 Now welcome back to Think Tech. I'm Jay Fidel here in a given Thursday. We're covering a lot of coronavirus issues these days. As a matter of fact, we've done something close to 110 of our talk shows about the subject. And yesterday we had Dwayne Gubber, who has been with the CDC, WHO, John A. Burns School of Medicine, and the National University of Singapore, Duke University in Singapore. And today we have Yuping Deng. He's a researcher with JABSOM and has been working on some pharmaceutical research that directly relates to helping people through coronavirus. Welcome to the show, Yuping. It's so nice to have you here. Let's meet with you, Jay. So tell us what your general work is, your general research is as a John A. Burns School of Medicine, and your training and previous experience in that research. Okay. Actually, I was trained as a PhD in China. My main research area, a PhD work, is for cancer research. So after I come to USA about 20 years ago, I started to study bioinformatics using computational technology to analyze biomedical data. So my research now actually is more focused on bioinformatics, but also I have wet lab to use them experimentally to mainly focus on different human diseases, such as cancer also infects the disease. Yes. Okay. And as it was reported in the newspaper only a few days ago, you're working on a drug called dexzopa-clone in collaboration with a researcher in Wuhan. Can you talk about that research in general? How did it get started? And what are your roles in the research? What are you doing in it? And what is the researcher that you're collaborating with in Wuhan doing? Okay. You know, because the coronavirus, this is 2019, it's so dangerous. There are so many people are dying right now who are dying. So we think we should do some because I have some connection with China. My hometown actually also is near Wuhan. So I think we should do some and some find some and some to help people, help patients. So at the time we're about in the middle of February 2020 this year. So we start to collaborate with Wuhan Tenure Hospital. The first is a medical doctor. The first is also Dr. Lin Hu, who usually who used to work in my lab in Chicago. So actually study is a retrospective chart review study. So we didn't purposely try to use this drug. We first tried to look at the medical record for those COVID-19 patients, about 323 hospitalized patients. So based on what a doctor had used for those patients, then we try to find very useful information such as drug or any risk factors to associate with clinical outcomes. Then unexpectedly, we found this drug, Dex Zopiconone, is a hyper-logic drug to help people to sleep. It has a very good clinical outcome to improve people to survive, to have a bad clinical outcome for this patient. Okay, so this is a repurposing as so many of the other drugs and for example, the anti-malarial drugs that Donald Trump talks about. This is likewise a repurposing of a drug that was developed for some other ailment. And I find interesting about this approach is that you already know what the side effects are to this drug because if somebody requires this hypnotic drug and it's been approved for whatever other purpose, then we know the side effects. And so now you're just looking at efficacy. You're looking to see whether it helps somebody who has coronavirus. And so you have to job is already done in terms of the fact that the drug already exists. It's already useful for some other purpose. And I suppose this is an approach which a lot of researchers are using now to repurpose drugs and apply them to coronavirus. Am I right? I want to clarify again, because actually we didn't propose it to do this study to try to use this sleeping drug to treat the patient. No, this is not our original purpose. Actually, this is a separation. I expected finding because people find the doctor find usually a patient has a strong anxiety with biggest stress. Many people couldn't sleep well. So they'll try to give the drug to have people to sleep. But after we look at the medical record, we separate and find this drug didn't work well. They can help people just patient to survive. So this is an expected finding. It's not a proposed design to try to use this drug. We propose to use those existing drugs to treat this virus patient. No, it's not our original purpose. But indeed we find it helps. So this means this finding is more convincing because this is more unbiased finding. So we are very happy with this finding. Okay. So what is the category of drugs, hypnotics? What does that mean? Is that it hypnotize you? What is hypnotics? Second. What is hypnotic? What is a hypnotic drug? A hypnotic drug is kind of a drug to help people to sleep. So I will say it's a try to treat it in so many ways. Yeah. So it's try to help people to sleep, sleep better. It's a sleeping drug. Yes. So why don't we just use ordinary sleeping drugs rather than this specific Zopaclone? Oh, I think probably, I don't know, first I don't know because this is based on what they have in China. I'm not a medical doctor. They gave me this data. I think probably it's based on what they used routinely in China. Maybe the side effect is much lower than other drugs. Maybe this is