Good morning, everyone. Welcome to the Jefferies Healthcare Conference. My name is Anthea Lee, part of the healthcare research team here at Jefferies. We're very fortunate to have Assembly Biosciences with us today. We have Jason Okazaki, CEO, and CMO Anuj Gaggar. Welcome. For those that are new to the story, perhaps we just start with a quick overview of the company, the pipeline, and the key catalyst that you see coming up for the rest of the year. Sure. Thanks, Anthea, and thanks for having us. To start off, look, the company over the past five years really evolved the portfolio from an HPV-focused drug to now we're of a broad-based antiviral portfolio. That takes us really to the key catalyst coming up. It's a big year for us, right? The next six months, actually, I would say we have four major catalysts. Why don't I just start chronologically, and I'll kind of cover pipeline and company in one fell swoop. The first up in the first half of the year, we've projected that we'll have data on our capsid assembly modulator 4334, and that's for HPV cure. Now, that's a phase 1B trial. It's a 28-day trial. It'll be de-risking for as far as it'll be in patients. We expect to see significant viral declines. That molecule is the most potent in our portfolio of CAMs. It's the second-generation inhibitor. We're expecting to see activity against both mechanisms. Of course, a 28-day trial is probably too short to see cure, but that'll set up an opt-in point for Gilead as well and a good discussion as to what is the next step for the HBV franchise. I think that's the first chronologically. Second, we've got a molecule called 6250, and that is focused on hepatitis delta. That's chronic disease treatment. That is a small molecule entry inhibitor. We'll have phase 1A data in that in Q3 or by Q3. That one actually will be quite de-risking because if you think about it, even in a 1A with healthy volunteers, there's a bile acid marker. We'll be able to see target engagement and hopefully good safety in that molecule. Despite being a healthy volunteer trial, that will give us a lot of information on the molecule, will be very important as far as PK/PD. Last but not least, we have our, I would say, the biggest catalyst driving us in the fall, two data points, two molecules. It's 5366 and 1179. Those are both long-acting helicase-primase inhibitors for treatment of high recurrence genital herpes. Now, 5366 we discovered in-house. 1179 we actually brought over as a unique part of the Gilead collaboration, but we were able to accelerate that molecule. It's basically on par with 5366 as far as timing. We plan to present the data on both those molecules in the fall. Just to talk a little bit more about that, and we can spend more time in the subsequent Q&A, but 5366, the potential is for a monthly or a weekly duration dosing, which is one unique thing. Of course, we're aiming for higher efficacy, but also on convenience as well, we think that's important for HSV2 patients. It has activity against HSV1 as well, but of course, right now we're focusing on HSV2 high recurrence genital herpes. That's the biggest unmet medical need, significant market, dynamic, and also the fastest path to approval for us. From that data standpoint, we'll expect to see basically in the 28-day trial, if we're addressing shedding, viral shedding, and also lesions, that's a secondary endpoint. That will actually be true proof of concept data on two molecules. Whether we call that a 1B or a phase 2A study, that's the one that, as I look at from a catalyst standpoint, I would say is definitely the highlight coming up. Great. I guess starting with herpes, can you just talk a little bit about the market? What do you see the size of the market to be, and how do you see your two assets potentially fitting into standard of care there? Yeah, so I'll start, and Anuj, feel free to jump in. From a market standpoint, we've looked at this from two ways, and one was just published in a paper in Esmed, actually co-authored by some independent scientists at the University of Washington. We looked at the historical subset of patients based on scripts, ICD-10 codes, diagnosis of recurrent genital herpes, basically a bottoms-up analysis. Long story short, the US patient demographic projected based on that, and the paper is public, is about 1.3-1.4 million patients in just the US. From a market dynamic, I would look at that as the floor essentially of kind of accessible patients. From an epidemiology standpoint, I think it points you more to like a 2 million patient number. If you just do simple math, Branded Valtrex was sold about $5,000 roughly a year. If we took 20% of even the low end of that market with a molecule that's not only superior in efficacy, but has the convenience of either a weekly or monthly oral dose on the upside, you could see the potential there is easily $1 billion and potentially more from there depending on how much better it is as far as convenience and efficacy. The patients are definitely there, not only U.S., EU demographics about the same. It's about 2 million patients. Globally, we're conservatively projecting $1 billion revenue, but there's much higher potential on