aTyr Pharma - Earnings Call - Q2 2021

Transcript

Speaker 0

Good afternoon, ladies and gentlemen, and welcome to the Atyre Pharma Second Quarter twenty twenty one 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, Director of Investor Relations and Corporate Communications.

Ms. Dunston, you may begin.

Speaker 1

Thank you, operator, and good afternoon, everyone. Thank you for joining us today to discuss aTyre's second quarter twenty twenty one operating results and corporate update. We are joined today by doctor Sanjay Shukla, our president and CEO, and miss Jill Broadfoot, our CFO. On the call, Sanjay will provide an update on our corporate strategy, including our clinical program for ATYR nineteen twenty three and our research and discovery program in neuropilin two, including our preclinical program for ATYR twenty eight ten. Jill will review the financial results and our current financial positioning 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 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 and included in our most recent annual report on Form 10 ks and quarterly reports on Form 10 Q. 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, Hire Pharma disclaims any obligation to update these forward looking statements to reflect future information, events or circumstances.

I will now turn the call over to Sanjay.

Speaker 2

Thank you, Ashley. Good afternoon, everyone, and thank you for joining us for our second quarter twenty twenty one results conference call. As we make our way through 2021, we continue to make significant progress in our mission to translate pathways into innovative therapeutics for improved outcomes for patients. Notably, we recently completed the last subject visit in our phase 1B2A proof of concept study of our lead therapeutic candidate, ATYR1923 or 1923 in pulmonary sarcoidosis, our lead interstitial lung disease or ILD indication. We expect to report results from this important study in mid September of this year.

This is a significant milestone for ATAR and the upcoming readout represents a key inflection point for our 1923 clinical program and tRNA synthetase biology platform. Platform. The clinical proof of mechanism for 1923 established from our phase two study in COVID-nineteen patients and the favorable safety profile demonstrated to date, along with the preclinical efficacy observed in multiple translational ILD models, support the potential for 1923 as a new therapeutic approach for pulmonary sarcoidosis and possibly other forms of ILD. We believe nineteen twenty three could potentially offer an alternate to current treatments such as steroids with improved efficacy and fewer side effects. In addition to finishing up the important work for our 1923 clinical program, we've continued to generate new data and publish research related to our preclinical program, further strengthening our pipelines.

As we begin today, I'll summarize a few additional highlights since we last spoke in May. We hosted a key opinion leader or KOL event on current treatment options for pulmonary sarcoidosis featuring Doctor. Daniel Culver, Chair of Pulmonary Medicine and Director of Diffuse Parenchymal Lung Disease at the Cleveland Clinic. Curon Pharmaceutical Company, our partner for the development and commercialization of 1923 for ILD in Japan, completed a phase one study in healthy Japanese volunteers. We had two abstracts for 1923 accepted for presentation at the upcoming European Respiratory Society or ERS International Congress.

We expanded our research collaboration with the Ohio State University or OSU to deepen the understanding of the immune mechanisms of sarcoid granuloma formation and identify potential biomarkers of efficacy for 1923 for pulmonary sarcoidosis. Doctor. Elliot Krauser, professor of pulmonology critical care and sleep medicine at OSU will serve as principal investigator. We received a patent grant from the US Patent and Trademark Office covering methods for the use of histidyl tRNA synthetase HARS, Fc fusion proteins, which includes the use of nineteen twenty three for reducing inflammatory response in the lung. We appointed doctor Sarah Zaknowen, a highly accomplished drug development and clinical research executive, to our board of directors.

Doctor. Zaknowin is a hematologist oncologist who has previously held chief medical officer positions at several biotech companies. We presented a poster at the Keystone Symposia Cancer Stem Cells Advances in Biology and Clinical Translation meeting related to preclinical research highlighting mechanistic insights into the tumor inhibitory effects of ATYR2810 or two thousand eight hundred ten, our lead anti neuropilin two or NRP2 VEGF antibody candidate in preclinical development for cancer. And finally, we presented a poster at the Antibody Engineering and Therapeutics Europe Virtual Conference related to a second anti NRP-two antibody, which demonstrated the selective blocking of that antibody to semaphoren 3F signaling. We've made significant progress during the first half of this year and we see the second half of this year shaping up to be as equally productive.

