Founder Stories: John Fowler, Co-Founder and CEO of Kezar Life Sciences

Thank you very much for joining us today. We hope that— obviously, we hope that you continue to stay with us throughout the day and enjoy the variety of different sessions. Wasn't that Hezekiah Walker session, music session, inspirational? Oh my goodness, I tell you, it's a way to get us going today. And we're looking forward to a variety of different sessions, including even some healthy cooking later on in the day. Also be aware that this coming Thursday, March 4th, we're actually also having a Black Health Matters Facebook Live from 7 to 8 PM Eastern Standard Time. It will be on kidney disease and FSGS, which is a rare form of kidney disease, and the subject matter and the feature will be about how to get access to expert care for kidney disease and FSGS. I'm introducing the next session, which will be on lupus, an important disease that not too many people know about, but we want to take this time to inform you about the significance of it within the African American community. The session is Rare Autoimmune Disease: A Closer Look at Lupus, Nephritis, and myositis, or myositis. According to the Lupus Foundation of America, lupus is 2 to 3 times more prevalent among women of color versus their Caucasian counterparts. Recent research indicates that lupus affects 1 in 537 young African American women. So it's a very prevalent disease that, as I said earlier, not too many people know much about. We have two distinguished presenters in the lupus field, the lupus area. We have Dr. Amit Saxena, an assistant professor of medicine in the Division of Rheumatology at New York University Grossman School of Medicine. He's the director of lupus clinical trials there, and has been the site principal investigator in over 25 industry, National Institute of Health-sponsored interventional and observational trials on lupus. He's also the co-director of the clinical trial design course for the NYU Master of Science of Clinical Investigations program. Dr. Saxena has received several grants to study long-term outcomes in patients with neonatal lupus, a rare condition that affects the heart or skin of children born to women with anti-SSA antibodies, an antibody commonly seen in lupus and Sjögren's syndrome. Doc— and excuse me, Dr. Amit Saxena will discuss it with John Fowler, who's the Keyzar Life Sciences Company co-founder and chief executive officer. John Fowler is also a member of the board of directors, bringing over 20 years of executive leadership experience to the Kizar Company. Mr. Fowler has been a successful operator in organizations ranging from high-tech startups to the U.S. government. He served as CEO of Aero Logistics from 2003 to 2008 and as CEO of HealthCPA from 2009 until 2014. That company is a provider of patient advocacy and insurance navigation services. We welcome them both to share their knowledge and information about lupus. Thank you very much, gentlemen, for joining us today in this historic Winter Health Black Health Matters Summit.

Thanks, Colin.

Thank you, Colin.

