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Posted On: 10/09/2020 8:39:14 PM
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"Interviews With CytoDyn Tell Story Of Leronlimab And Its Many Indications
Sep. 2, 2020 1:18 AM ET|About: CytoDyn Inc. (CYDY)
Summary
In depth story of the development of a drug - leronlimab, and how a blocker of the CCR5 receptor found other applications.
Covid-19 testing of mild-to-moderate cases was successfully completed with statistically significant results.
Company has gone to FDA for EUA (emergency use authorization) for an unmet medical need.
After $28.5 million funding and exercise of warrants the company has never had more cash.
The Investment Idea Behind It All
The bet is that an investment in a biotech, CytoDyn (OTCQB:CYDY), with a single drug with multiple applications will find its markets, generate billions of revenue, save lives, improve quality of life, and deliver an unusually high return to investors.
Source: https://bigcharts.marketwatch.com/
Results of a Mild-to-Moderate Covid-19 Study Were Excellent
CytoDyn has just completed a statistically significant Covid-19 study of mild-to-moderate subjects a week ago. The results were unusual on the safety end. Basically, you were at twice the risk of a SAE (severe adverse event) if you were in the placebo group. 5 SAEs out of 56 for the leronlimab group versus 12 out of 56 (2x of 6 out of 28) in the control group. In the usual case, an experimental drug hopes their safety will be as good as the control group (placebo). This kind of thing where the safety of the experimental drug is much better than control does not happen, according to Jay Lalezari, CytoDyn Interim Chief Scientist. So, it appears to be very safe indeed.
The efficacy was also outstanding in this study of patients in which both the control group and the leronlimab group are recovering from Covid-19 infection. Against a standard called NEWS2, leronlimab subjects saw 50% improvement versus 20% improvement by the placebo group.
Consequently, CytoDyn has applied to the FDA for right to sell the product under an EUA, an emergency use authorization for an unmet medical need. The government is under pressure to provide medicines against this malignant virus, but the problem is that even though the FDA authorized this small Phase 2 study of 75, they did not intend to approve it for sale on the basis of such a small study. So, they have to decide in this time of crisis where 10,000 people are dying each month whether to give it the green light, or hold out for more results. It will require nerves of steel whichever way they decide. Usually, FDA requires a larger Phase 3 to further establish the good results of a Phase 2 study. So, approval is not in the bag. It is typically a matter of numbers. Working in their favor are the excellent safety results so far. More than 800 HIV patients have been tested with no death or serious complications. And now there are more cancer subjects added to that, and the unusually good safety results of the Covid-19 patients.
When the CEO Dr. Nader Pourhassan was queried about doing another trial for FDA, he’s not bothered. A double blind study has just been completed in which the results were wonderful, indeed all of their trial results have been positive. Though sensibly they have pursued trials where the receptor CCR5 was implicated and studied and written about in the medical literature, so there were theoretical reasons to believe it might work.
Small biotechs are always short of cash, but CEO Pourhassan reports by virtue of the exercise of warrants, and a recent funding of $28.5 million at a conversion rate of $10 means that he has never had so much money in the bank.
Below are interviews with the CEO of CytoDyn, Nader Pourhassan, and the Chairman of the Board of CytoDyn, Scott Kelly. As the interviews will show, Pourhassan has the essential qualities of an outstanding CEO, a Ph.D. himself, he tracked down the best brains he could find, and learned from them. When advisors were hesitant, he went ahead anyway, and was proved correct. And when an inquiring doctor called the office asking about this possibility and that possibility, he recruited that doctor (Scott Kelly M.D.), who eventually quit his practice and joined the Board, eventually becoming Chairman, but staying true to his own north star, the drug’s possibilities, he took the additional job of Chief Medical Officer.
It is important to explain the word “indication”. An indication in biotech means the possibility that a given medical condition may respond to a medication, in this case we are speaking of CytoDyn’s leronlimab.
The Interviews
Thomas Barnard: So let's see, where shall I begin? How is your mother-in-law? [CytoDyn investors will know that she was the first lady with mTNBC – metastatic triple negative breast cancer – to receive leronlimab.]
Nader Z. Pourhassan, PhD
Nader Pourhassan: Doing much better than she was doing a few weeks ago.
Thomas Barnard: What happened?
Nader Pourhassan: She still has tumor in her brain, and she had a mild stroke a couple of weeks ago. It affected her right side, and the doctor said she would never be able to use the right side, and it won’t come back. But within three days she was able to walk on her own. Slowly, of course. Scott Kelly found published papers on CCR5 and stroke.
Thomas Barnard: What about her right arm? Can she do anything with that?
Nader Pourhassan: Yes, she eats with her right hand, and she’s using it.
Thomas Barnard: Wow.
Nader Pourhassan: Yes, it’s remarkable. We think it is the weekly doses of leronlimab that is helping her. It’s anecdotal, but we are having the doctor prepare a case report.
Thomas Barnard: Home testing of a new indication? So, let me ask you this: How did CytoDyn connect with Bruce Patterson? I mean, did he see your work and come to you or did you go to him or how did that work?
Nader Pourhassan: So Bruce Patterson was introduced to us through an associate of one of our old board members. And then I talked to him right after I heard about him. When I met with him he said he could do receptor occupancy tests for us. He could develop an assay for us and while we had other people who could do receptor occupancy tests, we went ahead and gave the project to him.
Thomas Barnard: A receptor occupancy test?
Nader Pourhassan: A receptor occupancy test tells you if the leronlimab is sitting on the receptor.
Nader Pourhassan: And he also was adamant that the cancer possibilities were great, but we were already doing cancer with Dr. Richard Pestell, and before that with Dr. Denis Burger. However, at that time, Dr. Pestell was our Chief Medical Officer. Dr. Pestell had already helped us to get the triple negative breast cancer trials under way. And when Bruce Patterson joined us as a consultant, he said that there's a lot of potential here and we were happy with that. In a few months we terminated Dr. Richard Pestell, and only worked with Dr. Patterson. Dr. Pestell gave us some fantastic information on receptor occupancy of cancer patients. It turns out that Dr. Patterson was not able to get the assay ready for receptor occupancy. So we got another lab, which was run Hallgeir Rui, M.D. Ph.D. So any cancer patient today who wants to get involved in the leronlimab trial must first have a biopsy. And then we send the biopsy to Dr. Hallgeir Rui, whose laboratory is in Wisconsin. And over there they analyzed to see if we have the necessary receptors.I mean, if the patient is qualified to be in the cancer study.
Thomas Barnard: So, let me understand, what you mean is that cancer must show the CCR5 receptor or forget it. Right?
Nader Pourhassan: The cancer patient’s biopsy is checked for a few things. First, does it have CCR5 on any of the tumor cells? And then there's infiltration of the leukocytes around the tumor cells. Do the leukocytes have any CCR5? And we checked both of those. Now, if they do, they're qualified to be in the trial.
It was around this time that Dr. Scott Kelly started asking me about what do you think about Covid-19 because he thought that ARDS was something we might work on, and which we had already discussed with other folks. I called Dr. Patterson. He also agreed that yes, you will be able to stop ARDS, which is the main cause of death in Covid-19. We immediately prepared IND and protocol and sent it to the FDA for a phase 2 trial. They said, no, you can’t file IND, you have to do pre-IND first, because you don't have any data. And that's when we got a call from Dr. Seethamraju. He said, My critical patients are not doing well at all. They are not going to make it. He called FDA and said, I agree with that theory leronlimab stops the trafficking of macrophages that was published in articles.So once he injected patients under an Emergency IND that made FDA feel more comfortable that our drug was not going to increase the cytokine storm, but perhaps give some benefit. After a couple of patients were extubated, they immediately gave us Phase 2 and Phase 3 green light without waiting three months or so.
Thomas Barnard: That's very interesting to know. So it was actually Scott Kelly, your Chairman and Chief Medical Officer, who was the one who thought working on Covid might be a good idea.
Nader Pourhassan: Yes, that's correct. But not only him, but there were other people who were telling me about it. We were talking to a company - I don't want to use their name, but a company, their chief medical officer, a very close friend of mine said we're looking at flu and you guys should probably have indication in flu. And I spoke to Dr. Denis Berger, who was a board member. And he's the one that conducted the study for M.S. [multiple sclerosis]. He had friends at the Providence Medical Center. After seeing the results of the animal study he thought M.S. is a huge indication. But it was Dr. Denis Burger, a former professor at Oregon Health and Sciences University, who had pointed to [M.S.] for many years, and he was the CEO for four successful biotechs. And I'm still in touch with Dr. Denis Burger. So the increase in the number of indications that leronlimab were found to have was because of Dr. Denis Burger and Dr. Scott Kelly. I had asked Dr. Burger about the cancer indication many years ago. And that's when we filed for patents for cancer (he is the inventor on many of our cancer patents). That was four years ago, it three years later, we got to know Dr. Patterson. Then we got started with Dr. Jay Lalezari in cancer. Dr Jay Lalezari was always involved with us from day one, but not in cancer originally, in HIV.
