic. Excited to talk about the data and kind of where we're going forward.
Okay, great. Perfect overview. Let's start with the general herpes sector. That was where most of the focus has been. Before we get to your data that you shared in August, just frame the opportunity here. I think a lot of people think of this as an older market, you know, some generic options that are out there. What is the unmet need, and what do you see as the opportunity to advance that?
Yeah, maybe I'll take that. Thanks again, Valmeek, Evan, for having us here. You know, with genital herpes, this is a disease that's not often talked about. I think there's a lot of stigma associated with it and some embarrassment from people to really discuss it. It's an area where there are still a lot of patients who are suffering and have inappropriate treatments right now and kind of inadequate treatments. You know, the last approval for the patients who suffer from recurrent genital herpes was almost 20 years ago now. While that treatment serves some of their needs, there's still a large population of patients who are suffering with multiple recurrences per year. This is a population that we've focused on the most. These are ones who are having three up to 10 lesions per year.
There are two important distinctions for those patients. One is the burden of disease is highest in those patients. The second, those are patients that are often prescribed daily suppressive therapy with valacyclovir or Valtrex. The downside of that is that first, they take a pill every day. Second is that even by Valtrex's own label, only one out of three patients can make it through a whole year without a lesion, meaning two-thirds of patients are failing every year on the current standard of care. We looked at that problem and said, how can we impact both aspects of that? From our history of antivirals, we know that if we choose better viral targets, that with more potency, you can increase efficacy.
The second piece was, can we make the patient experience or the convenience of taking the drug better, moving from a once-a-day to potentially once-a-week treatment? That is what we were really focused on and how we could address the needs of that patient population that we think is still inadequately treated with the current treatments.
Okay. You mentioned you have 5366, 1179. Can you talk just the rationale for having the two different programs? What are the differences there? How are you studying each one in phase one?
Yeah, maybe I'll start with just a description of the molecules. So 5366 was discovered and developed all internally at Assembly Biosciences. It's a helicase-primase inhibitor. It's extremely potent compared to the standard of care nucleosides. So valacyclovir is about 400 times more potent than that. We also designed it for long-acting use, oral long-acting use, and potentially injectable long-acting use. It had a very, very long half-life preclinically, and that translated into the early clinical data where it has a 20-day half-life for a small molecule, which is really exceptional. The second molecule is 1179. This is a molecule that was discovered at Gilead and then came over to us with the deal. It's also a very, very, it has excellent properties in terms of its preclinical package. Obviously, they have a great team at Gilead in terms of their antiviral discovery capabilities.
This molecule is about 1,000 times more potent than valacyclovir. The early clinical data shows that it has a four-day half-life, which still supports the TPP of having a once-a-week treatment. Two very potent molecules with excellent PK in their phase 1a studies.
Okay, great. Now let's talk about the data you released in August. That was super exciting data, interim data for 5366. Just if you can summarize the data and what are the key learnings, and then I think about the steps going forward.
Yeah, I think when we're doing these early-stage studies with genital herpes, the patient population we try to include are ones that are actually the patients suffering out there. People are having more than four lesions. On average, we had patients with about six to seven lesions per year on the study. When you're doing these studies, there are two major readouts you're looking for. One is a virologic readout, and one is a clinical readout. On the virologic readout, patients do swabbing of the anogenital area twice a day, and we look for the presence of virus on those swabs. When there's virus, how high is the viral load? The reason the height of the viral load matters is that's related to transmission. A lot of patients are also very worried not only about getting lesions, but then transmitting the virus to their partners.
We also look at lesions, so how the patients are having either symptoms like burning, pain, tingling, or they're actually having a lesion due to genital herpes. That was how the trial was designed, and we did that over a 28-day period. The data we released this past summer showed that compared to placebo, the second cohort that we evaluated, which is our higher-dose cohort, had a very significant impact on all of those measures. On the virologic measures first, we had an over 90% reduction in the shedding rate, so how often those swabs are positive. In the high viral load part, we had a 98% reduction in patients with high viral load swabs.
In the lesions also, we had, and we were not expecting that because we were not powered for that, but we knew that if we had a very strong effect, we could maybe see a difference in lesions also and saw a greater than 90% reduction in lesions also. All of those were statistically significant. Yeah, we were pretty excited by the data that we saw. When we look at that data in comparison to what has been developed in the past, so valacyclovir, acyclovir, and what is in development right now, it seems to stand out not only for the lesions, but also for the shedding. This is all with a once-a-week treatment. I think that is the other key component, moving away from the daily treatments. It is really now once a week. We are pretty excited with those data.