As you mentioned, my name's Amit Saxena. I'm a rheumatologist at NYU. And I focus on lupus. And other autoimmune diseases. And I'm going to do a very brief overview of what these diseases are. Now, obviously, I could talk about this for hours, if not days. But we'll try to just talk a little bit about what these diseases are and how they affect different populations. And as we go along, feel free to put in any questions you have into the chat. We'll do our best to answer them and take questions at the end. And I hope not to be— too overwhelming with some of this information, but I hope it can serve as a nice icebreaker on what these diseases are. These are my disclosures. And we're going to start by looking at lupus nephritis, which is kidney disease in lupus. If you look at the last part of the word, the -itis is just Latin for inflammation. And so you'll see that come up a bunch of times with a lot of diseases we study because autoimmune diseases, which I study, are inflammation diseases. So systemic lupus erythematosus, or what we're going to call SLE, it's a chronic relapsing and remitting autoimmune disorder. So we all have an immune system. These are cells in our body that are usually used to fight infections. But sometimes the immune system gets confused, and it can start attacking our own body by accident. And so that's what we call autoimmunity. And there's a whole lot of different types of autoimmune diseases depending on where that inflammation is actually happening. And lupus is one of those that's kind of a prototypical autoimmune disease because it can attack almost any part of the body. As you can see on the right here, there's a bunch of different what we call organ systems that are involved with lupus, including things like the heart and the lungs, all-around general manifestations, the stomach or gastrointestinal. And as you can see here, just all parts of the body. Lupus is what we call a flaring disease. It's a disease that can be quiet sometimes and then just come back out of nowhere. Where sometimes it can happen with certain exposures. Things like sun can sometimes flare lupus or infections. But sometimes it just happens on its own. And so that can make it very frustrating for patients who are generally doing well and then can sometimes be hit with a flare that can kind of knock them out of commission. And the disease course is unpredictable. Some people have very, very mild disease. And they have mild symptoms throughout their entire lives. But there are other people who can get more serious manifestations and require more intensive medications. The cardiopulmonary, or the heart and lung diseases, neurologic diseases, which are rare, and renal or kidney manifestations, which is what we're going to talk about today, are really the largest contributors to the people who actually get really sick from this disease. So most of the signs and symptoms of lupus are really nonspecific. And they can look like a lot of other diseases. And so that's why it can take a long time for sometimes for these disease to be actually diagnosed. There are some symptoms like just general fatigue, weight loss, low-grade fevers that could happen with a lot of diseases. And, you know, you go to your regular primary doctor and common things are common. They're not necessarily going to be thinking about lupus to begin with. But when it is found, obviously, there are lots of other manifestations that can happen otherwise, as we kind of mentioned. And I'll just point to a couple of the most common things that happen with lupus. Are really the, what we call mucocutaneous or skin manifestations, including different types of rashes, sores in the nose, sores in the mouth, and hair loss, and the musculoskeletal manifestations, particularly arthritis, which is a type of, in this case, is a type of arthritis that usually presents with things like red and hot and swollen joints, you know, real inflammation symptoms. But again, you know, the disease can manifest almost anywhere, and we're gonna focus today on the renal manifestations kidney manifestations. You know, the incidence and the prevalence of lupus are very variable, variable with age, ethnicity, gender, and race. It can occur at any point in life, in childhood, adult, or even late onset, although usually it presents in what we call the childbearing years for women between ages 15 and 45. And when it happens in men, it can happen a little bit later in life. One thing that's well established is that mortality is higher for non-white patients compared to white patients from the beginning of diagnosis through the end of life. And it's something that we have been trying to understand, but it's really been something that has been a factor that we know about from the beginning when we talk about this disease. It's overall a female predominant disease. It's 9 to 1 women to men. So there's probably some sort of hormonal aspect to it. But we're still not completely sure as to what drives lupus. There's a genetic part. Certainly, these diseases can cluster in families. But what goes beyond the genetics to tell us who's going to develop this disease is still not really known. Overall, it's still relatively a rare disease compared to a lot of things that affect the general population. But as we discussed, it can cause some pretty severe manifestations. So it's still an important disease for us to think about. So the kidney disease is really this serious complication. And it's not just serious, but it's serious and common. And so a lot of patients that present with kidney disease as their first manifestation of lupus can, can be, you know, sicker at a younger age, for example, and develop kind of long-term issues. And the thing that we're trying to prevent whenever we treat nephritis or kidney disease in lupus is what we call end-stage renal disease or ESRD. That's the part where the kidneys are so involved and so inflamed that you might require something like dialysis. And so our ultimate goal is to prevent people from getting to that stage. The most common feature that we see is something that we call proteinuria or protein in the urine. The kidney's job is to prevent, is to keep things into the body and filter things that should go out. Protein should stay in the body, but when the kidneys are inflamed, they can leave the body in the urine. And, you know, that can show up clinically. And what you can see is sometimes foamy urine. But the truth is, the vast majority of people who