The company just recently changed their ticker as well to ATYR, and has a lot of interesting, innovative programs ongoing right now. It's gonna be presentation format, and if there's some time at the end, we'll do Q&A, but thanks so much for joining us today, Sanjay.
Great. Thanks, Maury. And, yeah, the ticker just was changed today, and I think on the Nasdaq big board, it's up right now, so excited about that. Here to talk to you today about aTyr and what we do. We are probably the only evolutionary intelligence biotech out there. I'll explain a little bit what that is, since everyone is really familiar with artificial intelligence and can explain that back to me. Here's some of the forward-looking statements. At aTyr, what we're really involved in is a really novel area of immunobiology, translating insights from tRNA synthetases into new therapies, mostly targeting fibrosis and inflammation. I'll talk to you about these ancient enzymes, tRNA synthetases, and how we're doing this.
We own a large platform of around this biology, about 200 novel fragments, and these are extracellular functional proteins that have evolved out of tRNA and tRNA biology over really the last billions of years here. Potential new class of medicines here, a brand new modality that we are finding some exciting both clinical and preclinical insights around. These proteins seem to have a distinct focus around inflammation and fibrosis. I think it's highly differentiated, and right now we view this as an opportunity that could produce multiple opportunities in areas where there's unmet need.
The first fragment we looked at, and harnessed some of the power behind its immunomodulatory properties was, a fragment of histidyl-tRNA synthetase that's there in the helix-turn-helix, yellow motif that you see there, and we engineered then a protein fragment, a biologic that is a first-in-class immunomodulator that we're targeting interstitial lung disease, and I'd say we're the leading interstitial lung disease company right now, in the world. We established a clinical proof of concept with a phase 2 trial in pulmonary sarcoidosis that read out a few years ago with perhaps the best data set seen in the last 50 or 60 years, and currently, we are rounding the corner here to finish enrollment in a phase 3 trial, currently, being run in about 90 centers in nine countries all around the world.
Just as I said, rounding the corner here with enrollment, due to complete, final patient expected to be dosed next month. We also have a phase 2 proof of concept in scleroderma-related ILD. As of our last filing, we're well capitalized, really in a good position here to not only read out the data next year for our phase 3 trial, but get through a BLA filing. So let's talk a little bit about what's evolutionary intelligence. tRNA synthetases are enzymes that are in all of our bodies. We have about 20 of these synthetases.
They help us make proteins within our cells, and for really all we've ever known about these synthetases is for a long time, they conjugate a reaction between a specific amino acid and a tRNA, and this allows us to make a protein chain and part of the machinery of within our cells. But our founder, Dr. Paul Schimmel, discovered something rather unique, that these synthetases break apart into fragments, and the fragments seem to migrate out into different organ systems, and there they play a very non-enzymatic role. They seem to be local policemen of the immune system. And one thing we've seen is these domains have persisted through evolutionary pressure. So I know there's a lot of hype around AI and drug discovery and novel targets, but in all of our bodies, we have appended domains to these synthetases.
Lower level species share a lot of homology to these synthetases, but we have, over time, adapted due to evolutionary stress and pressures, to have additional genetic domains added to these synthetases. These domains, we think we are liberating, unlocking some unknown biologic activity, and when they're released locally from these full-length proteins, they serve as extracellular signaling molecules. So very much a preserved system that goes back billions of years and millions of species. So trillions of real-life experiments have created some of the unique functionality that we have already found modulate, for example, lung, inflamed lung cells, and that's what efzofitimod is based on. But we have other fragments from other synthetases that are biologically active in, for example, modulating fibroblasts. So very exciting times for us.
We're regulating complex systems where the normal small molecule or chemical or even monoclonal approaches have not been successful, and there's a growing evidence here that what these regulators are doing is restoring the balance, the local immune balance. I think that's really important from a clinical perspective because we're avoiding a lot of the sort of untoward safety effects that you might see with sort of more heavy-handed immunosuppressants and therapies that are currently on the market. The validation is really something that we've really focused on. As we're talking about new science and novel science, we wanna be well-published, and I think we'll probably view ourselves as a biotech that's probably one of the best published of any company that's even here.
