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spk03: Good afternoon, ladies and gentlemen, and welcome to the A Tire Pharma third quarter 2022 conference call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session, and instructions will be given at that time. As a reminder, this conference is being recorded for replay purposes. It is now my pleasure to hand the conference call over to Ashley Dunston, A Tire's Director of Investor Relations and Corporate Communications. Ms. Dunston, you may begin.
spk00: Thank you, and good afternoon, everyone. Thank you for joining us today to discuss ATAR's third quarter 2022 operating results and corporate update. We are joined today by Dr. Sanjay Shukla, our president and CEO, Ms. Jill Broadfoot, our CFO, and Dr. Leslie Nangle, our VP of research. On the call, Sanjay will provide an update on our corporate strategy, including our clinical program for Epsofitimod and research and discovery programs. Jill will review the financial results and our current financial position before handing it back to Sanjay to open up the call for any questions. Before we begin, I would like to remind everyone that except for statements of historical facts, the statements made by management and responses to questions on this conference call are forward-looking statements under the safe harbor provision of the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. Please see the forward-looking statement disclaimer in the company's press release issued this afternoon, as well as the risk factors in the company's SEC filings, including in our most recent annual report on Form 10-K, subsequently filed quarterly reports on Form 10-Q, and in our other SEC filings. Undue reliance should not be placed on forward-looking statements which speak only as of the date they are made, as facts and circumstances underlying these forward-looking statements may change. Except as required by law, ATAR Pharma disclaims any obligations to update these forward-looking statements to reflect future information, events, or circumstances. I will now turn the call over to Sanjay.
spk04: Thank you, Ashley. Good afternoon, everyone, and thank you for joining us for our third quarter 2022 results conference call. The third quarter saw the initiation of EPSO-FIT, a global pivotal phase three study of our lead therapeutic candidate, Epsofitamod, in patients with pulmonary sarcoidosis the most prevalent form of interstitial lung disease, or ILD. We dosed the first patient in this study in September, meeting aggressive timelines and guidance. Amid current market conditions, we intend to focus our resources on prioritizing EpsoFit, which is our highest value program to ensure a timely and successful completion of this study. As we begin, I will summarize a few additional highlights since we last spoke in August. We announced the publication of results from the Phase 1b-2a study of efsofitamide in patients with pulmonary sarcoidosis in the peer-reviewed medical journal CHEST. We presented a poster at the European Respiratory Society, or ERS, International Congress on findings for an antibody for immunohistochemical detection of Neuropilin 2, or NRP2, in patient tissue samples. NRP2 is efsofitamide's binding partner. And these findings suggest that this antibody may provide an extremely useful clinical tool, potentially aiding in patient selection or stratification. We received FDA Fast-Track designation for esophidamide for the treatment of systemic sclerosis, SSC, or scleroderma-associated ILD. We announced a research collaboration with Dual Systems Biotech AG, a company specializing in custom proteinomics to identify and validate 10 new target receptors for tRNA synthetases from our intellectual property, or IP, by 2025. This collaboration is a way to potentially accelerate drug discovery efforts and identify new drugs from our platform. And finally, we received a notice of allowance from the U.S. Patent and Trademark Office for antineuropillin-2 monoclonal antibodies which is the first to be granted to our IP estate for this program. We've experienced another quarter of crisp operational execution, both internally and in cooperation with our partners and collaborators, and we anticipate a strong finish to the year. Now let's focus on some more specific updates around our clinical program for Epsom Phenomot. As a reminder, Epsom Phenomot is a first-in-class immunomodulator for fibrotic lung disease. Epsilfitamide is a novel FC fusion protein based on the naturally occurring splice variant of the lung-enriched tRNA synthetase HARs fragment that downregulates aberrant immune responses in inflammatory disease states. Epsilfitamide has been shown preclinically to downregulate inflammatory cytokine and chemokine signaling and reduce inflammation and fibrosis. The NRP2 receptor is upregulated on key immune cells during active inflammation and is enriched in inflamed lung tissue. Efsofitamide binds selectively to NRP2 and therefore has the potential to normalize the immune system, serving to resolve inflammation and prevent progressive fibrosis, thereby stabilizing lung function and alleviating morbidity and mortality. We're developing efsofitamide as a potential treatment for patients with ILD, a group of rare immune-mediated fibrotic lung disorders. Our initial ILD indication is pulmonary sarcoidosis. Sarcoidosis is the most prevalent ILD and is characterized by the formation of granulomas, which can occur in any organ, but predominantly affects the lungs. If left untreated, this can lead to irreversible scarring or fibrosis, which greatly increases the risk of death. We estimate that there are close to 200,000 patients with pulmonary sarcoidosis in the US, and around 150,000 in the major European markets, with another 20,000 