ATYR - NASDAQ

Good afternoon ladies and gentlemen and welcome to the aTyr Pharma First Quarter 2021 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 Ashlee Dunston, aTyr's Director of Investor Relations and Corporate Communications. Ms. Dunston, you may begin.

Thank you, operator, and good afternoon everyone. Thank you for joining us today to discuss aTyr's first quarter 2021 operating results and corporate update. We are joined today by Dr. Sanjay Shukla, our President and CEO; Ms. Jill Broadfoot, our CFO; and Leslie Nangle, Vice President of Research. On the call, Sanjay will provide an update on our corporate strategy, including our clinical program for ATYR1923; Leslie will provide an update on our research and discovery programs in neuropilin-2, including our pre-clinical program for ATYR2810 and our bi-specific antibody program with our subsidiary, Pangu BioPharma. Jill will review the financial results and our current financial positioning before handing it back to Sanjay to open the call up 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 and included in our most recent annual report on Form 10-K 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, aTyr 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.

Thank you, Ashlee. Good afternoon, everyone, and thank you for joining us for our first quarter 2021 results conference call. 2021 is shaping up to be an impactful year for the company. During the first quarter, we made meaningful progress with our clinical, pre-clinical, and research and discovery programs. We remain focused on advancing our lead therapeutic candidate at ATYR1923 or 1923. With enrolment completed in our Phase 1b/2a clinical trial in pulmonary sarcoidosis, our interstitial lung disease or ILD indication, we are tracking towards readout from this important proof-of-concept study. Having gained key mechanistic insights regarding 1923 anti-inflammatory effects in patients from data obtained from our Phase 2 clinical trial in COVID-19 with severe respiratory complications, we look forward to the [Indiscernible] expected in the third quarter of this year. Furthermore, we generated additional ATYR2810, or 2810, our anti-neuropilin-2 or NRP2 antibody in pre-clinical development for cancer. As we begin our -- summarize a few additional highlights since we last spoke in March. With pulmonary sarcoidosis advocate, Andrea Wilson, Co-Founder and former President and member of the Board of Directors of the Foundation for Sarcoidosis Research for FSR, a patient advisor to the company. In collaboration with the FSR, we're participating in a Virtual Town Hall on Steroids and Sarcoidosis to discuss the burden of [Indiscernible] and the need for new therapeutic options. Details [ph] have been posted at the annual meeting of the American Association for Cancer Research on pre-clinical data for 28 in models of triple negative breast cancer and non-small cell lung cancer. We entered into an agreement with [Indiscernible], a leading contract development and manufacturing organization for the manufacturer of 2810 to support the progression of 2810 to clinical stage development. Pangu BioPharma, or Pangu, our Hong Kong subsidiary, together with the Hong Kong University of Science and Technology achieved a milestone for the first year of a two-year project funded in part by a grant from the Hong Kong government Innovation and Technology Commission to develop a high throughput platform for the development of bi-specific antibodies targeting NRP2. And finally, we promoted Dr. Leslie Nangle to Vice President of Research. Dr. Nangle will serve as a member of our executive leadership team, managing research and scientific operations. We're highly encouraged by what we've accomplished this year thus far. I look forward to building upon Hong Kong pre-clinical programs and discovery pipeline from our novel biology platform forward this year. Let's begin with our clinical program for 1923. We're developing 1923 as a potential treatment for severe inflammatory lung disease. 1923 is a potential first-in-class immunomodulator that downregulates aberrant immune responses in inflammatory disease states. 1923 has been shown pre-clinically to downregulate inflammatory cytokine and chemokine signaling and reduce inflammation and fibrosis. NRP2 is upregulated on key immune cells known to play role in inflammation and is enriched in inflamed lung tissue. 