Greetings, and welcome to today's CytoDyn R&D Investor update. My name is Diego, and I will serve as your moderator today. At this time, all participants are in a listen-only mode. If anyone should require operator assistance during the conference, please press star 0 on your telephone keypad. As a reminder, this call is being recorded today, December 7. I'd now like to turn the call over to Cristina De Leon. Thank you. You may begin. Good everyone for joining us today. This is Cristina De Leon with CytoDyn. Joining us on today's webcast is our President, Cyrus Arman, and our Scientific Advisory Board members, Dr. Mazen Noureddin, Dr. Stefan Glück, and Dr. Jonah Sacha. Before we begin, it is essential that we provide you with important cautionary language related to certain federal securities laws. Our remarks during today's webcast will include forward-looking statements. Forward-looking statements are not guarantees of future performance and involve known and unknown risks, uncertainties, and other factors that are difficult to predict. Actual results may be materially different from any future results expressed or implied by such forward-looking statements. These risks and uncertainties include, among other matters, statements regarding the leronlimab's potential efficacy in certain immunology and oncology indications, the Company's ongoing ability to raise additional new capital, that clinical trials may not commence or proceed as planned, products that appear promising in early trials may not subsequently prove to be viable on safety or efficacy grounds, products may not receive regulatory approval or market acceptance, competition may reduce the commercial potential of our products, we may experience product recalls, manufacturing issues or product liability, and our patents may be challenged or unenforceable. Forward-looking statements help to provide complete information about the company, forward-looking statements may be less reliable than historical information. The company undertakes no obligation to update publicly these forward-looking statements, except as required by law. Please refer to our recent quarterly and annual reports filed with the Securities and Exchange Commission for more information about the risks and uncertainties that could cause actual results to differ materially versus our current expectations. I will now turn the webcast over to Cyrus Arman. Thank you, Cristina. Welcome everyone, and thank you for joining us today. We are excited to take you through our R&D investor update. Our agenda for today is to review the company overview and background, discuss the previous clinical development programs, then have a discussion with select members of our scientific advisory board to discuss clinical and preclinical data in prioritized therapeutic areas that the company intends to focus on in the future based on existing clinical data that we already have from previous programs. These speakers include Dr. Mazen Noureddin, who is currently the Director of the Houston Liver Institute and former Founding Director of the Fatty Liver Program at the Cedars-Sinai Medical Center. Dr. Noureddin is a world-renowned key opinion leader in NASH, and he'll be presenting on the potential role of leronlimab in treating NASH and non-alcoholic fatty liver disease. We also have with us Dr. Stefan Glück, who is a former Sylvester Professor at the Leonard M. Miller School of Medicine at the University of Miami of Florida. He has served in senior leadership roles at both Regeneron and Celgene, and he will discuss the potential role of leronlimab in the tumor microenvironment for treating solid tumors. Finally, we have with us Dr. Jonah Sacha, who is currently a Professor at the Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, both of the Oregon Health & Science University, where he conducts research on infectious diseases. Sacha will share the latest research developments with regard to leronlimab derivatives and a potential HIV cure. These are our SAB disclosures. We're now gonna talk a little bit about the company overview, starting with CytoDyn's mission. At CytoDyn, we believe that we have a moral obligation to generate therapies that improve people's lives. We think that we have a real powerful agent with leronlimab and that we have an imperative to develop this and get this product to market. Our path to doing so is through a focused and disciplined clinical development strategy that we're gonna be discussing in more detail on this call. We think that by achieving that goal, we will be able to generate value and economic returns for our investors. A bit on the company's history. The company is headquartered in Vancouver, Washington. We currently have 15 full-time employees as of December of 2022. CytoDyn was founded in 2002, about 20 years ago. About a decade after that, it acquired the rights to PRO 140, now known as leronlimab. A couple of years after that, in 2014, it began its own HIV treatment clinical program. It later expanded into autoimmune diseases and specifically into GvHD in 2016. Later again, also began studying leronlimab in oncology in 2019, and in NASH in 2020. In 2022, we put out our refocused development strategy to get to our next value inflection point. I wanna take a moment to discuss our board of directors. Over the last year, we fully reconstituted our board. They're now a fully independent board. Recent additions, such as Stephen Simes and Ryan Dunlap, further enhance the independence of the board and bring additional biotechnology industry experience onto the board. Each of these individuals has a unique skill set and will be critical to the company's continued success and transformation. We'll continue to expand our board as needed in the future. In terms of our critical partnerships, we have ongoing relationships with both AGC Biologics and Samsung Biologics, who have in the past produced drug supply for both clinical trials, as well as to distribute commercial supply ahead of a BLA filing for the HIV MDR population, which we pulled earlier this year in October. CytoDyn has also recently attended numerous medical professional society conferences where we presented our data in both NASH and oncology. We continue to publish in academic peer-reviewed journals. We expect to have an upcoming publication on our CD02 data coming shortly. We also continue to work with a number of academic institutions on various studies, including some preclinical studies that can inform future clinical trial design for our future programs. I wanna take a moment to talk a little bit about CCR5 as a target and about leronlimab. The CCR5 CCL5 axis has been a hot target for research for at least the last 20 years. Primarily because it was identified initially, CCR5 was, as being one of two critical co-receptors in addition to CD4 and the other co-receptor being CXCR4, as being the portal through which HIV enters T cells. Once this discovery was made, a large research effort was taken throughout the industry to drug this target in an effort to try to develop therapies for HIV treatment. However, since then, it's also become apparent that this particular pathway has implications not only in infectious diseases, but through altering the pathway, it also has implications on cell proliferation, migration, angiogenesis, metastasis, and survival, which are all important for treatment of oncology and solid tumors. As well, it also has implications for autoimmune responses. What's also become apparent is that the precise binding location of a molecule on the receptor can have important downstream effects on immune function and downstream signaling. Now, leronlimab is a humanized IgG4 monoclonal antibody that is directed against CCR5. In 1999, it was first discovered that leronlimab actually binds to the extracellular domains of CCR5, and we'll talk about that in a little bit more detail shortly. Leronlimab is currently constituted as a once a week subcutaneous injection, but it can also be delivered in an IV form if needed. Leronlimab has received fast track designation for both metastatic triple negative breast cancer and HIV treatment. However, it remains an investigational new drug and is not yet approved or authorized by the FDA or any other regulatory authority for any indication. Taking a moment to look at the CCR5 inhibitor landscape. We've identified a total of 28 unique different assets that target CCR5. As you can see from the graph here, the vast majority of these are actually small molecules, and only three of them are antibodies, one of which is leronlimab. The other two were formulated as IV and have both been suspended. To our knowledge, leronlimab remains the only active subcutaneous antibody in development. To date, only Maraviroc has been approved as a CCR5 agent for the treatment of HIV. When we look at where these 28 unique agents have been studied in terms of which therapeutic areas, not surprisingly, we see that the vast majority of study has actually been in the HIV treatment and AIDS disease area. The next largest therapeutic area where CCR5 inhibitors have been studied as a group are solid tumors. As you can see here, colorectal cancer, breast cancer, pancreatic cancer, and