Hi, welcome back to the 41st Annual Cowen Healthcare Conference. Next session, we're very excited to have today, ESSA Pharma and several members of the management team to tell us about how they've got a very interesting novel way of targeting one of the most validated targets in oncology, the androgen receptor. With that, I'll turn it over to the team. We've got today, David Parkinson, CEO, Peter Virsik, COO, as well as David Wood, the CFO. I think they're going to tag team the presentation. With that, I'll hand it over to David Parkinson, who will lead it off. Thank you. Thank you very much, Mark. It's really a pleasure to be here today and to share what we're doing here at ESSA and why we're doing it. Peter, if you could move on, please. The first slide is the forward-looking statements, moving on. What we're going to tell you about is, as Mark indicated, a novel way of shutting down arguably the most validated pathway in all of medical oncology, and that is the androgen pathway association with prostate cancer. The majority of men, for the majority of the natural history of the tumor in those men, have the tumor driven by androgens, by male hormones, through the androgen receptor. What we're talking about here today is a novel way of shutting down that biology. It comes out of the work over some 20 years of two scientists at the University of British Columbia in Vancouver. Comes from a finding from an extract in a natural product that was shown to shut down androgen signaling, even in cells resistant to current antiandrogens. We'll talk about what the company is doing and where we're at and why we're excited about what our potential is for changing the natural history of prostate cancer. Next slide, please, Peter. With me here today are my colleagues, Peter and David. You can see we're all experienced drug and diagnostics developers. Not with us on the call today is Alessandra Cesano, our Chief Medical Officer. Again, very experienced medical oncologist who has led successful therapeutics and diagnostics development over her career. Next slide, please, Peter. As I indicated, the androgen pathway is the most important driver of prostate cancer. Prostate cancer is a huge public health problem, and the most important drugs in prostate cancer globally are the so-called anti-androgens. There's been a six-decade, that is 60 year history, of the development of incrementally better anti-androgens. What we'll talk to you about is the way in which those anti-androgens work, why resistance inevitably develops to those anti-androgens, and what the opportunity of a novel method of shutting down androgen transcription does to potentially change the natural history of prostate cancer. What's really important for this conversation today is to note that even in men who are progressing on current anti-androgens, in the majority of those men, the pathway is still on and still an important driver of the tumor. Next slide. This is an important slide. What you see is the cartoon of the androgen receptor. That receptor normally sits in the cytoplasm of prostate cancer cells. In comes the hormone dihydrotestosterone binds to the right part of the receptor in this cartoon, the ligand-binding domain. Activates the receptor, which then translocates to the nucleus. There's a dimerization phenomenon, and then binding through that central DNA binding domain to what are called androgen receptor elements. Very specific areas on genomic DNA that drive transcription and the gene expression associated with male hormone biology. That binding does not occur without the influence of the left side as portrayed here in this cartoon, the so-called N-terminal domain. We've tried to portray it here as kind of squiggly because this doesn't have a formal three-dimensional structure, the overall N-terminal domain. It's not possible to get a crystal structure, and even though it has been the source of a number of attempts to drug, and none of those have been successful. What we have in the upper left-hand corner is the six decades I referred to of antiandrogen development, and either antiandrogens that decrease the level of circulating androgens or those that are blockers, and these are all the lutamides that date back to the '80s, the most recent drugs being the three on the top there, darolutamide, apalutamide, and enzalutamide. These are great drugs. They change the natural history of prostate cancer. Men become resistant through the mechanism shown on the right part of this slide. Some of those mechanisms of resistance are at the DNA level with amplification, either of the receptor itself or its enhancer. Ligand-binding domain mutations which occur. Splice variant, that is RNA-based mechanisms of resistance with these truncated RNAs that lead to a constitutively activated receptor in the absence of large parts of the ligand-binding domain are a very important mechanism of resistance, it appears. Next slide, please. What's important about ESSA and the series of drugs that we have developed called Anitens, again, deriving from those original observations by the Vancouver scientists, are a series of drugs that bind to the N-terminal domain. One of the earlier of these drugs was shown by workers in the University of Barcelona to bind specifically to an area called transactivation unit five within the AF1 transcriptional region. By doing so, seems to interfere with cofactor formation and therefore with the binding of the activated receptor to those androgen receptor elements I discussed. 