1923 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 alleviate morbidity and mortality. Our lead program is focused on ILD, a group of rare immune-mediated disorders that cause progressive fibrosis of the lung. Our initial ILD indication of pulmonary sarcoidosis, the most inflammatory form of ILD, which is characterized by the formation of granulomas or clumps of immune cells in the lungs. If not then treated, it can lead to irreversible scarring and diminished lung function. Current treatment options are limited and often include treating the inflammation with corticosteroids or other immunosuppressive therapies, which have limited efficacy and a serious long-term toxicity. Additionally, many patients do not respond to this current standard of care. There remains a need for a novel treatment option for patients with progressive disease with better efficacy and side effect profile. We recently spent some time deepening our understanding of the need for these treatment options for patients with sarcoidosis, including steroids and we've made a conservative effort to better work with the needs of the community. As part of these efforts, we have now appointed Andrea Wilson, sarcoidosis patient advocate, as an advisor to the company. Andrea has dedicated the past 20 years to promoting awareness and generating support to accelerate research to find a cure for this disease. She Co-Founded the FSR, the leading international non-profit organization dedicated to finding a cure and improving care for these patients and previously served as President and a member of its Board of Directors. So, firsthand knowledge of the patient can bind to their long standing advocacy experience and relationship with the sarcoidosis community will help support patient strategies for advancing on 1923 clinical program in pulmonary sarcoidosis and we look forward to her contributions in the future. Officially, April was Sarcoidosis Awareness Month and as part of our effort attention to this chronic debilitating disease, we were invited by the FSR to participate in a Virtual Town Hall on steroids and sarcoidosis to discuss treatment options and strategies for patients living with sarcoidosis. I was honored to join this panel, which included two sarcoidosis patients and a leading pulmonologist. This panel brought provided in real-world and firsthand perspective, highlighting the toxic effects of steroids and shedding a light on the need for better and more effective. The majority of sarcoidosis patients will receive steroids at some point during the course of treatment. Corticosteroids are highly associated with obesity, malaise, decreased bone density, cataracts, hyperglycemia, and [Indiscernible]. Really each of these side effects on their own are a condition to treat and manage. Currently used steroids agents such as cytotoxic immunosuppressive, have limited clinical evidence supporting their use in sarcoidosis, are associated with significant side effects such as infection, liver toxicity, and even the malignancies. We believe that patients deserve better. 1923 presents a potential option to do better. In clinical studies today, 1923 has shown a favorable safety profile. This includes data from a Phase 1 study in healthy volunteers, a Phase 2 study in patients with COVID-19 related severe respiratory complications, and two the data safety monitoring board review from the ongoing Phase 1b/2a study in pulmonary sarcoidosis. In each of these studies, 1923 was assessed to be generally safe and well-tolerated with no drug related serious adverse events. Based on recent proof of mechanism, here favorable safety profile, 1923 could be a transformative alternative to steroids and other available treatments with improved patient outcomes. As a reminder, our ongoing trial in pulmonary sarcoidosis is Phase 1b/2a randomized double-blind placebo-controlled multiple ascending dose clinical trial in 37 pulmonary sarcoidosis patients. This trial consists of three cohorts testing doses of one, three, and five milligrams per kilogram of 1923 for placebo, dosed intravenously every month for six months. The primary objective of this study is to evaluate the safety and tolerability of multiple ascending doses of 1923. Secondary objectives include assessment of the potential steroid-sparing effects of 1923 in addition to other exploratory assessments such as lung imaging, lung function assessed by pulmonary function tests, and relevant serum biomarker. Based on our trial design, an integral element of this study of the steroid burden in the 1923 treatment groups compared to placebo. As we'll discuss here today, due to the side effects and toxicity in available treatments, there is a crucial need for alternative to existing treatment options including steroids. We look forward to the results of the study which we expect to report in the third quarter of this year. I'd like to not turn the call over to Dr. Leslie Nangle, VP of Research. As I mentioned, we recently promoted Leslie to the company's executive leadership team to manage research and scientific operation. Leslie has dedicated her career to tRNA synthetase and the pathways they regulate. Having studied under the proportion of aTyr's Co-Founder and having served in scientific research roles at aTyr since joining the company in 2007. We're very pleased to have her with us today to review recent updates from our research pipeline starting with our NRP2 antibody program.