That's good. Maybe one more from me, then I'll turn to Evan to talk about sort of the upcoming data release. Just, there's been some medical meetings that you guys have been attending. Can you share some of the feedback you've gotten from the community on the data so far?
Yeah, we presented these data at the IUCD conference in Europe. That is a sexually transmitted infection conference that is a lot of European investigators and then folks from Australasia as well. It was very well received. I think the data, everyone understood that in the world of sexually transmitted infections, there's just not as much development done for the patient's needs. For people to see a company doing work there and actually making an impact, I think the presentation was well received. The feedback from KOLs there was really well received. Now that we're what we'll talk about the upcoming data, we really want to get most of that data out next year so people can start looking at not just those two cohorts in a blinded fashion, but then the unblinded data and kind of the 1179 data.
A lot more data to come. But so far, the feedback has been great.
Okay. Evan.
Great, thanks. I think just you guys just reported earnings on Monday, and you guys announced that the data will be coming this December. Can you just highlight what you guys plan to share with that update, I guess, from both 5366 and with initial data from 1179?
Yeah, so for 5366, when we released data in the summer, one of the challenges of releasing that data was that the trial was ongoing and patients were still on blinded treatment. We could not do the unblinded data for those first two cohorts at the time when it comes to safety. We are very excited to share that unblinded safety data in the upcoming data release next month. That is one component. For that 5366 molecule, we are also evaluating the first loading period of a monthly regimen. This was always an upside for us. We think weekly is really the way to go and something we are going to move forward with. To have the opportunity with a 20-day half-life to look at monthly is something that we will be sharing that data in the next data release.
I think what's also very exciting for us is to share the 1179 data. We have the first two cohorts from that phase 1b study. It's designed nearly identically to the 5366 study with the identical readouts in terms of efficacy for virology and lesions. We'll be able to share those first two data sets also next month, which I think will give us and everybody a read on that other second very potent molecule that could have a great potential for HSV as well.
Great. You talked about that 90% reduction shedding and lesions seen in cohort two from 5366. Is that a similar bar of what you'd be looking for with the third cohort and with 1179?
Yeah, I think it's a reasonable bar. I mean, there is a lot of variability from cohort to cohort in the patients that come in. I think we have to be mindful of with small ends, you can have some variability. I think for us, it's set a mark of where we'd like to be, and we'd like to be within several % of where that is. I think preclinically, as Bill mentioned with 1179, that program, I mean, that compound is very potent, more potent than even 5366. We have high hopes for having kind of at least similar efficacious data for that molecule.
Can you just contextualize some of what the standard of care and competitors in the space have shown historically on shedding and lesions or on the shedding rates and the high viral shedding? How has that correlated to outcomes in the past?
Yeah, so a lot of these data that have been generated on the standard of care are really now 25 years old. They didn't have the same techniques sometimes and the same ways of assessing the drug. Trying to do head-to-head comparisons can be challenging on that. The treatments are not ineffective. Acyclovir and valacyclovir were actually great advances for patients at the time. We often see in the 1980s sort of a reduction in shedding and lesions, like 80% or so or some in that range. I think what's been useful for us is to see how these things have done subsequently. There's a really great another comparative molecule that has gone against valacyclovir head-to-head and has beaten it.
We know our data, at least on the phase 1b, is stronger than that initial phase 1b data for the other compound. We feel pretty confident in trying to connect the dots that when we get to the next trial, which we think is going to be head-to-head against valacyclovir, that we'll be able to beat it on both shedding and lesions. That's what we're kind of looking forward to.
Got it. You also touched on unblinded safety data. I guess, what are you looking for to confirm there?
So far, the data that we've generated for 5366, it's very meaningful safety data for a couple of reasons. One is that it has been very well tolerated. We're not seeing significant grade 3, 4 adverse events or lab abnormalities. Importantly, the way that molecule works is because it has a 20-day half-life. Even though we dose for 28 days, there's quite a bit of drug around later on. We actually get a really long exposure of the drug. That safety represents a very more than typical phase 1b exposure. What we'd like to show everybody is that the small kind of ends you see in the tables, when we can separate it out for placebo and active, we can look more carefully at dose trends. You can look at a low dose and a high dose versus placebo now on the safety side.
We hope to confirm for everybody what we feel about the molecule, which is that it's really well tolerated and a very safe molecule.
Great.
We've also finished chronic tox on it too. As far as de-risking, we're very comfortable with 5366's in development.
Great. I guess, what are next steps in determining the Gulf War regimen ahead of phase two? I think you've talked about a mid-2026 launch there.