7386, the drug we'll be discussing in more detail today, which is in the clinic now. We presume and have a lot of evidence indirectly to show binds to the same area. It definitely carries out exactly the same biology. We will be showing at the AACR meetings in April, more data consistent with the mechanism of this particular binding. Next slide. On this slide, on the top are the different approaches, the different stages of prostate cancer. On the second level are the approved treatments. Basically what you have historically in prostate cancer is a locally diagnosed disease followed by a rise in PSA indicating dissemination. The advent, either before or at that point, of what we called androgen deprivation therapy, these LHRH agonists or antagonists that work centrally at the hypothalamus to decrease the level of circulating antiandrogen, so-called chemical castration. When these drugs also begin to fail and when rising PSA occurred, that is the context in which the lutamides were developed, these blockers that I referred to. What's happened in the last five years is that the lutamides have been moved earlier in the treatment of prostate cancer, have been combined with androgen deprivation therapy. That combined greater suppression of androgens has led to improved progression-free and then definitively overall survival. The message here is that the deeper in prostate cancer you can suppress androgen biology, the greater that translates to clinical benefit. What we are talking about here with a novel way of shutting down transcription is where we have to start is in the lower right-hand corner, EPI-7386. We need to start in our drug development, in the men who have progressed on those current anti-androgens. As we'll talk about in the phase I trial, men who have been on latest generation anti-androgens, whose tumor is progressing, whose PSA is rising, are clinically selected on that basis, enter the clinical trial, and are treated with escalating doses of 7386. Next slide, please. The company brought into clinical development in late 2015, the first of the generation of anitens, EPI-506. Peter and I joined the company soon after that point. We, together with David, conducted the phase I clinical trial, and we showed that in these late-stage men resistant to anti-androgens, we could see a decrease in PSA. We had proof of concept. Those decreases were not deep enough, and they were not sustained long enough for this to be a clinically useful drug. What it did, what that phase I trial did was give us a guidepost on the kinds of characteristics that we needed to improve in a next generation of molecule. After we presented that data and after the phase I trial was complete, with the support of our investors, we reconfigured as a preclinical company and spent a year and a half developing a new molecule to meet all of those characteristics. At this point, next slide, please. I'm going to turn it over to my colleague, Peter Virsik, who led the activities to come up with that next generation drug we call EPI-7386. Peter, let me turn it over to you. Thanks, David. The reason we chose 7386 as our next clinical candidate is for these particular reasons listed here on slide 10. From a potency standpoint, 7386 is 20x more potent than that original clinical candidate, 506, and is now similar potency as the current leading antiandrogens. From a xenograft mouse activity perspective, 7386 works in both antiandrogen sensitive models as well as those resistant models where AR-V7, the splice variant, shows resistance and enzalutamide no longer works. From a ADME perspective, 7386 shows very good stability, very low metabolism in animals, and has a very long predicted half-life in humans. We're predicting over 30 hours, and we'll talk a little bit more about the clinical data generated to date. A very stable molecule. From a selectivity standpoint, very important to maintain that on-target N-terminal domain targeting while also making sure off-target activity is minimal. We believe we've achieved that, and in fact, we were able to achieve very high exposures in our tox studies, giving us greater comfort that we remain on target. From a drug-drug interaction standpoint, long term, as David mentioned, our goal is to be able to combine with the current leading anti-androgens in earlier-line patients. For that reason, we want to make sure that we can combine from a drug-drug interaction standpoint, but also that we don't have any combinability issues from a toxicology perspective. We've made sure that these molecules do not share the same tox profiles as the current anti-androgens. Lastly, from a CMC standpoint, this drug needs to be a simple-to-make synthetic product. It is, in fact, that it has a high melting point, crystalline. We, in fact, already have tablets that we have taken into clinic. From these preclinical data, we generated 14 and 28 day toxicology studies