Ladies and gentlemen, thank you for standing by, and welcome to the NextCure R&D Update Conference call and Webcast. At this time, all participant lines are in a listen-only mode. After the speakers' introduction, NextCure will host a question and answer session. Please be advised that today's conference is being recorded. I would now like to hand the conference over to Mr. Timothy Mayer. You may now begin. Thank you, operator. Good evening. My name is Timothy Mayer, Chief Operating Officer. Welcome to NextCure's virtual research and development update conference call and webcast. You can also join this conference call on NextCure's website at nextcure.com. We are using slides to accompany our remarks today, which can also be accessed from the investor relations section of our website. A replay of the conference call will also be available on our website following today's presentation. I'd like to introduce NextCure's President and Chief Executive Officer, Michael Richman, and our recently appointed Chief Medical Officer, Dr. Han Myint, who will also provide remarks today. Michael, Han, Steven Cobourn, our Chief Financial Officer, and I will be available to answer questions as needed. Before I turn the call over to Michael, I'll remind you of the following safe harbor statement. The matters we are discussing today include projections or other forward-looking statements about the future clinical, pre-clinical, and operating results, research and development goals, and future financial performance of NextCure. These statements are estimates based on management's current expectations and involve risks and uncertainties that could cause them to differ materially from actual results. We refer you to the risk factors discussed in our filings with the SEC, including our annual report filed on Form 10-K for the year ended December 31, 2020, and in NextCure's other financial filings. These filings identify important risk factors that could cause actual results to differ materially from those in our projections or forward-looking statements. We undertake no obligation to provide any updates to these forward-looking statements, even if our expectations change. Now I'll turn the call over to NextCure's President and Chief Executive Officer, Michael Richman. Michael? Thanks, Tim, and good evening to everyone. We're thrilled that you have joined us on today's call. We thought it was an opportune time to host a call to provide an update on our two clinical programs, NC318 and NC410. In addition to these clinical development updates, we have continued to push forward on the R&D side, and we are pleased to introduce NC762, a new program today. NC762 is based on strong science and aligns with our focus on developing next-generation immunomedicine to treat cancer and other immune-related diseases by restoring normal immune function. In terms of an agenda, slide three, I'm going to provide a brief introduction, and then I'll introduce you to Dr. Han Myint, who recently joined NextCure as our new Chief Medical Officer. Han will provide some initial remarks and then discuss recent updates on our two lead programs, NC318 and NC410. Tim will introduce our new program, NC762, and finalize the presentation, with an update on our FIND-IO platform. Before jumping in, I also wanted to note that we announced fourth quarter and full year 2020 financial results in our press release today. Thank you, Steve. We aren't going to review the financials in detail, but I did want to highlight that our current cash and equivalents are expected to fund the company into the H2 of 2023. As you will hear in today's call, we expect multiple pipeline milestones to occur between now and 2023. On slide four on NextCure highlights, I'd like to emphasize our fifth anniversary. Since initiating operations five years ago, we have, one, filed three investigational new drug applications for novel immune medicines with unique mechanisms of action. Two, taken two molecules into the clinic, and you'll hear about the third today, NC762. Three, built a GMP manufacturing facility and have produced clinical material to support all of our ongoing clinical work. Four, developed a discovery platform to identify novel proteins that modulate immune activity. We are incredibly proud of this productivity. In slide five, let me quickly walk you through the pipeline. This slide shows the breadth of our current pipeline. By the end of next year, we expect to file an IND for a fourth program. Given the continued productivity of our discovery efforts, we also anticipate filing another IND in 2023. We look forward to disclosing these programs when appropriate. In order to keep today's call somewhat brief, I'm going to let our other speakers provide additional detail. First, I do want to highlight that we have maintained the worldwide rights to all of our programs. In slide six, let me introduce you to Han. I'm very excited to introduce Dr. Han Myint. We conducted a thorough search, and we believe the depth of his expertise in oncology product development will prove instrumental in the advancement of our pipeline. Han has a strong industry track record highlighted by his contribution to several regulatory approvals both in the U.S. and globally. Many of you on the line probably know Han, but as a reminder, he comes to us with over 20 years of biopharma and academic experience, including holding senior roles at both Celgene and Exelixis. In his academic years, he worked at prestigious institutions, including King's College London, Rush University Medical Center and the University of Colorado in Denver. While Han