CytoDyn Inc. (CYDY) Earnings Call Transcript & Summary

Greetings, and welcome to the CytoDyn Investment Community webcast. [Operator Instructions] Please note that this conference is being recorded. I will now turn the conference over to our host, Antonio Migliarese, Chief Financial Officer. Thank you. You may begin.

Hello, everyone, and thank you for joining us today. This is Antonio Migliarese, CFO of CytoDyn. Joining us on today's call is our President and CEO, Dr. Nader Pourhassan; our Chairman, Chief Medical Officer and Head of Business Development, Dr. Scott Kelly; and our Chief Operating Officer and Head of Clinical Development, Dr. Chris Recknor. 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, amongst other matters, statements regarding 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 appeared 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. Although 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. Please note that we will not be addressing any questions on matters related to the Annual Meeting or the 13D Group. I will now turn the webcast over to Dr. Nader Pourhassan.

Thank you, Antonio, and thank you for all shareholders being on the call. We are now on Slide #3. The first 3 slides are designed to give you a sense of what does it take to get a drug approved through FDA. So drug development time line and required funding, what is that? Well, in regards to funding, we know that it's about $1 billion to $2 billion. It's reported in many sites. Let's go to the next slide, please, Slide #4. In regards to time lines, everybody could have their own opinion. However, it's very clear in medicinenet.com and in FDA.gov, many other sites report that clinical development of any product involves preclinical testing, Phase I, II, III and new drug application, which in our case would be BLA, biologics license application. If you look at the highlighted green -- number of years that I have highlighted in green in this slide, that's a total of 12 years. Make sure everybody understands that as you're investing in CytoDyn, we are a drug development company, and as an investor, you should know this time line. The next slide, Slide #5, please. So let's look at these time lines. I printed it again on this slide, on the bottom of the slide, you can see 12 years. CytoDyn purchased this product, leronlimab, which was called PRO 140 at that time, from Progenics Pharmaceuticals, a very well-known pharmaceutical biotechnology, which had tremendous, very talented employees. These guys were world renowned, some of them. And they went from preclinical to Phase II in 12 years. The conservative time line that we showed in the link that is provided so you can check it out yourself, said it should take 4.5 years. They took 12 years and then they sold the product. If you look at the second row on this table, from Phase II to approval, according to this guideline, it will take 7.5 years. In 2009, Progenics, while they were developing PRO 140, leronlimab, they went to FDA. An FDA minute clearly said that you have 3 weeks of efficacy of PRO 140, it's not enough to do Phase III. You need to do Phase II. That's when we bought the product. And we didn't do that trial that they were working on. It was a substance abuse population, potential market value for that is about $25 million if you get approved. We gave up on that. What we did is we did a quick study in 2014, showed 12 weeks of efficacy, went to FDA, got a Phase III in combination therapy for HIV and another Phase III for investigational Phase III for monotherapy. Opened up the market value to be $6 billion bio value. Why they reported about that and showed why is that much? Practically, in 1 year, we changed the outlook of the product, what Progenics was not able to do. Next slide, please. But that's not all we did in 7 years. Practically, according to that slide, it said 7.5 years, what we needed to develop this product to be in line with that conservative time line. We look at this product for many other indication, and that means we needed to raise more funds to develop, to explore all of these, namely COVID-19 era came, and we did not drop the ball when we got the call from Dr. Seethamraju from Montefiore Hospital saying that the drug worked on 2 of his patients who were dying. We didn't drop the ball. We continue developing the drug -- our drug, leronlimab, for those. Not only for COVID-19 critically ill population that it started with, but also for COVID-19 severe population. And also, we tested the drug for mild and moderate. But now we are also in long-haulers. HIV has 3 indications for us now. One is combination, one is monotherapy and prevention. We also have NASH trial. And most importantly, which I'm very excited about, Dr. Scott Kelly's presentation to you today is about 23 different cancer types that we have started Phase II on Basket trial and mTNBC. Next slide, please. So before I start talking about COVID-19, CD16 and 17, because this is our most important drive, I like for Dr. Scott Kelly to give us the update on the time line -- I mean on the population that we have right now that are affected by COVID-19. Please?

Yes. Thank you, Nader. So I would like to begin by just saying we are extremely excited about our trials in Brazil that we'll be talking about shortly. The greatest threat with COVID-19 is clearly mutations. We thought we were out of the woods in the United States, and then the Delta variant came along. But this is not surprising. That is exactly what viruses are supposed to do, they mutate. You now have variants beyond variants. Right behind Delta is the Mu variant and could abate certain antibodies, potentially vaccines. It is currently a variant of interest and more research needs to be done. It's hitting Colombia and Ecuador, particularly hard right now. It's concerning that although sequence cases are less than 0.1% worldwide, in certain countries like Colombia it's already at 39% and Ecuador is at 13%. There are currently 4 variants of concern, Alpha, Beta, Gamma and Delta. The clear message is this disease is not going anywhere. It will be endemic. We do believe the true advantage of leronlimab is that it's variant-agnostic. All of the current mutations are occurring in the spike protein. Leronlimab does not bind to the spike protein. And since its target is CCR5 it should not be affected by variance. This is a very important point. So the virus is now mutating faster than you can make new therapeutics to the mutations. Let me repeat that. The virus is now mutating faster than you can make new therapeutics to the mutations. This is why we are so persistent in our efforts to help those with COVID-19. Remember, all 3 authorized vaccines were designed according to the spike protein from the original version of the virus. And that is what other monoclonal antibodies, for example, Regeneron's, were designed to neutralize. Fortunately, the vaccines are still working effectively for now, but we don't know if this will remain true. Nader?

