All right. Great. Welcome, everyone, to Day 2, Jefferies London Healthcare Conference 2024. My name is Roger Song, one of the senior analysts covering small/mid-cap biotech in the US. It's my pleasure to introduce the next company, aTyr. And then we have a CEO, Sanjay, going to give us a corporate presentation. And then if we have time, we can have a few Q&A. Welcome.
Great. Thanks, Roger. So I'm Sanjay Shukla, CEO of aTyr Pharma. We're based in San Diego, California. So I'm grateful to be all the way over here on the trip for Jefferies. Here are some of our forward-looking statements. Today I'm going to talk to you about primarily our lead candidate and how we are targeting a group of diseases known as interstitial lung disease. Interstitial lung diseases are a group of diseases that you may have heard about primarily through IPF, which is a very fibrotic form of ILD. But these are diseases where there are about 200 known entities. Sometimes we know the causative agents. They're all severely inflamed patients that all progress to become fibrotic. This persistent inflammation really impacts the patient's quality of life. Acutely, there's a number of patients that have to deal with cough, fatigue, shortness of breath. So active acute morbidity.
But unfortunately, all of these conditions progressively become fibrotic. And it's that progressive fibrosis that really is a big problem here. And survival rates in many of these progressively fibrotic phenotypes are, frankly, worse than cancer. So a high degree of unmet need here for better therapies. We've been waiting, frankly, for generations beyond IPF to have better therapies. The current therapies used out there are quite toxic. We're largely reliant on steroids. So we're in the dark ages here in ILD. And certainly, there are no disease-modifying therapies. We believe we have a significant opportunity here with efzofitimod that for the last seven or eight years, we've been maturing from preclinical stage, early translational work, early clinical, and now on the cusp of having a major phase 3 readout. We are the furthest along of any really biotech or pharma out there.
ILDs represent, I think, the next frontier of pulmonary medicine. And we're ahead of, frankly, everyone worldwide. Here's a little bit more about interstitial lung disease. As I mentioned, most of these diseases present with inflammation and fibrosis. And here you see, on a sliding scale, a number of conditions, sarcoidosis being the most inflammatory in IPF, which has two approved therapies that generate about $4 billion-$5 billion in sales in pirfenidone and nintedanib. IPF representing the most fibrotic. You still see a little bit of inflammation in these patients. So over 200 diseases here, very poor quality of life, high degree of morbidity and mortality. We are currently focused through two of our trials, our phase three and phase two trial, in the more inflammatory phenotypes.
But aTyr believes, and we believe here that we can move into some of these other forms of interstitial lung disease, the other connective tissue disease, ILDs, chronic hypersensitivity pneumonitis. You look at other forms of rare ILDs that are bundled together. The etiologic cause may be different, but they all present with consistent inflammation and developing fibrosis here. A lot of upside potential here, but you can see the general market here. Obviously, if we were a big pharma, we'd be running phase twos in all of these indications. But we are prioritized to the more inflammatory side of the spectrum here. Large market opportunity, upwards to maybe $5 billion here, waiting for a better therapy. Efzofitimod is a first-in-class biologic. It targets the innate immunity right at the site of inflammation.
efzofitimod is a fairly potent myeloid cell immunomodulator, doing so in particular for macrophages, downregulating the activated and hyperimmune macrophages that's classically seen in many of these ILDs, but doing so in a much safer manner than steroids, for example. It's addressing a complex immune pathology. These are difficult multinodal diseases. We like efzofitimod because it works through different regulatory mechanisms with that macrophage. It's downregulating inflammation, but it's also positively impacting things like lymphatic regulation. And we've learned this over the last seven, eight years, publishing a lot of our work in a number of top-tier journals. By restoring that immune balance without evidence of suppression, this is what we need in this class of diseases. And frankly, most of the experts view efzofitimod as having steroid-like efficacy without steroid-like toxicity. We had some very promising clinical proof of concept data a few years ago. We published in CHEST.
