Good morning, everyone. My name is Denise Lee. I'm an associate here on the Healthcare Investment Banking team. We're excited to be continuing our 43rd annual J.P. Morgan Healthcare Conference this morning with aTyr Pharma. We're thrilled to be here with Dr. Sanjay Shukla, CEO of aTyr. And without further ado, please welcome Dr. Shukla.
Thank you. Good morning. So I'm Sanjay Shukla, President and CEO of aTyr Pharma in San Diego. And today I'm going to talk to you a little bit about our company and how we're approaching a really important new area of respiratory medicine and indications, a bunch of them in interstitial lung disease. So here are some of our forward-looking statements that you can read very quickly. So a couple of highlights that I want to start off with. aTyr is a company that has a real major Phase 3 catalyst later this year in Q3. And much of the presentation is going to center around the opportunity in interstitial lung disease with our therapy of efzofitimod. And it has been a journey to advance what we think is a paradigm-shifting therapy in a multibillion-dollar space. So we're carving out really new territory here.
We're the leading interstitial lung disease company in the world, with one of the only programs to ever even make it to Phase 3 in these indications. We come here with a strong cash position, with runway getting through not only this important catalyst, but being able to subsequently file a BLA submission. Very, very good shape that we've created and crafted. Obviously, this is a major readout. After that, we hope to update and continue to have this strong position. The company is founded on a very, very intriguing pipeline targeting inflammation and fibrosis, built on a, we use that word novel. I think we probably need to sunset that. It was novel a while ago, but now it's becoming validated around tRNA synthetases.
And I'll talk to you a little bit about that at the end of the presentation, because we're also excited about some of the pipeline opportunities that we look to unlock once we successfully move our efzofitimod into an approved therapy. So let's start and talk about interstitial lung disease and how we're approaching it. Interstitial lung disease, for those of you that don't know, these are severe and inflammatory and fibrotic lung diseases. And there's a cartoon there of an end-stage fibrotic lung. When you look at the pathology of these patients at end stage, it does resemble this caricature here in this publication from a few years ago. Interstitial lung diseases, the hallmark is chronic inflammation. And it's chronic inflammation that causes worsening lung function. Day- to- day, there's morbidity that these patients experience, extremely poor quality of life.
And unfortunately, the trajectory leads to this kind of phenotype in the lungs. Obviously, if you get to this stage, you're in really bad shape. And mortality is impacted. You likely need a lung transplant. And even then, you're talking about outcomes that fall off the cliff. Progressive fibrosis, as I mentioned, survival is really poor, worse in some cancers. So we're shining a light on a number of diseases here that, as I said, is really the next frontier in respiratory medicine, having made great progress in areas like asthma, COPD, IPF, pulmonary hypertension. Interstitial lung disease is now the next frontier that pulmonologists and worldwide physicians are looking for a better and safer therapy. And I want to highlight that safety, because the current therapeutic options are really poor. They're quite toxic. They're not disease-modifying.
Patients are demanding better treatments that control their interstitial lung disease and bend the arc of their disease progression. This is the problem. Efzofitimod is our lead asset in Phase 3. It's a first-in-class biologic with an approach to interstitial lung disease that is generating fantastic results thus far, and we'll talk to you about some of that data and why we feel that way and how we're addressing interstitial lung disease with efzofitimod. As we advance efzofitimod, as I mentioned, we are targeting interstitial lung disease, but we're focusing on a number of more inflammatory lung diseases on the ILD spectrum, and it starts with sarcoidosis. And sarcoidosis is a disease that I'll talk to you more about. We are shining a light on this indication, an indication that in many ways is a forgotten disease.
When I attend most of the pulmonary conferences, it's always mentioned that it's a bit of a forgotten disease. It's a large disease, 200,000 patients in the U.S. alone. Part of why it's forgotten may be who it afflicts. It afflicts populations that may not have a voice. You're talking about folks who work in labor and construction. You're talking about afflicting primarily African-American Black women. They have three times worse sarcoidosis, 12 times higher the mortality. You're talking about folks who cleaned up the debris in 9/11. They all developed sarcoidosis. So it's a toxic inhalation, likely of environmental particulates, that leads to a chronic inflammation. And we are the leading sarcoidosis company in the world, with this being the tip of the spear of a number of interstitial lung diseases that, as you can see, add up to a really large market.