one reason. But I guess maybe other sleeping drugs may also work, so we need to test. Yes. Okay. And just a couple of other questions. So this, we know that a patient who's having a problem, a symptomatic patient, doesn't get very good sleep. And as a result, his immune system or her immune system declines, makes him more vulnerable to the effect of the coronavirus. So, and then of course, you find that his immune system is reacting against the coronavirus. And when it gets in his lungs, it fills his lungs with the waste products of the process and the immune attack on the process. So how does this affect the immune system so as to moderate the immune system? And no, you can say if actually many diseases are due to immunofunction, for example, even cancer, diabetes, or whether you can live a longer or shorter. For example, if people can sleep well without other diseases, you can even live a longer life because the immunofunction will be good. So sleeping is very important in any aspect of a human life. So if you sleep well, then when you sleep, your immunofunction, your immune system will active, then fight against this virus. Your T cell or B cell will be functional, will be active, then we have killed the virus. So this is not directed like other antivirus or antibacterial drug to direct the kill virus. No, this is through, I was improved the immunofunction such as activate T cell or B cell to kill virus. So many are fine. So, for example, why this one works, I can give you an analytic example. For example, because this is an emerging disease, it's a fast disease, it's a self-limited disease. So the virus usually they will not last in your body for a very long time, it's very similar as a flu. So it's a self-limited disease. This means if a patient, serious patient can overcome those very difficult time, maybe for two weeks, to four weeks, then the people will survive. It's not just survive, they will recover it because it's a self-limited virus will again. Then if they cannot overcome those difficult time, the patient will die, those critically ill patients. So this means with this sleeping drug, to try to overcome, help the patient to go through those very difficult time, your sleep, you cannot, your cough, but your sleep, then your cough will become less, right? Then your weapon will be less anxiety, more relaxed, by this way your immunofunction works, then you can go through those very difficult time just for maybe one to three weeks. Then you'll survive, your disease will be recovered. So this really makes sense because it's a self-limited disease. This is not something you must cure the virus, no. You just need to live together with this one to go through a month's time, then you'll win. That would help you. So and you've been successful in improving the chances of a substantial percentage, about 95% of the trial patients you've checked on have been benefited by the drug, right? Yes. If we compel with this drug, without this drug, actually I just want to make sure I tell you, even for a serious patient, probably based on our study, more than 80% of patients will be able to recover, okay? We'll be recovered, our role. But even if we compel with the serious patient, serious, very serious patient, we have a sixth patient using this drug, 355 patients are recovered. We are recovered. Three patients without a good outcome, but finally we fall apart when one patient died, okay? No, no. For serious patients, nobody died, nobody died, only for critical ill patients. But for if we saw the drug, we saw the use of this drug for serious patients, there were 67 patients, 67 patients, but you can see that I can look at the figure. Then the 67 patients, 17 patients didn't recover. What I say, we had unfavorable outcome. Fifthly, our 67, about 74% had a good outcome, but using this drug, there are 94, more than 96 patients, 95% had a good outcome. So it's more than 20% improvement. So am I right to say that this is a drug, therefore, you should take in the continuum when you are having trouble sleeping, or is it all throughout the process of the disease? I think if you go through the disease, you may not need it, or I'm not sure, that you need to continue to eat or not, or take the drug. But at least when you have had virus, especially for those serious cases, it may be good to use it. Dr. Deng, you had a bunch of slides, and I wonder if we could go through them now, and you can explain each one of them as a handful of them. So why don't we start the slides since Dr. Deng can't explain. This is your cover sheet, the title of your research. Yeah, my title is I will say, yes. So it's a kapeurotic, it's a sleeping drug, significant improved clinical outcome of a patient with this virus, okay, coronavirus, okay. So the study design is a retrospective study based on electronic medical record, with 23 hospitalized patients with this COVID-19 disease, who were admitted on January 8th to February 20th this year in Wuhan Tianyu Hospital. The final follow-up date was March 10, 2020. Patient was classified into three disease groups based on the stages nine, zero, zero, and critical year status. So based on the symptom and the clinical presentation, clinical outcome was designed as favorable