Thank you, and good afternoon, everyone. Welcome back here to another session on the first day of Oppenheimer's 34th Annual Life Sciences Conference. Really delighted to have with us as our next company that will be featuring ESSA Pharma, and this company is working in the area of prostate cancer. We have the company's CEO, Dr. David Parkinson, and he's joined by Peter Virsik, who is COO, as well as David Wood, who's the company's Chief Financial Officer. We'll be running this in a fireside chat format, so kind of an informal discussion about the company's current programs and plans. But maybe first, just sort of to set the stage here, the androgen receptor, this has been obviously a very well-established target in prostate cancer, and whether the drugs directly block it or perhaps lower the level of testosterone or other androgens, that's been the mainstay of treatment. And we've gotten really good at that. We see a number of drugs in the market that have done considerable sales into the $ billions for later-stage prostate cancer. These tumors have also become really, really exceptionally good at finding ways to get around or escape those approaches. So before we kind of get into the specifics on ESSA, maybe, David, you could share with us what we know about sensitive, castration-resistant prostate cancer and how tumors evolve as they're treated with these antiandrogens. Well, Lel and I think you've set the stage very well. It's been known since the late 1950s that prostate cancer is uniquely related to androgen biology, male hormone biology. So we have a six, 7-decade history of the development of incrementally better antiandrogens. Each improvement, whether it be half-life or potency, has led to improved clinical benefit when these drugs are applied to early-stage prostate cancer. The reality is, though, that all men will eventually, if they receive the drugs for long enough, become resistant. The resistance mechanisms are really quite well understood at the moment, and they can occur at the DNA or the RNA level, but they uniformly involve the ligand binding domain of the receptor, the C-terminal end of the receptor, not surprisingly, because that's where, as you indicated, all current antiandrogens work. What we are focused on is a group of compounds which are called Anitens as a suffix, which shut down androgen transcription but do it at the other end of the receptor. That has many advantages, potentially, because experimentally, we bypass the resistance mechanisms associated with the other end of the receptor. We initially went into this thinking that that's, in fact, what we would be able to do is, to late-stage patients with prostate cancer, give them our Anitens; in our case, the latest drug is masofaniten, and basically reverse the resistance of antiandrogens. The reality is a little bit more complicated in the sense that after these men have had antiandrogens for five or 10 years, frankly, they develop all sorts of other genomic changes. So what we came to understand is that the better role for our drug is in earlier-stage patients where the biology is more AR dominant and the patients are more homogeneous and they haven't had five or 10 years to develop resistance. In addition, we have been doing a lot of preclinical work suggesting very strongly that if we can approach the treatment of these early patients with a 2-pronged attack, if you will, shutting down the receptor from both ends, both the N-terminal domain and the classic ligand binding domain, that we get deeper suppression and consistent with the history of drug development in this area, that should translate to better clinical benefit. So that's why we're doing what we're currently doing. That's why we're now focused on combination therapy in earlier lines of patients. But we had to earn our way into those earlier lines by showing the drug was safe, well tolerated, appropriate for early patients, and actually could be given safely. And we're in the process of showing that with all the various current antiandrogens. ESSA is really the only company that's working in this N-terminal domain side of the receptor, is that right? Peter, can you comment on that? I think you're absolutely correct, Leland. But Peter? Yeah, no, Leland, you're right. We're the only company that has a clinical N-terminal domain inhibitor. The approach has not been something that others didn't want to try, but the problem is the target is intrinsically disordered, and so it is not really amenable to traditional research methods of screening. The reason we were able to come up with the Aniten class is because we had an initial hit from many years ago, 20 years ago now, that gave us the chemical structure to start from, which we've evolved over time. So to this date, we don't know of anyone else that's in the clinic who has an N-terminal domain inhibitor. So we are unique. You touched on a large part of the focus that you're executing on is to bring masofaniten forward with enzalutamide in metastatic castration-resistant prostate cancer. You've begun a randomized phase II of that combination versus enzalutamide alone in patients who are naive to the second-generation antiandrogens, such as enzalutamide and some others. This offers obviously complementarity, as you've discussed. We've had encouraging dose escalation data that you've shown at some conferences, very deep declines in PSA in that type of patient population. Some of them may have received prior chemotherapy as well, which, of course, is the next step after you fail all of these androgen receptor-directed approaches. We did see a nice update at the ASCO GU conference just a few weeks ago. I think just to bring everyone up to speed, if you could review some of the highlights of the data that you showed at the conference and also maybe get into a bit why getting to a very deep PSA response is particularly important. Peter? Sure. So let me address that. So from a preclinical standpoint, David already mentioned