urothelial cancer are among them. The remaining indications are comprised of neurologic, immunologic, metabolic, and other infectious diseases. When we look at the active development pipeline, we can see that most of the treatments are currently in Phase 2, and most of them are actually small molecules. A vast majority of those total of 28 unique CCR5 inhibitors have actually are no longer in development. You can see here that leronlimab currently in Phase 2 for NASH and solid tumors. There are other agents from BMS, Merck, and AbbVie that are also looking at solid tumors or other infectious diseases. Leronlimab, we believe is unique in terms of the active development pipeline because of how it binds CCR5. CCR5 is a G protein-coupled receptor. This is a seven-transmembrane receptor, which is typically very hard to fully inhibit with anything smaller than even a peptide. A small molecule binder would typically bind deeper into one of these pockets that you can see here on the image on the right. Whereas leronlimab binds to the N-terminus of the receptor, as well as to the second extracellular loop detailed here. Now, as previously discussed, you know, where you bind can have differential effects on how the various chemokine ligands that interact with this receptor can function and can ultimately lead to differences in downstream signaling. Looking at the clinical development history for leronlimab. Over the last decade, leronlimab has been studied in various therapeutic areas, including infectious diseases, for both HIV treatment as well as COVID-19 treatment. Within oncology, for triple negative breast cancer, with a basket trial as well that was looking at a total of 22 different solid tumor types. We'll be talking a little bit about the colorectal cancer data that we collected from that basket trial later today. Within liver disease, we've run a single trial in NASH, which Dr. Noureddin will be taking us through momentarily. And also, within autoimmune diseases for graft versus host disease. This clinical development history represents over 20 different clinical trials and over 1,500 patients. Some of these patients have been on treatment for many years, particularly within the HIV segment. Generally, what we've seen is that the drug is well-tolerated at multiple doses that have been studied. With that being said, we did receive a clinical hold from the FDA earlier this year, and I wanna take a moment to talk about that in a bit more detail because it is a really important issue that the company is working through currently. As I said, in March, we did receive a full clinical hold for COVID-19 and a partial clinical hold for HIV treatment. We voluntarily withdrew the IND for COVID-19, and we're actively working on resolving the partial clinical hold for HIV. How long it takes to get off clinical hold is dependent on what the agency is asking for and what data that the company has that's readily available at the time. In our case, the FDA requested five items. An updated investigator brochure, which we submitted in September of this year, data safety update report, which we submitted in October this year, a safety management and pharmacovigilance plan, which we submitted in November of this year, and we continue to work on the remaining two items, being an aggregate safety analysis and a benefit risk analysis. We're nearing the end of the analysis for those two remaining items. Thus far, we have not seen any systemic concerns with how leronlimab has been tolerated across the previous 22 trials, and we look forward to submitting these final two items very shortly to the FDA. Turning now to future development. As we previously presented, we're narrowing and focusing our forward-looking strategy to emphasize the highest value opportunities where we have the strongest supporting clinical data. That's gonna be in NASH and oncology. Again, we're gonna present some of that supporting data on this call. We're also still committed to HIV, but we're really looking at it more through the lens of developing longer acting agents. Dr. Sasha will be talking about that at the end of our discussion today. Within oncology, we're interested in studying what would be referred to as immunologically colder tumors, and Dr. Stefan Glück will present on what we mean by that later. We think that these are areas where more recent advancements from checkpoint inhibitors have yet to really have a large impact in those markets. We think that there's a unique opportunity based on the data we already have in some of these colder tumors to make an impact. Within NASH, we're particularly excited about the data that we have there, NASH will be our primary focus going forward. We'll also talk a little bit about a unique opportunity to study and look for the effect of treatment effect for leronlimab in people living with HIV who also have NASH. We think that we might be in a unique position to address that population. Going forward, we're focusing on NASH, oncology, and earlier line HIV indications through longer acting agents that inhibit CCR5. Again, we've already generated promising clinical signals in both NASH and oncology. Within NASH, we're exploring the opportunity to study a segment of patients of those NASH patients who are also living with HIV. Within oncology, we wanna pursue colorectal cancer and breast cancer specifically. Within the colorectal cancer population, we wanna focus on the microsatellite stable group, which represents about 85% of all diagnosed colorectal cancers. Within breast cancer, we wanna focus on the hormone receptor-positive HER2-negative population, which is about 70% of all diagnosed breast cancers, and the TNBC population since we have data in that space. All of these are quite large markets. You know, looking at third-party market reports, we've estimated what the potential market size is out to 2028 for each of these groups. As you can see, these are all large multi-billion dollar opportunities. To further substantiate that, we've looked at what the epidemiology is for each of these, and we use this information when we build our own net present value models. As you can see, these are tracked out to 2046, so over about a 25-year forecast period. As an example, you can see that within the U.S. and the EU5 and Japan, which is where we do most of our modeling, for NASH alone, there's roughly about 40 million patients that are gonna have that disease during that forecast period. Taking a moment now to talk a little bit about NAFLD and NASH. As we saw from the last slide, this is a highly prevalent disease, but there are currently no approved agents for to treat NASH. NAFLD requires that there would be evidence of hepatic steatosis without any secondary causes of fat accumulation in the liver, like heavy alcohol consumption, the use of any steatogenic medicines or any hereditary disorders that could lead to accumulation of fat in the liver. In addition to being able to reduce fat through therapy, also being able to demonstrate the attenuation or the reversal of fibrosis is critical, since the extent of fibrosis is really what's linked to worsening outcomes for patients. When we look at what the disease progression for NAFLD and NASH looks like, it looks like this. Roughly 15%-30% of all people in the U.S. or in Western economies actually have NAFLD. Again, very large numbers. Of them, somewhere around 25% have some stage of NASH. It's generally believed that while you're in these stages, this can be reversed either through diet and lifestyle, or potentially through therapy that would be related to weight loss. But the real challenge to date has been in being able to attenuate or reverse the inflammation and scarring in the later stages of NASH before it actually moves into cirrhosis or hepatocellular carcinoma, at which point where it's generally believed that these are more difficult to treat and are potentially irreversible. One of the exciting things that we're gonna be looking at and that our early clinical data supports is potentially the ability to attenuate or reverse the fibrosis in the liver. Taking a moment just to talk about the HIV NASH population. The burden of liver-related morbidity is especially high among HIV patients. And the impact of NAFLD is even more significant in that group, where the prevalence can be as high as 50%. Now, both the HIV infection itself as well as the actual treatments that the people living with HIV are taking can actually contribute to the development of NAFLD and NASH in various ways. You know, having HIV itself also makes you more susceptible to other infections like HCV, which of course is implicated in liver disease. Again, the antiretroviral therapies that these patients are on, particularly the earlier generation versions, can also have also been associated with the development of NAFLD and NASH. Now, what's really critical here is that this particular subset of patients who have NASH and HIV are typically excluded from other NASH clinical trials. This creates a real clinical unmet need that isn't being addressed generally by the industry. As far as we're aware, there's really only one other company that's looking at this particular population in detail. A bit on