Thank you, Dr. Kelly. So let's give you guys update on CD16, the critically-ill population of COVID-19. As we develop the drug in the United States, we reported the results for CD12, and the results were fantastic in regards to a small population of 62 patients out of 394 that was in CD12. That was critically-ill population. We immediately went to overseas where the problems with critically-ill population was pretty high, and that was Brazil. We started signing of a contract with a new CRO, Einstein Research Organization. And then we signed an agreement with a biotech company -- I mean I'm sorry, pharmaceutical over there, Biome. Usually, that takes about a year according to anybody if you check it out, and we did it in less than, I believe, 2 or 3 weeks. And the study was supposed to start by the end of June. And we're delayed. This is what happens in drug development. There's a lot of moving pieces that you're going to manage. We have to make sure that all the comments from ANVISA, the FDA in Brazil, is 100% satisfied. They require that. We had a huge team working on that, had meetings every week, twice with that team in Brazil and our team. And we were successful, and we got green light from ANVISA to do CD16 critically-ill population. However, this study was with IV, not subcu, 4 dosage, not 2. Remember, in CD12 we had about 78%, 79% reduction of mortality versus placebo in first week and then it became 82% in 2 weeks. And third and fourth week, it dropped to 50% and 30% because we didn't give any third or fourth dosage. We corrected that. We made it 4 dosage. But better than that, we have through IV. But then ANVISA had a problem with the stability of the product in regards to particles that could be produced when you mix the leronlimab in an IV bag, and we had to do special tests. So we have to go to drawing board. Dr. Nitya Ray and his team did a fantastic job getting that test done very quickly and getting positive results, which we are very proud of. And getting that to ANVISA -- the final report is either going to ANVISA today or it's already been perhaps there. But because we had green light for this study based upon these results only, we have shipped the product already. Now that's another problem, shipping product to another country. I don't know if everybody remembers, but we did sign a deal with Philippine Airlines. And now, I understand how valuable that is because getting the product to go in the airplane took 10 days in Los Angeles Airport before it was taken for product CD17 drug. And CD16 is also on its way to Brazil. And we believe that this trial can inject the first patient next week. But I want to bring some very important aspect of this study to everybody's attention. What is the primary endpoint in this study. It is death or respiratory failure until day 28. Now we didn't have a primary endpoint like that in the older study we did CD12, but we did have endpoint, 1 endpoint that said how fast patients were critically ill walk out of the hospital. That's even more stronger. And the result with 62 patients was 166% better in leronlimab versus placebo. So getting this primary endpoint and ANVISA agreeing to do this is a fantastic situation for us. Now 28 days, 4 injection, 700 IV every week. That's just fantastic for us. And the primary endpoint, when we did the power analysis, if we're going to go for this primary endpoint, 62 patient results that we have indicated that we needed about 90 to handle our primary endpoint. But now we're going to have an interim analysis, that's 40%, which is 127 patients. Do we think we're going to hit our primary endpoint on this? So I'd like for Dr. Chris Recknor to also elaborate on this. He helped tremendously getting this protocol all ready to go. Dr. Recknor, do you have anything to add?

Absolutely, Nader. We're really excited about the studies going on in Brazil. The difference really, when you look at it, like you pointed out, is the 2 doses versus 4 doses. And if you recall, the mortality reduction was seen at day 14 in that critical group. The other key difference is that where there's one trial, CD12 that's looking at critical and severe, we're actually breaking that up into 2 separate trials to really focus in on the critical group, and you already talked about that primary endpoint, and then the severe group, the critical group is getting a 700-milligram and IV and times 4. The severe group is getting the 700-milligram dose times 1 subcu and then 3 doses weekly at 350. And what we've done is we've taken and accentuated the differences with these patients that are severe moving in a different direction to them getting worse versus those that are really sick getting better. And we think the way that we've set up the endpoint optimizes our chance in addition to making sure that the patient numbers are adequate to hit the endpoint. The other key difference that I'd like to say is that rather than just the all-cause mortality, we're defining how the patients would move from 1 ordinal scale category to another. And so for CD16, we have -- moving to 3 different points within the ordinal scale, the same in the opposite direction now for CD17. So I think we're really poised for a great result and very excited about it. And screening has already started.

Thank you, Chris. So in regards to CD16 only, I want to make sure Dr. Recknor talk about also CD17, but I want to make sure everybody understands. In regard to CD16, that's critically-ill population. And in that regard, that's 4 dosage IV, 700-milligram. And the primary endpoint is based upon what we saw in CD12, for that endpoint, it was 166% better in leronlimab arm. And this criteria is even more relaxed, but we believe we can hit it by 90 -- with 90 patients, the primary endpoint, and now we have 127. Now what Dr. Recknor said that is very crucial also for everybody to note is CD17, which is the next one, CD17, we have 612 patients. Why? Why not 316 like we did with critical? Because the result clinical benefit in critically-ill population was not -- for severe was not as good as critical. But it was good. If you do any clinical trial and you have a difference between the drug arm versus placebo arm, that means if the delta is, let's just say, 5 points, then you want to have more patients to be able to hit your primary endpoint. It's just a matter of having more patients. The difference between the drug arm and placebo in tocilizumab trial was 1%. That's absolute delta. And they hit their primary endpoint. So if you have benefit you're just going to make a larger trial. So severe, we made it larger based upon the benefits that we saw. And the primary endpoint, as Dr. Recknor said, is very clear in that slide, everybody can read it. And we believe we can hit that primary endpoint. And we don't know what's going to happen at the interim results, but in regards to critically-ill, we believe that we are very, very strong in our belief. And our very educated guess is we're going to hit the primary endpoint. And to enroll 127 patients, it's just a matter of us getting some time lines from a -- from our CRO at Brazil, and we let everybody know where it is. Now this is just 2 trials that are very crucial to us. Why is the first patient in CD17 severe COVID-19 not injected yet? I want to make sure everybody understand that, make sure you pay attention to facts, not fiction, not noise, just facts. When we go and take a company and take all of our BLA, IND all the stuff that we have from our clinical information, transfer it to another country, then you're ready to get going and the drug gets stuck in the airport for 10 days, then it goes to custom and it gets stuck over there for 10 days, nothing you can do nothing, nothing you can do. You've got to wait and let it get done. The severe population CD17 study has initiated. And ANVISA has approved it and the trial is screening right now. We will be announcing first patient injection any second. I want to make sure everybody is clear on that. We overcame all the obstacles, thank God for that. Now let's -- we're not done with COVID-19. We got another excitement that Dr. Recknor and his team has done a fantastic job, and that's called long-haulers. But before we go to Dr. Recknor, I'd like to ask Dr. Scott Kelly to tell us the situation with long-haulers. Dr. Kelly?

