NextCure, Inc. (NXTC) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by, and welcome to the NextCure R&D update conference call and webcast. [Operator Instructions] 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 Richmond; and our recently appointed Chief Medical Officer, Dr. Han Myint, who will also provide remarks today. Michael; Han; Steve 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, preclinical and operating results, research and development goals and future financial performance at 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 CEO, 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 2 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 aligned with our focus on developing next-generation immuno medicine to treat cancer and other immune-related diseases by restoring normal immune function. In terms of an agenda, Slide 3, 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 additional remarks and then discuss recent updates on our 2 lead programs, NC318 and NC410. Tim will then introduce our new program, NC762 and finalize the presentation with an update on our FIND-IO platform. But 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 second half of 2023. And as you will hear in today's call, we expect multiple pipeline milestones to occur between now and 2023. On Slide 4, on NextCure highlights, I'd like to emphasize our fifth anniversary. Since initiating operations 5 years ago, we have, one, filed 3 investigational new drug applications for novel immune medicines with unique mechanisms of action; two, taken 2 molecules into the clinic, and you'll hear about the third today, NC762; three, build a GMP manufacturing facility and have produced clinical material to support all of our ongoing clinical work; and four, developed a discovery platform to identify novel proteins that modulate immune activity. We are incredibly proud of this productivity. In Slide 5, 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 our 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. But first, I do want to highlight that we have maintained the worldwide rights to all of our programs. In Slide 6, 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 provide instrumental -- will prove instrumental on 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 NexImmune. In his academic years, he worked at prestigious institutions, including King's College London, Rush University Medical Center and the University of Chicago -- sorry, University of Colorado and Denver. While Han has been with us for less than 2 months, he has hit the ground running and is already having a substantial impact on our clinical plan. I thought it would be beneficial to have can 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 410 could have bring the opportunities for the treatment of cancer. And also look at the pipeline that you have in preclinical program, and those are very exciting for us. As Michael alluded to earlier on, and I am a newbie at NextCure, less than 2 months old, but with the help of the team here getting fully up to speed in that short tenure. And even with this introduction by the team here, I'm more and more optimistic about the potential of the pipeline and the platform. I'm looking forward to speaking with you all in the greater detail in the coming months. So 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 immunosuppression. Siglec-15 is expressed on the tumor cells as well as M2 macrophages, and that led to potently suppressed the T cell function, and NC318 reversed that effect. On the Slide 8, I'm going to talk to you about the update of our clinical program, and I'm going to highlight 2 main updates. Top, you can see a current Phase II monotherapy continue to accrue. And I'll show you some clinical responses in the next couple of slides. And also, we are developing the assay for selecting the patient 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 combination with pembrolizumab, which I will again explain to you more in the next couple of slides. So 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. Now let's draw the attention to Phase II part of the program, we gave 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. And now we have a confirmed triple-negative patient who responded. And again, I'll give you more detail in the next slide. But I think the exciting thing to note here is that the patient with -- head and next 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. And as I mentioned, because of those responses, we are now moving forward to this second portion of the Simon 2-stage trial. And we are also very pleased to announce to you about the clear validation of the Siglec-15 staining. And we will be getting the final results by the end of first quarter. And 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 this 318 program to you in the fourth quarter of this year. As I alluded to earlier on the Slide 10, I can show you that -- I can show you the 2 rows you like to look at. The top row is a patient with head and neck cancer. And 53 year old with the 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, 3 rounds; 3 rounds of radiation. And patient was also given nivo and pembro in a different time frame, but within the 3 months' time frame patient progress. And 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 37%, and that is why patient is recorded as partial response. Next is the second row, the next role after that, is a patient with triple-negative breast cancer. This is an unusual case. It's a 7-year-old with a triple-negative breast cancer, very low PD-L1 staining, less than 1%. And patient had previously been treated with 3 cycles of chemotherapy, one cycle of radiation, and patient was given pembrolizumab and the best response of stable disease, but then patient had a progression. This patient, as I mentioned, had a skin lesion, and you can see on the left-hand side and compared with 8 weeks later on the right-hand side. It dropped from 80 millimeter down to 14 millimeter, which is target lesion decreased by 82%. And this patient remains to be on treatment. The next one, I'm very, very excited to tell you about this because you may recall, we dropped non-small lung cancer in the past, but the World authority, Dr. Roy Herbst and Scott Gettinger from Yale are very excited about our