metastatic colorectal cancer. This CRC is the second deadliest and the third most commonly diagnosed form of cancer worldwide. The most commonly prescribed therapies for the earliest lines of metastatic CRC are angiogenesis inhibitors like Avastin, which is known as bevacizumab, which is available for most tumor types in addition to various chemotherapy combinations. Other drugs such as Erbitux, Braftovi, Keytruda, Opdivo, and [Neupro] are limited by gene expression, meaning that you have to have a certain genotype in order to qualify for that therapy. The most recent advancements in the colorectal cancer space have come in the last few years, and come from the PD-1s such as Keytruda and Opdivo. They're really only indicated for a subset of metastatic colorectal cancer patients that have microsatellite stability high designations. Again, this is only 10%-15% of all CRC. The same in PD-1 inhibitors have failed to show success in the larger microsatellite stable population to date. This is the group that we're gonna be potentially focusing on in future trials. Looking now at breast cancer. Hormone receptor-positive breast cancer is the most common subtype, which is approximately 70% of all diagnosed breast cancers in the U.S. and Western economies. This is actually the fourth leading cause of cancer-related deaths, regardless of gender, despite the fact that most of these are actually caught very early on. They occur in such high numbers that for those who do progress to metastatic disease and ultimately death, that it is actually the fourth leading cause. All right. With that, we're going to turn now to the presentation on NASH and leronlimab. Is Dr. Noureddin with us? I am right here. Great. All right. I'll advance your slides, Dr. Noureddin. All right. Can you hear me well? Yes, we can. Perfect. I think I'm in control of the slides. I'm gonna move it. Cyrus, it's thank you for having me here. I'm Mazen Noureddin, from the Houston Liver Institute that I just arrived to Houston after being a decade at Cedars-Sinai in Los Angeles. I also work at Methodist Hospital. I'm gonna just take you through some slides of NASH, which I have been doing for the last decade or so and publishing on it. It's not a surprise anymore or, it's a disease that is very prevalent, it's pandemic and waiting for treatment. With the type 2 diabetes and obesity that have been increasing in the world, non-alcoholic fatty liver disease is the cousin of those diseases and affected by them. It's a separate entity. It needs its own treatment. What is fatty liver? Fatty liver is when the fat comes and deposits in the liver, and the liver cannot get rid of it. Over time, not all patients, but significant portion of them progress to non-alcoholic steatohepatitis. What I tell my patients, it's easy. Like, if you have fat, alone, it's probably okay. A lot of people have that. When you get inflammation, this is when the problems start. It's kind of catches on fire. The inflammation leads to activation of inflammatory cascades, and eventually leads to scarring or fibrosis and cirrhosis as Cyrus showed, one of the slides. Why this is significant? We do have a lot of patients nowadays dying from this liver disease. It's the leading cause of transplant in women from data we published, and it's the most common liver disease. It correlates, once you get inflammation on fibrosis stage two and higher, you are more likely to die and have morbidities. This is why this disease has been on the focus. I mentioned inflammation, but one of the key mechanisms of inflammation is targeting this chemokine mediated inflammatory signaling pathway, which actually can reduce both the fat inflammation and scarring. I will show you a cartoon in a second walking us through this story. Let me reemphasize on the slide that Cyrus actually mentioned. You have about 30% of the population, they have this yellow fatty liver at the beginning, and the problem start in a subpopulation, still a lot of people, millions, 12%-14% of them, they get non-alcoholic steatohepatitis. Over time, scarring forms and lead to fibrosis. It's not jumping from NASH to cirrhosis all of a sudden. You get scarring, scarring, and then when you hit 2 and higher, this is when you get morbidity and mortality, and then you get the cirrhosis, which is 4 on the scale of 0- 4. This is very important. Once you get the cirrhosis, it's very hard to reverse, if any. You start getting eventually decompensation, meaning the liver stop working and liver failure, and also a lot of patients get liver cancer. NASH is actually now the most common cause of liver cancer. Let me walk you through this cartoon, and I want you to look at these pink cells. What happens in these pink cells, once you start getting like the fat deposition and injury, what it... That accumulation do is cellular stress. You see that arrow, that leads to release of this chemokine CCL2 or MCP-1. Once this is released, this is the bloodstream here on the top. What you see is these inflammatory cells, namely circulating monocytes, start being recruited, and those are CCR2, and this is very important. These inflammatory monocytes, when they get to the liver, they release a lot of chemokines and cytokines such as TNF-alpha, IL-18, IL-6, galectin, TGF-beta. What that leads is to, you see these yellow cells, the stellate cells, those are the problems. If it gets activated, they get to this, I guess, let's call it the monster activated myofibroblast. It gets strong and started secreting collagen is the mechanism of the scar. Guess what? In these myofibroblasts, you see you have the CCR5 inhibitor. The CC or the, you have the CCR5 receptor. It's plausible that if you target that, you stop a lot of this cascade, including the inflammatory as well as the fibrosis signal. You're kind of at the right spot. CCR5 is expressed in stellate cells, and it gets involved in the pro-fibrogenic activation proliferation. This is a key concept and the key area of the pathophysiology. What's CCR5? It's a G protein-coupled receptors, and it's the receptor for these chemokines, where they hit and affect the cascade, especially the harmful cascade. Its conjugate ligands include CCL3, CCL4, and CCL5. I showed you earlier that these important monocytes, and that they turn into macrophages, and they activate the cascade of inflammatory signal, as well as eventually the stellate cells and myofibroblast. CCR5 present on all these pathways and play a key role mechanism. For us, NASH researchers, it has been really key mechanism that we're interested in, yet we still not need more targets for that pathway. What is the evidence? I already showed you the cartoon that in it's the CCR5 involved in monocytes and macrophages, but that has been shown in NASH patients in particular, that the NASH patients have high level of CCR5 and its associated ligands. Thus it's very appealing and attractive to target that pathway in NASH patients. That's why a lot of research and literature has been done on this, and that's why it makes sense to target that pathway by hitting that pathway. I don't wanna go into animal models much, but in animal models of NAFLD and NASH, using CCR5 have led to improvement in sclerosis, inflammation, and fibrosis. Let me take you to the human data. This is the NASH CD01-NASH 01 study using leronlimab, and that was initially designed as multi-center Phase 2a trial, which subsequently converted into exploratory study to evaluate the dose. We needed to find the dose, its efficacy and safety, and we compared 700, 350, and in the part 1 there was a placebo. That design helped us to discover the efficacy of all doses in addition to their safety. Looking at part 1, it was double-blinded, placebo-controlled, randomized, and then the treatment was received for up to 13, 14 weeks, and there was a follow-up period. The part two had a single arm open label of the 350 milligram. Those are the demographics, nothing fancy or different from NASH trials that I have been involved in. What you wanna look at is the, I guess the red and blue, the 700 milligram and 350 milligram, and they were equivalent distribution in terms of race, ethnicity, and gender. Let's look at an important concept, especially for liver disease and patients with liver disease. There were really no difference in adverse events in that trial between the 700 mg, 350 mg. You will hear along this presentation that we have the type patients where CCR5, because it could be there's a potential defect in some CCR5 receptors. We did add additional precision medicine for with haplotyping. There was probably a little bit more GI side effects on the 700 mg, but that was not way different from others and did not was not overall safety signal or anything like that. Indeed, look at the number of adverse events. There was no statistical significance between placebo 700 mg, 350 mg and the 700 mg haplotype patients. That's good in terms of safety signal. Here is where the money is. Right now, what we use for Phase 2a data or proof of concept are two techniques, and I'm sure a lot of people on this call heard of them multiple times. Indeed, I was involved in the first publication of fat fraction that when we said back in 2013 when we said it's