Let's begin with our clinical program for 1923. We're developing 1923 as a potential treatment for patients with ILD, a group of rare immune mediated disorders that can cause progressive fibrosis of the lung. There are more than 200 types of ILD, but roughly eighty percent of these patients fall into four main disease categories, pulmonary sarcoidosis, chronic hypersensitivity pneumonitis, connective tissue disease ILD, and idiopathic pulmonary fibrosis. All of these diseases have limited standard of care with substantial morbidity and mortality. 1923 has the potential to address this unmet need by targeting the aberrant immune responses central to ILD pathology and preventing progression of fibrosis.

The key driver of poor outcomes in these patients. We estimate there are over five hundred thousand ILD patients in The US alone, and over three million patients globally. While our initial focus for 1923 is pulmonary sarcoidosis, the mechanism of action, or MOA, data from preclinical models, and demonstrated effects on key inflammatory biomarkers in patients with COVID-nineteen pneumonia, suggests that 1923 could have potential in other ILD indications as well. Our initial ILD indication for 1923 is pulmonary sarcoidosis. A hallmark disease characteristic of pulmonary sarcoidosis is the formation of granulomas, or clumps of immune cells in the lungs.

The formation of these granulomas is driven by aberrant inflammation. If left untreated, it can lead to irreversible scarring or fibrosis and diminished lung function, which may lead to respiratory failure or the need for a lung transplant. We estimate the patient population for pulmonary sarcoidosis to be approximately two hundred thousand patients in The US, although estimates do vary. About half of all patients will require some form of systemic therapy. And unfortunately, thirty percent of all patients will have chronic progressive disease despite available treatments.

The current standard of care for pulmonary sarcoidosis typically includes treating the inflammation with corticosteroids and other immunosuppressive therapies. While these treatments can help manage inflammation and alleviate symptoms, such as cough and shortness of breath, they have no demonstrated efficacy on disease progression and can result in serious long term toxicity. Additionally, many patients do not respond to currently available treatments. So there is a substantial need for a safer, more effective treatment that could reduce or replace the requirement for chronic corticosteroid or other immunosuppressive therapy. This need was recently reinforced by one of the leading experts in the field, Doctor.

Daniel Culver at the Cleveland Clinic. In June, we hosted a KOL event with Doctor. Culver, who discussed limitations with the current standard of care and unmet medical need for treating patients with pulmonary sarcoidosis, including the toxicity burden of chronic steroid use and the need for better steroid sparing agents. Through this event, we heard firsthand from Doctor. Culver about some of the side effects related to steroid use in sarcoidosis, including some staggering statistics related to metabolic complications, quality of life, economic burden, and risk of mortality, leading him to believe that there is no safe maintenance dose of corticosteroids in patients with sarcoidosis.

If you are unable to attend the event, I encourage you to listen to the replay, which can be found on our website. Now let's talk a bit more about nineteen twenty three and why we believe it is a potential first in class immunomodulator for some of the inflammatory lung diseases we've been discussing, including pulmonary sarcoidosis. Nineteen twenty three is a novel Fc fusion protein based on the naturally occurring splice variant of the lung enriched tRNA synthetase HARS fragment that down regulates aberrant immune responses in inflammatory disease states. Nineteen twenty three has been shown pre clinically to down regulate inflammatory cytokine and chemokine signaling, and reduce inflammation and fibrosis. NRP-two is upregulated on key immune cells known to play a role in inflammation, and is enriched in inflamed lung tissue.