develop kidney disease in lupus don't actually have any symptoms in the beginning. And that's what makes it kind of really important that we're monitoring our lupus patients. And even when patients are doing well, I still see them every 3 months to check their kidneys to make sure that this isn't developing. But when things do get more severe, the symptoms can include things like swelling in the body, particularly at the legs, or in the stomach is what we call ascites. Or if that swelling goes into the lungs, that's called a pleural effusion. And again, that happens because protein helps keep water into our body spaces. And when we lose protein through the urine, water builds up in different parts. So again, there's varying demographics of lupus, including lupus, but also lupus nephritis. And so again, Black patients, Hispanic and Latino patients, as well as Asian Americans, are more likely to have lupus nephritis than Caucasian patients. It's 2 to 3-fold higher for Black patients compared to white patients. And the prognosis, the overall development to end-stage renal disease is worse in Blacks and Hispanics compared to white patients. And as we mentioned, women are more common to get lupus in general, and thus more common to get kidney disease in lupus. You know, when men do get lupus, though, often it's their more severe cases too. So that's one thing that we know is that when men do get lupus, they themselves are at higher risk of getting lupus nephritis. And so here you can see that there's obviously an increased death rate for Black compared to white women in the United States. And so the three Black lines involve women of different— Black women of different ages. And you can just see that, you know, over the years, you know, even including relatively recent time periods into the late '90s, that there was still a significant difference. You know, even as we started learning more about the disease and more about how to treat it, that disparity remained. And again, the incidence rates of the actual end-stage renal disease, that last part, due to lupus nephritis, again, as you can see, significantly increased in Black patients compared to other ethnicities. And so what causes these type of health disparities? There's a huge amount of issues that can be dealt into, again, for days. And we talk about this, and not just with lupus, but all diseases. But, you know, there are issues on all sides of the case. You know, a lot of this can come down to problems with our own healthcare system, issues that make it difficult for us as doctors to practice, as well as the fact that maybe a lot of doctors don't have the cultural competence to really interact with different types of ethnicities and different areas of where we might actually have clinics all on the left side of this chart here. And then there's things that can prevent people from going in and getting treatment, whether it's issues that are more grand scale, like poverty or environmental stress, or individual things, some that are not really changeable, like your own genetics, but other things that maybe we can address, like people's understanding of these diseases and awareness of these diseases. But all of these issues, wherever there's any sort of deficiencies, will lead to these differential outcomes in lupus and lupus disease activity and disease damage. And unless we address all of these things, we're not going to really level the playing field and actually have equity here. So the whole reason why we want to do this is because lupus and lupus nephritis, it causes a substantial disease burden. Whether it's physical, mental, social, emotional, all of these things are affected by lupus and lupus nephritis. It can impair your ability to work, losing income. Spending too much time in the hospital or going to emergency rooms, higher rates of people having to do that, obviously, when they have diseases, chronic diseases, and, and more severe diseases like kidney disease and lupus. And of course, the annual healthcare costs for people with lupus are going to be exorbitant. And that doesn't even begin to touch on the question about insurance and availability of insurance. So our goals here with lupus are really to obviously decrease the disease activity and cause what we call a remission in lupus, which is— we don't usually use the term cure for a disease like lupus, although we'd love to get there. But at least we can put the disease into remission. And we do that by, you know, decreasing obviously the amount of protein in the urine and dealing with all the other things that go along with lupus. For the most important thing is to preserve the kidney function and increase patients' quality of life and increase their survival rates. And so that's where we're trying to get. When we treat lupus. And so I'm not going to go into too much detail here. This is just the way that we kind of treat when kidney disease happens. And the overall idea here is that we try to blast people with really strong medications that can lower the immune system in the beginning. Because the immune system is so overly active, it's causing a lot of inflammation throughout the body, particularly the kidneys. So when that's happening, to prevent long-term damage, we have to hit them hard. With medicines that lower the immune system to start. And that usually begins with a type of medication that's called a corticosteroid or steroid. And you probably have heard of the name of a medicine called prednisone, which is used for lots of different diseases. And so we'll use that as our first line to bring down inflammation quickly. But we'll also use heavy, what we call immunosuppressants, medicines that bring down the activity of the immune system. And we'll do that initially over the course of 3 to 6 months to bring things down intensely. And then we'll move to what we call a maintenance maintenance treatment where we then use lower intensity medications, but for longer periods of time to keep the inflammation down and prevent that end-stage renal disease. So again, I'm not going to go into too much detail on all of these different medicines. But there's a lot of things that are available to us, but not a ton that have been specific for lupus. We've kind of usurped a lot of other medicines that were made for other diseases in order to— that we knew decreased the immune system. And so some of these medicines are commonplace, we use in all of our like hydroxychloroquine, which is an antimalarial