gonna help in Phase 2a study, and now it's validated as a tool. The FDA actually gave it thumbs up for these for this MRI-PDFF for Phase 2a studies. There's another tool also called MRI cT1. They are the same MRI. You have two softwares. The first software is basically fat signal. It tells you we measure three areas in the liver or more, we tell you, like, the percentage of fat in these three areas, for instance. What the radiologists do at the end of the trial, they go back to these three areas and tells you if the fat was reduced in these areas. There's another technique that I told you about, again, at the same exam, different software, cT1, which measure both actually the fat and the inflammatory signal, which is very important. That cT1, we used to do a liver biopsy only for the inflammatory signal, but with the cT1, now we're able to measure that inflammatory signal. Many companies now use cT1 in their Phase 2a study. Here let's look at the full analysis set with PDFF. What you see here, statistical significance drop in MRI-PDFF in the 700 milligram haplotype, but not in the 700 milligram non-haplotype. The pool analysis when you add the 350 milligram was also statistically significant. Look, let's look at this 350 milligram, which is a very attractive dose. On this blue, the overall population is has reduced their MRI-PDFF and was statistically significant compared to the placebo. What we also did subanalysis, I guess we looked at these patients on the cT1, that they have inflammatory signal, which is eventually the population we're gonna target. We used two numbers for inflammation on that cT1, 875 and then 950, both in the literature correlates with outcomes and more severe disease. With that 870, with the 350 and the 875 inflammation signal, it was also statistically significant and thus with the more 950, showing you that these patients also reduced their fat on MRI-PDFF. This is the cT1, which is very good. You see here the placebo. You look at the 700 milligram haplotype, and you see statistical significance when compared to the placebo. The 350 had a reduction in the overall population, and those were more than 875, meaning more inflammation, it's even further. With those more than 50, which is more inflammation group, it even went up for the improvement was more pronounced. Which makes sense, more inflammation, people with anti-inflammatory antibiotic drug here also reduce fat, you see more improvement. Let's look at some of the data. To mention, not everyone started with elevated liver enzymes, but those that had elevated liver enzymes, there was a signal to increase liver enzymes. The PAPS was significant in the 350 and ALT and AST moved the right direction as well. While the placebo did not have much reduction, if any, four compared to 29 units, and their cT1 increased the placebo versus the others decreased. You see here the inflammatory signal reflected on liver enzymes. Digging deeper into signals and mechanism of actions, because we wanted to understand what's happening. You see here the CCL3 as well as the CCL18 statistically significantly reduced in the 350 milligram arm by various sub-analyses. Those have been reduced. The CCL2 actually, which is important, you see here also signal toward reduction. The red asterisk actually shows you the statistical significance. A lot of biomarkers are being reduced. There's also more analysis, and this is important, VCAM, which is VCAM is a recruitment of these inflammatory cells. It's a marker. We're hitting that as well, showing that you reduce the recruitment of inflammatory cells, monocytes, and other cytokines to the liver. EN-RAGE is a very important marker, has been also decreased with these 350 milligram dose with various sub-analysis in those that they had fat and inflammation as well. More data on other chemokines and cytokines, IL-1RA, you see IL-8 and TNF receptor 2, they've all reduced. Many are statistically significant, confirming the inflammatory fibrotic signal, and I showed you the fat reduction as well at the beginning. Keeping on that, you see that this is more data on the inflammatory signal. You see the neutrophils, the Tissue Inhibitors of Metalloproteinases, and we talked about the EN-RAGE as well as the VCAM. Those are the conclusions. The design was converted from a randomized controlled trial into exploratory design to study safety as well efficacy, and I showed you that in the slide. Treatment with leronlimab was tolerated in both parts 1 and 2, and although the 700 milligram did not reduce PDFF and cT1, the 350 milligram significantly had the reduction in PDFF and cT1 within 14 weeks compared to the placebo. There were tons of biomarkers that have been reviewed showing you the mechanism of action, an important inflammatory signal in alcoholic hepatitis patient, giving you confidence that we're moving the needle toward the right direction. Definitely this drug should be carried out into later stages in terms of trial designs such as 2B and 3. I think that is my part and yeah. We'll take it back to you, Cyrus. Great. Thank you, Dr. Noureddin. All right. Can I regain slide control, please? Thank you. All right, I'll now be presenting our clinical data in metastatic triple-negative breast cancer and CRC, before turning over to Dr. Stefan Glück, who will present on the role of the immune system and the tumor microenvironment in treating advanced stage solid tumors, and who will provide a summary of our clinical data. To set the stage here a little bit, what we're gonna present is a pooled analysis across three different studies that we opened it for triple-negative breast cancer. The first one being a Phase 1b/2 study that had 10 patients. The next one being a compassionate use study, also in triple-negative breast cancer that had 16 patients, and two patients from our basket study who had triple-negative breast cancer, for a total of 28 patients that are gonna be in the analysis that we're gonna present here. All of these patients received at least one dose of leronlimab, and the total range of doses was anywhere from 1- 33. One of the trials was a dose-ranging trial, and patients were escalated from 350- 525, and had the ability to go up to 700. Four of those patients did reach dose escalation per the study protocol. The average age for the patients was 52 years, with a range of 33- 75. 52 might sound quite young, however, triple-negative breast cancer typically does emerge in a younger population, so that's not too surprising. All of this data was as reported as of August 15, 2021. I want to take a moment to highlight that we do use standard of care and sacituzumab as references to provide benchmarks for the study. However, neither of these were directly evaluated in a head-to-head manner in these studies. They're really just used as historical control references. Across those three studies, a variety of drugs were used in combination with leronlimab as background therapy. All of these are already approved in the treatment of metastatic triple-negative breast. We've listed what those agents are here. At the time atezolizumab was approved under an accelerated approval. This is a PD-L1 inhibitor. It is currently no longer available, but other PD-1 inhibitors are. No cross reactions were observed from a drug-drug standpoint. However, the sample sizes are small, we don't draw any conclusions from that with these studies. Starting first with the safety data across this pooled analysis. We looked at treatment-related adverse events, treatment emergent adverse events, and serious adverse events in these 28 patients. The distinction between treatment emergent and treatment-related events are that treatment emergent events are any events that occurred after the induction of the study, and the treatment-related events are those that can actually be tied back to the investigational product, in this case, leronlimab. As you can see from the graph on the right, out of a total of 68 treatment emergent adverse events that occurred, eight of them were actually attributable to leronlimab, and only one of them was a grade 3-4 event. When we look more specifically at the serious adverse events, which are the grades 3-4 events, only 1 of them was related to leronlimab. The vast majority of the serious events actually came out of the compassionate use study, which is not surprising as these were patients that were potentially more advanced in their disease. When we look at the top 13 treatment-related emerging adverse events, by type, you can see them here. The majority of them were 1-2 events, and in blue, the 3-4 events are in red. Only one grade 3 or 4 event was attributable to leronlimab, and again, this was a gastrointestinal disorder. Which is also what was a small signal for we've seen in the NASH study that Dr. Noureddin presented. Overall, we don't see any, in this, you know, pooled analysis, of patients who are on therapy for a short period of time. We don't see major causes for concern with regard to safety. Looking at the Kaplan-Meier curves and the survival curves. All of these analyses is broken down into progression-free survival and overall survival. The progression-free survival standard for patients who have received third-line