Ladies and gentlemen, welcome to CytoDyn's Investment Community Webcast. At this time, all participants are in a listen-only mode. A question-and-answer session will follow our formal presentation. You may submit your questions at any time during the webcast by typing them into the Q&A box found to the left side of your screen. 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 presentations 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 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 by 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 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 and marketability of any product that is approved. The existence or development of vaccines, drugs or other treatments that are viewed by medical professionals or patients as superior to the company's products. Regulatory initiatives, 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 or 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 the 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 four 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. Christopher Recknor. Our finance, Mr. Antonio Migliarese, will be on the call. 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. 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 from ex-GSK.
We were able to hire a bioanalyst, Dr. Darshana Jani, who's an ex-Pfizer person. We hired recently a clinical regulatory person, Dr. John Andrews. Now, Dr. John Andrews is ex-Roche, but he was part of the team that brought the first drug approved for HIV, AZT. He also was part of the first cocktail that was approved with HIV. He's very knowledgeable. We really need his expertise for our clinical section that we're gonna be filing. We 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. We are hoping to let you know today what to expect in 2022.
When I explain what we're gonna do in 2022, we should answer some questions. When did we initiate each program that we have currently? Whatever we have right now, when did we initiate it? We initiated a lot of programs. What happened to them? Where did we get to? Did we do positive things with them? We just started something just for the sake of starting. We should answer the question, how far have we advanced each program? Were we successful? 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 gonna start with what we have started, and where is that program now, and where we think it's gonna go in 2022. The shareholders should base their decisions about our company upon, in my opinion, where we started each program, where we took it, and can we take it further. With that said, let's look at what we had in 2013. We only had one thing in 2013. The only thing was we purchased leronlimab. 2014 and 15, again, one task, one major task. 2014 was HIV monotherapy phase II. That's all the company had. 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. 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. That in 2017 was monotherapy for HIV program. I talk a lot about HIV program monotherapy. That was something we were very excited and we still are very excited. In 2018, we add one more. Instead of just continuing with the last four, we added another program. We entered the cancer arena. Metastatic triple-negative breast cancer. Phase I-B/II was granted to us by FDA.
2019, we added one more program, NASH. We will talk about that. Thanks to Dr. Christopher Recknor, and we have a lot to say about that today, and he does too. 2020, all of a sudden, we added quite a bit more. Three m ore. 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 it's put a burden on our team to keep carrying these new tasks. We're doing that, but we're not dropping the ball in the past ones. 2020, the three tasks were, we actually realized leronlimab is working on a mechanism of action that can have effect in 22 solid tumor cancer, in our opinion.
Our animal studies show this. Pandemic starts, so we did two trials in moderate and severe, and we completed those trials. In 2021, five tasks were added. I mean, if you see that, we did long haulers, thanks to Dr. Recknor single-handedly. Brazil, two trials. U.S., we just filed the critically ill population. We're 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, from 2013 - 2021. What we're gonna say about 2022, it's very important that people look at what we did in 2013 - 2021. If we're not capable based upon that, then that's something the shareholders should know.
If we are, they should pay careful attention, very careful attention, in my opinion, in my humble opinion. 2013 - 2021, all the programs that we list right here. This is gonna be on our website. People, please go look at it. We completed the monotherapy phase II. GVHD, we paused it. It was a small population compared to other ones, so we paused that. We had problems with our CRO. The combination therapy HIV, our main part, we hit a primary endpoint, statistically significant. We continue with the phase III monotherapy with 600 patients almost, and we have got fantastic results that we reported constantly. That phase III monotherapy was not a pivotal study. We need a pivotal study to get approval. Metastatic triple-negative breast cancer. We find a Breakthrough Therapy 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 gonna talk very quickly about the rest of them, but you can see yourself, and I'm not gonna go through it, that we complete projects that we start. If with Brazil, we are now running into problems with enrollment, what's the chances of us being able to solve that problem? 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, you know, responders rate." We solved that problem, thanks to God and the beautiful team that we have. When we had problems with other indication, what did we do? We solved the problem. We will be solving the problem with Brazil also.