Thomas Barnard: Gotcha. Let's go back to the breast cancer thing, that was actually the thing that that moved me to buy shares a while back, because I thought that was an extraordinary result. Now I'm reading up. And it seems like Pfizer has a drug called Maraviroc, which they wrote about it in February of 2019.So that would seem to have indicated that when you tried it out on your mother-in-law, it wasn't out of the blue, you had a foundation actually that this might work.Is that right?
Nader Pourhassan: So, yeah. So Pfizer had started a cancer trial with Maraviroc, I believe, several years ago. And they started even before we did. As I told you at the beginning, about three or four years ago we applied for patents with Dr. Denis Burger. So Pfizer accidentally found all these new indications in graft versus host disease for Maraviroc. How was that? Well, the patients who have HIV for a long time usually develop AML, acute myeloid leukemia, or DMS, and they need bone marrow transplant. When Pfizer looked at the data they realized that these patients who get bone marrow transplant don't get graft versus host disease if they were HIV patients who were on Maraviroc.They all of a sudden say, wait a minute, this might have indication. Maraviroc might have indication in GvHD [graft versus host disease].
Thomas Barnard: (laughing) I see. By accident.
Nader Pourhassan: Let me tell you the most interesting part at that time. At CytoDyn we had a very strong cancer person, key opinion leader.And that person and Dr. Denis Burger both believed in the potential GvHD indication for leronlimab (called PRO 140 at that time). I wanted to do an animal study of graft versus host disease with leronlimab. When we held a key opinion meeting Dr. Paul Maddon, inventor, was on the call at my request. I had asked him to come on the call. He said no, no, no, no. There is no GvHD [graft versus host indication] for leronlimab. This was four and a half, five years ago. And he said, No, no, no, everything must stop. Maraviroc stops chemokines from binding. Leronlimab doesn't do that. And that's why we don't have any side effects or toxicity. So stop everything. Everything gets stopped, and the next day or two I told Denis Burger: I want to know why the video that shows mechanism of action of leronlimab by Paul Maddon had indicated that chemokine binding hardly doesn't happen. “Hardly” doesn't mean zero in mathematics. Hardly means something. Need to go check with the company who did the toxicology of leronlimab and find out what amount of PRO 140 [leronlimab] do we need to use to make that happen?And Dennis Burger said, no, no, no, leave it alone, you don't know what the hell you are talking about. Stop it.
Dr. Bruce Montgomery (a board member at that time) says no. Paul said no. I said, Well, I'm going to get it myself. So I had Amarex call Nobel Lifesciences, Dr. Stephen Horrigan. He knows me very well from that time, because I thought, I'm doing this without my board members support. And I sent twelve thousand dollars to do the in vitro study. And this study showed that leronlimab was better than Maraviroc in GvHD in an in vitro study. I had Amarex send the data to the FDA without the board members approval and submitted a protocol. And Denis Burger said, Oh my God, you were right. And FDA immediately gave us Phase 2 and asked for animal data in order to give us Orpha Drug Designation. So I told Denis Burger, Please now go do the animal study that the FDA is requesting. The FDA suggested that in our animal study that we inject 32 mice with human bone marrow. We knew they all would die from GvHD. If some of the mice in the half (16) that get leronlimab stay alive, we’ll give leronlimab Orphan Drug Designation. All the mice stayed alive! And all the mice in the control arm that did not get leronlimab died. And Denis Burger said, “Oh, my God, leronlimab has potential for many so many things.” Dennis Burger became my hero at that time because he was forced to stay with GvHD by me, and that opened the door for him to explore M.S., cancer, and many more indications for leronlimab. I loved Denis and still do.
And then he took the product to Providence for an animal study in M.S., and he cried almost at the board meeting. The three mice that got leronlimab had zero paralysis. Zero. And the people at Providence Medical Center said, Where did you get this product? Oh, my God. And then Dr Jonah Sacha said, “Nader, every time we show the results of leronlimab to the scientists, they say where did you get this product? This product is worth billions and billions. This is unbelievable what it can do for humanity.”
Thomas Barnard: Good. So I'm understanding then that leronlimab works better than Maraviroc.
Nader Pourhassan: Absolutely. Maraviroc has approval for HIV. But it has a black box warning, it has liver toxicity. Our product, we believe, probably helps with liver restoration; it helps all kinds of different autoimmune and cancers. So, if our bodies suffer for whatever reason, any virus, Covid-19, flu or whatever, or any scratch or any foreign object goes your body…the immune system must fight it. Many of our immune cells have CCR5 on their surfaces - macrophages and on T regulatory cells. And we believe that probably leronlimab binds to a very, very special place on CCR5, which is a work of art by Dr. Paul Maddon and William Olson, Ph.D. from MIT.
Thomas Barnard: Did Maddon know what he was doing when he did this? I mean, did he…
Nader Pourhassan: He was focused on getting this molecule to bind to the exact location that HIV binds. Just keep in mind, Paul Maddon got his M.D. and Ph.D. from Columbia University, his dissertation, his research for his Ph.D. was on where HIV binds first, which was the CD4 receptor on a T-cell. So he was the first man who discovered that. Then, he founded Progenics, a biotech company. And then he discovered the interaction of HIV with CCR5. Then he made an antibody against CCR5. And Dr. David Ho, who ended up saving millions of lives of HIV patients by developing HAART and became Time magazine Man of the Year, was a very close colleague of Dr. Paul Maddon. Ho found an antibody against CCR4. Paul Maddon felt he had a better target, and said, I want to go after CCR5. Now at Progenics, where he founded Progenics and where he was CEO for 30 years. He got the molecule to bind to the optimal site on CCR5.
He first found a molecule and it was called (I believe) PRO 540, not 140. In the first year of development of PRO 540, the viral load drop wasn't good enough because it wasn't binding to exactly the right place. Dr. William Olson, (Ph.D. from M.I.T.) worked for Dr. Maddon, said to me that not long after the PRO 540 failure, We went back to the drawing board. I went through thousands and thousands of antibodies, and one morning I came in and I had isolated one antibody and I thought, my God, it binds to one hundred eight point percent of the HIV binding sites. That would mean that HIV would have no way to bind to that site.
He said immediately when they got that molecule they had to humanize it, which cost them a lot of money in 1999. And we, CytoDyn, still pay a royalty because of that. And they immediately went to the clinical trial and boom! - it was safe even with people who did not have HIV. Two trials were done on HIV negative people. Very very safe. The FDA gave a fast track designation based upon the safety and then Progenics did a Phase 2a and the viral load drop was one point six logarithm in just one week. Dr. Jeffrey Jacobsen from Jefferson University said that the viral load drop we saw for PRO 140 was better or as good as any HIV drug they have ever seen (at that time).
So, Dr. Paul Maddon stepped down as its CEO due to a lot of things including his own personal life. And immediately the new CEO said, what's the path to approval for PRO 140?
And the company said to him, well, you know, we need to do a Phase 2b. Well, how long does that take? Fifteen years. Ten years. The Phase 2b designed was in a substance abuse population. Then after that you need to do a Phase 3 (similar to a Phase 2 but five to ten times larger). In 2009 the FDA had told Progenics - You have to do a phase three on top of that Phase 2b. So now you've got 20 years of different trials to go through, and all of that for what possible outcome?
Thomas Barnard: Ha, ha, right … for substance abuse.
Nader Pourhassan: Yes, exactly. That's a population worth maybe 20 million dollars revenue per year. And then the new CEO took over… He said, sell this damn thing. And he was vulgar about it. And when we went there to pick up the product, he was saying, get this S-H-I-T out of here. Take every damn thing that has to do with this. They had spent hundreds of millions of dollars on manufacturing. There were eighty kilograms, equal to like half a million doses of this product, which they had made, and which they had stored at negative 80 degree Celsius.
They sold all of that and they had NIH money, $6 million, to conduct their Phase 2b substance abuse population. Dr. Jeffrey Jacobson was in charge of that. He had published several papers on PRO 140 and done all the Phase 1, 1a, and 2a. So I met up with him and had dinner with him several times. And I said, I'm not going to do this study. And he said, what do you mean? You don't know what the heck you are talking about. Who are you anyway? I explained that I had talked to Dr. Robert Schooley who you know, and he doesn’t think that is the way to go. Jacobsen says, Chip thinks that? So he called Dr. Robert Schooley and he said, Yes, there should be a study that compares leronlimab to Maraviroc or something like that. I had Chip outline every possible path to approval (and there were 5 or 6 of them). And I have a letter from him that I still keep for history [laughing].
