CytoDyn Inc. (CYDY) Earnings Call Transcript & Summary

Greetings, ladies and gentlemen, and welcome to CytoDyn's Investment Community Webcast. [Operator Instructions] Please note that this webcast is being recorded. I will now turn the webcast over to 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 webcast is our President and CEO; Dr. Nader Pourhassan; our Chairman, Chief Medical Officer and Head of Business Development, Dr. Scott Kelly; our Chief Operating and Technology Officer, Dr. Nitya Ray; and our Senior Executive Vice President of clinical operations, Dr. Chris Recknor. Before we begin today's presentation, it is essential that we provide you with important cautionary language related to certain federal securities laws. Today's presentations and remarks made during today's presentation will include certain forward-looking statements that involve risks, uncertainties and assumptions that are difficult to predict. Words and expressions reflecting optimism, satisfaction or disappointment with current prospects as well as words such as believes, hopes, intends, estimates, expects, projects, plans, anticipates and variations thereof or the use of future tense in identifying forward-looking statements, but their absence does not mean that a statement is not forward looking. Forward-looking statements, specifically include statements about leronlimab, its ability to provide positive health outcomes, the possible results of clinical trials, studies or other programs or ability to continue those programs, the ability to obtain regulatory approval for commercial sales and the market for actual commercial sales. The company's forward-looking statements are not guarantees of performance and actual results could vary materially from those contained in or expressed by such statements due to risks and uncertainties, including the regulatory determinations of leronlimab's efficacy to treat HIV, COVID-19 patients, cancer patients, NASH patients, NAFLD patients among other indications of the U.S. FDA and various drug regulatory agencies in other countries. The company's ability to raise additional capital to fund its operations, the company's ability to meet its debt obligations, the company's ability to enter into partnership or licensing arrangements with third parties, the company's ability to identify patients to enroll in its clinical trials in a timely fashion, the company's ability to achieve approval of a marketable product. The design, implementation and conduct of the company's clinical trials, the results of the company's clinical trials, including the possibility of unfavorable clinical trial results, the market for end marketability of any product that is approved, the existence or development of vaccines, drugs and other treatments that are viewed by medical professionals or patients as superior to the company's products, regulatory initiatives in compliance with governmental regulations and the regulatory approval process, legal proceedings, investigations or inquiries affecting the company or its products, general economic and business conditions, change in foreign political and social conditions, stockholder actions and proposals with regard to the company, its management or its Board of Directors and various other matters, many of which are beyond the company's control. The company urges investors to consider specifically at various risk factors identified in its most recent Form 10-K and any risk factors or cautionary statements included in any subsequent Form 10-Q or Form 8-K filed with the SEC. Except as required by law, the company does not undertake any responsibility to update any forward-looking statements to take into account events or circumstances that occur after the date of this presentation. I will now turn the webcast over to Dr. Nader Pourhassan.