All of these diseases have poor outcomes with only toxic cobbled-together therapies that are being used for the last 50 to 60 years. Our view at aTyr is it's time to sunset some of these archaic therapies that have been on the shelf for the last 50, 60, 70 years. Interstitial lung disease is an area demanding better options. We have potential here for upwards of a $5 billion market. I think this is an area that we're fortunate to have advanced further than any other company. As we look to get data in sarcoidosis, we're also paying attention to diseases like scleroderma-related ILD. That's the next small Phase 2 that I'll also highlight here in this presentation. The goal here is to advance up that fibrotic curve. The drug, as we know it, is an extremely potent anti-inflammatory. It's a safe drug thus far.
The idea here is let's prevent that progression of fibrosis and really change the lives of these patients. That is a segue into the summary here for efzofitimod. It's targeting the innate immune system. We've spent a lot of time understanding how this new modality works. It does so by downregulating a number of pro-inflammatory signals. By doing so, we are changing and nudging the immune system into a less fibrotic state. We're addressing complex immune pathology. You've seen a lot of therapies out there target single cytokines. It's time to also think beyond just that hammer approach. We have what I would describe as a rather elegant immunomodulator, something that is doing things subtly, safely. In a disease where there's complex immune pathology, we need to think about a different kind of modality. That is efzofitimod.
Restoration of that immune balance without evidence of suppression. This is something that you're going to hear me say several times in this presentation. This is what's essential and why I think this is a therapy that, as Dan Culver, our lead PI, Chair of Pulmonary and Critical Care Medicine at Cleveland Clinic, he said, this is paradigm shifting if we can get this across the finish line. There's promising clinical proof of concept that we have published. And I'll go through some of that data. It was quite striking to all of us that we were exploring a number of endpoints here: steroid reduction, quality of life. We're looking at lung function. In all of those subjective and objective measures, the drug performed brilliantly. And why do I say that? We had a dose response.
And I'm sure you've heard a lot of companies over the last several days talk about dose response. We not only saw dose response, but we saw it in all of those endpoints we measured. So it gives us a lot of confidence moving here into Phase 3. Last thing, no known safety issues. We are replacing toxic therapy. So patients deserve something that is not going to create a new burden of toxicity. This modality offers that opportunity. And it's why patients who are currently finishing our trial are demanding to remain in our trial right now, even though they're blinded and we are blinded to what they're receiving. The respite from some of the toxic therapies that they've been receiving for sometimes five or 10 years in this trial has been something that they want more of.
So let's talk about sarcoidosis, which is our lead indication that we're attacking here with interstitial lung disease. As I mentioned, it's the major form of interstitial lung disease. The disease is characterized by these granulomas. It's a hallmark of sarcoidosis. And a granuloma is a clump of immune cells that is largely observed in this population in the lungs. Therefore, pulmonary sarcoidosis is the area we focus on. And for decades, we've been searching for what's the etiologic cause. When I was in medical school, there was a thought that it could be a bacteria that is creating an insult to the lungs, and then you get a granuloma around it. We have not found that bacteria. Others have looked at more environmental agents, inhalation of toxic particulates. This may be also the cause. But thus far, we don't know the etiology.
However, it presents in this classic fashion where there's cough, shortness of breath, a debilitating course that eventually maybe a pulmonologist looks at a chest X-ray, they see a granuloma, you biopsy that, and then the pathologist can say, this is sarcoidosis because it's a non-caseating granuloma, so you are seeing incidence rise in sarcoidosis, largely because the clinicians are saying, we need to look a little bit more closely for sarcoidosis, so it was one of these mystery diagnoses that was always discussed in shows like House 20 years ago, but now we've come a long way, and now lung disease experts say, look, we got to get a handle on if this is sarcoidosis or not, so not very difficult to diagnose with that compatible clinical presentation, the pathology, and you're excluding things like tuberculosis, which is also quite easy.