in Japan. Up to 75% of patients require treatment for their disease, and approximately half of these will have progressive disease despite treatment. Around one in five of all patients will go on to develop lung fibrosis. First-line treatment is typically corticosteroids, which may effectively control symptoms, but are associated with severe debilitating side effects, particularly with chronic treatment. In patients unresponsive to steroid treatment, cytotoxic immunosuppressants or biologic immunomodulators may be used, but are also known to cause serious side effects. The use of all of these therapies is empiric and not supported by current clinical evidence standards. We believe the addressable market for efsofitamide in the three geographies mentioned is around 200,000 patients. Even with conservative assumptions, this represents a significant market opportunity in sarcoidosis alone. Efsofitamide has received orphan drug designation and fast track designation from the FDA for sarcoidosis. We see upside potential for efsofitamide in other forms of ILD. This includes indications such as scleroderma-related ILD, where we have also garnered FDA orphan drug and fast-track designation. Also other connective tissue disease-related ILDs, and chronic hypersensitivity pneumonitis, among others. These diseases share overlapping immune pathology with sarcoidosis, and others having limited treatment options, and efsofitamod has demonstrated efficacy in animal models of these diseases. Taken collectively, this represents a multi-billion dollar market opportunity for efsofitamod in ILD, and ATIRES poises a front runner in this expansive opportunity. Now let's recap the data we have generated for efsofitamod and some updates on the current efsofit study. In September 2021, we reported clinical proof of concept for efsofitamide based on positive results from a Phase 1b-2a study in pulmonary sarcoidosis. The study, which included a forced steroid taper, demonstrated safety, tolerability, and consistent dose response for efsofitamide on key efficacy endpoints and improvements compared to placebo, including measures of steroid reduction, lung function, sarcoidosis symptom measures, and inflammatory biomarkers. Just this past week, the full results from this study were published online in the peer-reviewed medical journal, Chest, with Dr. Daniel Culver, Chief of Pulmonary Medicine at the Cleveland Clinic, serving as lead author. This marks the first peer-reviewed publication of clinical data for efsofitamide, or for that matter, any tRNA-sensitase-derived therapy, in a major medical journal. These data indicate that efsofitamide is providing substantial benefit to patients, improving lung function and symptoms of cough, shortness of breath, and fatigue, all while reducing their toxic steroid burden. According to medical experts, this is the first randomized placebo-controlled trial of any therapy for pulmonary sarcoidosis that demonstrates effects on physiologic and quality of life measures concurrent with steroid reduction. With the full data set now available for review, we expect this publication will generate additional education, awareness, and support for efsofitamod among the specialist and generalist provider community, particularly as we are currently enrolling for efsofit. Efsofit is a global pivotal phase three randomized double-blind placebo-controlled study to evaluate the efficacy and safety of efsofitamod in patients with pulmonary sarcoidosis. It is a 52-week study consisting of three parallel cohorts randomized equally to either three milligrams per kilogram or five milligrams per kilogram of efsofitamide or placebo, dosed intravenously once a month for a total of 12 doses. The study intends to enroll 264 patients with pulmonary sarcoidosis at multiple centers in the US, Europe, and Japan. The trial design incorporates a forced steroid taper and the primary endpoint of the study is steroid reduction. Secondary endpoints include measures of lung function and sarcoidosis symptoms. We've dosed the first patient in the study and have several sites in the U.S. open for enrollment. We expect additional sites to open in the U.S. later this year. And we'll remind you that this is a global study. We held a productive meeting with European investigators during ERS in September, and we now have rapidly achieved regulatory approval to proceed with the study in a number of countries, including the UK, Netherlands, France, and Spain. We anticipate sites opening for enrollment in those countries in the coming months and early 2023. Finally, our partner, Cure and Pharmaceutical, has also completed submission of the Clinical Trial Notification, or CTN, in Japan, and we could see a center there open for enrollment by the end of the year. We're highly encouraged by the rapid pace of this progress, as it permits us to initiate the study in those regions and signifies alignment with these regulators on the trial design, including the steroid-sparing primary endpoint. I want to give kudos to our regulatory group, led by Dr. Bob Ashworth, for skillfully navigating towards these regulatory approvals. Epsilfit is expected to be the largest interventional study for patients with sarcoidosis to date. It is also the largest study that Atire has undertaken in the history of the company. We're laser focused on assuring that this study receives the resources it requires, and we intend to focus our resources on FSOFIT to ensure its completion. Shifting to our preclinical and discovery programs, let's discuss some of the progress with our pipeline. This includes ATYR 2810, and today we'd like to provide a strategic update regarding this program, which we have advanced to be phase one ready. Due to current market conditions and the need for prioritization