Nineteen twenty three selectively binds to NRP-two, 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. As a reminder, our ongoing trial in pulmonary sarcoidosis is a Phase 1BA, 1B2A randomized, double blind, placebo controlled, multiple ascending dose clinical trial in thirty seven pulmonary sarcoidosis patients. The trial consists of three cohorts testing doses of one, three, and five milligrams per kilogram of nineteen twenty three, or placebo, dosed intravenously every month for six months. The primary objective of the study is to evaluate the safety and tolerability of multiple ascending doses of nineteen twenty three. Secondary objectives include assessment of the potential steroid sparing effects of nineteen twenty three, in addition to other exploratory assessments of efficacy such as lung imaging, lung function assessed by pulmonary function tests, and relevant serum biomarkers.

Based on our trial design, which includes a forced steroid taper, an integral element of the study is to assess steroid burden in the nineteen twenty three treatment groups compared to placebo. As we have discussed here a bit today, and reinforced by Doctor. Culver, there's a crucial need for alternatives to existing treatment options, including steroids. We look forward to the results of this study, which we expect to report in mid September of this year. While we have advanced our clinical program for 1923, we continue to conduct research to deepen our understanding of nineteen twenty '3 MOA and advance our understanding of sarcoidosis disease pathology.

We are pleased to have announced that we have two abstracts for 1923 that have been accepted for presentation at ERS in September. One of these abstracts will present the biomarker data from our phase two study in patients with COVID-nineteen pneumonia. Earlier this year, we released some findings from this data, which showed substantial anti inflammatory effects in patients, consistent with findings from our animal models. This data provides the first inpatient mechanistic proof of concept for 1923. And we look forward to sharing more details about the data at ERS.

A second abstract will present data from a pilot proof of concept study conducted in collaboration with Doctor. Elliot Krauser, a leader in sarcoidosis research and treatment at OSU, which demonstrated the ability of a splice variant, HARS, the active component in portion of 1923, to disrupt sarcoid granuloma formation in vitro. Based on these successful pilot study findings, we announced just earlier today that we are expanding our research collaboration with OSU and Doctor. Krauser to continue this important work. The collaboration is intended to deepen our understanding of the immune mechanisms of sarcoid granuloma formation, and identify potential biomarkers of efficacy for 1923.

The study will assess the effect of 1923 on sarcoid granuloma formation in vitro, using blood samples taken from sarcoidosis patients. We'll also focus on identifying the relevant immune mechanisms triggered in granuloma formation, and analyze promising biomarkers predictive of strong granuloma formation in order to assess whether they could be used as a predictive biomarker for treatment selection or treatment response to 1923. We're very excited to continue our work with Doctor. Krauser and his lab at OSU. The research generated from this collaboration may help direct us to biomarkers indicative of a population that may be sensitive to treatment with nineteen twenty three, which could present the opportunity to take a much needed step forward in managing this disease and lead to improved patient outcomes.

To wrap up our discussion on nineteen twenty three, we're pleased to inform you that Curon Pharmaceutical, partner for the development and commercialization of nineteen twenty three for ILD in Japan, has completed its phase one study, which investigated the safety pharmacokinetics or PK and immunogenicity of nineteen twenty three, known as KRP R120 in Japan, in 32 healthy Japanese volunteers. In this study, nineteen twenty three was observed to be generally safe and well tolerated with no drug related serious adverse events. And PK findings were consistent with previous studies of 1923. Before we turn to our preclinical program, I want to take a minute to highlight an important business update that occurred in the second quarter. May, we announced the appointment of Doctor.

Sarah Zaknowin to ATAR's Board of Directors. Doctor. Zaknowin, a hematology oncologist by training, is an experienced pharmaceutical drug development and clinical research executive, who's previously held Chief Medical Officer positions at several biotech companies. She also has a wealth of experience working at large pharmaceutical companies including Novartis and Sharing Plough, now Merck, where she was involved in supporting the development of a number of important marketed therapies, including Gleevec, Tasinia, Exjade and Temodar. We believe Doctor.