medicine that we found had an effect on the immune system, the corticosteroids like we mentioned, different types of what we call biologic medicines, which are medicines that are actually aimed at the immune system in specific ways. But then the key part are these what we call immunosuppressants. And again, I'm not going to ask you to memorize all this stuff. If we have a quiz, it'll be pass/fail. I don't think you're going to have to worry about that. So the takeaway point here is that there's a lot of options but if you can see on the right, there's a lot of side effects. The whole issue with lowering the immune system means that we can increase the risk for infections in our patients. And so that's the balance that we always have to weigh and making sure that the benefits of our medicines outweigh the risks of them. And so it's a game that we have to play. And, you know, of course, without better medications and without, you know, more targeted medications, we're gonna run the risk of having these types of kind of broad side effect profiles like we have with the medicines that were available now. So there's really an unmet need here with lupus. There's no cure. Again, we don't throw that word around. And there's a lot of patients that when they have lupus and lupus nephritis, they can progress even to death within a few years. And some of these numbers that we're seeing that are on the screen of 5% to 25% are based on older data, especially before we had a better gauge on how to treat this disease. But still, we see these very poor outcomes occasionally, and certainly things like progression to dialysis, which is really what we want to prevent. We really don't have many medications that are actually approved for lupus. There were two that were approved for lupus nephritis just recently, which was kind of the biggest win that we've had. Because the last thing before these two drugs were approved in the last year was when this first drug, belimumab, was actually approved for lupus overall, which was now 10 years ago. And before that, there was no approved medication for lupus for 50 years. So there's a huge need for new medications and better medications. You know, the other issues that we have with lupus and lupus nephritis is that it's just such a variable disease. It's heterogeneous. A lot of different patients will have different reasons their immune system is acting, you know, out of whack. And it's hard to find the right treatment. One treatment might work beautifully for one patient and not for another patient. And so again, having more options to use is really important for us going forward. And as I mentioned, the standard treatments that we have for lupus and lupus nephritis have serious side effect profiles. Things like infections, organ damage, cancers can even happen with some of our medications. And we need to use these medications for long periods of time in a lot of cases. And so the longer we use them, the more likely we're going to have to actually have these types of side effects. And even with the medicines that we have, still a lot of patients will just not respond. You know, some patients don't even respond to the steroids that we use in the beginning. And less than 60%, I'd say even less than 40% of patients with the kidney disease will achieve a complete response to the induction therapies. So we are looking at a lot of different types of medications for lupus and lupus nephritis. And again, I'm not going to go into too much detail. But the thing about these medicines, as opposed to the medicines that we've used in the past, is that now we have a better scientific understanding of what lupus is and how it works on the immune system and kind of what specific chemicals are abnormal in lupus patients. And so when we have that knowledge, then we can start targeting those kind of— those abnormally responsive chemicals, for example. And so that's what all of these medications are looking at. And you can see there's lots of different pharmaceutical companies that are looking into this. Everybody knows that this is a major unmet need for a disease a disease that's very serious. And so there's a lot of looking into this. And, you know, as we learn more about the immune system in general, there's potential that these medications could be used for other autoimmune diseases as well. And so I'm going to move quickly now from here to myositis, which is a different autoimmune disease, a rare autoimmune disease, but one that can be treated in similar ways. So that's why they're kind of— I'm putting them together. And so myositis or idiopathic inflammatory myopathies are rare heterogeneous disorders. Again, they're characterized by muscle weakness and muscle inflammation. There's a few different types that we look at. Names are polymyositis and dermatomyositis, inclusion myositis, and something called necrotizing myopathy. But the kind of points that are similar for all of them is that they involve what we call the proximal muscles. So like the neck and the shoulders and the hips and the upper legs. So you'll feel weak. It's less pain, but it's more weakness that people feel. So a lot of the tasks that people have trouble with are things like getting out of a chair, climbing stairs, lifting objects, combing your hair. These are things that sometimes can be associated with this type of inflammation. Even as severe when it gets to this point of swallowing or holding up your neck can be affected. When it's really severe and things are advanced, it can progress even to the distal muscles like the hands and the feet, making things like walking, walking or holding objects, buttoning things difficult. And some of these disorders can have associations with things like rashes, which is the dermatomyositis, you know, kind of systemic symptoms like fevers and joint pains. Raynaud's syndrome, which is something that can happen where the fingers turn or the toes turn colors and the cold, and can also involve organs here too, like the heart and the lungs. So it's characterized again by this proximal weakness. The polymyositis is the version that doesn't have any other kind of symptoms that go along with it. It's just the muscle weakness. And it's something that we call a diagnosis of exclusion. Again, it's hard to really get to this diagnosis. If you think about it, there's just so many reasons why people can feel weak. Weak. And so getting to this very rare disease can be a difficult slog to get there. So it's often