Evening and welcome to the Assembly Bio conference call. At this time all participants are in a listen only mode. There will be a question and answer session after the prepared remarks. To participate, press star one one on your telephone. Please be advised that today's conference is being recorded and will be available for replay on the Assembly Bio website. I will now turn the call over to Jason Okazaki, President and CEO of Assembly Bio. Jason, you may begin. Thanks, Carmen, and thank you all for taking the time to join us this afternoon. I'm joined by Dr. Anuj Gaggar, our Chief Medical Officer, on this call. Before we get started, I would just like to quickly remind everyone, we will be making forward-looking statements, so please refer to our SEC filings for a full list of disclosures. Today we're excited to be able to share what we believe are truly impressive results from our phase I-B clinical studies of our long-acting helicase-primase inhibitor candidates ABI-1179 and ABI-5366 in participants with recurrent genital herpes. This is an important moment for the company and individuals living with this disease as both candidates met or exceeded all key objectives of the study. With this data, we believe we now have a path to a potentially best in class therapy across key parameters including dosing interval and improved efficacy versus approved agents. In a moment we will dig into the data, but first I want to provide a brief overview of the results we are presenting today, which are provided in slide three of the accompanying deck. As a quick reminder, in August you might recall that we announced positive proof of concept interim data on ABI-5366 in its phase I-B clinical study treating participants with recurrent genital herpes, with participants dosed once weekly over 29-days. In cohort B2 of ABI-5366, we saw an astounding 94% reduction of HSV-2 shedding versus placebo and a 97% reduction in virologically confirmed lesions. Today we announced interim efficacy data from two weekly dosing cohorts of ABI-1179, our second long-acting helicase-primase inhibitor candidate, in participants with recurrent genital herpes. Results from cohort B1 of the study show similarly impressive reductions in HSV shedding of 98% and virologically confirmed lesions of 92% versus placebo. We also released today two additional updates from the ABI-5366 phase I-B study. First, we've now updated the interim safety data from the study to include both interim blinded safety data from the third Cohort B3, looking at proof of concept monthly dosing for ABI-5366 and also unblinded safety data from the first two weekly dose cohorts of the phase I-B trial that were released in August in blinded form. Second, we released interim efficacy data from the monthly dosing Cohort B3. This cohort also showed potent antiviral activity, but suggests that we may have additional work to do to maintain the same high level of suppression seen in the weekly dosing cohort. I'm excited to know. Turn it over to Anuj to walk you through each of these important interim data results. Thank you, Jason. We'll first turn to 1179 and slide four outlines the design of the study. This is a double-blind placebo-controlled study evaluating the safety and antiviral activity of ABI-1179 following weekly dose administration over 29-days and participants seropositive for HSV-2 with recurrent genital herpes. An evaluation period for collection of anogenital swabs, quantification of HSV levels and reporting of genital herpes lesions extends from day eight through day 35 inclusive. Within each cohort, 20 participants are assigned to ABI-1179 and five to placebo. The three treatment regimens which have been initiated to date are 10 mg, 20 mg and 50 mg weekly. The results released today cover cohorts B1 receiving 50 mg weekly oral and B2 receiving 20 mg weekly oral and include complete HSV shedding data and safety data through day 57 for the two cohorts. As the 10 mg cohort is ongoing, no data are reported here. Additionally, as follow up is ongoing for cohorts B1 and B2, the safety data are reported collectively for 1179 and placebo recipients within each cohort in order to maintain blinding until the study database is locked. Turning to slide five. Overall baseline demographics and disease characteristics were well balanced between the two cohorts. The enrolled population was predominantly white and aged 40 years. A higher proportion of female participants was enrolled in the 50 mg cohort. Of specific note is the enrollment of a population with active disease having on average five to six genital lesions in the prior 12 months or prior to initiation of suppressive therapy. Approximately 75%-80% of enrolled participants were receiving suppressive therapy with nucleoside analogs at screening. Now looking at slide six. Overall 1179 was well tolerated. On the two treatment cohorts, 71%-92% of participants reported a treatment emergent adverse event, the majority being grade one or two. A single grade three treatment emergent adverse event of migraine was reported by a participant with a medical history of migraines. In the 50 mg placebo cohort, 32%-38% of participants experienced a treatment emergent laboratory abnormality, all being grade one or two. No adverse events led to treatment discontinuations and no serious adverse events