He wrote to me and explained that I asked him to write a letter outlining all the paths to approval for PRO 140 so that I can share with the board. After that we had an analysis done by smart analysts on all these paths and potential revenue of each path should PRO 140 be successful in any of them. Smart analysts provided me with a ninety thousand dollar report said that this product (PRO 140) has no value. The head of Harvard University Medical School at that time said that this product will never make any money. So I went to the board that day and all the board members said, well, we're done. We should just shut down CytoDyn. And when they say there's no path forward, I said, wait a minute, guys. I think I can change the HIV paradigm with this. They ask me: What are you talking about? Well, it's not me. Here's this letter from Dr. Robert Schooley. I put his letter up on the screen. It was five or six paths forward. And I told the board, I am choosing [HIV] monotherapy as the path for leronlimab’s future.
Thomas Barnard: And this is...
Nader Pourhassan: So I talked to one of the inventors [of leronlimab], Dr. William Olson, and he said it was binding one hundred eight point five percent of the binding sites of HIV. So why would anybody say it won’t work in monotherapy? I think it will work. Dr. Robert Schooley says maybe it'll work and maybe it won’t. He said,You don't know till you try it. So I'm going to try it. The FDA was not happy with the idea of monotherapy. We also had to terminate our scientists who couldn't help us with the regulatory path. It was me a mechanical engineer trying to build something in monotherapy, and I only thought I had a 50% chance at best. Though Dr. Robert Schooley thought I had a chance, and also Dr. Jay Lalezari, who said, If this works Nader, you’ve hit a homerun. And I said, Let’s see. And we abandoned the NIH’s grant of $6 million and went the monotherapy route.
Thomas Barnard: Robert Schooley, was he the guy that you called in Africa?
Nader Pourhassan: [laughing] Yes, he was.I have tremendous amount of respect for him. When you talk about top person in the world, for me, that's Dr. Robert Schooley, Dr. Scott Hammer, Dr. Paul Maddon and Dr. Jay Lalezari. These four people carried me through this, especially Dr. Paul Maddon, who became my mentor and my very close friend. We used to talk almost every day.
Thomas Barnard: Really? So you're still in touch with the inventor then?
Nader Pourhassan: Absolutely. Yes, I love Paul. Jay Lalezari was very big also and still is, and Dr. Scott Hammer was very kind to go to all the FDA meetings with us.
Thomas Barnard: How did you connect with Dr. Lalezari?
Nader Pourhassan: Lalezari’s dad, Dr. Parviz Lalezari, read my book, which is called The Corruption of Muslim Minds. And he was also from Iran. A Jewish Iranian guy who after the revolution also had a hard time like my Dad did. When he read my book and he realized I'm COO of CytoDyn (at that time), he said - you should work with my son. So when I checked his son out, I found he was a key opinion leader in a clinical trial. So after I became the CEO, I asked Dr. Lalezari to help me and he agreed to do so.
Thomas Barnard: So that's how you connected with him. So, as I understand it the breast cancer trial is entirely composed of EIND patients or compassionate use patients?
Nader Pourhassan: No, no. We have a Phase 1b/2 in mTNBC [metatastic triple negative breast cancer]. In the compassionate use we have over 10 patients enrolled. In the emergency IND I have one patient, which is my mother-in-law. And then in the basket trial we now have six or seven patients. The basket trail is designed to include solid tumor data of 22 different cancers.
Thomas Barnard: Right. Right.
Nader Pourhassan: The patients that we have right now I don't know exactly which cancers. But prostate cancer is one of them.
Thomas Barnard: That's good. Good. I mean, I'm a man. So now I'm happy to hear that you working on that. You have a lot on your plate.
Nader Pourhassan: We have one drug with maybe 30 different indications.
Thomas Barnard: In your capacity, let's say, as chief safety officer, we are led to understand that over 800 patients have been enrolled in HIV testing without death or serious complication. You told Dr. Mobeen Syed that there are basically no complications with other drugs. That's what you said yesterday.
Many people are wondering to themselves, since there have been over one hundred thousand deaths in the U.S. alone, since you made your first announcement about a corona virus trial on March 9th. And understanding that I am asking this question within a very narrow frame, knowing that you must work with FDA, that indeed you are a fan of FDA, but understanding the severity of the disease, and understanding that I'm not asking you a policy question, but a very narrow question about safety. Would there be any harm in some kind of temporary approval to sell this drug until testing is completed?
Nader Pourhassan: So that's a very good question. And let me say this, if you're going to sell a product to, let's just say, five million people, what kind of sample size would give you complete assurance that nobody is going to get harmed from this drug? For five million, how many patients should I use? Now, when you say you have 800. FDA says 800 is great. And they've been very accommodating, allowing us to use the data from previous trials, even though the data was intended for a different indication. So they went out of their way. Something that usually ninety nine point nine percent of the time they don't do. They said for your combination therapy for [HIV], we would use your monotherapy data safety because you don't have enough data. If you do want to get the data from combination therapy it will take you five years. It took us three to four years for 50 patients in that population to be enrolled.
So with that said, now it comes to coronavirus. Should they take some chances? FDA wanted us to go through the normal path that they gave to 200 other applicants for Covid-19 treatment. They said go through pre-IND, and then IND, which would take three months minimum. They changed that immediately when they saw two patients from Dr. Seethamraju, one of them extubated. And Dr. Seethamraju immediately asked for nine more EIND’s. So FDA said good, it looks like you have something. Go ahead and do your Phase 2 and do your Phase 3 if you can help critical patient. They did that for hydroxychloroquine. They did that for remdesivir where they gave around a thousand three hundred patients to be studied even though their safety wasn’t really proven yet. With us, they accepted 390 patients for that same scenario because for safety, they were a little bit more comfortable with us, I'm guessing. I'm not putting words in FDA’s mouth. Then with regard to Phase 2 FDA allowed CytoDyn to conduct a trial of 75 patients. Unfortunately, some of investors criticize FDA unjustly. They complain, Why doesn't FDA give us more? But FDA is expert at that, they don't have just one person working. They have many, many experts working there. And they have been doing this for many, many years. For us to go there and say to them - What? Why not this, why not that? They are the people who run that show, and I believe they do a good job. And the last thing I want to do is to second guess the FDA, especially when I don't have all the data that they would have. We have to give room to our agency [FDA] who is respected all over the world, and whose findings are accepted everywhere in the world. We should accept their decisions. Why? Because they have tremendous credibility. Let's be happy about what we have in this country. Let’s enjoy that.
Thomas Barnard: So all right. So what you're saying is you really don't want to respond on safety because you don’t have all the data FDA has, and maybe you don’t have the expertise, and that’s their job. Okay.
Thomas Barnard Nader Pourhassan: Covid-19. You know that all these scientists are still saying we don't know a lot of things about it. They are saying that all the time. So they don't know. How do they know? How would they know what leronlimab would do, even though it has shown safety in HIV population? We need to have some kind of safety on coronavirus. Just look at it very carefully. I don't know about those things. I don't know what standard they had, but they’ve got 200 companies, and don’t give approval to anybody unless they can pass the test. Do they want to have more people dying [from a new drug] than what are dying [from Covid]. So we have to go through the same rigorous steps and make sure that we comply. I do that as fast as we can, and agree with the way the system is working.
Thomas Barnard: Okay. Thank you.
Nader Pourhassan You know, I mean, we're almost there.
Thomas Barnard: I as I said in my question, you know, one hundred thousand people have maybe died since you started your studies.What harm would there be? I mean, I don't know the answer. I'm just voicing what I think a lot of people are curious about. And what you're saying is safety requires numbers.
Nader Pourhassan: Safety requires numbers. And FDA is expert at that. If they believe it is safe, then we can take that to the bank.When I say that it’s safe, it’s just me, and I’m CEO and I believe in this company and its drugs. So that is not something the FDA should take seriously unless I can provide data and I have not done that yet but we are very close (in my opinion) of doing so. They should take the data seriously, and data in Covid-19.
Thomas Barnard: I have read that leronlimab has an indication for Alzheimer’s, what can you tell me about that?
Nader Pourhassan: I am going to direct you to Dr. Kelly, who is both our Chief Medical Officer and our Chairman.
= = = =
So, I connected with Dr. Scott Kelly and asked him about the Alzheimer’s trial.
Scott Kelly Chairman Cytodyn
Thomas Barnard: We understand that an Alzheimer’s trial is in planning or in progress. Can leronlimab get through the blood brain barrier?