diagnosed after other things have been excluded, like other types of myopathies that are caused by different types of drugs, other types of muscular dystrophies that people are born with, and the other types of inflammatory myopathies have to be ruled out before you can say that this is polymyositis. It can be diagnosed also with with certain types of tests like electromyograms and muscle biopsies. As you can see on the right, there's a prototypical way that it looks under the microscope that helps us diagnose it too. But with this polymyositis, like I mentioned, there's no real rash. It doesn't really have other types of like genetics like the muscular dystrophies do. And obviously these people were not exposed to different types of drugs, for example. Dermatomyositis is slightly more common. It's characterized by the same type of muscle weakness but has some associated rashes. And you can see here on the right, some of the more typical rashes we look at are what we call a heliotrope rash, which is around the eyes, other types of red rashes that can just be anywhere on the body, and then this issue that we call mechanic's hands and Gotrindt's papules, which are on the hands where you can see a discoloration of the finger joints, essentially. And so these are prototypical rashes that can be somewhat easier to diagnose this when you have these types of rashes. But again, a lot of these autoimmune diseases can overlap with each other. You can get features of all sorts of different types of diseases. And sometimes the rashes can look different based on what these overlaps are. So again, it is a somewhat difficult diagnosis to make. Again, this is a very rare disease. There are variances again with gender and race. Here you can just see here that it's again higher in females than males, not quite as much as lupus is, but still there is that difference in the sex ratios. And again, there's probably some sort of hormonal incidence to this. But again, these myositis are disproportionately higher among Black patients. And they can impose, again, a substantial disease burden, especially quality of life issues when we talk about energy, difficulty actually getting out, getting to work, interacting in society. It can be very limited when this disease has progressed. Annual income loss can be significant. Healthcare care loss, again, can be significant. And again, sometimes patients will require hospitalizations, use of really severe or strong medications. And so what are we trying to do with this disease is essentially the same. We're trying to decrease inflammation. So that you can get your muscle strength back and preserve your organs so that that doesn't involve the organs and overall improve your quality of life, which of course is the most important thing whenever we talk about medicine in general. While we sometimes can get fixated on things like making sure the numbers are better, obviously we need to make sure patients are feeling better because that's the ultimate, the endpoint that we're going for. And so the, you can see here that some of the treatments that we look at are essentially the same because the idea is the same. We're trying to lower down the immune system in order to prevent this inflammation. And so we still use those steroids when things are very active and in the beginning of the disease. And we'll use different types of biologics, again, the antimalarials. We can use something called immune globulins, which are just a whole bunch of antibodies that are, that are received from people after they give their blood. And we can put that into people and that can sometimes bind bad antibodies. We use that in this disease a lot. And again, we use those immunosuppressants, the same types that bring down the immune system. And it's, it's the same type of ideas, though. We're still dealing with the same types of bad side effects with these medications. And so we need better medicines for something like this. Again, unmet needs, a lot of them. They're heterogeneous diseases. We really have to have a better way of diagnosing these diseases because it can take a long time to actually get there before. And by the time that people do get diagnosed, the disease could have become more intense in their body. Obviously, we still have a ways to go even in understanding these muscle diseases so that we can get more targeted treatments. We're a little bit further along in lupus than we are in myositis. And again, we have to deal with the fact that there's increased risks of death and severe illness with patients with these diseases, threefold higher compared to the general population when people have polymyositis and dermatomyositis. And again, malignancies are something that can happen. Cancers— this is one thing that is a little bit separate from lupus is that cancers have been seen associated particularly with dermatomyositis. And so whenever somebody is diagnosed with this, we have to do a full cancer workup because sometimes people can have hidden cancers underneath. So that's a big issue. And again, most of our diseases are— most of our medicines for this disease are just trying to broadly decrease the immune system, not really getting at what makes what makes this particular disease abnormal. So we have a role— we have a goal to get to. And there again are pipeline drugs here with this, and maybe a little bit less than lupus, but still there are people looking into this. And it's an important thing to look at so that we don't miss treatment or don't treat a disease that even though it's rare can be very significant and one that can affect certain populations more than other populations. So just to round out, again, lupus and lupus nephritis, chronic relapsing and remitting autoimmune disorder. It's a serious manifestation, the kidney diseases, that might progress to this end-stage renal disease if it's not adequately treated. And goals of our treatment include early diagnosis, early treatment, reducing the disease activity and preserving the organ function, managing comorbidities, and reducing the adverse events of the treatment. And we have a lot of side effects with our treatment, so we need better medications. Same type of situation with polymyositis and dermatomyositis. Rare disorders, muscle weakness, inflammation, skin manifestations in the dermatomyositis. Again, the same types of therapies, but still an unmet need for safer and more effective drugs. So with that, I'm going to toss it over to Dr. John Fowler.