Thank you, Antonio, and thank you, everyone, for being on this call. Today's presentation is to update everyone about what we will be looking for to have in [ 2020 ]. Our future with 4 important indications, HIV, NASH, cancer and COVID-19. Our drug development plan will be explained by myself, Dr. Nitya Ray, Dr. Scott Kelly and Dr. Chris Recknor; and our finance, Mr. Antonio Migliarese will be on the call. So far, we have had problems with our CRO so we have come up with new CROs. We have signed an agreement, thanks to Dr. Recknor, leading that project and Dr. Ray. And our new team, we are hiring very important people in very important positions. For example, we have hired a biostatistician and I'm honored to let everyone know, it's Dr. Alok Krishen, ex-GSK. We also got hire -- we were able to hire a bioanalyst, Dr. Darshana Jani, who's ex-Pfizer person. I know we hired recently clinical regulatory person, Dr. John Andrews. Now Dr. John Andrew is [indiscernible], but he's the first -- he was part of the team that brought the first drug approved for HIV, AZT. And then he also was part of the first cocktail that was approved with HIV. So he's very knowledgeable. We really need his expertise for our clinical section that we're going to be filing. And we also already have Dr. Seenu Srinivasan, and that's from CMC regulatory. A lot of credit goes to our Dr. Nitya Ray for hiring these talents. And we are hoping to let you know today, what to expect in 2022. So when I explained what we're going to do in 2022, we should answer some questions. When did we initiate each program that we have currently? Whatever we have right now, when do we initiate it? We initiated a lot of programs. What happened to them? What did we get to? Did we do positive things with that or we just started something just for the sake of starting. And then we should answer the question, how far have we advanced each program? Do we -- were we successful? And what is our 2022 outlook for each program? Based on the past progress, how far can we realistically take each program in 2022? That's very important. That's why I'm going to start with what we have started. And where is that program now, and where we think it's going to go in 2022. The shareholders should base upon their decisions about our company based upon in my opinion, where we started each program, where we took it and can we take it further. So with that said, let's look at what we had in 2013. We only had 1 team in 2013. The only thing was we purchased leronlimab. In 2014 and '15, again, on task, 1 major task. 2014 was HIV monotherapy Phase II. That's all the company had. And then we added GvHD Phase II. Then we added in 2016 one task HIV combination therapy Phase III. Now one of these tasks is good enough to have one biotech company and just get that to the finish line, and that would be a huge success. So when we add one more in 2017, we didn't drop the ones before that. That's why I put this picture together. We continue the progress of the old one, but we keep adding to our workload. And that in 2017 was monotherapy for HIV program. I talked a lot about HIV program monotherapy. That was something we were very excited, and we still are very excited. In 2018, we had one more. Instead of just continuing with the last 4, we had added another program, we entered the cancer arena. Metastasis triple-negative breast cancer, Phase 1b/2 was granted to us by FDA. 2019, we added one more program NASH, and we will talk about that. Thanks to Dr. Chris Recknor and we have a lot to say about that today, and he does too. In 2020, all of a sudden, we added quite a bit more, 3 more, this is not normal -- this is not normal for a biotech company to keep adding more things. The reason we're adding all of these is because leronlimab keeps showing positive and is put the burden on our team to keep carrying these new tasks, and we're doing that, but we're not dropping the ball in the past one. So in 2020, the 3 tasks were -- we actually realized leronlimab is working on the mechanism of action that can have effect in '22 solid tumor cancer in our opinion, our animal study showed this. And we -- pandemic starts, so we did 2 trials in moderate and severe and we completed those trials. In 2021, 5 tasks were added. I mean, if you see that -- we did long holders, thanks to Dr. Recknor single-handedly. Brazil 2 trials, U.S., we just filed the critical year population, and we are revisiting the monotherapy situation, which is we already had given the Phase III protocol to the FDA, but we're just going to now finalize that protocol. Now -- so from 2013 to 2021, what we're going to say about 2022, it's very important that people look at what we did in 2013 to '21. And if we're not capable based upon that, then that's something that shareholders should know. But if we are, they should pay careful attention, very careful attention in my opinion, in my humble opinion. In 2013 to 2021, all the programs that we did is right here. This is going to be on our website. People, please go look at it. We completed the monotherapy Phase II. GvHD positive. It was a small population compared to other ones, so we paused that, and we had problems with our CRO. But the combination therapy HIV, our main part, we had a primary endpoint statistically significant, and we continue with Phase III monotherapy with 600 patients almost, and we have got fantastic results that we reported constantly. But that Phase III monotherapy was not a pivotal study. We need a pivotal study to get approval. Metastatic triple-negative breast cancer. We found a breakthrough designation, how many companies get to do that. We generated data that was very strong, and we talk about it. NASH, we completed -- we're going to talk very quickly about the rest of them, but you can see yourself, and I'm not going to go to it that we complete projects that we start. And if Brazil, we are now running to problems with enrollment, what's the chances of us being able to solve that problem? Well, the chances are what we have done in the past, when there was a problem with monotherapy Phase III, FDA says, stop, you need to have higher responders. We solved that problem, thanks to God and the beautiful team that we have. When we had problems with the other indication, what do we do? We solved the problem. We want to be solving the problem with Brazil also. We will get to it at the time that we talk about that. So 2022, we don't have 3 or 5. We have 8 new tasks that our team are going to talk about right now. So the first 1 is HIV/BLA submission to FDA. The tremendous miss that we had from our Amarex folks was cleaned up most of it with Dr. Chris Recknor, that took a lot of his time. If you should ask how many hours did he work, I will say quite a bit. So I'm going to ask Dr. Nitya Ray, who took over that because Dr. Chris Recknor is working on too many projects and we will get to those projects that are very exciting in a minute. But Dr. Ray explain to us, please, where we are with BLA for HIV.

Right. So the HIV/BLA, we have submitted the nonclinical and CMC modules. The last one is submitted CMC module by the end of last month. So we are working very expeditiously to finish the clinical module, Module 5 -- and we have solved some of the issues, the technical issues that we faced with the receptor occupancy assay. So the method is working but we are in the process of validating the method. Once the method is validated, we'll be analyzing the samples, and we are very confident that we are going to make it. And as you know that we had -- previously, we had lot of issues with the receptor occupancy assay. To be honest, it is not a simple assay. It is pretty -- it's a difficult assay to do. And given that the dynamics of the receptor, CCL5 receptor because they're internalized. And -- but we are solving it, we are working with a CRO, very well-known CRO. And we have also hired internally. We have strengthened our team that Dr. Pourhassan was talking about Darshana Jani, she just joined this week, and she is an expert in this area. She will be responsible for Clinical Biosciences. And she has worked with many CROs, on the receptor occupancies, she's an expert in this. She is well known in that community -- in the scientific community. And she joined our team, and I'm very excited about that. And she'll take full responsibly to make sure that will get it done on time, and that will meet FDA's expectation.

Thank you so much, Dr. Ray. And the fact that you were able to find these great talent for us, we're very thankful. But I think each one of them have expressed to you how excited they are with a molecule. Am I right about that?

Absolutely.