Scott Kelly: Nader and I were discussing effector cells crossing the blood brain barrier in Multiple Sclerosis, and the possibility of leronlimab working on Alzheimer’s. We believe there is a neuroinflammation component to Alzheimer’s, and leronlimab can mitigate the recruitment and immigration of immune cells across the blood brain barrier. In addition, since neuroinflammation, and CCL5, can disrupt the blood brain barrier, it would potentially allow leronlimab to enter the central nervous system directly.
Thomas Barnard:How far along is this work?
Scott Kelly: We are pretty far along on the protocol. When that is complete, we’ll apply for a Phase 2 study.
Thomas Barnard: And the liver disease NASH, how did that come about?
Scott Kelly: Dr. Dan Lindner did a study at the Cleveland Clinic, which showed a 3 fold reduction in hepatic steatosis in the leronlimab group as compared to placebo.
Hepatocytes secrete RANTES, and CCR5 is present on both stellate cells and hepatocytes. We also know that stellate cells are what produce the scar tissue in the liver.
Thomas Barnard: Stroke was mentioned somewhere as a possible indication.
Scott Kelly: Stroke is a more recent possibility. Doctors have been discussing this with us, and we think leronlimab could work based upon the relationship of CCR5 in stroke recovery as well as traumatic brain injury.
Thomas Barnard: The results of the mild-to-moderate study were pretty straightforward. Very good improvement (50% vs 20%) against the NEWS2 standard, but the surprising thing, I thought, were the safety results. On the conference call Jay Lalezari was saying that these safety results were exceptional. The impression he left was that most experimental drugs were happy just to match the safety results of the control group, much less improve on them. Further, he was saying that this should be one of the endpoints of the study, even if it wasn't planned that way at the study outset. I heard this and rolled it around in my mind, and it seems to me one reason this might be the case comes with the theme of these interviews, which is that leronlimab seems to work against many diseases, and that the reason it was so safe was that aside from dealing with the Covid-19 infection, it was perhaps treating other conditions the patient may have had. Do you think this might be true?
Scott Kelly: I think the safety results are better in leronlimab than placebo in the Covid-19 population because the effect of the virus is not limited to the lungs but affects multiple organs. It is a multisystem disorder and that is represented in SAE’s and AE’s.
Thomas Barnard: Those are caused by Covid-19, but I’m wondering if other secondary conditions that patients have had before the disease, and which contribute to a bad picture. Could those also be improved by leronlimab?
Scott Kelly: That is also possible.
Thomas Barnard: When the basket cancer trial was announced, I did not quite get the connection to the CCR5 receptor, but I presumed there must be one, so I looked them up one by one against the cancers mentioned in the press release, and I found a study or studies related to every single one. There appears to be just an awful lot of research on the CCR5 receptor. Have you found this to be true yourself?
Scott Kelly: Yes, absolutely. This is research being conducted by scientists all over the world independent of CytoDyn.
Thomas Barnard: How did you get involved in CytoDyn? Nader Pourhassan was tired of traveling to China, or maybe his wife was tired of him traveling to China, and one of his friends asked him to get involved in this company he was over-invested in. When you did buy your first shares?
Scott Kelly: I believe it was 2016 when I bought my first shares. But I was following it as early as 2011. My interest in CytoDyn rose because they were doing HIV. And I wanted to find the next company Gilead would acquire. Gilead is a leader in HIV and their HIV treatments still make up the majority of their revenue. I liked the concept of blocking the CCR5 receptor, because I believe it makes more sense to block healthy cells from HIV entry. Why wait until the virus enters the cell and begins to make billions of copies of itself before you decide to fight it? It doesn’t make sense. I watched the CytoDyn closely for years to try and find a reason the technology would fail either from an efficacy standpoint or safety standpoint. It never did. The efficacy and safety continued to astonish me. Once I realized the same receptor was involved in multiple disease processes, I felt it was important to pursue those opportunities so I became more involved to assist in those efforts.
At first I spoke with Michael Mulholland, and I would ask him: What am I missing? Still wondering about safety and efficacy. And then I would ask him why they weren’t pursuing other possibilities for leronlimab, and he said I should talk with Nader. And I asked Nader: What am I missing? And he said, Nothing. And I asked him about all these other possibilities, graft versus host, and others, and he said, Who are you? I am a doctor and an investor in biotech. And he said, You will need to sign an NDA [non-disclosure agreement], so I can talk to you. And, when that was done he explained that others on the board were only interested in the HIV indication.
Nader was interested in these other indications, and he told me the story of Humira, which stands for “human monoclonal antibody for rheumatoid arthritis,” a TNF blocker [tumor necrosis factor] which became one of the most successful drugs in history. The story was similar to leronlimab. He asked if I would join the board. And I said that I had a medical practice, and I would have to get back to him. Eventually, I agreed to join the board. There were all these indications and I felt many patients would benefit. And I needed to become more involved to pursue those other possibilities.
Thomas Barnard: So, when you were first bought was it mainly for HIV? But you also knew about some of these other possible indications.
Scott Kelly: Yes, but I realized as I learned more about the drug that were more indications for leronlimab than I had originally seen.
Thomas Barnard: And you bought more shares?
Scott Kelly: Yes
Thomas Barnard: I think it is a common occurrence. I bought with the breast cancer results and then I wrote a piece about four biotechs. CytoDyn was one of them, and I bought some more after I interviewed Nader. But I also wrote about Sorrento…
Scott Kelly: I have followed Sorrento, and have invested in their company. The stock is up on the news of the saliva test. I have been a biotech investor for years. And as I said, I was looking for Gilead’s next acquisition. I thought Gilead would acquire Kite, and I also purchased Juno which was acquired by Celgene.
Thomas Barnard: Wow! That’s impressive. Though I always felt CAR T was just too expensive. $300,000 per treatment. And would be supplanted by something less expensive.
Scott Kelly: It is expensive, that’s true. But I think there will continue to be a use for it. The beauty of leronlimab is that it can be used with any of these cancer treatments - chemotherapy, CAR T, radiation, checkpoint inhibitors. There do not appear to be any drug interactions.
Thomas Barnard: I know leronlimab has these three possible actions in cancer: 1) it stops metastasis, 2) the anti-angiogenesis effect, and 3) the re-polarization of macrophages, but the one effect that I thought would be in every oncologists toolkit was that it stops metastasis. If you stop metastasis, there are a number of ways to knock out the primary tumor.
Scott Kelly: You’re right. In animal studies, it was 98% effective in stopping metastasis.
Thomas Barnard: Is there anything else you’re excited about?
Scott Kelly: We are working on PrEP (prevention of HIV) through a once a month injection, and cure in HIV patients who are receiving allogeneic bone marrow transplantation. The only two patients ever cured of HIV received bone marrow transplants with cells deficient in the CCR5 receptor.
Thomas Barnard: I think I understand…if there is no CCR5 receptor, then HIV has no place to land.
Scott Kelly: That’s right. One of people on our scientific advisory is Gero Hütter, who cured the first HIV patient, known as the Berlin patient.
Thomas Barnard: That’s handy.
Scott Kelly: Another is Hope Rugo, who is a famous breast cancer researcher at UCSF.
Thomas Barnard: Also handy, since you doing a trial on triple negative breast cancer patients.
Scott Kelly: The prognosis for those patients is not very good.
Thomas Barnard: So far it looks like leronlimab can help. Thank you, Dr. Kelly.
= = = = = = = = = = = = = = = = = = = = = = = = = = == = = = = = =
The Indications
The indications for leronlimab so far include HIV (where studies are completed and an application for sale has been made to the FDA), Covid-19, multiple sclerosis, graft-versus-host disease, breast cancer, and other cancers expressing the CCR5 receptor, influenza, stroke, and Alzheimer’s Disease. A small 30 subject Phase 2 trial is on-going to test the drug against 22 different types of cancer.
Precision Medicine
We are in a new era of “precision medicine” based on an understood method of action. CytoDyn’s results appear to affirm that kind of understanding:
Covid-19 – viral load drops to zero/undetectable
HIV – viral load drops to zero/undetectable
Triple Negative Breast Cancer – CTC’s (circulating tumor cells) drop to zero/undetectable
Animal studies also seem to confirm these kinds of results. In Multiple Sclerosis all of the control animals that did not get leronlimab, were paralyzed. All the animals that got it were okay. In GvHD (graft versus host disease) all the animals that got the leronlimab lived, all those that did not died. These are striking results.
Former Director of Virology at Stanford, Dr. Bruce Patterson, said in his TEDx Talk, that this is the kind of drug that the nation should be stockpiling against the next viral outbreak. Time will tell.
Disclosure: I am/we are long CYDY.
I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it. I have no business relationship with any company whose stock is mentioned in this article.