We will get to it at the time that we talk about that. 2022, we don't have three or five , we have eight new tasks that our team gonna talk about right now. The first one is HIV BLA submission to FDA. The tremendous mess that we had from our Amarex folks was cleaned up, most of it, with Dr. Christopher Recknor. That took a lot of his time. If I should ask how many hours did he work, I would say quite a bit. I'm gonna ask Dr. Nitya Ray, who took over that because Dr. Christopher Recknor is working on too many projects, and we'll get to those projects that are very exciting in a minute. Dr. Ray, explain to us please where we are with BLA for HIV.
Right. For the HIV BLA, we have submitted the non-clinical and CMC modules. The last one, we submitted CMC module by the end of last month. We are working very expeditiously to finish the clinical module five, and we have solved some of the issues, the technical issues that we faced with the receptor occupancy assay. 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, you know. As you know that, you know, we had a lot of issues with the receptor occupancy assay. You know, 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, CCR5 receptor, because they internalize and but we are solving it. We are working with the CRO, very well-known CRO, and we have also hired internally. We have strengthened our team that Dr. Pourhassan was talking about, Darshana Jani . You know, she just joined this week, and she's an expert in this area. She'll be responsible for clinical biosciences and she has worked with many CROs, you know, on the receptor occupancy. She's an expert in this. She's well-known in the community, in the scientific community, and she joined our team and I'm very excited about that. She'll take full responsibility to make sure that, you know, we get it done on time and that will meet FDA's expectation.
Thank you so much, Dr. Ray. The fact that you were able to find these great talents for us, we're very thankful. I think, each one of them have expressed to you how excited they are with the molecule. Am I right about that?
Absolutely.
All right. The HIV phase III pivotal monotherapy. When we started that trial, we were hoping to have a higher response rate. We got that and we went. We filed phase III with FDA. Why didn't we go forward with that? A good question would be, where is that program since we filed it with FDA? Well, FDA at that time had very little limited data from us. They wanted to get more understanding of the monotherapy. This is not an easy thing because it's dangerous to take people out of their current regimen. What's gonna 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. FDA was happy to let us do a large trial. That large trial, we needed more responder rate. Now, the new protocol, this is where we are discussing with FDA. The new protocol, there are superiority trial or non-inferiority. We either have to do those with the drugs, or we have to do it with the monotherapy by itself with couple of arms, perhaps a 350 arm versus 700 milligram arm. It'll be a 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 two weeks first, and then every one month for the viral load.
In real life, the maintenance should represent every three months viral load check. Those things we're finalizing, and then we believe we're gonna be able to hit our primary endpoint with phase III because we have seen a high responders rate, specifically after 24, 30 weeks in all the arms. The next task is long haulers. I was approached by Dr. Christopher 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. Dr. Scott Kelly indicated that Dr. Christopher Recknor knows what he's talking about, you don't. I listened to him, and we started the long hauler trial. The results everybody saw in 56 patients, what we got. 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. The background is that in CD10 we didn't have a specific time period from when they had COVID. Back when COVID was first starting up and we were doing CD10 and CD12, we were actually looking at long haulers in those patients. We observed that several of those patients improved after leronlimab treatment after the unblinding happened. We saw who got and who didn't get. 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. 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 cross the blood-brain barrier, and in macaque studies, we're at 75% receptor occupancy in the brain. We think it will help.
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 we with that?
Yeah. FDA gave us additional comments. They actually put it out for three different divisions to help. They came back with some excellent remarks, which we've adapted, and we're getting ready to resubmit that shortly to them. I think that helps us both. The FDA is helping us make a better protocol.
Who's our CRO?
The CRO for CD18 will be Symbio.
Symbio. Thank you so much. The next program that we will be having results and have that as our main, one of our main goals is NASH. Now with NASH, again, this was something that I was for that. Dr. Recknor started it. We were very happy, Scott Kelly, and I was against him adding 350 mg arm open label. 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. There are some people asking question, which I'm gonna after Dr. Recknor give us the detail of this NASH that we are so excited and why we're excited. I'm gonna ask you some question that the short sellers are asking. Dr.