that what we saw across a variety of different studies was this deeper, broader inhibition of AR biology. And our hypothesis was that if we were to translate that into patients, what we should look for in combination in patients who are sensitive to an AR inhibitor would be faster PSA responses that are deeper in more patients and that would then potentially last longer, be more durable. And so at ASCO GU, we presented the complete phase I dose escalation data for masofaniten plus enzalutamide. It was our 4-dose cohorts. These are in first-line metastatic CRPC patients. Similar patient population as to the original approval PREVAIL study that enzalutamide enrolled many years ago now and a few other subsequent studies. Basically, what we've shown here in this patient population is that indeed, we're seeing very deep, rapid responses in these patients. That occurs in more patients. At ASCO GU, we started to talk more about the duration of that time to PSA progression and the durability factor. So we would typically expect to see in this patient population about a 40%-50% PSA 90 response. I'll explain why PSA 90 is important. We saw 81% in our study, and it's not necessarily completed at this point. So a very good incremental improvement. The reason we're looking at PSA 90 is because when you look at the historical data, and we've already touched upon it here, is that the deeper you can suppress AR biology, the deeper PSA is suppressed, the better patients do long term. There have been studies with PREVAIL in the first-line metastatic CRPC population, in the PROSPER study with enzalutamide, in the non-metastatic CRPC, and even in the ARCHES study, which is the metastatic hormone-sensitive population with enzalutamide. Each of those studies show that the deeper you can suppress PSA, you get to that PSA90 or even beyond, the better patients long term and have better overall survival. So it's a very good proxy for us to get a near-term marker regarding how patients are doing on the combination. And you saw those fairly rapid reductions together with what looked like encouraging durability of patients staying down. Maybe after some time, a few patients began to rise, but I guess that would be expected in a few patients. But in addition to that, we also learned that that population that was shown in the ASCO GU update, many of them had a few risk factors for early enzalutamide failure, I think it was about 75%. So that presumably supports going right to the combination with your drug when going to a second-gen antiandrogen. Is that correct? Yeah, no, Leland, you're exactly right. I mean, the data are pretty intriguing. I mean, the question we've had along the way, which is, okay, the PSA responses, and when you look at the spider plot of the PSA responses over time, they look pretty promising. Okay? But the question should be asked then, okay, but did you somehow select patients that were easier to treat? And so we did an analysis using risk factors, as you indicated, that were used most recently in the ENZA-p study that reported at ESMO in the fall. This was ENZA-p is testing and enzalutamide versus enzalutamide alone in a similar patient population. But what they did is they made sure that these were higher-risk patients that they enrolled. What they did is they took these high-risk criteria that were originally developed from PREVAIL many years ago now that were shown to basically predispose a patient to an early ENZA failure. Patients to enroll in ENZA-p needed to have at least. And we showed in our studies, you just indicated, 75%+ of our patients had at least two of those risk factors. So these were not easier to treat patients, from our perspective. They were probably a little bit harder. And so the durability data that we generated to date, 16.6 months so far and counting, we'll see where it goes, compares pretty favorably to the 7.8 months for ENZA-p or the 11 or 12 months for the other larger studies for time to PSA progression. And that's really the next major clinical time-paced endpoint that we're going to be looking at. Yeah. And investors, you know, often focus on PSA and patients entering the trial—what's their baseline PSA levels. They may look at those trials. Obviously, you're comparing across trials, but they believe that coming in with a lower baseline PSA, as I believe came in the population that you've been looking at, may have been perhaps easier. It sounds like that's probably not the case. No, no, it's interesting. When you look at the ENZA-p criteria, it doesn't look at baseline PSA level. It looks at baseline PSA doubling time as a risk factor, so how quickly the PSAs are rising. The reason we've kind of already tried to address this, we had a lot of patients that were post-ENZA in our sorry, post-docetaxel or post-chemo in our study, 44%. And these patients came in with a lower PSA level because they had responded to docetaxel on ADT initially, but were clearly not doing well. PSA doubling times were rising rapidly. And so our median PSA may have been a little bit lower. But remember, and we've talked about this, Leland, studies were done with PREVAIL looking at low PSAs versus high PSAs starting less than 10, more than 10, and it made no difference with respect to PSA 90 rates of the patients. And so I think there's been a lot of talk, and people have kind of gotten more educated around, be it baseline PSA levels, really don't and aren't really prognostic the absolute levels. You have to look at what happened before and why they were at that level and what the trajectory is, really, to get a say and a feeling for how that relates for the risk factors. Right, right. And the phase II, you've begun. You're taking patients into various sites. I don't believe you've given any guidance on when we may see data from that study, but any updates you can share on the progress of the randomized phase? Just that we have significant investigator enthusiasm. We have 25+ open sites. Those are in