of capital, most importantly focusing our resources on the FSOFIT study, we made the strategic decision not to use our internal resources to initiate a phase one study of 2810 this year. We intend to look at other potential non-dilutive avenues, including academic collaborations or other funding sources to bring this program forward. Multiple academic centers are particularly interested in advancing 2810 in rare aggressive cancers where many patients remain unresponsive to currently available treatments, such as neuroendocrine prostate and pancreatic neuroendocrine tumors. Recent published literature regarding the role of NRP2 in these types of cancers and interest from these centers have encouraged us to consider interrogating an anti-NRP2 agent, such as 2810, in these indications. This includes an exciting publication recently from one of our key collaborators, Dr. Kastubh Dada, and his colleagues from the University of Nebraska Medical Center, indicating the role of NRP2 in promoting metastasis and conferring therapeutic resistance in neuroendocrine-like prostate cancer, which outlines the potential for the therapy in this aggressive tumor type. As a reminder, 2810 is phase one ready, having completed IND enabling activities, including GMP manufacturing and GLP tox studies. And we have been granted allowance from the US Patent and Trademark Office for the patent for anti-NRP2 antibodies, which covers us for 2810. I'll close with reiterating how excited we are with our tRNA Synthetase platform and what it's yielded thus far as we get closer to our mission of translating our tRNA synthetase biology into new therapeutics for fibrosis, inflammation, and cancer. We've advanced efsofitamide, which is derived from a fragment of histidyl tRNA synthetase, or HARs, into now a Phase III study. Meanwhile, we've identified and validated the receptor target for a fragment of another tRNA synthetase, allonyl tRNA synthetase, or ARs, and we expect to reveal the receptor of yet a third fragment This one from aspartyl tRNA synthetase, or DARS, in the near future. I'll now turn it over to our Chief Financial Officer, Jill Broadfoot, to review our financial results.
spk06: Thank you, Sanjay. We ended the third quarter 2022 with $79.6 million in cash, restricted cash, cash equivalents, and investments. Research and development expenses were $9.9 million for the third quarter 2022, which consisted of product development and manufacturing costs for the ESSO FITimod and 2810 programs, as well as startup costs for the phase three ESSO FIT study. General and administrative expenses were 3.6 million for the third quarter 2022. Common shares outstanding were approximately 29 million and fully diluted shares were 34 million as of September 30th, 2022. From a balance sheet perspective, we are comfortable with our current cash position, which we believe enables us to carry out the most meaningful value driving catalyst for the company. While running a large global phase three study in a rare disease such as EFSA-Fit is capital intensive, we do share a portion of the cost with our partner, Curent, who is responsible for the cost of all operations and patient costs in Japan, and purchases drug supply from us with a small markup. And as a reminder, under our agreement with CURIN, we are eligible to receive up to an additional $165 million in milestone payments, of which the majority are development and regulatory related. As we stated on the call today, we have made some important decisions around our pipeline that will allow us to better manage our cash. At this point in time, we have a financial and strategic plan for the company to fund operations to the data readout for EPSO-FIT. This plan contemplates our current cash balance, the potential for milestones from Kieran, and potential proceeds from the use of our existing equity vehicles. Now, I'd like to turn the call back over to Sanjay before we open it up to Q&A.
spk04: Thank you, Jill. Highly dedicated team with a track record of exceptional execution, and we continue to make outstanding progress with efficient use of capital. We understand that the markets have been challenging as of late, and certainly know that they do not in any way adequately reflect the intrinsic value of the company, including the data and progress we've generated for EFSO-FIDAMOD, considering its stage of development as a late phase asset and its potential to address a multi-billion dollar market. The prioritization we've discussed today provides us with the ability to ensure adequate resources to successfully advance the highest value driving catalyst for the company. I'll close with a comment recently from one of our top shareholders. Utomi HR is a platform company that's generating transformative research and clinical opportunities from our tRNA synthetase biology estate. This is a company that I think is poised right now to be a leader in an area of interstitial lung disease where, as I mentioned, we are the front runner. So we appreciate your interest, continued support. At this time, Jill and I will be happy to take your questions. Thank you.
spk03: Ladies and gentlemen, as a reminder, if you would like to ask a question, please press star 1-1 on your touchtone telephone. Again, for any questions, please press star 1-1. And our first question will come from Gregory Renza of RBC. Your line's open.
spk11: Hi, this is Yingalong for Greg. Congrats on the progress, and thanks for taking our questions. Maybe first on the Phase III trial, As some companies in the space are seeing some clinical trial conduct slow down, could you just provide some color on what you're seeing around site activation and enrollment cadence, as well as your confidence level in the guided timeline of the phase three trial? Thank you.