Recknor, explain to us about NASH, please.
NASH is fat and fibrosis in patients that leads to liver failure and cirrhosis. We noticed in the animal models that we're reducing the fat in the animals by 75%. That led to us starting the NASH trial. Our primary endpoint is looking at fat reduction because that's what we saw with animals. In the open label, we're seeing excellent results with reduction of fibrosis. 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 where we'll see what happens with the higher dose of 700 milligrams.
Yeah. We know that, you know, hepatocytes contain CCR5, right? We also know that the cells that produce scar tissue in the liver also contain CCR5. We think we work by both mechanisms. That's what we're gonna be seeing with the results.
Comparing this data that we have so far with the normal placebo, it looks like we should be able to hit the primary and secondary endpoint if you compare it 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 isn't make sense to me. Dr. Recknor, they're saying that, 107-millisecond drop in the fibrosis cT1 is really nothing. Is that right?
That's a huge decrease in patients. This study that we did did not look at biopsy. That'll be for the phase III study. 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. 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 cT1 that actually I think will get an accentuation with the biopsy results in the phase III. 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.
The data we said in the title was 80% of the patient 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, 50. I wasn't doing that. This is the results, and this is what we're gonna be showing to the FDA, hopefully, as soon as we unblind the rest of it. Tell us about the unblinding and when do you think we're gonna 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 to be able to produce the top-line report before Christmas vacation. This gives us the ability to look at what's going on with the 700 mg dose, which I'm very excited to see, and looking at the 350 mg dose as compared to the placebo in the double-blind portion, part one. We're really excited.
Yeah. Some people are saying that if there's other NASH trials, they do 1,000 patients, so we probably need partnership. 1,000 or 2,000 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 out. 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. Dr. Kelly, tell us a little bit why we are excited about the basket trial.
Well, we're excited about the basket trial. I'll start by saying, you know, we just presented at the San Antonio Breast Cancer Symposium. When I say presented, there was a poster on December 10th, and that was in regards to results with metastatic triple-negative breast cancer in combination with carboplatin CCR5 positive metastatic triple-negative breast cancer. I 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. I mean this among practicing physicians, the academic world as, probably as well as Big Pharma. I think we're more advanced in this. We've really been looking at the mechanism of action in the tumor microenvironment to see leronlimab's impact across multiple different oncologic indications.
You know, we also think that we can pair 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, you know, Tregs, and Tregs come in and turn off the immune system. We know that they have a high prevalence of CCR5, but we can block that. We can actually maybe leverage the immune system. If we look at macrophage repolarization, that's another potential opportunity. You know, our animal studies showed a significant reduction in angiogenesis. I think it was 62% in total vessel area and 80% reduction in small vessel area. We know the tumors need a blood supply to grow, and if we can help limit that, then we think we could have benefit for patients.
The last is obviously, you know, 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 sprouting up CCR5, and we believe that's a contributor as to metastasis. We have multiple different mechanisms, and we're continuing to find more as we go along that we're gonna be evaluating.
Yeah. The breakthrough designation that we filed, Dr. Nitya Ray did a fantastic job on that. There were some patients with brain metastasis. Dr. Ray, explain to us, for a breakthrough designation strategy, are we going to file for brain metastasis and perhaps maybe later on, if we do get breakthrough designation on the original submission, maybe we wanna ask for basket trial et cetera. But tell us about the brain metastasis data, please. You are muted, Nitya. Nitya, you're muted. Please.
Yep.
Okay. Can you hear me? Yeah.
Yeah. Go ahead.
Well, the breakthrough designation application that we submitted, it has like 28 patients from three different trials. Out of the 28, like six of the patients had brain metastasis. These are all metastatic triple-negative breast cancer patients. We have submitted all the results, including the patients with brain metastasis now with the FDA, and FDA is reviewing it. We're waiting for the FDA to respond to our BTD application, and we expect to hear from them in about two weeks, two to three weeks. About 60 days after it's submitted, the application, that was done, I believe, on November 5th. By January 5th, we should hear from FDA. Then we are going to discuss with FDA and see that what our path forward with the brain metastasis.