has been with us for less than two months, he has hit the ground running and is already having a substantial impact on our clinical plans. I thought it would be beneficial to have Han provide some brief comments today. Welcome, Han. Thank you, Michael. I'm incredibly thrilled to have joined NextCure. As I was looking at the opportunity back then, I came to realize that the important impact that both NC318 and NC410 could have bring the opportunities for the treatment of cancer. Also look at the pipeline that you have and preclinical program, and those are very exciting for us. As Michael alluded to earlier on, and I am a newbie at NextCure, less than two months old, but with the help of the team here, getting fully up to speed in that short tenure. Even with this introduction by the team here, I'm more and more optimistic about the potential of the pipeline and the platform. I am looking forward to speaking with you all in greater detail in the coming months. Let's start with the NC318 update. I would like to echo Michael's earlier comments about the significant progress that we have made and our enthusiasm going forward. Just a reminder, NC318 targets Siglec-15. In short, we call it S15. You can see from the cartoon that it blocks this S15-induced immune suppression. Siglec-15 is expressed on the tumor cells as well as M2 macrophages, and that led to potently suppressed T cell function, and as NC318 reversed that effect. On the slide eight, I'm going to talk to you about the update of our clinical program. I'm going to highlight two main updates. Top, you can see our current phase II monotherapy continue to accrue. I'll show you some clinical responses in the next couple of slides. Also, we're developing the assay for selecting the patients with Siglec-15-positive tumors. The next is the Yale collaboration. It is a very important collaboration for us because we're looking at NC318 as monotherapy as well as a combination with pembrolizumab, which I will again explain to you more in the next couple of slides. This is the update for the phase II program. You may recall, during the phase I, we have one CR patient and one PR patient. I am glad to report that the CR patient remains on treatment until 118 weeks ongoing, and the PR patient remains on treatment over 92 weeks. Let's draw the attention to phase II part of the program. We give you the update back in December of 2020, and we mentioned the patient with the squamous cell carcinoma of head and neck who has partial response. Now we have a confirmed triple-negative patient who responded. Again, I'll give you more detail in the next slide. I think the exciting thing to note here is that the patient with head and neck patient is now more than lasted for 40 weeks, but now the patient has discontinued. The triple-negative breast patient is still ongoing at 21 weeks. As I mentioned, because of those responses, we are now moving forward to this second portion of the Simon two-stage trial. We are also very pleased to announce to you about the clear validation of the Siglec-15 staining. We will be getting the final results by the end of Q1. Therefore, in the Q2 of this year, we're going to revise our protocol to select Siglec-15-positive patients to enroll in our new amended protocol. Hopefully, we can provide additional clinical results from the NC318 program to you in the fourth quarter of this year. As I alluded to earlier on slide 10, I can show you the two rows you like to look at. The top row is a patient with head and neck cancer. A 53-year-old with multiple lesions, and the patient at that time had a PD-L1 staining was less than 50%, and patient was given different therapies in the past, chemotherapy, three rounds of radiation. Patient was also given nivolumab and pembrolizumab in a different time frame. But within the three-month time frame, patient progressed. You can see from the X-ray from the left to the right, baseline with the right ring around with the red color and the week 24 target lesion has decreased in 37%. That is why patient is recorded as partial response. Next is the second row. The next row after that is a patient with triple-negative breast cancer. This is an unusual case. It's a seven-year-old with a triple-negative breast cancer. Very low PD-L1 staining, less than 1%. Patient had previously been treated with three cycles of chemotherapy, one cycle of radiation. Patient was given pembrolizumab. The best response was stable disease. Patient had a progression. This patient, as I mentioned, had a skin lesion. You can see on the left-hand side, compared to the eight weeks later on the right-hand side. It dropped from 80 millimeter down to 14 millimeter, which is target lesion decreased by 82%. This patient remains to be on treatment. The next one, I'm very excited to tell you about this because you may recall we dropped non-small cell lung cancer in the past. The world authority, Dr. Roy Herbst and Scott Gettinger from Yale, are very excited about our science, and they liaised with Merck and brought pembrolizumab into their study design. What they're trying to do is non-randomized, 3-armed study, and in the monotherapy arm, they're going to select patients who are Siglec-15 positive and PD-1 failure, PD-L1 axis treatment failure population. In the combo arm, what they're going to do is two arms. One arm is PD-1, PD-L1 axis naive patient, and the other arm is going to be those with failed PD-L1, PD-1 failed population. They're going to start accruing in Q2 of this year. Depending on the results, we may be able to add more patient into this study, and additional results