spk04: Sure. Appreciate the question. So it's quite early to necessarily get into projections and the trajectory. But what I can tell you is the excitement from the PIs worldwide They've been waiting 20 years, sometimes longer, for a therapy like this to get to this stage. So certainly from that perspective, I think you can look at the pace of our regulatory approvals and even the fact that we were able to get a patient enrolled basically about three months from getting the green light from the FDA. This speaks to the rapid sort of interest and uptake to enter our trial. I also think the data we produced is checking the box in all the areas that these experts have been waiting for probably going back really 50 years. A drug that can reduce, improve symptoms, improve lung function, and all doing that while reducing steroids. This has never been seen before. So what do I anticipate? I anticipate a fast start. I'm glad we've started fast with the first patient. I also have seen the quick pace of regulatory approvals Uh, I will be at three sites, uh, next week. Um, so I think, I think it's something it's off to a fast start here. We're going to have to watch to see as this is the largest sarcoidosis trial ever, how we really progress here. And I think I'll have a better estimate of that. You know, once we get a good 30, 40 centers up and let's allow them to enroll, let's allow them to enroll for a few months. I think our publication is also really, really important. This is the first. major sarcoidosis publication from a clinical trial, I'd say going back to the infliximab data in the 2000s. So this is a field that's hungry to actually interrogate afsofitamide. They like the initial data. And I can tell you that patients certainly are responding well in that we are really trying to address their steroid burden. So I will get back to you to see how we're doing here, but early signs here are very, very encouraging.
spk11: That's great. Thanks for the color. And then maybe secondly, could you talk a little about your latest development strategy in scleroderma ILD, and what do you see as the key differentiation of the mechanism of action that could drive clinical potential in this indication? Thank you.
spk04: Great. Yeah, so scleroderma, I think it's something that, in honesty, is an adjacent condition. We are seeing a number of pulmonologists and rheumatologists after seeing our EPSO data in sarcoidosis become very interested. Conversely, we've also received, maybe rather surprisingly, some nice designations early from the FDA. Scleroderma ILD represents probably the worst form of scleroderma. It's where some of the morbidity and mortality is just really quite dramatic, and these patients don't have treatment options. So while we have a good kind of feel from patients and providers and regulators, we have to be careful about thinking about how do we keep our eyes focused on sarcoidosis first. So at this point, I think we are really keeping the eyes on sarcoidosis, but it is really encouraging that based on really our data, and even going back to our preclinical data, we have animal efficacy showing efsofitamide can impact sclerodermatous plaques and lung inflammation in mice. So the translation is there. So the story is there, but right now, you know, we are staying focused on sarcoidosis. Last thing I'll say is we are looking more closely at neuropillin expression in scleroderma patients. There's anecdotal evidence that neuropillin is quite upregulated in some of those sclerodermatous plaques, but I think we have some time to look more closely at that, but certainly, That is an opportunity that, you know, if we had abundant resources and infinite resources, certainly is another large market opportunity sitting there for us.
spk11: That's great. Thank you very much.
spk02: One moment. And our next question will come from Joe Pensionis of H.C.
spk03: Wainwright. Your line is open.
spk05: Hey, everybody. Good afternoon. Thanks for taking the question. So first, just a little more on EFSO-FIT. Obviously, it's early and, you know, just wanted to see – I'm not implying these are any rate-limiting steps. We wanted to get your sort of early views on how, you know, you view the ease of screening patients and any particular geographies, even in just the U.S., that you might see outperform even before the European sites come on board.
spk04: Yeah. Hi, Jill. Great question. You know, we've made some tweaks to our protocol based on our last study that I think are going to address some of your points here. Number one, moving into Europe and Japan, there tends to be slightly less steroid administered in those patients. That could have to do with the physiology of those patients, but also There's a larger cohort of African Americans, of black patients here in the U.S., which typically those patients have a more severe disease and may require more steroids. With that in mind, we've lowered the threshold in this current protocol to allow entry at 7.5 milligrams as opposed to 10. We think this is going to help us enroll and better fits the sort of treatment paradigms of Japan and Europe where they tend to use a little bit less. I'll start there and say that's gonna help us. I'll also say that compared to the last study where PET scans were used as an inclusion criteria and have now fallen out of favor five years later, we're now using HRCT, which is gonna be a little bit easier to administer and read out, more commonly viewed as a better instrument to detect fibrotic patients or not. We wanna exclude those patients that are highly fibrotic and bring those patients in that are inflamed. HRCT is, I would say, a more validated instrument than PET scans. This is going to help us. So I think those are two early sort of tweaks that we've made in this protocol to allow for easier entry into our trial. And then the last thing I'll say is our data from the last study. The fact that we showed steroid reduction and we are the first therapy to really ever show the ability to improve symptoms and lung function while reducing steroids, this is really important to patients. So now that there's that experience from that last trial, patients are very, very interested in our therapy because we're not just showing nominal improvement in one or two endpoints. It's really all the endpoints and the one they care most about is, can I get off steroids or can this help me reduce my steroid burden? That's gonna be a real attractive asset for us as we think about enrolling worldwide.
spk05: That's helpful, thanks. And then when you just look at the, especially in this current environment, it's glad to see you guys being thoughtful about your resources. So how would you describe, you know, how much you're putting your background overall NRP to work, not on the back burner, but just sort of, you know, pausing a little bit from a cash spend standpoint?
