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. 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 Dr. 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 preclinical program for ATYR2810 and our bispecific 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, preclinical, and research and discovery programs. We remain focused on advancing our lead therapeutic candidate, ATYR1923 or 1923. With enrollment completed in our Phase Ib/IIa clinical trial in pulmonary sarcoidosis, our initial 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 II clinical trial in COVID-19 severe respiratory complications, we look forward to the pulmonary sarcoidosis trial readout expected in the third quarter of this year.
We generated additional preclinical data for ATYR2810 or 2810, our anti-Neuropilin-2 or NRP-2 antibody in preclinical development for cancer. As we begin, I'll summarize a few additional highlights since we last spoke in March. We appointed leading sarcoidosis advocate Andrea Wilson, Co-founder and Former President and member of the board of directors of the Foundation for Sarcoidosis Research, or FSR, as patient advisor to the company. In collaboration with the FSR, we participated in a virtual town hall on steroids and sarcoidosis to discuss the burden of steroid treatment and the need for new therapeutic options. We presented two posters at the annual meeting of the American Association for Cancer Research on preclinical data for 2810 in models of triple-negative breast cancer and non-small cell lung cancer.
We entered into an agreement with Lonza, a leading contract development and manufacturing organization, for the manufacture 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's Innovation and Technology Commission to develop a high-throughput platform for the development of bispecific antibodies targeting NRP-2. 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. Highly encouraged by what we've accomplished this year thus far, I look forward to building on Hong Kong's programs and discovery pipeline from our novel biology platform as we move 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 down-regulates aberrant immune responses in inflammatory disease states. 1923 has been shown preclinically to down-regulate inflammatory cytokines and chemokines signaling, and reduce inflammation and fibrosis. NRP2 is upregulated on key immune cells known to play a 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 alleviating 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 is 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 left untreated, it can lead to irreversible scarring and diminished lung function. Current treatment options are limited and often include treating the inflammation with corticosteroids and other immunosuppressive therapies, which have limited efficacy and 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 a better efficacy and side effect profile. We recently spent some time deepening our understanding of the need for new treatment options for patients with sarcoidosis, including alternatives to steroids. We've made a concerted effort to better recognize the needs of the community.
As part of these efforts, we have appointed Andrea Wilson, sarcoidosis patient and 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 sarcoidosis patients, and previously served as president and a member of its board of directors. Her firsthand knowledge as a patient, combined with her long-standing advocacy experience and relationship with the sarcoidosis community, will help support patient strategies for advancing our 1923 clinical program in pulmonary sarcoidosis, and we look forward to her contributions in the future.
Additionally, April was Sarcoidosis Awareness Month, and as part of our efforts to bring 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 block provided a real-world and firsthand perspective, highlighting the toxic effects of steroids and shedding a light on the need for better and more effective treatments. 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 edema. Nearly each of these side effects on their own are a condition to treat and manage.
Currently used steroid-sparing agents such as cytotoxic immunosuppressants have limited clinical evidence supporting their use in sarcoidosis and are associated with significant side effects such as infection, liver toxicity, and even malignancies. We believe that patients deserve better. 1923 presents a potential option to do better. In clinical studies to date, 1923 has shown a favorable safety profile.
This includes data from a phase I study in healthy volunteers, a phase II study in patients with COVID-19 related severe respiratory complications, and two independent data safety monitoring board reviews from the ongoing phase Ib/IIa 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 and its 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 a phase Ib/IIa 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 or 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 the assessment of potential steroid-sparing effects of 1923. 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, an integral element of the study is to assess steroid burden in the 1923 treatment groups compared to placebo.
As we have discussed here a bit today, due to the side effects and toxicity of currently available treatments, there is 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 the third quarter of this year.