Zakinon's experience in advancing programs at both biotech and large pharma companies is ideally situated to support and guide ATAR as we prepare for the next clinical stage program to emerge from our tRNA synthetase biology platform. Now Now I'd like to take a few minutes to discuss our preclinical program, which includes the development of anti NRP-two antibodies for cancer and inflammation. NRP-two is a compelling therapeutic target in a number of disease areas, including oncology and inflammation. When it comes to cancer, NRP-two is upregulated on a variety of solid tumors and is particularly enriched in highly aggressive tumors, with expression linked to worsened patient outcomes in several cancers, which may include drug resistance to current therapies such as chemotherapy or targeted agents. NRP-two is also highly expressed on key immune cells implicating in regulating cancer progression, including tumor associated macrophages and myeloid derived suppressor cells, among others.

Antibodies that can selectively block different aspects of NRP-two signaling pathways may have the therapeutic potential in these aggressive cancers where NRP-two is implicated. Our lead anti NRP-two antibody and IND candidate is 2,810, a fully humanized monoclonal antibody that specifically and functionally blocks the interaction between NRP-two and VEGF. The role of NRP-two and VEGF signaling in the tumor microenvironment, and its potential importance in the progression of certain aggressive cancers, is becoming increasingly validated. We have generated a body of compelling preclinical data in both human derived and animal models demonstrating 2,800 ten's blocking ability and tumor inhibitory effects. Notably, we've continued to strengthen our mechanistic understanding of the link between NRP-two and the critical process of epithelial mesenchymal transition, or EMT, which is of great importance in regulating tumor growth, progression, and metastatic cascade, as well as being implicated in tumor evasion of the immune system.

At a recent Keystone Symposia of Cancer Stem Cells Advances in Biology and Clinical Translation, we presented a poster demonstrating that in preclinical studies, 2,810 sensitized certain patient derived xenograft models of triple negative breast cancer to chemotherapy. And we are actively working to understand the underlying gene signatures that confer responsiveness. These findings build upon our mechanistic understanding of 2,810, and demonstrate the molecular basis for selectivity by directly obstructing the VEGF binding site of NRP-two. P2810's ability to affect EMT and cancer stem cell properties may be one mechanism by which it mediates the anti tumor effects we have observed. This work moves us closer to identifying the underlying characteristics within a tumor that may confer responsiveness to treatment with 2,810.

IND enabling activities for two thousand eight hundred ten to support advancement in clinical trials in cancer in the future are ongoing. I will now turn it over to our Chief Financial Officer, Jill Broadfoot, to review our financial results.

Speaker 3

Thank you, Sanjay. Cash, cash equivalents, and investments as of 06/30/2021, were $44,100,000 Research and development expenses were $7,700,000 for the 2021, which consisted primarily of $19.23 and 2,810 program costs, including increased manufacturing costs. General and administrative expenses were $2,800,000 for the 2021. We do expect expenses to continue to increase throughout 2021 as research and development of 1923 and 2810 progress, including additional manufacturing costs for both 1923 and 2810 to prepare for future clinical trials. However, we have sufficient capital to take us through the readout of our trial in pulmonary sarcoidosis and initiate a patient trial in cancer for 2,810.

Common shares outstanding were 16,900,000.0, and fully diluted shares were 18,700,000.0 as of 08/09/2021. Now I'd like to turn the call back over to Sanjay before we open it up to Q and A.

Speaker 2

Thank you, Jill. We're highly encouraged by what we've been able to accomplish in the 2021. And we are looking forward to the upcoming readout for our proof of concept study for 1923. We've taken a very methodical approach to the development for 1923. When you look at nineteen twenty three's MOA, we've shown that nineteen twenty three down regulates innate and adaptive immune responses during active inflammation.

We've shown nineteen twenty three binds selectively to neuropelin two, a receptor that we've shown is upregulated on key immune cells during inflammation, including sarcoid granulomas. And now, based on data we will present at ERS, we've shown that the active portion of nineteen twenty three has the ability to disrupt sarcoid granuloma formation in vitro. We've established a library of data demonstrating nineteen twenty three's favorable clinical safety profile, which has consistently shown that nineteen twenty three is safe and generally well tolerated with no serious drug related adverse events. This now includes data from two phase one studies in healthy volunteers, a phase two study in COVID-nineteen patients, and two independent data safety monitoring board reviews from our current study in pulmonary sarcoidosis patients. And finally, we've demonstrated potential efficacy, which includes a robust portfolio of translational work demonstrating nineteen twenty three anti inflammatory and anti fibrotic effects in multiple preclinical models of ILD.