It's a different granuloma, but not a big problem to diagnose these patients. What you're seeing in the EPI is more and more patients, as I said, being diagnosed. When we started this program, that number under the U.S. flag there was closer to 160,000 to 170,000. It keeps rising every year. So we are seeing more and more of this. And worldwide, you're seeing respiratory disease pick up in developing nations, largely due to a lot of that industrialization that's occurring in places like China and India. Air pollution doesn't help. A large patient population, over one million patients worldwide, are afflicted. And that number continues to rise. We have new EPI data that we'll be looking to present at a major medical conference here in the spring. It will be the first refreshed EPI data, perhaps in the last 15 years, looking at claims data.
We are seeing numbers and codes in there that indicate it's a very, very large indication. Prognosis, it's poor. One in five of these patients are going to develop fibrosis despite the toxic therapies that they have to take. It's very much, as experts say, it's a devil's bargain. If you don't address the day-to-day inflammation, you may get granulomas in other organ systems beyond your lungs. Then you really have debilitating disease. I've seen patients who have granulomas in their heart, in their nervous system, in their liver. It creates a whole secondary host of problems for these patients. They still live under the fear of developing fibrosis. One in five are developing fibrosis. Most of the patients need some kind of therapy within three years. There can be some patients that might resolve.
Once you have day-to-day cough and shortness of breath and you see this inflammation, you've got to address it so you don't end up with a granuloma in another organ. You need that lifelong immunosuppression. Mortality is rising. We have new data that we'll be also putting out there in poster form at a major medical conference. Fibrosis is really the biggest driver, as I mentioned, of mortality. I want to describe a little bit of the patient journey here. Sarcoidosis really robs patients of their quality of life. That's largely due to the fact that they develop a second disease. That disease is steroid toxicity. This is a therapy that we think is addressing two diseases, sarcoidosis and toxic burden of steroids. Steroids remain the first line, unfortunately.
And it's time to get beyond the fact that, oh, these drugs are cheap and available. They do a whole host of other things from a health economic standpoint, but also from a patient standpoint. You could see the risk of diabetes, hypertension, osteoporosis, weight gain. See, some patients get put on steroids. They're gaining 60 to 70 pounds in half a year. Think about what that physiologically does to a patient. That then creates major socioeconomic impact. The days lost from being able to work are sometimes an additional month or two. Recently, at ERS, this was presented. All of us have those days we can take off. Maybe it's two or three weeks a year. These patients sometimes are out of work several months a year. Very difficult to even get out of bed. And then you lose your job. So it's a slow and steady decline.
In some ways, if there was more of a dramatic decline, like in some diseases like IPF, we may take notice. Again, this is a silent killer in a population that is not only underserved, but maybe you don't hear of. The alternatives are, once you progress, even more toxic. You're going on to other therapies beyond steroids as you get more fibrosis. It's time to put an end to this. We think we can address this. aTyr Pharma is targeting a large population. Here are some of the data that we're learning about. Let's just first look at disease severity. There's approximately 40% to 50% of the patients here that have this progressive phenotype. As I mentioned, unfortunately, you get 20% of these patients who have this burnt-out fibrotic lung. It's hard to do anything at that point for those patients.
Our target is really there in the yellow. There are some asymptomatic or mild patients that we're watching and waiting. They may become candidates. But again, that yellow part of this pie chart is growing. And as the incidence is picking up, that's where you're actually seeing the larger share developing. What we see from treatment, looking at some of our analysis, this is also growing with regard to steroid utility. So as more and more patients are getting diagnosed, we're still reaching to these last-generation therapies, steroids. So now three-fourths of the patients require steroids. This is also different than when I was in medical training. That no treatment or observation number used to be 50%. And then it went down to 35%. Now you can actually see in claims registries that, look, we're using a lot more steroids with these patients. And that's not good.
That's not good for long-term outcomes. So aTyr Pharma is positioned as a frontline steroid-sparing and/or reducing agent. We are seeing quite remarkable steroid-sparing effects in our blinded reviews. But the idea here is, can we reduce, at a minimum reduce, or maybe even eliminate steroids? And let's avoid some of those toxic effects. And let's also then avoid getting to those third-line agents, which don't work well either, and also come with their own toxic baggage. So upwards of 75% of the patients we think here could be targeted with aTyr Pharma. We've done some pricing work. This is preliminary. But you see drugs that have offered steroid-sparing benefit, drugs like Tavneos, Nucala, Fasenra. These are another indication. Those drugs are viewed as important by agencies around the world.