will be available early part of next year. Now let's switch attention to very exciting LAIR science. Just reminder, I want to go through step by step from the left to right so that you can follow me very well. LAIR1 is a membrane-bound receptor expressed on the T cells and dendritic cells, and it binds to either collagen or C1q on the tumor that expressed this. When this happens, it has an inhibitory effect on the immune function. LAIR2 is a natural occurring decoy molecule of LAIR1. It differs in two aspects. One, it is a soluble protein, and two, it has a higher affinity to the collagen and C1 ligands. Competitively binds to those so that those two collagens and C1q cannot bind to the LAIR1. You can follow the cartoon to the right. You can see that LAIR2 modulates the LAIR1-mediated immune inhibition, therefore activated T cells can do the job of tumor killing. On the slide number 13 is the what is NC410. NC410 is a human fusion protein of LAIR2 and is a decoy for the LAIR1. What it does is promote the T cell function and T cell activation, a dendritic cell activation, as I mentioned earlier. I show you with the data in the next slide. This was presented by Linji Qian at SITC, there are three point I want to make in the three rows that you can see. The most important part of 410 is the extracellular matrix remodeling, which is very significant about this particular molecule that we're very excited about it. You can see from the middle pictures that you can see the granzyme B-mediated collagen fragmentation, MMP-2-mediated collagen fragmentation. You can see that when this is given at week four, you can see the level on the graph. The next step, it promotes antitumor immunity. It does it locally and systemically, and you can see from the picture again and the figure again that using interferon and granzyme B local and in the tumor itself. What does it do? It enhance the T cell infiltration and tumor killing. More importantly, it brings back the normalization of the immune function. That's the most important part of 410. The other effect of this is the combination potential. This was presented by Dr. Lucas Horn at SITC, and I want to give you left and right. On the left, you can see with the PD-L1. On the right is the bevacizumab combination. PD-L1, you can see whether it's alone or 410 alone or anti-PD-L1 alone. You compare the combination tumor volume, you can see from the graph very clearly that combination is better than either of those one. I think more importantly, the most exciting thing is the right-hand side figure that you can see. Bevacizumab, try to remember it is a bifunctional fusion protein. It's a extracellular domain of human TGF beta 2 trapped to a flexible linker to the heavy chain of IgG1 of the antibody to PD-L1. You can see the combination on the red color at the bottom. You can see that the tumor is cured in this model that they did. Next is I want to tell you where we are with the clinical program on the slide number 16. This is a classic phase I/II study. At the moment, we're in phase I, and we're doing classic 3 plus three dose escalation, and we're looking at safety and tolerability of this NC410. What we are looking at tumor types was advanced metastatic solid tumors such as non-small cell lung cancer, ovarian, and pancreas. We're on track and accruing quite well. We hope to give you the results of the clinical data from the phase I portion of this study towards the end of the H2 of 2021. With that, I'd like to call over to Tim. Tim? Thanks, Han. I'm pleased to introduce NC762, our new program we are disclosing today. NC762 is a humanized monoclonal antibody that targets B7H4. B7H4 has low expression in normal tissue but is upregulated in multiple solid tumor types, including non-small cell lung cancer, ovarian cancer, breast cancer, and several others. B7H4 has been reported to inhibit the proliferation of T cells, suppress antigen-presenting cells, stimulate proliferation of T regulatory cells, and promote tumor growth. Multiple publications have demonstrated that B7H4 expression in tumors correlates with poor clinical outcomes. Expression of B7H4 has also been shown to not overlap with PD-L1 expression in non-small cell lung cancer. While other B7H4 monoclonal antibodies are in clinical development, we believe NC762 has unique anti-tumor properties. Preclinical data demonstrate that binding of NC762 to tumors expressing B7H4 results in inhibition of tumor growth in vivo. Natural killer cells contributed to the enhanced high anti-tumor activity mediated by NC762. NC762's inhibitory effect on tumor growth was not dependent on T cells. On slide 18, we provide the in vivo data for NC762. In these preclinical studies, NC762 was shown to inhibit melanoma tumor growth alone but was enhanced by the addition of human immune cells. The figure on the left shows tumor inhibition versus control. The study also included other versions of NC762 that was designed to restrict ADCC activity, and as you can see from the results, tumor inhibition was independent of ADCC activity. The figure in the center shows that for a parent of NC762, tumor inhibition was enhanced with the addition of the natural killer cell. The figure on the right demonstrates that purified T cells alone were not required for activity. We believe this profile is incredibly encouraging with a mechanism of action that clearly differentiated from other B7H4 targeted programs in development. We have filed an IND with the FDA and expect to initiate a phase I clinical trial in the Q2 of this year to assess safety and tolerability in patients with solid or metastatic