Not only our clinical data, but then we follow up with review articles, exposure response analyses, and we were fortunate to be highlighted on the cover of Science Translational Medicine last year. That's an immune cell stained for neuropilin, the receptor in which efzofitimod binds to. So a lot of validation in peer-reviewed journals. We think that's important when you talk about new areas of biology. Scientists, clinicians, they want to learn more about the MOA, and I would expect even further literature to come out of our data. The Chest journal was really the landmark publication that I'd encourage everyone to look at. That was our proof of concept that validated our science. So growing pipeline of tRNA synthetase-derived biologics, focusing first on interstitial lung disease. We follow the data.
Efzofitimod is a fragment of histidyl-tRNA synthetase, and it modulates neuropilin 2. Neuropilin 2 is a cell surface receptor highly expressed on myeloid cells. So by turning down these myeloid cells, we think it could be useful in sarcoidosis, SSC-ILD, and potentially other ILDs. We have two preclinical candidates right now that are also binding well-known receptors, TGF-beta family, LTBP1, which is a modulator of fibrosis, and O750 is another exciting program that comes out of another tRNA synthetase that modulates FGFR4. So these are being explored right now in preclinical models of fibrosis, liver, lung, kidney. So really excited to see some of that progress and that validation that we got out of efzofitimod.
Now, in turn, we're turning to, you know, run the same types of phenotypic screen and understanding of how we move these programs forward into the clinic in future years. Let's talk now a little bit about efzofitimod, because I think this is what is most important and top of mind to most investors. First-in-class biologic, as I said, targeting interstitial lung disease. It's an Fc fusion protein that takes a novel domain of histidyl-tRNA synthetase that has unique properties that immunomodulate myeloid cells, and we fuse it to a human IgG Fc, thereby conferring a better PK signature. These proteins have very short half-lives. By creating this engineered protein, we now have a half-life that this drug can be administered once a month through a one-hour IV infusion with a half-life of about nine days. That active domain, we noticed, is enriched in lung tissue.
In all of our bodies, I can assay that fragment, and we'll see that it seems to play a role in the background of controlling lung immune regulation. It's downregulated, as I said, through Neuropilin-2. We're downregulating myeloid cells. That was through a very selective screen of about 5,000 known receptors, found a very selective affinity to Neuropilin-2, and we've learned Neuropilin-2 is a really interesting immune regulator in local inflamed systems. The anti-inflammatory and anti-fibrotic effects that we saw in ILD models, we ran a really comprehensive translational study of over 6 animal injury models, and I think a lot of companies, they look at one or two animal models, and then they jump into the clinic.
For us, we wanted to really see those consistent effects in experimental lung injury models, Bleomycin, ILD models, like the scleroderma, graft mouse model. Some of these are direct, some of them are indirect lung injury models. In all of these models, we saw consistent effects. We published this data. This actually led to a partnership with Kyorin in Japan, where we've been able to license the therapy at preclinical stage for interstitial lung disease. As I mentioned, dosed once a monthly through a one-hour IV infusion, and clinical proof of concept was demonstrated in Pulmonary Sarcoidosis. Here's our hypothesis. In a number of interstitial lung diseases, the hallmark is immune pathology, and unremitting immune pathology can have come from different origins. It can be related to an autoimmune disease like scleroderma, now it attacks your lungs.
It can be related to antigens, such as pigeon dander or even particulate matter, that causes things like hypersensitivity pneumonitis. In the instance of sarcoidosis, though we don't know the etiology, it's probably an environmental antigen that you breathe in, and it causes a constant immune and adaptive loop of inflammation, and the macrophage itself is the quarterback here that we think we're downregulating. We've seen macrophages in these myeloid cells express neuropilin, specifically in sarcoid granulomas and even in scleroderma plaques, and efzofitimod binds neuropilin, and that's how we basically are turning down some of the hot acting inflammatory signature of these macrophages. The goal here is let's restore that immune balance, let's improve lung function, resolve symptoms, and hopefully, we also prevent the progressive fibrosis.