And they are commanding prices that I think you could look at that and say, well, that's replacing maybe a cheap therapy. But I think even payers understand that putting folks on steroids, you have a whole host of other issues that develop. And again, that health economic burden becomes rather large. Rare diseases, some of those same drugs I mentioned, you see some of the recent launches there. Efzofitimod would be targeting a rare disease. ILD treatments like Ofev, Actemra, that only just slow the reduction of decline. There's a spectrum here of what we think efzofitimod would fit within this range. That then coupled with some of the EFZO data, you can see how this can very rapidly become a multi-billion-dollar market.
And because we would be the first and only approved therapy in the last 50 to 60 years, steroids have grandfathered in as approved therapies. We really think that this would be, at a minimum, a second line. And some experts think, why would I even use steroids? I'd go straight to efzofitimod. So with that, let's learn more about efzofitimod. So I've mentioned efzofitimod is a biologic targeting ILD. We have engineered a protein, a protein that comes from our library of immunoproteins that have really, as I said, elegant properties here in nudging the immune system. And for those of you that like crystal structures and fancy design and how we have done this, that little yellow helix-turn-helix domain, that's in all of our bodies. That's a 59-amino-acid small fragment of an enzyme that exists in all of our bodies called histidyl-tRNA synthetase.
And our founder, Paul Schimmel, out of Scripps Research, discovered that these enzymes, which are known to just help us make proteins, have a completely different function when they break apart into fragments. Those fragments migrate out into different organ systems. And they play a local role in immune policing. That is really intriguing. When I joined aTyr, I'll admit this sounded more like science fiction than science. But we have now shown in validated clinical studies that we are seeing benefits here that have never been observed before. So we've really validated our platform through the development of efzofitimod. So it's a fusion protein taking that small immune actor, adding it to a human IgG1. This enhances the PK characteristics. So now we have a drug that can be administered once a month through a one-hour IV infusion.
It selectively binds a receptor called Neuropilin, Neuropilin-2, to be exact. This is a receptor not most folks know about. We discovered it as the binding partner. Makes perfect sense to me that if you have a real novel biology approach, that it's targeting something that maybe people haven't heard of. It makes actually good sense to me. If we were hitting a receptor that everyone knew about, I think that would be rather strange to me. So we've become Neuropilin-2 experts. And as it turns out, Neuropilin-2 has some real potent effects directly on a macrophage. And that macrophage is a key player in interstitial lung disease. These are cells in our bodies that eventually the immune system activates peripherally, enters into a monocyte, to be specific, will go to an organ where there's some damage. It then differentiates into a macrophage.
That is one of the bad actors, one of the key bad actors in interstitial lung disease. In the sarcoid granuloma, the clump that I mentioned is largely composed of macrophages that have taken hold and are, frankly, stuck in this immune loop that they are programmed in normal healthy tissue to act a certain way. Something is happening in sarcoidosis that is unabated, that immune loop. Neuropilin is expressed on these macrophages. We see it. We've visualized it using ISH and IHC techniques. We made the cover of Science Translational Medicine two years ago with an immune cell stain for Neuropilin. Very intriguing receptor working with our intriguing biology. As I mentioned, anti-inflammatory effects, very consistent. Anti-fibrotic effects, over half a dozen animal models. When you talk about a new biology, we took the additional step.
Many biotechs might run one animal model, jump right into the clinic. We looked at direct lung injury, indirect lung injury, experimental types of injury models to these poor rodents. No matter how they were injured, when we then administered efzofitimod, we saw consistent anti-inflammatory effects. Gave us a lot of confidence that we could move into a number of interstitial lung diseases, but we had to pick one for POC. That's why we prioritized sarcoidosis, because it is the most inflammatory form of ILD. That Neuropilin expression, you may ask, do you see it in these granulomas? Yes. We even look specifically in that tissue of greatest pathology and Neuropilin lights up. So we know that substrate, that binding partner to our drug, is right there in the tissue that is causing the biggest problem for these patients. Thus far, a very desirable safety profile.