Additional disclosure: I may acquire more shares in the next 72 hours."
"Interviews With CytoDyn Tell Story Of Leronlimab And Its Many Indications
Sep. 2, 2020 1:18 AM ET|About: CytoDyn Inc. (CYDY)
Summary
In depth story of the development of a drug - leronlimab, and how a blocker of the CCR5 receptor found other applications.
Covid-19 testing of mild-to-moderate cases was successfully completed with statistically significant results.
Company has gone to FDA for EUA (emergency use authorization) for an unmet medical need.
After $28.5 million funding and exercise of warrants the company has never had more cash.
The Investment Idea Behind It All
The bet is that an investment in a biotech, CytoDyn (OTCQB:CYDY), with a single drug with multiple applications will find its markets, generate billions of revenue, save lives, improve quality of life, and deliver an unusually high return to investors.
Source: https://bigcharts.marketwatch.com/
Results of a Mild-to-Moderate Covid-19 Study Were Excellent
CytoDyn has just completed a statistically significant Covid-19 study of mild-to-moderate subjects a week ago. The results were unusual on the safety end. Basically, you were at twice the risk of a SAE (severe adverse event) if you were in the placebo group. 5 SAEs out of 56 for the leronlimab group versus 12 out of 56 (2x of 6 out of 28) in the control group. In the usual case, an experimental drug hopes their safety will be as good as the control group (placebo). This kind of thing where the safety of the experimental drug is much better than control does not happen, according to Jay Lalezari, CytoDyn Interim Chief Scientist. So, it appears to be very safe indeed.
The efficacy was also outstanding in this study of patients in which both the control group and the leronlimab group are recovering from Covid-19 infection. Against a standard called NEWS2, leronlimab subjects saw 50% improvement versus 20% improvement by the placebo group.
Consequently, CytoDyn has applied to the FDA for right to sell the product under an EUA, an emergency use authorization for an unmet medical need. The government is under pressure to provide medicines against this malignant virus, but the problem is that even though the FDA authorized this small Phase 2 study of 75, they did not intend to approve it for sale on the basis of such a small study. So, they have to decide in this time of crisis where 10,000 people are dying each month whether to give it the green light, or hold out for more results. It will require nerves of steel whichever way they decide. Usually, FDA requires a larger Phase 3 to further establish the good results of a Phase 2 study. So, approval is not in the bag. It is typically a matter of numbers. Working in their favor are the excellent safety results so far. More than 800 HIV patients have been tested with no death or serious complications. And now there are more cancer subjects added to that, and the unusually good safety results of the Covid-19 patients.
When the CEO Dr. Nader Pourhassan was queried about doing another trial for FDA, he’s not bothered. A double blind study has just been completed in which the results were wonderful, indeed all of their trial results have been positive. Though sensibly they have pursued trials where the receptor CCR5 was implicated and studied and written about in the medical literature, so there were theoretical reasons to believe it might work.
Small biotechs are always short of cash, but CEO Pourhassan reports by virtue of the exercise of warrants, and a recent funding of $28.5 million at a conversion rate of $10 means that he has never had so much money in the bank.
Below are interviews with the CEO of CytoDyn, Nader Pourhassan, and the Chairman of the Board of CytoDyn, Scott Kelly. As the interviews will show, Pourhassan has the essential qualities of an outstanding CEO, a Ph.D. himself, he tracked down the best brains he could find, and learned from them. When advisors were hesitant, he went ahead anyway, and was proved correct. And when an inquiring doctor called the office asking about this possibility and that possibility, he recruited that doctor (Scott Kelly M.D.), who eventually quit his practice and joined the Board, eventually becoming Chairman, but staying true to his own north star, the drug’s possibilities, he took the additional job of Chief Medical Officer.
It is important to explain the word “indication”. An indication in biotech means the possibility that a given medical condition may respond to a medication, in this case we are speaking of CytoDyn’s leronlimab.
The Interviews
Thomas Barnard: So let's see, where shall I begin? How is your mother-in-law? [CytoDyn investors will know that she was the first lady with mTNBC – metastatic triple negative breast cancer – to receive leronlimab.]
Nader Z. Pourhassan, PhD
Nader Pourhassan: Doing much better than she was doing a few weeks ago.
Thomas Barnard: What happened?
Nader Pourhassan: She still has tumor in her brain, and she had a mild stroke a couple of weeks ago. It affected her right side, and the doctor said she would never be able to use the right side, and it won’t come back. But within three days she was able to walk on her own. Slowly, of course. Scott Kelly found published papers on CCR5 and stroke.
Thomas Barnard: What about her right arm? Can she do anything with that?
Nader Pourhassan: Yes, she eats with her right hand, and she’s using it.
Thomas Barnard: Wow.
Nader Pourhassan: Yes, it’s remarkable. We think it is the weekly doses of leronlimab that is helping her. It’s anecdotal, but we are having the doctor prepare a case report.
Thomas Barnard: Home testing of a new indication? So, let me ask you this: How did CytoDyn connect with Bruce Patterson? I mean, did he see your work and come to you or did you go to him or how did that work?
Nader Pourhassan: So Bruce Patterson was introduced to us through an associate of one of our old board members. And then I talked to him right after I heard about him. When I met with him he said he could do receptor occupancy tests for us. He could develop an assay for us and while we had other people who could do receptor occupancy tests, we went ahead and gave the project to him.
Thomas Barnard: A receptor occupancy test?
Nader Pourhassan: A receptor occupancy test tells you if the leronlimab is sitting on the receptor.
Nader Pourhassan: And he also was adamant that the cancer possibilities were great, but we were already doing cancer with Dr. Richard Pestell, and before that with Dr. Denis Burger. However, at that time, Dr. Pestell was our Chief Medical Officer. Dr. Pestell had already helped us to get the triple negative breast cancer trials under way. And when Bruce Patterson joined us as a consultant, he said that there's a lot of potential here and we were happy with that. In a few months we terminated Dr. Richard Pestell, and only worked with Dr. Patterson. Dr. Pestell gave us some fantastic information on receptor occupancy of cancer patients. It turns out that Dr. Patterson was not able to get the assay ready for receptor occupancy. So we got another lab, which was run Hallgeir Rui, M.D. Ph.D. So any cancer patient today who wants to get involved in the leronlimab trial must first have a biopsy. And then we send the biopsy to Dr. Hallgeir Rui, whose laboratory is in Wisconsin. And over there they analyzed to see if we have the necessary receptors.I mean, if the patient is qualified to be in the cancer study.
Thomas Barnard: So, let me understand, what you mean is that cancer must show the CCR5 receptor or forget it. Right?
Nader Pourhassan: The cancer patient’s biopsy is checked for a few things. First, does it have CCR5 on any of the tumor cells? And then there's infiltration of the leukocytes around the tumor cells. Do the leukocytes have any CCR5? And we checked both of those. Now, if they do, they're qualified to be in the trial.
It was around this time that Dr. Scott Kelly started asking me about what do you think about Covid-19 because he thought that ARDS was something we might work on, and which we had already discussed with other folks. I called Dr. Patterson. He also agreed that yes, you will be able to stop ARDS, which is the main cause of death in Covid-19. We immediately prepared IND and protocol and sent it to the FDA for a phase 2 trial. They said, no, you can’t file IND, you have to do pre-IND first, because you don't have any data. And that's when we got a call from Dr. Seethamraju. He said, My critical patients are not doing well at all. They are not going to make it. He called FDA and said, I agree with that theory leronlimab stops the trafficking of macrophages that was published in articles.So once he injected patients under an Emergency IND that made FDA feel more comfortable that our drug was not going to increase the cytokine storm, but perhaps give some benefit. After a couple of patients were extubated, they immediately gave us Phase 2 and Phase 3 green light without waiting three months or so.
Thomas Barnard: That's very interesting to know. So it was actually Scott Kelly, your Chairman and Chief Medical Officer, who was the one who thought working on Covid might be a good idea.
Nader Pourhassan: Yes, that's correct. But not only him, but there were other people who were telling me about it. We were talking to a company - I don't want to use their name, but a company, their chief medical officer, a very close friend of mine said we're looking at flu and you guys should probably have indication in flu. And I spoke to Dr. Denis Berger, who was a board member. And he's the one that conducted the study for M.S. [multiple sclerosis]. He had friends at the Providence Medical Center. After seeing the results of the animal study he thought M.S. is a huge indication. But it was Dr. Denis Burger, a former professor at Oregon Health and Sciences University, who had pointed to [M.S.] for many years, and he was the CEO for four successful biotechs. And I'm still in touch with Dr. Denis Burger. So the increase in the number of indications that leronlimab were found to have was because of Dr. Denis Burger and Dr. Scott Kelly. I had asked Dr. Burger about the cancer indication many years ago. And that's when we filed for patents for cancer (he is the inventor on many of our cancer patents). That was four years ago, it three years later, we got to know Dr. Patterson. Then we got started with Dr. Jay Lalezari in cancer. Dr Jay Lalezari was always involved with us from day one, but not in cancer originally, in HIV.