Yes. Thanks, Nader. Quite frankly, in long-haulers, in my opinion, this is the next tsunami and will overwhelm the health care system, and it's truly a global health emergency. Now in one of our previous calls, I told you all that I was concerned we might exceed 200 million cases of COVID-19 by the end of 2021, in September, we've already passed 223 million cases. Now I also told you that it could affect 10% to 30% of those infected, leaving 20 million to 60 million patients without effective treatment options. Now those numbers seem extremely conservative and more mutations are consistently evolving. There was recently a study published out of Norway in Nature Medicine that said that more than 50% of young people with mild COVID-19 infections experienced long COVID. So if that's the case, the 221 million people that survived COVID-19, over 100 million people could have persistent symptoms. Remember, this is a multisystem disorder that is ruining the quality of lives of millions of people. It can affect the heart, the kidneys, liver, musculoskeletal system and the brain. There's a physical aspect and emotional aspect and a financial aspect. And it's been estimated that 45% of long-haulers were working reduced hours and 22% couldn't work at all. These people needed help yesterday. The overlaps are substantial with other post viral symptoms including myalgic encephalopathy. One thing I can assure you is this virus does not discriminate. It affects the young, the middle aged, the elderly, and it doesn't care whether or not you've been hospitalized or whether you've been treated as an outpatient. Its goal is to destroy every organ that comes in contact with either by the virus or the immune dysregulation of the inflammatory response that follows. Fortunately, CytoDyn saw this very early. We completed our investigative trial, and we believe we're in a very unique position to help those with long-haulers as soon as we get the green light to proceed, and we are ready. Nader?

Thank you, Dr. Kelly. So in regards to long-haulers, we spoke to FDA and they asked for primary endpoint, which is the sum of all 24 symptoms and to see what we have. When we did that, when we added all the 24 symptoms, the drop on severity of 24 symptoms in this 57-patient study in placebo was negative 8, in leronlimab was negative 16, 100% relative delta, 100% better than placebo. The p-value was 0.269. Obviously, with leronlimab arm having 27 or so patients is very difficult to hit primary endpoint. So you now do your power calculation and you can see that with 100, 150 patients, you could hit the primary endpoint. Well, we are going to have a protocol 200 to 300 patients, and Dr. Recknor already sent that protocol to the FDA. Can you please go to the next slide, Slide #8. So the FDA now has the protocol that we like to go forward with the long-haulers, which would be a very historical day for us. And we have a manuscript that's ready to go forward with CD16. And we have submitted the protocol and the primary endpoint and the CSR to the FDA. So the next 3 slides and this slide, Dr. Recknor will explain to you all the results again. Dr. Recknor, could you please?

Yes. So this is an exploratory study. So we had a limited number of patients. But I think what you see from this next slide in green is improving, yellow is staying the same, and red is worsening. And for the leronlimab treated...

You point Slide #9, correct? The next slide, Slide #9.

I'm sorry. Yes, I'm sorry. Okay. So yes. I'm sorry. So the graph. So in leronlimab-treated, 17 symptoms improved of the 24. In the placebo group, 18 of those 24 symptoms worsened. And that's key. And so we see with leronlimab that these patients are doing better. But why and what's going on with them? If you move to the next slide, we were surprised actually in what we were finding. And not from -- the CD10 trial, we saw that there was immunosuppression. Immunosuppression is noted post-COVID, but we started looking into how leronlimab is working. In CD10, we saw superimposed infections. And as you recall, the placebo group had about 30% increase in adverse events versus leronlimab-treated. Why is that? A lot of those might have been urinary tract infection superimposed, pneumonias post-COVID and sequella. What else also in CD12 did we see? In CD12 if you recall, just shortly, within about 14 days, we saw restoration of the CD8 counts. And look at what we're seeing here in leronlimab-treated patients at week 8 on the far side. So the CD8 cells, this is very consistent with what we're seeing with the CD12 trial. You have a p-value 0.014, highly significant where we're increasing the CD8 count. What about the natural killer cells? We're increasing that as well with leronlimab. And additionally, even back at week 4, we're improving CD4 counts and B-cell proliferation as well. Essentially, really, what we're doing is we're rebooting the immune system. We're resetting it. And in these patients, it's suppressed. Now a lot of the long-hauler patients now we're finding out have reactivation of viruses, Epstein-Barr, sometimes cytomegalovirus. Why is it that leronlimab is doing this was our question. And we started looking into this, and we think it's related to CCR5. And actually, leronlimab does bind to CCR5, and that's what prevents HIV from entering the receptor. But we were interested in knowing also that the CCR5 helps stabilize the cell surface expression. Why would that be important? If you look at some of the literature, there's actually a genetic potential in terms of your haplotype for CCR5 that increases your risk. So those patients that have low CCR5 expression on their cells have a higher risk of critical COVID if that's in the lung. The CCR5 is actually the wheels that allow the car, the cells to move. And what leronlimab does is it stabilizes those wheels. It also makes those wheels do things differently. And so what we're studying is how leronlimab makes the cells work differently. It may be that also it works so that its adhesion is better and that it doesn't move to areas or changes cell types. If you look at the next slide, we then correlated the cellular changes with changes in IL-10 and CCL2. The CCL2 is associated with a lot of problems. And you see in week 8, we have a decrease, and in week 4. Scott, do you want to comment some on this because it's pretty interesting, what we're seeing.

No. I think it's unique in what we're seeing, Chris. And I'm also thinking right now about what you're seeing and how this is applicable to many of our other opportunities, including cancer. So I think it's really interesting about rebooting the immune system and giving these patients a chance.