spk04: Yeah, I mean, I think 2810 is something that, frankly, when I – When I think about its opportunity, we've landed on these indications that this is the best fit for 2810. So moving forward, these really rare third-line cancers, especially these neural endocrine phenotypes, is really the indication where it makes most sense for 2810 to advance. Now, when you think about these rare cancers, they can be slow to enroll. certain academic centers are specialists in these sort of rarer types of cancers. So it makes sense for us to partner with those academic experts. And because these are rarer cancers, we actually have more access to non-dilutive ways of funding because there is money out there for these sort of rarer cancers. So it's an intersection of our data, number one, pointing us in that direction, that these are, cancers that we should actually target with 2810 and conversely it allows us to also work with academics which at the end of the day serves us well under these current conditions so it's an intersection of really I think our data the opportunity with these experts in these rare cancers and then the fact that you know given current conditions we're grateful that we're probably going to have avenues at these centers so I think it's it's It makes sense for us, you know, based on a lot of different factors, to progress the program side by side with these centers. And conversely, you know, of course, it does help us focus on esophitamide as well. Great. Thanks for the call, Sanjay.
spk02: One moment. And our next question will come from Hartaj Singh of Oppenheimer.
spk03: Your line's open.
spk10: Great. Thanks, Sanjay and team, for all the updates. Sanjay, we just got a different kind of question. I think it might be a little early for this, but just our first question is, you know, we kind of, we did a survey of high prescribing, you know, physicians, pulmonary sarcoidosis, and we were, I mean, we shouldn't have been, but we were shocked at, you know, just how much they use steroids and how much they want, not want to use steroids, right, 90 plus percent. 100% use steroids and 90 plus percent want their patients to get off steroids or reduce steroids. So there's this burden, right? And you've talked about all the patient numbers that go into, you know, the potential to have some fit them on. What about on the value side? I mean, have you done preliminary work as to what could be comps for an etzofitamide if the data was to recapitulate itself in phase three and it was to get approved? What sort of comps are we thinking about assuming the drug gets approved? I just got a follow-up question.
spk04: Thank you. We have spent some time this last quarter looking a little bit more closely at that. We've done our own internal analysis, actually with an external firm that has interviewed experts and done some early payer work that you might be hinting to. Our estimates were a little light, and I think we're all learning that, first of all, more patients are on steroids than we expect. It's a bigger issue, and patients want to get off steroids. Conversely, from a pricing standpoint, most experts have come back to us and say, The pricing of this drug, if we start to see these kinds of steroid reduction effects while also improving lung function, improving quality of life, it could be upwards to, you know, kind of what Humira is getting. That's probably on the high end, but you look at those drugs like Ofev and Esbriet, these are drugs that generate billions of dollars of revenue for Roche and BI. Our drug would, I think, fall into a similar pricing bucket. Look, those drugs just reduce the lung function decline. Our drug is preserving and improving lung function. It's improving symptoms, which those drugs are not doing. And it's doing so while removing steroids. So I think we're very confident now that from a pricing standpoint, we would approach some of those similar IPF drugs which is why a lot of the modeling estimates, not only internally, but also with some of you guys, have been actually changing. So I do feel better, again, after our data, that it's generating a bit more confidence that the potential pricing of the drug could be much higher than we initially expected.
spk10: Yeah, no, that's great, Sanjay. And then the other question I just have is, you know, I was at ERS, and there was a lot of data presented by larger companies, but I was a little surprised, not in a bad way, but just how much buzz there was around your presentations, even though I think you had far greater presentations at ATS. You know, what are you thinking in terms of strategic sort of view? You know, there seemed to be a buzz as ATAR being, you know, kind of a small-cap company with a product that could, you know, play really well to a multinational company, you know, that wants to take this product out into a you know, many countries, many geographies all over the world. What are you thinking, you know, if I can turn in that regard? Thanks for all the questions.
spk04: Yeah, I think it's a factor of a couple things. First, the data needs to just get absorbed. I mean, we put it out at ATS. It takes a minute to kind of get worldwide. I think the publication is really going to help us, and we've already seen, even in the couple days it's been up, we have, you know, new interest from other parts of the world. You know, pulmonologists are busy. They're managing a lot of conditions outside of the specialist. This is why I said the generalists will start to pick up on this. The other thing that's happening is we're seeing a contraction in the ILD space with the number of companies kind of moving out of the space. They're finding their therapies are not working as well in preclinical and early phase testing. You see larger companies Moving out of the space. So this is why we feel like a tire is getting that buzz that you picked up on at Barcelona That our therapy is doing things previously not seen in sarcoidosis with other therapies And we are the furthest along Combine that with some competition, you know kind of going away here. We think that can help us certainly enroll and again, we could be we could come out of this sort of at the top of the wave here and in a few years as what I think is a leading ILD company. Last thing I'll say about ERS, and I think you picked up on this, interstitial lung disease is where asthma and COPD was about 15 years ago. At the ERS conferences around 2000, 2005, better new steroid sparing therapies were needed and they came out. You know, Lama Lavas, some of the anti-muscarinics, things like that for asthma and COPD. Now the shift for respiratory experts is how do we get better drugs in ILD? You've seen United do some things with pulmonary hypertension ILD, but right now we are kind of the leader right now for, we certainly are for sarcoidosis, but our therapy is something that could be really useful in a number of those other conditions. This is why we think it's a multi-billion dollar opportunity, and we're hopeful to get noticed you know, more and more in the sort of coming years as we, you know, get this data out.