that we ran on the program in rats and dogs. In those toxicology studies, we were able to achieve very high exposures of drug, area under the curve, AUCs, as you call it. With those very high exposures, very minimal toxicities, we were able to provide a recommended starting dose to the FDA of 200 milligrams, a very favorable starting dose in our view. Our projections indicated that at that dose in patients, we would achieve an exposure, an AUC, in patients of roughly 130,000 or 140,000. Looking at this slide on Slide here 11, on the left-hand side, translating that level of exposure of 7386 in one of our xenograft models, you'd see that that level of drug would indicate a biologically active dose in this xenograft model, indicating that in the clinic, we might see, in some patients, perhaps, even at the starting dose, some signs of activity. Regardless, a very good starting dose for us to get into the clinic. Our target here, though, is to be able to get to exposures of over 300,000 AUC, we're projecting that that would be roughly at the 600 milligram or 800 milligram doses. The reason we're targeting 300,000 is because that is the exposure where we saw good, consistent antitumor activity across all of our xenograft models with the molecule. David, I'm going to go ahead and turn it back over to you to talk a little bit about the clinical program. As I indicated earlier, we have a group of patients who've been on antiandrogens whose PSAs are rising as their tumor is progressing. We know the pathway's on because PSA is an androgen-driven gene, or actually the protein expression of a gene called KLK3, which is an androgen-driven gene. It's a classic design, three plus three design. We started last summer, a little slow to get started because of COVID-19-related site issues, as you can imagine. The trial has moved along very, very nicely. I'd like to make the point that although patients are clinically selected in the manner I indicated, we are using a series of technologies to characterize these patients biologically. We're doing circulating tumor DNA, looking at 70 prostate cancer-relevant genes, including the mechanisms of action that I described earlier. We're looking at circulating tumor cells. We're characterizing AR-V7 and other splice variant approaches or variants in those circulating tumor cells. That's the monotherapy strategy. I'll come back and discuss a little later the approaches that we're using in combination studies, but let's move on to the next slide, Peter, please. This is a slide taken right out of the poster session at the ASCO GU meeting, and what we set out to do at this meeting was show the performance characteristics of the drug. We reported on the first cohort, the 200 milligram cohort, that same cohort that Peter indicated we had projected would have a meaningful, in terms of biological effects, albeit at the low end range of that, meaningful exposures. What we described is the 200 milligram cohort level. What we also indicated that we were at the time of the ASCO GU meeting, some three weeks or so ago now, we were enrolling patients at the 600 milligram level, indicating that the 400 milligram level had cleared in terms of safety and tolerability. We just didn't have the pharmacokinetics ready to show at that particular meeting. Next slide, please, Peter. The projections that we had for this molecule, as Peter indicated, were that the 200 starting dose would give us exposures of around 140,000. We projected, therefore, because all of the studies in the preclinical models suggested a dose linear relationship to exposure, is that the recommended phase II dose would end up being somewhere around 600 milligrams- 800 milligrams with exposures in patients that should be above that 300,000 AUC level that Peter had talked about. We were looking for a projected half-life in the 30 plus hour range. On the next slide, we'll show you what we actually found in that first cohort. What we found was, and maybe Peter, I'll ask you to comment on the Pharmacokinetics and finding, and then I'll come back with the clinical comments. Basically, the bottom line here is if you look at the 28 day AUCs, we showed in patients at an AUC of roughly 147,000. That's very close to our projection of 140,000. Our half-life, we believe we're reporting 24 hours, but that does not include our longest half-life patients. We believe our 30 hour projection will be accurate. Importantly, looking at a 4-beta-hydroxycholesterol measure which looks for induction of CYP, we do not think that we are inducing CYP. Overall, we look and feel like we've achieved our goal here of being able to achieve a very good exposure in patients and do not show signs of CYP induction. These are the patients who were treated in that 200 milligram cohort. Four patients entered the cohort. Three of them finished it. One patient progressed fairly rapidly after three weeks. This is a patient who had entered with metastases to his liver and his lungs, and after three weeks, entered the emergency room with a brain metastasis. You'll see that that patient and one of the other four patients in the cohort had markers subsequently received that showed neuroendocrine dedifferentiation, and