aTyr Pharma, Inc. (ATYR) Earnings Call Transcript & Summary

We invite Dr. Shukla and Dr. Aryal to share their screens. So welcome today to our webinar. We are very pleased to have you all here with us. A couple of bits of housekeeping for everyone. If you have any questions during today's webinar, please type them into the Q&A. The chat has been disabled, but you may receive some links from us in the chat throughout the webinar. We're now pleased to turn this over to John Carlin, Host of the FSR sarcoidosis, Sarc Fighter Podcast. Welcome, John.

Well, thank you, and good morning, everyone. This is a wonderful opportunity for all of us to learn more about potentially new and better treatments for sarcoidosis. So this is officially the foundation for sarcoidosis researches, this is a town hall discussion transitioning of steroids and into new and investigational therapies. And again, I'm John Carlin. I'm the host of the FSR Sarc Fighter Podcast and the co-chair the Patient Advisory Committee, and I have the honor of guiding this very important discussion around the experiences that folks have transitioning from or reducing steroid treatment and on to new and investigational therapies. And we are just so honored today to see so many friends, family, clinicians and staff with us. So thank you again for joining us for this important event because this is really groundbreaking stuff that we are working on here today. These are -- this is an area that has never before in the history of sarcoidosis treatment been explored at this level. So before we get started, I do want to just share a little bit of quick housekeeping for everyone here. There will be no time for Q&A today. However, if you do have questions for the staff, please put them in the chat or reach out to FSR, and the team will get back to you with the support. And a link to today's conversation will be shared with all the registered attendees and that will be made available on the FSR YouTube channel. Now, the foundation for Sarcoidosis Research officially would like to thank to aTyr Pharma who are providing the generous support to make this event possible today, and we'll be hearing more from their CEO here in just a moment. In fact, let me get to the introductions for today. First of all, I would like to introduce a good friend of mine, Jim Kuhn, patient advocate and patient navigator for the foundation, for sarcoidosis research, and a fellow Sarc Fighter. Jim does so much heavy lifting on behalf of the disease and you'll be hearing from Jim here shortly. So Jim, welcome. Mary McGowan is the Chief Executive Officer for the Foundation for Sarcoidosis Research. And Mary, thank you for all you are doing on behalf of patients and the entire world that is sarcoidosis right now; Dr. Shambhu Aryal, who is the Medical Director for Inova Lung Transplant Program and the Inova Sarcoidosis Center. And I would be remiss if I didn't point out that Inova is a founding member of the FSR Global Sarcoidosis Alliance. So Dr. Aryal, thank you for joining us. And of course, Dr. Shukla, CEO and President of aTyr Pharma, working on a therapy that potentially could reduce the need for steroids in our treatment. When we say steroids -- for the most part, we're talking about prednisone. So at this point, I want to turn it over to Mary for some welcoming statements and sort of an overall look at more of what we're doing today. Mary McGowan, our CEO.

Thank you, John. We are so pleased to have you moderate the discussion today, and welcome to our esteemed panelists and to all the attendees to this important discussion on transitioning off steroids and on to new and investigational therapies. Thank you all for being here today to participate and to learn from our panelists. I would like to again extend a special thank you to aTyr Pharma for sponsoring this timely discussion. So today's event was shaped in direct response to our sarcoidosis community. FSR recently surveyed the community about the challenges in transitioning to new therapies from steroids. Thank you to all who took the time to share your feedback and reflections. So 64% of survey respondents are currently taking steroids and 80% experienced unwanted side effects from the steroid treatment. 100% of respondents want to learn more about nonsteroid-based treatment, and I imagine that's why we have most of you who have joined us today on this webinar. Based on results of the survey, we believe today's discussion is an opportunity to ensure that patients who want to learn more will gain the information and insights they need to fully consider their interest and support for new and investigational therapies. And what I'm most excited about today is talking about how new therapies in development have the potential to bring forth sarcoidosis-specific therapies that provide powerful alternatives to steroids. Today's discussion will focus on the process of transitioning from steroid treatment, how currently available clinical trials are shaping the future of the treatment landscape and ways for us to improve the process of transition from steroids in the future. Again, thank you all for joining us today. And John, I'll turn it back to you.

Great. Thank you, Mary. 100%, say they are interested in learning more about nonsteroid-based treatments. And I have been down that road. People on the podcast have been down that road, and I'm not surprised that, that number is 100%. So thank you so much, Mary. There have been a lot of advancements in the past few years, all spearheaded by FSR in partnership with committed companies like aTyr who are looking for a better understanding at the molecular level, the mechanism of showing how sarcoidosis forms and impacts the body and in the development then of new potential sarcoidosis specific therapies. And I know today, we'll be talking about all the therapies that are out there that people are taking, none of them have been developed specifically for sarcoidosis. So to break through and have sarcoidosis specific therapies and perhaps one that would eliminate the need for prednisone or steroids would be amazing. So steroids right now are the definition of a double-edged sword. My fellow patients and I, we've had many conversations on the podcast about our love-hate relationship with how steroids and their side effects -- yes, they work. They're the first line of defense, but the side effects are so bad, people have said over and over and over on the podcast, they don't know what's worse. The side effects from the medicine or the disease itself. So it's heartening to know that these new potential therapies are on the horizon and that this could be a big breakthrough in fighting sarcoidosis. So now I want to hear from each of our panelists today to share a few words and I want to start with Dr. Sanjay Shukla, the President and CEO of aTyr, Dr. Shukla.