Now, these are not the only brain, you know, cancer patients with the brain metastasis, because these are only patients that metastatic triple-negative breast cancers. We have other patients in the basket trial that are not mTNBC at the brain metastasis. We are very excited about that, you know, that what's happening with these patients. We are going to again discuss with FDA, and we do plan after we receive the 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 metastasis.
Cancer breakthrough designation that we filed, we should hear hopefully soon. When this is gonna 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 still gonna immediately do a trial, you know, the magnitude where we can hit a P-value. Sacituzumab had a phase I-II. 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 two tasks that I put there, I only put critically ill population for Brazil.
With the Omicron going through the roof right now, the numbers, we might even finish the severe population data that, I mean, the current trial. We might have nine tasks that could complete in 2022 or initiate in 2022. The critically ill population where we are, we now have about 20 sites. Am I right, Dr. Scott Kelly?
That's correct. Mm-hmm.
Okay.
We're adding more.
Yes. I think they said that they're gonna have about. They could have up to 40 in the next two months after December.
Correct.
By end of December, we should have 20-25. If those sites are in place, enrolling 51 patients or 50 patients, because 40% of 126 is 50.4, so maybe 50 patients, but whatever, that's not gonna be a problem if there is a spike in the COVID-19 cases. Now, people keep saying, "Why did you reduce it to 50 patients and, you know, this is gonna, you're not gonna hit the primary endpoint?" We explained our endpoint that we have is different than survival, and we already had powered the study based upon that data, very valuable CD12 data. If we do an interim analysis at 51 patients, and we don't hit our primary endpoint, so we continue. As a matter of fact, we might do more than 126.
We might do 200, whatever the DSMB sees fit to give us. This is not shooting ourselves in the foot in any way, shape, or form. Critically ill, and I'm sorry, the severe population COVID-19, that's gonna go forward, and we will get the latest data and always update the page, the shareholders with what we have. 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 United States where the ICUs are getting packed again. We wanna pin down those states and open sites over there immediately and perhaps do our study. We would be working with CROs. We are currently working with PPD. Where are we with those discussions, Dr. Recknor?
You talked to them, and I talked to them. Where are we with those, with PPD?
We're progressing nicely.
Okay, great.
Developing the protocol, et cetera.
Yeah. Nader, I'll add about Omicron. You know, it's interesting. We do believe this is gonna be the dominant strain. We do believe it's gonna be more contagious. We don't know if it's gonna cause more severe disease. We just don't know that. But if you look, I mean, I think it's already in 32 states right now. I mean, this is how quickly this goes. So ultimately, it will, I think, overcome Delta and be the most dominant strain. We just don't know if it's gonna cause severe disease, and that's something that time will tell.
Yeah. The latest news yesterday, Boris Johnson from England, the Prime Minister, indicated that there was one death already from Omicron.
Yes.
The CDC this morning said that 3% of the cases in the United States are now from Omicron. How much
That's right. Yeah. It's gonna spread, you know, exponentially as we know. The other thing is I would add is that we don't know how that's gonna 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, you know, the 10%-30% that people say is out there. I mean, if you look, there's already been 271 million cases of COVID. You're looking at, you know, well over 27 million patients that will be potentially affected by long haulers.
What I'm puzzled is. I'm sorry, go ahead, Chris, please.
I'm gonna say to that point as well, many of the long haulers are those that have gotten COVID more than one time with different variants.
Right.
We're starting to see that there may be a cumulative effect with the amount of exposures as well in patients.
Yeah. We don't know how these people are gonna respond to the vaccination, so this is just the truth. We just don't know. You know? We don't know yet.
Yeah. When I look at the whole thing, I'm so proud of our team that, you know, 2022 long hauler, thanks to Dr. Recknor, we already have enough data to go forward with FDA and say we wanna go to the next level. Having NASH, having cancer on 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. Let's go to the next slide. I just wanna show everybody that from all the way to 2020, every task that we added to our workload was continuous progress. Then we did three more tasks in 2020, five more in 2021, and eight more in 2022. This is what we have.