Thank you so much. And that was a Really powerful and at times very sobering presentation. I also want to say a big thank you to Colin and the whole BHM team for hosting this session during this week, which is actually Rare Disease Week. And our— my company, the one of the Keysight Life Sciences I have the privilege of leading, is, is really laser-focused on trying to develop new therapies for rare diseases and rare autoimmune diseases. In particular. And it's really the core of my mission to, you know, try and partner with the leading lights in the field like Dr. Saxena, who just spoke with you, to try and roll out these clinical trials and bring these experimental new therapies to patients in need. And we are vividly aware here at my company of the unmet need and the way this unmet need is disproportionately spread across communities of color, and particularly the Black community. As you heard, almost 1 in 500 Black women will wind up getting lupus during their lifetimes. That's, that's unacceptable at a basic level to our perspective. And I think particularly sad that there aren't enough adequate therapies to help all these patients manage the different symptoms. It's a severe disease. And I just want to take a couple minutes here before we wrap up to talk to you about my company, Here's a picture here you can see of some of my amazing teammates who are all around the country, based here in San Francisco, but scattered throughout the country and working so hard to bring these medicines to patients. And I'll talk to you about the key medicine that Dr. Saxena showed on some of his slides, KZR-616. I know it's sort of a technical name. It'll have a real name one day soon, we hope. But this is a really, really exciting new medicine that brilliant scientists on my team developed several, many years ago, actually. And it's now in what we call mid-stage clinical trials. You can see here two trials in particular that are Mission Study and our Presidio Study are in phase 2, which is sort of the middle of the road on developing a drug. And we're giving it to patients with lupus nephritis, which you just learned a lot about, as well as dermatomyositis and polymyositis. We're really excited that, that Dr. Saxena and his clinic at NYU is a partner in our MISSION study. But we have many, many other clinics throughout the country and frankly around the world to try and make the medicine as available as possible to patients with active lupus nephritis, and also the myopathies that we discussed. Well, we won't be able to talk today about our efforts in oncology. That we feel we've got some unique new medicines for cancer as well. And I hopefully I'll be able to come back here in future years because we're committed to partnering with BHM. And if any of you, like so many of us, have been touched in our families by cancer, well, maybe we'll have something to offer there as well. I mentioned that it's Rare Disease Day. You can see that nice graphic at the bottom. We've been posting on social media and we're really committed to this community. And, and leverage our efforts towards diseases where there— it's not millions of patients, but every life matters. And, uh, the, the U.S. FDA designates an orphan disease or rare disease as 200,000 patients in the U.S. or less. And both lupus nephritis and the myositis diseases I just talked about qualify for those, uh, designations. And we actually got a formal recognition of that designation from the FDA late last year, which was a really big deal because it helps us get more partnership and cooperation from FDA to develop KZR-616 in dermatomyositis and polymyositis specifically. And I'll talk a little bit about the two diseases. I don't— not too much because I think Ahmet did a wonderful job introducing both of them and what serious diseases they are and the fact that there's limited treatments. And you can see there's a lot of patients, 150,000, up to 150,000 in the US and with lupus nephritis and 100,000 or maybe even more with dermatomyositis and polymyositis. So they're rare, but not that rare. And we think that 616, our drug, can have a really powerful effect. And I think the drug is very different from the other investigational treatments that are being tested in clinics around the world. And what makes it different, we believe, is what we're doing. This very attractive little illustration here, that's actually the target of our drug, KZR-616. It's called the immunoproteasome. It's a 7-syllable word. It took me a long time to learn to say that word as well. And like Amma said, we're not going to be having a quiz at the end of this. But suffice to say, and I hope you take away, that this is a really profound part of all of our biology. We believe through all of our scientific work, this actually serves like a master regulator of immune cell function in many ways. And what our drug does when we inhibit its function on a temporary basis, it sort of calms down the immune system, especially when it's having an overactive response. And the goal is to take an overactive immune system and bring it into harmony with the body so it's not attacking healthy cells. And that, that's, that is at a basic level what autoimmune disorders are doing. We need to restore harmony in the immune system. And the immune system is a multifaceted, multi-part, very powerful machine. What we— this is a technical illustration here, but we're trying to show that there's— these are 3 of many different types of immune cells, or what we think of as white blood cells, that each have different jobs. And typically, some of the medicines that Dr. Saxena talked about will target one aspect of this. Steroids will target it all and be a broad immunosuppressive, but biologics and other newer therapies are more narrowly focused, reducing inflammatory proteins and reducing antibody levels. But what our drug is, it's hitting all these different parts of the immune system. And so we have this image of a— that's actually the structure of our molecule there, holding a baton and conducting the orchestra, trying to restore the immune system like I said, back to harmony. So this is a slide that I would encourage you all to take out your cell phones, take a picture of, get a screenshot. I know we're also recording this session. And you can visit it on the BHM Fee Fairs website. But these are our two clinical studies with sites, again, all around the United States for patients with lupus nephritis and patients with active polymyositis or dermatomyositis. It's very important to us that these are, these are trials that are accessible to all patients in all communities. And to that end, we as a company step up and sponsor additional services. If you want to have a nurse come to your home, we can do that. If there's any travel expenses or other expenses incurred, we're prepared to cover those expenses and make it easy to participate because the sooner we can get these medicines tested, and closer to approval from the FDA, the more people will benefit from them. So we encourage you to share this information with loved ones, with friends, with acquaintances, with anyone, because these are open and actively recruiting studies. So thank you, everybody, for attending today. It's so wonderful to see more than 200 people taking part with this particular session. I saw a couple hands get raised.. I promise you that between us and Dr. Saxena, any and all questions will be answered and answered in a thorough manner. Just put them in the chat. We're gonna get a full recording as well as a list of all the questions. And also my company, Kizar Life Sciences, will have a virtual booth here all day today at the BHM Summit with wonderful team members and colleagues of mine staffing it. So please stop by that booth, ask questions, and learn more about these diseases and about how we hope to play a part in treating them. So again, Collin and the BHM team, thank you so much. And Dr. Saxena, thank you for that amazing presentation. And thank you everyone for being a part of today's talk.

