Great. Thank you, Charles. Always a pleasure. Thanks for making this so easy, and being so patient. Hey, everybody, we're almost to the lunch hour, actually, at the lunch hour. We've got Viracta with us, two representatives of the company, Mark Rothera, President and CEO, and Darrel Cohen, Chief Medical Officer. Both of them have joined, I think, in the last about a year to a year and a half, roughly, and have given really some great updates, the R&D day recently, a few months ago, in talking with them at J.P. Morgan out in San Francisco, and more recently, we're gonna be doing a KOL call with them, in a couple of days from now. So looking forward to that. But we'll ask Mark to give an update for about 3-5 minutes on the company, and then launch into the Fireside Chat. Great, Hartaj. Thank you so much for the invitation today. So, you know, Viracta, for those of you who are less familiar, is focused on virus-associated cancers. And today, I really wanna focus the discussion around our lead program, Nana-val, for EBV-associated cancers. And I think we're at a very exciting time for the company, as Nana-val is looking to address an area of high unmet medical need. For those of you who don't know, EBV-associated cancers represents around 2% of all cancers worldwide. That's more than 300,000 patients per year affected by cancer with EBV. And I think what's distinctly different here is, if you have EBV-associated cancer, your prognosis is generally a lot worse. There really isn't a targeted treatment for EBV-associated cancer today, across a broad spectrum of lymphomas and solid tumors, and that's what we're trying to do here with Nana-val, is to bring a first-in-class, EBV-targeted treatment to address a whole range of cancers, whether it's lymphomas or solid tumors associated with EBV. And as I said, we're at an exciting time because we're in a pivotal phase II trial for the lymphoma program. We're focused on a lead indication, peripheral T-cell lymphoma. We're also focusing on DLBCL and post-transplant, all EBV-associated. And as you know, we can discuss in a minute, you know, I think we're at an exciting juncture with the data coming out in that lead indication and the idea that we're going to be speaking to the FDA by mid-year to discuss the path to accelerated approval. So I think this is a seminal moment, and we're very excited about the data that we're looking forward to share with the world in the coming, you know, months. That's fantastic, Mark. A really nice synopsis. And, I mean, you know, I think... And by the way, kudos on the synopsis, because I think one of the things that maybe, you know, we've also struggled with as an analyst following the company, is you've got so much going on. You know, for a small-cap biotech company, there's so much going on, and I think, you and Darrel have come in and really honed in on, you know, the lead project. So maybe we talk about that. You know, can you just kinda talk to us a little bit about NAVAL-1, and where you are right now? This is your pivotal trial, you know, with certain, looking at various cancers, one, two, or more that could move on to being approved. Can you just talk about, give us an idea about what, you know, that trial, and how do you get to that meeting with the FDA for accelerated approval, and which cancers could that be? Sure, Hartaj. So NAVAL-1 is a basket trial consisting of three indications that we're studying. So EBV-associated PTCL, DLBCL, and PTLD. And it's a Simon Two-Stage Design. So in Stage I, we're enrolling 10 patients per indication, and if we see an efficacy signal that is at least 2 patient responses, we will continue then into Stage II for a further 11 patients. And in Stage II, when we look at the 21 patients' worth of data, the plan is to take that data to the FDA and discuss the onward path to a potential accelerated approval. So PTCL is our lead cohort. We have completed Stage I. We are now enrolling Stage II and intend, and expect to complete Stage II enrollment this quarter, and then meet with the FDA by mid-year. I think that, you know, is the one that we're really looking to, to push forward as fast as possible towards an approval, because it's an area of very high unmet medical need, as I mentioned. For example, if you have EBV PTCL, you have an 11% five-year survival rate, so it's a, it's a very devastating condition, and we're bringing the only targeted EBV-associated treatment, at this time, to these patients. No, that's really nice, Mark. And, you know, Darrel, what I was wondering was, you know, you've had extensive experience in, you know, oncology development, I'm sure interact with regulators often. You know, assuming you see, you know, a really, you know, good signal from Stage II in PTCL, what do you think the FDA could be looking for in order to, you know, seriously contemplate an accelerated approval kind of pathway? ... Well, thanks, Hartaj. And you're exactly right. So, the FDA has certainly been open to affording its accelerated approval mechanism for products that demonstrate