were reported. Now moving over to efficacy in the phase I-B study. As with the ABI-5366 study, we looked at both viral shedding and genital lesion recurrence rates. We're looking to achieve an 80%-85% reduction in HSV-2 shedding versus placebo as our key efficacy measure for this study. We also wanted to see directionality for the clinical endpoint of genital lesion recurrence rate. Slide seven shows HSV-2 shedding rates over the evaluation period of 16.9%, 1.4% and 0.4% for placebo 20 mg and 50 mg cohorts, respectively. For both ABI-1179 dose levels. The differences from placebo and HSV-2 shedding rates were statistically significant. The shedding rate for the 50 mg dose represents a 98% reduction compared to placebo. Turning to slide eight, high viral load shedding, that is shedding of greater than 10 to the fourth copies per mL is considered a surrogate marker for increased HSV-2 transmission. At the end of the evaluation period, high viral load shedding rates of 11.8%, 0.5%, and less than 0.1% were reported for the placebo 20 mg and 50 mg cohorts, respectively. Near complete elimination of high viral load shedding for the 50 mg dose represents a greater than 99% reduction compared to placebo. Given this greater than 99% reduction, we are not able to calculate a reliable P value, but this reduction level is consistent with a significant effect and the reduction in high viral load shedding for the 20 mg cohort was statistically significant. Slide nine shows a summary of the virologically confirmed lesion rate, which includes any lesion that had any positive HSV-2 swab taken during the duration of the lesion. At the end of the evaluation period, virologically confirmed genital lesion rates of 8.4%, less than 0.1% and 0.7% were reported for the placebo, 20 mg and 50 mg groups, respectively. Notably similar to the results seen for the 50 mg cohort for high viral load shedding, a P value could not be reliably calculated for the 20 mg dose level given the greater than 99% reduction in virologically confirmed lesion rate compared to placebo. However, the difference is consistent with a highly significant effect. The virologically confirmed lesion rate for the 50 mg dose level represents a 91% reduction compared to placebo. For the 50 mg dose level, the difference from placebo in virologically confirmed lesion rates was statistically significant. Slide 10 summarizes that overall ABI-1179 met or exceeded the goals Assembly established for this phase I-B study. ABI-1179 has been well tolerated with no safety signals identified in humans or animal studies to date. The antiviral and clinical activity profile exceeded the established goals with the 50 mg weekly regimen demonstrating 98% greater than 99% and 91% reductions compared to placebo for HSV-2 viral shedding, high viral load shedding and virologically confirmed genital lesions. With these results, we are pleased to now have two highly promising helicase-primase inhibitor candidates that have exceeded our phase I-B efficacy targets in cohorts evaluating weekly oral dosing in participants seropositive for HSV-2 with recurrent genital herpes. Now let's turn to ABI-5366 beginning on slide 11. The phase I-B study is similar in design to that previously described for ABI-1179 evaluating the safety and antiviral activity of ABI-5366 following weekly administration over 29-days and a simulated monthly dose regimen in participants seropositive for HSV-2 with recurrent genital herpes. With the longer plasma half-life of ABI-5366, the follow-up period is extended through day 98. Three treatment regimens have been evaluated which are cohorts B1 150 mg loading dose with a 30 mg weekly dose, B2 350 mg weekly dose and B3 with five 350 mg loading doses given during the first week of the study and then no further dosing over the 29-day evaluation period to simulate a monthly dose regimen. We previously released interim data for the weekly dosing cohorts B1 and B2 in August, which included 98% of shedding data and all lesion data through the evaluation period. Here we are now also including cohorts B3 evaluating a monthly dosing regimen, and this data set now includes complete HSV-2 shedding and lesion data for all cohorts, complete and unblinded safety data for cohorts B1 and B2, and blinded safety data up to at least day 43 for Cohort B3. Slide 12 shows that overall baseline demographics and disease characteristics were well balanced across cohorts. The enrolled population was predominantly white and aged 44 years. A higher proportion of female participants were enrolled in the monthly cohort. Similar to ABI-1179 study, the ABI-5366 study enrolled a population with active disease having five to six genital lesions in the prior 12 months or prior to initiation of suppressive therapy. Approximately 60% of enrolled participants were receiving suppressive therapy with nucleoside analogs at baseline. Turning to safety on slide 13, overall, ABI-5366 was well tolerated. 