Thanks, John. Thrilled to be here to talk to you today on Saturday in San Diego. So happy to really talk to the large clients, thrilled to talk a little bit about the work we've done at aTyr and what we've been working on really for the past, I'd say, 7 or 8 years to try to get us a therapy for sarcoidosis patients, specifically something that can reduce or even spare steroids from patients because we know that this is the frontline therapy. It struck me that the survey talked about 100% of the respondents who want to get off steroids and it occurred to me that years ago, when I started this journey, a Board member and even some folks on Wall Street said steroids are just fine for sarcoidosis patients. And that still sticks in my mind and bothers me because it was such a disconnect to what I knew from my limited experience going back to medical school on how sarcoidosis patients felt and the realities of what steroids do to their bodies. I've spent the last 20 to 25 years, frankly, bowing steroids, working in other conditions like lupus and myasthenia, where now there are better therapies, specific therapies that have alleviated and sometimes eliminate steroids from the treatment arsenal. So aTyr has been really committed to sarcoidosis. I would say that we're leading the way here and thrilled to see that other companies have joined us. We have a groundbreaking trial right now. Groundbreaking, why do I say that? Dr. Baughman in Cincinnati pointed out to me that we're the only trial that's reached Phase III, ever. I think that in itself is a monumental achievement for us to move a therapy into Phase III is something that's never been seen before. Phase III is that last leg of the journey, but perhaps the most difficult. It requires a real commitment not only from a company like aTyr but also, frankly, the patients. In other areas, diseases where a specific therapy is targeted for that specific disease. That's the goal here. Sarcoidosis patients deserve something better than just something off label. So we're going to talk about that today. So our trial EFZO-FIT is currently enrolling in about 10 countries. We're targeting 80 hospitals around the world. Dr. Aryal is one of our centers up in Fairfax and really happy to be starting that trial. We have an opportunity here to have the first therapy approved for sarcoidosis. And while we are targeting pulmonary sarcoidosis, we'll talk about ways where I think our therapy could benefit all sarcoidosis patients. But it's going to come down to the clinical trial, the commitment of the patients, we're reliant on patients and the data they produce. We'll talk about that. And I know it can be concerning participating in a clinical trial, but I'll say something that I said last month, I was with Mary in Miami. This data set, 260 patients that we're trying to enroll, if you're one of those 264 patients, you may be part of a data set that goes to the FDA, that gets some approval that can help tens of thousands, maybe hundreds of thousands of sarcoidosis patients. So when you talk about -- I know we talked about Sarc Warriors here, this is another call to arms and aTyr is committed to meet folks halfway. This is a trial that I think is designed by listening to patients around how steroids need to be removed from the toolkit. That's how I designed the trial many years ago, side by side with the experts and the FSR. So really excited that our drug can potentially be the first, and I'm hopeful that others follow because we're going to need a broader toolkit here. All clinicians know this. And no one company should claim that something is curative. We're starting here. I think we can really address some concerns and happy to be part of this roundtable.

Great. Thank you, Dr. Shukla. Dr. Aryal, let's hear from you now.

Thank you, John. You guys hear me, okay? Perfect. Hello, everyone. Thanks, John, Mary, Jim and Dr. Shukla. Thank you for the FSR team that's made this possible. My name is Shambhu Aryal, I'm the Medical Director of Lung -- of the Sarcoid Program here at Inova Fairfax Hospital in the outskirts of D.C., but the other hat I wear is also, I'm the Medical Director of Lung Transplant Program here. And I wanted to mention that because as a lung transplant provider physician, I end up seeing many patients with end-stage sarcoid that end up having to go to transplant and transplant is so hard. Time after lung transplant is limited and often you're left with having to take a lot of medications, and it's a totally different journey. As many of the other panelists pointed out, steroids are the -- and many of you are -- as you're living your life, steroids are the first line of defense, but they're [ fraud ] with a lot of complications, which I don't need to point out here. So I'm really excited that there is something new that's being developed. And I'm very, very excited to be a part of this journey, along with all of you as a researcher and as a provider and I really look forward to enrolling patients in this trial and eventually finding something that will help patients get off steroids, which I think is going to be a major paradigm shift in the last -- in the history of sarcoidosis. Thanks again.

Okay. Dr. Aryal, thank you so much for joining us here today. And Jim, let's hear from you, from the patient perspective.

Thanks, John. Hi, everyone. I'm Jim Kuhn, unlike my esteemed colleagues that you've heard from, I am not a doctor. However, I do support quite a few on my health care team quite generously. So it's -- it's great to be part of the discussion today, representing our patient community. I also am quite excited by the trials and new developments that are finally happening in the sarcoidosis world. I am quite hopeful about what this might mean for my health and the health for all of the sarcoidosis patients and how I might feel on a day-to-day basis. However, it also can be quite frightening to move off of steroids or other therapies that are working today, even though as John mentioned, it is a double-edged sword, moving off could cause concerns about flare ups when you move off or other side effects or other problems that can happen when you change therapies. Personally, I've been on merry-go-round of therapies trying to find something that will work for me and cover at least some of my symptoms: Pain, fatigue, chronic cough. Few patients who were on the call know the list I'm talking about, you all probably have many of the same symptoms on your list. I've been on and off steroids a bunch of times over my years. And I've had serious flare-ups requiring trips to the ER, urgent care or other specialists. I've taken a risk in trying all these other therapies that were meant for other people, not for people like me and like us with sarcoidosis. So I think it's finally time for us to try therapies that were designed just for people like me, like us, people with sarcoidosis. So I'm quite excited to hear more from Dr. Shukla today about therapies that were designed for people just like us. So John, I'll pass it back to you, so we can hear more of these exciting news.