tumors. We expect to provide initial phase I clinical data in the Q2 of 2022. Finally, I'll highlight our powerful discovery engine we call FIND-IO for functional integrated NextCure discovery in immuno-oncology. The platform integrates multiple components to assess immune function resulting from cellular interactions. The system entails individually transfecting each gene from our library of over 9,000 genes into a host cell, which will then express the protein on the surface of the cell. We combine the transfected cell expressing the single gene with an immune cell. Finally, and most importantly, we have our functional readouts we observe through our discovery screens, which provide important insight into identifying genes that modulate immune cell activity. We view the immune system holistically, and rather than target one specific immune cell type, we focus on understanding biological pathways, the interactions of cells, and the roles each interaction plays in an immune response. Our future pipeline will continue to focus on how the immune system interacts within its microenvironment and shapes disease. Given the versatility and flexibility of the FIND-IO platform, cells and functional readouts can be altered, and the platform can be applied to identifying targets in other therapeutic areas. We are currently investigating what we call FIND-AI for autoimmune and inflammation targets. Alternatively, the system can be applied to microglial cells and astrocytes to identify novel CNS targets for neuroinflammatory diseases. Moving forward, our anticipated near-term milestones include NC318 and providing phase II monotherapy data in the fourth quarter of 2021, and Yale starting the phase II non-small cell lung cancer combination trial in the Q2 of 2021, with anticipated initial data in the H1 of 2022. Reporting NC410 initial phase I data in the H2 of 2021 and initiating the NC762 phase I trial in the Q2 of 2021 and reporting initial data in mid-2022. In summary, we're excited to have Dr. Myint as part of the team and draw upon his vast experience in developing oncology products. We continue to make progress on NC318 with the continued advancement of the phase II monotherapy study and the return to non-small cell lung cancer with Dr. Herbst in Yale. NC410 continues to advance in the clinic, and we look forward to sharing data later this year. We look forward to starting NC762, the third candidate we have advanced to the clinic in five years, and using the unique anti-tumor properties of the antibody in inhibiting tumor growth. We would like to thank everyone for joining the call this evening. With that, we'll now open the call up for Q&A. Thanks, Tim. Is the operator there? Sorry for the technical difficulties. Again, to ask a question, please press star one on your telephone keypad. Your first question comes from the line of Edward Tenthoff from Piper Sandler. Your line is now open. Great. Thank you. Good evening, everybody, and thanks so much for the time. It's a pleasure to get to meet you, Han. I'm trying to get a sense with respect to NC318, what we could be expecting in the fourth quarter. Which different cancers are we looking at that end? Then sort of same question with respect to combination with anti-PD-1. What indications are you looking at presently? Thanks. Yeah, thanks, Ed. Han, would you like to take that call? I think the combo parts of the Yale study is quite easy to answer because Yale is only concentrating on the non-small cell lung cancer only. They will do both monotherapy, as I alluded to earlier on, and the combo with the pembro in the PD-1, PD-L1 axis naive as well as failed population. There are three arms, as I mentioned. The program is ready to kick off at the end of this month, early next month. We're expecting to see some of the results very quickly. That's why, I think, we're hoping to see the results by the end of this year, early next year. As far as the company-sponsored study, we're still ongoing, enrolling patients with head and neck cancer, triple-negative breast, and that's where we are right now. As mentioned, once we have the S15 clear validation stainings complete by the end of the month, in next Q2, we'll be looking at revising the protocol, and we can update you at that time. Great. Thank you guys for the update, and I'm excited to hear about the new candidate. Great. Thanks, Ed. Your next question comes from the line of Robert Hazlett from BTIG. Your line is now open. Yes. My congratulations as well. Could you discuss a little bit more about the assay development with regard to Siglec-15? What remains, where would you intend to employ it in the future? Will the Yale investigators be employing something in their study as well? I have one or two more. Yeah. Thanks, Bert, and good to be speaking with you. That's a great question. As most of you know, we've been very focused on developing a validated IHC test that we could use on biopsies taken from patients to determine whether or not a given subject is S15 positive. This test has been developed. It's been in validation over the last few months and will be available to use in our ongoing phase II trial that Han walked you through. Moving forward, from NextCure's perspective, we will be applying the CLIA-validated NC318 test to select for S15-positive patients. With respect to our ongoing relationship with Yale, there's a number of arms to that study. Over time, we will be integrating the use of that test as it relates to the monotherapy components. As we move forward and start generating more data, we'll also be ultimately integrating that into