Okay. Thank you so much, Dr. Recknor, Dr. Kelly. And the good news for our shareholders is that thanks to [indiscernible], we have patented all of these ideas, which is very fantastic idea that we do not want it to be taken by anybody. So we went ahead and patented all these for the shareholders. So let's talk about next slide, please, Slide #12. What is our situation with CD -- I mean COVID-19 in Philippines. A lot of people ask me this question, and they think that there should be quite a bit of orders coming in. Compassionate use is something that the cargo pharmaceutical at Philippine has to be able to get to the hospitals and talk to them and see if they like to use this. This is not as easy as just selling your product. So that's quite a bit of hurdles still ahead of them. But they did have the good news of having their FDA allow them to get more than just 1 order per patient, but many vials per hospital. When the FDA had a letter about us saying that leronlimab doesn't have effectiveness in COVID-19, what that meant was we didn't hit our p-value. The FDA clearly said in that letter that we are encouraging -- they are allowing the company to do a trial in COVID-19 critically-ill population. So they did see that critically-ill population data was positive. In Philippines, they started questioning that and there was a lot of explanation that needed to be done by doctors over there to the people of what's going on. And they overcame that and we sent the first PO of the product. And it was stuck in customs for, I believe, 4 to 5 weeks. We overcome that and we learn all the details of what we have to do for the next shipment to don't have all these problems. And the next PO just arrived a couple of days ago for us -- or yesterday, I should say. So we are very happy that, that -- this process is back on track. But more importantly, there are now VIP people that have been using this for themselves or their family members when they get in deep trouble with critically-ill COVID-19 problems. And because of that, there is a campaign now that they would like to get us approved very quickly so that process of emergency use authorization potential is back on track and they are going forward. Does that mean we're going to get EUA next week? No. Does that mean we won't get it a week after that? I don't know. I'm only reporting to everyone as everything is happening, just like in everything else for the last 9 years. So here we are -- that's what we are with Philippines. Next slide, please. Now in regards to NASH, we have 50 out of 60 patients that's going to be done with the 14 weeks of the trial, which is on September 13, which is only 5 more days. That means we can do interim analysis with 50 patients. And if we do show that fatty deposits has dropped and fibrosis has dropped, we have very, very strong case for Phase III in NASH. And this would be very, very important. As everybody knows, NASH is a disease that no pharmaceutical has shown positive results that allowed the FDA to give them approval. We are hoping to be the first one. So in the September 13, when we get the 50 patients, if we only show fatty deposits dropped, which we showed that already in animal study, like cancer where we showed the animal study was positive, we went to a human it's positive. If we show just that, that means we have indication in NAFLD, and I'd like to ask Dr. Kelly to talk about just if we have only fatty deposit drop in patients, what do we have?

Yes. I mean in NAFLD, it's a tremendous opportunity. It's a little bit different than NASH because it's such a bigger market. It's 30% to 40% of the population, whereas NASH is like 3% to 12%. So also, I think it's important for people to realize that with our effectiveness in HIV, a lot of the HIV patients have an increased risk of NAFLD and also an increased risk of NASH. So not only we'd be particularly useful in the general population, but also in the HIV population.

Thank you. So in this trial, in this NASH trial, I believe we broke the world record in enrolling as fast as we did. That's what I believe. We will check to make sure it's right. But Dr. Chris Recknor has done a fantastic job, and I'm very excited for him to explain to you now his take on NASH indication. Dr. Recknor, please?

Sure. Well, the interim with 50 patients would be on September 13. But right behind that is the 60 patients for the full part of the Phase I in mid-October. And that was recruited in record time. I think the results from what we see from the long-haulers in terms of the biochemical markers, fit with what we see in the animal model from NASH in terms of PDFF. And I think that also is going to apply to the CT1, which is the fibrosis.

Excellent. Thank you so much. So next slide, Slide #14. Let's talk about our cancer program. We have our application for breakthrough designation ready to be submitted. The reason it's not submitted is we need to get the sequence. We are changing CROs and we are needing to get those sequences, but the application is ready. We have 2 conditions for any breakthrough designation that needs to be met. Number one, it has to be a condition that's unmet medical need metastasis triple-negative breast cancer, we believe, is that. And the second is you've got to show efficacy. And efficacy means you at least need to have 5 patients in a clinical trial showing better results in overall survival or progression-free survival. We believe we have done that with mTNBC with 10 patients. We also have 30 patients together. We show the data for that, which we are very, very excited about. But this is very important for us to get a breakthrough designation. Our chances is very high now with the data that we have in our opinion. And our Basket trial is right behind it, which is doing very well. Actually, we have some patients who have -- most of the patients who are on there right now have passed 12 months. But I'd like for Dr. Kelly to now make the case about potential of leronlimab in cancer and kind of give us a little bit detailed history and why CytoDyn could be an oncology company. Dr. Kelly?