substantial efficacy that's durable with an acceptable safety profile in patients with diseases with high unmet medical need, no alternative available treatments that are serious and life-threatening to the patient. And certainly, EBV- associated lymphomas fit that bill. And with the early suggestions of substantial efficacy, including five out of eight evaluable EBV positive PTCL patients who were relapsed or refractory to prior treatment, having responses, including three of those eight patients having complete responses. In the NAVAL-1 trial, the first 5 patients seeing 2 responses, both complete responses, that were durable. If we can continue to show that in a sufficient number of patients, and we're projecting on the order of around 60-90 patients worth of data, we have a very real possibility that the FDA will consider those results for accelerated approval. Especially since they approved agents, other histone deacetylase inhibitors, such as romidepsin and belinostat, in an EBV unselected patient population, which includes patients with more favorable prognoses, at a much lower response rate, on the order of about 26%, lasting on the order of about 9 months. Given past precedent, given FDA's interest in advancing therapies for patients with serious life-threatening diseases with no alternative treatment options, including relapsed refractory disease settings, such as relapsed refractory PTCL, especially EBV positive PTCL, where there really is no standard of care, the opportunity to potentially have a pathway towards accelerated approval is quite likely. Yeah. No, that helps a lot, Darrel, and thank you for helping us understand what, you know, the large number of patients that you're gonna have, and then the kind of data you might, you know, hopefully will be presenting, you know, talking to with the FDA. Mark, if, you know, assuming you get kind of like, you know, the equivalent of a thumbs up from the FDA on accelerated approval type of pathway, what's the next step? What could we see after that from the company in terms of, like, clinical and regulatory next steps? And then maybe after that, we talk about the market and how big that could be. But just what would be the clinical and regulatory- Sure. Well, the great thing about the design of the NAVAL-1 study is that patients are gonna continue to seamlessly enroll beyond Stage 2 into the expansion phase. So there's no holding up while we wait to have a discussion with the FDA. And I think that's important because, you know, for patients with relapsed refractory PTCL, there is no standard of care today, and trials are what is recommended. So for patients, especially with EBV, where the prognosis is so much worse, they have the potential, given the data that Darrel has just shared with you, you know, to continue to be able to receive treatment while we engage with the FDA, to continue to be enrolled into the expansion phase. So I think the goal with, you know, the meeting that's coming up is really to align, as Darrel was indicating, on how many more patients, you know, do we need to enroll in that expansion phase in order to fulfill the FDA's requirement for the accelerated approval pathway. So that's a key, key outcome. You know, assuming a, a positive outcome, and I think there's plenty of reasons to be confident about that, given the unmet need and the data that we've generated so far, is then, you know, full-tilt enrollment. I mean, we've done a lot already to, I think, enhance and accelerate enrollment, as, as evidenced by the speed with which we're going from Stage one to Stage two. You know, the idea will be to complete that enrollment and go to the FDA, most likely the year after next, for approval. Yep. Um- Now, you mentioned- Go ahead. -the market. Well, I mean, just to say a little bit about that lead indication. In the U.S., there are about 5,600 patients with T-cell lymphoma that, you know, the incident population. And of that population, in our PTCL cohort, we're studying subtypes that equate to about 2,600 patients per year, with these particular PTCL subtypes. And then just to remind you, 40%-65% of those patients have EBV. So I think it's a very, very good first indication for us to be seeking approval around, given the high unmet need, given the speed with which we think we can move this forward. But also, you know, we're excited about the fact that behind that, we're looking to bring EBV-associated DLBCL and PTLD indications as supplementaries to PTCL. ... Yep. No, Mark, that's very, very helpful. And we'll just kind of circle back on just PTCL, the market again. But just wanna check, you know, go back to Darrel. Darrel, one of the things that, you know, when we've spoken with KOLs over the last couple of years, we've shown them the, you know, the early data in the hematological malignancies, you know, with Nana-val. They've always been fascinated, and they're sort of aware of EBV positivity, you know, and the fact that a lot of those patients who have that and have cancer have worse prognosis. But what is the