Thank you, Sanjay. I'm thrilled to continue my tenure at aTyr and expand the scope of my responsibilities related to our research and scientific operation, particularly at a time when we are really starting to see some encouraging results from the work that we've been piecing together over the past few years. About two years ago, we initiated collaborations with experts in the NRP2 biology field to help advance our program. It is extremely gratifying to see these collaborations bear fruit, particularly in regards to helping us better understand the underlying mechanism of our therapeutic antibodies targeting NRP2. I am very pleased to be here today to discuss some of the exciting research that we've been generating both in-house and with our--. I'll begin with a bit of background about NRP2, which is a compelling therapeutic target in number of disease areas, including oncology and inflammation. NRP2 is upregulated on a variety of solid tumors such as breast, renal, lung, and glioblastoma, and it's particularly highly enriched in aggressive tumors. In addition, as we reported earlier this year, NRP2 is highly expressed on key immune cells implicated in regulating cancer progression, including tumor-associated macrophages and myeloid-derived suppressors among others. High NRP2 expression has been linked to worsen patient outcomes in several cancers, which in some cases may include drug resistance to current therapies, such as chemotherapy or targeted agents, tumor recurrence, and overall survival. Antibodies that can selectively block different aspects of NRP2 signaling pathways may have therapeutic potential in these aggressive cancers where NRP2 is implicated. aTyr has generated a panel to selectively target distinct domains of NRP2 including those interacting with some foreign, VEGF, and certain chemokine such as CCL-21. The roles NRP2 and VEGF signaling in the tumor microenvironment and its importance in the progression of certain aggressive cancers is becoming increasingly validated. 2810 is fully humanized monoclonal antibody developed and optimized internally by our antibody engineering team, specifically and functionally interaction between NRP2 and VEGF. Based on compelling pre-clinical data in oncology models, both human-derived and animal, we selected this candidate to advance to investigational new drug or IND enabling activity. Just last month, we presented two posters at this year's American Association for Cancer Research Annual Meetings, which build upon our pre-clinical work related to 2810 and strengthen our understanding of the blocking mediated NRP2 signaling as a potential approach to inhibiting tumor growth. The research presented in these posters was conducted in collaboration with leading cancer researcher Dr. Arthur Mercurio, one of our scientific advisors, and his lab at the University of Massachusetts Medical School. These posters represent significant progress we have made towards understanding part of the underlying mechanism by which walking NRP2 VEGF signaling in tumor cells can inhibit tumor growth and metastasis. Specific insights strengthen the link between NRP2 and a seminal process involved in tumor progression, epithelial mesenchymal transition, or EMT, which is the acquisition of mesenchymal or stem cell like features by epithelial cells in the tumor that confer migratory and invasive properties to the cells. EMT is of great importance in the tumor microenvironment, regulating tumor growth, progression, and metastatic cascade, as well as being implicated in tumor of the immune system. The data we presented demonstrate the therapeutic potential of inhibiting EMT through blocking the NRP2 VEGF signaling assays in various types of solid tumors. In the work we presented, we generated two types of tumors with high NRP2 expression, triple-negative breast cancer, or TNBC, and non-small cell lung cancer. In TNBC, patient derived organoids as well as tumor xenograft models, 2810 sensitized tumors have two widely used anti-cancer therapeutics, including the chemotherapeutic agent cisplatin, or the targeted VEGF therapy bevacizumab, increasing the SI tumor effects of each stages. Furthermore, treatment was 2810 was shown to down regulate genes associated with EMT and stemless, in particular, down regulating the expression of [Indiscernible], a central regulator of these processes. This data suggests that 28 times ability to impact EMT may be one that into mediates its anti-tumor effects. In addition to TNBC, we have also generated data demonstrating efficacy in other solid tumor models, including non-small cell lung cancer, both as a single agent and in combination with chemotherapy. The ability of this antibody to promote the differentiation of aggressive tumor cells away from stem cell phenotype and render them more susceptible to conventional cancer therapies has the potential to be a significant advancement because there'll be resistance. Those data with tumor recurrence and metastasis is a major challenge for patients with aggressive cancer. We continue to invest the 2810 and its ability to block the NRP2 VEGF signaling assays, including its effect on sensitizing aggressive cancers to chemotherapy, in particular through its effect on inhibiting EMT and cancer stem cell properties. We expect to present more findings from our research on this evolving mechanism, including in models of patient derived xenograft at the upcoming [Indiscernible] on cancer stem cells scheduled for later this month. We are very pleased with the pre-clinical data generated for 2810 thus far and plan to leverage the progress that we've made in further understanding its mechanism of action both on tumor cells themselves, as well as critical immune cells and tumor microenvironment to build a compelling data package to inform our clinical strategy for 2810 in treating aggressive solid tumors. We really look forward to continuing IND enabling activities for 2810 to support example trials in the future. As we continue with our IND enabling activities for 2018, we are committed to progressing this program to clinical stage development. Last month, we announced that we've entered into an agreement with Lonza for the manufacturer of 2810. We are very pleased to be working with a partner with extensive proven capabilities in antibody manufacturing for the production of our first anti-NRP2 antibody. Having a manufacturing commitment at this stage of development for 2810 is especially important due to the rise in the supply chain and increased demand for biopharma manufacturing, which was in part a result of the uptick in activity due to the COVID-19 pandemic. We feel that investing in and securing these capabilities now will help us to best serve this program moving forward. In addition to our in-house antibody engineering platform that is developing antibodies to selectively target distinct domains of NRP2, our Hong Kong subsidiary Pangu is working on a bi-specific approach based on role in regulating inflammatory processes and interaction with various co-receptors. We believe that bi-specific antibodies present a unique approach to create highly specific agonists in the system, which may be therapeutically relevant in certain disease states. Last year Pangu together with the Hong Kong University of Science and Technology or HKUST was awarded a grant of approximately $750,000 from the Hong Kong government Innovation & Technology Commission, the high throughput platforms for the development of bi-specific antibodies targeting NRP2. We are pleased to have announced this week that Pangu and HKUST have achieved a milestone set forth in the first year of the project. An integral part of this project was the development and implementation of a novel single-cell antibody discovery approach, which has so far yielded numerous candidate high affinity NRP2 co-receptor antibodies targeting VEGFR2 and PLXNA1 currently same screen and functional assets. Bi-specific antibody approaches are increasingly being considered as a novel and differentiated approach to relevant targets and present a unique pipeline opportunity for us to explore. We are very excited about this progress thus far and look forward to the outcome of the second year of this project. With that, I will turn it over to our Chief Financial Officer Jill Broadfoot to review our financial results.