And clinical proof of mechanism from our phase two study in COVID-nineteen. With biomarker data showing that nineteen twenty three reduced inflammatory cytokine levels in patients consistent with preclinical models, including cytokines that are directly implicated in sarcoidosis and other forms of ILD. Based on the totality of this data, we believe nineteen twenty three has the potential to be a transformative alternative to steroids and other available treatments, with improved outcomes in patients with pulmonary sarcoidosis. This upcoming readout represents years of hard work and dedication to developing and advancing our tRNA synthetase biology platform to one that can generate new therapeutic targets, and from which we can develop a new class of medicines. We look forward to sharing the results from this important study with you in mid September.

We appreciate your interest, continued support at this time. Jill and I will be happy to take your questions.

Speaker 0

As a reminder, to ask a question, you will need to press Your first question comes from the line of Prakhar Agrawal of Jones Trading. Your line is open.

Speaker 4

Hi. Thanks for taking my questions. On 1923, I had a couple. On the healthy volunteer trial update from Curin, could you expand on what has been seen in the safety database? I understand there were no drug related SAEs, but on other adverse events, how did that compare with what has been seen with 1923 previously?

Was there anything new? Secondly, as we think about the September readout, what data will be disclosed at the time of press release? What exploratory efficacy endpoints we might see and or what endpoints we might need to wait? And then I had a follow-up.

Speaker 2

Sure. Thanks Prakhar. So with respect to our PARTNERS trial, as I mentioned, this trial is complete. Nineteen twenty three tracked well, very consistent to what we saw in our trial. No serious adverse events related to drug effect.

And generally safe and well tolerated. So very much consistent with the findings we saw several years ago with our phase one trial. Those are the details that I can share with you, about that trial. With regard to your second question around the readouts in September, we expect to not only report the primary, objective, which is safety and tolerability But we will be focusing on those, key, exploratory endpoints, namely around steroids, steroid burden, looking at, pulmonary function tests, imaging, inflammatory biomarkers.

So really, we're looking at the totality of all of that data, in an attempt to really get it all out really at once. I do not expect things to trickle in after that. We're looking to look at all the data here and read out all of the primary and secondary objectives of the trial.

Speaker 4

Got it. Same question on NRP-two 14, the that, the second antibody that blocks NRP-two interaction with semaphorelin and lexin. Could you expand on how this could play a different role than 02/2010? And what are the potential next steps for this antibody? Thank you.

Speaker 2

Yeah, this is an early opportunity for us. 2,810 emerged out of the suite of specific antibodies that block different, epitopes of neuropilin-two. Our 2,810 blocks VEGF signaling. This is the next opportunity that we're looking at, blocking semaphoren signaling. With regards to how tuning neuropilin biology could be different, it could be useful in some instances in cancer.

We of course are seeing some effects, rather early on with two thousand eight hundred ten. With regard to semaphorens, they're broadly implicated a bit more with inflammation. So we now want to look at how that signaling could be useful either in cancer or inflammation. The idea here is by tuning neuropilin biology, our suite of antibodies could be useful, not only in cancer, but also potentially as even a more targeted anti inflammatory, when you think about semaphorein biology. But again, the first thing we did there was to make sure that it's a good strong blocking antibody.

We have observed that. Now we'll start to tease out a little bit more of our mechanistic understanding of that, next generation antibody.

Speaker 0

Your next question comes from the line of Emmanuela Brancetti of H. C. Wainwright. Your line is open.

Speaker 5

Hi, then. Thank you for taking my questions. A couple for me. So with regards to the upcoming Phase onetwo readout, obviously we are excited to see the potential for steroid tapering with the entire 1923. But in this regard, do you expect a certain level of variability in patients' responses based, for example, on the length of treatment with steroids?