that. Anuj, anything to add? No, I think just from the patient side, what are the needs of the patient right now? Currently, that 1.4-2 million patients really do suffer right now from recurrent genital herpes. From their perspective, they're looking for medicines that are more effective than the current standard of care and medicines that are less impactful for their daily lives. I think those are the things we're trying to address with our programs, is how do we actually improve from standard of care, both on efficacy, but also convenience for the patient. One thing that Jason's kind of hinting at also is that when you have generally better treatments that are easier to take, you bring more patients actually into the fold for treatment also, so they're more amenable to take those drugs. I think part of what we'd like to have in our profiles is medicines that patients can look at and say, "This really fits with how I want to deal with my disease," and then you bring more patients then into the fold that way too. Great. So you have two assets in herpes, right? Talk about your decision to move those concurrently, and how do we compare and contrast between the two? Yeah, I mean, I think we knew that this was an area where we could really innovate for patients. We knew that what are the barriers for patients right now. For those 1.4-2 million patients, we know that they suffer from the disease by having multiple recurrences every year. With those recurrences, of course, they're painful. They impact their daily lives. These patients are also worried about transmitting the virus to others and spreading it. We know these are really important things. We knew we wanted to make an impact there, and we designed ABI-5366 to address those issues. We were fortunate that Gilead was also working on ABI-1179 with the same goal in mind. Having two molecules to address what we both had thought and still think are really important things for patients is a great place for us to be. Because they are both essentially two great lead molecules, we wanted to bring them both forward to really make sure we choose the best one moving forward. We've taken these both medicines and put them into nearly identical phase 1B/phase 2 studies. In that way, we'll be able to really look at how each medicine impacts those things that we know patients care about. Lesions, shedding, safety. The nice thing about our trials is they're not very small 1B studies of 10 patients for a short duration. We're really talking about 25 patients per cohort, up to four cohorts, so hundreds of patients that will be together between the two trials. With long-acting medicines, the other really nice thing is you get a lot of exposure in patients once you dose them. For example, for ABI-5366, it's a 20-day half-life. That means we give a dose, and it lasts for a very long time. In this trial, when we dose for 28 days, we really follow those patients for another 100 days and get a lot of great safety data from these studies. We look at these two studies for 1179 and for 5366 as extraordinarily de-risking studies from efficacy and from safety. We can talk more about the efficacy endpoints that we're looking at, but we think these are really important ways to take both forward, benchmark both, and then make the best choice for patients as we move past that. Yeah. The only thing I would just add to that just really quickly, I think if I think about this simply from a 30,000-foot view, you're looking at two things, efficacy and then convenience. Then convenience, like Anuj said, our baseline projection or TPP for that is a weekly, basically oral pill. 5366 has the upside potential of a monthly oral pill. Let's just say everything was equal other than ABI-5366 was a monthly. Of course, that would probably be a more compelling sell. That being said, from a preclinical standpoint, testing standpoint, we know 1179 is slightly more potent, and obviously 5366 has a longer half-life. I do think there is a use case for both scenarios. I mean, you can imagine a scenario where you've got a long-acting injectable for one, maybe a monthly and weekly oral for another. I think ultimately, as a small company, it's probably not something we could do those multiple trials, but I think with a partner like Gilead, it's certainly something that could be on the table. It's obviously their decision, but I do think from an addressable patient population, very similar HIV, where there's long-acting treatments and kind of there's a regimen for every kind of patient, whether they want oral, whether they want injectable, whether they want monthly, half-yearly, yearly. I think that's where the field of antivirals is really going. I think we hope to kind of follow that path. Yeah, and I guess to expand on that, what is the bar for success in this upcoming readout? If you could recap some of the 1179 phase 1A data as well, that would be helpful. Yeah, thanks. Maybe I'll go over the phase 1A data quickly for both molecules, and then we can get into the phase 1B readout. For the phase 1A, of course, the main goal was safety PK of those two drugs. We wanted to make sure we could achieve this TPP that Jason's talking about, which is