I'll talk to you a little bit about that, but what I was looking for was, could we reduce steroids? Or maybe would we see signals in lung function? Could we also improve symptoms? As it turned out in that study, all three of those endpoints, subjective, objective endpoints, all moved in a very positive manner. This is what got the pulmonary community really excited about our therapy. Going three for three with these endpoints was really unexpected, and I think this is even why, even recently, at the CHEST conference in Boston, Efzofitimod was highlighted as Best of CHEST, and so the general pulmonary community is now getting quite excited about our therapy. I want to highlight that last thing. No known significant safety issues.
We need to make sure we have shown over the last six or seven years the drug continues to track and is a safe therapy. This is important because we are trying to replace a rather toxic steroid that's used as a frontline agent. Let's talk a little bit more about sarcoidosis now, the most major form of interstitial lung disease, high unmet need. Sarcoidosis is a disease that, although we don't know the cause, it presents with this characteristic clump of immune cells, largely myeloid cells. It's a macrophage that has changed and differentiated into a giant cell, mostly seen in the lungs. But you can see sarcoidosis develop in heart, liver, even in the spinal cord. Very severe, debilitating disease, poor quality of life. But most of the time, the patients are presenting with pulmonary manifestations.
200,000 patients in the U.S., approximately 150 to 200 in Europe, 20,000 in Japan. Age of onset seems to be moving to a younger incidence. Some of that has to do with better diagnosis. We are capturing more sarcoidosis worldwide, more seen in women, and in the U.S., in particular, it's three times more common in the Black population. The presentation, as I said, you look for this granuloma largely seen in the lungs. You want to do a biopsy. If it's a non-caseating granuloma, you can rule out TB, and generally, then you're thinking about sarcoidosis at that point. It's not a difficult diagnosis once you actually have that biopsy. Most of these patients need treatment in the first three years. You'll hear about sarcoidosis. Patients can self-resolve.
Yes, you can have a small proportion of these patients, maybe 20-30% from our recent analysis that we're looking at these self-resolving patients. But 70% of these patients need some sort of day-to-day immunosuppression. And unfortunately, the PIs, really pulmonologists, are really just reaching for steroids for the last 50 years. 20% of these patients are developing fibrosis. So steroids are not blunting that progression. If you look at some of the IPF data, the Panther trial, steroids can maybe even make fibrosis worse. So these patients are in dire need of a better therapy. Mortality is rising. We have some new data that we're hoping to publish here in the next year. You could see about 10% of these patients dying from sarcoidosis. Fibrosis is really the biggest driver of mortality in these patients.
The patient journey, sort of two sides of the coin here. Sarcoidosis itself presents with a lot of, obviously, inflammation in the lungs, leading to fatigue, cough, shortness of breath. This causes a big impact to the quality of life of these patients. Major socioeconomic impacts, debilitating disease. Three weeks ago, there was a five- or six-hour listening session with the FDA where patients are really talking about how poor their quality of life is with sarcoidosis, and a long time ago, when I would see some of these sarcoidosis patients, they don't acutely look morbidly ill. But when you really drill into what the disease is doing to them, it's robbing them of really their quality of life, and again, a quarter, a fifth of these patients are becoming fibrotic.
Corticosteroids, these are used, I would say abused with some of the use of the steroids in these patients, cause a host of chronic issues. Remember, these steroids are being used sometimes for five, 10, 15 years in these patients. So when you talk about these comorbidities, diabetes, hypertension, weight gain, I talk to patients, they're gaining 60, 70 pounds in the first six to eight months of getting steroids. You just can't cope with that sort of cardiometabolic burden. Limited alternatives. Sometimes we're using off-label drugs like methotrexate, even infliximab, which has limited efficacy. So some of the experts, rheumatologists from other areas, recently pointed out to me, they said, "What I really like about Efzofitimod is treating two diseases. It's treating sarcoidosis, but it's also treating steroid toxicity." So a very, very nice risk-benefit here, largely beneficial for the patients to be able to treat these two diseases.