Thank you, Leslie. Total revenues were $0 and $8.1 million for the three months ended March 31st, 2021 and 2020, respectively. Revenues for the three months ended March 31st, 2020 consisted primarily of license and collaboration agreement revenues under company’s license agreement with Kyorin. Research and development expenses were $4.5 million and $3.6 million for the three months ended March 31st, 2021 and 2020, respectively. The increase was due primarily to manufacturing costs related to 1923, increased research and development expenses related to 2810, and increased expenses related to the research program between Pangu, HKUST and the Hong Kong government. General and administrative expenses were consistent between periods at $2.7 million and $2.6 million for the three months ended March 31st, 2021 and 2020, respectively. During the first quarter of 2021, the company raised gross proceeds of $9.9 million through its at-the-market offering program with H.C. Wainwright & Co., LLC and $15.3 million through its common stock purchase agreement with Aspire Capital Fund, LLC. As of March 31st, 2021, we had $50.6 million in cash, cash equivalents, and investments. We expects our expenses to continue to increase in 2021 as research and development of 1923 and 2810 progress. This includes additional manufacturing costs for both 1923 and 2810 to prepare for future clinical trials. Now, I'd like to turn the call back over to Sanjay before we open it up to Q&A.

Thanks Jill. Our accomplishments this year to-date reflect the hard work, dedication, and thoughtful approach that we have invested in our clinical pre-clinical programs. The readout for our Phase 1b/2a proof-of-concept study of 1923 and pulmonary sarcoidosis represents a key inflection point for a -- really solid foundation for and invested heavily in a robust portfolio of translational work for 1923, which we believe presents a strong rationale for its potential in incredibly -- implementing the same thoughtful and [Indiscernible] for 2810, regenerate pre-clinical data and evolving our understanding of the mechanism of action to inform our clinical strategy in cancer. We have sufficient capital to take us through the readout, in pulmonary sarcoidosis and launch a Phase 2 trial 2810 and cancer, which supports our ongoing activity to generate value for the company as we progress throughout the year. We appreciate your interest and continued support and look providing you updates in the future. At this time, Jill, Leslie, and I would be happy to take your questions.

[Operator Instructions] Your first question comes from the line of Hartaj Singh from Oppenheimer. Your line is open.

Thank you. Hi, everyone. Good afternoon. It's Jackie in for Hartaj. Thanks for taking our questions. First, just the upcoming readout, I remember when last year you announced the trial got slowly recruited, I think that show study enrolled 36 patients, today's trial study show 37 patients. So, maybe first, just wondering is that some patient dropped and then you reenrolled additional patients? And then second, obviously 37 is not an even number, I was just wondered, which that additional patient kind of fit into your treatment or placebo group, which cohort that person really are? And third, are you going to announce the last patient last visit? Thanks.

Sure. Thanks Jackie. So, we have previously announced that we had met target enrollment. At that time, as you can imagine, several patients are in the queue. One additional patient at that time -- final count is 37, I think ethically would be difficult to turn away a patient that's being eligible and passed through screening. So that occurred right at that time when we were announcing that we met target enrollment. So, the final enrollment is 37. Your second question is really around which cohort, they have not been assigned backwards into our one or three milligram cohort, they are in our five milligram cohort. So, the most important point here is, it's not a backfill, it's simply a patient that, as I said, had moved through screening at the same time as our 36 patients and therefore, we really want to do the right thing and allow that patient to join. So, over enrolment, not a big issue, not anything really tactical, but really more around clinical operations ethics. With regard to last patient last visit, that’s something we'll consider, I think the main thing is we're on target to have full readout here in the third quarter. And that's really what we're focused on is that 37 patients to basically finish up those things, and any follow-up visits and I think we're very much on track to have a Q3 readout.