therapy or greater is 2.3 months, and the overall survival standard for patients who have received three or more lines of therapy is 6.5 months. The graph on the left here in blue shows what the Kaplan-Meier curve was for leronlimab in those patients. We got a median progression-free survival of 3.8 months, which again is greater than the historical control. Again, not studied in a head-to-head way, but just using a historical measure of what progression-free survival looks like in that population of 2.3 months versus 3.8 months. In the overall survival group, it was quite similar to the standard of care at the pool level. When we look at a subpopulation of patients who did not have prior brain metastases, we had a progression-free survival of 3.8 months versus 2.3. Again, this is greater than standard of care from historical control standpoint. When we look at the overall survival group, where the standard is 6.5 months or 6.6 months, more than 50% of the patients were still alive when the study ended, which is greater than the OS standard and is similar to sacituzumab. When we break down the same patient sets based on the dose they received, broken down into either the 350 milligram dose or the higher doses at 525-700 milligram doses, we can see that there's a clear trend for better survival at the higher doses with both progression-free survival as well as for overall survival. When we focus the study down just to patients who are on carboplatin and leronlimab, the line in red here is the survival curve for the leronlimab patients. What we can see here is that we got a median PFS of 3.9 months, which is greater than the standard of care, again, from a historical control standpoint. On the overall survival, the, this population, the subpopulation did very well. In fact, they outperformed the historical controls for both standard of care as well as sacituzumab. This may be a population that we would focus on in future clinical studies, is those that would receive leronlimab in combination with carboplatin. When we look at the changes in tumor growth by PET-CT, we see some very encouraging results here. This is 12 patients who did receive scans that were then qualified using RECIST criteria. What we can see is that all the patients had either stable disease or at least a partial response over the course of the study. This is a very encouraging result. You can see from the waterfall on the right that the vast majority of the patients stayed within the stable disease range. With, you know, within oncology, this is, you know, a positive indicator that disease is not getting worse. With the subset of patients, the tumors were certainly getting smaller. When we look at the patients from just the Phase 1b/2 study and then break them out by the dose they received, again, you can see that the majority of patients actually did see reductions in their tumors. Some of the patients actually discontinued carboplatin and remained on leronlimab as a single agent for some time. Interestingly, those patients did have the largest reductions in their max change in their tumor size. Finally, what I'll present here before showing the colorectal cancer data is data from a poster presentation at the AACR conference earlier this year. This looked at changes in circulating tumor cells that are, you know, that have been associated as or can be looked at as a surrogate for progression of disease. What you can see here is that the progression-free survival for patients who received at least one dose of leronlimab, they had and those that had an absence or a decrease in circulating tumor cells had a trend for better survival than those who had an increase in CTCs. Similarly, we saw a similar sort of trend on the overall survival curve. This is not surprising. You know, other agents that would look at a similar breakdown in terms of CTCs would see a similar effect. When we also look at tumor-associated cells, we see a similar trend towards better survival when these tumor-associated cells drop in the peripheral blood measures. I want to show just a little bit of data on this from the CRC patients from the basket study, where we had a total of six. When we look again at their tumor growth through the spider grams and through the waterfall plots, that we only had six patients here, but as you can see, all of them remained within the stable disease and many actually achieved partial responses over the course of the short study. One of them actually had no measurable lesions on the PET scan at follow-up, and the remainder saw either stable disease or partial responses. I'll now turn it over to Dr. Stefan Glück, who will talk a little bit more about the tumor microenvironment, immuno-oncology, and the role for leronlimab in attenuating the tumor microenvironment. Dr. Glück, are you there? Yes. Can you hear me? Yes. Wonderful. Sorry for the initial hiccups here technically. I joined a few minutes later, but I am here. I do see the slides, and it seems like you're hearing me. Thank you very much for giving me the opportunity. Quick introduction. I have been practicing medical oncology for 38+ years. The last 12 years, I was the director of the breast cancer program at the University of Miami, but practiced also other, actually even hematology, not only oncology patients. My research is focused on breast cancer, and all its molecular subsets, including microenvironments. I can tell you about it a little bit. I believe you will be pushing the slides forward. Next slide, please. I think what we have learned, and I'm intentionally very broad here. I'm not going too much detail. I just want you to understand why I am so excited about the concept using CCR5 as a target, particularly having a monoclonal antibody like leronlimab. What we have done over decades, we targeted the tumor cells in cancer patients and tried to eliminate and cure patients. I think it is a good start, but now we are focusing more on the immune system, which consists mainly of a variety, huge variety of lymphocytes, which are those immune cells that are learning to target unknown tissues like tumor cells and Natural Killer cells, which are the first line or part of the first line of immune system, which are targeting anything and everything. They are quick, fast and effective. Next slide, please. This all happens in the tumor microenvironment. The tumors are not growing simply where they arise, let's say lung cancer in the lung or breast cancer in the breast, they actually create through a variety of very different cytokine releases, an environment which makes the environment reasonable and favorable to growing cancer cells. This environment, very briefly, very simply depicted here, includes a number of cells that are important, and some of them are macrophages and Natural Killer cells, as you see on the right upper and right side. These are those cells that immediately react and do not need learning to attack the cancer. They attack it immediately. Some of these macrophages and some of the Natural Killer cells actually have a phenotype which is suppressing the immune system. That's exactly where the CCR5, and we heard it just 20 minutes ago from Dr. Noureddin, impacts on the variety of cytokines. Actually it is very much related to the liver disease that we heard about. Now I will not focus on the other, on the T cells on the middle and left side. I will not focus on the very important fibrotic tissues that are equally important for the microenvironment, but I will focus on something different. Next slide. You know what? We can skip it because I just said it basically in other words without this picture. Yeah. The immune cycle, where the cancer is being actually actively destroyed, needs a number of steps. This is one of the most known slides of the immune cycle from 2013, so almost 10 years old. What we need to take home here is that usually the gray tumor cells on the lower part need to release something which we call neoantigens. These are proteins or polysaccharides that are not recognized by the body as cells. The recognition happens in step number 2, the so-called cancer Antigen-P resenting Cells, APCs, like dendritic cells. That's why they have these dendrites, these fingers. They give the immune system, the T cells, the whole story and show them, "Attack this tumor if it has this particular neoantigen." These cells go to the blood vessel and infiltrate in step number 5 into the tumor. They recognize the cells, and there are two or three different stopping proteins, so-called anti PD-1 and PD-L1 inhibitors on the step number 7. These are upregulated by cancer cells, so this system stops working. Next slide. This system was discovered by two now Nobel Prize laureates a few years back, four years back, James Allison from MD Anderson in Houston, and Tasuku Honjo from the University of Tokyo. They identified these two pathways, and at the same time, they postulated, if we stop these stopping pathways, the immune system can work again. You will see why I'm mentioning it so in detail. Next slide. The reason is very simple. We have huge success using anti PD-1 and anti PD-L1 monoclonal antibodies and anti CTLA-4 antibodies. It's a multi-billion dollar enterprise. For example, if