The target population. I've already mentioned 20% of these patients are highly fibrotic. You're looking at about 40%-50% of these patients that are steroid dependent, need steroids every day. Our focus is really that steroid dependent population, which is upwards to three-fourths of the patients worldwide right now are still being used. We're still using steroids to deal with that day-to-day immune pathology. The idea here is, how do you reduce or eliminate steroids? We don't have good alternatives. Once patients become fibrotic, they go on more heavy-handed immunosuppressants. We want to be able to blunt that. And this is why we believe we have a disease-modifying therapy. Large addressable population. We are seeing more evidence through insurance claims and also some analysis that we're working on internally. Hope to publish that also in the next year. It's a bigger problem.
It's a sicker population, and it's a more steroid dependent population than we previously understood. Efzofitimod is really positioned well. When you think about other therapies that either had steroid-sparing benefit or are in the ILD space or even in the rare disease space, you look at some of these recent approvals like Nucala, Tavneos, steroid reduction was part of their drug label. Efzofitimod is really positioned quite well here, and experts believe this would be a frontline therapy. Why would we ever use steroids as a frontline therapy if you can demonstrate that this is effective? The idea here is, let's get this approved and let's really help patients. Based on some of the pricing that we've seen here, we think we could also get a premium price here worldwide. Let's dig into a little bit more about efzofitimod.
So this is a checklist of about five, six years' worth of work at aTyr. This is a compound. This is actually the structure of efzofitimod based on RIP. aTyr is a company that really focuses on fragments of tRNA synthetase. This fragment is a 59 amino acid helix-turn-helix domain. That fragment is in all of our bodies. In healthy individuals, it's probably in some way immunoprotective. aTyr is really built to look at these proteinaceous fragments. And this fragment early on had some really unique properties downregulating activated myeloid cells. This is a fragment that's also enriched in lung tissue. So we're learning about a very new area of biology that we are tapping into. That little guy has been fused to a human IgG. This confers a nice nine-day half-life now for this therapy.
This is an engineered protein biologic that is administered through an IV infusion once a month. How does it work to actually downregulate a macrophage? It selectively binds to a receptor called Neuropilin-2. We discovered this through a screen of five to six thousand known receptors. It got a very selective hit. So many investors, they want new biology, new targets until you give it to them. And then they get nervous about that. But we've become experts around Neuropilin-2. It makes perfect sense to me. If we've got this rather innovative biological platform, it should bind something new. So Neuropilin-2, we've learned, is a really potent regulator of VEGF and also Semaphorin. So it's got some unique properties here to downregulate the immune system, but also perhaps actually help some of the lymphatic resolution that you see a lot of these patients with blunted lymphatics.
That's why you have all that immune cell residence in their lungs. We ran a really large translational campaign five or six years ago. We published at American Thoracic Society. Direct and indirect experimental, whatever form of lung injury, unfortunately for those rodents, we use different kinds of agents. Efzofitimod had a very, very consistent anti-inflammatory signature. So I'm not a big believer in animal models. But when I saw this consistency, five, six, seven different types of models, scleroderma models, sarcoidosis models, bleomycin, which is used for IPF, Efzofitimod time and time again showed the same ability to downregulate those sort of pro-inflammatory and pro-fibrotic cytokines. Neuropilin, we went looking to see if it was expressed in sarcoid granulomas. It was. It lit up on ISH and IHC. We, in fact, made the cover of Science Translational Medicine last year. We can send you that issue.
That's our cell with Neuropilin lit up. So it's a really, I think, a very intriguing receptor that we're learning a lot about. It's also in systemic sclerosis patients. We learned in the skin plaques of these patients. So think about this as a precision immunology approach. Without the systemic risk, we're able to really modulate a local inflammatory hyper-response, if you will, at the organ level. Really exciting new modality that we think we've landed on here based on our platform. We've got exclusivity out till 2039. Proof of concept. This is what we're going to talk about in a minute. Here's a basic hypothesis. No matter what interstitial lung disease you have, there is a mix of pro-inflammatory and fibrotic cells that is unremitting in these patients. And these myeloid cells is what we're targeting here. And that chronic inflammation is leading to progressive fibrosis.