All right. So the HIV Phase III pivotal monotherapy. When we started that trial, we were hoping to have a higher responders, we got that, and we went -- we find out Phase III with the FDA. So why didn't we go forward in that? A good question would be where is that program since we filed that with the FDA. Well, FDA at that time had very limited data from us. They wanted to get more understanding of the monotherapy. This is not an easy thing because [indiscernible] to take people out of their current regimen. What's going to happen if they don't make it, they fail, the viral load fails. Do they go back to their original regimen safely. That was number one question. Do they get resistance to maraviroc, maybe? Do they lose a component of their regimen. We answered those questions because FDA is very specific about those safety issues. And FDA was happy to let us do a large trial. And at large trial, we needed more responders. Now the new protocol, this is where we are discussing with FDA in the new protocol, there are superiority trial or non-inferiority. We then have to do those with the drugs or we have to do it with a monotherapy by itself with a couple of arms, perhaps 350 arms versus 700-milligram arm. It will be an induction maintenance protocol and we're working with FDA to hopefully be able to do it by comparing lower dose with higher dose in monotherapy and have an induction and maintenance. Induction, we will look at the patients more closely, perhaps every 2 weeks, first and then every 1 month for the viral load. And then realize the maintenance should represent every 3 months viral load check. So those things we will be finalizing and then we believe we're going to be able to hit our primary endpoint with Phase III because we have seen a high responder rate, specifically after 24, 30 weeks in all the arms. So the next task is long-haulers. I was approached by Dr. Chris Recknor that he said he really likes to do a long-hauler study, and I originally told Dr. Scott Kelly. I'm not really big on it, but Dr. Scott Kelly indicated that Dr. Chris Recknor knows what he's talking about, you don't. So I listened to him and we started the long-hauler trial. And the results -- everybody saw in 56 patients what we got, but Dr. Recknor tell us where we are, give us a little bit background about it and then tell us whatever you can, please.

Sure, Nader. So the background is that in CD10, we didn't have a specific time period from when they COVID. And back when COVID was first starting up, and we were doing CD10, CD12, we were actually looking at long-haulers in those patients. And we observed that several of those patients improved after leronlimab treatment after the unblinding happen, we saw who got and who didn't get. So then we started looking at doing a long-hauler trial, which led us to the exploratory trial, which showed excellent results from symptom reduction in these patients. And we're further honing down what we're looking at with patients. The majority of problems that long-hauler patients have are cognitive fog and fatigue, and we're really going to be focusing on helping people with that, especially given the fact that we across the blood brain barrier and in mechanic studies, we're at 75% receptor occupancy in the brain. So we think it will help.

So where are we with the protocol that you submitted to FDA for Phase II or Phase II-III? I think they said no Phase II-III, Phase II. Where are with that?

Yes. So FDA gave us additional comments. They actually put it out for 3 different divisions to help they came back with some excellent remarks, which we have adapted, and we're getting ready to resubmit that shortly to them. And I think that helped us both the FDA is helping us make a better protocol.

Who's our CRO?

The CRO for CD18 will be Symbio.

Okay. And the next program that we will be having results and have that as a main -- one of our main goals is NASH. Now with NASH, again, this was something that we -- I was for that. Dr. Recknor started that we were very happy, Scott Kelly, and I was against him adding 350-milligram arm open label. And thank God, he did not listen to me. Dr. Kelly always makes sure that Dr. Recknor gets his way. And because of that, we now have beautiful results to submit. So there are some people asking questions, which I'm going to ask to Dr. Recknor give us the detail of this NASH that we are so excited and why we're excited. And I'm going to ask you some questions that the short sellers are asking. But Dr. Recknor, explain to us about NASH, please.

So NASH is fat and fibrosis in patients that leads to liver failure and cirrhosis. And we noticed in animal models that we're reducing the fat in the animals by 75%. So that led to us starting the NASH trial. Our primary endpoint is looking at fat reduction because that's what we saw with animals. But in the open label, we're seeing excellent results with reduction of fibrosis. So it's known that when you reduce fat, you can get some fibrosis reduction, we appear to be doing both in the open label and soon to be locking database and where we'll see what happens with the higher dose of 700 milligrams.

Yes. And we know that hepatocytes and as well as -- you know hepatocytes contains CCR5, right? And we also know that the cells that produce scar tissue in the liver also contains CCR5. So we think we work by both mechanisms. That's what we're going to be seeing with the results.

And comparing this data that we have so far with normal placebo, it looks like we should be able to have the primary and secondary endpoint if you compare to the placebo, the data that I received for placebo from other trials that failed. But some of the short sellers, I believe, that's what I believe they are shorting the stock and then they're asking questions -- that is I think they're actually shorting their own brain because they're asking something that doesn't make sense to me. So Dr. Recknor, they're saying that 107 millisecond drop in fibrosis, CET1 is really nothing. Is that right?

That's a huge decrease in patients. And this study that we did, did not look at biopsy, that will be for the Phase III study but we wanted something that would be quick, that we could get results back and look at 350 versus 700 and see if we had a signal. In -- when you do biopsies, you're looking for about a 40 millisecond change, 80 millisecond, you're going to get biopsy changes that represent the decrease in that CET1 that actually, I think we'll get accentuation with the biopsy results in the Phase III. So 80 milliseconds is phenomenal. The most impressive thing though is this is in the severe -- we're seeing this in severe patients where we didn't previously think you could get resolution of fibrosis.