I'd like to now turn the call over to Dr. Leslie Nangle, Vice President, Research. As I mentioned, we recently promoted Leslie to the company's executive leadership team to manage research and scientific operations. Leslie has dedicated her career to tRNA synthetase biology and the pathways they regulate. Having studied under Dr. Paul Schimmel, 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 operations, 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 collaborators. I'll begin with a bit of background about NRP2, which is a compelling therapeutic target in a 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 is 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 suppressor cells, among others. High NRP2 expression has been linked to worsened 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 of antibodies to selectively target distinct domains of NRP2, including those interacting with semaphorins, VEGF, and certain chemokines such as CCL21.
The role of NRP2 and VEGF signaling in the tumor microenvironment and its importance in the progression of certain aggressive cancers is becoming increasingly validated. 2810, a fully humanized monoclonal antibody developed and optimized internally by our antibody engineering team, specifically and functionally blocks the interaction between NRP2 and VEGF. Based on compelling preclinical data in oncology models, both human-derived and animal, we've 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 meeting, which build upon our preclinical work related to 2810 and strengthen our understanding of the blocking VEGF-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 blocking NRP2 VEGF signaling in tumor cells can inhibit tumor growth and metastasis. These mechanistic 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 these cells. EMT is of great importance in the tumor microenvironment, regulating tumor growth, progression, and metastatic cascade, as well as being implicated in tumor evasion of the immune system.
The data we presented demonstrate the therapeutic potential of inhibiting EMT through blocking the NRP2 VEGF signaling axis 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 tumor cells to widely used anti-cancer therapeutics, including the chemotherapeutic agent cisplatin or the targeted VEGF therapy bevacizumab, increasing the anti-tumor effects of each agent. Furthermore, treatment with 2810 was shown to downregulate genes associated with EMT and stemness, in particular downregulating the expression of ZEB1, a central regulator of these processes. This data suggests that 2810's ability to impact EMT may be one mechanism by which it 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 therapy resistance, which is associated with tumor recurrence and metastasis, is a major challenge for patients with aggressive cancers. We continue to investigate 2810 and its ability to block the NRP2 VEGF signaling axis, 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 xenografts, at the upcoming Keystone Symposia on Cancer Stem Cells scheduled for later this month. We are very pleased with the preclinical 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 in the 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 advancement to clinical trials in the future. As we continue with our IND-enabling activities for 2810, 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 manufacture 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-NRP-2 antibody. Having a manufacturing commitment at this stage of development for 2810 is especially important due to the recent trends in the supply chain and increased demand for biopharma manufacturing, which is 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 NRP-2, our Hong Kong subsidiary, Pangu, is working on a bispecific approach.
Based on NRP-2's role in regulating inflammatory processes and interaction with various co-receptors, we believe that bispecific antibodies present a unique approach to create highly specific agonists of 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's Innovation and Technology Commission to build a high-throughput platform for the development of bispecific antibodies targeting NRP-2.
We are pleased to have announced this week that Pangu and HKUST have achieved the milestones 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 candidates, candidate high-affinity NRP-2 co-receptor antibodies targeting ErbB3 and Plexin A1, currently being screened in functional assays.
Bispecific 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 31, 2021, and 2020, respectively. Revenues for the three months ended March 31, 2020, consisted primarily of license and collaboration agreement revenues under the license agreement with Kyorin. Research and development expenses were $4.5 million and $3.6 million for the three months ended March 31, 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 31, 2021, and 2020, respectively.
During the first quarter 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 31, 2021, we had $50.6 million in cash equivalents, and investments. We expect our expenses to continue to increase in 2021 as research and development of ATYR1923 and ATYR2810 progress. This includes additional manufacturing costs for both ATYR1923 and ATYR2810 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, preclinical, and discovery programs. The readout for our phase Ib/IIa proof of concept study of 1923 in pulmonary sarcoidosis represents a key inflection point for aTyr, and we have laid a solid foundation for and invested heavily in a robust portfolio of translational work for 1923, which we believe presents a strong scientific rationale for its potential in inflammatory lung disease. We're implementing the same thoughtful and building block approach for 2810 as we generate preclinical data and evolve our understanding of its 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 II trial for ATYR2810 in 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 forward to providing you updates in the future. At this time, Jill, Leslie, and I would be happy to take your questions.
Your first question comes from the line of Hartaj Singh from Oppenheimer. Your line is open.