Efzofitimod is binding Neuropilin, which is the inflammatory substrate on the cell surface of these macrophages. So whether you have sarcoidosis or scleroderma-related ILD or pigeon breeder's disease, which is a form of hypersensitivity pneumonitis, vaping-induced lung disease, that's a chemical pneumonitis, you always have this hallmark of inflammation. We can tap into that by basically binding Neuropilin, retune that macrophage. And what happens is you offer acute benefit, less cough, fatigue, shortness of breath, and bend the arc of that progression of fibrosis. This is our basic hypothesis. The data. The data was published, as I said, in CHEST. Dan Culver is our lead PI. He's the Chair of Critical Care and Pulmonary Medicine at Cleveland Clinic. Again, we were looking and hoping to see trends in one of these endpoints. In all of these endpoints, we showed efficacy.
And I think the one thing to pay attention here is the dose response. Over and over again, as you administer more of our therapy, better steroid reduction. Our top two doses, higher up the dose, the better the lung function and efficacy improvement. Same thing here. As you actually administer more of the drug, you get here less fatigue is good, but you also get better shortness of breath scores. And KSQ Lung is right here. King's College has a sarcoidosis quality of life instrument. Dr. Birring across the river said this is the best data he's ever seen with the index that he created about 20 years ago. Dose response is really important here.
I've asked you all to look at biotechs here in phase two and say, "You better have dose response, and you better show it in multiple endpoints before you move into phase three." This is why I think we were highlighted in Best of CHEST even just recently in Boston. Some recent data that we published in ERJ about a month or two ago. Post hoc analysis, that was an underpowered trial, 37 patients. I would say it's actually harder to show trends when you have less M than more M. But in this trial, we pooled the therapeutic doses and compared it to subtherapeutic. There you see the Kaplan-Meier highly significant in time to first relapse. And we also look at those sort of ultra responders where they have a KSQ of three times the MCID. Again, we see a really, really nice stat signal.
This was published in ERJ just recently. Further evidence that the drug here is really producing outstanding benefit in these patients. We had an end of phase 2 meeting to align on endpoints. We actually went in with FVC as a primary. We're guided away from that. A lot of variability in FVC in sarcoidosis patients, unlike IPF, where there's a predictable natural history of decline. We landed on steroid reduction. That's viewed as perhaps the most important and clinically relevant endpoint in these patients, a nice feel and function proxy. But we're also going to look at FVC and KSQ lung as secondary endpoints. We have obviously just finished enrollment in the largest and first ever phase 3 sarcoidosis trial. Here's a little bit about how we set that up. We enrolled patients anywhere between seven to 25 milligrams, stably treated steroid dependent patients.
I was looking for folks who at least had a diagnosis for six months, biopsy proven, and we're following patients for a year. We enrolled them in three arms, 88 per arm, took our top two doses where we saw efficacy in the last trial, compared it to placebo, so now this is a well-powered trial. In fact, it's overpowered. 92% power that either five or three still stat sig compared to placebo. I'm looking for steroid reduction. I'm following these patients. After week 12, there's a period here of four-week steroid taper down to zero over the first 12 weeks, and then we follow patients. It's a very real-world type of trial. If you're on placebo, I expect you to fail the ability to not be maintained on zero milligrams of prednisone. They will taper back up.
In the efzofitimod-treated arms, we have a chance to show low or maybe even no dose of steroids here. The taper protocol is really tight. We learned, we sat down with the regulators. We're using the PGA every two weeks. We're assessing these patients, and at the end of this trial, when we look at these 268 patients, we're going to get an average daily prednisone dose, and that's where we think we can actually show a significant benefit compared to the placebo population. I'll point out here that we actually had patients finishing our trial who have been steroid free sometimes for the first time in a decade, and they're now refusing after leaving the trial to go back on steroids, so we have a little bit of a problem, but a good thing. I'm blinded.