Got it. Thank you for that. And then great event with Sarcoidosis Foundation last night -- side effects of steroids. And if you could talk a bit more on the side effects, those non-steroidal [Indiscernible] drugs, both short-term and long-term? And then second, thinking about your upcoming third quarter readout, what types of data should we be expecting there, will be a steroid reduction, time to achieve that, or different -- those cohorts, if you could help us frame that talk by release that would great.

Yes, great questions about some of the toxic effects, you heard quite a bit about what steroids can do from a patient's highlighted -- one patient in particular on that call, really talked a lot about weight gain and some of the other mood and irritability, insomnia effects. So, many of the things that we see in steroids, we know are quite toxic to these patients. In those patients that have moved on to even the more heavy hitting immunosuppressant, that's really where you get even scarier complications, things as a higher degree of infection risk, malignancy is also a concern once you actually move to those agents, many of those agents were actually originally approved for chemotherapy. So, you're really talking about a heavy, toxic burden of some of those more subtle toxic immunosuppressants that these patients had to advance to. So, there's a tremendous amount of interest and it's growing and it's accelerating to therapy, which I mentioned, I think, is something that could be rather transformative in changing the paradigm and how we treat sarcoidosis. One of the ways and probably the most important way we're going to be looking at it from an activity standpoint is the focus on steroid burden. The experts have said this is a key way that they will burn around the -- and feel good about the activity of 1923. But we will be looking at things here and highlighting these things really in the upcoming months around what to expect with regards to percentage reduction, we'd like to see absolute reduction, we'd like to see a cumulative burden over six months, how much better we can [Indiscernible]. So, these are all the things that we're focused on. We'll look to actually have a potentially another event to really set the table here around expectation. So, from what I can understand from the experts, they are looking for that signal of steroid reduction in this trial. And I think that really increased a tremendous amount of clinical confidence as we move into Phase 3 if we were able observe that in our current trial.

Got it. That's very helpful. And then last question is, I saw a press release earlier this week that bi-specific candidate coming from University of Hong Kong, you talk about the rationale -- European tour involving bi-specific format, what kind of advantages you can avail versus, I guess, put in some combination therapy more specific format.

Yes, I'll comment even ask Leslie to chime in as well. But our strategy is really as we understand current biology, we like much of our in-house, which is, of course, working on targeting specific episodes to neuropilin-2 and tuning the biology just looking at neuropilin-2. [Indiscernible] also informed us that your colon is a really interesting receptor, and that it can quarterback other interactions with other receptors, such as toxins, integrins, other VEGF receptors that Leslie pointed out. So, how do we leverage and learn more about that mechanism and potentially even create new types -- this is why the Pangu collaboration doing is basically bring in non-dilutive capital from the Hong Kong government, on the bi-specific approach is really exciting. And I think it offers us another opportunity to create a new pipeline of discovery candidate by really understanding and mining that side of the biology. Leslie, do you want to add anything about just some of the opportunities and some of those other receptor engagement with neuropilin-2?

Sure, Sanjay. I mean, I think one important aspect of this as well is that it provided us an opportunity to expand our antibody engineering into the bi-specific realm, and to bring on some really cutting edge technologies and advanced some of those things forward with some non-dilutive funding in the grant -- under this grand scheme that we have, is really about setting up a platform. But Sanjay is absolutely right that if you're thinking about NRP2 as a receptor, it is actually coming together with these other types of co-receptors, there are novel ways to actually sort of tune those reactions and create agonists. So, most of the time with our mono-antibody or monoclonal antibodies, we're going to be blocking the natural ligand of NRP2. In this case, we can actually bring the receptors together, the co-receptor and NRP2 itself to derive some of that signaling. And so in certain disease states, for example, you may want to [Indiscernible] and that actually drives a response in that net capacity. So, it lets us come at it from the other side of the coin as well.

I'll just add one -- I'll just add one other thing. A bi-specific approach -- a few bi-specifics on the market, but we've seen already that market at close to eventually $20 billion in the quarter when you think about bi-specifics. So, it's really, a technology [ph] for us to look into this platform approach -- bi-specific approach. And the fact that we can do with accessing these grants with the Hong Kong government, I think is a smart way for us to tap into what could be a really large commercial opportunity in the future.