Thank you, Jim, and thank you, everybody. So now we know to whom we are listening as we go through our seminar here today, and it's just so amazing. So many people who have come on the podcast, talk about every time they try to taper-off of steroids, they wind up with another flare -- and that's -- and they want to go off prednisone so badly because of the side effects and yet they -- every time they do, something goes sideways for them. So now since investigational therapies are really very new, as we've discussed so far to the sarcoidosis community and honestly, to the world in terms of what we're talking about right here, right now, today, what information do we want to bring to the forefront of this conversation.

So I want to start with a question of what do patients want and need to know about alternatives to steroids because they just don't want their life going sideways, but they want to have that something that's effective instead of the steroids. And Mary, let's start with you.

Well, thank you, John. It's really an important question. And it follows the conversation that we've had with the FSR community and from the community survey results that we've seen. So I want to share a little bit more about the survey results in that specific area. So we found that 52% of patients had switched off steroids who completed the survey and 51% reported that their health care providers have brought up nonsteroid-based treatment with them. However, the other part of this is 80% said that they had questions about what to ask their doctor about alternatives to steroids. So it seems that our patients are not sure what they need to be discussing with their doctors and what questions they should be asking. So I see real opportunity to empower patients with information and awareness through discussions like the one we're having here today. It's just really important that health care providers also are informed about research and that the discussions between the providers and patients is candid and informative. We really want patients to know what to ask their own health care providers, what considerations supply to their own health, we also want healthcare providers to understand the unique concerns of their patients and be able to respond with up-to-date and accurate information. So providers who treat patients with sarcoidosis have a responsibility, right, to stay current on research and investigational treatments. The sarcoidosis community, as we all know, has been misunderstood and poorly understood for far too long, updates to our collective knowledge of sarcoidosis are long overdue and the best way that I see this happening is through increased dialogue and awareness on all levels. The go-to treatment option for -- really for far too long, as we all know, has been steroids and some patients have access to off-label medications, but insurance doesn't always cover them and the off-level -- label medications have mixed success. So if sarcoidosis specific treatments are developed and tested by the community, healthcare providers will be able to better treat their patients unique sarcoidosis symptoms. And sarcoidosis disease is unique to each body as we know, a specific way that sarcoidosis affects individuals is just that, it's individual. And that's why we nicknamed sarcoidosis as the snowflake disease. I see good reason and a real need for development of many new therapies in part because of sarcoidosis community experiences unique symptoms and unique combinations of symptoms. Our survey respondents reported like -- one of them, reported like feeling like a guinea pig because their doctor just kept trying one off-label treatment after another with no success, and we can and must do better than this. Only 28% of survey respondents reported feeling confident that they understood alternative treatments to steroids. If the community has low confidence in their understanding, they're going to be less likely to try alternative treatments and they're going to be less likely to participate in the clinical trial. And as a result, the opportunity to advance the scientific understanding of the disease and treatment will not open. And again, we can't let that happen. Also half of the survey respondents said they experienced a flare when they transitioned or reduce steroid treatment. So patients have real concerns about how switching medications will affect them, like Jim was talking about. They're going to want to understand what to expect, what to look out for if they're going to reduce steroids and try something new. Patients are going to want to have confidence that they will be monitored, really taken care of during the transition time. They may also want some confidence that the transition will be worth it for them. So we're very excited about -- and Dr. Shukla, this is just extraordinary Phase III trial, we're so excited on behalf of the whole sarcoidosis community for your leadership, for your team's incredible work in this area. We're so excited about this. And we do want to be able to provide confidence to the sarcoidosis community as we continue looking at opportunities for taking patients off of steroids. Thank you. I'll turn it back to you, John.

Great. Thank you, Mary. And the survey is just spot on in terms of what I've heard anecdotally from the folks that I've had on the podcast and one of them is Jim. He's been on the podcast a couple of times. So Jim, let's hear the patient perspective on this now.