And the data that we said in the title was 80% of the patients had 50% -- I mean 50-millisecond drop and 50% had 80-millisecond drop average. Now somebody sent me a question thinking that I was writing a poem and I'm trying to match the poem, 50, 80, 80, 50. I wasn't trying that. This is the result. And this is what we're going to be showing to the FDA, hopefully, as soon as we underline the rest of it. Tell us about the underlining event, do you think we're going to have that because that's a huge event for us because of what we're seeing in the open label so far.

We're working on database lock right now shortly thereafter, we're looking at before Christmas vacation being able to produce a top line report. And this gives us the ability to look at what's going on with the 700-milligram dose, which I'm very excited to see and looking at the 350-milligram dose as compared to the placebo in the double-blind portion of Part 1. So we're really excited.

Yes. And some people are saying that if there is other NASH trials, they do 1,000 patients, so we probably need partnership, a 1000 or 2000 or 10 patients, if you had your primary and secondary endpoint, that's a huge deal. We don't know if we have because we haven't unblinded, but we're really waiting to see how that comes up. But the next task for 2022 is cancer basket trial, 22 indications. We have a lot of talk about patients who talk to Dr. Kelly. Dr. Kelly is involved with a lot of patients who want to get on leronlimab. And Dr. Kelly tell us a little bit why we are excited about this basket trial?

Well, we're excited about the basket trial. I'll start by saying we just presented at the San Antonio Breast Conference. When I say presented, there was a poster on December 10, and that was in regards to results with metastatic triple negative breast cancer in combination with carboplatin, CCR5 positive metastatic triple-negative breast cancer. And I'll tell you the reason we're excited about the basket trial is I think that there's a growing acceptance that the tumor microenvironment is the next frontier for immunotherapy. And I mean this among practicing physicians, the academic world is probably as well as big pharma. And I think we're more advanced than this. We've really been looking at the mechanism of action and the tumor microenvironment to see leronlimab's impact across multiple different oncologic indications. And we also think that we can pare this with a checkpoint inhibitor, chemo, radiation, antibody drug conjugates as well as maybe even a potential monotherapy in certain patients that don't qualify for other treatments. We think it goes down to the mechanism of action with Tregs and Tregs come in and turn off the immune system. We know that they have a high prevalence of CCR5. We can block that, we can actually maybe leverage the immune system. If we look at macrophage repolarization that's another potential opportunity. Our animal study showed a significant reduction in angiogenesis. I think it was 62% in total vessel area. An 80% reduction in small vessel area. But we know that tumors need a blood supply to grow. And if we can help limit that, then we think we could have benefit for patients. And the last is, obviously, we know that normal cells normally CCR5 is only present on immune cells, but we know that when cells undergo malignant transformation that they start sprout up CCR5, and we believe that's a contributor as to metastasis. So we have multiple different mechanisms, and we're continuing to find more as we go along that we're going to be evaluating.

Yes. And the breakthrough designation that we filed, Dr. Nitya Ray did a fantastic job on that. There were some patients with brain metastases. Dr. Ray explain to us for a breakthrough designation strategy, are we going to file for brain metastases and perhaps maybe later on, if we do get breakthrough designation on the original submission, maybe we want to ask for a basket trial with the data. But tell us about the brain metastasis data, please. Nitya, you are muted, please.

Okay. Can you hear me?

Yes.

Well, the breakthrough designation application that we submitted it, it had like 28 patients from 3 different trials. And out of the 28, I guess, 6 of the patients had brain metastatic disease. These are all metastatic triple-negative breast cancer patients. So we have submitted all the results, including the patients with brain metastases. Now it's with the FDA, and FDA is reviewing it. So we're waiting for the FDA response to our BTD application, and we expect to hear from them in about 2 weeks, 2 to 3 weeks. About 60 days after we submitted application, that was done I believe on November 5. So by January 5, we should hear from FDA. And then we are going to discuss with the FDA and see whatever forward with the brain metastasis. Now these are not the only patients with the brain metastasis because these are only patients with metastatic triple-negative breast cancers. So we have other patients in the basket trial that not TNBC have the brain metastasis. And so we are very excited about that what's happening with these patients. And so we are going to, again, we discussed with FDA, and we do plan after we received a response from FDA on the BTD's application that is submitted. We are going to plan for perhaps another BTD, just focusing on the brain metastases.

Cancer breakthrough designation that we filed, we should hear hopefully soon. And when this is going to happen in 2022. If the breakthrough designation is there, we will be doing -- if there is a need for Phase III or whatever it is, and we will move forward for approval. If we don't get breakthrough designation, we're still going to immediately do a trial of the magnitude where we can hit the p-value. [indiscernible] had a Phase 1/2, their data was strong, hopefully our data is strong enough to impress the FDA and get a breakthrough designation. But we'll know soon. The next 2 tasks that I have put there, I only put critically ill population for Brazil. But with the Omicron going to the roof right now, the numbers. We might even finish the severe population data [indiscernible] trial. So we might have 9 tasks that could complete in 2022 or initially in 2022. So the critically ill population where we are is -- we now have about 20 sites. Am I right, Scott, with Dr. Kelly, 20 sites we have about?

Yes. Right. We're adding more.

Yes. And I think they said that they're going to have about -- they could have up to 40 in the next 2 months after December, right?

Correct.