90%-100% of participants reported a treatment emergent adverse event and all were grade one or two. Approximately 54%-90% of participants experienced a treatment emergent laboratory abnormality, most being grade one or two. Three grade three treatment emergent laboratory abnormalities were reported, all in cohorts B1 and B2 that are now unblinded. Decreased neutrophils in a placebo patient, exercise associated increased creatine kinase in a 30 mg recipient and worsening of cholesterol elevation in a subject with a grade two elevation at baseline in a 350 mg recipient. No adverse events leading to discontinuation or serious adverse events have been reported. Now turning to efficacy on slide 14 at the end of the evaluation period, HSV-2 shedding rates were 14.9%, 14.5%, 0.9%, and 3.5% in the placebo, 30 mg weekly, 350 mg weekly, and monthly regimens, respectively. For the 350 mg weekly and monthly regimens, the differences from placebo and HSV-2 shedding rates were statistically significant. The shedding rates for the 350 mg weekly dose level was reduced by 94% compared to placebo, which is unchanged from the interim data release in August for this cohort. For the monthly dose cohort we saw a statistically significant 76% reduction in HSV-2 viral shedding rate compared to placebo over the evaluation period, which is our key marker of efficacy for this 29-day phase I-B study. This reduction reflects encouraging potent antiviral activity and recall. Our target for the study was an 80%-85% reduction in shedding and we saw almost 90% of those shedding events occurring in just the last two weeks of the cohort. We plan to continue to optimize exposure of ABI-5366 to further evaluate its potential for monthly oral dosing. Given the level of antiviral activity seen for weekly oral dosing of ABI-5366. Slide 15 presents that over the evaluation period, high viral load shedding rates of 11.8%, 9.4%, 0.2% and 2.2% were reported for the placebo 30 mg weekly, 350 mg weekly and monthly regimens, respectively. With the 350 mgs weekly regimen, the high viral load shedding rate of 0.2% represents a 98% reduction compared to placebo. Turning to slide 16 over the evaluation period, virologically confirmed genital lesion rates of 16.2%, 11.5%, 0.5% and 2% were reported for placebo 30 mg, 350 mg and monthly regimens, respectively. For the 350 mg weekly and monthly regimens, the differences from placebo and overall lesion rates was statistically significant. The virologically confirmed lesion rate for the 350 mg weekly dose regimen represents a 97% reduction compared to placebo. Slide 17 summarizes that overall ABI-5366 met or exceeded the goals Assembly established prior to the conduct of the phase I-B study. ABI-5366 has been well tolerated with no safety signals identified in human or animal studies including chronic toxicology studies. The antiviral and clinical activity profile exceeded the established goals with a 350 mg weekly regimen demonstrating a 94%, 98% and 97% reduction compared to placebo in HSV-2 shedding, high viral load shedding, and virologically confirmed genital lesions. Slide 18 provides a visual representation comparing the impressive efficacy of ABI-1179 and ABI-5366 weekly regimens in these phase I-B studies to historical placebo-controlled phase I-B studies. As you can see, it's a great demonstration on the improvement in shedding reduction rates for both ABI-5366 and ABI-1179, as well as a decreased pill burden. Not only do weekly regimens in both of these highly promising compounds exceed our phase I-B targets for reductions in HSV-2 shedding, but we believe these results are very encouraging for our eventual goals for the program to develop a therapeutic that can improve on the standard of care and offer increased efficacy and better convenience for people living with recurrent genital herpes. Thank you Anuj. Based on these very encouraging phase I-B results, we believe that ABI-5366 and ABI-1179 both have the potential to change the treatment paradigm for individuals with recurrent genital herpes. On slide 19, I will quickly touch on next steps for these programs and upcoming milestones across our broad pipeline, as previously guided, we expect to initiate a phase II clinical study of ABI-5366 in mid-2026 and have also begun phase II enabling activities for ABI-1179 given the strength of the data presented today. As a reminder, our partner Gilead Sciences has the right to opt into an exclusive license for this HSV program with the first option time point continuing through the completion of their review of the phase I-B datasets for ABI-5366 and ABI-1179. We are also continuing chronic toxicology studies on ABI-6250 and continuing preparation for its phase II clinical study in chronic hepatitis delta, which we anticipate initiating by end of 2026. With the financing we close in August, we have a strong financial foundation to execute on these programs over the next several years. We expect our cash runway to fund the company into late 2027, not including potential future payments under the collaboration with Gilead or from potential warrant exercises, either of which would further extend our cash runway beyond 2028. Our cash position supports key activities, including the advancement of both our HSV and HDV programs into phase II. While continuing our efforts to discover and develop new programs. We look forward to keeping everyone updated on our progress next year. Thanks again for your time today and happy holidays to everyone. We'll now move into the Q and A session where Bill Delaney, our Chief Scientific Officer, and Katie Kitrinos, our SVP of Preclinical R&D, will also be joining us. Carmen, I'll turn it over to you. Thank