John, and Mary, you're absolutely right. I've tried steroids and just about every off-label medication available and none have fully helped, really, my symptoms. Just to explain, off-label means that you're using a medication for a purpose, which really wasn't originally intended or approved. And what I mean by approved is approved by the FDA. For example, I've been prescribed several medications that have been approved by the FDA for rheumatoid arthritis. And for example, Remicade or Humira and they've been known to help some sarcoidosis patients. Sometimes they work and sometimes they don't. Sometimes they work for a little bit and they stop and then you have to try another. As Mary mentioned, each sarcoidosis patient is different and each patient reacts differently to each off-label drug. And then you have to just keep trying, and you get on this merry-go-round, and you go up and down and just keep trying. And it's very wearisome. That's the problem with therapies that were designed for someone else with -- for a different disease. They don't always work for people like me, people with sarcoidosis. I knew it was time to transition from steroids and that I need to try something different because of the terrible side effects that I was experiencing from steroids: insomnia, mood changes, weight gain and migraines that continue even today. That was 9 years ago and I still have migraines today, 9 years' worth of migraines because of steroids. At that time, fortunately, my doctor understood and agreed and we laid out a plan to taper off the steroids and I began my first non-steroid medication methotrexate. That wasn't great, but at least it wasn't steroids. Personally, I've been through 8 different off-label therapies in my 10 years as a sarcoidosis patients plus other medications, all with varying degrees of success and failure. Recently, my rheumatologist who's my most trusted health care provider, you have to have at least one of those as an anchor on your health care team, she alerted me to a new gene study that can tell you if a TNF blocker type of medication will work on you. Well, I happen to be using an off-label TNF blocker right now. So I took this moderately expensive test, which my rheumatologist also help me cover the cost. She's great, and it came back that these type of therapies would be 90% ineffective on my type of body, my type of disease. I got the test results back, and I was crushed. So much time and effort in getting it approved. Mary talk briefly about that, that we have to fight the insurance company to use approved because it's not a type of therapy that is made for us, not approved for us. So I spent all this time in getting it approved and jumping through hoops, and now it's not effective for me, which I spent all that time, I spent all that money, I went through all that pain and now it's back to square one. So like many other sarcoidosis patients, I initially look forward to the opportunity to try something other than steroids because of what the side effects were doing to my body and my life. As a steroid patient, we're not alone in the side effects that we have. It affects all those around us too. I was shocked to find out at that time that there was not anything officially approved for sarcoidosis then I had a fight for something that may or may not work, because the drugs were designed for people with a different disease. That's why I'm so hopeful to hear about all the new trials and therapies designed just for sarcoidosis patients. We need FDA-approved medications that are targeted specifically for sarcoidosis, not for arthritis or Parkinson's or cancer or any other disease. Those are definitely worthwhile diseases, and they need their own therapies, but for our own disease, and we need our own treatment. Don't get me wrong, moving off of steroids is a double-edged sword, John mentioned that earlier. They are painful and nasty, and steroids are definitely bad, but they work. And starting a new treatment you don't know about, could be scary and you don't know if it will work, these all make steroids -- stopping steroids harder. Plus transitioning off of steroids is not an easy process, you can't do it in just a day and the next day decide to start another drug. It requires a step-down process, and you need to have time to allow your body to slowly adjust and moderate. I have seen and heard from other sarcoidosis patients that they've got incorrect instructions to just stop high-dose steroids right away, cold turkey, and it always causes problems. So my last word and advice is if you get this kind of instructions, go get a second opinion. Back to you, John.

Thank you, Jim. Get a second opinion and get it fast because...

Yes. Get it before you implement that.

That's for sure. And I just -- I noticed you said you've taken 8 different off-label therapies in 10 years, Jim, and that is sad. Unfortunately, it's true for many folks, everything we take is off-label. I'm also taking Humira right now and for me, it's working, thank God, but it's still off-label, and I still have battles every year with the insurance company, they want to get it renewed and then they deny, deny, deny and then at the last minute, so far, they've said, yes. So that's a common refrain. I've heard it from folks on the podcast and what you're saying is totally true. So let's build off the concerns that Jim has just talked about and the results that Mary has talked about. I think they're very much in agreement with one another. Many of the things that Jim has said are true for the sarcoidosis community at large, not just Jim. So let's go to Dr. Shukla now and hear a little bit more about this off-label therapy, how do researchers approach this and what do patients need to know about the research and Dr. Shukla, the trial, the Phase III trial that you mentioned that you have going on right now?