Go back to animals, healthy volunteers, even in our Phase 2 trial. The things you might worry about with a new form of immunomodulation is, do you see more infection or immunosuppression acutely? We don't see that. It's a biologic. Any company here that has a biologic that's infused, you might worry about infusion-related reactions. We don't see that thus far. It's chronically administered. Do you have any immunogenicity that's developing? Again, we're not seeing that thus far, and we've had three positive drug safety monitoring boards in our Phase 3 trial. So again, this drug has to remain safe, and I'm really proud that it is safe, because that's going to be a key component to the value proposition if and when we get approved here. Clinical proof of concept, that's been demonstrated, and I'll show you some of that data.
Patent life, some have asked, how long do we have patent life here? It goes out to 2039. So we really are positioned nicely here to have a therapy that can really generate outstanding therapeutic benefit, but also commercial runway here to do great things and meet this market. So in a nutshell, how are we mechanistically? I've described a lot of this already. Immune triggers recruit monocytes. Those monocytes differentiate the macrophages. They express Neuropilin-2. We know this. This has been presented at multiple conferences. I'll tell you, all of our MOA data is actually going to be in a very large and important publication that has recently been accepted. I can't get into the journal yet. It's in the final stages.
This will be a culmination of seven or eight years of work from our outstanding research team in San Diego that really understands now that aTyr Pharma is nudging these macrophages in a more positive direction. Because in normal patients, you see this inflammatory matrix and a number of these cytokines I highlight. We highlight here MCP-1, TNF. They go haywire. And we're resolving some of that by retuning the macrophage into a more resolution state. Again, I call it an elegant immunomodulator, because it's not a real overt hammer. But it's working with our biology to retune the system here so that we actually have healthy lungs and not inflamed lungs. Our clinical proof of concept was presented years ago and written up in the journal Chest. And we recently were awarded Best of Chest.
They said this is one of the most viewed, if not the most viewed, articles in the last four years. I mentioned we were looking for improvements, some trends that we might see here. We saw trends in all of the endpoints. In steroid reduction, when you placebo adjust, you see that our highest dose improved things 22% more than placebo. Overall, it was a 58% decline in steroid use. What happened when we reduced those patients by 58%? You started to see lung function improvement. You start to see improved fatigue scores, improved dyspnea, improved cough, so by removing steroids and adding efzofitimod, you're seeing better results than even the baseline steroids that they were receiving without that toxic effect, so this was presented years ago. This compelled us to move into Phase 3 .
I encourage all of you to take a look at the Chest article. Dan Culver, as I mentioned, is our lead PI, chair of pulmonary and critical care at the Cleveland Clinic. We've done further work. We've looked at some of our what we call therapeutic doses, the two that we took into Phase 3. You see really fantastic signals in time to relapse and also looking at how well patients are performing using the KSQ-Lung. This is a King's Sarcoidosis Questionnaire from King's College London. It's the most robust quality of life instrument. Anything greater than a four is viewed as clinically important. We're seeing people with 12 or greater improvement. These people are feeling great. A lot of that is attributed to the drug, but also getting off steroids makes people feel great.
I mean, all of us in this room, if we took steroids for about a week, we'd feel great. But after that, we'd feel miserable. These patients are on steroids sometimes, as I said, for years, if not decades. So removing some of that toxic stimuli, they love it. So this was also recently published in ERJ. I'd encourage everyone to take a look at that. We had an end of Phase 2 meeting. Trial design was aligned. Primary endpoint, steroid reduction. But we're also looking at function with forced vital capacity. And then again, we're looking at this very robust quality of life instrument. I was really proud that once we had this discussion with the FDA, we aligned. We also then went to European regulators, Japanese regulators. Everyone has really gotten behind us.
Dare I say, I think the regulators are really hoping that we're successful here, because they know how bad interstitial lung disease is in all of their regions. Our global Phase 3 design is fully enrolled. Good timing for all of you. We're finished with enrollment. And now we're just waiting for data. This was now a well-powered and highly powered design trial, 88 patients per arm. We took the two efficacious doses in Phase 2 forward. We finally enrolled 268 patients. Some key things here. In the last trial, we noticed we could knock down steroids pretty well down to 5 mg . But we're leaning into that signal a little bit more in this trial. And we're attempting to taper people to zero. And we're already seeing benefit in many of the patients, as I mentioned, who have finished the trial.