the U.S., Canada, and Australia. And we're in the process of adding somewhere around 15 additional sites in Europe, in Belgium, France, and Spain. And so, as you indicated, it's a 120-patient study, 80 patients receiving the combination, 40 the enzalutamide alone. And you're right, we haven't given guidance yet because we don't actually know yet. And we'll let this study run for two or three more months. And when we believe we have a sense of how long it'll take, then we'll give some guidance. To do so at this particular point in time would be only speculative. Yeah, that's fair. And in terms of maybe potentially other data, as you do have multiple studies ongoing with masofaniten and with some of the other antiandrogens, maybe if you could just kind of briefly describe those for us and could we see data from those combination studies or your monotherapy study later this year? Yeah. Peter, do you want to comment on that? Sure. So with J&J, we've got combination studies underway with their two drugs, abiraterone and apalutamide. With abiraterone, we're testing in a 3+3 phase I design. So these aren't large numbers, but the combination of masofaniten and abiraterone in two- patient populations. First one is metastatic CRPC, so similar to what we're doing now or perhaps even one stage later. And then more importantly or more interestingly in some ways is the metastatic hormone-sensitive or castrate-sensitive population that we're also going to be treating. Because remember, these are the patients that are earlier, have not yet had any antiandrogen therapy, and where we believe the dual effect could perhaps help patients the most. So those data are being generated now. We are screening and enrolling patients in that study. We also have an apalutamide combination study with masofaniten. It's a non-metastatic CRPC patient population. An interesting part of that study is we have three months of monotherapy of masofaniten, and then we add apalutamide. So we're currently screening and enrolling for that study as well. We should have some datasets from one or more of these in the fall. Won't be large, but we hope to be able to talk a little bit about the compatibility, safety, and other clinical data we can generate from that. So the fall, we're hoping to have some of the data from those combinations. We probably won't be able to get into any of the investigator-sponsored trials that are ongoing right now. We've mentioned in the past the combination with darolutamide in a neoadjuvant setting with high-risk prostatectomy patients testing darolutamide alone versus the combination for three months and looking at a lot of biological parameters. That's underway, and it's enrolling right now, but we probably won't have data from that. But then we will have a good update on the phase I combo study we were just talking about with enzalutamide. And at that point, we should have a pretty good feel for the total PSA responses. Remember, we're looking at things like PSA less than 0.2, PSA 90 rates. Some of the patients we brought in have only been treated for six months when we reported last. By the fall, we should have a complete picture on that. And then also, the durability will also be a nice update at that time. Terrific. And you did do, as part of your early clinical work on the combination of masofaniten and enzalutamide, looking at sort of the effects of each drug on the other. You did see, even though there was no effect of your drug on enzalutamide, there was some reduction by enzalutamide on masofaniten. So you were giving that twice a day, enzalutamide given once a day. I guess two questions there is, do you expect that to be an issue that may also creep up with some of the other antiandrogens such as darolutamide or apalutamide? Or could you see those maybe being kind of a once daily for both, which would be even easier for patients who are able to hopefully stay away from things like chemotherapy and whatnot and be able to manage their disease in a fairly low-burden type of fashion? No, good comments. Yes, in fact, enzalutamide does increase the metabolism of our drug. That was totally anticipated. Enzalutamide is notorious as a CYP3A4 inducer at inducing the more rapid metabolism of other drugs. Hence, because we had anticipated that, we'd gone to the 600 milligrams twice a day to combine with full-dose enzalutamide. We would expect a similar effect, maybe slightly less, from apalutamide because the drugs are so similar in terms of those characteristics. We expect no interaction at the drug-drug interaction level with darolutamide and similarly with abiraterone. And in fact, we have seen some early data with the abiraterone from the Janssen. We've talked about this in the past that would suggest that that is, in fact, the effect. So with abiraterone or darolutamide, no effects. With enzalutamide, the toughest one to combine with. We've done that already, shown that the toxicity profile of the two together is no different, at least in our experience to date, of enzalutamide alone. So I think we're good. Good, good. Yeah. And it makes complete sense, obviously, to be going for earlier sort of line, initial second-gen antiandrogen with enzalutamide or sorry, with masofaniten, given the data you've seen. At the same time, you've also seen some efficacy data from single agent, maybe in a more recalcitrant population. How should we think about kind of what the opportunity is for your drug to be used on its own without a second-gen antiandrogen combination? Well, we started as a single-agent approach, late-stage patients. The drug performs as designed. The problem is the patients are more complicated biologically, the majority of these patients. And so part of the reason for going to expansion phases in our single agent, that is, the monotherapy late-stage patient studies, the dose escalation, was to see whether we could identify a group of men who, after having been on classical antiandrogens for a number of years, had