Thanks, John, and great comments, Jim. Off-label presents another challenge to patients that they don't need to deal with. And it's one of the things that we thought about early at aTyr when we started this journey. Sarcoidosis requires, deserves, demands its own approved therapy. So we don't have to have these additional barriers beyond the disease and beyond what steroids do to battle insurance companies. I mean that's a -- that story just really burns me up to kind of hear that. And as an industry individual and a researcher, this is how we approached and thought about our therapy early on. Going back 7 years, we started thinking we need to do better, and we need to do -- really target a therapy that directly addresses and hopefully, disease modifies, that's an important term, disease modifies sarcoidosis because there's a lot of therapies out there that can maybe be add-on therapies. But why add-on to a toxic therapy like steroids. But early on, Efzofitimod started doing some interesting things. We noticed some things that it did with lung cells in -- basically in the Petri dish. It seems to down regulate lung cells, immune cells. And these are the same cells that kind of are going haywire in the lungs. So that was an initial clue. Our therapy also comes from our natural physiology, it's a real kind of innovative protein that exists in our -- all of our bodies, and we're essentially trying to supercharge it a little bit. That is important to me as a drug developer because any therapy that does good things for patients must be safe. So I think there is some natural, what I call, evolutionary intelligence that goes into our science. I won't go into that too much today. But what I will say is we progressed from those early research studies. We started testing in animals, in animals that had quite a bit of lung inflammation. The therapy seem to do a great job of basically quiescing that. And then we moved into Phase I trials. Phase I trials are healthy volunteer trials. This requires us to administer the therapy to make sure in individuals were healthy. We don't see any new untoward effects, no safety findings. It's always important to me that any new therapy must be safer than the existing therapies. It's got to be good things awhile, so add an additional burden to patients. That was conducted several years ago. We checked that box. We moved into Phase II. Phase II was this attempt, and I think we did something really innovative. We said, we want to try this therapy, but we also want to try to taper people off steroids. And Jim highlighted this, this can't be done overnight. So this was, I would say, a paradigm shifting trial, [indiscernible] our design, Dr. Culver in Cleveland Clinic has said that. He said, this changes the paradigm. No longer will any trial not have some sort of steroid sparing element. That is his opinion, my opinion too, and any trial that comes along to incorporate that. In that trial, what did I expect to see? I expected our drug would help patients with their lung inflammation and by removing some of that steroids slowly, I thought we might be able to also show that their quality of life improved. As it turns out in that small trial, 37 patients, we saw, in fact, the ability to improve lung function. That's great. Everybody wants to see Forced Vital Capacity get better. But if I was back in Georgia Avenue in D.C., treating patients, I can't just say Mr. and Mrs. Jones, your FVC is getting better with this drug. It has to be more than that. The quality of life has to be better. And I was thrilled to see that in our trial, of, fatigue, shortness of breath, they all improved and not just moderately, significantly improved. The last thing I'll say, we did all this while removing and reducing steroids. And surprisingly, we even had 3 patients out of 9 in our highest dose group, get off steroids completely in our trial. So all really, really outstanding findings, and we published this along with folks like Dr. Aryal recently in a major medical journal and that's also an accomplishment. There hasn't been a major medical trial data set in medical journal for, I don't know, maybe 15 years. So this sets us up now. The last thing I'll say on that last trial, again, it was safe. We didn't see any new effects. We don't want to see any of that. So now we've moved into Phase III, and we work closely with the FDA to sit down with them. This is what's required. And it's frustrating because it can take 7, 8, 10 years. But moving through systematically, this is why maybe some companies and bigger companies don't want to go into sarcoidosis. When I worked at those bigger companies, it was, sarcoidosis was too hard, too hard of a disease, too hard of a disease to understand. I guess I'm naive in the sense that, that challenge was something that I thought, well, if this therapy might have some efficacy here, let's go for it because I think we could significantly impact patients. Our therapy is designed to be disease modifying, and experts have said it's the first therapy that checks all 3 boxes, improves lung function, improves quality of life, while reducing steroids. That's what I wanted to see. I think that's what any patient would want to see if a new therapy was offered. Why did we go into pulmonary sarcoidosis? I get asked that question. It is the most predominant form of sarcoidosis. But again, our therapy is really targeted to the lung. That's not to say it couldn't help patients who have other symptoms, cardiac symptoms, neuro Sarc symptoms. However, when you design a trial you can go 1 or 2 ways. You can go after perhaps the most serious patients, and this happens quite a bit in cancer and oncology, people who have failed everything else. And certainly, folks who become progressively fibrotic in sarcoidosis and unfortunately, some of them have to go see Dr. Aryal, that could have been an area that we focused on. I thought our drug works better early on in the disease. Let's prevent that lung transplant. That's the way I thought about it. The second thing about it is pulmonary sarcoidosis, the most predominant form. If we can address that, perhaps then we can chip away into some of these other subtypes. So it's a question I get asked quite a bit. The goal here is to address the primary pulmonary sarcoidosis symptoms. If this therapy is approved, at that point, we can have the ability to start to look at smaller subsets of patients. So I'm really excited about our trial. As I said, it's a landmark trial. We've gotten to this last Phase III step. Whatever happens, we're going to have a tremendous data set that's going to help experts like Dr. Aryal, even if the therapy doesn't work, learn. And I'll point this out, too, that I've been involved in trials in certain diseases that the drug work. But in other times, it didn't, but it led to approved therapies. And this is why there is a call to action here to get involved here. Last thing I'll say is that cascade effect on other trials, I would encourage all patients to participate in trials that you're eligible for. But I will actually highlight here that this is maybe a once in a generation opportunity in Phase III. So this is something that I'm engaged with not only FDA but worldwide regulators in Japan, in England and Germany. And I think the interest is what I can say from regulators, they believe there should be a therapy for sarcoidosis, an approved therapy. And I'm thrilled that we're part of that journey. And frankly, I think we're kind of leading some of that. So that's just some of my comments. I think Dr. Aryal might want to say something.

Yes, thank you, Dr. Shukla. I think that's great, and I do want to pivot to Dr. Aryal. But let me just say that Jim and I, and all the other sarcoidosis patients who are on this call are pulling for you to be successful with this Phase III trial, and we are really hoping that it gets approved and that it's something that folks can start taking as a first line of defense against sarcoidosis sooner rather than later. Dr. Aryal, it's got to be frustrating for you because somebody walks in and after fits and starts, they discover, okay, it's sarcoidosis. And now you've got to look at your limited options in treating them, right?