Yeah, I think one of the key aspects of getting to the next stage, and so phase two is where we're heading. We would like to go head-to-head against Valtrex. We think that's really important for everyone to really appreciate the value of these molecules. It will be different so we'll be doing weekly dosing with our molecule versus daily dosing with Valtrex. It's going to be a longer duration study now, so we can not just look at a 28-day event, but look at a longer-term impact for those patients. On dose selection, that's a really important thing that we need to get right.
The way we're doing that is we're working with some of our KOLs at the University of Washington, Fred Hutch, who do more careful PK/PD assessments to help us narrow in on what is the exposure we're looking for that's going to predict safe efficacy into phase two. That is really a key component of what we're going to be doing over the next few weeks and months to really generate what the dose levels need to be. I think already our preliminary estimates, we're pretty confident we can hit those with very simple regimens moving into phase two.
The other interesting thing we think about, Evan, we'll have the 1179 data coming up. As we think about phase two, our base case scenario has been, continues to be, 5366. We'll proceed into phase two because, like we said, that data is going to be hard to top. 1179, like Bill noted, is more potent. It is possible it matches or tops 5366, in which case I think it sets up a very good problem for us to have in that you could either take 5366 forward as planned, you could take 1179 forward if the data was better, or you might want to take both forward, frankly, and have two great molecules that you pick one for phase three. That is why we're very interested to see the 1179 data.
I think it's an upside scenario, but it's a good kind of scenario for us to game plan around.
Great. Can you expand a little bit more on how you're thinking about the phase two design in terms of duration of treatment, the key endpoints here, population?
Yeah, so for population first, we would like to go for a population that's representative of the population who actually has this disease. It's going to be pretty open criteria, looking at patients with more than four lesions either in the prior year or the prior year to starting suppressive therapy should they be on suppressive therapy. We're going to allow those patients in who are on suppressive therapy like we did in the phase 1b study as well, and really have no specific exclusions that are going to make big populations not eligible for this trial. We think this trial will then represent what you should expect in phase three and then eventually beyond. The goals of the phase two study are very simple.
We want to choose the dose for phase three, and we want to be able to generate the data to help us power phase three. Because a lot of the data on valacyclovir is very old now, people did not measure lesion days the way that we would like to do that. In this phase two study, we will have, again, two arms of our drug, 5366, at some lower dose and some higher dose versus valacyclovir. After a 12-week period, most likely, we will be doing the evaluation. We are going to have both shedding and lesions as key endpoints. Shedding because it gives you a lot more power to differentiate highly effective doses one from another, and lesions because that is what we are going to need to power on for phase three. We want to make sure we have that data as well.
The final aspects of those designs are still underway, but I think those are the kind of framework around what we're looking at.
Great. As you're kind of thinking about the opportunity here, where does a once-weekly fit into the commercial landscape?
Yeah, so the TPP we always tested when we launched this program four years ago was a once-weekly better efficacy than Valtrex. We think about that opportunity. We tested it with payers. They say with that profile, you could expect a moderate premium to brand of Valtrex, which for benchmarking purposes was about $5,500 per treatment per year for brand of Valtrex. As far as the market, we've done two analyses. Top-down epidemiology, you've got 2 million patients, roughly U.S., 2 million in the EU, so split pretty evenly. We've also done a bottoms-up analysis with the University of Washington. We published this paper at Estimated where we looked at ICD-10 codes. We looked at basically Valtrex scripts for 90 days or more. Really trying to capture the chronic suppressive market, which would be our initial indication for 5366 or 1179.
That analysis shows there's about 1.3-1.4 million patients in just the U.S. that are recurrent genital herpes. Out of that, there's north of 800,000 on chronic suppressive therapy just extrapolating the scripts. Doing the dumb math, that's a multi-billion dollar market, even if you're looking at a relatively moderate premium to Valtrex and a moderate market share. We're very comfortable with that market.
Got it. Can you also talk on kind of opportunities beyond recurrent genital herpes, whether it's expanding in the HSV-2, HSV-1 space for life cycle management with the once-monthly or other formulations? I think one of the other interesting parts is the partnership with Gilead too. I guess, where could you bring this? Where could Gilead bring this?
Yeah, maybe I can start. Certainly in terms of the dosing frequency we've had in mind, we're testing in cohort B3 the potential for a monthly dose. The complete phase 1b data and the PK/PD analysis that we're doing will certainly help us with that. That could be explored subsequently. We've also had in mind the potential for subQ in both 5366, given its extraordinarily long half-life, and 1179, given its extraordinary potency, potentially could be used as long-acting injectables. Certainly, a lot of data generated in the HIV space shows patients have a very strong preference for those, particularly the less frequent injectables, the twice-yearly injectable with lenacapavir, for example. I think those are both things that will require some formulation work, but can be done in parallel with phase two potentially.