Thomas Barnard: Gotcha. Let's go back to the breast cancer thing, that was actually the thing that that moved me to buy shares a while back, because I thought that was an extraordinary result. Now I'm reading up. And it seems like Pfizer has a drug called Maraviroc, which they wrote about it in February of 2019.So that would seem to have indicated that when you tried it out on your mother-in-law, it wasn't out of the blue, you had a foundation actually that this might work.Is that right?
Nader Pourhassan: So, yeah. So Pfizer had started a cancer trial with Maraviroc, I believe, several years ago. And they started even before we did. As I told you at the beginning, about three or four years ago we applied for patents with Dr. Denis Burger. So Pfizer accidentally found all these new indications in graft versus host disease for Maraviroc. How was that? Well, the patients who have HIV for a long time usually develop AML, acute myeloid leukemia, or DMS, and they need bone marrow transplant. When Pfizer looked at the data they realized that these patients who get bone marrow transplant don't get graft versus host disease if they were HIV patients who were on Maraviroc.They all of a sudden say, wait a minute, this might have indication. Maraviroc might have indication in GvHD [graft versus host disease].
Thomas Barnard: (laughing) I see. By accident.
Nader Pourhassan: Let me tell you the most interesting part at that time. At CytoDyn we had a very strong cancer person, key opinion leader.And that person and Dr. Denis Burger both believed in the potential GvHD indication for leronlimab (called PRO 140 at that time). I wanted to do an animal study of graft versus host disease with leronlimab. When we held a key opinion meeting Dr. Paul Maddon, inventor, was on the call at my request. I had asked him to come on the call. He said no, no, no, no. There is no GvHD [graft versus host indication] for leronlimab. This was four and a half, five years ago. And he said, No, no, no, everything must stop. Maraviroc stops chemokines from binding. Leronlimab doesn't do that. And that's why we don't have any side effects or toxicity. So stop everything. Everything gets stopped, and the next day or two I told Denis Burger: I want to know why the video that shows mechanism of action of leronlimab by Paul Maddon had indicated that chemokine binding hardly doesn't happen. “Hardly” doesn't mean zero in mathematics. Hardly means something. Need to go check with the company who did the toxicology of leronlimab and find out what amount of PRO 140 [leronlimab] do we need to use to make that happen?And Dennis Burger said, no, no, no, leave it alone, you don't know what the hell you are talking about. Stop it.
Dr. Bruce Montgomery (a board member at that time) says no. Paul said no. I said, Well, I'm going to get it myself. So I had Amarex call Nobel Lifesciences, Dr. Stephen Horrigan. He knows me very well from that time, because I thought, I'm doing this without my board members support. And I sent twelve thousand dollars to do the in vitro study. And this study showed that leronlimab was better than Maraviroc in GvHD in an in vitro study. I had Amarex send the data to the FDA without the board members approval and submitted a protocol. And Denis Burger said, Oh my God, you were right. And FDA immediately gave us Phase 2 and asked for animal data in order to give us Orpha Drug Designation. So I told Denis Burger, Please now go do the animal study that the FDA is requesting. The FDA suggested that in our animal study that we inject 32 mice with human bone marrow. We knew they all would die from GvHD. If some of the mice in the half (16) that get leronlimab stay alive, we’ll give leronlimab Orphan Drug Designation. All the mice stayed alive! And all the mice in the control arm that did not get leronlimab died. And Denis Burger said, “Oh, my God, leronlimab has potential for many so many things.” Dennis Burger became my hero at that time because he was forced to stay with GvHD by me, and that opened the door for him to explore M.S., cancer, and many more indications for leronlimab. I loved Denis and still do.
And then he took the product to Providence for an animal study in M.S., and he cried almost at the board meeting. The three mice that got leronlimab had zero paralysis. Zero. And the people at Providence Medical Center said, Where did you get this product? Oh, my God. And then Dr Jonah Sacha said, “Nader, every time we show the results of leronlimab to the scientists, they say where did you get this product? This product is worth billions and billions. This is unbelievable what it can do for humanity.”
Thomas Barnard: Good. So I'm understanding then that leronlimab works better than Maraviroc.
Nader Pourhassan: Absolutely. Maraviroc has approval for HIV. But it has a black box warning, it has liver toxicity. Our product, we believe, probably helps with liver restoration; it helps all kinds of different autoimmune and cancers. So, if our bodies suffer for whatever reason, any virus, Covid-19, flu or whatever, or any scratch or any foreign object goes your body…the immune system must fight it. Many of our immune cells have CCR5 on their surfaces - macrophages and on T regulatory cells. And we believe that probably leronlimab binds to a very, very special place on CCR5, which is a work of art by Dr. Paul Maddon and William Olson, Ph.D. from MIT.
Thomas Barnard: Did Maddon know what he was doing when he did this? I mean, did he…
Nader Pourhassan: He was focused on getting this molecule to bind to the exact location that HIV binds. Just keep in mind, Paul Maddon got his M.D. and Ph.D. from Columbia University, his dissertation, his research for his Ph.D. was on where HIV binds first, which was the CD4 receptor on a T-cell. So he was the first man who discovered that. Then, he founded Progenics, a biotech company. And then he discovered the interaction of HIV with CCR5. Then he made an antibody against CCR5. And Dr. David Ho, who ended up saving millions of lives of HIV patients by developing HAART and became Time magazine Man of the Year, was a very close colleague of Dr. Paul Maddon. Ho found an antibody against CCR4. Paul Maddon felt he had a better target, and said, I want to go after CCR5. Now at Progenics, where he founded Progenics and where he was CEO for 30 years. He got the molecule to bind to the optimal site on CCR5.
He first found a molecule and it was called (I believe) PRO 540, not 140. In the first year of development of PRO 540, the viral load drop wasn't good enough because it wasn't binding to exactly the right place. Dr. William Olson, (Ph.D. from M.I.T.) worked for Dr. Maddon, said to me that not long after the PRO 540 failure, We went back to the drawing board. I went through thousands and thousands of antibodies, and one morning I came in and I had isolated one antibody and I thought, my God, it binds to one hundred eight point percent of the HIV binding sites. That would mean that HIV would have no way to bind to that site.
He said immediately when they got that molecule they had to humanize it, which cost them a lot of money in 1999. And we, CytoDyn, still pay a royalty because of that. And they immediately went to the clinical trial and boom! - it was safe even with people who did not have HIV. Two trials were done on HIV negative people. Very very safe. The FDA gave a fast track designation based upon the safety and then Progenics did a Phase 2a and the viral load drop was one point six logarithm in just one week. Dr. Jeffrey Jacobsen from Jefferson University said that the viral load drop we saw for PRO 140 was better or as good as any HIV drug they have ever seen (at that time).
So, Dr. Paul Maddon stepped down as its CEO due to a lot of things including his own personal life. And immediately the new CEO said, what's the path to approval for PRO 140?
And the company said to him, well, you know, we need to do a Phase 2b. Well, how long does that take? Fifteen years. Ten years. The Phase 2b designed was in a substance abuse population. Then after that you need to do a Phase 3 (similar to a Phase 2 but five to ten times larger). In 2009 the FDA had told Progenics - You have to do a phase three on top of that Phase 2b. So now you've got 20 years of different trials to go through, and all of that for what possible outcome?
Thomas Barnard: Ha, ha, right … for substance abuse.
Nader Pourhassan: Yes, exactly. That's a population worth maybe 20 million dollars revenue per year. And then the new CEO took over… He said, sell this damn thing. And he was vulgar about it. And when we went there to pick up the product, he was saying, get this S-H-I-T out of here. Take every damn thing that has to do with this. They had spent hundreds of millions of dollars on manufacturing. There were eighty kilograms, equal to like half a million doses of this product, which they had made, and which they had stored at negative 80 degree Celsius.
They sold all of that and they had NIH money, $6 million, to conduct their Phase 2b substance abuse population. Dr. Jeffrey Jacobson was in charge of that. He had published several papers on PRO 140 and done all the Phase 1, 1a, and 2a. So I met up with him and had dinner with him several times. And I said, I'm not going to do this study. And he said, what do you mean? You don't know what the heck you are talking about. Who are you anyway? I explained that I had talked to Dr. Robert Schooley who you know, and he doesn’t think that is the way to go. Jacobsen says, Chip thinks that? So he called Dr. Robert Schooley and he said, Yes, there should be a study that compares leronlimab to Maraviroc or something like that. I had Chip outline every possible path to approval (and there were 5 or 6 of them). And I have a letter from him that I still keep for history [laughing].