Yes. Sure, Nader. Thank you. So I'd like to begin by telling you why we are so excited about leronlimab in oncology. I'll give a brief history of our efforts in oncology. Some of this information from animal studies has never been made public, and therefore, I think you might find it of interest. In the next few days, I will put a slide presentation on the website that will give you further information of previously supported nonpublic information of the role of leronlimab in oncology that helps guide our efforts to bring us to where we are today. You see that the fascinating thing about CCR5 in oncology is that CCR5 is normally expressed only in the immune system. However, as cells undergo malignant transformation, CCR5 becomes overexpressed in several malignancies and is overexpressed particularly in metastatic triple-negative breast cancer. So ask yourself the question as to why this might happen. What is the goal of cancer? Well, the goal of cancer is to evade the immune system by becoming invisible, gain an advantage in the tumor microenvironment for the tumor to grow, bring in supportive cells to suppress your own immune response, create a new blood supply for tumor growth and then to metastasize, which ultimately causes the patient to die. This is an orchestrated effort by the cancer cells and supportive cells to kill the host. And the literature supports that CCR5 has a potential integral role in each of these processes. So why is CCR5 so important? While we know that the following from research outside of CytoDyn and from our own research on leronlimab, we know that the CCR5 receptor levels correlate with poor prognosis in breast cancer. We also know that upon transformation of breast epithelial cells, the increased expression of CCR5 results in increased motility and homing behavior to metastatic sites. We also know that overexpression of CCR5 promotes tumor invasion, migration and metastases. So leronlimab's mechanism of action is unique in working at multiple aspects in the tumor microenvironment, and we are continuing to learn more about the effects of leronlimab on subsets of immune cells on a weekly basis. And I think what Chris just shared with you is a prime example of how that is very, very important to what we're doing right now. And each week, we learn more. The first is the conversion of M2 macrophages or pro tumor into M1 macrophages, which are antitumor. And we have some new evidence that leronlimab has the potential to cause macrophage repolarization. You see macrophages have plasticity depending on their environment, and they can work to fight the tumor or to help it grow and metastasize. We believe leronlimab has the potential to help macrophages fight tumors rather than to enable the tumor to grow. Second, we know that leronlimab prevents tumor angiogenesis in animal models. Remember that CCL5 RANTES promotes VEGF-dependent angiogenesis, the formation of blood supply to support tumor growth, and I'll tell you more about this shortly. Third, the literature supports the Tregs, which turn off the immune system's ability to fight cancer in the tumor microenvironment is mediated by CCR5. And Tregs turn off anti-tumor cells, such as cytotoxic CD8+ T cells. Fourth, we also know that CCL5 suppresses cytotoxic T cell activity, increases recruitment of Tregs and promotes tumor angiogenesis. Fifth, we know that leronlimab binds to see CCR5 on human breast cancer cells and blocks CCL5 calcium mobilization. And this brings me to the synergistic opportunities for leronlimab with other therapeutics. Just as with HIV, cancer is often treated with multiple agents and the physicians and pharmaceutical companies are looking for new agents with a favorable safety profile that show enhanced efficacy. How might this work for leronlimab in the real world of oncology? Let's start with DNA-damaging agents. The presence of CCR5 augments resistance to DNA-damaging agents and is sufficient to induce cancer metastasis. CCR5 antagonist enhanced cell killing of cancer cells by DNA-damaging therapeutic agents. This is why we believe that pairing leronlimab with a PARP inhibitor makes intuitive sense. There's also the potential to lower the dose of radiation and chemotherapy. We're finding that CCR5 inhibitors enhance cancer cell killing by radiation and DNA-damaging chemotherapeutic agents suggests the potential for combining leronlimab with chemotherapeutics. This could potentially reduce the dose-dependent side effects of chemotherapy and improve the quality of life of patients. Remember, chemotherapy causes increased CCR5 expression and CCR5 overexpression is also associated with chemotherapy resistance. Now let's look at checkpoint inhibitors. There was a study called the COMBAT study and it combined the CCR5 antagonist with anti-PDL1 inhibitor and it stopped tumor growth and improved overall survival in pancreatic ductal adenocarcinoma xenograft. Remember, pancreatic cancer is one of the most difficult cancers to treat. I feel comfortable telling you now that we are excited about this opportunity, and we will be evaluating the combination of leronlimab with checkpoint inhibitors. And I do have a contract that I'll be signing today in regards to this. We're also going to be looking at antibody drug conjugates. Antibody drug conjugates are like missiles that attach to cancer cells and deliver chemotherapy in a targeted fashion. Leronlimab could work to control the tumor microenvironment while antibody drug conjugates complete their task. So what brought us to where we are today in the use of leronlimab in oncology? In the lab, we saw that leronlimab was shown to bind to CCR5 in multiple breast cancer cell lines. In fact, the efficiency of leronlimab binding to CCR5 positive human breast cancer cells was up to 98%. Leronlimab blocks human CCL5/CCR5-mediated signaling in human breast cancer cells, it blocks human CCR5-mediated signaling by CCL3 and CCL4 in human breast cancer cell lines and it blocks CCR5-mediated invasion of human breast cancer cells into the extracellular matrix. Now I'd like to talk to you about some animal studies that -- some of this has not been released to the public previously. We had a colon cancer model study at the Cleveland Clinic. This is what we found. Leronlimab delayed tumor progression. We saw the tumor volume in humanized mice was significantly delayed. We saw that leronlimab prolonged survival and decreased the liver metastatic burden by 59%. It also decreased the lung metastatic burden by 87% in leronlimab-treated mice. We then looked at a breast cancer model. Leronlimab reduced lung metastatic burden by greater than 98% at 8 weeks. But then we looked at why tumors were not growing while on leronlimab, and we try to understand the mechanism of action further. We looked at the blood supply to tumors and how it affected angiogenesis or the formation of a new blood supply in a colon cancer model. Blockade of CCR5 signaling with leronlimab clearly interfered with host processes required for neovessel proliferation surrounding growing tumors. Remember, in order for a tumor to grow beyond 2 millimeters, it needs a new blood supply. And this is what I want to share with you today. Leronlimab reduced angiogenesis significantly, including a 62% reduction in total vessel area, a 53% reduction in vessel linked density, a 61% reduction in number of large vessels, and most impressively, an 80% reduction in the number of small vessels. All of this work has led us to where we are today in human studies of triple-negative breast cancer and our Basket trial of 22 potential cancers, our compassionate use, our right to try, our emergency INDs of other tumor types. It's one thing to work in the lab in animals, but it must correlate with the clinical response in humans. We looked at 30 patients with metastatic triple-negative breast cancer receiving leronlimab as part of emergency use -- compassionate use, our metastatic triple-negative breast cancer trial and our Basket trial and looked at their clinical outcome data available for 12-month analysis. We found that 72% of these patients had a decrease in CAMLs after 30 days. We found that 73% of 30 patients had either reduced circulating cells after induction or at small circulating cells at baseline and have significantly better median progression-free survival and median overall survival. Leronlimab appears to have efficacy superior to the standard of care in specific populations. We've also had encouraging anecdotal evidence in breast cancer, colon cancer, prostate cancer and bladder cancer from patients and from their physicians. So when you take the laboratory data, the animal models and recent human data, I believe that the future of leronlimab in oncology is brighter than it's ever been. Nader?