Certainly, if Gilead opts into the program, they've got extensive experience in that area. That is the formulation. We see potential there. I think the other potential opportunity to think about is episodic use for recurrent genital herpes. Some patients do use it episodically. There is the whole oral herpes, which is usually caused by HSV-1. Both 1179 and 5366 are equally active against both HSV-1 and HSV-2. There are some potential opportunities there as well. There are HSV-1 oral herpes patients that take chronic suppressive therapy as well.
All right. Why don't we do, in the last five minutes here, let's touch on your other programs because you have other stuff beyond HSV. Hepatitis D, 6250, how that differentiates from potential competition in that space. And just if you can recap some of the recent data you've shared and your thoughts going into phase two.
Yeah, so maybe I'll start on kind of the origin of this program. It was really based on the very strong data that Gilead has shown from Bulevirtide, which is an injectable peptide. It's unfortunately a daily injection, but a highly effective drug in terms of its antiviral activity against hepatitis delta and in terms of the clinical benefit and in terms of normalization of ALT. They've shown excellent data now out through four years that it's a very durable, highly active mechanism of action. Our goal was to develop a once-daily oral medication to meet that same need. We're targeting the same mechanism of action, which is inhibition of the viral entry receptor, which is NTCP. It's actually a bile acid transporter.
We know exactly, we understand exactly how Bulevirtide works, and we designed a small molecule to do that. We came up with a very potent 15 nanomolar molecule in vitro that had excellent preclinical safety and preclinical PK. We have recently had the phase one results that Anuj can tell you about.
Yeah, so the phase 1a, it's a great phase 1a because it not only confirmed the important things, so safety and pharmacokinetics, a four-day half-life for once-a-day dosing, but we had the access to do a pharmacodynamic measure as well, which is bile acid elevation. Again, as the Gilead molecule, Bulevirtide, binds to NTCP and blocks the virus, it also blocks bile acids from getting in. You can measure an elevation in bile acids that tells you you're having target engagement. With the molecule 6250, we could show the same thing in the phase 1a. Really valuable to us because we can narrow down dose selection for phase two, which gets us to move a little bit faster. We've done the chronic tox in parallel. Now we can move forward with that molecule.
We just came back from AASLD, and there was a lot of great excitement on delta as well. Both the great data bulevirtide continues to show from Gilead on safety, efficacy, and tolerability over a long period of time that helps de-risk the target from our end. Also, the molecules from other companies are mostly all injectable molecules. I think where we see the value of 6250 as the only oral option for patients for hepatitis delta and why some might be okay with getting an injection, we know a lot of people would prefer a pill over lifelong injections, which is currently the standard of care for all the medications that are approved or in development. I think from a competitive side, we're pretty excited for what a small molecule can do. Great.
Hepatitis B, 4334, maybe we can just sort of where things stand there and the next steps.
Yeah, the goal of that program was really to benchmark the antiviral activity. Bill's team had done a really good job of making the most potent CAM we've ever produced. I think that's what we were able to demonstrate with our phase 1b study, where we had high antiviral effect at all doses tested very similarly, meaning that we're at the top end of the antiviral curve. We have completed that study, and now the data is being compiled, and then will be sent to Gilead for review for their option on that program.
Maybe just to wrap it up then, Jason, on the corporate side, your current cash position, then obviously the relationship with Gilead, just what are the next sort of decision points?
Yeah, so cash position after the raise, we just announced a quarter just north of $230 million, which we have a warrant structure, and we still have Gilead contributions that will hit hopefully in the next year. Conservatively, we're out to end of 2027, but realistically, we're probably beyond 2028 once you factor in those layering effects. The Gilead collaboration, like Anuj said, there is an opt-in right now period that started for the HBV molecule. HSV-2 opt-in won't start technically until after we have all the safety data, which would probably be, call it, January next year. As you can imagine, we're sharing the efficacy data pretty regular with them. We'd hope that they make a decision on the sooner side of that than the latter. I think the Gilead collaboration gives us a lot of optionality.
I think this 1B opt-in decision will help us kind of frame together with the data, are we bringing 1179, 5366, both molecules and kind of figuring out the path forward. Regardless, the good thing about our relationship and our history is that our goal is to bring those molecules to market fastest, right? We are not waiting for the opt-in. We are full speed ahead toward phase two and the next steps.
Okay. I think we'll wrap it up there given the time. I was just looking before. It looks like your stock's almost exactly doubled from where we were a year ago. So we'll see you next year at the same time. No pressure. All right, thank you.
Thanks, guys.