This is the bet that the shareholders make when they look at the company and look at the fundamentals of what we have. With 2022, I believe we are going to be able to very hopefully have results in December of our NASH trial, still not 2022 yet. The NASH trial results, we believe we can report this year. The breakthrough designation, we might even get answers if we get it sooner than January 15th. It could happen this year. The rest will be 2022. With that, does anybody in the panel have anything to add, Chris, Scott, Nitya?
I did, 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. We're incorporating with the signal that we're seeing with reduction of fibrosis, we think that we'll be able to do this systemically. We're incorporating that 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.
Yeah. No, I would like to mention, you know, I just recently presented at the World Antiviral Congress on November 30, and I think 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. I think that there's a growing interest in leronlimab as a platform molecule across, you know, multiple indications. I think what that's gonna do for us is, you know, in terms of partnerships, you know, we just brought back Dr. Brendan Rae, who worked with us in the past. Now that we have data, we think...
You know, Brendan's an attorney with virology experience, and we're gonna be looking at partnership, you know, 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. I think it's really exciting where we're going into this new year.
Absolutely. 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 hit our primary endpoint or secondary endpoint, we would immediately file those results with MHRA UK, Health Canada, Brazil, and Philippines because we have pharmaceuticals over there that we are working with. This is gonna go to a whole new level if we have a primary and secondary endpoint hit in either open arm or the blinded one. We will be reporting on that hopefully very soon. 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? Will the study be powered if successful to show statistical significance?
Albert Einstein Israelite Hospital in Brazil is responsible for studies that was done by Pfizer studies, the vaccine studies, and they publish in New England Journal of Medicine. We're not dealing with some people who just say things for the sake of saying it. They really do their homework. They are top people in Brazil. They're the one that verify that there's an Omicron case in Brazil. The government really counts on them, apparently. ANVISA Has a great relationship with them. They came to us, and they said, "Look, you're hitting your primary endpoint with 62 patients or 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 two, placebo and leronlimab, instead of being 16%, it has to be, like, 24%, something like that. We believe that that's very doable with 50 patients. Again, if we are not hitting the primary endpoint at 50 patients, no harm. We just continue the study. We have to have interim analysis at some point. I'm very happy that now it's 50, but this change will help us to expedite. We always try 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.
We get our enrollment update on Thursday, and on 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 gonna be able to have the 51 enrolled. That's what the people at Albert Einstein Israelite Hospital believes. That's all dependent on the spike, if the spike comes. Obviously, we are hoping that we can enroll, but everything depends on the enrollment. Next, please.
Okay. Next. With regards to NASH, how long is the NASH study, and is 10% decrease in fibrosis thus far in the small number of patients have any real clinical significance?
Dr. Recknor would answer that, please.
cT1 is the more sensitive way to look at fibrosis. A reduction of 16% is substantial for a 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 two. I strongly believe that we're gonna be able to achieve at least 16% with PDFF. 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.
The data that I got from one of our friends, there was nine or 10 company's data that was sent to us. I believe, if I read it correct, that placebo increased the fibrosis and some increase in the fatty deposit PDFF. There might be placebo that also reduce on the, especially on fatty deposit. 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.
Yes. When will the top line results for the blinded NASH results be available? Don't you think it would be better to present all the data, placebo 350 mg and 700 mg to the FDA in support of a breakthrough designation for NASH?
Yeah. Obviously, we would present all of it to FDA. It's not if it's better or not, that's what we are going to do. The fact that we update everybody is because we wanna make sure everybody knows where we are. That's a path that we took seven years, eight years ago, nine years ago when I became CEO. We wanted to always be crystal clear with the shareholders where we are at. Next, please.
Can 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.
Yeah.
to be able to announce before Christmas.
Yes. I will be calling Dr. Recknor every day. Will ask him, "Are we there yet?" Ramon will be doing that. Next, please.
Can you discuss the potential for partnerships in NASH and in cancer?