That's fantastic. And we are hoping that Dr. Kelly will put a lot of this in a PowerPoint and put it on our website shortly as soon as possible. So let's go to the next slide, Slide #15, please. This is the last slide before the manufacturing slide. So I just want to show everybody how we raise funding. So at the first few slides, we show that it takes about 7.5 years from Phase II to begin approval according to conservative time line. During the last 7 years that we have been in clinic -- clinical trials, we also had to raise tremendous amount of funding. But I have highlighted 3 years, the years that the leadership had -- was changed, and then we had to come and clean up the problem that was generated. Just in 2018 and '19, because of those change of leadership, we had to use 405 million shares just to raise $105 million or so. Next 1.5 years, when the leadership was left alone to do what it needs to be doing, the management team, we raised $198 million with only 49 million shares dilution. Pay attention, please, to these numbers because it will come and bite every shareholder if these numbers were going to be the same as before. That mean we would have been sitting at $1.5 billion dilution if we had not done everything perfect to get us to this point. And let's not take anything for granted. The team had to do a fantastic job, and I'm surrounded by beautiful people who have done that great job and was able to give us enough test to show to the world that, yes, we do have potential in COVID-19. We do have potential in cancer. We do have potential in NASH. We do have potential in HIV in all populations of combination, monotherapy, prevention. This is not a small task. Let's go to the next slide, please, the last one. That's our manufacturing, Slide #16. What would we do without having manufacturing perfectly taken care of? When we were first going to sign with Samsung, one of the Board members told me, how in the world are you going to come up with $25 million in 3 weeks -- or I'm sorry, 3 months if you sign this contract, which won't give us any product for another year or so. I said we always have to plan ahead of time. If we don't, we will fail. Today, we are sitting at over 1 million vials. The value -- potential value -- potential revenue value is almost close to $400 million that we have generated with your money, your -- the shareholders' money. While we spent $400 million to get 30 indications close to where we are, we also generated almost $400 million worth of revenue -- potential revenue that this product could have. So with that, let us go to Q&A, please.

Yes. Okay. First question. What is the status of leronlimab in the Philippines?

So we are very excited that we are now back on track and on Tuesday, I was delighted to see another PO larger than the first PO. And I'm hoping we can get to the point where we have 1,000 to 5,000 vials a week. We are not there by any means, shape or form, but we would get there if we continue this path that we are on.

Okay. Next question is related to the BLA. Is the BLA going to be completely submitted in October?

So as we got the comments from FDA, we were delighted to see that there are things that we can do to fix the problems that we had when we got refused to file. Most of the problems, we believe, we can be in a different CRO that could give us more time. The other CRO we are -- did a great job in Phase II trials, and we are very happy with those kind of things. But getting to the BLA was something that we were not getting what we needed. And Dr. Recknor was very brilliant by moving us to the position where we now can have a potential successful BLA submission and hopefully potential approval. But don't take this lightly. We cannot give time lines at this time until we have all the comments that the FDA said gave us, that we said it's doable, but we have to get time lines. So once we have those time lines, we will be sharing it with everyone.

Okay. When is the next long-hauler study going to be submitted to the FDA?

It already has been, and I want to thank Dr. Recknor for his brilliant work again by submitting that already. It was submitted, I believe, yesterday. Dr. Recknor, was it yesterday or today?

It was yesterday.

Yesterday. He's always ahead of me.

Next question. Please explain the long delay in starting the clinical trials in Brazil, which I believe you touched upon briefly a few minutes ago.

Yes, it's about -- it's okay. I want to make sure everybody understands, we are on pins and needles always trying to get things done faster, faster. Getting it signed a contract with a pharmaceutical in Philippines, I think, sticking up, we wrote an article, I don't know who the author was even, and they said that, how did I get a deal done within -- that takes about a year within a few weeks. They're very impressed. I appreciated that article. But we got that deal done without a pharmaceutical contract. We couldn't go forward. We got that. We got the right CRO that had credibility. They did trials with Pfizer for vaccine, and then getting the drugs to get there, going through ANVISA and getting everything they asked for was very, very difficult task. And I'm so pleased that we now have 2 trials. One already started. We are now in Brazil, the time is starting right now. It's ticking away. And every day, we're getting closer to a result that we were waiting for all this time, a result that we believe we could have got if we had done the right change of primary endpoint in CD12. But we didn't have a receptor occupancy and a lot of things that was not given to us due to many factors that hurt us in CD12. And therefore, we are now believe that we're going to be able to do the right thing. Go ahead.

Okay. What is the status of leronlimab in India?

So we started a very beautiful project with them. However, the cases of COVID-19 very soon drastically dropped. The pharmaceutical that we made a contract, we -- was not a CRO. So therefore, we needed a CRO to be linked to them. That would take a lot of time. But having 2 fantastic trials, we got everything we want in Brazil, the primary endpoint that we were looking for, for injection that we were looking for. Once you have those 2, you don't need to have 2 more trials some other country in parallel. It's a waste of time and money in our opinion. So we are holding. However, everybody should know that cancer, HIV, NASH, all of those can be pursued in India because we do have relationship with this pharmaceutical as we speak.

This next question is for Dr. Pourhassan and Dr. Kelly. Why have neither of you made open market purchases of CytoDyn stock at the current low level?

So I'll go first because this is a difficult question, I guess. I hate to talk about what I was blessed to do for the company, but I'm going to go ahead and say a few things. When I first started in this company, when it was in the brink of bankruptcy, I took no salary for a year. And I used my wifes money, credit card to go door to door, raise money to make sure this company doesn't fail. And at that time, my wife invested everything we have saved, we invested in CytoDyn. At that time, it wasn't like as good as this is. Currently, I have asked the legal team several times, can I invest -- I want to buy shares right now. And every time the answer has been, you're in position of inside information, and you have to wait. But buying shares in the open market is not what we are all about. I want to buy. But we don't know what it's about. It's about getting the clinical trials done. We're getting a couple of million dollars worth of trading right now. When I first got involved with this company, it was like $10,000 per year or something -- or $1 million per year trading. Now we've got $2 million a day. What if I have to buy $10 million worth every week, it is ridiculous. But Dr. Kelly how about you.

Yes. No, there's certain times we can purchase and certain times we can sell. We're currently in not 1 of those periods. I will say that I have made significant open market purchases in the past as has my wife.

Thank you. Good.

Next question. Have there been any new sales of leronlimab in the Philippines?

Well, we just got the PO and we're hoping that Mr. Antonio will be reporting on those at some point when we get to a certain level. Next, please?

All the HIV BLA issues seem to be due to combining the multiple doses of the monotherapy data with the original 350-milligram data. Is it possible to file the BLA with only the clean 350-milligram data from the original trial, then run clean, higher dose trials for monotherapy and combination therapies after approval?