spk10: Great. Thank you, Sanjay. Thanks for the questions and the updates.
spk02: One moment. Our next question will come from Edward Tintoff of Piper Sandler.
spk03: The line's open.
spk01: Great. Thank you very much. We appreciate the update. You know, really applaud the execution, especially on the phase three. Understand the focus. And one of the things I've always appreciated, Sanjay, about ATAR is your close relationships with the academic labs. I think it's a really smart way to be advancing 2010. My question kind of has to do with sort of the broader utility of the platform. And are there opportunities to do partnerships um with biotechs or big farmers around some of these other areas um or is the goal really to do a lot of the early work yourselves and then do more kinds of product type deals in the future so appreciate uh you taking the question thanks yeah i i do think uh thank you ted for the question i i do think the epsilon data has clearly validated our platform and we're seeing that
spk04: through interest with, you know, really across the spectrum. Academics, other companies, you know, really digging in. Our dual systems collaboration is really about taking the lid off of our synthetase estate. We think we can do it faster, better, and frankly cheaper now with this collaboration. As we crank out new targets, and thus far, you know, this summer we had a new target with fibroblast growth factor. coming out of one of our synthetase targets, I think we're going to have optionality now. We're going to have the ability to say, hey, do we want to take some of these forward? We're not going to be able to take all 10 forward ourselves. Let's just be honest. Not all 10, you know, are going to be necessarily winners. You know, that's the other thing. We like to be honest here at ATAR. But I think what's going to happen here is we're going to have an opportunity to look at these and, frankly, you know, engage in potential partnerships. That's another thing I'm loathe to talk too much about. But I do think that now we're at a position where we've generated more interest than ever in ATAR. ATAR was very much a show-me-something story. We've done that. Now we have a process. Now we even have a partnership with a group out of Zurich that can, I think, yield a number of pipeline opportunities. And I would say some of these will keep kind of under our umbrella. Others, we're going to have opportunities to partner. And, you know, I think that's something to expect here and prepare for in the years to come.
spk01: Great. Thanks, guys.
spk02: One moment.
spk03: And our next question will come from Yale Jin of Laidlaw & Company. Your line's open.
spk07: Good afternoon, and thanks for taking the questions. Due to your resources sort of focusing, do you still will conduct a preclinical study for some new targets or whether that approach, that department would also shrink their budget as well?
spk04: Thanks, Yale. No, I think this is really related to 2810 and the clinical program. As you can imagine, you're moving into clinical studies. That's where it really starts to get expensive. We have a mechanism and now a process that certainly from a discovery and preclinical standpoint, there's no slowing down. In fact, you'll see acceleration in outputs. But again, we are very, very capital efficient with some of those those efforts. It's really moving into the clinic, where right now, FSOFIT being the largest and a late phase program, we just thought it was smarter for us to really, really reiterate and focus resources there. But from a pipeline and discovery standpoint, no. These are all opportunities that we're going to still pursue. I think for 2810, we simply are taking a different strategy with that, which I think will do two things. Number one, it will put it in a home, and perhaps with some academic groups that, frankly, will be able to move it forward at virtually little to no cost to us, so we can still advance the therapy that way. But I think the game plan right now is to generate, certainly, more pipeline opportunities. And then we can decide. We can see, I've always said, let's look at the data, and then let's figure out you know, how we want to move this forward. It's an approach we've always taken. We want to be data-driven. And I think, you know, from a pipeline perspective, no, there is no contraction there.
spk07: Okay, great. That's very helpful. As we talk about 2810, do you have some estimate in terms of the dollar could be saved, you know, without the clinical work over the next few years? Do you have some sort of rough estimate on that?
spk04: So I didn't, oh, how many dollars could be saved?
spk07: Right, yeah.
spk04: I don't think we have, I'll let Jill also answer here. You know, I wouldn't necessarily look at hard estimates here because one of the things is these are rarer tumor types, which I think one thing we just have to call out here, it can take much longer to enroll in these rarer phenotypes. So this is another part of our strategy that who is best prepared, who has these sorts of patients and access to them. So I think from a time perspective, that's where we actually save quite a bit. From just a rough dollar perspective, Jill, do you want to add?