By end of December, we should have 20, 25. And if those sites are in place, in running 51 patients or 50 patients because 40% of 126 is 50.4%, so maybe 50 patients. But whatever -- that's not going to be a problem if there is a spike in the COVID-19 cases. Now people keep saying, why did you reduce to 50 patients, and this is going to -- you're not going to hit the primary endpoint. We explained our endpoint that we have is different at survival, and we already had powered the study based upon that data -- very valuable CD12 data. But if we do an interim analysis at 51 patients, and we don't have our primary endpoint, so we continue. As a matter of fact, we might do more than 126, you might do 200, whatever the DSMB give us. So this is not shooting ourselves in the foot in anyway, shape or form. And critically, I'm sorry, the severe population, COVID-19, that's going to go forward, and we will get the latest data and always update the shareholders with what we have. And the last thing we have is for the critically ill population that we just submitted to the U.S. FDA, we're excited to start that because, unfortunately, there are states in the United States where the ICUs are getting packed again. We want to hand down those states and open sites over there immediately and perhaps do our study. But we will be working with CROs. We are currently working with PPD. And where are we with those discussions, Dr. Recknor? You talked to them and I talked to them -- where are we dose with PPD?

We're progressing nicely.

I'll add about Omicron. It's interesting. We do believe this is going to be the dominant strain. We do believe it's going to be more contagious. We don't know if it's going to cause more severe disease. We just don't know that. But if you look, I mean if you look, I think it's already in 32 states right now. I mean this is how quickly this goes. So ultimately, it will think overcome Delta and be the most dominant strain. We just don't know if it's going to cause severe disease, and that's something that time will tell.

Yes. And the latest news yesterday Boris from England, the Prime Minister indicated that there was 1 death already from Omicron. And in CDC this morning said that the 3% of the cases in the United States are now from Omicron. So how much do you need.

So it's going to spread exponentially as we know. And then the other thing that I would add is that we don't know how that's going to affect the long-haulers I mean obviously, if you have a more contagious virus, there's a possibility that long-haulers might get even more than the 10% to 30% that's that people say is out there. And I mean, if you look where there is 271 million cases of COVID, so you're looking at well over 27 million patients that will be potentially affected by long-haulers.

So what I'm puzzle is -- I'm sorry, go ahead, Chris, please.

I'm going to say to that point as well, many of the long-haulers are those that have gotten COVID more than 1 time with different variants. We're starting to see that there may be a cumulative effect with the amount of exposures as well in patients.

And again, we don't know how these people are going to respond to the vaccination. So this is just the truth. We just don't know. We don't know yet.

And when I look at the whole thing, I'm so proud of our team that 2022, long-hauler, thanks to Dr. Recknor, we started already, have enough data to go forward with FDA and say we want to go to the next level. And having NASH, having cancer in our plate and HIV, hopefully approval for 2022 is very possible for us. I mean these things are amazing milestones, and we are very excited about 2022. So let's go to the next slide, I just want to show everybody that from all the way to 2020, every task that we added to our workload was continuously progress. And then we added 3 more tasks in 2020, 5 more in 2021 and 8 more in 2022. So this is what we have. This is the data that the shareholders make when they look at the company and look at the fundamental what we have. And with 2022, I believe we are going to be able to -- very hopefully have results in December, our NASH trial, still not 2022 yet, but the NASH trial results, we believe we can report this year and breakthrough designation, we might even get answers if we get it sooner than January 5, it could happen this year. And the rest will be 2022. So with that, does anybody in the panel have anything to add, Chris, Scott, Nitya?

I'll will add, Nader. One thing is that in keeping with the reduction in fibrosis that we're seeing, these long-hauler patients. And perhaps this is a signal of all post or many post-viral syndromes have a lot of fatty deposition in the liver and in the pancreas. Also, they have cardiac involvement as well. And so we're incorporating with the signal that we're seeing with a reduction of fibrosis, we think that we'll be able to do this systemically. And we're incorporating that in long -- in valuation of long-haulers in our trials as well. I think it's important to not only have a subjective patient reported outcome but also objective measures in terms of cognitive testing, MRI, et cetera.

Excellent. Thank you so much. All right.

Yes. I would like to mention, we just recently presented at the World Antiviral Congress on November 30. And I think this was really. We covered a lot of ground in that conference in a very short amount of time. We talked about HIV monotherapy, HIV prep, HIV cure project, combination therapy, COVID-19 critical population, long-haulers NASH and oncology. So I think we -- and I think that there's a growing interest as leronlimab as a platform molecule across multiple indications. And I think what that's going to do for us is, we just recently brought -- in terms of partnerships, we just brought back Dr. Brendan Ray who worked with us in the past. And now that we have data, we think Brendan is an attorney with virology experience and we're going to be looking at partnership opportunities in not only domestically, but China, Argentina, Taiwan, Southeast Asia, Mexico, Turkey, Korea, we're looking at multiple different things like oncology, HIV, NAFLD, NASH, so I think it's really exciting where we're going into this new year.

Absolutely. And the last thing is before we go to Q&A is if the NASH trial is as strong as we believe it's going to be when we unblind it, and let's just say with the open label, let's just say we had our primary endpoint and secondary endpoint, we would immediately file those results with MHRA U.K., Health Canada, Brazil, and Philippine because we have pharmaceuticals over there that we are working with. So this is going to go to a whole new level if we have a primary and secondary endpoint hit in either open arm or the blinded one, but we will be reporting on that hopefully very soon. So with that, let's go to Q&A, please.