tumors that were still predominantly driven by AR. And I think we're coming to the conclusion we'll report on that, as Peter indicated more formally in the fall, that if there is such a population, it's not very large, and therefore that the role for this drug in the future is to really, as we talked about earlier, take antiandrogen biology suppression to a whole new level. We believe we can do that. The preclinical data supports that. The phase I combination data is consistent with that. We're now moving to the higher level of evidence from the randomized trial. But single agent, we're not trying to compete with the current antiandrogens. They're good drugs. We have no evidence that we would be better than them as a single agent. What we really believe the next step in anti-androgen biology treatment of prostate cancer is shutting down that receptor from both ends, both N-terminal domain and ligand-binding domain inhibition. Yeah, absolutely. And in the trials that you're conducting with some of these other agents, large companies behind those, maybe just to give investors a sense of how you have arrangements with those other companies, kind of is it simply access to medication? Is it more of a kind of a collaboration? What do those look like? Peter? Yeah, sure. So we established the three collaborations we talked about. These are all clinical collaborations, meaning there's an exchange of clinical material, either from us to them or from them to us. That's what it is right now. And then, of course, an exchange of safety data and initial strategy and overall plans. So when we came up with the protocols, these were protocols that either our partner came up with that we talked about or we came up with that our partner reviewed. So the plans are pretty well vetted by both parties. Interestingly enough, most of the plans and the goals of the primary endpoint were pretty similar across all of these studies and goals. But these are really light, what I would call, collaborations. There's no long-term rights. There's no right of first refusal. There's no economics that are really exchanged. That's because it's really just clinical material that's exchanged and data and then know-how. Right. And as we've seen in the prostate cancer space, kind of a M&A sort of oriented part of the therapeutic universe, companies like J&J having done a few acquisitions there. So it sounds like you guys would be kind of free and clear to maybe be taken into one of those larger companies should things progress further with masofaniten in the pipeline and combinations between your drug and theirs are fruitful. So as investors, think about kind of the future of ESSA, would you still be kind of prepared to go on your own, or is that kind of the direction that you sort of see things happening maybe further down the road? Well, we recognize that while we can do the kinds of studies we're talking about here today, to get into the definitive registration-directed phase III studies with clinical endpoints, not biomarker-like PSA endpoints, would require, at a minimum, partnership, a collaboration. And how our future in terms of collaborating, partnering, whatever, with one or more of those large companies evolves remains to be seen. We'll complete the story of showing how our drug can be combined with one or another of those. And we believe it could be combined with any of those. So just how things evolve in that regard, listening to what you're saying, only the future will tell. We'll look forward to that. I don't want to leave this discussion without a chance for our third member of the team, David Wood, Company CFO, to add a few comments. Maybe, David, if you could just provide us a picture on ESSA's balance sheet and what you see as your runway for conducting your work. Yeah, thank you, Leland. Yeah, the cash at December 31st we reported this morning was $142 million. And that's a runway through the end of 2025 with a pretty solid balance at that point. We haven't given guidance on that. But that allows us through the period where we're going to have data from the various studies that have been outlined on the call today, including the phase II study with enzalutamide in 2025. So we feel we've got a good runway through a period where we will have data to report on. If there's a financing opportunity that makes sense for the company, we would definitely look at it. But at this point, we are comfortable with our runway. We have no debt on the balance sheet either, so we're in pretty good shape to execute. Fantastic. In terms of your stock, it looks like after some time of maybe being a bit off the radar, you guys have become much more front and center starting late last year as we've started to see some of the data come out. Looking forward to further catalysts, obviously, from the phase II and also the other studies as well. Please let me know if there's anything else we should look forward to in terms of the particular highlights this year. I think you mentioned, David, there'll be a couple of probably abstracts and posters. Sounds like we should kind of stay tuned for when we might start seeing updates from the randomized phase II. Yes, Leland. We'll give guidance along the way as to how we think the phase II is going and what we think the timelines could be for that. But as Peter indicated, we'll have information in the fall about the update on the longevity of the PSA declines that we've seen in the initial combination work. And then we'll have new information on our ability to combine with abiraterone, with apalutamide, and at some point maybe later with darolutamide. So stay tuned. This promises to be a very, very interesting next 12+ months for us. And we very much appreciate the opportunity to talk with you about that today. So thank you. Terrific. No, thank you. I think we're all looking forward to more to come. Thank you all for joining this discussion. Have a great day, everyone. Thank you. Thank you. Take care, everyone.