So first of all, people who don't know about leronlimab's history, please note that if we were going to give safety -- required safety to the FDA for BLA, for combination therapy at 350 milligrams, we would need 500 patients from that population. It took us 3 years to enroll 50. It was difficult enrollment. So 500 million will take us another 38 years. So the answer would be no for that reason. But the next reason is we already show that we have better efficacy with 700 milligrams. So FDA says it's reasonable to give these people 700 milligrams. Our team, which is very strong key opinion leaders, scientists and all of that, they look at everything. We don't make a decision based upon one person's decision. It has to be collaborative situation. Go ahead.

Next question. Can anyone explain what the latest clarification from the FDA was on the dosage justification for the HIV combo trial BLA.

Among other thousand things that we are doing, we are also taking care of that. And because Dr. Recknor is getting overloaded, we now are bringing our new regulatory person and Dr. Nitya Ray to help with that. And we are working on all those comments, and we will have time lines -- exact time lines when we are ready.

Will the long-hauler Phase III trial have a placebo arm? If so, will the placebo arm be promised access to leronlimab after the trial has ended?

Dr. Recknor, do you want to answer that?

Yes. As we currently have designed per FDA, there is a placebo arm, and we want to be able to provide access to patients that did not get after the trial. That is our intention.

Perfect. Next question. With COVID cases at an all-time high, why is leronlimab not being used in the Philippines? Please explain what exactly went wrong.

Nothing went wrong. Everything went right, that's why we are selling and we have sales. We have revenue. It's small. It's very, very small, but it's revenue. And we are moving forward with every one of these projects that we have closer and closer to the finish line. We're building a mountain of indications, and this mountain is getting closer and closer to a very fantastic finish line.

What is the plan for funding for all the studies going on.

So whenever you talk about funding, everybody will tell you, I can raise you $1 billion easily. It's called talk is cheap. So I'm not going to tell you I'm going to raise another $100 million, $200 million, but I'm going to do fund something, though. I'm going to tell everybody about the history of what we have done. Thanks to God. We raised $400 million for [ OTCB ] company. I'm not talking about a NASDAQ company, where you go to institution and you get to trade because they have tremendous arms to be able to raise your fund. We have raised $400 million. I hope this is a story of what we have done will be told as in the future, how to raise money when you're at $0.30 level so you don't get diluted the way we did when we had the change of leadership. So we are going to do what we have done in the past, and our resume speaks for itself. Next please.

Would you be able to provide an update regarding the financial health of the company as it pertains to the loan payment schedule?

Yes. I can take that one.

Yes, please.

So we filed an 8-K yesterday which we provided an update that we fully retired the November 2020 convertible note, which was for $28.5 million. The April 2021 notes of $28.5 million remain outstanding. We don't provide any sort of updates outside of public filings, so you guys can reference our 10-K, which we filed on July 30. And our upcoming 10-Q will be filed no later than October 12, which will provide additional information as well.

Next question. Welcome to the team, Seenu. What is the role of Seenu in getting the BLA completed? And what's his future role? How did this hiring come to be?

So all the good things that happens to this company somehow it has something to do with Dr. Nitya Ray. Every good thing that I can think. This is a person that I feel so close, Scott does too, and he's our brother in every way, shape or form. So Dr. Nitya Ray searched for that person and Seenu being an ex-Regeneron person, has tremendous talent, and we can't wait for him to help us with many aspects of BLA submission and other regulatory affairs. However, he's hired for the CMC part. He does have clinical experience somehow, but he's also helping us to now bring a regulatory person for the clinical side. We're also bringing an inside -- in-house biostatistician, bioanalytic. And we will have our own regulatory person, obviously, for the clinical activities.

Does the company believe the underlying mechanism of action of NASH is also similar to long-haulers?

Dr. Recknor, please?

Yes, we're learning a lot. So we're actually looking at biomarkers in the NASH patients like we have looked at in long-haulers. I think that from a clinical development standpoint, it's critical to be able to understand the mechanism of action as that affects us also with the design of trials. So for example, in our cancer trials, through TNBC, we know that 700 is the dose that we prefer. In the NASH, we're looking at a different dose as a Phase II. And in the long-haulers, we may explore that as well in the second study, the CD18, that we do.

Okay. Hold on. Go ahead.

I'd just also like to say to everybody, I mean, I've been with this company for quite some time, as everybody knows. And I can assure you that I have never seen the amount of progress in regards to the mechanism of action that we have made over the past 4 months now. It's just really mind-blowing. And a lot of that credit goes to Dr. Recknor, Jonah Sacha, Scott Hansen, all these people that have been really, really instrumental in helping us with this. And with NASH, we are learning a lot more about the disease. What I will tell you is stellate cells are really what produce scar tissue in the liver, and we know for a fact that they're loaded for CCR5. So we're very encouraged about the potential for NASH moving forward.

Next question. Are the Brazil trials designed to achieve the fastest results?

Absolutely. As we said in the critically-ill population, passed the study 166% better in leronlimab versus placebo in discharge from hospital was fantastic, yes.

Okay. The next question is rather long. With funds as tight as they are for the company, can you please explain why you're spending presumably large sums of our precious resources to fight the proxy group. I am by no means advocating for them but what they are doing is a normal, if not common, aspect of being a public company. If you are so confident in what you have achieved and are about to achieve, then I would think that you would be similarly confident in the outcome of a proxy vote, spending large sums to prevent an otherwise normal thing from occurring makes it look like you have something to hide and are just struggling to hold on to power. With all due respect, that's not a great look.

So thank you for the question. This is Dr. Scott Kelly's fault, not mine. As the Chairman of the Board, he has to follow the rules and regulations of a public company. When -- I already told him, I'd rather let the shareholders vote, I told him about 10x, let's not do anything, but he has the obligation to the shareholders to -- whenever there is a situation like this, to have the right attorneys to come in, and we have to follow that protocol. We can't do things based upon what emotional feeling we have towards anything. But shareholders own this company. Whenever they vote, we will follow exactly that vote. That's what we're going to do. Next.

For me, I consider the HIV BLA to be the most important discussion topic for today's conference call. What is the exact status of the HIV BLA to include the status of the various modules that compose the BLA? And do you expect to meet the October 15 deadline? If not, then when?