the combo study. That's terrific. You just touched on a little bit more of the Yale structure. Hey, could you give us anything with regard to size and endpoints with regard to the Yale study? Again, you touched on it a little bit there, but any more detail would be terrific. Yeah. Maybe Han can give you a general overview, Bert, I'd also kind of just reference clinicaltrials.gov, which kind of clearly delineates the trial in much more detail. Han, did you want to add any color commentary other than you're looking forward to going to New Haven, Connecticut? Thank you. I don't think, no. I think that would be enough, I think. Yeah. Bert, it's kind of a really interesting point because as most of you know, even though we're here in Beltsville, Maryland, NextCure's founding institution is at Yale. Pat LoRusso participated as one of our lead investigators in the phase I clinical trial for NC318. She participated in the phase II trial, through this, and through our founder, Lieping Chen, who actually discovered PD-L1, we got to know Roy Herbst and Scott Gettinger quite well. As most of you know, Roy is kind of the luminary in lung cancer on planet Earth these days. We're very fortunate to have both of them obviously working very closely and collaboratively with us on this trial in returning to a non-small cell lung cancer. I should also add that Merck obviously has choices on how they provide KEYTRUDA to looking into evaluating combo trials. To have the opportunity to work with our collaborators at Yale and also with Merck to provide KEYTRUDA, we think provides the enthusiasm that we all share for looking at this approach. Can't wait to see the data. Remember, when you're in New Haven, Sally's Apizza is the best. Thank you very much. We will remember that. Thank you. Thank you. We will. Your next question comes from the line of Jeff Hung from Morgan Stanley. Thanks for taking the questions and for the R&D update. Maybe if I can just ask a little bit further. In recent months, it looks like your strategies for the 318 combo study shifted from chemo combo to anti-PD-1 combo. I realize that the combo study is an investigator-initiated trial, but can you talk about what went into that decision and what gives you greater confidence in an anti-PD-1 combo versus a chemo combo? Then I have a follow-up. Yes. You may recall the "Nature Medicine" paper two years now, right? We're in 2021, so two years ago. There is a figure that I can easily refer to you, I think Figure six and Figure 10J in the supplementary. This beautiful preclinical work done by Lieping and others, a number of people from our NextCure was involved too, like Saal and Lindell and Dallas in that paper. What they showed is that if you combine the two together, tumor growth is definitely a lot lower than what you see, like response is much better with a combo compared to either of PD-1 that is nivolumab or NC318. As you all know that initially, as you know, the PD-L1 and Siglec-15 expressions are like exclusive to each other, but as you treat, then patient then start to stop responding to PD-1. That's where I think Siglec-15 comes in and help the function again and re-derives the function of the sort of pembro or nivolumab to do the job. I think that preclinical data is shown very nicely. I think that's why I think the world authority in lung, people like Roy and Scott are very excited to do that study. Anything to add? No, that's great. Thanks for that question, Jeff. Thanks. If I can follow back. In the interim phase II results, you saw the S15 expression in 13% of the valuable biopsies, but there was also some evidence that S15 status can change over time. I was just wondering if you could clarify how you're taking those pieces into consideration with the revised protocol selecting Siglec-15 positive patients, and what kind of requirements will you have for duration of Siglec-15 positive status. Thanks. Yeah, that's a great question. Obviously, through our studies, we continue to learn a lot. What we have confirmed is the non-overlapping expression between Siglec-15 and PD-L1. With respect to this dynamic change, obviously we're gonna continue to monitor that, but we no longer believe that a PD-L1 low selection will enrich for S15 positivity, and that's the rationale for developing the IHC test that we talked about earlier. What we do believe is, especially in the case of lung, we still believe 20%-25% of lung cancer patients are S15 positive, and if we could target those particular individuals using our test-Hopefully, we'll be able to move in the direction of many more responses. Han, any other comments there? No, I think you've done it very nicely. Okay, thanks. Great. Thank you. Thanks, Jeff. Your next question comes from the line of Alec Stranahan from Bank of America. Your line is now open. Hey, guys. Thanks for taking our questions, and thanks for the update. It's good to hear from you. Hi, Alec. First, I've got a couple of questions on the investigator-led study, and you've covered a bit of this, but I was hoping to dig a little bit more into the discussions you've had with the investigators, and sort of the rationale of restarting in non-small cell lung cancer. Is it that the lung cancer cohort was maybe excluded prematurely from the original study? If so, which data would you point to supporting this? I guess along those lines, do you imagine that both S15 and PD-L1 selection will be included for enrollment in the combo arm of the study? Then I've got a follow-up. Yeah, great question. A little history for the audience. You may recall in the phase I trial, we had looked at 49 