You know, here in New York, sarcoidosis is really important because most of the 9/11 workers who cleaned up the debris down in, downtown Manhattan, they basically came down with a very aggressive form of sarcoidosis that tipped over to progressive fibrosis very quickly. So we're advancing efzofitimod as standard of care for ILD. ILD, umbrella of about 200 phenotypes. Our current focus is the more inflammatory forms of ILD, but there's a lot of upside here to move into over, you know, 200 types of rare interstitial lung disease. IPF is the most commonly known ILD, very fibrotic, but we're really focusing on the inflammatory side of the fence. Right now, we don't have good therapies. Steroids seem to be the standard of care, but the problem is steroids come with their own cumulative burden of toxicity.
So our current focus, we think, is a $2 billion-$3 billion global market opportunity. There's upside in other ILDs and and even potentially in systemic disease, once we actually, demonstrate effectiveness in ILD. So here's some of the market opportunity. Sarcoidosis, about 200,000 patients in the U.S. Most commonly, the phenotype you see is a pulmonary form of disease, so granulomas are seen in the lung. But you can have granulomas in the heart, liver, also in the spinal column. Most of these patients, are treated with steroids. However, some of these patients, up to 20%, develop lung fibrosis, and that's really when morbidity and mortality fall off the cliff here. As I mentioned, standard of care, mostly OCS. Sometimes patients have to go to more heavy-handed immunosuppressants.
Anti-TNF antibodies are sometimes effective, but they all come with toxicity, and I think that's one of the key hallmarks of all of our therapies. A safe, physiologic, immune regulator that basically can improve quality of life, that's something that we think we have here with efzofitimod. Having new therapies that can disease modify and reduce that toxicity, we think efzofitimod is positioned as a first-line steroid-sparing agent. Why do we think that? Well, in our last trial, phase 1, 1b/ 2a trial, we attempted to look at trends in steroid sparing, lung function, and symptom control. When we started this trial, we were hoping to see maybe one or two of these families of endpoints move in the right direction. What turned out to happen is we were able to show some real steroid-sparing benefit.
We also showed lung function improvement that was really quite surprising, almost 3% on FVC in a very short study. But the symptom control is something that I think, I really liked, liked what I saw here. Fatigue, shortness of breath, and cough all improved dramatically, well beyond the minimally clinically important difference in all of these measures. The other thing I'll point out here, dose response. In every variable, every endpoint we look at, we see dose response over, and over, and over again, and I think that's really something that all biotech companies, before they move into phase 3, you better see dose response, and I like to see dose response in subjective and objective endpoints. That's what we saw here, even in a small trial. I also think what's not shown here is inflammatory biomarkers.
We also had a publication there where we showed dose response. So really robust results, probably better than we expected. This compelled us to move into phase 3. This is a phase 3 trial, currently enrolling, about to finish up enrollment. We took forward our two most effective doses, the 3 mg and the 5 mg dose, and we now compared it to placebo in a well-powered trial. So 88 patients per arm will be followed for 48 weeks. We have an aggressive steroid taper that over the first 12 weeks of the trial, we're gonna force people down to zero, and then we're basically watching to see what kind of relapse and what sort of Prednisone is required to control the morbidity of cough and shortness of breath.
Our belief is efzofitimod is gonna do a really good job compared to placebo, and we're powered to then see steroid reduction. Steroid reduction is viewed as a really cogent endpoint here for sarcoidosis. We met with the FDA, also worldwide regulators. We were guided towards steroid burden and looking at a steroid endpoint as primary, but we're also gonna be looking at forced vital capacity and also a PRO instrument, the King's Sarcoidosis Questionnaire lung subscore. Recently, we announced that we've kicked off a compassionate use program. This was really based on blinded review, where experts came to us and said: "Look, we have patients performing really well in your trial. They've been able to get off steroids. They now are finishing your trial.