we want to make at least once a week treatment for patients. Both compounds did very, very well in that. We had around a 20-day half-life for 5366, around a four-day half-life for 1179, both of which make it very amenable for once-a-week treatment. Like Jason said, for 5366 with a 20-day oral half-life. Just to be clear, this is an oral-delivered medicine, so there's not a formulation issue or a subcutaneous depot or anything. This is just a pill you take with a 20-day half-life. It opens up the possibility for once-a-month treatment. With those data, we moved into 1B. Again, these 1Bs are very large, more like a phase two study, dose ranging with large numbers of patients. There are several readouts which are really critical in that trial. We look at it in two ways. One is on the virus side, and one is on the clinical endpoint side. We powered it for the virus endpoints, and the viral endpoints in these trials are shedding. Basically, patients do an anal genital swab twice a day, and we look for two aspects. One is, do they have virus present in those swabs? The second is, when they do have virus present, how high is the level of the virus? We know that the more days you shed virus and the higher the viral load, the more likely you are to get a lesion and the more likely you are to get transmission. Those are very important virological endpoints that you can very well assess in a 28-day evaluation period. The unpowered part, but we think is really important, is looking at lesions. Looking at patients and saying, how many fewer lesions are you actually having in a 28-day period? That is a clinical endpoint that we think is important for future trial design also. Both of those aspects will be evaluated in this study. The goal is to have treatments that have substantial reductions in shedding and at least directional improvement in lesions in that short duration study. We know from previous, so one thing we haven't talked about is the class of molecules these are, are helicase-primase inhibitors. And we're fortunate that there have been other helicase-primase inhibitors that have been evaluated in recurrent genital herpes. And what they've shown and in other herpes virus infections, and what they show was, one, that these are safe medicines. They can be given over to millions of patients, like some are in Japan right now, and that they can be efficacious. And we had a previous molecule that actually beat standard of care in a short duration shedding study. And so we know that if we can benchmark to what those medicines have done and what this class can do, that this phase 1b/2 readout is really de-risking for future development. So we're looking at, yeah, virus and clinical endpoints in this one. And of course, safety. In terms of choosing which asset to move forward with, how would you order kind of your priorities there? Is it efficacy in terms of your viral endpoint or lesions or safety? Is it convenience? Just rank order those for us. Yeah, I can start. That's a really good question. I think it is going to be a marriage of all of those in the end. We know when we talk with patients, they really care about efficacy. What their day-to-day life is like is impacted the most by two things. One is how many lesions they get, and the second is what's their risk of transmitting. That really matters to them. We know we don't want to have a regimen that has low efficacy. That is going to always be the main bar we look at. I think after that, convenience plays a big part in it as well for patients. We've seen what happens in the HIV space where going to less frequently dosed medicines not only improves compliance with medicines, but it also has a psychological impact where that patient doesn't have to think about their disease every day. If you were to be able to get the same efficacy but have once-a-month therapy, then I think that's really advantageous from a patient perspective. We also know that we expect these patients to take these medicines for years. Safety, I don't want to underscore that. That safety has to be there. That's almost the table stakes. It has to be a safe molecule to begin with. I would say, yeah, efficacy, then convenience. Do you think this upcoming readout is sufficient for you to make that decision in terms of which to bring forward? Yeah, I think definitely the way the study is powered and the number of patients we have, like Anuj said, there'll be at least 100 patients on these drugs. There'll be plenty of placebo patients to compare. Based on our experience from antivirals in the past, nothing's guaranteed, of course, but 1B indications or phase two indications tend to be indicative of future kind of results. I think the studies beyond this, certainly you take a longer term to make sure, particularly this is a long-acting regimen. Whether or not a weekly or a monthly where you have that dose, you certainly want to take that in a larger dose population, longer term to make sure, A, it's effective and B, it's safe. Like Anuj said, safety is the minimum bar for us. I think I look at it as basically efficacy and convenience are also frankly equal, because if the drug is not efficacious, then it does not matter how