We don't know what they're on, but we have to step up with a compassionate use program rather early. Typically, you do this after you unblind, so even tomorrow, I'm going to be sitting with some PIs in France who want access to the therapy. This is an individual patient access program. It's not an open label extension. We weren't required to do that, but it's really a one-on-one center-to-center where they have to file their own individual IND, and I can give them five milligrams per kilogram of efzofitimod. The other reason I can do that is we've had two positive DSMBs. So in a world where these patients are all placebo patients, we at least know that the drug is safe thus far, so we can administer efzofitimod to these patients. I'll end here quickly with the SSc trial.
This is an expansion opportunity in a more fibrotic indication. SSc is also a really, really bad morbid disease, maybe even a higher amount of mortality. It's the worst phenotype of if you get scleroderma, which is an autoimmune disease typically affecting the skin. Large unmet need worldwide. Mycophenolate is the mainstay, but unfortunately, we don't have good options here. Tocilizumab and nintedanib have been approved based on some FVC less reduction to decline data. But I think SSc is an interesting opportunity because, again, neuropilin is highly upregulated in those skin plaques. So we are conducting a small phase 2 in the U.S. only, 25 patients. I'm looking to get some interim data out in Q2. I'll come back in Q1 to see kind of where we are with enrollment, likely to prioritize the skin readouts in this trial.
But I'll come back to you exactly with what kind of readouts we expect in Q2. Again, this is a proof of concept to expand into a more fibrotic ILD. I don't think it has a lot of read-through with SARC. It's just an opportunity to test the drug in, again, a more fibrotic phenotype. So I'll end here talking about how we are a company that also has a nice pipeline. I talked to you a lot about efzofitimod today, but we have some exciting new opportunities from two other fragments in our IP library that are modulating myofibroblasts in the case of DARS ATYR0101. ATYR0750 is a really nice fibroblast modulator. ATYR0101 is actually going to be highlighted at the Keystone Fibrosis meeting next month. Really exciting data on how we modulate myofibroblasts. Could be a true anti-fibrotic. I know you hear that a lot.
I want to see something that really peels back fibrosis rather than just sort of stops the progression. That's what our research team is working on. Here's our corporate summary. I'll end here with our cash because everybody here wants to know that. We have adequate cash to get through not only our data, but through our BLA filing, almost $90 million in cash when you add up where we had proceeds last quarter and adding in some ATM proceeds as well. We do have a partnership with Kyorin, a Japanese partner. We brought in $20 million of $175 million in milestone payments thus far. Disruptive technology that we are learning more about and been able to advance here in a lead candidate that's a large market opportunity. So with that, I'll give you 90 seconds to ask a question, Roger or two.
Maybe a very quick exciting news that we see data readouts expected next year for the sarcoidosis. Maybe just to remind us, what's the specific co-primary for the steroid sparing? And also clinically, what is considered to be the meaning for the steroid sparing?
Yeah, I'll start with the last point. Think about this as steroids are used every day. And the docs have said even one milligram less adds up over time. It's a cumulative burden of steroids in these patients that think about it that way. Nonetheless, in the last trial, we saw a 20%-25% reduction in a six-month trial. I think we can do a little bit better in this trial. The goal here is about a 30%-35% placebo-adjusted difference. In gross terms, that's three, three and a half milligrams different.
That may not seem like a lot, but if that adds up day after day in these patients, and then removing that steroid burden for these patients is going to benefit some of those other comorbidities. We're 90%, as I said, 92% power to be exact, that three or five can hit stat sig on that amount. That is going to be a very meaningful amount because if we show that, that's also going to be more than a 50% reduction from when they even came into the trial. Because remember, I'm forcing placebo down, and then it's going to rise over the course of the trial. So we're going to be able to see that delta. Most experts view this as it's definitely a first-line therapy. I think it goes one or two ways.
is either going to show and demonstrate efficacy, or frankly, the sarcoidosis population is going to have to change their treatment guidelines because we will have effectively shown you can be managed on really no steroids. So that would be new news for them for the last 50 years. Thank you. Thank you.