Great. Thanks for all the color and really appreciate all the questions. Thank you.

Next question comes from the line Emanuela Branchetti from H.C. Wainwright. Your line is open.

Good afternoon, guys and thank you for taking my question. And happened before to me, so while waiting for the data in fact, with higher 1923, and the potential pivotal trial, are you guys planning to do any formulation work to explore the possibility of a different formulation for a ATYR1923 other than--

Hi Emanuela. So, that's a great question. I think as a small company, we want to establish proof-of-concept with our IV administration. But I think from a patient perspective, certainly, once a month therapy is great, but then very quickly, from a lifecycle point of view of these patients who wants something perhaps that could be administered even easier than that. When you look at when you look at subcu administration, a lot of companies as they advancing in their lifecycle planning, they consider things like that. I think from a formulation standpoint, your question makes a lot of sense -- strategy. But I think first things first, we're going to establish proof-of-concept here then absolutely we can look at formulations that -- even make therapy more attractive to patients, perhaps a subcu administration that could be administered every three to six months. That's what you see with some of the therapies as they advance in lifecycle planning.

Sure. Thank you for that. And with regards to the fight throughputs platform being developed by Pangu, should we expect multiple INDs coming forward from this program? And can you give us a sense of your expectation in terms of timelines? Also, how should we see potential clinical development entities assets? Would they start in China and then move to the U.S. or have you -- I know, it's certainly, but have you -- can you share your thoughts on this?

Yes, it is early. I like the way you're talking. We definitely think that this is an area. We tend to really start to understand the biology and then start to advance our discovery thinking, but the goal here really is to be described, we'd like to be able to identify a discovery opportunity that leads to an IND candidate from this platform. I think there's an ability to do that. I hesitate to put a timeline on it just right at this moment, because we have just gotten through the first step of this milestone. But I do think that as we look to provide updates during the future, that's the kind of things to pay attention to. Do we have a discovery candidate in the work thereby specifically? With regard to development, I think, it's a little bit too early to say with regards to how we would interface with China. Hong Kong is a little bit of a different situation, although, it is becoming much more -- you have to think about it a little bit more as the -- those connection to Mainland is a little stronger here. But I think that's a strategy that we'll be working on and we'll be getting back to you. We would like to actually emerge with a new discovery pipeline candidate from that platform.

Sure. Thank you. And, again, another maybe forward looking question. When looking at the results reported the AACR in the triple-negative breast cancer models, ATYR2810 seems to inhibit tumor growth when used in conjunction with cisplatin and bevacizumab. So you talk more before about the mechanism of action behind these effects. But how do you think the drug would be better positioned for the treatment of triple-negative breast cancer, should you decide to move forward with the clinical development in this population?

Sure. And again, I'll have Leslie chime in here, but clearly a very aggressive form of cancer where we still have a lot of room to improve efficacy. We made really amazing strides in the last couple of years treating TNBC. There's quite a bit of resistance and also still develops. And I think what we are learning is our drug can add utility, not only to have that tumor inhibition and growth, but you're also seeing quite a bit of exciting data that can help patients who might become resistant to existing therapy. And that we have a mechanistic understanding of how that might be occurring. So Leslie can also add some of her thoughts more specifically about that data.

Yes, absolutely. So we have a number of different types of aggressive solid tumors. And we've made the most amount of -- we generated the most amount of data specifically in triple-negative breast cancer, because of our strong connection with UMass and Dr. Arthur Mercurio’s lab, where they have a strong focus there. So that is where we're getting a lot of early data coming out that you're seeing. And I think Sanjay captures it very well. And this is a very aggressive type of tumor that has very high NRP2 expression, and has a lot of issues with resistance to current therapies. And so we're seeing especially interesting to me is that tumor organoids that we see. So we are directly patient derived tumor organoids, where we're seeing a response of sensitizing the tumor organoids to these chemotherapy or bevacizumab type treatment, conventional therapies. And we're understanding the mechanism in those organoids and able to see gene changing that are indicating the processes surrounding ENT, or this development of a stem cell are being reversed in the presence of 2810. And so we're starting to piece together that mechanism and figure out that that will be -- that is a potential population that could be really be helped with something that could do that in particular.

Got it. Got it. Thank you very much.