Hi. Thank you. Hi, everyone. Good afternoon. This is Jackie for Hartaj. Thanks for taking our questions. First, just on the upcoming readout. I remember when last year you announced the trial got fully recruited. I think that press release showed the study enrolled 36 patients, and today's press release showed 37 patients. Maybe first just wondering, is that some patient dropped and then you re-enrolled additional patient? Second, obviously 37 is now an even number. I just wonder which that additional patient going to fit into your treatment or placebo group and which cohort that person will be on. Third, are you going to announce the last patient last visit? Thank you.
Thanks, Jackie. We had 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 was eligible, therefore, our final count is 37. I think ethically it would be difficult to turn away a patient that's already been deemed eligible and has passed through screening. That occurred right at that time when we were announcing that we met target enrollment. 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. The most important point here is it's not a backfill. It's simply a patient that, as I said, had moved through screening pretty much at the same time as our 36 patient.
Therefore, you really want to do the right thing and allow that patient to join. Over enrollment, 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 readouts here in the third quarter. That's really what we're focused on is getting that 37 patient to basically finish up dosing and any follow-up visits. I think we're very much on track to have a Q3 readout.
Yeah. Got it. Thank you for that. Great event with Foundation for Sarcoidosis Research last month, educating the side effects of steroids. If you could talk a bit more on the side effects of those non-steroidal anti-inflammatory drugs, both short-term and long-term. Second, thinking about your upcoming third quarter readout, what types of data should we expecting there be, like steroid reduction, time to achieve that, or all different those cohort? If you could help us frame that top-line release, that would be great.
Yeah, great questions about some of the toxic effects you heard quite a bit about what steroids can do and from the patients 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. Many of the things that we see in steroids, we know they're quite toxic to these patients. In those patients that have moved on to even the more heavy-hitting immunosuppressants, that's really where you get even scarier complications, things such 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. You're really talking about a heavy toxic burden of some of those more cytotoxic immunosuppressants that these patients have to advance to.
There's a tremendous amount of interest, and it's growing and it's accelerating to have a therapy like ours, which I mentioned I think is something that could be rather transformative in changing the paradigm on 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 learn and feel good about the activity of 1923. We will be looking at a number of things here, and highlighting these things in the upcoming months around what to expect with regards to percentage reduction that we'd like to see, absolute reduction we'd like to see, cumulative burden over six months, how much better we can do versus placebo. These are all the things that we're focused on.
We'll look to actually have potentially another event to really set the table here around expectations. From what I can understand from the experts, they are looking for that signal of steroid reduction in this trial, and I think that would really increase a tremendous amount of clinical confidence as we move into phase III, if we were able to observe that in our current trial.
Got it. That's very helpful. The last question is, I saw your press release earlier this week on that bispecific candidate coming from your subsidiary in Hong Kong. Can you talk about the rationale, getting your team to involve in a bispecific format? What kind of advantages you can unveil, versus, I guess, putting some combination therapy in mono specific format?
Yeah, I will comment, and I may even ask Leslie to chime in as well. Our strategy is really as we understand Neuropilin-2 biology, we like much of our in-house work, which is of course working on targeting specific epitopes to Neuropilin-2 and tuning the biology just looking at Neuropilin-2. The literature has also informed us that Neuropilin-2 is a really interesting receptor in that it can quarterback other interactions with other receptors, such as plexins, integrins, other VEGF receptors that Leslie has pointed out. How do we leverage and learn more about that mechanism and potentially then create new pipeline opportunities? This is why the Pangu collaboration and our ability to basically bring in non-dilutive capital from the Hong Kong government on this bispecific approach is really exciting.
I think it offers us another opportunity to create a new pipeline, a 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 with some of those other receptor engagers with Neuropilin-2?
Sure. Sanjay. I think one important aspect of this as well is that it provided us an opportunity to expand our antibody engineering into the bispecific realm and to bring on some really cutting-edge technology and advance some of those things forward with some non-dilutive funding under this grant scheme that we have. It's really about setting up a platform. Sanjay's absolutely right.