We're now refusing to go back on steroids. So we've had to step up with an expanded access program rather quickly here, working with certain regions that allow it. But this is a trial where we'll look to taper down from an entry dose of 7.5 to 25 and then observe patients from week 12 to week 48. What we expect to see in the placebo population is flaring, exacerbation. And you'll see that prednisone dose jump back up. We think using our drug, we can keep patients at low or no dose. But that's really what we're trying to basically see with our statistical delta. We're trying to see a difference in that average daily prednisone dose. And even if we could peel away one or 2 mg, agencies look at that as important. Why? Because it's a cumulative reduction of that burden.
10, 15, 20 less milligrams of prednisone a week, 80, 100 less a month, that adds up to positive benefit for these patients with their quality of life. If we can do that and maintain that immune balance, I think we have something really special here. I'll wrap up with SSc-ILD , a smaller trial we're looking at with our next indication. A common deadly manifestation of systemic sclerosis is the worst form and phenotype of scleroderma. Once it impacts the lungs, you're talking about a lot of scarring that patients can go downhill rather quickly. aTyr Pharma is being tested in this trial. Diagnosis here, this is an ILD that's more fibrotic. Obviously, they have autoimmune disease. But now it's attacking the lungs. Here you have a few therapies that have shown less reduction and decline. But again, this is an area that we need better therapies.
Most of the patients are diagnosed quite early in their life, 45 to 55 years of age. A big mortality risk once you get lung damage. And efzofitimod, I think, is positioned here nicely, because we already had good preclinical data in scleroderma mouse models. We got Fast Track designation rather quickly because of that. And because of our SARC data, many of those pulmonologists who work down the hall at the Cleveland Clinic said, "I actually want to try this in my patients, because I think there's a lot of inflammation in their lungs. And efzofitimod could be useful." More patients are developing fibrosis with SSc. So we're doing a small Phase 2 trial just in the U.S., just to look at proof of concept here, similar to what we did with sarcoidosis.
We're taking two doses, 450 mg and 270, 10 patients each, comparing it to placebo. We'll have some interim data here in Q2. I think what's intriguing about this is we have access to tissue with skin samples. Sarcoidosis is a little bit hard to assay the granuloma during the trial. It's also probably not ethically appropriate to do that. Here we're going to be able to see the local effects of efzofitimod by looking at some of that immune damage in the skin. Stay tuned for some small data here to read out here in Q2. I'll end by just talking about this approach. Our modality comes from our pipeline of tRNA synthetase biology. Efzofitimod represents the first that we're looking at interstitial lung disease. There I mentioned HARS and the target Neuropilin.
But we have 0101 and 0750, which come from two other synthetase fragments that are doing interesting things in modulating fibroblasts in the case of 0750 and myofibroblasts in the case of 0101. And myofibroblasts are real important players that once you develop fibrosis, those myofibroblasts are the ones that really are there in the scar. And dare I say, 0101 has the potential to be anti-fibrotic. A lot of companies talk about anti-fibrotic. It's mostly fibrostatic drugs they're creating. This is a therapy that has been highlighted at the Keystone, because we're seeing apoptosis of myofibroblasts. That's what I want to see. Let's develop game-changing, real therapies that aren't just looking at less reduction and decline of fibrosis. Can we unwind some of that biology? So these are things that we're excited about, obviously focused more on aTyr Pharma. I'll wrap up here with a corporate summary.
The platform, as I mentioned, is something that we're really proud of. But we're being very careful to advance that first one, efzofitimod, across the finish line. This is a candidate, obviously well positioned for a very, very large market. The pipeline, we are a company that is really focused on inflammation and fibrosis. That's where we think the biology is best positioned. And we follow the data. So we have no particular narrative that we say we have to go into lung. We're looking at kidney disease. We're looking at liver. Where can we actually best position this biology? And I'll end by saying we're in a really strong financial position to get through some of these near-term catalysts and learn more about where we are next year. So with that, I'll take some questions.
Thanks. If anyone has any questions, please just raise your hand so we can pass you the mic.