education, well, you know, what are the concrete steps you're gonna have to take, you know, assuming, let's say, again, accelerated approval, to kinda get the medical community up to speed on this, so that, you know, you can hit the ground running, as, you know, assuming you get approval? Well, I think if we have sufficient efficacy and safety of the product, and we're able to reproduce that in many more patients, I think the data will speak themselves. Especially again, if for relapsed/refractory PTCL, for example, unless the PTCL is systemic ALCL CD30 positive, there really is no available therapy for these patients. And so, an approval with a product with substantial objective response rate, duration response, especially complete response rate, that we've seen... Yep, and a favorable safety profile that's manageable, if not versatile, I think will speak for itself, Hartaj. In addition, we have plans in each of our indications to conduct confirmatory clinical benefit studies, randomized clinical trials that will hopefully carry on post-marketing in frontline treatment settings. Including reproducing studies in combination with chemotherapy in frontline PTCL treatment setting. So, results of those studies, if favorable, will also reinforce the added value that a targeted therapy like Nana-val has against EBV-positive PTCL and other lymphomas will be made more clear to treating physicians. Yep. No, Darrel, that's very, that's very, very helpful. In fact, actually, you know, your hire and meeting and talking to you is probably one of the ones that made me the happiest. Because, you know, again, our KOL calls have indicated... And, you know, Lisa already done a fantastic job, but I think a lot of this kind of like, you know, you know, sort of fundamental work you have to do to kind of prepare the market is so critical, right? And Mark, you know, maybe as we're talking, you know, well, you mentioned the size of the market. You know, what do you think are the kind of like the, you know, what could be the bottlenecks to make sure, you know, that you think Viracta is gonna have to focus on, you know, in order to make the, you know, the uptake as quick as possible? Well, and maybe I'll just build on your prior question, Hartaj. One of the things that is in our favor is that the NCCN guidelines for lymphoma do propose that you should measure EBV status. The problem is, you can measure it, but you have no actionable treatment today. And I think as Darrel said, you know, if we continue to generate this compelling data on the efficacy and safety side, and get our Nana-val through to accelerated approval, it will mean that now there is an actionable treatment. And I think that the environment that's already in place, I think, can be very supportive, once you now have something that you can bring to the world to help patients. So, you know, we'll continue to educate around the EBV status and why that is important. And you could argue that could be a bottleneck, but I think there are many reasons why, you know, we can try and minimize that bottleneck, given that there's already awareness around the importance of EBV testing. Yeah. No, Mark, you're absolutely right. I mean, that's one of the things that just is very interesting to us. You know, KOLs, you know, unequivocally like your data, the earlier phase I and II data. And, you know, some have even gone as far as said, "Oh, we'd love to be involved in a larger trial." You know, so, so that, that, that already exists. To Darrel's point, you know, the data will kind of speak to itself. What, what's the next sort of cancer after PTCL or other subtype in the hematological space that you think has real potential, Mark? Well, we're very excited about EBV DLBCL. And, and you know very well that DLBCL as a whole is an area where there's a lot of interest, and there are many different, potential medicines that have been developed for patients with DLBCL. However, for the 5%-15% of DLBCL patients that are EBV positive, we believe that there is a distinct unmet need. If you look at the, survival curve, the prognosis of the disease in patients with EBV positive DLBCL, it's substantially worse, than those that are EBV negative, and there is no targeted treatment for the EBV-associated DLBCL patients. So we're excited about that because we do believe there's a high unmet medical need. We also think it's quite a considerable opportunity from a market potential perspective, in addition to PTCL. So that is, you know, what we see as, if you like, the next indication behind PTCL, and our goal this year is to enroll Stage I, the 10 patients that make Stage I, and hopefully advance to Stage II, as we have already done for PTCL. Just to build on Mark's response, Hartaj, I think it's very important to emphasize that EBV-positive DLBCL is much different than EBV-negative DLBCL. It's classified as a distinct disease by the WHO. It is genetically different, it is biologically different, it is much poor prognosis, as Mark mentioned. And we've seen evidence that, you know, at