And also, I guess, what would be the main drivers of this variability?

Speaker 2

Okay, so your question is really about, duration of prior steroid therapy, Emmanuelle? That Yeah.

Speaker 5

Yeah. Correct. So I know that the the inclusion criteria was, at least four weeks on stable steroid doses, if I'm correct.

Speaker 2

That's right. That's right. And most of these patients, we can sometimes be on steroids for years. So this will be an important, element for us to look at closely in our trial. What we understand from the experts, however, is once you progress to needing at least ten milligrams of prednisone a day, upwards to twenty five, that's really what we've enrolled in our trial, you now have moderate disease.

And in many ways, these patients are similar, whether they've received therapy for six months, or sometimes for several years. But it is going to be an important characteristic for us to look at, to determine whether or not duration of steroid burden contributed to any of the responsivity. But I think that's an open question. I will say though, one of the things we really look to do is to eliminate folks who self resolve. This is why we focused in on a population, receiving a moderate to high dose of steroids in our trial, to create a bit more homogeneity amongst the patients enrolled.

But that will be important for us to look at for sure.

Speaker 5

Got it, got it. Thank you, that's very helpful. And also, it's nice to see, the update on curing phase one. But in this regard, I was wondering if you can provide more color on the strategy for the development of ATHYR1923 with curing. So should the ATHYR1923 move to pivotal, should we expect Curin to participate in a parallel development in sarcoidosis?

Or would they focus on other ILDs?

Speaker 2

So the plan at this moment is for, Curin as our partner to potentially join our next trial, if we are advancing this program forward. In addition, there's also the ability to move into other interstitial lung diseases with Curin, something that obviously we will sit down and map out that strategy. Curin has the ability to look at interstitial lung disease in Japan independently or together with us. So I think these readouts are going to solidify a little bit more of the strategy. But at this point, our aim here is to conduct, potentially a worldwide trial, next in which Curin, can hopefully support us, with Japanese experts and trial sites.

Speaker 5

Got it, got it. Thank you very much.

Speaker 0

Your next question comes from the line of Hartaj Singh of Oppenheimer. Your line is open.

Speaker 6

Great. Thank you for the questions. Nice update, Sanjay. Looking forward to September. Just a couple of questions from my part or from my end.

One is, when I look at the secondary outcome measures, Sanjay, clintrials.gov, they're listed total cumulative steroid dose. Results in number of patients who achieved and maintained the taper dose. My question is, which of these would you consider more important? Is it trying to get the patient down that targeted taper dose? Is it the total cumulative dose?

I know also during Doctor. Culver's presentation, he had some opinions there. Just your thoughts there. And then I just have a couple of follow ups.

Speaker 2

Yeah, great question, Hartaj. I think the way to think about this is we really are looking at steroid burden, a couple ways. First off, we want to be able to evaluate whether or not folks were able to maintain a response. And response being able to be on five milligrams or less in our trial. I think that is a sub therapeutic dose.

And if patients do well on our therapy and are able to maintain that kind of dose, remember, these are patients that have had very difficult time even dropping one milligram. They've sort of landed somewhere between ten to twenty five milligrams, sometimes for several years. So that's number one. Number two, looking at the total steroid dose over time, over the six months, with regards to what Doctor. Culver talked about, this could be obviously have a big impact on that sort of toxic burden over time.

And if we can show some differences between placebo and treated populations there, that could also be a nice win for us. So I think those are the kind of ways we're looking at this trial. Of course, we have the ability that if a patient was able to even taper to zero, I think Doctor. Culver highlighted that that would be a real outstanding finding, if we were able to do that even in the short trial. These patients at the end of the day want to get off or on their way to getting off steroids.

And if we're able to observe anything like that, I think that would be a real, tremendous finding. With regard to some of the secondary endpoints, I think, right now we really are looking closely at some of those inflammatory biomarkers in addition to some of those other endpoints that you see on clintrial.gov. Biomarkers have become really important, in particular after we demonstrated some nice improvement in COVID-nineteen patients.