They don't want to go back on steroids." So we, we were compelled to move forward and said: "Look, we have drug supply. We have positive DSMB. We have two positive DSMB reviews. Let's provide drug." It's not an open label extension, but it's a classic compassionate use. It's a good early sign that things are moving in the right direction for this trial, and as I said, this is a trial that's expected to complete enrollment here, really any week now. I'll jump now to SSC-ILD, a more fibrotic form of interstitial lung disease. It's our next foray, kind of upstreamed, or downstream to go into that one more fibrotic phenotype. Here you have about 60,000 patients in the US. If scleroderma patients get ILD, it's the worst phenotype.
It's really where you start to see a large amount of these patients develop lung fibrosis, and it's the scariest, you know, subphenotype of scleroderma. Unfortunately, the drugs that are available, like mycophenolate or cyclophosphamide, again, come with a lot of toxicity, and no therapy thus far has improved quality of life for these patients. Why do I like this opportunity? Again, neuropilin. We've seen neuropilin highly expressed on the scleroderma plaques of these patients. We have a fast track designation because we ran a model in a scleroderma mouse that showed really nice effects in ameliorating skin and lung fibrosis/inflammation, and I think right now, efzofitimod is positioned as something that could replace first-line MMF. We may even be able to expand into systemic sclerosis if we actually show benefit in this proof of concept trial. So this is a small trial.
Here we're trying out a fixed dose because I'd like to just see what happens with a fixed dose. We may actually see a few more points of efficacy here. A fixed dose will also allow us to do a more robust clin pharm PK/PD analysis, maybe give us some insight on how maybe if we commercialize a drug, should we go to a fixed dose? But 450 and 270 approximate 5 mg/kg and 3 mg/kg . This is an efficacy trial targeting lung function here. More tried and true FVCs is more of the frontline primary endpoint that you use in SSC, but symptom control, some of the skin outputs, this is something that I'm hopeful to give an update here later this year on, when we'll have some readouts.
I'd like to hopefully get some interim data out, at a minimum, some interim data out by the end of the year, on this trial. So I'll sort of wrap up here the value proposition. We really have a, a, obviously, a novel biology platform here that's targeting a, a really interesting, area of biology, synthetases with Neuropilin-2, a binding partner that seems to be upstream. This is not a repurposed or failed approach. It's really a new target. Again, going back to those AI drug discovery companies, they look for new targets and new diseases. We have this. We have an asset that actually we can see the binding, and we have functional effects. That's how we actually move things forward. We're targeting innate immunity at the site of inflammation. This is important.
This is how we avoid some of the systemic toxicities that some of the current therapies have. I think that's a unique benefit to our platform, and again, the efficacy that we've already observed. To go three for three, improve lung function, resolve symptoms while removing steroids. We were really the first therapy to show something like that. At this point, no known safety issues in animals, healthy volunteers, all of the clinical data we have thus far. But I think one of the value proposition for this asset is that these are safer physiologic immune modulators that come from our own evolution. So I think we're unlocking some of that, and it's why we're really excited about efzo's readouts here. I'll end with our preclinical pipeline and some of the new targets we have.
It's a unique drug discovery platform, leveraging some of the understandings, and over time, more and more of these fragments we think are gonna bind important receptors. We don't really follow a narrative here and say, "Hey, we wanna be a lung company or a kidney company." If, for example, we see receptor binding that's relevant to, say, kidney fibrosis, we'll explore that in animal models. If we see robust efficacy there, then we'll think about progressing and moving forward. I think there's a pipeline of candidates here targeting, as I said, inflammation and fibrosis, two areas that we actually know a lot of companies are working on new therapies because there's a dire need to impact the patients and have more disease-modifying treatments. Highly capable research department.