Is there any basic testing that doctors should do first to diagnose lupus versus going through extreme testing?

You know, a lot of times primary doctors will check a couple of basic lab tests that can point us towards lupus or an autoimmune disease. There's a very nonspecific test that's called the antinuclear antibody. It is not a lupus test. It does not mean you have lupus if you have that test positive, but it's kind of a general screening test for autoimmune diseases.. And so a lot of times primary docs will check that when they have the idea that there might be something going on. And there's other general tests for inflammation that are, again, nonspecific. But, but if there's evidence of inflammation throughout the body, that might lead them to send a patient over to see us as rheumatologists.

Great, thanks. Okay, so next question: Is the volume of the cases for lupus higher in African American women due more to diet diet, heredity, or both, or neither?

I would definitely say heredity for sure. I think there's probably social aspects to it. Diet is probably the number one question that we get asked as rheumatologists because it's one of those things that we know does have a role with the immune system. There is no doubt that different diets for different patients can lead to increased inflammation. But it's not something that we've been able to really pinpoint that, oh, you got to eat this or you can't eat that. You know, aside from eating healthy foods, it's not something that we tell people like, oh, if you didn't eat this, you wouldn't have gotten lupus. So I don't think that diet would cause lupus. Whether or not there's certain foods for different people that might induce more flares or symptoms, that's something that we're still trying to work out.