you so much. And as a reminder to ask a question, simply press star one one on your telephone and wait for your name to be announced. To remove yourself, press star one one again. One moment for our first question, please. It comes from the line of Salim Syed with Mizuho. Please proceed. Hey Jason. Hey guys. Congrats on the data. Just a couple from me on maybe ABI-5366, just the language in the release here around pursuing optimization. Could you just clarify exactly what that looks like and when we could see the data from those optimization efforts? And then also if you don't end up having the monthly, does that change the opportunity set here for you guys for ABI-5366? Thank you. Thanks, Salim. Good to catch up today. So why don't I start and then Anuj and Bill, feel free to chime in. So second question first. You know the TPP for these programs has always been once weekly better efficacy than standard of care. So you know, our programs have always been on that profile. So the monthly, what we think of as an upside is probably going to be the next generation regardless. So even when we started this endeavor, we always plan for weekly first, monthly second. So it actually doesn't alter the opportunity at all in our eyes as far as optimizing. I'll start. You know, it's really right now we're looking at formulation. If there's any way to make some formulation tweaks to increase exposure levels, you know, how deep we'll have to go on that or what kind of alterations. I think it's too early to tell, but it's fair to say that we keep doing that in parallel with advancing the weekly regimen, and it would be like a long-term life cycle management as we think about monthly, and in the past we've discussed even potentially quarterly sub- Q regimen. So I think there's a lot of, you know, potential franchise expansion down the road. But the weekly is the great first step for us. Anuj, Bill, anything to add? Yeah, just echo what you're saying, Jason. You know, now that we've completed that Cohort B3, we have a better idea of the drug levels we'll need to maintain at trough through the monthly dosing. Obviously we're working with the University of Washington and Josh Schiffer to continue to refine the pharmacodynamic model and with the results we have now and some additional formulation work as Jason indicated, that we'll pursue next year, we'll continue. To work towards that. But you know, the first order of business is to pursue the weekly. Okay, super helpful. Thanks so much guys. Congrats again. Our next question is from Evan Wang with Guggenheim Securities. Please proceed. Hi, guys, this is Evan Wang on for Vamil Divan at Guggenheim. Super encouraging data across both 5366 and 1179. Just two from us, I guess. First, you know, want to get a sense of next steps prior to advancement into phase II for 5366, you know, over 75 patients now from 5366 and 50 from 1179. Do you feel like you have sufficient exposure in clinical data and the modeling kind of dynamics required to determine the dose? Go forward dose for phase II with the three cohorts worth of data from each? And then second question is really stellar results from 1179. So it looks like there's flexibility to explore the dose relationship. It looks like you're doing that with a 10 mg just given the strong shedding in lesion reductions. I'm just curious, with two strong programs now in 5366 and 1179 in both on the weekly right now, can you talk about how you're thinking about the opportunity for clinical development for both programs? Will it be similar or could there be an opportunity for kind of unique development? Thanks. Yeah, when I started the second program and then I'll kick it over to Anuj. So as far as the weekly, you know, I think we had always talked about the baseline being moving 5366 forward in a phase II. I think with this data, it does create an interesting dilemma for us. A very positive element to have of, you know, do you take both forward in a 5366 and like you said, Evan, is there different kind of addressable patient populations or something you can do with that? So I think it's too early to say that, but you can assume that we are analyzing all efforts as far as phase II programs for both of those molecules. And of course with the partner we've had, those discussions are ongoing with them as well. Anuj, I'll turn it over to you. Yeah, and thanks, Evan. This is Anuj. So I think the question of how we are looking at the data that we've collected so far for both programs for choosing doses and moving forward into phase II. It's a great point. And we think we are there with both compounds with the three cohorts of data. As you know, we're doing some PKPD modeling with the University of Washington and Fred Hutchinson Cancer Center with Josh Schiffer. And that really helps us take these data and zero in on doses that we can move to phase II. So we're pretty confident with the data we have in hand and again finishing the Cohort B3 for 1179, that we'll have the data we need to be able to choose those doses. And so we're really pushing forward to phase II as fast as we can. Maybe one follow up, I guess. Would it be kind of interchangeable as you're thinking about mid-2026 start between ABI-5366 and the ABI-1179 or are there kind of considerations we think about in terms of, I guess, choosing one or the