this is a phenomenon that occurs in late stage prostate cancer, whereas the cells start to differentiate in a different direction. They look more like small cell lung cancer, and they are not driven by the androgen receptor. We are now screening and trying to not enter any patients. In general, that cohort was well tolerated at the 200 milligrams level, despite exposures that were reached that were very nice and exactly as predicted, as Peter indicated. The only really likely side effect, I believe, in that cohort in grade two hot flashes, which is on target, that's an effect of androgen deprivation. The others can easily be explained. The neutropenia, that man had entered with grade one neutropenia from previous chemotherapy. It was safe, it was well-tolerated, and three patients finished the cohort. Now, two of those patients progressed fairly quickly in the several weeks after starting therapy, and you see them on the right in the top line. One patient is of particular interest, not to make any clinical claims, but because he is so instructive about the mechanism of the drug being achieved. This is a man, as you can see, who had a several-year history of therapy, who had progressed in the past on previous bicalutamide or Casodex, on enzalutamide, progressed through PROVENGE, and progressed pretty steadily all the way through a course of abiraterone. Here's a man whose PSA was rising. It was above 100. Well, I guess when he entered the trial, it was 150. Over a 12 week period, we began to see a decline in PSA, which has continued and we described at the ASCO GU meeting, continued through the presentation at that meeting. This man has felt well. He's now been on the drug for more than six months. He has just been moved to the 400 milligram level, so we've just doubled his dose in the last three weeks or so, and it will be very interesting to follow. Here's an example that strongly suggests the drug is on target and well tolerated and that we're on the right track. Peter, I'm going to turn it back to you to comment on the size of the markets that we are addressing. The initial markets are those on the left, of course. Just very briefly, the initial markets we're focusing on are really latest line metastatic CRPC, third line. These are large markets in and of themselves. What's important to note is that the field has moved towards earlier lines. There's more of these patients that are on therapy for longer, so the markets become even more expansive the earlier you go in therapy. David, do you want to comment, please, on our financial status? We reported cash at December 31st at $74.5 million. Last week we closed $130 million of a total raise of $150 million, and just this morning we completed that over allotment of $20 million. That total $150 million raise is a very solid addition to our balance sheet and gives us a good cash runway through 2024. That allows us to complete the phase I dose escalation that's currently underway, expansion study, combination studies with anti-androgens, as well as phase II pivotal study, and we'll also do preparatory work for a phase III confirmatory study. We also have pipeline work underway, and these additional funds will allow us to expand that as well. We have a very good financial cushion that we have to work with. The share price has been holding up very well. We priced the financing at $27, and we're at about $27.30, I think, this morning. We have about 46 million shares out there. There's 6.4 million pre-funded warrants that don't get included in our reported market cap. Those were issued in lieu of shares at a financing in 2019. We have a very solid base of investors. As you can see from the slide, Pfizer participated in the financing last year. We had very solid support from existing investors. This time around, BVF, Soleus, Avidity, and Janus as well. A very good base. Analyst coverage is as noted there. Mark Breidenbach from Oppenheimer, Joe Pantginis from H.C. Wainwright, and Maury Raycroft joined us last year covering the company from Jefferies, and David Martin from Bloomberg. We feel we have a good, solid base of financing to move forward with the program. Yes, let me just pick up on David's comments. This recent financing has been important. We were financed adequately, actually, for the early development work, the phase I, the phase II, and the initial combination studies work. The early experience in the phase I trial, we believe, has risk-managed the molecule. It seems to be performing exactly as designed. That allows us to really move with this financing to increase value to shareholders in a number of different ways. Perhaps the most important way is to prepare to be ready for an aggressive single-agent registration strategy if we continue to see the kind of evidence for on-target activity in these end-stage resistant patients that we've just described one example of. We're moving towards a recommended phase II dose. We expect to achieve that in the second quarter and then move on to an expansion phase in the phase I trial. We will be reporting much more fully biologically characterized patients treated at the recommended phase II dose at the ESMO meetings and possibly the triple drug