Absolutely, John. So that's exactly the situation I'm in. General pulmonologists and regular primary care physicians refer patients over to us with -- and large lymph nodes in the chest and there's a concern for cancer, and we do a bronchoscopy, and we're really happy to say you don't have cancer. But now you got something called sarcoidosis. And this is something that does not really have an approved therapy, steroids work, like Jim said about his experience. But it's really frustrating, as you alluded to, John, dealing with insurances for off-label therapies. So as a provider, it's really, really frustrating for us to have a very limited toolbox in treating diseases like sarcoidosis. It's like the analogy of you need to put a screw in the wall and you don't have a screwdriver, but you have a butter knife or a credit card to kind of put it in the wall. And you can imagine how frustrating it is. So we're really looking for that screw driver, drilled that to help with that. And I'm really hoping the current trial is going to be successful in providing something that's specific to treat sarcoidosis, so we improve the quality of life. We're able to use the drug without any hassles of insurance and actually modify the disease. As I mentioned earlier, too many a time, I see patients where disease has progressed while on these different trial therapies with off-label therapies like Methotrexate or Mycophenolate, Imuran, going all the way to Infliximab and Humira. Patients have suffered from a lot of side effects and continue to progress, and we unfortunately have to go through to the process of lung transplantation. So all I'm really hoping that this is going to be the tool that we can have in our arsenal to help our patients. There are also, as many of you kind of pointed out, problems prescribing off-label medications that I just mentioned, and you know insurance, dealing with insurance for you and for us is equally challenging. Go through -- we got to go through several hoops, call it, spending that time while you're visiting patients in clinic, like and then trying to get hold of the insurance company and trying to do a peer-to-peer, gets rejected. You got to go back again. And it's really, really frustrating. And then it gets approved for a very short period of time. You got to do this over again. So that becomes really, really challenging. So I think if we have something that's specific to sarcoidosis like this, then we should be able to help our patients better. And hopefully, there won't be any hassles with insurance and access to treatment. The information that I also try to share with my patients that they understand I'm prescribing specific treatments include some terminology. It's important to understand the difference between approved therapies, off-label treatment, investigational therapy versus a new therapy or alternative treatments. This is all -- these terms all mean specific things. And many of times, they're used incorrectly and interchangeably. So I think that's important to understand that as well. And the final thing that I want to say to the panel and my patients and all the listeners, is, I think, while there is a lot of hesitation with clinical trials, nowadays clinical trials are very well guarded for problems. There is a data safety monitoring Board that is monitoring the data independently. And if there is any signal of harm, the trial gets stopped early. On the other hand, if the drug does work or if the compound does work, you have the benefit of being on it, for at least a year or 2 beforehand, before it actually becomes mainstream. And we saw this in the Idiopathic Polymer Fibrosis and other fibrotic lung disease back in 2012, 2013, when we're participating in the trials of now approved therapies of Nintedanib and Pirfenidone, patients who were actually on the trial from our institution, they got to be on the drug for well ahead of 2 or 3 years before the drug became available. And when you look at something like IPF, it means a lot. And I think you derive the benefit of the trials in such a way. We actually -- as Dr. Shukla pointed out, participated in Phase II trial. And we are very, very excited with the results and really excited about Phase III results. So I think I would urge all of you to look at the possibility of enrolling in -- or at least inquiring about this trial and other trials that are currently looking as for improving your quality of life and treating sarcoidosis. Back to you, John.

Well, thank you so much, Doctor. It's got to be frustrating for you when you want to go put that screw in the wall, and you don't have the screwdriver, you just have the butter knife as you said, the corner of a credit card and you're trying to get it done the best way you can, but you just don't have the right tool for it. So we're getting closer and closer to inventing the screwdriver here, if I can continue with that analogy, with this Phase III trial. So right now, I want to go to Dr. Shukla and Mary to look at this new therapy. And Dr. Shukla, how close are we? What should patients know? Why is it so important to participate in these clinical trials? And just tell us what's next on the horizon.

Well, as I've mentioned and has been discussed, having a targeted therapy, an approved therapy for the disease, can impact really thousands of patients, and it could be very specific to those patients. Folks talk about they are rooting for us. Once you kind of get into Phase III, it's interesting. Much of the success is in the hands of the patients themselves. And I'll reference a disease, cystic fibrosis and we know it well here in San Diego because a company that essentially created the disease-modifying therapy for that, Vertex, right down the street and we even have a few folks who work there. That drug would not be available for those patients worldwide, if it wasn't for the patients and the job they did in getting involved in the clinical trial. So success is tied to the patients, especially when you get into Phase III. As a drug researcher, I look at things and I say, once you kind of get to Phase III, you've got at least a 50-50 shot. That's generally the ratio here. And yes, you may find something new. From a safety perspective, you don't want that to happen. Dr. Aryal pointed out, there are a lot of safeguards to prevent that. We always want to keep our patients safe. But then you want to design a bigger trial, a statistically significant trial and when you think about cystic fibrosis, they did that, but that wouldn't have happened in that rare disease if those patients didn't actually participate in that trial. Disease-modifying is important here to us. I think the way we've designed Efzofitimod is -- as a therapy that over the course of once a month, this is an IV infusion. It's meant to actually reduce or replace or even maybe spare you from steroids. But our trial is designed, it's a 1-year trial. It's designed that the drug is administered through a 1-hour IV infusion and folks have said, "I don't like needles," things like that. I get it. I get it. It can be a burden. Hopefully, in the future, if the drug is approved, we have ways to reformulate and get the drug delivered in a less sort of cumbersome manner. But for this trial, it's a 1-hour IV infusion, the drug is administered once a month, we are following 264 patients for a year. So there's essentially 12, 13 visits there. This is a drug that modulates some of those immune cells that we noticed in granulomas, as I said, are kind of going haywire. These are myeloid cells. I am really excited that the mechanism, we really start to understand how it's really pertinent and relevant to sarcoidosis. And I'm thrilled in a couple of months, we're going to be at American Thoracic Society in D.C., and we're presenting some of our mechanism of the drug to really get the experts' understanding and we are going to be in a big symposia talk there. So it also speaks to the medical community really digging in and wanting to understand how the drug works. The drug incorporates a steroid taper over the first 3 months. But as Dr. Aryal said, we want to keep people safe, and we want to do that slowly and carefully. One other thing I'll point out that the question was asked recently by a patient, what if I get put on placebo. Your placebo interestingly is a necessary part of showing your drug actually does something. And I'll venture to say that the patients that we don't know what you're on, whether you're on treatment or placebo. But in many ways, the placebo patients are perhaps the most important in the trial. You're serving a purpose and the 80 to 88 patients that are in our trial that will get placebo. Again, you are establishing a baseline of understanding the disease, and we will keep you safe but that could show up in that difference. And that's what disease-modifying means, to have a patient that basically does not get the drug to essentially say, if you get the treatment, are you really seeing a difference in lung function? Are you really seeing a difference in cough and shortness of breath? Are you really seeing a difference in the ability to really reduce and maintain steroids? So these are some of the objectives of our Phase III trial. It's being conducted in, as I said, 10 countries, about 80 centers around the world. We have an opportunity here to be a front-line therapy. It's going to require the patients now joining us as part of this journey, and I'm really grateful for the patients that have already joined our trial and really looking forward to in a few years because it is a 1-year trial, hopefully, in the 2025 time frame, maybe have an approved therapy. John, we talked years ago and I said it could take 7, 8, 10 years. This was maybe in 2018, but if you think about it, I can almost see that we swum out a few years ago, and I can almost see the other side now. So I'm just going to keep swimming here, and I think I'm grateful for the patients that are kind of joining me in this last part of this journey.