He wrote to me and explained that I asked him to write a letter outlining all the paths to approval for PRO 140 so that I can share with the board. After that we had an analysis done by smart analysts on all these paths and potential revenue of each path should PRO 140 be successful in any of them. Smart analysts provided me with a ninety thousand dollar report said that this product (PRO 140) has no value. The head of Harvard University Medical School at that time said that this product will never make any money. So I went to the board that day and all the board members said, well, we're done. We should just shut down CytoDyn. And when they say there's no path forward, I said, wait a minute, guys. I think I can change the HIV paradigm with this. They ask me: What are you talking about? Well, it's not me. Here's this letter from Dr. Robert Schooley. I put his letter up on the screen. It was five or six paths forward. And I told the board, I am choosing [HIV] monotherapy as the path for leronlimab’s future.
Thomas Barnard: And this is...
Nader Pourhassan: So I talked to one of the inventors [of leronlimab], Dr. William Olson, and he said it was binding one hundred eight point five percent of the binding sites of HIV. So why would anybody say it won’t work in monotherapy? I think it will work. Dr. Robert Schooley says maybe it'll work and maybe it won’t. He said,You don't know till you try it. So I'm going to try it. The FDA was not happy with the idea of monotherapy. We also had to terminate our scientists who couldn't help us with the regulatory path. It was me a mechanical engineer trying to build something in monotherapy, and I only thought I had a 50% chance at best. Though Dr. Robert Schooley thought I had a chance, and also Dr. Jay Lalezari, who said, If this works Nader, you’ve hit a homerun. And I said, Let’s see. And we abandoned the NIH’s grant of $6 million and went the monotherapy route.
Thomas Barnard: Robert Schooley, was he the guy that you called in Africa?
Nader Pourhassan: [laughing] Yes, he was.I have tremendous amount of respect for him. When you talk about top person in the world, for me, that's Dr. Robert Schooley, Dr. Scott Hammer, Dr. Paul Maddon and Dr. Jay Lalezari. These four people carried me through this, especially Dr. Paul Maddon, who became my mentor and my very close friend. We used to talk almost every day.
Thomas Barnard: Really? So you're still in touch with the inventor then?
Nader Pourhassan: Absolutely. Yes, I love Paul. Jay Lalezari was very big also and still is, and Dr. Scott Hammer was very kind to go to all the FDA meetings with us.
Thomas Barnard: How did you connect with Dr. Lalezari?
Nader Pourhassan: Lalezari’s dad, Dr. Parviz Lalezari, read my book, which is called The Corruption of Muslim Minds. And he was also from Iran. A Jewish Iranian guy who after the revolution also had a hard time like my Dad did. When he read my book and he realized I'm COO of CytoDyn (at that time), he said - you should work with my son. So when I checked his son out, I found he was a key opinion leader in a clinical trial. So after I became the CEO, I asked Dr. Lalezari to help me and he agreed to do so.
Thomas Barnard: So that's how you connected with him. So, as I understand it the breast cancer trial is entirely composed of EIND patients or compassionate use patients?
Nader Pourhassan: No, no. We have a Phase 1b/2 in mTNBC [metatastic triple negative breast cancer]. In the compassionate use we have over 10 patients enrolled. In the emergency IND I have one patient, which is my mother-in-law. And then in the basket trial we now have six or seven patients. The basket trail is designed to include solid tumor data of 22 different cancers.
Thomas Barnard: Right. Right.
Nader Pourhassan: The patients that we have right now I don't know exactly which cancers. But prostate cancer is one of them.
Thomas Barnard: That's good. Good. I mean, I'm a man. So now I'm happy to hear that you working on that. You have a lot on your plate.
Nader Pourhassan: We have one drug with maybe 30 different indications.
Thomas Barnard: In your capacity, let's say, as chief safety officer, we are led to understand that over 800 patients have been enrolled in HIV testing without death or serious complication. You told Dr. Mobeen Syed that there are basically no complications with other drugs. That's what you said yesterday.
Many people are wondering to themselves, since there have been over one hundred thousand deaths in the U.S. alone, since you made your first announcement about a corona virus trial on March 9th. And understanding that I am asking this question within a very narrow frame, knowing that you must work with FDA, that indeed you are a fan of FDA, but understanding the severity of the disease, and understanding that I'm not asking you a policy question, but a very narrow question about safety. Would there be any harm in some kind of temporary approval to sell this drug until testing is completed?
Nader Pourhassan: So that's a very good question. And let me say this, if you're going to sell a product to, let's just say, five million people, what kind of sample size would give you complete assurance that nobody is going to get harmed from this drug? For five million, how many patients should I use? Now, when you say you have 800. FDA says 800 is great. And they've been very accommodating, allowing us to use the data from previous trials, even though the data was intended for a different indication. So they went out of their way. Something that usually ninety nine point nine percent of the time they don't do. They said for your combination therapy for [HIV], we would use your monotherapy data safety because you don't have enough data. If you do want to get the data from combination therapy it will take you five years. It took us three to four years for 50 patients in that population to be enrolled.
So with that said, now it comes to coronavirus. Should they take some chances? FDA wanted us to go through the normal path that they gave to 200 other applicants for Covid-19 treatment. They said go through pre-IND, and then IND, which would take three months minimum. They changed that immediately when they saw two patients from Dr. Seethamraju, one of them extubated. And Dr. Seethamraju immediately asked for nine more EIND’s. So FDA said good, it looks like you have something. Go ahead and do your Phase 2 and do your Phase 3 if you can help critical patient. They did that for hydroxychloroquine. They did that for remdesivir where they gave around a thousand three hundred patients to be studied even though their safety wasn’t really proven yet. With us, they accepted 390 patients for that same scenario because for safety, they were a little bit more comfortable with us, I'm guessing. I'm not putting words in FDA’s mouth. Then with regard to Phase 2 FDA allowed CytoDyn to conduct a trial of 75 patients. Unfortunately, some of investors criticize FDA unjustly. They complain, Why doesn't FDA give us more? But FDA is expert at that, they don't have just one person working. They have many, many experts working there. And they have been doing this for many, many years. For us to go there and say to them - What? Why not this, why not that? They are the people who run that show, and I believe they do a good job. And the last thing I want to do is to second guess the FDA, especially when I don't have all the data that they would have. We have to give room to our agency [FDA] who is respected all over the world, and whose findings are accepted everywhere in the world. We should accept their decisions. Why? Because they have tremendous credibility. Let's be happy about what we have in this country. Let’s enjoy that.
Thomas Barnard: So all right. So what you're saying is you really don't want to respond on safety because you don’t have all the data FDA has, and maybe you don’t have the expertise, and that’s their job. Okay.
Thomas Barnard Nader Pourhassan: Covid-19. You know that all these scientists are still saying we don't know a lot of things about it. They are saying that all the time. So they don't know. How do they know? How would they know what leronlimab would do, even though it has shown safety in HIV population? We need to have some kind of safety on coronavirus. Just look at it very carefully. I don't know about those things. I don't know what standard they had, but they’ve got 200 companies, and don’t give approval to anybody unless they can pass the test. Do they want to have more people dying [from a new drug] than what are dying [from Covid]. So we have to go through the same rigorous steps and make sure that we comply. I do that as fast as we can, and agree with the way the system is working.
Thomas Barnard: Okay. Thank you.
Nader Pourhassan You know, I mean, we're almost there.
Thomas Barnard: I as I said in my question, you know, one hundred thousand people have maybe died since you started your studies.What harm would there be? I mean, I don't know the answer. I'm just voicing what I think a lot of people are curious about. And what you're saying is safety requires numbers.
Nader Pourhassan: Safety requires numbers. And FDA is expert at that. If they believe it is safe, then we can take that to the bank.When I say that it’s safe, it’s just me, and I’m CEO and I believe in this company and its drugs. So that is not something the FDA should take seriously unless I can provide data and I have not done that yet but we are very close (in my opinion) of doing so. They should take the data seriously, and data in Covid-19.
Thomas Barnard: I have read that leronlimab has an indication for Alzheimer’s, what can you tell me about that?
Nader Pourhassan: I am going to direct you to Dr. Kelly, who is both our Chief Medical Officer and our Chairman.
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So, I connected with Dr. Scott Kelly and asked him about the Alzheimer’s trial.
Scott Kelly Chairman Cytodyn
Thomas Barnard: We understand that an Alzheimer’s trial is in planning or in progress. Can leronlimab get through the blood brain barrier?