science. And they -- liaised with Merck and brought pembroluzimab into the steady design. So what they're trying to do is 3 arms, non-randomized 3-arm study. And in the monotherapy arm, they're going to select patients who was Siglec-15-positive and PD-1 failure -- PD-1, PD-L1 axis treatment failure population. In the combo arm, what they're going to do is 2 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 fail population. And they're going to start accruing in Q2 of this year. And depending on the results, we may be able to add more patients into this study and additional results will be available early part of next year. So now let's switch attention to very exciting LAIR science. So 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 the membrane-bound receptor expressed on the T cells and dendritic cells, and it binds to either collagen or C1q on the tumors that expressed this. And then when this happened, it has an inhibitory effect on the immune function. LAIR2 is a natural occurring deploy molecule of LAIR1. It differs in 2 aspects: one, it is a soluble protein; and two, it has a higher affinity to the collagen and C1 ligans. So competitively binds to those, so those 2 collagens in C1q cannot bind to the LAIR1, and you can follow the cartoon to the right, you can see that LAIR2 modulates LAIR1-mediated immune inhibition. Therefore, activated cells can do the job of tumor killing. On the Slide #13 is the -- what is NC410. NC410 is a human fusion protein of LAIR2, and it's a decoy for the LAIR1. And what it does is promote the T cell function and T cell activation -- tentative cell activation, as I mentioned earlier. And I'll show you with the data in the next slide. This was presented by Linjie Tian at SITC, and there are 3 points I want to make in the 3 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. And you can see from the middle pictures that you can see, Granzyme B mediated-collagen fragmentation, MMP-2-mediated collagen fragmentation, you can see that when this is given at week 4, you can see the level on the graph. The next step, it promotes antitumor immunity. It's not only -- it does that locally and systemically and you can see from the picture again in the figure again, that using gamma interferon and Granzyme B local and in the tumor itself. So what does it do? It enhance the T cell infiltration and tumor killing, and more importantly, it brings back the normalization of the immune function, and that's the most important part of 410. The other effect of this is the combination potential. And 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 bintrafusp alpha combination. PD-L1, you can see whether it's alone or 410 alone or anti-PD-L1 alone. When compared to combination tumor volume, you can see from the graph, very clearly, that combination is better than either of those parts. I think more importantly, the most exciting thing is the right-hand side. figure that you can see. And bintrafusp, if you try to remember, it is a bifunctional Fusion Protein. It's a extracellular domain of human TGF-ß II trap to a flexible linker to the heavy chain of IgG1 of the antibody to PD-L1. So you can see the combination on the red color at the bottom, you can see that the tumor secured in this model that they did. And then next is I want to tell you where we are with the clinical program. On the Slide #16. So this is a classic Phase I/II study, the Phase I -- at the moment, we're in the Phase I, and we're doing classic 3 plus 3 dose escalation, and we're looking at safety and tolerability of this 410. And what we are looking at tumor types-wise advanced metastatic solid tumors, such as non-small cell lung cancer, ovarian and pancreas. And we're on track and accruing quite well, and we hope to give you the results of the clinical data from the Phase I portion of the -- this study towards the end of -- second half of 2021. With that, I'd like the 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 B7-H4. B7-H4 has low expression and normal tissue but is up-regulated in multiple solid tumor types, including non-small cell lung cancer, ovarian cancer, breast cancer and several others. B7-H4 has been reported to inhibit the proliferation of T cell, suppress antigen-presenting cells, stimulate proliferation of T regulatory cells and promote tumor growth. Multiple publications have demonstrated that B7-H4 expression in tumors correlates with poor clinical outcomes. Expression of B7-H4 has also been shown to not overlap with PD-L1 expression in non-small cell lung cancer. While other B7-H4 monoclonal antibodies are in clinical development, we believe NC762 has unique antitumor properties. Preclinical data demonstrate the binding of NC762 to tumors expressing B7-H4 results in inhibition of tumor growth in vivo. Natural killer cells contributed to the enhanced [ ISI ] tumor activity mediated by NC762. However, 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 inhibition 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 parent of NC762, tumor inhibition was enhanced with the addition of the natural killer cells. Finally, the figure on the right demonstrates that purified T cells alone were not required for activity. We believe this profile is incredibly encouraging with the mechanism of action that's clearly differentiated from other B7-H4-targeted programs in development. We have filed an IND with the FDA and expect to initiate a Phase I clinical trial in the second quarter 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 second quarter 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 a single gene within immune cell. Finally and most importantly, we have our functional readouts we observed 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 second quarter of 2021 with anticipated initial data in the first half of 2022. Reporting NC410 initial Phase I data in the second half of 2021 and initiating the NC762 Phase I trial in the second quarter of 2021 and reporting initial data in mid-2022. So in summary, we're excited to have Dr. Myint as part of the team and draw upon a 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 5 years and using the unique assay tumor properties of the antibody in inhibiting tumor growth. We would like to thank everyone for joining the call this evening. And with that, we'll now open the call up for Q&A.