Our biology and some of our technology comes out of the Scripps in San Diego, out of the lab of Paul Schimmel. Paul's a unique scientific entrepreneur that founded Alnylam, Repligen, Alkermes, Cubist. We're hoping to be another successful Paul Schimmel company. So with that, I'll wrap up here with the summary slide. That's our platform I've been talking about. Lead program, as I said, expected enrollment to finish up here. A growing pipeline, very much a pipeline company here that is leveraging new biology. And from a cash position, we feel like we're, we're in a really good position here to get through this next major catalyst. Thanks so much.
Thanks. Thanks, Sanjay. Maybe we'll do a couple questions. I'm wondering for the expanded access program, if you can say more about how many patients have enrolled into the study? And any other anecdotal observations about what you're seeing?
Yeah, it's a question I've been asked a lot today, exactly how many are going in and things of that nature. I don't want to really get into the numbers. What I have said previously is we had, you know. I think I said, you know, more than a dozen investigators, for example, 3, 4 months ago said, "Hey, we need to do something here." I would say that number is growing. At ATS, we just had in San Diego maybe 30 investigators there. They're very grateful that we are seeing the ability to provide compassionate use, but it's gonna be dependent on their own institutions on whether or not they can administratively get things, you know, moving forward. We have drug and drug supply to, as I said, treat many of these patients.
I don't think every patient will want to go into the compassionate use. We're really talking about the people that are resolving and actually being able to get off steroids. I think that's the key point here is we're seeing, frankly, a better signal, if you will, granted it's blinded, than we might have expected, so we wanna be ready to support the patients. I think it would be a little bit much to get into the numbers because then you have to say, "Well, how many of these are placebo?" We don't know. We won't know until we unblind, but I think it's actually a good signal. I would rather have patients wanting to remain in the trial than, you know, looking to finish up and get done.
Got it. And, any more anecdotal stories about just patients being off steroids completely? I guess, are you seeing anything else on some of the symptoms they talked about or even lung function?
Yeah, I mean, I think all of these patients, remember, if to remain on a low or no dose, they have to continue to show FVC benefit, and their cough and shortness of breath have to be maintained well. So their quality of life, I think we can all understand, you remove steroids, your quality of life is gonna get better. I think that's why we saw such dramatic effects in the last trial, so we're hoping to replicate that. But we may even see further steroid reduction in this trial because we're taking folks down to zero. What I can tell you, some of the stories of individuals who have been on steroids for five, six, eight years, they're in our trial now, and they're steroid-free six, seven, nine months. So whatever's in that IV infusion bag is working some magic.
This is something that they're very happy with, and they don't wanna go back on steroids. So we're stepping up to the plate. Ultimately, we hope that once we unblind, you know, these patients are on, you know, one of the two treatment arms.
Could you do some sort of an update from the EAP before the end of the year? Is that a possibility, or would you not want to release?
I think it's something we'd consider, but, you know, I, as soon as I do that, it's gonna be exactly how many, you know, what are the numbers? I think the point here is that we had to step up a little bit earlier than we expected. I'll just point to the fact that that last trial, we had about 30% of the patients, you know, 3 out of 9, in the high-dose group, wean off and stay at zero for the last 8 weeks. I'd say in this current situation, we're tracking, you know, at least to that, if not better, but as patients are finishing the trial, we'll kind of evaluate, and see where we are.
The important thing is we have drug supply, and I think we're in good shape here to, if anybody is responding, to be able to give them therapy. Once we unblind the trial, if the results are positive, we would move into a formal EAP with the regulators, and that's something different. So this is more one, you know, one-off, ad hoc, compassionate use if an investigator wants something here, but if the drug is successful, we would go into something formal to bridge between the time of unblinding and approval.
Got it. And for the Phase 2 study, you said you could do an update from that one by the end of this year. Can you talk more about what you could show in that update?
Yeah, I think we have a couple endpoints we can look at. We can look at some of the skin biopsy data, maybe seen some immunohistopath changes and improvement. That's a big bar. No drug has shown that. I think we have a shot there. The other thing is forced vital capacity improvement. It's a six-month trial, so we may have a subset of patients, if we're not fully enrolled, to report out, perhaps at American College of Rheumatology in November.