That if you're thinking about NRP2 as a receptor and the fact that 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. Most of the time, with our monoclonal antibodies, we're going to be blocking the natural ligands of NRP2. In this case, we can actually bring the receptors together, the co-receptor and NRP2 itself, to derive some of that signaling.
In certain disease states, for example, you may want a semaphorin mimetic that would actually drive a response in that capacity. It lets us come at it from the other side of the coin as well.
Yeah. I'll just add one other thing. A bispecific approach, obviously, there's just a few bispecifics on the market, but we've seen already that market at close to potentially $20 billion that has been quoted even this week when you think about bispecifics. It really, I think it's smart strategy for us to look into this platform approach, a bispecific approach. The fact that we can do this by 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 a lot, Connor, and really appreciate all the questions. Thank you.
Your next question comes from the line of Emanuela Branchetti from H.C. Wainwright. Your line is open.
Good afternoon, guys, and thank you for taking my questions. A couple for me. While waiting for the data in fact with those with ATYR1923 and the potential pivotal trial, are you guys planning to do any formulation work to explore the possibility of a different formulation for ATYR1923 other than IV?
Hi, Emanuela. That's a great question. I think as a small company, we want to establish proof of concept with our IV administration. I think from a patient perspective, certainly, a once a month therapy is great. Very quickly from a life cycle point of view, these patients will want something perhaps that could be administered even easier than that. When you look at subq administration, a lot of companies, as they advance in their life cycle planning, they consider things like that.
I think from a formulation standpoint, your question makes a lot of sense as a strategy. I think first things first, if we can establish proof of concept here, then absolutely, we can look at new formulations that I think would even make therapy more attractive to patients. Perhaps a subq administration that could be administered every, say, three to six months.
That's what you see with some of the therapies as they advance in life cycle planning.
Sure. Thank you for that. With regards to the high-throughput platform being developed by Pangu, should we expect multiple INDs coming forward from this program? Can you give us a sense of your expectation in terms of timelines? Also, how should we think about the potential clinical development of these assets? Would this start in China and then move to the U.S.? I know it's early, but can you share your thoughts on this?
Yes. It is early. I like the way you're thinking. 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. The goal here really is, as you 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. I do think that as we look to provide updates here in the future, that's the kind of things to pay attention to. Do we have a discovery candidate in the works, a bispecific antibody?
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 you have to think about it a little bit more as the connection to Mainland is a little stronger here. 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. 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. You talked more before about the mechanism of action behind this effect, 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. 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've made really amazing strides in the last couple of years treating TNBC, but there's quite a bit of resistance that also still develops. I think what we are learning is our drug can add utility to not only some of 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 therapies. We have a mechanistic understanding of how that might be occurring. Leslie can also add some of her thoughts more specifically about that data.
Yeah, absolutely. We are looking at a number of different types of aggressive solid tumors, and we've 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.
That is where we're getting a lot of early data coming out that you're seeing, and I think Sanjay S. Shukla captured it very well in that this is a very aggressive type of tumor that has very high NRP2 expression and has a lot of issues with resistance in patients, resistance to current therapies. What we're seeing, especially interesting to me, is the tumor organoids that we see. These are directly patient-derived tumor organoids where we're seeing a response of sensitizing these tumor organoids to these chemotherapy or bevacizumab-type treatment conventional therapies.
We're understanding the mechanism in those organoids and able to see gene changing that are indicating that processes surrounding EMT or this development of a stem cell-like phenotype are being reversed in the presence of 2810. We're starting to piece together that mechanism and figure out that is a potential population that could really be helped with something that could do that in particular.
Got it. Thank you very much.
Your next question comes from the line of Zegbeh Jallah from Roth Capital Partners. Your line is open.
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 bispecific platform, or is that some kind of agreement that you have in place?
Yeah, certainly. That's a great question, Zegbeh. Yes, we are retaining full rights for the work that we do there. I think that's a key component of retaining the value of what we think is a really outstanding opportunity for us to explore bispecifics.