In cancer, I'm gonna give it to Dr. Kelly in a minute. The NASH and the other indications, when Dr. Nitya Ray joined us before, and then we didn't have any data, he said, "Guys, there's nothing there." Now when we talk to him, and he talked to Dr. Kelly, saying that, "You guys, if you have any positive NASH data, the potential of partnership is very high." In regards to cancer, we're talking to people. Dr. Kelly, what would you like to tell everybody?
Yeah, I mean, we can't be too specific about that. What I will tell you is that there is a, you know, a growing understanding that the tumor microenvironment is really the next frontier, like I said earlier, in immunotherapy. I think that people also realize they're 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. I think there's gonna be no lack of opportunity in 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, Nitya and I talked about that, and he said, "You know, if this data is compelling, I don't think we'll have any trouble getting a partner." Now, we can't promise that, but, you know, I think that if you look at the people who have failed in NASH, then you'll understand there's a growing appetite for NASH opportunities and NAFLD opportunities.
Great. Thank you. In regards to NAFLD deal, we will move forward the same as we are moving forward with NASH. If the data is as good as we hope to be for 700 mg, we will file not only breakthrough designation, but fast track designation for both. We need to discuss that a little bit more in detail after the data is unlocked. Next, please.
The short seller said you data sneak 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 the trial in NASH?
Dr. Recknor, you wanna respond to that?
Well, I mean, overall, we're seeing a reduction in all. This is 20 of the patients in the open label portion. 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, six patients, but still that's very impressive given cT1 is greater than 1,000, that they would respond in the way that they are. 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 impressive reduction.
Again, we will get the results shortly to be able to.
I-
Let it lay where it is.
Yeah. 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 kinda results, and if you compare that 20 patients or whatever number of 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 the end of the story. You know, we were successful completely. But we wanna wait and get that result. Obviously, we don't know if it's gonna be yes or no, and please don't take my smile or my frowning or anything as a, you know, indication of anything because I don't know the results.
Yeah. 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.
Yep.
Okay. Originally, you had mentioned that we might not file for breakthrough designation in NASH due to the FDA requiring a placebo arm. Recent PRs indicate that we might file for a breakthrough designation in NASH. Can you comment on what changed?
Well, the data are getting stronger and stronger, as you can see in the press releases. If the placebo comparison shows that we hit a primary endpoint, then definitely we will file the breakthrough designation. Originally, I didn't know if that 20-patient is gonna be that strong, but now the strength is quite a bit. Dr. Recknor, could you also tell everybody about severe NASH, which we indicated that cT1 more than 1,000. 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?
Yeah. That's what, again, we talked on this, but you know, you're seeing out of six patients, five of them are responding, which is fantastic. Around 84% response rate. What you wanna try to do is reduce fibrosis. The hardest one to reduce that in are those severe patients, those that are progressing on to cirrhosis. 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 just need to you know, have the focus on reducing the fibrosis in these patients. I think we are more of a fibrosis reducing agent than what we are fat reducing, but we're still seeing reductions in fat as well. Again, when we unblind, we'll know.
Yeah. The stellate cells are what produce the scar tissue in the liver, like we were discussing earlier. We know that those will oftentimes contain CCR5. 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.
Dr. Ken Sherwood indicated in a published paper, Dr. Scott Kelly, you know about that when you talked to him, that HIV patients they could have NASH. If they do, because of the liver toxicity on 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't take those, then you have to take the old ones, but which they have liver toxicity. He, Dr. Ken Sherwood, suggested in his article that there should be a regimen, there should be CCR5 antagonist product part of everybody's regimen. Can you talk about that, Dr. Scott Kelly?
Yeah. Dr. Ken Sherwood, he said that he felt that, you know, 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. 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.
I think that's one of the things, and make it more convenient as a once a week than a daily pill. We do know the rates are higher for NAFLD and NASH in HIV population versus the general public, which is already off the charts, right? It's a huge market opportunity for both indications.