least some of the standard treatments may not do as well against this disease. Now, the NAVAL-1 study of Nana-val in patients with relapsed or refractory DLBCL is limited to patients who are transplant-ineligible and ineligible for CAR T-cell therapy. But so far in the previous Phase 1b/2 study, with two-thirds of nine patients having a partial response, a third complete response, and some patients up to four years of response, if we can continue to demonstrate that in more patients, that'll be amazing accomplishment for this product, given the distinct biological nature of the disease and the much more difficult to treat poor prognosis condition these patients are in. So I think the opportunity is tremendous, in spite of all the available therapies there are and the emerging therapies there are for this disease that is not selected for EBV status. Yep. And we just have a question online, which I'm just gonna pull up real quick. You know, they're asking that: "Do you think showing separation of Nana-val from nanatinostat monotherapy arm in PTCL will help convince KOLs an exciting new mechanism of action? Yeah, let me take that one. No, we're very excited about the opportunity to clearly distinguish Nana-val and its unique mechanism and mechanism of action from nanatinostat monotherapy. This, by the way, was an FDA requirement anyway, and I probably should have said, Hartaj, that the stage one that we've completed for PTCL includes 10 patients of Nana-val combination therapy and 10 patients of nanatinostat monotherapy. So we're looking forward to sharing that data at a medical meeting later this half of this year and looking to address that question, which is, you know, does the mechanism of action of Nana-val distinctly differentiate from, you know, monotherapy with low-dose nanatinostat? Yep. The FDA is gonna wanna be reassured that we need both drugs in the combination, because HDAC inhibitors have historically shown activity against these diseases. Although with Nana-val, we're using the nanatinostat, the histone deacetylase inhibitor, about a quarter of its MTD, maximum tolerated dose, because we're using it as a viral inducer, not so much as a cytotoxic agent, to induce the virus out of latency and express its protein kinases to activate the antiviral agent and kill the cancer cell. And so we have every reason to believe that the randomized stage one portion comparing Nana-val and nanatinostat alone will read out positively. And we also have a hint of that because in the Phase 1b/2 study, we've seen Nana-val work, the combination nanatinostat, valganciclovir work, in at least two relapsed refractory PTCL patients who failed prior HDAC inhibitor, that the cytotoxic that's named romidepsin, came onto the study and had. One patient had a complete response lasting nearly six months, and another patient had a partial response lasting over 10 months. So, we have every reason to believe that the combination will outperform the monotherapy, convincing FDA and treating physicians with drugs, and it makes biological sense, biological and scientific sense as well. Darrel, the patients on nanatinostat monotherapy, are they still on the same dose as you're using for Nana-val? 'Cause the- Yes. Right. So it's- Yes. Okay. Yes, and they're offered the opportunity to cross over to combination therapy, if they don't respond to the monotherapy. Yeah. And I think we should just point out that the nanatinostat dose that's being utilized in the Nana-val combination is suboptimal compared to other HDACs, right? So, Yeah ... one of the reasons why, you know, this, you can give the combinations, you're not giving it at those higher doses, which leads to a lot of the toxicity we've seen with HDAC inhibitors. Yeah, we're using- And- ... Sorry, we're using it as a viral inducer, not as a- Right ... toxic agent per se. Correct, correct. Darrel, can you just point out a little bit to us, a little bit more, you'd mentioned that the EBV DLBCL, you know, patient subgroup is different. What's the kind of patient numbers and, you know, that you'd like to see before having a conversation with the FDA, assuming Stage 2 is complete, on next steps? And then, you know, just remind us again, what does the data look like until now in EBV positive DLBCL? Yeah, as I mentioned earlier, we have reported so far data from our Phase 1b/2 study, Nana-val, 9 evaluable patients, 6 responses, including three response, three complete responses, including responses that have lasted up to 4 years, which is impressive. As Mark mentioned earlier, I think we have a meeting scheduled with the FDA, primarily to talk about PTCL one, accelerated approval pathway there. We hope to complete enrollment of stage 1, DLBCL cohort this year. As we enroll more patients, if we can advance that cohort into stage two, and we have every belief that we will, and see that we are seeing the same level of responses that we saw in the previous study, we would then meet with the FDA again and rely on accelerated approval pathway, and come up with the appropriate