Your next question comes from the line of

Hi, guys. Thanks for taking my questions, and congrats Leslie, really exciting for you. Just have a couple of questions. I think just follow-up to some of the questions that have been asked. I think the first one for me, is in terms of relationship with Pangu, just wanted to make sure that you're retaining full rights to the bi-specific platform, or is that some kind of agreement that you have in place?

Yes. Certainly, that's a great question,

Thank you. And then the next one, again, another follow-up for 1923. I know we're still waiting for the data, but like someone else alluded to the call that you participated on was really good in terms of really articulating the concerns about using steroids in patients with pulmonary sarcoidosis. And so I was just wondering, that's kind of how this Kyorin study is set up in terms of figuring out if patients who use less steroids, I was just wondering if that's probably going to be the same setup for your Phase 2, 3 potentially pivotal study?

Yes. I think we are well to -- basically interrogate an endpoint that is accelerating in its validity that something that may -- really need to look at closely. I think you've heard the FSR that they are spending quite a bit of time with the FDA, educating them with Mary over their new CEO, around working in clinical meaningfulness causes endpoint, plus get off steroids. We always thought that at the doses we’re looking at 10 milligrams or higher, that was certainly the case, but I think what you heard on the call is, some patients now, they don't want to go on steroids at all. So very quickly, I think our therapy is being looked at as a first line therapy, something that we can -- corticosteroids standard approach. But there's more and more momentum, we just have a better alternative with steroids, based on proof of mechanism in particular, I think, our therapy, as I said, could be transformative here as a first line option for sarcoidosis patients, especially given the fact that we thus far demonstrated really a great safety profile. And I think we're poised well in the sense of this endpoint is becoming more and more spotlighted by the FSR.

Thanks, Sanjay. And then the last follow-up here, just on your efforts with your NRP2 antibody got excited with the AACR data then the partnership with Lonza. I was just wondering what else is left to kind of be done for the IND? And then lastly, adding comments on some of the discovery efforts with CSL Behring, I think at one point you guys mentioned, focusing on NK cell biology. I just wonder any updates on that because that sounded really exciting?

With regard to what our next steps for the neuropilin program, as I said, we'd like to get in to -- we expect to be inincredible progress here in cancer. So as we continue to look at different in vivo models, tumor models, we know neuropilin is implicated in a number of different tumor sides. So we'll can take that a few other models. And that will then allow us to basically focus in on where we have our best effects to where we think our best indication should be for our first cancer trial. So I think that what you can expect to see as the active for the remainder of the year with a follow on data, which then should focus everyone's attention to, okay, this is where 2810 has its best utility. And here's the best opportunity to really help patients who will be finishing some of that translational work throughout the course of this year. We'll complete some of that toxicology work that is required before we actually move into the clinic. And this is another reason why it was important for us to highlight the Lonza collaboration because we're working with the preeminent, if you will, CDMO out there, very important for us to actually get that relationship locked up. So we can actually have really clinical material ready to go into the clinic. Also important right now, I think a lot about the companies are estimating the supply chain demand with manufacturers. So for us to get ahead of that, it's not something we hear a lot about, and companies talk about, because I think they're struggling with their ability to actually engage and plan ahead with those with CDMO. So this is not going to slow us down. And we are really thrilled to have a top notch like Lonza. With regard to some of the findings we put out earlier this year with NK cell, we have still a lot of interest there to mature some of those findings and getting receptive candidates, we want to be transparent about that, put that out in some form of publication or abstract. So that's tracking well. I think the important thing there is, we're now in the process of validating those receptor targets on them. We like to be very, very thoughtful and make sure that we cross all the T's, dot all the I's there. But I aspect they would change from that program as well to be able to highlight what I think is going to be our next receptor target, much like we did in the neuropilin-2 a few years ago. I think that's what's in the cart there for that program.

Perfect. Thanks again and congrats on this.

[Operator Instruction] Your next question comes from the line of Yale Jen from Laidlaw. Your line is open.

Good afternoon, and thanks for taking the question. Just want to -- first question is about the 1923. Just a little bit forward looking questions, which is that, if the readout on the third quarter is robust, I assume you guys going to advance into a potential pivotal study. My question is that if the steroid-sparing type of endpoint could be accepted by the a primary endpoint or you need to conduct more functional type of endpoint plus the way to potentially gain approval?