Speaker 6

Yeah, that's very helpful Sanjay. It would be great, like you said, in a twenty four week trial to show these effects, that's not very long. What is the other question I had was, Sanjay, assuming you had a positive readout in mid September, what would be the next step with regulators and the timing on that? And then in association, how important is your OSU collaboration or looking at what could be a potential diagnostic type or diagnostic strategy be? How important would that be to that interaction with regulators?

Thanks for the question.

Speaker 2

Sure. So obviously, we would want to move really quick here. We're working in rare disease. These patients can't wait. So after these readouts, we would look to get aggressive, have an aggressive timeline to get back to the FDA.

Some of that will also involve us sitting down with the investigators of our trial, and really mapping out their thoughts. But we would want to quickly get to the FDA, so that we could start what's hopefully a single pivotal trial next year. Again, that's pending some of that FDA dialogue. But our approach here would be that in rare disease, these patients can't wait. And our approach would be to really move forward with an aggressive regulatory strategy.

With regard to your question around the OSU collaboration, absolutely this could be an avenue for us to develop an ex vivo assay, which can effectively identify patients sensitive to nineteen twenty three prior to even dosing these patients. So I think as you point out a kind of companion predictive diagnostic, this would be something that we would work towards, and potentially use to, at a minimum, enrich our target population, patient population for the next trial. So I think it sets us up really nicely to create even more homogeneity around those patients that respond to 1923.

Speaker 6

Great, thank you Sanjay.

Speaker 0

Your next question comes from the line of Yale Jen of Laidlaw and Company. Your line is open.

Speaker 7

Good afternoon, and thanks for taking the questions. My first question is that to sort of follow-up with the previous one, which is that in terms of the Japan, study versus the study you have done in healthy volunteer, was there any PK differences, between the Japanese and, I guess, American? Or there's not much? Do you have other follow ups?

Speaker 2

Yes. Hi, Yale. No, we saw consistent findings. Our half life of our drug is somewhere between eight or nine days. And those PK findings tracked in the Japanese population as well.

So we more or less are in the same ballpark, which is one of the reasons you conduct this trial. Because there sometimes can be differences in PK between, the populations.

Speaker 7

Okay, great. And, the second question is that, in terms of the readout, in mid September, in what venue you think you will communicate to the street? Would that be analyst investor call or other means just call just a press release?

Speaker 2

We would we would we would plan to to to have a call, certainly. This is an important inflection point for us. So, we'll certainly wanna get, everybody on the line and go through the data with, each of you.

Speaker 7

Okay. And then maybe one more two more quick one. First one is that in the consent.gov, in terms of the secondary outcome measure, there's one thing called the incident and the lit titers of anti GL, GL one antibodies. Would you give a little more color what is that?

Speaker 2

Sure. So as we are working with a class of medicines coming from the tRNA synthetase world, there is an ultra rare condition called antisynthetase syndrome. In this example, antisynthetase patients sometimes develop antibodies to a protein fragment of full length of histidyl tRNA synthetase. So as we are working in the same class, part of our safety is to ensure that we do not develop any autoimmunity. These JEL-one antibodies are something that we are going to be required to watch for.

However, I will tell you that antisynthetase patients who develop antibodies to histidyl tRNA synthetase, they develop interstitial lung disease. So in many ways, we're dealing with patients that already have interstitial lung disease. And another way to think about this is, those patients that where you knock out this clinical pathway around tRNA biology, In some ways it demonstrates proof of concept, if you will, that this is an important pathway. This protein fragment is involved in regulating the development of interstitial lung disease. But as we are working with this class, the FDA, from a safety perspective, we have to monitor because we are a tRNA synthetase platform company.

Speaker 7

Okay. Great. Maybe the last question is a housekeeping one. In terms of the licensing and the collaboration agreement revenues for the remaining of, 2021. Do you see any potential revenue insight in in this time frame?

Or how should we think about that that piece of the line?