Thank you. The next one, again, another follow-up for ATYR1923. 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. I was just wondering, that's kind of how this kind of study is set up in terms of figuring out if patients are using less steroids. I was just wondering if that's probably going to be the same setup for your phase II-III potentially pivotal study.
Yeah, I think we are poised well to basically interrogate an endpoint that is accelerating in its validity as something that maybe the FDA 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 there as the new CEO around the importance and the clinical meaningfulness of this endpoint. Patients want to get off steroids.
That at the doses we're looking at, 10 milligrams or higher, that is certainly the case. I think what you heard on the call is some patients now, they don't want to go on steroids at all. Very quickly, I think our therapy is being looked at as a first-line therapy, something that we can even, in our mind, we don't have any form of steroid-sparing approach.
There's more and more momentum to just have a better alternative than steroids. Based on our proof of mechanism in particular, I think our therapy, as I said, could be transformative there as a first-line option for sarcoidosis patients, especially given the fact that we've thus far demonstrated really a great safety profile. I think we're poised well in the sense that this endpoint is becoming more and more spotlighted by the FSR.
Thanks, Sanjay. The last follow-up here is just on your efforts with your NRP2 antibody. I got excited with the AACR data, then the partnership with Lonza. I was just wondering what else is left to be done for the IND. Lastly, any comments on some of your discovery efforts with CSL Behring. I think at one point you guys mentioned focusing on NK cell biology, and I was just wondering if you had any updates on that, because that sounded really exciting.
Yeah, with regard to what are next steps for the Neuropilin program, as I said, we expect to be in a clinical trial next year in cancer. As we continue to look at different in vivo models, tumor models, we know Neuropilin is implicated in a number of different tumor settings. We'll continue to look at a few other models, and that will then allow us to basically focus in on where we have our best effects and where we think our best indication should be for our first cancer trial. I think that is what you can expect to see us be active for the remainder of the year with follow-on data, which then should focus everyone's attention to, okay, this is where ATYR2810 has its best utility, and here's the best opportunity to really help patients.
We'll 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. 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 premium clinical material ready to go into the clinic.
Also important right now, I think a lot of biotech companies are underestimating the supply chain demands with manufacturers. For us to get ahead of that, it's not something you hear a lot of biotech companies talk about, because I think they're struggling with their ability to actually engage and plan ahead with those like CDMO.
This is not going to slow us down. We are really thrilled to have a top-tier partner like Lonza. With regard to some of the findings we put out earlier this year with NK cells, we have still a lot of interest there to mature some of those findings and get a receptor candidate. We want to be transparent about that, put that out in some form of publication or abstract. That's tracking well. I think the important thing there is we're now in the process of validating those receptor targets on NK cells. We like to be very thoughtful and make sure that we cross all the T's, dot all the I's there.
I expect big things 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 with Neuropilin-2 a few years ago. I think that's what's in the cards there for that program.
Perfect. Thanks again, and congrats on the progress.
As a reminder, ladies and gentlemen, if you would like to ask a question, please press star, then the number one on your telephone keypad. Again, that is star one. Your next question comes from the line of Yale Jen from Laidlaw & Company. Your line is open.
Good afternoon, thanks for taking the question. First question is about 1923. Just a little bit forward-looking questions, which is that if the readout on third quarter is robust, I assume you guys are going to advance into a potential pivotal study. My question is that, is the steroid-sparing type of endpoint could be accepted by the FDA as a primary endpoint, or you need to conduct more functional type of endpoint as the way to potentially gain approval?
Thanks, Yale, for the question. Our plans, and this will involve interaction with the FDA, is to propose and move aggressively into a pivotal trial. I think when you talk about a rare disease like sarcoidosis, patients don't have a lot of time to wait, and we can't be on a life cycle of 10 years of running trials here. Many of these folks need therapy today. We know, and we are learning more and more. These patients want to desperately get off steroids, and the ones that are newly diagnosed even don't want to be put on steroids.