When we did the long hauler study, Dr. Recknor generated quite a bit of data that was very interesting. One of the data that he generated for a part of that primary endpoint, it wasn't the whole primary endpoint. The whole primary endpoint was 24 symptoms. One of the symptoms, the joint pain was 350% clinically better in just 226 patients or so that we had, two arms, 26 each or something like that. 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. 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 effects. To me, it's just stunning to be blessed to have this opportunity to bring a drug like leronlimab with all the aspects that we are finding out about this drug. 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 or Right to Try in the U.S.?
We're talking about COVID-19, correct, Antonio?
Yes. I think the second question is outside of COVID-19.
Okay. With the Right to Try, obviously the laws are very clear what we can do, we cannot, and we follow those laws. We have people on Right to Try. With the expanded access that we filed for HIV multi-drug resistance, obviously that's a very important filing. We have problem with our protocol and it needs to be modified. We didn't do a good job filing the protocol that we did. We're now gonna do a better job, and FDA told us that, and we are gonna send the right protocol the right way, and they give us guidance as always. With the other indications, I mean, that we have, if somebody asks for right to try, we just have to follow the laws. Expanded access, we are very excited for also cancer to file that.
Hopefully, if we get breakthrough designation, we have 15 days to file that. In regards to charging the patients with something we're gonna need because of a little company, having 40 patients in extension arm for almost four years in HIV, seven years and five patients in another arm, and all these emergency INDs and compassionate use being given. 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 cell phone if I need to. 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 regulations, whatever that is. Antonio, I'm sorry I said that. Go ahead. Please go to the next.
The pressure's on. Hi. Can you tell us the total revenue thus far from the Philippines and any revenue guidance for 2022? I can answer this.
Please. Yes, please.
We don't give revenue guidance. However, in our 10-Q, our last filed 10-Q, we did report about $40,000 of revenue, and we also did disclose that we received another $200,000 in orders from the Philippines. That's where we stand with regards to that question.
Let me just say one thing, Antonio. One quick thing is we also sent $300,000 worth of product to Philippines on top of those that Antonio just said, but that's not a purchase order. We sent that because we realized it takes four to eight weeks to get a product from here to there. We made an agreement to put the product there. That way the next purchase order, they can just take it from that. Am I correct on what I'm saying, Antonio? Did I say anything incorrect?
Yes. 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 significant amount of time from the time we received an order to be able to get to the end customer. 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, we only got three more minutes, so go ahead, give us the last one or two question, please.
Okay. Is the HIV BLA application on schedule despite the issue with Amarex? Did we extract and clean the needed data?
We're working on all of that, and we will be giving update on that. I don't wanna say one way or another. As long as we have everybody focused, our deadline is end of March. That's what we put for everybody. Can we meet that? Are we gonna get delayed? We will let everybody know, you know, as soon as we have more information. In regards to the meeting with 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 was 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. Nitya, you're muted, I think.
Oh, I know.
Okay.
Yes, you're right. We are working on the type B meeting request, and hopefully this meeting request will go out very soon, and we'll have a meeting, the type B meeting should have probably in January or February, we should have a meeting. At that time, we are going to discuss with FDA our BLA filing strategy for the clinical module and what we have achieved. That discussion we'll have with FDA. Yes, our target is still by end of March to complete the BLA. But we are going to update, you know, as we have more information on the different activities.
Great. Antonio, do you wanna read any more, or do we kind of?
Let's just do one last question.
Okay.
Since we have one minute. When do you anticipate the FDA will give an answer with regard to the triple-negative breast cancer BTD?
For the breakthrough designation, as we said, January 5th will be 60 days. Anytime before that, we expect to get the results. 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. 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 gonna pursue next year very aggressively. We have the NASH trial that could give us breakthrough designation if the results are good, and if not, then we will do phase III. Metastatic triple-negative breast cancer and basket trial cancer will be our focus also.
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. That will be able to give us something very strong. The outlook of the future for us is very strong. Critically ill population in United States, I don't wanna forget that, but that's also something we will pursue. With all that, thank you everyone for being on this call, and have a Merry Christmas and Happy New Year if we don't have another call before that.
Thank you for your participation, and you may disconnect at this time.