spk06: Yeah, from a dollar perspective, it's not as significant, and obviously it depends upon the trial design, which You know, we've looked at a couple different trial designs depending upon how we wanted to approach this. But you could say on average from clinical costs, maybe, you know, around 10 million or so. But it's really what Sanjay was talking about is how long that takes. So that $10 million doesn't really include all of that overhead and distraction to the company as well that could occur over that you know, two-year, two-plus-year period?
spk04: That's right, yeah. Early-phase clinical oncology trials can sometimes take, there's a number of hurdles to move through. It's also a rare phenotype, but roughly speaking, you know, I think $10 million for a program like that is a comp that most companies would look at there. The distraction part is, I wouldn't necessarily say that We're able to do a lot of things here at ATAR, but I think this is the best thing for us. And frankly, putting it in the hands of folks who maybe have these patients with neuroendocrine phenotypes, they're quite excited to move the asset forward there. And it also comes with the benefit that we may be able to tap into funding because we are focusing on these more rare and ultra-aggressive tumor types.
spk07: Okay, great. And maybe the last question here is, is that in terms of the clinical study in Japan, are you guys going to review in terms of probably the size and then maybe any other colors of that part of the trial? And thanks.
spk04: I would say, roughly speaking, A region like Japan, regulators typically like to see, at least from a global trial, at least about 10% of the patients come from that region. An indication, a rare disease like this, partners are piggybacking off of our global data. So it's obviously difficult to enroll and power a trial in a specific region like Japan, but I would anticipate right now, early on, you know, somewhere around 10% of our patients will need to come from Japan, somewhere in that number, around that range.
spk07: Okay, great. Thanks. Appreciate that. And congrats on some good decisions you've made so far.
spk03: Thank you.
spk02: One moment. Our next question will be from Sean Kim of Jones Trading. The line's open.
spk09: Yeah, hi. Thank you for taking my questions. And I apologize if I'm repeating questions that have been asked previously. But, you know, for the Phase III episode speed trial, can you kind of remind me what the statistical plan has been, including the statistical powering also, you know, how much of a separation from placebo has been baked into that kind of calculation?
spk04: Sure, sure, happy to do that. So our trial is powered, we have 264 patients, three dose arms. There's a five milligram, a three milligram, and a placebo arm, and each arm is 88 patients. We power this trial over 90%, 92% to be exact, for either the three milligram or the five milligram dose of showing statistical superiority So we have essentially two shots on goal with either of these two at a much higher clip. Typically, you want to power these studies at at least 80%. We've actually done them both with both of these doses at over 90%. In layman's terms, what are we trying to show in steroid reduction? An absolute reduction of somewhere between 2.5 to 3 milligrams difference is, in our eyes, meaningful. In the eyes of experts, for example, if you have a patient coming in at 10 milligrams and getting on Efso, gets them down to seven and a half, that's meaningful benefit. It may not seem like a lot for us, but every day, removing two to three milligrams of prednisone, this adds up. Removing that decreases the overall cumulative burden, and over the course of six, nine, 12 months, this is gonna help you with cardiovascular, metabolic, neural effects of what steroids do. So hope that provides a little bit of color there. Very, very well powered. I'm a little bit very particular about statistics, having a background in that. So I think that's something that we wanted to overpower, if you will, and we have two shots on goal to essentially show about that two and a half and three milligram difference.
spk09: Okay, that's very helpful. Thank you. And I guess just one follow-up question on that is, you know, you have three arms, you know, with 3mg and 5mg placebo. Just curious, you know, what the rationale behind going after, you know, two different doses versus just going after, you know, higher dose, you know, that might provide, you know, improved efficacy and, you know, maybe, you know, increase the stitch tolerance.
spk04: Yeah, so this was actually an initial approach and dialogue we had at the end of phase two meeting, because our last data set showed that five was rather outstanding. But even the agency pointed out that our effects in three milligram are actually quite good. We showed improvement in symptoms, we showed lung function improvement, and we showed a reduction of about 49% in the three milligram arm. The view was it would be good to also interrogate that dose because it provides a backup to if five milligram, for example, we see any emerging toxicity. Now we haven't seen any toxicity with any of our high doses, any of our doses from the last trial, but let's also understand that that data set had less than 10 patients in arm. Now we're getting up to close to 90 patients in arm. So there is a possibility of course that safety at any time might emerge as you start to look at more and more patients. By having the three milligram dose, it also de-risks any potential safety, emerging safety signal that might exist. And this has occurred, I've had this occur in another program at previous company I was at where we, the backup dose, it was good that we actually had it in there because there were some tolerability issues and it allowed the lower dose to get approved. So this was something actually at the behest of the agency. I actually thought it was a good idea. It's the reason why our numbers have bumped up. Previously, I was telling investors with one dose and one placebo, the trial could probably be adequately powered at somewhere around 220, 230 patients. When you add this additional arm and you still want to be over 90%, this is how we get closer to 264. So I think it's a combination of de-risking for a potential effect that may or may not emerge. We don't think it will. And it gives us another shot on goal.