you look at the right side, there you will see non-small cell lung cancer, renal cell cancer, esophageal cancer, gastric cancer, and melanoma. These cancers together alone create more than $50 billion revenue. Lung cancer alone, $12 billion. Breast cancer, not much yet. What this slide shows you is the following. The huge success, which is the response rate in dark blue, it's a minuscule, small, very small part of the cancer continuum. There's many other cancers, they do not actually respond to these treatments, and many cancers they do respond, but only 10, 15, up to 20% of all patients. The vast majority is the grayish or light blue portion, and that's where that huge unmet need is. Next slide. The unmet need can be described by the immune microenvironment. Those tumors, like on the lower left side, that show preexisting immunity, which is no more than 40% of all cancers. Actually, of all immunologically active cancers on the right side of the previous slide, they show that these cells are present. They include macrophages, mature killer cells and T cells. Sometimes they're being stopped and are not functioning, like on the second panel on the left lower side. These cells are still present but are non-functional. Sometimes, like in pancreatic cancer, they are excluded. These cells cannot penetrate into the cancer. See the margin on the third side, slide, in the lower panel, and do not penetrate into the cancer tissues. Finally, there's an immune desert. There's some cancers, they don't have any immune reactions, this is the vast majority of cancers, these may be so difficult to treat because they are not even responding to chemotherapy. Next slide. That's where chemotherapy and the immune system needs to be activated. If you look at the chemotherapy in the middle, you just heard from Cyrus that the combination of leronlimab and carboplatin, which is a typical chemotherapy agent for triple-negative breast cancer, actually works extremely well. Overall survival, you heard from Cyrus, is more than a year, unheard of in triple-negative breast cancer, even in 1st and 2nd line. The survival is barely a year in 1st line, the survival is about six months in 2nd and 3rd line. Incredibly data, sure, small numbers, very early studies, but shows you the progress or the promise of this type of treatment. One more thing, the polarization of regulatory cells such as Th1, CTLs, Tregs, myeloid-derived, then myeloid-derived stem cells, and finally, NK cells and macrophages are being upregulated in the right direction. Down-regulated for the suppressor and upregulated into the inducer efficacy of the immune system. Just a beautiful biology. We have to prove it in clinic that it's true. The indications so far in triple-negative breast cancer are here. Next slide. These are, in summary, what I said, data supported... Sorry, statements supported by data. The macrophage repolarization to non-suppressive function is clearly demonstrated in preclinical models. It's demonstrated very clearly that the metastatic tumor volumes are reduced, including the size and number of metastases. The CCL5, the ligand CCR5, the RANTES promotes another interesting item, which is the VEGF angiogenesis. Angiogenesis has been successfully utilized as a target, and with VEGF receptor and VEGF antagonist. May I remind you, all these compounds that are very effective and relatively non-toxic are monoclonal antibodies. Whereas TKIs, tyrosine kinase inhibitor, and other small molecules that target VEGF and VEGF receptors do not function well, and if they do, they are very toxic. If you go to one of the first slides that we heard from Cyrus, that there's so much competition, so many compounds in competition. Actually, there's none because all these TKIs, the small molecules, are not really competition due to the lack of efficacy and the higher and much higher toxicity. The efficacy is, if anything, short-lived. The other two monoclonal antibodies, they have been withdrawn from development because they don't show the signal that you have seen as presented by Cyrus in two diseases, hard to treat the diseases. Finally, the CCL5 suppresses also the cytotoxic T cells that I mentioned. Hence, promotes the growth of Treg, regulatory cells and Th responses, which means it suppresses the immune system. There you go with leronlimab binding to the CCR5 apoptotic breast cancer cell and cell lines in up to almost, not quite 100% efficiency. Next slide. I will not repeat the role here. We have seen it's a transmembrane molecule seven times through the membrane and can be easily targeted by amounts and a large amount of different molecules. I think the monoclonal antibody concept is the similar best one that we have seen so far. Next slide. In these 28 patients that Cyrus presented, those two in the basket study and compassionate use and truly 10 patients on a Phase 1b study, they show us these data that we learned. Progression-free survival seems to be so much better. Remember, this is a high unmet need in breast cancer. Triple-negative patients, if they already have 1, 2, 3 therapies like these patients from these studies and compassionate use, they have progression for two and a half months, and they live no more than half a year. Whereas on these studies using leronlimab, particularly in combination with carboplatin, you reached again at least a year. Now, these are usually younger patients, so every single week almost, I would say, definitely every single month, longer survival counts here. Next slide. These are some of the CTC studies that you also heard, but I would like to emphasize that circulating tumor cells, which actually I published in the 1990s, I was probably the first one published on CTCs in breast cancer, show two things. Number one, if you can detect CTCs in peripheral blood, so in liquid biopsy, either alone or in combination with cell-free DNA, and there are some tests that are available now that are very sophisticated, then they have a worse prognosis. If after treatment, even only one dose of a given treatment, the CTCs fall down, or disappear completely, then the survival of these patients is much better, much longer. I would argue there will be some patients that actually might be even cured or have a long-term survival like measured in years and not months anymore. This is the number 2 point here, the absence. Now if they increase, then of course the survival is not much worse. As you saw, very small studies, but extremely promising and a signal for an oncologist like myself is so strong that I'm enthusiastic about it. We as oncologists need to be positive because otherwise, we cannot treat patients and tell them something better is coming. Leronlimab decrease of these tumor cells actually did relate both in triple-negatives and in colorectal, and this improves survival. That's amazing. Next slide. Carbo, as I mentioned before, is a very typical compound for triple-negative breast cancer, and it is being used in first or second line, and this was used here in patients or heavily pre-treated. They progressed on treatments, tumor progressed on treatments already, and in all three dose levels it was well tolerated. As predicted, leronlimab is not toxic like TKIs or small molecules. It does not have liver toxicity, which would be for the other diseases we heard about before, the NASH and NAFLD. Very detrimental sequences. It does not. This is very good. You have seen very early preliminary but extremely promising data in two different diseases. For cancer, unlike for liver disease, the weekly 700 milligrams dose is probably the best. Now whether or not we'll continue with three-week carboplatin or we could reduce it also to weekly with a lower dose and therefore even further reduce toxicity remains to be seen by the studies that are being planned and that of course, many patients will want to participate because for them there's not much alternatives left. Next slide. Conclusions from my side here, I think we have 28 patients as you have seen. The median progression survival is at least as good and in some instances, particularly in combination with carbo, more than a year, unheard of in the past. The median overall survival, number 2 here, that received higher doses is also impressive. Finally, the median progression-free survival, which is a surrogate. This is not so important, and the FDA doesn't like it too much for some, for a number of reasons I can definitely mention and discuss with you if you wish. It is important for the individual patient. Just remember, a patient has, let's say, stage 4 triple-negative breast cancer and being started on something which gives her two or three months progression-free survival. Progression-free survival usually means also good quality of life or gives her six months, like here, four and a half, five, six months of progression-free survival. She has longer and better quality of life, particularly now in this time of the year, you know, holiday season is coming up, and patients want to spend maybe the last Christmas or last Hanukkah or what they, whatever they do, with their family because they may not be alive next time in a holiday season. If they survive it with better progression-free survival without