sample size they would need to see and approve. Again, convincing them that, while there are a number of approved agents for relapsed refractory DLBCL, there's nothing approved specifically for EBV positive DLBCL, particularly in patients who are transplant ineligible or not eligible for CAR T-cell therapy, and it still represents a high unmet need. Yep. And Darrel, and Mark, you know, can you just give us an idea? I think you just touched on it earlier, but maybe just a little bit more in depth as to what's the size of EBV positive DLBCL, you know, relative to a PTCL? I'll do my best to remember this off the top of my head, Hartaj. But we're talking about 5%-15% of a much larger number of patients, which is more in the order of sort of 50-100,000 patients incident per year. I will come back to you with a bit more precision. But my point is, it is a very meaningful subset of a large hematological cancer indication. And when you think about Nana-val, it's really a pipeline of conditions, all EBV-associated, that make this a very attractive opportunity commercially. You know, each one of these has high unmet need. I think that supports pricing. We're seeing, as Darrel has described, some quite attractive median duration of responses coming out of the data that we've already generated. And if we continue to, you know, demonstrate that going forward, I think we're trying to address a high unmet need, high value indication with durable responses, a good safety profile. I think it's really the aggregation then of, so far, three indications in lymphoma, and we haven't touched on the fact that we're also looking at two solid tumor indications, NPC and gastric cancer. It's really this very unusual aggregation of rare and specialized conditions under one umbrella, the Nana-val umbrella. Yep. No, you're absolutely right. You know, Mark, it's kinda interesting because we've talked with investors about, you know, Viracta, the market cap. It's just fascinating to me that a company that's got so much going on has a market cap. But I think as you keep executing and delivering, you know, there should just stairstep up, right? You touched on solid tumors, Mark. Can you just give us and Darrel just a quick update as to where we are with the solid tumor study? I know you're focusing on different doses of nanatinostat and maybe the dosing regimen, et cetera, but just a quick update there, where we are and what we could expect in 2024. I'll let Darrel speak first, and then I can speak to the milestones. Sure. Well, as you know, we are currently running a Phase 1b/2 study of Nana-val in patients with relapsed refractory solid tumors, and initially dose-escalating Nana-val in patients with recurrent metastatic EBV-positive nasopharyngeal carcinoma. We've seen a couple of durable partial responses on the way up, and we're also evaluating a novel split daily dosing regimen that was worked out nonclinically to have superior antitumor activity in mouse gastric cancer xenograft model, with where you give the nanatinostat 7 days a week, so 4 days a week on a split dosing schedule to prolong activation of the protein kinase. And we're currently enrolling the first cohort in the absence of DLTs at the earlier cohorts, enabling us to do so. If we can safely enroll and treat these patients at these higher dose levels on a split daily dosing schedule, we hope we can drive even deeper and more durable responses in more of these patients. So stay tuned. Mark? Yeah, so I think that's the new frontier. We're looking for a distinct dose for the solid tumor setting. You know, it's more difficult to get into the solid tumors, so I think we're finding a very interesting and intriguing new dosing approach for solid tumors. And maybe, Hartaj, I should just, you know, summarize by saying this has been, you know, a great last 12 months. I think the execution on our trial has really picked up to a new level. I think we have a lot of milestones ahead this year, in the near term, as well as throughout the year, as we look to demonstrate Nana-val's activity in multiple different lymphomas and solid tumor settings. No, no, Mark, I completely agree. And I can also see it in just the focus of the team, and then just the cohesion, you know, and you all seem to be having fun, too. Last question online from an investor saying: "Is Viracta providing guidance on when DLBCL or PTLD may advance to Stage 2? For both of those indications, what we've said is that we intend to enroll 10 patients in Stage 1 for both indications this year, and hopefully, as a result of the data we generate, we'll then be able to advance into Stage 2 in both of those. But that is data dependent. Yep. I guess we're getting closer and closer, just months away, hopefully, instead of years away. Absolutely. Great. Well, thank you so much, Mark and Darrel. Always a pleasure. Darrel, we'll be touching base with you in a couple of days. And thank you again for participating. We look forward to keeping the conversation going. You bet. Thanks for the invitation, Hartaj. Thank you.