patients, 15 different tumor types, and about a fourth of those patients were non-small cell lung cancer. As Han reported earlier, that's where we reported the CR and the PR, both of those individuals that remain on drug today. We also reported a number of stable disease. That gave us a fair amount of confidence moving into the phase II trial, and in particular, the non-small cell lung cancer cohort. Obviously, we were very disappointed and surprised when we started looking at the data and didn't see any responses in the phase II that would've justified moving to stage two of that Simon two-stage study. When we went back and we looked at the biopsies regarding the ones that were available, we just did not see that many S15 positive individuals. I think through the experimental data, that made us go back and rethink our strategy. We weren't writing off non-small cell lung cancer, but we did need to use the last six months or so to learn a lot more. Moving forward, we will continue to look at PD-L1 status. That's an easy test to do, and many of the individuals that will be coming onto the trial in non-small cell lung cancer will be refractory or would've failed prior treatment with KEYTRUDA or IMFINZI or another PD-1 or PD-L1 therapy. We will be selecting for S15 positive patients. Now, more specifically your question, on the monotherapy arm, we will be selecting S15 patients. In the combo, we may be ramping into that over time. Ultimately, we'll be moving in that direction. The Yale folks are eager to start, but our tests will be available shortly, and once available, we'll be moving in the direction of selecting for those individuals. Han, anything else to add? No, I think you covered everything. Yeah. Okay, great. Thanks. One more, if I may, actually on your new asset, NC762. Should we assume that the phase I will be structured similarly to studies for your other assets? Do you have a sense, based on the literature or your pre-clinical observations, which tumors might be the most amenable to targeting of B7H4? I guess, looking longer term, is the plan to limit investigation to oncology, or do you also expand studies to, say, autoimmunity or inflammation? Yeah. That's a great question or several questions. With respect to B7H4, and one thing we have learned in NextCure is that moving forward, developing the tools for patient selection and developing the assays for biomarker analyses will be integrated into all of our programs. That speaks to where we are now backtracking with NC318 lung, but we'll be applying in NC410 in LAIR, and then to your point, NC762. Many gynecological cancers are heavily overexpressing B7H4, so we see this in ovarian cancer, breast cancer, fallopian tube cancer, and many other types of cancers. The phase I, with respect to looking at rapid enrollment and looking at safety and tolerability, will be enriching for those patients that are naturally B7H4 positive. As we segue into the phase I-B and phase II, we also have a test that will be CLIA validated mid-year that we'll be able to apply for selecting patients. We're also building an extensive toolkit on the biomarker side to give us much more insight to what NC762 will be doing immunologically and clinically as we dose patients. Is that correct, guys? Yeah. All right, good. Keep me real. Good answer. Yeah. Thanks, Alec. Thanks, guys. Your next question comes from the line of Asthika Goonewardene from Truist Securities. Your line is now open. Hi, guys. Thanks for taking my questions. Hi. Hi there, and Han, good to meet you. Let's start off with, I want to jump in on another question on the Yale study. Particularly with the PD-1 failures, I'm wondering if the recruitment target here in PD-1 failures with the Yale side, we're recruiting enough patients to delineate between primary progresses and subsequent failures, and I'm just wondering if there's any sort of updated thinking on that interplay between PD-L1 and S15 in this particular group? Then I got a few follow-ups as well. Currently, the way they were looking at is the patient who had seen either Nivo or Pembro or any of those PD-1, PD-L1 therapies, and Yale being the big lung center as you know, they have about two to four patient type per month that they will see. That's what they were looking at to come onto the study. We haven't stratified, as far as I recall, in the primary numbers from what you catch from very beginning or the one that already failed. I think that's why we had the arm called naive population. Currently they have other studies ongoing that these are going to wrap up. Once those studies wrap up and you can predict right from some of the base on, especially with the Pembro, with the MSI-H and what have you, and they could have easily predict those and that in future will be used in their naive population. Right now, I think they're considering on the failure population first. Got it. Okay. In terms of the B7H4, I know there have been maybe some other attempts on that as well, but maybe can you talk to us a bit about what makes NC762 unique, its epitope that you're going after, et cetera. Yeah, that's a great question. Yeah, I think how we differentiate this is when we look at product development, we look at targets, we look at candidates, and then we look at patient population. We've always felt B7H4 is a really important target, and I think our earlier question, someone was asking about autoimmunity, and it potentially does have application in looking at autoimmune diseases. With respect to the differentiation, our molecule does recognize a different epitope. We have done comparative studies