Are you still recruiting? Very quickly...

We are currently recruiting, actively at maybe about 40 centers in the U.S. And certainly, we can -- the FSR team can guide folks who are interested, after this call.

Very good. Mary, what do you think of what Dr. Shukla just said. Are you as excited as the rest of us?

I am extremely excited. First of all, Dr. Shukla was kind enough to say, he's great for FSR and some of our efforts. And I want to turn it right back on you, Dr. Shukla. We are so excited about this. You and I, of course, have been talking about this for a long time, and I had the honor of being with you at FDA talking about this. But every time I hear you speak, and today is no different. I get chills for the sarcoidosis community when I learn more about this and your efforts and your leadership and all the extraordinary work that you were doing to make this trial as successful as we're all confident that it's going to be. Not only going to impact sarcoidosis patients, but as Dr. Aryal was talking about really expanding the toolbox for doctors to be able to provide better treatment for sarcoidosis patients. So it's just so exciting. There just hasn't been this is spotlight, like we see now on the sarcoidosis community and that is really leaning to this shining moment. And again, a big part of this is because of your leadership and your passion for this effort and for all the patients who are signing up for the trial and are very excited about this as well. So I have so much hope that we can continue to inspire partnerships between researchers and industry providers and patients and that we really can make a difference for the entire population of people living with sarcoidosis and as I've mentioned, also for doctors. I believe that we have the interest from the scientific community. I believe that the FDA is starting to see the path to developing new and better treatments for rare disease are a big part of this, of course, will require more flexibility and forward thinking and I believe that providers and advocates are working to ensure equitable access to treatments for all people living with sarcoidosis. And it's a very important time for the stakeholders to come together, as I said, with this common goal in keeping -- moving this momentum forward. Back to the survey, for a minute, in our community survey, respondents who said they felt confident in our understanding of steroid alternative therapies reported thinking about transitioning off of steroids at a higher rate than respondents who are not confident in their understanding. So empowering our patients with confidence, as I mentioned, is really critically important as this. We want patients to know what is happening in research and with industry. We want our patients to know who you are, Dr. Shukla and what you are working on and why this is critically important for our patients and community. The same patients who felt confident in their understanding of steroid alternatives reported experiencing more unwanted side effects from steroids. So these patients do want to learn more and in FSR it's our responsibility to empower patients and provide confidence. About half of our community reported that their health care provider brought up nonsteroid-based treatments with them. This was truly eye-opening for us at FSR. The community is telling us that the discussions with their providers about nonsteroid-based treatments are only being started about half the time. We encourage all healthcare providers to talk to their patients about nonsteroid-based treatments for sarcoidosis and again, about trial opportunities. And then one more thing that respondents who reported that their health care providers brought up nonsteroid-based treatments reported more understanding of the difference between off-label medications and sarcoidosis investigational therapies at more than twice the rate of those without those healthcare provider discussions. So from that, we might infer that health care providers are a meaningful source of education and awareness raising for the patient population. So we continue to encourage our providers who are treating patients with sarcoidosis to work with FSR to empower the patients and improve the knowledge and understanding for specific treatments. So I hope this spotlight, and I'm confident, will continue to shine on the sarcoidosis patient population. I hope that researchers, providers, patients, caregivers and advocates continue to share information, open dialogue about this really opportune time. As we say, at FSR, the time is now. This is the shining moment for sarcoidosis to continue to build on this momentum. And we hope the opportunity blossoms into additional trials, improved disease understanding and insights, real insights into causes and genetic components and sarcoidosis specific treatments becoming available in the very near future. So very exciting times. We're really so grateful to the entire sarcoidosis community and moving the needle forward for sarcoidosis patients who -- we just -- as I said earlier, our nation must do better for this world. They must do better in caring for those living with sarcoidosis.