Yeah. Thanks, Yale for the question. Certainly, our plans and this will involve interaction with the FDA to propose and move aggressively into a pivotal trial. I think when you talk about a rare disease like some patients don't have a lot of time to wait. And we set on a lifecycle of 10 years of running trial here. Many of these folks need therapy today. Secondly, we know and we're learning more and more as these patients want to desperately get off steroids. And the ones that are newly diagnosed don't want to be put on steroids. So it's easy. The second question, there's ever a time for the regulators to really look seriously at steroid-sparing certainly as the primary end point. I can tell you that in the years I've been involved in this program, there is significant momentum moving in that direction. And this is the reason why engaging more with the patient community, how we have done this internally, bringing in Andrea, as a patient advisor, and also the FSR is focused on highlighting the toxicity of steroids here. I think it sets up really well for us to have a discussion with the regulators and say this action should now be thought of more as a primary endpoint. So I think right now, what the outcomes of those discussions will be with worldwide regulators. But I will say that right now, the momentum is really building for a steroid reduction endpoint to be at a minimal part of a composite primary endpoint. I think it sets up really well for us as we've been focusing on endpoint --.

Okay. Great. That's very helpful. And another question is that the -- for 2810, which is involved in a process called EMT you mentioned and that seems to be a space very few competitors at least, we cannot find any. Do you have any comments in terms of you guys find either so competing program also in this space, or you are potentially could be the first-in-class therapy, if successful?

So Yale, we're cutting-edge science companies, we literally came out of Paul's lab. Paul has been a tremendously successful scientific entrepreneur, talk to you about the founding of mylamin [ph], Cubist and replica in places like, so we were not afraid to be bold around some of the times as long as it makes sense and we can see it mechanistically. So our findings for me in two year, we're really excited about that. We think and some authors have even said that this could potentially be a backbone type of therapy, if we are remodulating some of those mesenchymal cells, that that as Leslie pointed out to stemless there. We significantly can make leaps here in cancer and attack resistance. So I do think that it's an area that we think is very much untapped. Our biology is pointing us on mechanistic understandings pointing us in that direction. So we're going to follow it. And I think, again, we get the lead here, potentially an area where even at ACR, is in this last meeting in the meeting for that you see more and more interest in EMP. So perhaps in about five years, this will be an area where we can teach some other companies what we've learned about it. So stay tuned for that. I really think that that's an interesting area that Leslie certainly is going to be working hard on.

Okay, great. And maybe the last question here is all your bi-specific approach. I understood the NRP was not necessarily an IO immune oncology therapies. But given that the -- they generally work in the tumor microenvironment, in terms of device specific would it be consider one of the by target will be -- will could be in any kind of checkpoint related or other type of immune related targets? I don't know whether that make any sense as a consideration? And thanks.

No, that makes sense to me, for sure. And I'm going to have Leslie, say something as well here. But the colocation we don't want to does here is the other receptors I like to aggregate and co locate next to neuropilin-2. So it's very much a quarterback that we can we create a by specific essentially to agonies and create a bridge and say another receptor, you are absolutely right, this could be another asset that we could turbocharge an immune response, if you will an attack cancer cell. But we have to understand that mechanistically improvement. So I think this is really part of our scientific rationale. And it's why we were able -- we were awarded the grant because I think the letters I pointed everything in that direction, now we're working to basically build a candidate that, we may exactly do what you say here. Leslie, do you want to add anything for you?

Absolutely. So you know, I think we alluded to it a little bit as we walked through the call today around this expression that we see for NRP2 on these T cells that are located in the tumor microenvironment. So not only the tumor cells itself, but also tumor-associated and myeloid-derived suppressor cells to name a couple of them. So we presented a poster earlier this year out of Keystone where we walk through that with. And we're definitely in a mode of heavy investigation to understand the role for neuropilin-2 on those cells and how that might be interplaying with the activity and what's happening with these more mesenchymal epithelial cells of the tumor. So I think, it's stay tuned, we're heavily at work on that and really investigating it. And I think the mechanism itself will bear out whether or not it makes sense to go at that with advice specific approach or whether there's really a monoclonal strategy that can work as well. So we're -- as Sanjay said, we try to be cutting edge and on really open to new science and let the mechanism in the data drive us where we should go. And so I think we're very open to the best way to drug these targets. And so, stay tuned.

Okay, great. Thanks a lot. And again, congrats on the progress so far.

And there are no further questions over the phone line at this time. I would like to turn back the call over to Sanjay Shukla, sir.

Thank you. Great questions today, obviously a large interest in not only our clinical program, but the advances we're making in neuropilin biology or bi-specific platform and Pangu as well. I think many of you have picked up on really intriguing new area that opens up a lot of potential for our pipeline. Really appreciate the questions and interest from everyone today, looking forward to speaking to you on future calls. So thanks, everyone, be well.