So when a person doesn't answer the question straight head on, that means the answer is probably no. But let's leave it at that. October 15 is for BLA submission. But October 15 also could be the date that we will read the results of COVID-19 to get emergency use authorization. If we do get that, do we have enough vials? No. [ 1.2 million, 700-some thousand ] is already dedicated to a contract that we signed in Brazil, and if we won't have any. So the most important thing for us is to make sure our manufacturing is ready to make enough vials because the success is coming and it's coming in a big way, in my opinion. Now BLA, if we are delayed 1 month, 2 months, we will give you the exact time line. But we have to get the contracts signed to do the certain assays that the FDA has asked us to do. And if those are 100% coming to be October 15, we'll announce that. But if it's December 15, we're going to announce that. But you guys have to be patient. There are 30 indications, remember that. The one that's very close to getting approval is not HIV. It's called COVID-19. This is 2 months or 3 months from today. We could have interim analysis readout. That's powerful. Next please.

Are children doses being looked at for possibilities? Is there any data to suggest any appropriate dosage for a child?

I'll take that, Mike. So we're not studying this currently, but we certainly plan on doing it in the future.

Okay. Next question. Where is the long-haulers full data? Why is it taking so long for it to be made public? Where are we with Phase III for long-haulers? Why has this not started yet?

I know -- when you do 30 indication, and it takes 12 years to get approval, that's 360 years. We're doing this in a speed that we are very, very happy with. Dr. Recknor is working. I believe he sleeps 2, 3 hours a day. I'm going to be talking to him about that. But having said that, he already submitted the report, CSR, to FDA. He already submitted the protocol. As soon as we hear from agency, then we will let everybody know. And then everybody gets to see the protocol also.

Okay. Have we submitted for breakthrough therapy designation for metastatic triple-negative breast cancer? If not, when are we going to do that?

So I'm very frustrated with that also because we have the application ready. Everything is set to give to the FDA. But this is cancer patients' lives, and I have pleaded with our CRO, the past one, to give us the sequence and they haven't. So we are forced to go and find the sequence from some other way, which is going to delay it. And I'm hoping that delay is not more than a couple of weeks or so, but we have to wait and see.

Next question. Are you currently working with a PR firm?

I'll take that. Yes. Sloane & Company is our PR firm from New York City.

What is the difference between receptor occupancy and tropism, which is needed for the BLA?

So tropism test is something that was put in place when maraviroc got approval in August of 2007. So that process has been set for a long time ago. Tropism is taken -- so we know that the patient is pure CCR5 and the virus is R5. But in this test that we are doing, receptor occupancy is needed so that they can see that all the receptors are occupied. So it's a whole different process. Next, please.

What are your thoughts on leronlimab as a monotherapy for cancer versus partnering? If partnering with another drug, which do you believe it pairs better with? Are you speaking with any companies in that regard?

The answer is yes, we are speaking to major pharmaceutical companies about that as well as major academic institutions. In fact, like I told you earlier, I have a contract on my desk to sign today with a major academic institution. I think, as I said before, I think a checkpoint inhibitor is a logical pairing partner, PARP inhibitors, chemo, antibody-drug conjugates, all of the above. I don't think that we'll see any significant drug interactions. And I think that we're looking for a synergistic therapeutic benefit with any of these agents. And as I said before, a lot of times, cancer pairs multiple agents together. You don't always want to use this as monotherapy. That being said, we have had patients that couldn't tolerate other -- again, this is anecdotal, I'm thinking off the top of my head about a bladder cancer patient, but some have not been able to tolerate other agents well and have been on leronlimab as a monotherapy and done extremely well. So we're looking at all different aspects of whether we pair or monotherapy, partnerships, academic and major pharmaceutical companies.

Okay. Yes. Due to time constraints, this will be our last question. Dr. Kelly, why have you not replaced Dr. Pourhassan as CEO?

Okay. I'll take this on. I want people to understand that this is not a new concept. Leadership, as Nader mentioned earlier, was changed during 2017 and 2018. And to say the least, it was a very, very challenging time for CytoDyn. Now I guess I can tell you this now, what people don't know, and this has never been made public before, is that I did call for a new CEO search. It was late October of 2019 and continued into the first quarter of 2020. And I want to be very clear with people, I made this decision. It wasn't a reflection of Dr. Pourhassan's performance at all. I told Nader the truth and the stock was basically at $0.30, and I was very candid and he understood. And this is what I learned through that process that I'll share with you today. First of all, there was no guarantee that any CEO could raise the funds necessary to implement our ambitious strategic plan, and Nader alluded to this earlier. A lot of times, people will tell you what they can do. I think Nader has a proven track record in this regard that anybody would have a difficult time refuting. It was also recommended, which I found very interesting, and I think this is important as well is that not to bring in the new CEO unless Nader agreed to stay for a minimum of a year. And the reason for this that people don't understand is there is a tremendous learning curve to this company to all the different 30 indications. The past history of the molecule, the CMC, the nonclinical, the BLA, the different opportunities, where leronlimab will work, where it will not. So I literally begged Nader to stay if we were to hire a new CEO and he agreed. I'm not so sure he would do it again, but he did agree to that previously. And the other thing that we were a little bit surprised about is that the new CEO would require significantly more equity in the company than Nader has ever received or was receiving at the time. And so during the CEO search, Nader backed off, and we were looking around for the right people to get involved and the company struggled until I had to go back and ask Nader to step in and resume control of the company. So I will tell you this, Dr. Pourhassan found the molecule, he purchased it for $3.5 million, he turned it into a potential multibillion-dollar company. As we said earlier, it now has 30 different indications. He's raised over $400 million, and we have about $400 million in inventory, potentially, with our current contracts. So if somebody has an idea of a candidate that equals that, that has really accomplished these same things, I would love to meet that person. So I'll leave it at that.

Thank you. Thank you, everyone, for being on this call. To wrap it up, I'm just going to say that please note that the most important thing for us right now, 2 COVID-19 trial in Brazil. We are hoping to have interim results this year, the sooner the better. We will give you time lines. Any day, we will be announcing first patient injection. The trial has started officially and is screening that CD17. CD16 will hopefully do that next week. We have long-hauler trial that we have submitted a protocol to FDA, waiting for that. We also have breakthrough designation that we are hoping to file for cancer. And our HIV, again, we will update everybody as we go forward. Have a great day, everybody. Bye-bye.

Thank you. This concludes today's call. All parties may disconnect. Have a good day.