To your second question, if there's ever a time for the regulators to really look seriously at steroid sparing and a steroid endpoint as a primary endpoint, I can tell you that in the years I've been involved in this program, there is significant momentum of moving in that direction. 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 then also the FSR's focus on highlighting the toxicity of steroids here. I think it sets up really well for us to have a real discussion with the regulators and say, "This actually should now be thought of more as a primary endpoint." I can't predict right now what the outcomes of those discussions will be with worldwide regulators.
I will say that right now, the momentum is really building for a steroid reduction endpoint to be, at a minimum, part of a composite primary endpoint. I think it sets up really well for us that we've just been focusing on this endpoint from the get-go.
Okay, great. That's very helpful. Another question is that for ATYR2810, which is involved in the process called the EMT you mentioned, and that seems to be a space very few competitors, at least we cannot find any. Do you have any comment in terms of, do you guys find other competing program also in this space? Or you potentially could be the first in class therapy if successful?
Well, we're a cutting edge science company. Leslie came out of Paul's lab. Paul has been a tremendously successful scientific entrepreneur. I've talked to you about founding Alnylam and Cubist and Repligen, places like that.
We're not afraid to be bold around some of the science, as long as it makes sense and we can see it mechanistically. Our findings from EMT, yes, we're really excited about that. We think, and some authors have even said that this could potentially be a backbone type therapy. If we are remodulating some of those mesenchymal cells, that as Leslie pointed out, the stemness there, we significantly can make leaps here in cancer, and maybe even attack resistance. I do think that it's an area that we think is very much untapped. Our biology is pointing us, our mechanistic understanding is pointing us in that direction.
We are going to follow it. I think, again, we get to lead here, potentially an area where even at AACR, in this last meeting and the meeting before that, you see more and more interest in EMT biology. Perhaps in about five years, this will be an area where we can teach some other companies what we've learned about it. Stay tuned for that. I really think that's an interesting area that Leslie certainly is going to be working hard on.
Okay, great. Maybe the last question here is about your bispecific approach. I understood the NRP2 is not necessarily an IO immuno-oncology therapy. Given that it generally work in the tumor microenvironment, in terms of the bispecific, would it be considered one of the bi-target could be in any kind of checkpoint related or other type of immuno-oncology related targets? I don't know whether that make any sense as a consideration. Thanks.
No, that makes sense to me for sure. I'm going to have Leslie say something as well here. The colocation, what we know Neuropilin-2 does here is you see other receptors like to aggregate and colocate next to Neuropilin-2. It's very much a quarterback that we can, if we create a bispecific essentially to agonize and create a bridge with Neuropilin and, say, another receptor, you're absolutely right.
This could be another asset that we could turbocharge the immune response, if you will, and attack cancer cells. We have to understand that mechanistically and prove it. I think this is really part of our scientific rationale, and it's why we were awarded the grant because I think the literature and the science pointed everything in that direction. Now we're working to basically build a candidate that may exactly do what you say here.
Leslie, do you want to add anything for Yale?
Absolutely. 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. Not only the tumor cells itself, but also tumor-associated macrophages and myeloid-derived suppressor cells, to name a couple of them. We presented a poster earlier this year at a Keystone where we walked through that work. 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 and epithelial cells of the tumor. I think, stay tuned. We're heavily at work on that and really investigating it.
I think the mechanism itself will bear out whether or not it makes sense to go at that with a bispecific approach or whether there's really a monoclonal strategy that could work as well. As Sanjay said, we try to be cutting edge and really open to new science and let the mechanism and the data drive us where we should go. 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.
There are no further questions over the phone line at this time. Now let's turn back the call over to Sanjay Shukla. Sir?
Thank you. Great questions today. A lot of interest in not only our clinical program, but the advances we're making in Neuropilin biology, our bispecific platform in Pangu as well. I think many of you have picked up on how that could be a really intriguing new area that opens up a lot of potential for our pipeline. Really appreciate the questions, the interest from everyone today. Looking forward to speaking to you on a future call. Thanks, everyone. Be well.
Ladies and gentlemen, this concludes today's conference call. We thank you all for participating. You may now disconnect. Have a great day.