spk09: Okay, thank you. And, you know, about the timing and the sequence of, you know, different events. So, you know, from clinicaltrials.gov information, it looks like the trial is scheduled or expected complete in late 24, early 25. So is that the kind of ballpark, you know, timing that, you know, that I should be kind of expecting the study to complete? And also related to that is, you know, for the other, you know, programs, you know, scleroderma and CHD, you know, would you be expecting, like, to complete the episode trial and see the outcome before kind of embarking on phase two for the other programs or would the two programs be sequenced somewhere in between as far as timeline goes?
spk04: But at this point, I'll answer the second part first. At this point, we're focused on this one indication. So while we have some encouraging signals with additional ILD indications, right now we're focused on this trial and focusing on getting it done. When you look at clinchrials.gov, We have to put down something. This is our best early estimate, but as we get into enrollment, I'll be able to look at that and say, does that timing still make sense? Should it be pulled in? Should it go out further? This will be predicated on how we do here really over the next six months, but most sponsors have to put something, an early estimate, and I think we have that for something like January 2025 right now.
spk09: OK, thank you. And I guess my last question is about the cash runway. I haven't seen the guided number on the press release, so I just want to make sure if I'm not missing anything. Have you guided the cash runway? And also, now that you are not pursuing 2810 development, how much of additional kind of expansion that you kind of expect from, in terms of cash runways, from kind of not, you know, working on 2810?
spk06: Yeah. This is Jill. We don't typically give a cash runway because we look at it by projects. And like we said during the script, you know, we do have financial and strategic plans to be able to get through the data readout for FSOFITs. So that's using our current cash. We'll be getting milestones from Kiran and then also use the current equity vehicles that we have out there right now. We're saving some money from not doing 2810 in the clinic like we just discussed with Yale. Those types of trials just generally typically are maybe around 10 million-ish. But it's more, that's just the cost of the trial. It's more the time that those take and the overhead that is needed just to continue running those over a period of, you know, two or plus longer years.
spk04: And I'll just reiterate, you know, we're still retaining that value for 2810. So any IP, that's the other reason we talked a little bit about, I know we had some patent language in this script, we're still retaining that value of any data that's also coming out of these potential collaborations. So I think it's a really smart way for us to move things forward in the hands of experts, spend less cash ourselves, but still retain that upside should we see signals in those neuroendocrine phenotypes.
spk09: Okay, very helpful. Thank you very much.
spk02: One moment. And our last question will come from Kumar Raja of Roth.
spk03: Your line's open.
spk08: Thanks for taking my questions. So with regard to the clinical trial site from the phase two trial, what are you seeing in terms of those sites coming on board in the phase three trial? And also you talked a little bit about the side effect profile. So what are your expectations in terms of the dropout rate here in the phase three trial? Thank you.
spk04: So the trials, thanks Kumar for the question. For the trials sites that were previously involved, we are seeing obviously good uptake initiation. Many of these were all centers in the U.S. and those that were involved previously obviously are very, very excited about participating in the next trial. If you look at our CHESS publication, you can look at each of those investigators on that publication. All of those sites are going to be what I would consider our lead sites. And some of these are bulky academic institutions, but even some of the timelines of approval has been rather quick in my estimation on how quickly we're moving things forward. That's because we have good data. That's because we have the data that we can talk about, and those local ethics and IRB committees, I think our team is doing a really, really good job, but I also have to tip my hat to those institutions that they are also responding quickly because they want to get patients into this trial. And I know many of these centers are also prioritizing our study over even any other sarcoidosis smaller trials that are out there, early phase trials. They realize a late phase trial like this is really, really important. So I think that's key. You also asked the question about dropouts. With 264, the estimation we have here and what we built into the power calculations is seven to eight patients per arm if we have that kind of cushion. So I want to be at 240 patients. So the worst case scenario here is 24 patients or so, eight per arm, and then that would actually not impact the power calculations as long as we stay within that And other than reasons outside of our control, sometimes there's some operational reasons, we do not expect anyone necessarily to need to drop out to go back to, say, standard of care, because that's written into our protocol. So if folks are not doing well, they can go back up on their steroids. In fact, we want that to happen because we think that's going to happen at a much, much, much more greater rate in the placebo population. So nonetheless, we still have a cushion of, as I said, seven to eight patients per arm for dropouts.
spk08: Very helpful. Thank you so much.
spk04: Sure.
spk03: And I'm showing no further questions. I would now like to hand the call to Sanjay for closing remarks.
spk04: Well, I want to thank everybody. Great questions today. Lots of questions. We appreciate it. Really staying, obviously, laser-focused here on the EPSO-5 trial. Appreciate a lot of updates today, some strategic decisions that we've made. Look forward to interacting in the near future, and we really thank everyone's support listening on the line here, our investors. Thank you so much.
spk03: Ladies and gentlemen, this concludes today's conference. Thank you for your participation. You may now disconnect.
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