convenient it is. If it is convenient, it still has to be on efficacy too. We actually have two prongs we have to hit, which is a high bar, because we know that there is generic Valtrex available. We also know by that label, two-thirds of patients still have recurring lesions or breakouts. I think we are trying to basically make sure that we are far exceeding that bar because Valtrex is once daily, we have a weekly, and we are suppressing virus and shedding and lesions to a much greater extent than that. We are actually offering advanced therapy and technology to patients. I would just add, this would be a great problem to have. We have two medicines that are both hitting our TPP that both can provide value to patients. If they're looking really neck and neck, it might be a difficult decision to make, but that's a great place to be where we have two medicines that both can work. I think Jason pointed out that there may be just homes for different molecules in different areas. We're only looking at recurrent genital herpes right now because it's the area we think we can address the quickest and has the most meaning to patients who have the highest need. We hear this a lot from KOLs and others on why are we not doing HSV1 also, that that market is still, there's room to innovate and do better there. I think these are things that are open to us. And if we have two molecules that are both hitting our TPP, we'll love to have that problem at that point. Yeah, that's fair. How does Gilead's kind of collaboration with you feed into that decision as well? Are there kind of room for joint development efforts? Yeah, let me take that from a holistic point of view. The Gilead collaboration works incredibly smoothly. I think obviously many of us have a history with Gilead, so I think we know each other very well. We are truly collaborators in that. We have regular, as you would expect, committee meetings on the development side, research side for future discovery. We are thinking about, I would say, unlike a lot of companies in our position or small companies, we're truly thinking about the fastest path to approval, which certainly aligns with what Gilead wants. It certainly aligns with what's in the best interest of patients. We talk all the time about, okay, assuming success, where do we go from here and what's the fastest path? That includes the decision process, because like you mentioned, there is going to be a decision most likely on which is the better molecule. There is a possibility to bring them both forward, but traditionally, most companies would bring a lead and a backup. I think we are setting up for that scenario and trying to get the data sets for our analysis, for their analysis, because of course, from our standpoint, if we get positive data, we would love for Gilead to opt in, but that is their decision. They could defer, they could opt in, or they could pass. If the data is important, we know that we have got a strong product that we can bring forward for patients. The collaboration is all built around getting basically the best treatment of patients. That applies to discovery programs. We still have early discovery programs that certainly we're collaborating with Gilead on. Going back to your point on the later stage commercialization, we would have, even if they opt in, not a right to commercialize directly on these early compounds, but we'd have a right to opt into a 40/60 cost profit share split in the U.S., which I think is very important for us to build our business and grow beyond that. Not to mention beyond our current clinical candidates for next generation research candidates, we would have a co-development option in the US for co-commercialization options. That is where I think we really build from a discovery platform to a broad-based end-to-end antiviral company years down the road. That's the goal of Assembly and as I think about the collaboration, how you build our company and basically get innovative treatments to market. Okay, great. Moving on to Hep D, can you talk a little bit more about the market there as well, what the treatment paradigm looks like? Yeah, so thanks for bringing that one up too. The world of hepatitis viruses has evolved quite a bit in the last decade from hepatitis C cures, hepatitis B, better chronic therapy. One area that had been slightly neglected was hepatitis delta. It happens to be a very severe form of hepatitis, still a high prevalence globally and underdiagnosed, undertreated. The current standard of care is the only approved therapy is Bulevirtide from Gilead, which is approved in the EU only right now. It is a very effective molecule. It is an entry blocker. Basically, the virus can no longer get into a hepatocyte because it blocks the receptor NTCP and does not allow the virus to get into a cell. It has been shown now for more than three years of data that it is very safe, very well tolerated, and very effective. The downside of the medicine is just that it's a daily subcutaneous injection. The patients have to do quite a bit of work to get that medicine and actually get that effect, though they're willing to because of just the high need. I think it speaks to how desperate