to determine that. It's got a different affinity, and I think most importantly, as Tim walked through earlier, it has a different functionality. When we talk about function or mechanism of action, NC762 is clearly different. We've spent a lot of time doing a lot of in vitro and in vivo work to not only study the mechanism of action, but also to ascertain how best to position this for when Han would join us and to move this into the clinic. Tim, anything else you'd like to add? No, that's exactly the answer. Great. Lastly, on NC410, are you able to give us any update on where you are on the dosing, dose escalation, and or how far you are from completing recruitment? Where we are right now, we're in the phase I part of dose escalation. We're kind of working our way towards, I guess, the middle of the various cohorts. As Han mentioned, we'll be reporting an update on that trial later this year. Great. Thank you, guys. Yeah. Thank you very much. Your next question comes from the line of Tony Butler from Roth Capital. Your line is now open. Hi, Tony. Hey, thanks very much for the time. Appreciate the update. Just a couple of very simple questions, I think. When you put in the Siglec-15 inhibitor, it doesn't matter the tumor, do you actually peripherally get an increase in T cells? If you get an increase in T cells, do you have any data that would be, of course, in vitro that they are directed against a particular tumor? That's question one. Then in question two, again, going back to the Yale study. Is the assumption that non-small cell lung cancer naive patients might actually be Siglec-15 negative, versus, of course, those that have failed PD-1 because the majority of them will have been on a PD-1 regimen at some point and clearly may have become PD-L1 negative, and thus perhaps Siglec-15 positive? Just curious your thoughts there. Thanks. I guess the first question is looking at T cells, and all of our in vitro work, and data we've generated, has demonstrated that we can enhance T cell proliferation and interferon gamma. With respect to the immunophenotyping that we've done on samples from patients, we have seen T cells. With respect to an overall proliferation, it's difficult to quantify that data at this time. Your other question is a little more complex to answer with respect to, I guess, non-small cell lung cancer and looking at kind of naive patients that maybe have not been exposed to PD-1 or PD-L1 therapy and what impact that might have on S15 expression. What we can say outside of non-small cell lung cancer is we have treated or analyzed other patient samples that have not received PD-1, where it may not be approved, and we do see some sort of S15 expression in those samples. In the case of non-small cell lung cancer, any thoughts on the naive versus the refractory population and the impact that might have on S15 expression? I'm not sure we know that. No, I don't think we know that. That's where we are today, I think. Especially with the pembro, I'm sure being the center like Yale, they will be doing a lot of other markers, right? MSI is one, and then there's many other markers that they've been looking at. They're looking at RNA-Seq and so on. There's so many ways that they've been determining. I think we will learn a lot from them. That's why I think we're very excited for them to look at the naive population as well. To answer that question directly to you all the way you framed it, I don't think we know the answer. Yeah. As we talked about today, in the case of Yale, we've got, again, the mono arm, the combo arm, and in the part of the combo, we've got the naive and refractory patients. We'll be learning a lot, and we'll be looking at both S15 expression and PD-L1 expression. Okay. I agree. I think it's a great trial, so look forward to that data set. Appreciate it. Thank you. Thanks. Thank you. Your next question comes from the line of Reni Benjamin from JMP Securities. Your line is now open. Hey, good afternoon, guys. Thanks for taking the questions. Hi. I have a couple on the head and neck and triple-negative and then a follow-up. I guess for the head and neck, very nice results. How many patients overall have been treated in both the head and neck trial and the triple-negative study, and how many do you plan on enrolling after the protocol amendments? I know you mentioned the PD-L1 staining, at least for the head and neck patient, but any color you can give us regarding the Siglec-15 expression or staining from these patients that are responding? Yeah. With respect to the Siglec-15 expression, we don't have any of that information at this point. Obviously, we've collected biopsies from these patients, and we'll be looking at that. I'm sorry, the other question? Just how many patients total have been enrolled in the head and neck and the triple-negative, and how many do you plan on enrolling after the protocol amendment has taken place for the two studies? Right. Yeah, thank you. Sorry. It's a Simon 2-stage study. We haven't disclosed actually how many patients we've enrolled, but we have reported, even in today's press release, that we've advanced both the head and neck and the triple-negative breast cohorts to stage two of that Simon 2-stage study. Got you. Michael, how many patients should we think about in terms of the phase II portion, or that hasn't been disclosed either? We've said in the past that our phase II trial will look at about 100 patients in total. Correct. Got it. Okay. Thank you for that reminder. Just switching gears to NC410. It seems like a big component, and I think you mentioned it before, is, of