and unfavorable, favorable and unfavorable, based on the disease progression and the response to treatment. For example, if they are recovered, if they are from more serious status, go to mild status, we think these are favorable outcome. Unfavorable outcome means if the patient died or the patient from a mild become more serious symptom, we think they were unfavorable outcome. Next slide. Okay. So you can see we separate and find, from the medical record, we are not purpose using this drug. We're based on a drug that has used for those patients, okay. So you can look, if the 82 patients use this drug, only five patients had unfavorable outcome, but in this five patients, when one died, 77, 77, okay, had favorable outcome. But if you compare those without using drugs, so you can say there's 50 patients had unfavorable outcome, about 155 had favorable outcome. So you can say using drugs, only 9.1% compare these 55 unfavorable outcome, 91% with unfavorable outcome, with using this drug. But without using this drug, 50 is more than 95% with unfavorable outcome, without using this drug. So we can say, we can say M minus 82 patient who using this drug, 77, had a bad favorable outcome, and we are recovered discharging. And the five patients receiving hypolytics who had unfavorable outcome, only one died. You can say, if you compare the P-value, it's very significant. It's less than 0.001, compared with all three stages, with using drug, yes, or without using this paper logic drug. Next slide. Yeah, that's very successful. Yeah, go ahead. Yeah, because the first one likes to compare all stages, people will say, how if we compare this drug at the same stages, for at least three stages, non-serial, such as mild or a little bit typical status, or serious status, serious patient, or critical year patient, critical year patient. So if we just go one example, for example, for this series, if also unfavorable outcome, unfavorable outcome, if we go to the needle, because we have more patients, for example, we have six patients with serious status, okay? Fifty-seven patients using this drug are recovered, have had favorable outcome, only three had unfavorable outcome. But if you look here, this without using drug, 67 patients without using drug, 17, okay, had unfavorable outcome, 50 had favorable outcome. So you can see here, if we say this 57 hour 60 is more than 95 percent, this is the 50 hour 67 is 74. So it's more than 20 percent improvement. So you can see the blue bar higher is better, okay? The red bar lower is better, this is unfavorable outcome. For you can see, using drug, the red bar is much lower than without using this drug. The blue bar is much higher with using this drug than those blue bar without using this drug. If you compare the serious status, it's the same. You can see the blue bar with using drug is much higher than without using drug. But the red bar is lower than without using drug, okay? But using drug is lower than high is without using drug. For critical status, it's the same. You can see the red bar is much lower for using drug than without using drug, right? The blue bar is much higher than this one. So very significant. More serious status is much stronger. So this is very good, okay? So next slide. So because PCR we find, in China, they find the PCR, there was a very high forced positive rate. This means some patients, they already have this disease, like a CT, with typical CT chest binding, okay? Already infected in the lung. But using PCR in the throat, you couldn't find the PCR is positive. So we want to compare the PCR positive and the PCR negative patient, how they will behave using this drug, compare using this drug without using this drug. For PCR positive patient and the PCR negative patient, PCR negative patient actually, they already have a typical symptom of this virus. Also, the CT scum picture image are positive. This means those patients with typical chest finding based on CT scum image, okay? You can see, if we compare the PCR positive patient, you can see for three stages, non-serial, severe, and the critical stage, you can see, if we see the middle severe patient, you can see the blue bar is very high, using the drug, compare the blue bar much lower without using the drug, right? For the red bar, you can see very low, using the drug, but the red bar, unfavorable, is much high, compare using the drug, right? The same for critical stage, for all is the same, you can see. For critical status also, the red bar is much lower, using the drug, compare without using the drug, it's much high. Also, you can see, for the critical stage, if you without using this drug, it's almost no ending people survive. One thing is clear, Dr. Deng, is that you always do better if you are taking the next subclone, always do better, all right? Yes, yes, yes. If you use the RTPCR patient, it's even better than those for all including both RTPCR positive and RTPCR negative patients, so I think it's very good. Okay, let's go to the next slide. Then the people may ask me, oh, because how do you know this effect is because of this drug or because of something else? Because you have other drug, you have different age, different sex, you have different, some people