Afternoon, everyone, thank you for joining the H.C. Wainwright 2021 Global Life Sciences Conference. My name is Tatenda Zenenga, and I'm an investment banking analyst here at H.C. Wainwright. While we are virtual this year, we're confident we're going to be able to provide value to you with over 425 companies presenting at this conference, as well as via your interactions through one-on-one meetings. As you know, H.C. Wainwright is a full-service investment bank dedicated to providing corporate finance, strategic advisory, and related services to public and private companies across multiple sectors and regions. We have a total of 18 publishing senior analysts and 493 companies covered across all sectors. Please visit hcwco.com for more information. From a logistics standpoint, please make sure to reference your virtual conference online portal that provides your individual links to your meetings and all presentations. Panels and all presentations are available on demand from March 9th through the 10th. With that being said, have a productive and an enjoyable day, and I'd like to introduce our presenter, Mr. David Parkinson, the President and CEO of ESSA Pharma. David, take it away. Thank you, Tatenda. Well, it's a pleasure to be here with you today. I'm here representing ESSA and the staff at ESSA. What I'd like to do over the next 20 minutes is tell you about a unique way of shutting down male hormone-driven signaling, an important driver of prostate cancer. This is a company based on technology originally coming out of the University of British Columbia, the British Columbia Cancer Agency in Vancouver. We currently have sites in Houston, South San Francisco, and Vancouver. What we're talking about are a series of agents we term anitens, which shut down hormonal signaling in prostate cancer and do so in a unique way. That is, they interfere with transcription by working at the other end of the androgen receptor, thereby bypassing the resistance mechanisms associated with current anti-androgens. I'll be talking a little bit about where we are with the program and why the biology and the mechanism of action of this agent is potentially so important to the natural history of prostate cancer. I'm here representing my colleagues today, Peter Virsik, our Chief Operating Officer, David Wood, our Chief Financial Officer, and Alessandra Cesano, our Chief Medical Officer. As you can see from slide four, we're all experienced drug and diagnostics developers, so we know the drug development space. The reason we're here to talk to you today, the reason we're doing what we're doing, relates to the fact that it's been known since the 1950s that prostate cancer is uniquely driven by male hormones. That has translated into 60 years of drug development, with incrementally better ways of shutting down male hormone-driven biology through the androgen receptor. Currently, the latest generation of anti-androgens represents a global market of greater than $7 billion in annual sales. The unmet medical need still remains. All patients, eventually, if they live long enough, will become resistant to current anti-androgens. We'll talk about the mechanisms of that and what's really important to today's discussion is that even when these tumors progress on current anti-androgens, the pathway is still on, and it is believed that the drive behind these tumors is still androgen-driven biology in large part. On slide six is a cartoon representing the androgen receptor. This normally sits in the cytoplasm of prostate cancer cells. In comes dihydrotestosterone, an androgen, male hormone, binds to the right side of the cartoon, activates the receptor. The receptor translocates to the nucleus, a dimerization event occurs, and then the activated receptor is binding to the genomic DNA in very specific sites called androgen receptor elements, and thereby driving transcription of the genes associated with male biology. Now, t hat specific binding does not occur without the left part of the molecule as represented in this cartoon, the N-terminal domain. The reason it's portrayed as a squiggly kind of representation is that it is intrinsically disordered, doesn't have a formal three-dimensional structure, that is the overall N-terminal domain, t here are subsets of probable structure. It's impossible to get a crystal to date of the N-terminal domain, and therefore, classic ways of going at drugging the N-terminal domain have not been successful. Also on this slide in the upper left-hand corner is the results of 60 years. That's six decades of drug development, increasingly better antiandrogens, finally resulting in the four big androgens. ZYTIGA, which interferes with synthesis of androgens and decreases the level of circulating androgens, the four big recent lutamides, enzalutamide, apalutamide, and darolutamide, all of which are important blockers of androgens binding to the right side of the receptor. Also on the right side of the slide are listed the mechanisms of resistance to these antiandrogens, unsurprisingly, whether at the DNA level or at the RNA level, they represent interactions and mechanisms of resistance based on the ligand-binding domain, that right side of the cartoon. On the next slide is represented the work of the scientists in Vancouver, Marianne Sadar, biologist, Raymond Andersen, natural products chemist, who found an extract from a sponge in a harbor in Papua New Guinea, showed that that extract shut down androgen-based signaling, even in prostate cancer cell lines resistant to anti-androgens. Subsequent work at the University of Barcelona showed that a compound derived from that initial extract actually bound to an area called transcription activating Unit 5 or TAU5 in the AF1 region of the N-terminal domain. By doing so, it seems as though conformational change occurs. The assembly of the cofactors necessary for the activated receptor to bind and transcribe at those specific areas I mentioned on genomic DNA is interfered with. A unique mechanism of action leading to unique ways of shutting down androgen biology. On this next slide eight, is represented by, again, a cartoon form, the natural