Thank you so much, Mary. And I'll tell you, what FSR is doing is just amazing. You're keeping all these balls in the air in terms of you're fighting the fight on the -- in Washington, with regulators. You are working with patients. You are our best and biggest advocate, and you're bringing everybody together so that sarcoidosis really does stand out as a disease that is deserving of consideration and research and all of that and -- so all of those of us who are the snowflakes as it were, have a path forward with our individual flight. Jim, just very quickly, I know we had scheduled about 2 minutes for closing statements, but we're running out of time here. We want to keep this pretty close to an hour. But Jim, just quickly, are you feeling more optimistic after everything you've heard today?

Probably better with the [indiscernible] going on. As I mentioned earlier, I am really excited by all the new trials and all the new focus that's finally happening in the sarcoidosis world. There needs to be something better for people like us living with sarcoidosis. Frankly, because there is no approved and effective treatment. I'm losing valuable moments of my life, each and every day. I'm not the only one that lives with these experiences and the roller coaster of therapies, it's not unique to just us sarcoidosis patients. I've spoken to so many of my other fellow chronic rare disease friends who face the same struggle every day, just like you and I do, John. Yet we get up and fight, and we fight on every day in the hopes of new therapies that are just now coming about. Both Dr. Shukla and Dr. Aryal mentioned 1 outcome of new therapies is improved quality of life. Honestly, that's really a little beyond comprehension for me right now. But if I could just get a little more time back with my family, and a little bit of time with my friends, that would be amazing. I know I speak for all of us who had to miss out on a family event because we weren't feeling up to it or we had to cancel a time with some friends because of a flare up. I know that happens to all of us, just to have some semblance of a normal life back would be great. So in summary, on behalf of all the patient community, I can say we are ready to transition-off of steroids -- we need to be confident of the treatment solution, but we are ready and now is the time. We really can't wait any longer. Thanks for having me here today. Thanks, Mary, for again, all you can do. Dr. Shukla, we're behind you. Anything you need from the patient side, we're ready. Back to you, John.

Thank you, Jim. Dr. Shukla, Jim said it so well. So how -- if somebody is listening right now, you want to give them hope. Let's talk about the impact of this drug and when you think that somebody might be able to start taking it.

Well, like I said, we're in the final leg here, and I'll just keep this short in saying that we're committed at aTyr. We've got a team really heads down working hard to enroll this trial this year. It is a 1-year therapy. So of course, that last patient when they enroll, it's a year from there. My expectation is early 2025 to be able to look at the data. And let me just say one thing here. We didn't create the data, the patients did, and the patients will in the next trial. So this is not aTyr's data, it's not FSR's data, it's not Fairfax Inova's data, we all work together. But the patients created the data that demonstrated great things. I'm hoping to replicate that in a larger trial and hopefully, in 2025, be able to present it to the worldwide regulators and have a discussion and have a good outcome. So I really appreciate everyone on this call, the FSR, you John, Jim, Dr. Aryal, the site coordinators who help us, but most importantly, those patients. Thank you to those patients for listening and/or participating.

Thank you, Dr. Shukla and Dr. Aryal. I know you're very excited about the opportunity to look a patient in the eye and say, guess what, we have a drug for that.

Absolutely, absolutely. It's been over 150 years since sarcoidosis was first described and we're finally looking at a Phase III trial or making history. This is a monumental moment for the whole sarcoidosis community, and I'm really looking forward to enrolling patients here and having a positive trial. So as you said, John, looking at my patient's eyes and saying, we got something that's going to treat this.

Thank you. And Mary, you just want to put a ball on here and just talk about how optimistic we all are?

Yes. So I'll keep it short and sweet. But in summary, really, this year, or next should be a real turning point for people engaged in sarcoidosis research, through trial participation and communication between the stakeholders and the research community, we can soon have a better understanding of the causes and uniqueness of the disease and most likely better therapies are on the horizon. And just to say that we are all unified by an extraordinary list of opportunities, including that the patient community will experience better care and better quality of life. And this is what FSR stands for. It's what we are all working on every day diligently. Dr. Shukla it's what you stand for and your extraordinary team at aTyr and the work that's being done in this third trial -- third phase trial for sarcoidosis. Dr. Aryal, your extraordinary leadership at Inova for joining forces with the FSR Global Sarcoidosis Clinic Alliance, to all of the clinics are working together in this united effort, and thank you for being a site for the trial. And for John and Jim, your extraordinary leadership on the patient front, sharing your stories and constantly advocating for the patient community for sarcoidosis and we just appreciate all that you are doing. And for all of the people who completed the survey and for the patients who are signing up for the trial, as was mentioned earlier, you really have the power, an extraordinary power and opportunity to change the lives of people living with sarcoidosis today and well into the future. And that's an extraordinary opportunity. So again, thank you to all. This was an extraordinary event. We need to be doing more of these to keep the dialogue going. And we are so very grateful for the partnership for everybody in this unique and vibrant community. Thank you.

Thank you, Mary. Thank you to Dr. Shambhu Aryal, to Dr. Sanjay Shukla and to our patient representative and advocate on behalf of FSR, Jim Kuhn. I think we've had a great discussion here today. And we have a wonderful opportunity to take the next step in battling this disease. So thank you all for serving on the panel. And of course, thank you to the many, many, many people, hundreds of people who have signed up to watch this. And of course, it will be available on the FSR YouTube channel and as an audio recording soon, sooner rather than later, hopefully, on the Sarc Fighter Podcast as a bonus episode. So thank you all for joining us here today.

Thank you all for being here today. Please look for the follow-up e-mail on Monday with the post-event survey and the recording of this event. We rely on your feedback to shape future discussions, and thank you in advance for your feedback.