are overweight, some people may have core mobility condition, like has diabetes, may heart attack or hypertension. How do you know this effect is because of this drug? This good effect after using this sleeping drug is because of this drug or because something else. How can we figure out? We do comprehensive statistics, we call it multivariate data analysis. Multivariate analysis means you put all the variable, all the fact, this effect together, then to an independent study, to do a justification, say whether this effect is independent, this means if it's independent, this means they are alone will have a good effect without affected by other factors. You can say, we see the hyperlottics, okay, this left side is for very bad outcome. You can say that right side, we have seven this effect is for worse outcome. Only one had good outcome is hyperlottics. It's independent factors. This means they are either justified by other factors. This fact also the P value you can say is less than 001, very, very significant. Also it's independent of any other factors. This means this effect alone should work, okay. So this is very good news for seniors, it's very good news for people who are compromised. Yeah, because that's very important. Why you let me show I can give evidence, why we do this? Because many people think, oh, how do you know? You have so many factors. Okay, you use this drug, you may also use another drug. How do you know? It's because of him, not something else. Based on this, we demonstrate, yes, it's because of him, not something else, okay. So we also do a survival analysis, survive because we want to find outcome is to survive or die, right? So you can say if you compare survival analysis with using the red line, this means the using drug, the blue line is without using this drug, you can say the red line is much, survive much longer. So the P value is 0011, it's very significant. So for another evidence, you use this very good. Okay, so not by accident, this is a true evidence. Okay, yeah, next slide, next slide. So this is the, so what's the drug exactly name? There are so many, there are many types of sleeping drug. So specifically the drug, we used the lemon cord dex throbicloin. So we show the chemical structs, we show the formula, molecular weight. So most important, how it was used and mistreated in the hospital for the patient. So this was, it was made as a tablet, about three milligrams for one tablet. But for an initial dose for a patient enrolled in a hospital, we, the doctor gave them initial doses of one milligram per day, one milligram. So maybe one third of the tablet. But it can be based on the patient's age or maybe weight or maybe the effect of sleeping, sleeping effect. It can be increased to two or to three milligrams per day. It depends case by case. Okay, somebody, but most people can, can be probably give it to two milligrams, should have a low problem. But if for all the people or the, if the, the breast is not, it's very, not very good. Maybe serious in, in the high risk damage for breast. Maybe you can initial dose one milligram. The side effect is so they, they, they, they were not so heavy. So no, no many, almost no side effect. But we also need to be observe the instruction of a medical doctor, a medical doctor before using this drug. Okay. So the drug, the drug is manufactured synthetically. It's manufactured synthetically. Who, who manufactures it and where is it manufactured? It's probably manufactured in China. I think probably the similar drug also will be made in USA. I didn't check carefully. Yeah. But I don't know which factory to manufacture, but to manufacture it. But I think probably you should be able to find similar drug in Japan, in China, in India. Yeah. I think other type of maybe sleeping drug may work too. Yeah. Okay. So, so, so usually when the patient come to the hospital, so you can use them, usually an average stay in the hospital for those three, 23 patients is about three weeks, 19 days. So I think somebody may only stay for one week, somebody may sleep for three weeks. So I think one week to three weeks, usually is the time a patient to take, okay, to take this drug. Okay. Do you have any questions? Yeah. Okay. So, so, so the next slide, next slide. So we want to know what's undermined mechanism, why this drug works, right? Because we found that the doctor found, based on the medical record that people said, usually with this disease, a patient usually has stress anxiety, sleep deficiencies, and oxygen is sufficient. I think because your line is infected, you cannot, so this means your oxygen, you usually have oxygen insufficiency. This is maybe the reason to make people cannot sleep well. So after you have sleep, then you will have immunofanx system. So you have, you cannot sleep well, then you will have immunosystem abnormalities. So you have good sleep quality and stress reduction. Using this drug could be one partial reason to explain why this drug works. Also, some other study already found, good sleep can exert some immunosupportive effect and can enhance effective T cell function. We know T cell is immunosupportive function. Okay, so by this way, you can, you can really make your sleep good also to help