history of prostate cancer and the history, if you will, of the development of therapeutics against prostate cancer. Initially, the disease is often found localized. It's given localized treatment with surgery or radiation. Patients are followed by the marker PSA or prostatic-specific antigen. As PSA rises, that has been the setting in which the lutamides or androgen deprivation therapy was introduced. These are the LHRH agonists or antagonists that work centrally to decrease the amount of circulating androgens. Subsequently, if PSA rose again, that's the setting in which the lutamides were developed. What's happened in recent years is that the use of these lutamides has been shown to be even more beneficial when moved up in combination with androgen deprivation therapy, thereby shutting down both the amount of circulating androgen as well as the ability of the remaining circulating androgen to bind to the receptor. That has translated into improved prostatic or progression-free survival and improved overall survival. These are important drugs. They're great drugs. They're generally quite well-tolerated, and they've been important additions to the therapeutic armamentarium over the last several years in prostate cancer, but all men become resistant. What we will be talking about here in the next few minutes is basically the introduction of our latest generation aniten. That is an N-terminal domain androgen receptor inhibitor, which interferes with transcription in the manner that I described and which we have just entered over the last several months into clinical trial in men with advanced prostate cancer. The history of the company goes back to the early 2000s, and then around 2009, 2010, the company was initially formed. In the year late 2015, early 2016, a phase I study was initiated by the company with a first generation aniten, EPI-506. We arrived at the company around that time with the phase I trial underway, managed the phase I trial, showed that this was an operative mechanism of activity, that these men who entered the clinical trial with rising PSAs did show, in the men who received the highest levels, did show some decline in PSAs. Frankly, the drug was well-tolerated as the toxicology had predicted, the PSA declines were not sustained and were not deep enough to represent clinically meaningful effect. We knew we needed a better drug. We reconfigured as a preclinical company, spent a year and a half developing a next generation molecule that made up for the issues that we found in that first generation molecule. We worked to improve the potency and came up with EPI-7386, which is 20 times more potent than EPI- 506 in in vitro studies. We also needed a drug that would continue to maintain the same specificity and selectivity that EPI- 506 had shown, EPI- 7386, by all characterizations, does so. We needed a drug that showed the same clinical activities or preclinical activities in animal models that was active not just in androgen-sensitive models, but in anti-androgen resistant models, and EPI- 7386 does that. We also needed a drug with a long half-life. We're attempting to interfere with transcription, and for that, we need drug present 24/7, so a long half-life. We needed a drug that could be combined with other drugs. These are older men in general. They are receiving other medications. In addition, as we'll talk about, the importance of EPI- 7386 is not just as a single agent to rescue men who are progressing on current anti-androgens, but potentially in the future, even more importantly, to be combined with those same anti-androgens in earlier line men, and basically to shut down androgen biology to levels not seen to date, both quantitatively superior but also qualitatively with additional biology captured or interfered with. Finally, we needed a drug that could be given as an oral tablet once a day. We have such a drug now. On slide 11, we basically show that in the animal models with exposures, area under the curve, these are units of at least 80,000, we could see activity in certain sensitive models. Once we were past 300,000 area under the curve, we in fact were seeing reproducibly activity in the whole range of antiandrogen resistant models that we studied. The toxicology was very clean because of a suspension formulation that we were able to develop. We were able to give huge amounts of drug and showed that the drug was extremely specific and extremely well-tolerated in these animal models, allowing us to start at a dose of 200 mg with a predicted AUC of 137, which, as I indicated, would be in an area where we might expect to see biological and potentially even clinical activity. On slide 12, we basically show that the phase I trial of EPI-7386 began last summer in the middle of COVID, but nevertheless, the trial has moved along quite well. As you might expect, these are men who have been on antiandrogens and often many other lines of therapy and have had the disease for five or 10 years. It's a classic phase I design with 3 + 3 design. The goal was to get to a recommended phase II dose, show safety, tolerability, and, if possible, clinical effects, but certainly PSA responses would be a good biomarker of interference with the pathway. Importantly, we're doing a lot of parallel biological studies because, in fact, these are late-stage patients. They have complicated biology. We know that while AR may be the predominant driver in these late-stage patients, many of them have also received chemotherapy, and many of them have other genomic changes that are partial drivers in addition perhaps to AR. The study has been ongoing since the late summer last year. We'll be talking a little bit about the combination clinical trials that we intend to begin later this year. At the ASCO GU meeting a few weeks ago, we showed the first clinical data. This was a poster designed to show the performance characteristics of the drug. We had had a first-generation drug. It seemed to be on target. It seemed to have that right mechanism of action. What it didn't have was good pharmaceutical characteristics. We spent a year and a half improving the pharmaceutical characteristics, and