symptoms and not in the hospital, how good is that? The FDA is forgetting this type of endpoint. Lastly, the vast majority of patients have measurable lesions, and it is important for clinical trials to measure the lesions. Why? You can actually quantify. They are going down, they are stable, even stable disease for patients mean means they change or we change with treatments like leronlimab, hopefully soon, the aggressiveness of the disease and the patients are dying from growing of overgrown by the tumor to something chronic. Even stable disease, if the tumor stops growing, is already success. Let me tell you, stable disease is much more important than the clinical trials indicate. If I see the waterfall plot from Cyrus that you have seen a few minutes back, and you see the vast majority of patients have either responses, maybe complete responses, but also a lot of them, no growth of disease, and that's very important for patients' outcome. I think this my last slide is the next. Not quite. Yeah, this is basically the last slide that I would like to remind you of. The hallmarks of cancer include many, many things, and now since this year there have been added two more such new dimensions, if I may, and this includes now clearly the tumor-promoted inflammation. I think Dr. Noureddin will love it that I'm saying it because that's exactly what also causes the disease that he's treating, NASH and similar. But it causes also cancer. Obviously, the other important portion of this cycle is the immune regulation. The avoiding immune destruction and avoiding the immune escape. We call it escape. These cancer cells escape our immune system. Now with compounds, that are targeting CCR5, and you heard why I believe, leronlimab is the one, probably only one winner, once you have, further Phase 2 and hopefully Phase 3 studies, is targeting these two new things, in the hallmarks of cancer. I finish here with this slide. Thank you. Great. Thank you, Dr. Stefan Glück, for your thoughts on leronlimab and the TME and the immune cycle, and for the summary of the clinical data. Okay, we are now going to pivot to our last portion of the R&D update call, which is with Dr. Jonah Sacha to discuss the role of CCR5 in HIV prevention and cure. Dr. Sacha, are you with us? I am. Excellent. Great. Thank you. Thank you for that introduction, Cyrus. Good morning, everyone. My name is Jonah Sacha. I'm excited to present some data to you today that is from our preclinical non-human primate, our rhesus macaque model, which I think will help illustrate why we are so excited about the potential of leronlimab to positively and significantly impact the HIV epidemic by slowing and limiting further spread of the virus. Next slide, please. For those of you who don't know, CCR5, as Cyrus alluded to earlier, was discovered in 1996. In that same year, a flurry of papers came out because it was shown to be the major co-receptor of HIV. In fact, it was quickly found that individuals that naturally bear a 32 base pair deletion in CCR5, and therefore don't express CCR5 on the surface, are highly resistant to sexual transmission of HIV. This is due to the fact that when HIV infects new individuals, it almost exclusively uses CCR5. Even though in a, the individual transmitting the virus may have both R5 and X4 tropic viruses, it's usually 99.9% only the CCR5 tropic HIVs that transmit. Next slide, please. It was because of this known protective ability of CCR5 deficiency that Dr. Gero Hütter who performed the first allogeneic bone marrow transplantation and cured a patient, shown here, Timothy Ray Brown, the Berlin patient, used a stem cell donor who was CCR5 deficient. Timothy Ray Brown was in HIV remission for over 13 years. Next slide, please. Unfortunately, he died in 2020, but before he died, he was joined in his cure brotherhood by Adam Castillejo, the London Patient, who also received a CCR5 deficient allogeneic stem cell transplantation. Next slide, please. There are currently three other unpublished case reports that will be coming out very shortly, where these there's three further individuals who were also cured by receiving a stem cell transplantation from donors who are CCR5 deficient. Most excitingly is the first woman who's ever been cured of HIV. I think what this does is set the stage to really show the power of how central CCR5 is to the biology of HIV. When you starve the virus of its ability to interact with CCR5, you can actually do the previously thought unthinkable, which is cure HIV. Now these case studies really have illustrated the power of targeting CCR5. There is now a flurry of activity around lots of gene therapy approaches to try and edit out CCR5, which is a very tall order. Next slide. We posit actually that instead of going through this ability, you can simply use leronlimab to and give it to a patient and block HIV. The reason that is shown here. As you can see, HIV binds to its major co-receptor CD4, but in order to enter the cell, it also has to interact with CCR5. You can see that on the right-hand side, leronlimab binds to the exact same domain of CCR5 that HIV wants to use. In contrast to the allosteric small molecule inhibitors like Maraviroc, the virus can't interact with CCR5 at all because leronlimab is sterically hindering. It's sitting in the site that HIV wants to use. This is a very potent mechanism of action. We know that Maraviroc has failed as a PrEP agent because the virus, for whatever reason, can just simply adapt to the Maraviroc bound form and still continue its infection. Leronlimab is a competitive inhibitor, which I believe will allow us to mimic the CCR5-Δ32 phenotype. This is the CCR5 deficient phenotype. Next slide. We tested this in our non-human primate model of macaques. This is a previously published study in Nature Communications, where we dosed macaques, uninfected macaques with a low and a high dose, and that resulted in statistically significant and full sterile protection respectively from acquisition of SHIV. That's Simian-H uman Immunodeficiency Virus. That's an macaque SIV or HIV that carries the actual HIV envelope. This is important because it's the HIV envelope that is binding to CCR5. What this does is it shows us this leronlimab can really pharmacologically mimic the CCR5-Δ32 phenotype. This is really critically important. I will stress that all of this is done pre-clinically in non-human primates or rhesus macaques. For those of you who don't know, we refer to macaques as the gatekeepers of the clinic. Many FDA-approved substances will be first tested in macaques for safety and efficacy, as you will see with long-acting cabotegravir, which was recently approved for PrEP or prevention of HIV. Next slide, please. As I just mentioned, the field has really gone from, you know, taking a pill every day to longer acting injectables. The reason is because patients really don't want to take a pill, a daily pill. This is, there's both a stigma attached to it, and also many, many patients forget or they feel side effects. There's a real movement towards long-acting injectables. Long-acting means greater than weekly, so once a month, once every two months. As I mentioned, with cabotegravir, which is an integrase inhibitor on the left, this approach using long-acting cabotegravir was first tested in macaques, the exact same model that I just showed you in the previous slide. This eventually resulted, as you can see on the right, in the FDA approval last year of a long-acting cabotegravir for HIV prevention or PrEP, pre-exposure prophylaxis. Next slide, please. How can we take leronlimab, which is currently a once weekly, which is great, but how can we make it longer? What we did is we made a tool compound for our macaque studies. We took the, we call the Fc, the constant of crystallizable fragment. That's the bottom of the Y here. We swapped out the human version of the molecule for a macaque version. There's many ways in which you can extend the half-life of antibodies in circulation, but we chose what's called the LS mutation. That's simply two amino acids that you replace in this same region. What this does is it allows the antibody to escape the natural recycling mechanism, so that instead of being recycled and degraded, the antibody can escape from that pathway and then be put back out in circulation. We chose this because there's been a lot of FDA-approved drugs that have used this most recently. Next slide. What I want to show you is some data where we've made a long-acting version of leronlimab that I think really shows the power of this approach. What you're looking at here are four rhesus macaques. We gave a single 10 mg per kg or low dose of subcutaneous dose of the long-acting leronlimab. You're looking at the plasma leronlimab levels on the Y-axis versus days post-injection. When we give these macaques a single dose of the parental leronlimab, it's cleared from circulation by about 20 days. Here you can see that we have a detectable leronlimab in plasma out to 100-160 days. About four months from a single small dose injection. That's quite promising. Next slide, please. With leronlimab, what you really have to look at is what we call receptor occupancy. In this bottom left, what