you to cure virus through the immunofanx system. This is another study. We have six references, you can say, to, based on other people's study, to support the story why a sleeping drug can help a patient to cure virus. So, for example, another study to show, this drug could be due to enhance gamma, gamma aminobutric acid, it's called GABA signaling. This signaling has a very important function. They can really promote all of these activation, also improve a function, a human immunofanx, mainly immunofanx, and promote host protection against infection. We can say we have six references, at least six references to support our findings. Yes, based on other people's to understand the mechanism. Yes. Do you have any questions? Then we can go to the next slide. I do have a couple of questions. So there are other studies going on. Will you do another study? Is your study complete? And how will you conduct your follow-up study? Will you do it in China? Will you do it in the U.S.? Will you do it in Europe? Where will you do it? And will it be larger than the study you've been working on? Okay, first I will note, no other people so far in the U.S. I'm not sure if U.S. has begun to use the drug or sleeping drug to treat a patient. But for those references, not used for the virus. I just saw from other references to understand the mechanism. Those references didn't use this drug to treat the coronavirus. Okay, so in terms of how we can continue to do the study, I think first we want to publish, if based on your news, based on our publication, then people can use the drug or similar drug to test, to do more, because it's already FDA approved the drug. They can try to do more clinical trial or test in more patient to see whether this drug don't work in more patients. I think we need more study. Absolutely. I suggest other hospitals, other doctor to use this drug to test whether it will work, truly works or not. I think most likely it will work. Yes, okay. If I looked at the study and I listened to your description and I say to myself, this sounds very promising. And then the next day I wind up getting coronavirus and winding up in a hospital. And I'm interested in having this drug. I'm interested in having a course of treatment with dexobaclone. And I say to my doctor, can you give me dexobaclone? What would happen? I think if you want to get, it's better to first listen to the instruction of the medical doctor, right? So I think most likely if you use this one, you also need to be, first dose is important. For example, usually the initial dose is one milligram. But you don't use very high dose, for example, more than two tablets may not be good enough, right? So I think usually if you take one to two milligrams per day, this is in the safe days range, probably we are happier patient. But be careful, especially for some people, maybe have some other chronic disease. Maybe, for example, if we all have liver damage, you need to be very careful. So I think it's better to listen to the, first you read the manual carefully with the drug, also listen to the instruction of a medical doctor. But I will say most of the patients, based on our experience, based on the medical record we studied, based on chatting with the medical doctor, collaborating with us, I think most of the patients, even for, you can say, for clinical ear patients, for serious patients, can use the drug, yes. Oh, very disencouraging. And it is available, I can find it, I can, I can get some if I need some. Okay, you have more slides? Yes, I have one more. This is a piece we show, based on what we show, other drug, you can say, if you compare, just one example, two example, for example, we find the Kali drug, Kali drug is anti-viral drug, meaning for HIV, you can say, if you compare yes or no, you use this drug or no use drug, you can say that almost, if we do the, if we will compare a serious case, okay, you can say that after use, the even has a high unfavorable outcome compared to without use. So you can say, for good outcome, the blue bar is lower than this one, than without use, okay? It's totally opposite. This means it's not all the drug work the same way as hypnotics. Like this one, all these four ways we find, almost you can say, after use is blue bar, is blue bar, is blue bar, is almost after use, the blue bar is becoming lower. This means even for using invasive ventilation, we didn't find it work. Another publication published in Lancet also find, after use invasive ventilation, a patient may not benefit well. So this means, if a patient, unfortunately, if you're patient, if you go to the stage, using invasive ventilation, based on our finding, there may not be, you may not be a good sign. Can you ask a question? So overclone sounds like it's better than any of the ones on this slide. So you really have identified the best possible hypnotic for use with coronavirus. This is a great finding. So I know you were in the newspaper, but are you, are people recognizing this around the world? What kind of acceptance have you had in the therapeutics industry, in the pharmaceutical industry? Is this something that is mainstream yet? Are people are people aware of it, you know, in other places and around the