course, biomarker development. Can you give us a kind of sense as to how you might be looking at biomarker development for the NC410 asset? Yeah. Boy, how much time do you have? I love talking about NC410 biomarkers. Yeah. As Han walked you through, NC410 is a fusion protein of LAIR-2, which works through a decoy mechanism to basically stimulate T-cells and dendritic cells to restore immune function. LAIR-1 and LAIR-2 bind two key ligands, collagen, and this is monomeric collagen expressed on the tumor that impacts the extracellular matrix and the architecture of the tumor and the TME. It also binds C1q, which is also an important part of the complement system and impacts the immune system. What we've done is, our team has been, I think, going a little overboard on developing the tool from a biomarker perspective. We can look at LAIR-1, we can look at LAIR-2, we're looking at collagen and collagen degradation products. We're looking at C1q. This becomes a little bit of a bioinformatics puzzle, where we're generating all of this data, not only in the patients, we're also looking at these various markers in different patient populations and healthy individuals to give us the ability to do some comparative analysis. Independent of the traditional PK and PD analyses that we would do in looking at immunophenotyping, looking at cytokines and chemokines, NanoString. Many of the biomarkers that most people are familiar with in immuno-oncology, we've added onto that with respect to LAIR-1, LAIR-2, collagen, and C1q, and I'm sure by tomorrow, there may be a few more. Thanks. Got it. Maybe just one for Tim. The 762 asset came out of the FIND-IO platform. Is that correct, or did you guys find it in another way? No, the NC762 asset, as we said, targets B7H4, and that did not come out of FIND-IO. Now, historically, Dr. Chen has worked on the B7H4 program, and that would've been before the advent of the precursor of FIND-IO. It's a homegrown product candidate. Got it. Thank you guys very much for taking the questions. Thank you. Your next question comes from the line of Aydin Huseynov from Benchmark. Your line is now open. Hi. Good afternoon. Congrats on the progress, and thank you for taking my questions. The first question I have is about the phase mono study. Initially, you planned lung, head and neck, TNBC, and ovarian. Lung, you essentially stopped. Head and neck, you got one response, TNBC, one response. Did you see any responses in ovarian cancer? Yeah. We did not see any responses in ovarian cancer. We also didn't generate the number of biopsies that we had hoped to. There is a possibility of going back to ovarian cancer, but under such an arrangement, we would request biopsies and select for S15 positivity again. Okay. Understood. For non-small cell lung cancer, for the two responses that you had, did you measure the S15 expression at any point, especially lately or at any point of the treatment? Unfortunately, we did not have biopsies in those patients. Both of those individuals, the original CRPR, were in our phase I dose escalation study where biopsies weren't collected at that time. That's most unfortunate. Fortunately, both patients are still around today. Right. Yeah. For B7H4, for NC762, do you see any potential synergies with PD-L1 or any targeted therapies in the future? That's a great question. Our research folks are doing in vivo comparative studies. There's some things that come to mind, maybe PD-1 or PD-L1, but there may be some other molecules like PARP inhibitors that are already approved and being used in gynecological cancer applications. That work is still in research. Like all of our programs, we're going to be open to investigating combos with a clear focus on patient selection and looking at biomarkers. Anything else, Han? No, I think you covered it. Okay. Okay. The last question I have is a general question. It's about your business development plans, if you have any in 2021. I think in the past you mentioned that you have active business development team. I'm just curious about any plans that you may have in 2021. Yeah. We haven't provided any guidance with respect to any specific partnerships that might be consummated. You are correct, we have a very proactive business development team that Tim leads, and we're constantly and consistently engaged in multiple discussions on multiple fronts. We remain opportunistic, but no defined guidance at this time. All right. Thank you very much. Thank you. We have a follow-up question from the line of Mr. Tony Butler from Roth Capital. Your line is now open. Thanks again. Sorry for the follow-up, but it's just brief. The dosing of the Siglec-15 is every other week, if I recall correctly from, I guess, the deck. Importantly, how do you do the trial, or how do you think about doing the trial in conjunction with PD-1, or at least pembro, given its dosing which is clearly different? Thanks again, and appreciate the time. Thank you. Currently, I think the Pembros have been dosed at every three weeks, and our drug is being given every two weeks. That's the current design. As we talked about earlier, this is a moving target, right? We can think about how they could modify the study as we go along. Right now, that's just how they designed it. Thanks, Han. Thank you, Han. Appreciate it. There are no questions in queue. Speakers, you may now continue. Great. Well, thank you very much, everybody. We appreciate you taking the time for the update and look forward to continuing our discussions. Have a nice evening. Thank you very much. This concludes today's conference call. You may now disconnect.