Scott Kelly: Nader and I were discussing effector cells crossing the blood brain barrier in Multiple Sclerosis, and the possibility of leronlimab working on Alzheimer’s. We believe there is a neuroinflammation component to Alzheimer’s, and leronlimab can mitigate the recruitment and immigration of immune cells across the blood brain barrier. In addition, since neuroinflammation, and CCL5, can disrupt the blood brain barrier, it would potentially allow leronlimab to enter the central nervous system directly.
Thomas Barnard:How far along is this work?
Scott Kelly: We are pretty far along on the protocol. When that is complete, we’ll apply for a Phase 2 study.
Thomas Barnard: And the liver disease NASH, how did that come about?
Scott Kelly: Dr. Dan Lindner did a study at the Cleveland Clinic, which showed a 3 fold reduction in hepatic steatosis in the leronlimab group as compared to placebo.
Hepatocytes secrete RANTES, and CCR5 is present on both stellate cells and hepatocytes. We also know that stellate cells are what produce the scar tissue in the liver.
Thomas Barnard: Stroke was mentioned somewhere as a possible indication.
Scott Kelly: Stroke is a more recent possibility. Doctors have been discussing this with us, and we think leronlimab could work based upon the relationship of CCR5 in stroke recovery as well as traumatic brain injury.
Thomas Barnard: The results of the mild-to-moderate study were pretty straightforward. Very good improvement (50% vs 20%) against the NEWS2 standard, but the surprising thing, I thought, were the safety results. On the conference call Jay Lalezari was saying that these safety results were exceptional. The impression he left was that most experimental drugs were happy just to match the safety results of the control group, much less improve on them. Further, he was saying that this should be one of the endpoints of the study, even if it wasn't planned that way at the study outset. I heard this and rolled it around in my mind, and it seems to me one reason this might be the case comes with the theme of these interviews, which is that leronlimab seems to work against many diseases, and that the reason it was so safe was that aside from dealing with the Covid-19 infection, it was perhaps treating other conditions the patient may have had. Do you think this might be true?
Scott Kelly: I think the safety results are better in leronlimab than placebo in the Covid-19 population because the effect of the virus is not limited to the lungs but affects multiple organs. It is a multisystem disorder and that is represented in SAE’s and AE’s.
Thomas Barnard: Those are caused by Covid-19, but I’m wondering if other secondary conditions that patients have had before the disease, and which contribute to a bad picture. Could those also be improved by leronlimab?
Scott Kelly: That is also possible.
Thomas Barnard: When the basket cancer trial was announced, I did not quite get the connection to the CCR5 receptor, but I presumed there must be one, so I looked them up one by one against the cancers mentioned in the press release, and I found a study or studies related to every single one. There appears to be just an awful lot of research on the CCR5 receptor. Have you found this to be true yourself?
Scott Kelly: Yes, absolutely. This is research being conducted by scientists all over the world independent of CytoDyn.
Thomas Barnard: How did you get involved in CytoDyn? Nader Pourhassan was tired of traveling to China, or maybe his wife was tired of him traveling to China, and one of his friends asked him to get involved in this company he was over-invested in. When you did buy your first shares?
Scott Kelly: I believe it was 2016 when I bought my first shares. But I was following it as early as 2011. My interest in CytoDyn rose because they were doing HIV. And I wanted to find the next company Gilead would acquire. Gilead is a leader in HIV and their HIV treatments still make up the majority of their revenue. I liked the concept of blocking the CCR5 receptor, because I believe it makes more sense to block healthy cells from HIV entry. Why wait until the virus enters the cell and begins to make billions of copies of itself before you decide to fight it? It doesn’t make sense. I watched the CytoDyn closely for years to try and find a reason the technology would fail either from an efficacy standpoint or safety standpoint. It never did. The efficacy and safety continued to astonish me. Once I realized the same receptor was involved in multiple disease processes, I felt it was important to pursue those opportunities so I became more involved to assist in those efforts.
At first I spoke with Michael Mulholland, and I would ask him: What am I missing? Still wondering about safety and efficacy. And then I would ask him why they weren’t pursuing other possibilities for leronlimab, and he said I should talk with Nader. And I asked Nader: What am I missing? And he said, Nothing. And I asked him about all these other possibilities, graft versus host, and others, and he said, Who are you? I am a doctor and an investor in biotech. And he said, You will need to sign an NDA [non-disclosure agreement], so I can talk to you. And, when that was done he explained that others on the board were only interested in the HIV indication.
Nader was interested in these other indications, and he told me the story of Humira, which stands for “human monoclonal antibody for rheumatoid arthritis,” a TNF blocker [tumor necrosis factor] which became one of the most successful drugs in history. The story was similar to leronlimab. He asked if I would join the board. And I said that I had a medical practice, and I would have to get back to him. Eventually, I agreed to join the board. There were all these indications and I felt many patients would benefit. And I needed to become more involved to pursue those other possibilities.
Thomas Barnard: So, when you were first bought was it mainly for HIV? But you also knew about some of these other possible indications.
Scott Kelly: Yes, but I realized as I learned more about the drug that were more indications for leronlimab than I had originally seen.
Thomas Barnard: And you bought more shares?
Scott Kelly: Yes
Thomas Barnard: I think it is a common occurrence. I bought with the breast cancer results and then I wrote a piece about four biotechs. CytoDyn was one of them, and I bought some more after I interviewed Nader. But I also wrote about Sorrento…
Scott Kelly: I have followed Sorrento, and have invested in their company. The stock is up on the news of the saliva test. I have been a biotech investor for years. And as I said, I was looking for Gilead’s next acquisition. I thought Gilead would acquire Kite, and I also purchased Juno which was acquired by Celgene.
Thomas Barnard: Wow! That’s impressive. Though I always felt CAR T was just too expensive. $300,000 per treatment. And would be supplanted by something less expensive.
Scott Kelly: It is expensive, that’s true. But I think there will continue to be a use for it. The beauty of leronlimab is that it can be used with any of these cancer treatments - chemotherapy, CAR T, radiation, checkpoint inhibitors. There do not appear to be any drug interactions.
Thomas Barnard: I know leronlimab has these three possible actions in cancer: 1) it stops metastasis, 2) the anti-angiogenesis effect, and 3) the re-polarization of macrophages, but the one effect that I thought would be in every oncologists toolkit was that it stops metastasis. If you stop metastasis, there are a number of ways to knock out the primary tumor.
Scott Kelly: You’re right. In animal studies, it was 98% effective in stopping metastasis.
Thomas Barnard: Is there anything else you’re excited about?
Scott Kelly: We are working on PrEP (prevention of HIV) through a once a month injection, and cure in HIV patients who are receiving allogeneic bone marrow transplantation. The only two patients ever cured of HIV received bone marrow transplants with cells deficient in the CCR5 receptor.
Thomas Barnard: I think I understand…if there is no CCR5 receptor, then HIV has no place to land.
Scott Kelly: That’s right. One of people on our scientific advisory is Gero Hütter, who cured the first HIV patient, known as the Berlin patient.
Thomas Barnard: That’s handy.
Scott Kelly: Another is Hope Rugo, who is a famous breast cancer researcher at UCSF.
Thomas Barnard: Also handy, since you doing a trial on triple negative breast cancer patients.
Scott Kelly: The prognosis for those patients is not very good.
Thomas Barnard: So far it looks like leronlimab can help. Thank you, Dr. Kelly.
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The Indications
The indications for leronlimab so far include HIV (where studies are completed and an application for sale has been made to the FDA), Covid-19, multiple sclerosis, graft-versus-host disease, breast cancer, and other cancers expressing the CCR5 receptor, influenza, stroke, and Alzheimer’s Disease. A small 30 subject Phase 2 trial is on-going to test the drug against 22 different types of cancer.
Precision Medicine
We are in a new era of “precision medicine” based on an understood method of action. CytoDyn’s results appear to affirm that kind of understanding:
Covid-19 – viral load drops to zero/undetectable
HIV – viral load drops to zero/undetectable
Triple Negative Breast Cancer – CTC’s (circulating tumor cells) drop to zero/undetectable
Animal studies also seem to confirm these kinds of results. In Multiple Sclerosis all of the control animals that did not get leronlimab, were paralyzed. All the animals that got it were okay. In GvHD (graft versus host disease) all the animals that got the leronlimab lived, all those that did not died. These are striking results.
Former Director of Virology at Stanford, Dr. Bruce Patterson, said in his TEDx Talk, that this is the kind of drug that the nation should be stockpiling against the next viral outbreak. Time will tell.
Disclosure: I am/we are long CYDY.
I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it. I have no business relationship with any company whose stock is mentioned in this article.
Additional disclosure: I may acquire more shares in the next 72 hours."
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