other? Yeah, I think one of the major parts of our phase II program is to do longer term dosing. And so in order to do the longer term dosing, we do need to complete all the chronic toxicology requirements which have been completed for ABI-5366, and they're planned to be completed later on for ABI-1179. So I think the timing is going to be dictated more by the requirements to do the study we'd like to do with 5366 happening first. Awesome. Thank you so much. Thank you. Our next question comes from the line of Dennis Ding with Jefferies, please proceed. Hi, this is Georgia on for Dennis. Thank you for taking your questions and congratulations on the data. I had a question on 1179 and that it nearly eliminated shedding, but the lesion reduction was less compared to like 5366, and just wondering if you can help me understand the relationship between the lesion reduction and the shedding reductions and whether this reflects differences in tissue penetration, immune mediated lesion formation, or something else. Thank you. Yeah, it's a good point. I think in general, we always knew that lesions are a bit more of a stochastic process when they occur compared to shedding, which is why it was not the powered endpoint for the study. We know they track very well, but they're not necessarily always a one to one relationship. These are also patient reported lesions. And so it's not always the case that what gets listed as a lesion is truly a lesion or the duration of the lesion is all virologically is due to the virus. Now, we do look at virologically confirmed lesions and that's an important way of trying to get at what are lesions due to HSV-2, which ones are not. That being said, those lesions are also, you know, the resolution of them have to do with the immune response and other things that are not just the virus itself. So I think when we started off with this program we really just wanted to see the shedding primarily directionality on lesions and we know they are related to one another and I think in a longer term study the correlation will get even tighter. So right now it's just a short duration study. Got it. Thank you. Thank you so much. One moment for our next question. And it comes from Patrick Trucchio with H.C. Wainwright. Please proceed. Thanks. Good afternoon and congrats on the data. Several follow up questions from us. The first one is, is there a specific criteria that would drive the decision to advance either ABI-1179 or ABI-5366? Secondly, do you view the near elimination of high viral load shedding as a surrogate for transmission reduction? How could that be incorporated into a phase II? Or is that part of regulatory discussions? And then lastly, I was just wondering if the collaboration structure, if you could remind us if it differs economically or strategically depending on whether 1179 or 5366 is advanced. Thanks, Patrick. Why don't I start with the last one? So collaborative structure, the option, there is no economic difference between the two assets. They're treated identically as our programs. And then for the first question, you know, thought process on ABI-5366 versus ABI-1179. You know, I think the base case that I've said is we'll go forward with ABI-5366 as a weekly regimen and that's, that's scheduled to, you know, initiate by mid-2026. So that's, that's ahead. And like Anuj alluded to, we still do chronic tox on ABI-1179. So we couldn't just pick one and both start them both in mid-2026. That being said, certainly we are, you know, speeding up things on ABI-1179 to give the option that asset as well to ABI-1179, sorry to bring that to phase II as well. So I think the scenario you could have is, you know, 5366 initiates mid-2026 and then depending on, you know, what the final cohorts in 1179 turn out, we may be trying to accelerate that to also bring out the phase II, which would be a new thing that we hadn't previously contemplated, and of course to your last question, all this is subject to the overarching collaboration. Right. And there's an opt-in structure. So certainly that makes the decision process a little bit more complicated. But again, good problem to have in our book. Anuj, you want to take the second one? Yeah. And it's a great question on how we look at the high viral load reduction, high viral load shedding. So yes, this is correlated with reduced transmission. This will in the end require discussions with the regulators as to how we use this virological endpoint to inform the risk of shedding or risk of transmission. And I think we have pretty good standing because of what the work that valacyclovir has done before which has shown the reduction in transmission with treatment. And our goal in the phase II program is to benchmark 5366 and 1179 versus valacyclovir so we can really understand the impact on the virus in relation to high viral load shedding and shedding in general. And I think we would assume that if we were to do better than valacyclovir on both of those metrics, that it should result in a reduction in transmission as well. And like you said, that will require discussion with the agencies at that point. Terrific. Thanks so much. Thank you so much. And as I see no further questions in the queue, I will conclude the Q and A session and conference for today. Thank you all for participating. You may now disconnect.