Okay. Why was the COVID-19 study in Brazil downsized to 51 patients versus standard of care? And will the study be powered if successful to show statistical significance?

So Albert Einstein Research Organization in Brazil is responsible for studies that was done by Pfizer studies, the vaccine studies and they published in New England General Medicine. So we're not dealing with some people who will just say things for the sake of saying it, they really do their homework. And they are top people in Brazil. They are the one that verified that there is a Omicron case in Brazil, the government really counts on them apparently. [indiscernible] has a great relationship with them. They came to us and they said, "Look, you're hitting your primary endpoint with 62 patients or an endpoint with 62 patients for the same endpoint that is now your primary endpoint. We can power this, the same power 80%. And the difference between -- absolute difference between the 2 placebo and leronlimab instead of being 16% has to be like 24%, something like that. And we believe that's very doable with 50 patients. So again, if we are not hitting the primary endpoint at 50 patients, no harm, we will just continue to study. We have to have interim analysis at some point. So I'm very happy that now it's 50, but this change will help us to expedite. We're always trying to expedite without sacrificing the quality. Next, please.

Okay. On the same Brazil topic, there's been quite a few questions asking for an update with regards to the enrollment numbers for both the severe and critical studies in Brazil.

So we get our enrollment update on Thursday and in the next time that we speak, we will update. I don't think there's any changes yet. The cases were very low. Omicron just started. And we are expecting by the end of December or January, we'll be able to enroll more. By February, obviously, we believe that we're going to be able to have the 51 enrolled. That's what the people at Albert Einstein Research hospital believes, and that's all dependent on the spike if the spike comes. Obviously, we will -- we are hoping that we can enroll, but everything depends on the enrollment. Next, please.

Next, with regards to NASH, how long is the NASH study? And is 10% decrease in fibrosis thus far, the small number of patients of any real clinical significance?

Dr. Recknor will answer that, please.

So CT1 is more sensitive way to look at fibrosis. A reduction of 16% is substantial for PDFF change to reflect the fibrosis. Again, we're interested in reducing fibrosis. The change that we're seeing needs to be compared to what happened in placebo. If placebo is getting way worse, and we're seeing that we get better, it's the difference between the 2. So I strongly believe that we're going to be able to achieve at least 16% with PDFF. And from what it looks like in the open label, I'm very impressed with the millisecond reductions that we're seeing, especially in these severe patients.

And the data that I got from one of our friends, there was 9 or 10 companies data that was sent to us. And I believe if I read it correct, the placebo increased fibrosis and some increase in the fatty deposit PDFF, but there might be placebo that also reduced the -- especially in fatty deposits, but we're just not very far away from that exciting day, in my opinion, to read the data and tell everybody what we have. Next, please.

Just when will top line results for the blinded NASH results to be available? Do you think it would be better to present all the data of placebo 350-milligram and 700-milligram to the FDA in support of a breakthrough designation for NASH?

Yes. Obviously, we will present all of it to FDA. So it's not -- it's better or not. That's what we are going through. The fact that we update everybody is because we want to make sure everybody knows where we are. That's a path that we took 7 years, 8 years ago, 9 years ago when I became CEO, we wanted to always be crystal clear with the shareholders where we are at. Next, please.

Could you please explain the NASH trial results in comparison to trial results by Madrigal and others in the space?

Dr. Recknor, do you know anything about those trials? Or should we defer that to the next time?

I think we're just about to lock the database, and we'll know -- be able to announce before Christmas.

Yes. And I will be calling Dr. Recknor every day, will ask him, are we there yet?

Can you discuss the potential for partnerships in NASH in cancer?

So in the cancer, I'm going to give it to Dr. Kelly in a minute, but the NASH and the other indications, when [Dr. Brandon Ray] joined us before and then we don't have any data. He said, guys, there's nothing there. But now when we talk to him and he talk to Dr. Kelly saying that you guys, if you have any positive NASH data, the potential for partnership is very high. And in regards to cancer, we're talking to people, but Dr. Kelly, what would you like to tell everybody?

Yes. I mean we can't be too specific about that. But what I will tell you is that there is a growing understanding that the tumor microenvironment is really the next frontier, like I said earlier, in immunotherapy. And I think that people also realize that looking for agents to pair their drugs with, which we find very interesting. They're also looking for less toxic available therapies out there, which we think leronlimab kind of speaks for itself in that in regards to other things such as chemotherapy. So I think there's going to be no lack of opportunity in the future if the data continues to pan out. We'd like to get a partnership as well for a trial potentially in oncology. The other thing about NASH and Nader is exactly right, is Brendan and I talked about that, and he said, this data is compelling. I don't think we'll have any trouble getting a partner now. We can't promise that. But I think that if you look at the people who have failed in NASH, then you will understand there's a growing appetite for NASH opportunities and NAFLD opportunities.

Great. Thank you. And in regards to NAFLD, we will move forward the same as we are moving toward with NASH. If the data is as good as we hope to be for 700-milligram, we will file not only breakthrough designation, but fast track designation for both, but we need to discuss that a little bit more detail after the data is unlocked. Next, please.