meeting, the NCI meeting in the fall. In the meantime, the other thing we are doing is moving ahead very aggressively on the combination front. As Peter indicated, we've designed this drug to be a good combination partner. All of the work we have done, both pre-clinically and in preparation for combination studies in patients, have strongly suggested the value of doing so. Taking that principle that I talked about earlier, that deeper suppression of androgen biology and broader suppression, we have shown both. We have shown increased genes suppressed with both mechanisms of transcription inhibition, the anti-androgens, and our N-terminal domain inhibition. Quantitatively better suppression translate eventually to patient benefit. We have now set up collaborations with both Janssen for their drug apalutamide and abiraterone. They will be running those trials. We expect them to start in the third quarter of this year. We have just announced a collaboration with Astellas and Pfizer that will allow us to run collaboration combination trials with enzalutamide. Our goal is to examine, in the clinic, our ability to combine our drug with each of the late-stage anti-androgens which are currently on the market. We believe that will be technically possible. One doesn't know till one tries. In summary, what we're talking about here today is a unique approach to shutting down androgen-driven transcription. We believe that can be translated in the clinical situation into major benefit for patients with late-stage prostate cancer progressing on anti-androgens, and in the longer term, in a much, much larger context, into earlier stage patients in combination with those same anti-androgens. The drug characteristics, as we represented them with data at the ASCO GU meetings, are entirely in line with what we set out to design. A drug with greater potency, longer half-life, and good pharmaceutical properties that would be necessary for a successful drug globally. We believe we've got excellent initial proof of concept as shown at ASCO GU, and we look forward to the next couple of years of development, and to show the true place of N-terminal domain inhibition in the treatment of men with prostate cancer. Mark, let me turn it over to you at this point. Thanks for that, David, and Peter. We do have a few minutes for a couple questions, which people can submit top right of your screen in the webcast, or you can email me directly. We do have one that was submitted while you were presenting. This question's about how well do you know where the drug is binding? Is it truly just binding to the N-terminal domain? Is it possible that there's some activity from other sites of binding? No, it's a great question. I'm going to let Peter comment on that. Please. It's a good question. We're actually doing a lot of the biophysical assays right now to be able to prove definitively exactly where it's binding. We've already done quite a bit of work to date and published those and presented them in posters last year. We believe based upon the chemical structure of 7386 and its similarity to that first drug, 002, the active ingredient of 506, which was known to bind in this N-terminal domain region. We believe we are very likely binding that same region. We know we don't bind in the ligand-binding domain. We don't very much bind other areas or other targets. Our toxicity profile is quite clean, and so we have high confidence that we are likely binding to the same pocket as with that original drug. Hopefully later this year, we'll be able to definitively show that in further poster data. Okay. Then maybe another one, just thinking about these combination trials that you're going to get up and running shortly. By combining together, how much deeper do you think you're really going to be able to suppress signaling on an acute basis? Is that really the benefit that you'll get deeper responses up front, or is it more about boxing in the tumor so that there's less available resistance mechanisms? I think both possibilities are true. I'm very much influenced by my experience with aromatase inhibitors in breast cancer back in the early 2000s, late 1900s and early 2000s. Seems like a long time ago. The deeper we could suppress estrogen, the better the clinical results. And so letrozole was one example of that when I was at Novartis. That's exactly what the history of prostate cancer has been. 60 years of deeper suppression. We know we've done a lot of transcriptomic studies. We know we capture additional genes. There's additional biology, which is really quite interesting. We'll have more of that in April at AACR. We also know quantitatively, and that should, if history is the case, Mark, translate to clinical benefit. That's why we really find this to be an extremely interesting approach. You have raised the other two complementary ways of shutting down the same validated important pathway should, if history is the case with combination therapies, delay the emergence of clinically meaningful resistance. Okay, with that, unfortunately, we are out of time, so we'll have to stop here. Thanks a lot for the presentation and thanks for everyone joining online. It was a pleasure. Thank you very much.