I think you maybe had a slide on this, and I might have missed it. But in sarcoidosis, what is the sort of fibrotic pathology in terms of presentation and how that evolves over time? And then I guess the lead-on question is, from patients that you've enrolled and from a regulatory and a clinical standpoint, what's the relevance of the fibrosis side?
Sure, sure. Patients in sarcoidosis are obviously on the more inflammatory side of the spectrum. There is a slow decline of fibrosis. A patient who has more than 20% fibrosis on high-res CT starts to resemble an IPF patient. It is a gradual process that you may see develop over time. It can be variable. Some patients can become fibrotic within three to five years. Others might take 15 to 20 years. The presentation is a gradual process. It may look radiographically different than a pneumonitis or a scleroderma patient. There is a gradual parenchymal involvement in some lower parts of your lungs that start to develop fibrosis. You have this granuloma, which is a target for inflammation. You then start to see parenchymal damage. In our trial, we are excluding the highly fibrotic patients.
What we noticed in Phase 2 is there were a few patients in the one milligram cohort who had a bit more fibrosis. In our view, it's a little bit hard to move these folks and really see some of that efficacy when you have that fibrosis already entrenched. But this is something that also we'll learn more about in scleroderma. Can the drug work well in more of a mixed phenotype? But at least for proof of concept, we're trying to basically enrich by looking more at the inflammatory patients. So there is an exclusion criteria that if you have more than 20% fibrosis, we're going to actually exclude you for this trial. But it may be something that we'll learn more about, hopefully after we get efzofitimod approved for sarcoidosis.
Maybe I'll ask the next question. As it relates to the Phase 3, can you explain the steroid taper protocol? How is it similar or different to the Phase 2? And how are you thinking about minimizing the PI discretion and subjectivity?
That's a great question, because with some of those approved therapies that are out there, there was a lot of contentious debate, because there's investigator subjective judgment, and one of the things we worked with the agency is, let's have a validated tool that guides taper decisions, and perhaps they even learn from the Tavneos approval, so we have a tool we use, the PGA, it's a validated instrument that every two weeks we're assaying these patients. How are you doing? How have your last two weeks been? And if there's any worsening on that PGA, even a one-point worsening, there's an automatic edit check that goes out from data management, even saying we should see a steroid increase, so patients are asked to follow their prednisone dose every day in their trial. If there's a worsening in PGA every two weeks, it's being assayed.
That guides some of that judgment. So we're taking a little bit of the keys away of the car from the pulmonologist here, because we want to have that titration based on the PGA. How is it different? One of the key differences, as I mentioned, we knocked everyone down to 5 mg and then looked to see if they flare in the last trial. This trial, we're knocking folks down to zero. So what we expect is more unmasking of disease in placebo, more steroid rescue there. That could then serve as, how I said, with the area under the curve, a delta emerge. So those are some of the key differences on how we're minimizing some of that investigator bias, but also potentially seeing a greater signal of steroid sparing with efzofitimod.
Thank you. Any other questions from the audience? OK. One last question for me then. How are you working with your partner in Japan? I believe Kyorin Pharmaceuticals. And for that Phase 3, will they be able to use that data to file over there?
Yeah, Kyorin has been a great partner. They came in quite early, even before our clinical data. When I talked about some of that translational data that we had, we presented at ATS in Dallas. We were approached by them saying, look, these are real remarkable changes you're seeing in some of these animals. We want to get involved. So Kyorin joined our Phase 3 trial. There are a number of centers, about 15 centers in Japan, part of the 90 centers that were in the Phase 3 trial. That subset of Japanese patients will serve as the approval in Japan. So it won't be carved out of the whole signal. We'll look at all of our data. But they have contributed patients to this trial. And the PMDA, the Japanese regulators, view that as an appropriate subset of patients that look at the whole data.
Provided there isn't any real differences in the population, this will serve as an approval. If we get the drug approved in aTyr Pharma, we will be eligible for up to an additional $155 million in milestone payments. We've received already $20 million in milestone payments with Kyorin. This is a big problem in Japan, ILD, sarcoidosis. It's been a really nice partnership in an area where the Japanese PIs have been demanding something better for their patients.
Thank you. Thank you, Dr. Shukla, and the entire aTyr team. Thank you.