you're seeing in red is how much CCR5 is coated and are covered up by leronlimab on the surface of CD4 T cells, the target of HIV in peripheral blood. What you see is there's one animal in the circle that dropped out and lost its leronlimab by about 100 days. Most of these animals maintained it for 140-160 days. 100% receptor occupancy. This is well past our target, which was 90 days or three months. On the bottom right, what you're looking at is the amount of Anti-Drug Antibody or ADA. What that is the body making its own immune response against the drug or against leronlimab. You can see essentially we were able to avoid the elicitation of anti-drug antibodies. Next slide. What I find most exciting... Oh, sorry. Can you go back one? Unfortunately, it appears the last graph did not render, which is unfortunate. What the last slide, which, you know, you can't see unfortunately is we took biopsies of the rectum, and we looked at the receptor occupancy of CCR5 on CD4 T cells in the rectum. This is important because that's the major site of sexual SIV transmission. There, in all of these macaques, we saw full receptor occupancy that was maintained for 90 days in that site. What that means is that with a single dose, we were able to get coverage of about a three-month window where individuals would be protected from sexual transmission. These PrEP studies are ongoing. I've recently presented these data, actually on Monday at the HIV DART meeting in Cabo San Lucas, and we'll also be presenting these results next week at the Miami Reservoirs meeting. These are really, you know, breaking data that is very exciting, for both us and the field. Next slide, please. That's why we think that leronlimab can help with PrEP or pre-exposure prophylaxis. What about cure? As I mentioned, all the individuals to date that have been cured of HIV were cured through an allogeneic stem cell transplantation. That is not a process that we can simply roll out and universally do. It is very expensive. It is very dangerous. It has a mortality rate of about 40%. We wanna ask the question, if we're gonna cure HIV, it has to be something that patients would wanna do. Ask yourself, if you had HIV and you wanted to be cured, would you go through a bone marrow transplantation? I'm gonna wager that the answer would be no. However, would you be willing to go in and get a single intramuscular injection? I bet you would. I know I would. Next slide, please. Really looking forward to where the field is going, this is in vivo gene therapy. Currently the state-of-the-art is AAV vectors or Adeno-Associated Virus. And what you can do is you can actually take leronlimab and sequence, you can put it into this vector. You can then inject that into the muscle, and these myocytes muscle cells will pick up the AAV vector, and they will then turn into little antibody factories and produce leronlimab for the rest of your life. Next slide, please. We tested this proof of concept in an animal that is SHIV infected, an animal that was infected with simian human immunodeficiency virus. Remember, this is the HIV envelope. On the top left, we're looking at the amount of leronlimab following a single injection of this AAV vector. You can see that the animal's muscle cells are indeed making leronlimab. We can detect it in the plasma over time. This is still an ongoing study. We're only about 12, 13 weeks out. On the bottom left, you can see that one week following this injection of the AAV gene therapy vector, we get full receptor occupancy. Leronlimab made by these muscle cells is fully coating CCR5 on CD4 T cells, the target of the virus, thereby blocking access of the virus to infect its target cells. On the top left, what you can see is a little anti-drug antibody response that happens about the week 3-6. This is interesting because if you look at the bottom right, what we've done is I've overlaid the receptor occupancy of the targets of the virus in blue. With the virus load, on the right, you can see SHIV. This is a log scale. Prior to the injection, this animal had about 1,000- 10,000 copies of the SHIV circulating in its blood. Following injection of leronlimab, when we get full receptor occupancy, as you can see here at week 0, the virus then decreases down. At week 3 and 4, it's fully undetectable. Remember, we had this little anti-drug antibody response. What this means is that a little bit of the leronlimab being made is being cleared. You can see a little bit of receptor uncoating begin to happen at four weeks, and you see this little peak of virus that comes back. Look at what happens when this goes away at about week 8 or 9 when the anti-drug antibody disappears. The virus load shown here in black goes back to 0. This animal is currently fully suppressed. There's no virus replicating in it following a single injection of an AAV vector expressing leronlimab. Next slide, please. This is why we are so optimistic about the future of leronlimab long-acting for HIV prevention and cure. We think the a long-acting molecule like this where a patient could at home subcutaneously dose themselves once every three months or perhaps even longer will have very high uptake and will be very attractive to patients. For functional cure, by that I mean control of viremia, the goal here is to develop something where you could just go in, get a single shot, and you have, you know, your own body will make leronlimab. This is only possible because leronlimab appears to be very well tolerated in patients and also in our preclinical studies. I believe that's my last slide. Thank you. Thank you, Dr. Jonah Sacha. Very exciting data, potentially game changers for patients living with HIV, and certainly has applications beyond HIV as well, for other diseases where CCR5 is a promising target. We're now gonna conclude the presentation with some closing thoughts. Coming back to our focusing the pipeline on the highest value opportunities. We've gone through our clinical rationale for why we're focusing in on NASH and oncology. We've seen from Dr. Sasha, you know, this exciting opportunity for longer-acting molecules that can play a role in HIV prevention as well as cure, and potentially other indications as well. We continue to believe that leronlimab and CCR5 blockade through leronlimab can be a promising mechanism to treat each of these diseases that has continuing high unmet needs. In terms of how we wanna get there. You know, with NASH, you know, we intend to raise capital and execute trials. With oncology, we do see opportunities with co-development partnership. Within the development of longer acting agents, you know, we intend to invest in the future there and continue to try to advance these approaches. In terms of what potential timelines could look like, I think it's really important to highlight that, you know, from a value creation standpoint, I've mentioned this before, we truly do need to generate a large, robust, and what I call unequivocal data set that will leave no questions left on the table, right? That a strategic partner would find attractive and attractive enough to do a real value accretive deal with the company. We've gone through and mapped out what the potential timelines are across each of the different areas that we presented on today. You know, as I mentioned before, NASH and oncology are our priorities. However, you know, because this is all gonna be funding dependent, you know, we're gonna focus on NASH initially and work with co-development partners to the extent that we can to develop in oncology. What do we expect in 2023? Our largest priority is the removal of the clinical hold in HIV. This is essentially a gating step for us to be able to get back to normal operations as a company and do what biotech companies do, which is advance therapeutics and try to bring them to market. Following the lift of the clinical hold, we expect financing to fund operations and to achieve this value inflection point that I've just alluded to. We intend on initiating a new NASH trial. We would like to, you know, commit to an investment in and advance longer acting CCR5 molecules as this is potentially the future of at least certainly HIV therapy, as Dr. Sacha presented. We continue to contribute in medical meetings and peer-reviewed publications. Again, the CD02 trial data is in process for that right now. We're gonna continue to reshape our team and our capabilities in order to meet our goals. At some point following the, you know, the achievement of earlier metrics listed on this slide, you know, we're exploring a corporate rebranding as well. To conclude, I wanna say thank you to everyone for joining us on this call. You know, we hope that the presentation of the clinical rationale for our development strategy was insightful and helpful. As I mentioned, we will be fielding questions in our upcoming quarterly investor update that will be occurring in the new year. Please feel free to submit questions to us via the website, as many of you have done in the past, and we will incorporate them into our discussion on the next regularly scheduled quarterly investor update. Again, thank you all, and that is our presentation for today. Thank you. That concludes today's webcast.