to do so, we brought this agent into clinical trial. Again, same kind of design, same kind of patients. They have been on antiandrogens. Their tumor is progressing. Their PSAs are rising. They enter the trial. On slide 14, we just show the kind of predictions that we had made and that we showed the results of our clinical characterization in the first cohort at the ASCO GU meeting. We had predicted the drug with a long half-life, some 30 hours. We predicted that we would get exposures at the 200 mg level of around 137,000, as I just mentioned. That would tell us that we probably were aiming to get to 600 mg to 800 mg a day, again, oral tablets once a day, to get the kind of exposures that we would expect to be uniformly effective against the androgen receptor. What we see on slide 15 is that basically we have achieved all of those characteristics. The half-life here is listed at 24 hours or so. In fact, it's probably 30 or more for technical reasons. It's hard when patients are taking a long-lived drug once a day to get an accurate T one half, but it's probably going to be around exactly what we have projected. Just as important are the exposures, and at 200 mg at day 28 after the drug had accumulated, because long half-life drugs takes about a week to equilibrate. At the day 28, we were seeing exposures of 147,000 as opposed to our predicted 137,000. Already we were seeing in the context of a drug that was quite safe and was very well tolerated. Excuse me. The drug was at the exposures that we were hoping to see for this first cohort. In addition, by the way, we measured the ratio of 4β-hydroxycholesterol to total cholesterol and showed no induction, at least at that initial cohort. The importance of this is that we don't want to see a drug that is a huge inducer of CYP3A. That would complicate interactions with other drugs. The clinical results are shown here, and importantly, the drug was very safe, was well tolerated. The toxicities that are possibly associated are in the lower right-hand corner. The only one that is probably directly associated were the hot flashes, which is a good sign of androgen inhibition. There were four patients on the first cohort and three of them progressed, one of them quite rapidly, didn't even make it through the four weeks of observation. The more important patient to discuss is 01002 on the next slide. On the top are PSA changes in the three patients who made it through the four weeks of observation. Three of the patients progressed fairly rapidly. These are really late-stage patients with very aggressive disease. Patient 01002 is a very important patient in terms of representing on-target and mechanism of action. This is a man you can see had several years of therapy for his prostate cancer. He had metastatic prostate cancer to bone and to pelvis. He was treated with several lines of therapy, had responded previously to Casodex, which is bicalutamide and enzalutamide, had never responded to abiraterone in recent years. When put on our drug, it took about 12 weeks, but his PSA began to decline, and as we indicated at the ASCO GU presentation, was continuing to decline at the time of the last measurement before the presentation was created. The man has no side effects to speak of except hot flashes, so very well tolerated, feels well, and has now been on the drug for more than six months. As we indicated for the ASCO GU presentation, in addition, we have now treated this man for more than six months, and we indicated that we had cleared the 400 mg level and moved on to the 600 mg cohort. We therefore recently moved this man up to 400 mg once a day. On slide 18 is just a representation. We are starting of the relative prevalence of disease in this area. We are starting with the left-hand side cohorts, the metastatic CRPC, castration-resistant prostate cancer. As I indicated, we have generated data to suggest that combination therapy with our drug with anti-androgens is actually potentially extremely effective because of its ability to shut androgen biology down broadly. That is a huge market to be explored. We will be exploring that in collaboration with the companies with the late-stage antiandrogens. We've already announced a collaboration around two separate studies with Janssen, with their antiandrogens, and most recently with Astellas/Pfizer with their antiandrogen enzalutamide. In terms of where the company is financially, we're in good shape. We had reported $74.5 million at the end of December. We just, in the last couple of weeks, raised another $130 million in a very successful financing, and we have excellent shareholders and very good analysts covering us. Milestones to watch this year. We will be declaring a recommended phase II dose sometime in this next quarter and move on to an expansion phase. Meanwhile, in the third quarter of this year, we will be initiating these combination studies I just referred to. In addition, we will be presenting clinical data on the results of our phase I/II trial in the fall of this year. In summary, what we have in EPI- 7386 is a unique way of shutting down male hormone biology through inhibition of the N-terminal domain. We have a drug that is, in many ways, improved over the first-generation compound but retains the same specificity and has excellent pharmaceutical characteristics. It therefore represents, we believe, an important new direction in offering a rescue mechanism for men who are progressing on current anti-androgen and whose tumors are still driven by male hormone biology. Very importantly for us to study will be earlier lines of therapy in men in combination with current anti-androgens. Thank you for your attention today, and I look forward to future discussions with you. Take care. Thank you, David. Thank you for taking part in what has been a very productive and informative presentation. We appreciate the time and the effort that went into preparing it. Well, thank you. Hopefully our next conference will be one that we can hold in- person rather than virtually. In the meantime, we're grateful for your flexibility and your presence online this year. Thanks again, David. Thank you.