Speaker 3

Yes. While we haven't really disclosed when each of those milestones are, the majority of the remaining $165,000,000 is geared towards development. But we did see the 2,000,000 milestone received upon the last patient in for their trial. So, you can basically kind of think of that as what we received from a Phase I perspective. So the next milestone would, you you can think of as coming in that next stage of development, which would not begin this year.

Speaker 7

Okay. So, but the last patient in was not the one you completed completed the enrollment. Right? Complete the treatment reported earlier this year.

Speaker 3

Right. They they had the last patient in in December, and we received in the first quarter of this year.

Speaker 7

Okay. Great. Thanks a lot. Appreciate that, and thanks for taking the questions.

Speaker 0

Your next question comes from the line of Zeddia Jala of Roth Capital Partners. Your line is open.

Speaker 8

Hi. Thanks for taking my question. Just have a few. The first one is just on how many patients, you know, you plan to have for the biomarker data on COVID-nineteen. And then since they'll be presented before the pulmonary SOC data readout, how would you be comfortable with investors in faring from that data readout?

Speaker 2

Sure. Thanks, Zegba. So this was, again, we presented this data earlier this year. There were thirty two patients in that, COVID-nineteen mechanistic proof of concept trial we ran. Previously it presented that over eighty percent, eighty two percent of those inflammatory markers substantially declined when nineteen twenty three was used on top of dexamethasone.

So this is a poster which essentially brings all that data together. So, there isn't exactly new information coming from that. We have previously released it to the street. But we thought it would be useful, and the community, would like to see this in a medical conference. So that's really what, that poster is about.

Previously, we've highlighted this data, with interferon gamma, IL-six, MCP-one, significant knockdown in those COVID pneumonia patients. These are the same biomarkers that we saw really move significantly in our animal studies. So this poster, basically gets its arms around all of that information that we presented back in Q1, and is being presented at European Respiratory Society. Which happens to be, as it turns out, you know, just in a short period right before we're about to announce data from sarcoidosis.

Speaker 8

Thanks, MJ. And then just a follow-up regarding the pulmonary start data that's going be coming out next month. Would it just be highlights, or would it be full patient by patient detail?

Speaker 2

We'd like to be as detailed as possible. There's no top line, no interim. We're aiming for full results, being able to look at not only all of the safety endpoints, but even those exploratory efficacy endpoints that we've highlighted.

Speaker 8

Thank you, Vlad here. And then just a follow-up to that one actually. Was just also wondering, you know, with the small sample size, are there any data points where you would expect to see some variability? And how do you plan to tackle that or leverage other data points that kind of determine the Go For Our strategy?

Speaker 2

Yeah, I think Doctor. Culver highlighted this, that pulmonary function tests sometimes can be perhaps the most variable in this population. The way we look at it is we may be able to look at pulmonary function tests and stratify, based on response. We may learn something there. Our current trial did not, create a stratification or inclusion criteria around forced vital capacity.

We were advised, by the experts to, as this endpoint is pretty variable, leave it alone. I think with regards to some of the lung imaging, of course that's an unvalidated PET scans are a new biomarker being used out there. So we're going to learn, that's why these are exploratory endpoints. I think the way that what we are really prioritizing is the safety, looking at steroid sparing effects, and looking at those biomarkers. Patient reported outcomes are also going to be really important here.

Cough, fatigue, shortness of breath, are all areas that if patients are doing well, and we're able to also see improvement, in knocking down their steroids, well, then I think those two PD markers going in the same direction, as doctor Culver pointed out, could be really, really, impactful.

Speaker 8

Thanks Sanjay. Looking forward to the data readout.

Speaker 2

Thank you.

Speaker 0

There are no further questions at this time. I will now turn the call over to Sanjay Shukla for closing remarks.

Speaker 2

Great. Well, we thank everyone for their interest. Great questions today and looking forward to getting back to everyone very soon here in the near future. So thank you everybody. Have a great day.

Speaker 0

This concludes today's conference call. Thank you for participating. You may now disconnect.