The short seller said you data sweep for NASH like you do with all other headlines. Can you explain why there was such a big decrease in some, but it looks like there was an increase in half of the trial in NASH?

So Dr. Recknor, do you want to respond to that?

Well, I mean, overall, we're seeing a reduction in all -- and this is 20 -- 20 of the patients in the open-label portion and what you're looking for is a reduction of about 40 milliseconds. We'll then compare that to placebo and see what the overall is. I can't tell you at this point. Again, we look at patients that have severe and we're responding with leronlimab in all but one of the cases. Yes, it's a smaller number, 6 patients. But still, that's very impressive given CT1 is greater than 1,000 that they would respond in a way that they are. So I think the shorts are -- I can't comment on what their thought is with this, but I do know that 80 milliseconds is very pretty impressive reduction. And we will get the results shortly to be able to let it weigh where it is.

Yes. I mean you -- everybody has the right to short the stock, but don't short your brain. I mean the data and the fundamentals are in front of you. Question us on all of these, and we will answer you, but seeing that kind of result. And if you compare that 20 patients or whatever number end up being -- with the 30 patients in placebo, which is not unblinded yet. And if it happens, that we hit a primary endpoint with that then that's end of this story. We were successful completely. But we want to wait and get that result. Obviously, we don't know if it's going to be yes or no, and please don't take my smile or my frowning or anything as an indication of anything because I don't know the results.

Yes. I mean I think the duration of the trial too Nader and Chris, wouldn't you agree, I mean, at 14 weeks, if we're seeing changes. I mean I think that's pretty impressive, but let's see what the data shows.

Yes.

Okay. Originally, you had mentioned that we might not file for breakthrough designation in NASH due to the FDA required a placebo arm. Recent PRs indicate that we might file for breakthrough designation and NASH. Can you comment on what changed?

Well, the data are getting stronger and stronger as we can see in the press releases and the placebo comparison shows where we had a primary endpoint then definitely, we will file the breakthrough designation. Originally, I didn't know if that 20 patients is going to be that strong, but now the trend is quite a bit. Dr. Recknor, could you also tell everybody about severe NASH, which we indicated that CT1 more than 1,000, and you look at those numbers, and they were very impressive. I believe that you said that this is really strong, but could you emphasize on those severe ones?

And that is what -- again, we talked on this, but you're seeing out of 6 patients, 5 of them are responding, which is fantastic, about an 84% response rate. What you want to try to do is reduce fibrosis. The hardest one to reduce that in are those severe patients, those that are progressing on to cirrhosis. So to me, as a clinician, having the ability to treat these patients which they can have rapid progression of fibrosis and death is very exciting. I think I just need to have the focus on reducing the fibrosis in these patients. I think we are more of a fibrosis-reducing agent what we are fat reducing, but we're still seeing reductions in fat as well. Again, when we unblind we'll know.

produce the scar tissue in the liver like we were discussing earlier. So we know that those often times contain CCR5. So I think the mechanism of action makes a lot of sense. I mean, I think that there's a lot of different people going down different paths in NASH. But I think from a mechanism of action standpoint, and what we've seen in our animal studies, it really makes a lot of intuitive sense that leronlimab might have an effect, and we'll just have to see what the data shows.

So [ Dr. Kenneth Sherwood ] indicated in a published paper, Dr. Kelly, you know about that, when you talk to him, that HIV patients, they could have NASH. And if they do, and because of the liver toxicity and a lot of these drugs that are out there, even though they're very, very good right now, a lot of them. But if you can take those, then you have to take the old ones with which they have liver toxicity. Then he, Dr. [ Ken Sherwood ] suggested in his article that there should be a regimen. There should be CCL5 antagonist as part of everybody's regimen. Can you talk about that ?

Yes. [indiscernible], he said that he felt that CCR5, if it shows like, for example, if we get this data -- and again, it makes intuitive sense, if we get this data that shows that we have a reduction in NAFLD and NASH, we see a higher rate of NAFLD and NASH in the HIV population. So the question is, why wouldn't you try to do that to have CCR5 as kind of the foundation of an HIV regimen. And it's a very good point that he's making, I think, Nader. I think you could help the HIV, but you might ameliorate some of the -- or make it better, I'm sorry, for both NAFLD and NASH potentially. And I think that's one of the things and make it more convenient as a once a week than a daily pill, but we do know the rates are higher for NAFLD, NASH in HIV population versus the general public, which is already off the charts, right? It's a huge market opportunity for both indications.

So when we did the long-hauler study, Dr. Recknor generated quite a bit of data that was very interesting. One of the data that we generated from the part of that primary end point, it wasn't the whole primary endpoint. The whole primary endpoint was 24 symptoms. But one of the symptoms, the joint pain was 350% clinically better in just 26 patients or so that we had 2 arms, 26 each or something like that. And when you see p-value for that being 0.02 or 0.01 was statistically significant. To me, as a layman person, I see that this product can help if it can help joint pain, if it can help fatty deposit reduction, if it can help fibrosis, if it can help cancer tumors to shrink and maybe people who have a cancer and they take the cancer tumor out, maybe they can have recurrence. So to have this to prevent it, if that's the case, if we can show that, then our label of our product would have to have all of these benefits as much as well as the side effect. And to me, it's just starting to be blessed to have this opportunity to bring a drug like leronlimab with all of the aspects that we are finding out about this drug. So with that, let's go to the next question, please.