patients are for treatments there. What our scientists did was really look at that problem and say, we understand that the mechanism is a great mechanism. It's well tolerated and it's safe and it's effective. Can we do something better than a daily subcutaneous injection of a peptide? Our team was able to make a small molecule that also does the same thing. It actually touches the same receptor NTCP, prevents the virus from entering the cell, and essentially will expect to get the same outcome as the marketed treatment in the EU. With that molecule, we've been very excited about how that can add value to patients. How I think it stands out right now from even the competitors in the field is the other medicines are generally antibodies or siRNAs that are still injectables given every two or four weeks apart. We think having an oral pill was really advantageous for patients who are already taking a pill for their hepatitis B concurrent infection. That medicine is currently in a phase 1A study. Jason kind of alluded to this, that in that phase 1A study, it's a little bit more than a typical 1A because it's not just about the safety and the PK. What we also get is a very important pharmacodynamic readout. When the approved therapy in the EU, Bulevirtide, blocks the receptor NTCP, you also block the entry of bile acids into hepatocytes. You can measure that by looking at serum bile acids, and you can see that it is elevated when treated with Bulevirtide. We have the same pharmacodynamic response so far in animal models where if we apply ABI-6250 to animals, and we just presented this at EASL a few weeks ago, you can see an elevation in bile acids in the serum. It is a very important on-target pharmacodynamic measure that says our molecule is docking on NTCP and therefore likely to block the virus as well. We expect that from our phase 1A study in humans now, where we can look at safety, pharmacokinetics, but now this important pharmacodynamic marker that really sets us up for success for the next stage of development. I would just add, as far as study design and the path, that one's actually a little bit unique. You might have seen at the end of last year, we amended our collaboration with Gilead because basically we found a way to accelerate this. We are going to go straight from 1A, assuming positive safety, and we are seeing the bile acid marker, straight to phase two. We are accelerating a lot of efforts on that to basically catch up with the field because we know that there are a lot of competitors out there. The faster we get a small molecule oral pill to the market, we are the only people I know of working on a small molecule once a day oral pill. Of course, we know from experience that, of course, people prefer pills, especially over an injectable daily. I think that program is of high need, not only patients, but a high priority to collaboration as well. How are you thinking about dosing for the oral? Are you benchmarking efficacy to the injectables, or do you feel like there could be a little bit of a delta there given the convenience play? Yeah, you bring up a lot of really good points there. Our preclinical models would suggest that we will be able to do once-a-day treatments with ABI-6250. Again, we'll be waiting for the human PK data to confirm that. From an efficacy side, when you look at the data with Gilead's treatment, you can see that when they dose to higher levels, there is potential upside of increased response on the virus for ALT elevation. There is a possibility with a small molecule you can deliver more of that than you can of a peptide, and we might have an upside of increased efficacy. That being said, I think if we just even match the efficacy of the existing treatment, the difference from going from a daily subcu injection to a pill is so substantial that you will not only, I think, solve the need of the patient, but you'll bring more patients into treatment also. We saw this with hepatitis C where once treatments got better, more people were willing to get treated for that disease, which means more physicians are willing to diagnose that disease and test for that disease. We think that really has a huge advantage, even if we just match the efficacy. There are lots of competitors out there right now with antibody or other siRNA-based approaches. I guess our view is that that's largely all still trying to do entry inhibition just through different mechanisms. Whether you remove the virus from the serum or prevent surface antigen from being produced from a hepatocyte, in the end, we're trying to protect the next hepatocyte from being infected. I believe the efficacy will be similar in all the other modalities and we're not expecting to be any worse off than any other one. Similar just to, you should think about strategic pipeline and patient need too. I mean, obviously, if you've got a once-a-day pill, we know from treatment, obviously, therapy on HBV, you could have potentially a once-a-day pill that included nuke as well. Obviously, that's an expansion upside, but that's something that certainly is in our minds as we think about how to treat the field. Of course, there's an entry mechanism that's inherent