industry? No, no, very few people know, very few people know. Only so far probably only in Hawaii, even in Hawaii, many people don't know that. So I really want more people know to benefit more patients. Absolutely. I feel this makes sense. Yeah. So we talked about, you know, Dr. Dang, we talked about before, before we started the show, we talked about, you know, why you set this up, why you established this relationship, this collaboration, and what part it plays in the larger global collaboration that Dr. Goobler and I talked about yesterday. Can you tell people, you know, why you're so motivated, why you're so dedicated? We don't need this slide anymore. Why is so dedicated, you know, to this, this project, why you're devoting the time and energy to it, why you're pursuing it this way? And, you know, what does it mean to the Cancer Research Center at Japsum? What does it mean to Japsum? Where does it put Hawaii on the map? Because it sounds like, to me, this is a pretty good bet for somebody with coronavirus. And maybe it offers light and hope, but we had, we didn't have such light and hope before. Tell me your thoughts about that. Yes, yes. I think you're doing science. It's not just for publication. Many, so we first, our original purpose is to try something. If we can find some risk factor to predict a patient outcome, based on this risk factor in the early stages, or then a doctor can make an early decision to treat a patient with this virus. But surprisingly, we find, because if you find, for example, if we find a high BMIL, our way to people has worse outcome compared to normal way to people. We find if a patient with diabetes, with heart disease has worse outcome, but this is okay. This is a good finding, but you cannot change the status of a patient. For example, if the all-weight after the meat into the hospital, you cannot change the weight. Even for diabetes, you cannot change the diabetes. But as a horizon, we find, well, this drug, hypnotic drug, can improve a patient outcome. But this way, your doctor can control. Why? Because we can try to use this drug. If you have a chronic disease, you cannot change. So I think this is more important because we find a drug can have a supportive treatment effect. So I think this is very useful. So the reason I think if we do research, we really want to save people, help people, to treat people well. So this makes me motivated. I think we want to make more people know we are not just for publication. Our purpose for research is to really try to benefit people. It's basically in this crisis, if we can really save people's life, every day more people are dying right now. So I think maybe it's most likely a self-limited disease. With this drug, the people can go through or come maybe one to four weeks. Then with relax, then the people may recover because it's a self-limited disease. It's another chronic disease. So I think use this drug to treat people. That doesn't make sense yet. So Dr. Dan, where would you put this in the world of hydrochloroquine and erythromycin? The combination that Donald Trump has been suggesting. Can you take these all at the same time? Would you take them all at the same time? Is this one more proven, more better than hydrochloroquine? Can you give us a handle on how they might compare and contrast in the hospital course? First, I do hope there are more drug available. It's much better than just this one good drug. There are more drug is better. But whether hydrochloroquine or hydrochloroquine or erythromycin are good or not, I don't know yet. Because so far, based on my understanding, there's no conclusion whether it's two drugs or that works or not. Based on my understanding, the article published in the JALO, the person is the editor-in-chief of this JALO. This paper has already been retracted. I just let you know. I just got the news. It has been retracted. People think because only use mild status patients without using serious patients, we know that most more than 90% of mild status patients without using the drug, they will recall. So we need a good design to make sure those two drugs, these drugs really works or not. So there's no conclusion whether those two drugs work or not. But there's two possibilities. One possibility is drug. Chloroquine doesn't work. Then our sleeping drug, there is another hope. Second, if they may work, that's okay. Then if they work, then they may be used both drugs. So whether the both drugs can be used at the same time, I don't know. If both drugs works, I don't know. This needs more experiment, more clinical trial to test whether it can work by both drugs. We have no data, but it may be okay. Why? Because maybe it's okay. Why? Because in our study, we also, for example, like some anti-wired drug has been also used by both anti-wired drug and anti-wired drug. It looks for some patients, same as okay, but I don't know until we have real data. Dr. Yu Ping Dang, I've really learned a lot from you, and I really appreciate your work, your commitment, and I really appreciate that Japsim is supporting you and you are a credit to Global Medicine and certainly to Hawaii Medicine. Thank you so much for coming on our show. I hope we can circle back to you later as the process.