Okay. Can any severe or critical patients in COVID-19 get treatment with leronlimab, what pathways are open with respect to compassionate use for right to try in the U.S.?

So we're talking about COVID-19, correct, Antonio?

Yes. And then I think the second question is outside of COVID-19.

Okay. So with the right to try, obviously, the laws are very clear what we can do and what we cannot, and we follow those laws. We have people on right to try. And with the expanded access that we find for HIV multi-drug-resistance, obviously, that's a very important filing. We have a problem with our protocol, and it needs to be modified. We didn't do a good job filing protocol that we did. We're now going to do a better job and the FDA told us that, and we are going to send the right protocol the right way and they give us guidance as always. And with the other indications, I mean, that we have, if somebody asked for right to try, we just have to follow the laws. But expanded access, we are very excited for also cancer to file that. Hopefully, we get breakthrough designation, we have 15 days to file that. But then in regards to charging the patients with something we need going to need because we are a little company, having 40 patients in extension for almost 4 years in HIV, 7 years on 5 patients in another arm and all these emergency INDs and compassionate use being given. Dr. -- Mr. Antonio Migliarese is our CFO and everybody should call him every day and ask him where are we with that filing that he needs to give to the FDA, to allow us to charge. I'll give you guys his cellphone if I need to. But he's working hard with the folks that are putting the package together. Once we give that to FDA, I think that's the last package and we might be able to charge and allow people to have it under the laws and regulation, whatever that is. Antonio, I'm sorry, I said that. Go ahead. Please go to the next.

The pressure is on. Can you tell us the total revenue thus far from the Philippines and any revenue guidance for 2022. I can answer this. So you don't give -- so we don't give revenue guidance. However, in our 10 -- our last filed 10-Q, we did report about $40,000 of revenue. We also did disclose that we received another $200,000 in orders from the Philippines. So that's where we stand with regards to that question.

And let me just say 1 thing, Antonio, 1 quick thing is we also send $300,000 [indiscernible] to Philippine on top of those that Antonio just said. But that's not a purchase order. We sent that because we realize it takes 4 to 8 weeks to get a product from here to there. So we made an agreement to put the product there that with the next purchase order, they can just take it from that. Am I correct in what I am saying, Antonio, did I say anything incorrect?

Yes. So we've established a consignment warehouse in the Philippines, in order to expedite the movement of the leronlimab from U.S. to Philippines, as we were working through the supply chain, it was taking a significant amount of time from the time we received in order to be able to get to the end customer. So as we grow and we mature these are some of the things that we're doing to help cut down on that time.

Perfect. Okay. So we only got 3 more minutes. So go ahead, give us the last 1 or 2 questions, please.

Okay. Is the HIV/BLA application on schedule despite the issue with Amarex? Did we extract and clean the needed data?

So we're working on all of that, and we will be giving updates on that. I don't want to say one way or another as long we have everybody focused. Our deadline is end of March. That's what we put for everybody. Can we meet that? Are we going to get delayed. We will let everybody know as soon as we have more information. In regards to the meeting with the FDA, Type B meeting, we will be filing that hopefully soon. We have so much on our plate and our team is exhausted, but we will be doing that also to meet with FDA and go over everything we have or if there were some shortage and see where we can get. But we will update everybody on that when we can. Anybody wants to add anything, Nitya or Chris? Okay. Nitya, you're muted.

Yes, you're right. So we are working on the Type B meeting request. And hopefully, this request will go out, turn very soon, and we'll have a meeting. If the Type B meeting, probably in January or February we should have a meeting. And at that time, we are going to discuss with FDA, our BLA filing strategy for the clinical module and what we have achieved. And so that discussion will happen with FDA. So yes, our target is still by end of March complete the BLA . And -- but we are going to update as we have more information on the different activities.

Great. Antonio, do you want to read any more? Or do we?

One last question. Since we have 1 minute. When do you anticipate when the FDA will give an answer with regard to the triple-negative breast cancer EUA?

So for the breakthrough designation, as we said, the January 5, will be 60 days. So any time before that, we expect to get the results. So with that, let's just say a few words for conclusion of this meeting. I hope our shareholders are looking at the fundamentals. In this month, we could get very strong results from NASH, hopefully, primary endpoint, secondary endpoint will be announced also. And the breakthrough designation, hopefully, we can get it this month or a few days into January. We have monotherapy that we talk about HIV monotherapy that we're going to pursue next year very aggressively. We have the NASH trial that could give us breakthrough designation if there is also good and if not, then we would do Phase III metastasis, triple-negative breast cancer and basket trial cancer will be our focus also. And COVID-19 in Brazil, we're very comfortable saying that we feel very strong that the team at Brazil are fantastic, and they are doing everything they can to get the enrollment for that 51 patient critically ill population by January or February. So that would be able to give us something very strong. So the outlook of the future for us is very strong and critically ill population in the United States, I don't want to forget that, but that's also something we will pursue. So with all that, thank you, everyone, for being on this call and having Merry Christmas and happy new year if we don't have another call before that.

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