Great, thank you. Do you think that one factor for the increased mortality for African is the lack of early access and early treatment.

100%. I think that is without a doubt. You know, the disparities are real. Again, there very well may be genetic or biologic differences, but there is a lot else that's going on here. So I do think that that plays a role.

Do we still have time, Colin, operator, for a couple more questions, or do we need to wrap up?

I believe you still have a few more.

You can probably get 2 more quickies in.

Okay, great.

I'm the founder. Oh, thanks, Rosalyn. Okay. All right, so here's another one. Should— all for Dr. Saxena. Should patients be seeing a cardiologist and nephrologist regularly in addition to a rheumatologist?

Uh, probably not necessarily regularly. Uh, a nephrologist usually would only be necessary if if there was some evidence of kidney disease, which is something that most rheumatologists should be looking for. I think doing a consultation with a cardiologist might not be a bad idea. You know, for one point, we do know that there's an increased risk of cardiac disease in lupus patients, that inflammation seems to affect the heart. Again, as a rheumatologist, you know, who focuses on lupus, I'll be doing some general checks for things like that, as will a primary doctor. But I think there's no harm or foul in seeing a cardiologist, you know, even if it's just once as a basic screen.

Great, thank you. Um, are the number of lupus cases just as high in other countries for people of color, for example, people of color and white people in Europe, or is there something about the US that makes a difference?

There is higher rates in Europe. It's just that there's much smaller numbers of of Black populations in Europe. So if you look at a lot of the European studies, they will often be nowhere near as diverse as the studies that we have over here. I think the interesting thing that we've been trying to look into is whether or not there's increased rates in general in Africa itself. And that's still an open question, too. So, you know, when we talk about what are the differences between genetics and— we call our diseases two-hit phenomenon. There's a genetics that makes you at some risk of getting the disease, but there's something something that pushes you into actually getting the disease. Even identical twins, you know, only 30-35% of identical twins will both get lupus. So there's something beyond that. And whether that's something about Western culture, you know, we have not figured that out yet.

That's great information. I think we have time for maybe one more. Does chemotherapy for cancer have any relationship to suppressing or reducing symptoms of lupus?

That's a great question. It absolutely does. And so we use chemo in our most severe cases and in patients with lupus nephritis because the way the chemo works is that it actually wipes out your entire immune system. And so if you have an overactive immune system, it can often wipe it out and then reset it for longer periods of time afterwards. And so they do play a role, but obviously we save them for the most severe cases. Cases.