in HBV cure as well. That's something we would look at as well in the future. Right. You mentioned that it's an interesting trial design. Can you expand a little bit on that and what you're looking at beyond target engagement? Yeah, so I think there's a couple of parts. One, on this phase 1A study, it's actually a much more standard phase 1A just with a more pharmacodynamic evaluation for the bile acid elevation. What we're trying to do, though, is rapidly go from that to a longer-term study in humans. Kind of skipping a traditional phase 1B study and going straight to more of a phase 2 study. I think that's the part where the 1A PD markers allow us to make that jump. We have more conviction and confidence in what the dosing is going to be that we can skip the 1B and go straight to a phase 2. Just to highlight what was, I think, a fantastic way in which Gilead and Assembly collaborate is we really take our strengths and our understanding of the field together to make the best plan moving forward. I think that's what we did for this program. I think that helps us get that treatment, which we think is highly valuable to people living with hepatitis Delta, to them faster. I guess that's the innovation on this one is that it's really skipping the 1B study. Got it. Okay. And in the last five minutes, last but not least, 4334 for HBV, talk about your kind of what you've shown so far and what you expect to see in terms of the 400 mg update. Yeah, so maybe if I can just take a step back for a second and say hepatitis B, many of us have been working in hepatitis B cure for a long time. It's a really exciting area, high need for patients for sure, but a really challenging area too. One thing we still have high conviction on is that really maximum antiviral pressure will be a key component of a curative regimen. Where 4334 really fits in is in providing that advanced antiviral pressure in addition to a nuke that we think can be a key backbone for a cure regimen. We presented the 1A data in the past just to show the fee PK and safety and presented the first cohort data of ABI-4334, 150 milligrams at the end of last year. The 400 milligram dose is what we think will be a very highly effective dose. We would imagine that we'll be hitting now two mechanisms of action of capsid assembly modulators. Just as a refresh, the first mechanism of action is just the antiviral, so stop making the virus. Mechanism number two is, can you protect hepatocytes from being infected by a virus? You have to get to higher concentrations to get to and more potency to get to that mechanism number two. We're pretty very confident so far that this medicine, 4334, will be able to do both of those actions, mechanism one and mechanism two. It really then maximizes the antiviral pressure. At the end of this 1B study, we'll have done 28 days dosing. Like Jason said, we don't expect to cure anybody in these studies. They're way too short for that. It is a way to benchmark the antiviral efficacy of the drug, the safety of the drug, and really have it ready for when it's more clear how to use that maximum antiviral pressure for HBV cure. I know you don't expect to see functional cure in this update, but in future trials, what do you think is the benchmark for success in terms of cure rate? I think I'd be speculating here, but I think what I'd say is we're seeing the data. I was just at EASL, and there was a lot of great data being presented. Of course, Bepirovirsen from GSK is sort of in the lead right now for showing that it's possible to cure, what mechanisms might be there, and then what bar you need to hit. I think traditionally we've always felt, and the KOLs seem to think that 30% of patients getting functional cure is the bar we really need to hit to make a real big impact in treatment paradigms. I think GSK will be showing that even with potentially lower than that cure rates, there's still an impact for patients and many patients who would love to take a treatment even with a lower cure rate. I think that's going to be very important to watch is how the market reacts to the GSK regimen. I think the whole field will be able to reset and recalibrate based on that data for the future. Lastly, talk a little bit about your cash. I know you have runway into mid-2026. Kind of what are the pushes and pulls there? Yeah, so I would just say as background for the mid-2026 cash runway, we are very conservative on that guidance. We are not including opt-ins, deferrals, or any kind of subsequent results on the collaboration. As you recall from the collaboration, in 2026, there is an extension fee of $75 million. As I think about financing, really, if we get to 2027, which is called six months plus away, right, you have got a multiplier effect, so to speak, that if we are successful on these big cows coming up, you could think about a deferral and opt-in potential financing, and then you have got an extension fee. You would get a multiplier effect of essentially you could be well beyond 28 and have a totally different financial runway, which, of course, would enable us to do a lot of these things we're talking about as far as expansion potential. Great. With that, thank you so much.