[Operator Instructions] Your first question comes from the line of Ted Tenthoff from Piper Sandler.

I'm trying to get a sense with respect NC318. Sort of what we should be expecting in the fourth quarter? Which different cancers are we looking at that end? And then sort of same question with respect to combination with anti-PD-1, what indications are you looking at presently?

Thanks, Ed. Han, would you like to take that one?

Yes. So I think the combo part of the Yale study is quite easy to answer because Yale is only concentrating on the non-small lung cancer only. So 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 3 arms as I mentioned. So the program is ready to kick off at the end of this and early next month. So we were 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-sponsor study, we're still ongoing, enrolling patient with head and neck cancer to the negative breast, and that's where we are right now. But as mentioned, once we have the S15 clear validation staining is complete by the end of the month into next Q2, we will be looking at revising the protocol, and we can update you at that time.

Your next question comes from the line of Bert Hazlett from BTIG.

My congratulations as well. Maybe you just touched on it, but could you discuss a little bit more about the assay development with regard to Siglec-15. What remains? And where would you intend to employ it in the future? And will the Yale investigators be employing something in their study as well? And then I have 1 or 2 more.

Yes. Thanks, Bert. And good to be speaking with you. That's a great question. So 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. So 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 relationships with Yale, there's a number of arms to that study. And over time, we will be integrating the use of that test as it relates to the monotherapy component, and 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 the -- a little bit more of the Yale structure. 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.

Yes. Maybe Han can give you a general overview. But Bert, I also kind of just referenced ClinicalTrials.gov, which kind of clearly delineate the trial in much more detail. But Han, did you want to add any color or commentary other than you're looking forward to going into New Haven, Connecticut?

I don't think -- no, I think that will be enough, I think. Yes.

Bert, it's kind of a really interesting point because as most of you know, even though we're here in Beallsville, Maryland, NextCure's founding institution is in Yale. And Pat LoRusso participated as one of our lead investigators in the Phase I clinical trial for NC318, who participated in the Phase II trial. And 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, it's kind of the luminary in lung cancer on planet earth these days. So 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. And I should also add that Merck, obviously, has choices on how they provide KEYTRUDA to looking into evaluating combo trials. So they have the opportunity to work with our collaborators at Yale and also with Merck to provide KEYTRUDA, we think, that provides the enthusiasm that we all share for looking at this approach.

Can't wait to see the data and remember when you're in New Haven, Sally's Apizza is the best.

We will remember that.

You will.

Your next question comes from the line of Jeff Hung from Morgan Stanley.

Maybe if I can just ask a little bit further. In recent months, it looks like your strategy for the 318 combo studies shifted from chemo combo to anti-PD-1 combos. So 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 chemo combo? And then I have a follow-up.

Yes. So you may recall the Nature Medicine paper 2 years now, right? We are in 2021, so 2 years ago. And there is a -- I mean, the figure that I can easily refer to you, I think, figure 6 and the figure 10j in the supplementary. This beautiful preclinical work done by Lieping and others. I mean, a number of people from our NextCure were involved, too, like Sol and Linda and Dallas in their paper. And what they showed is that if you combine the 2 together, tumor growth is definitely a lot lower then what you see like response is much better with the combo compared to either of PD-1 that is nivo or NC318. And that's the major driver. And as you all know that -- initially, as you know, the PD-1 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 redrives the function of the sort of pembro or nivo to do the job. So 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.

And if I can follow-up. 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. So I 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?

Yes, that's a great question. And obviously, through our studies, we continue to learn a lot. What we have confirmed is the nonoverlapping expression between Siglec-15 and PD-L1. With respect to this dynamic change, obviously, we're going to 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 lungs, we still believe 20% to 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?

I think you've done it very nicely.

Okay. Thanks.

Your next question comes from the line of Alec Stranahan from Bank of America.

So 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 have -- you 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. And if so, which data would you point to supporting this? And 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? And then I've got a follow-up.

Yes. Great question. So a little history for the audience, so you may recall in the Phase I trial, we had looked at 49 patients, 15 different tumor types, and about 1/4 of those patients were non-small cell lung cancer. And 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. So 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're very disappointed and surprised when we started looking at the data and didn't see any responses in the Phase II that would have justified moving into stage 2 of that Simon 2-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. So I think through the experimental data, that made us kind of go back and rethink our strategy. We weren't writing off non-small cell lung cancer, but we did need to use the last 6 months or so to learn a lot more. So 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 have failed prior to treatment with KEYTRUDA, nivo or another PD-1 or PD-L1 therapy. So 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. So ultimately, we'll be moving in that direction. The Yale folks are eager to start, but our test 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.

Okay, great. And one more, if I may, actually on your new asset, NC762. Should we assume that the Phase 1 will be structured similarly to studies for your other assets? And do you have a sense based on the literature or your preclinical observations, which tumors might be the most amenable to targeting of B7-H4? And I guess looking longer term, is the plan to limit investigation to oncology, or do you also expand studies to, say, autoimmunity or for inflammation?

Yes. That's a great question or several questions. So with respect to B7-H4, and one thing we have learned in NextCure is that moving forward, developing the tools for patient selection and developing the assays for biomarker analysis will be integrated into all of our programs. So that speaks to where we are now backtracking with NC318 lung, but we'll be applying an NC410 in LAIR and then to your point, NC762. So many gynecological cancers are heavily over-expressing B7-H4. So we see this in ovarian cancer, breast cancer, fallopian tube cancer and many other types of cancer. The Phase I with respect to looking at kind of rapid enrollment and looking at safety and tolerability, we'll be kind of enriching for those patients that are naturally B7-H4-positive. But as we segue into the Phase Ib or Phase II, we also have a test that will be CLIA validated midyear 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, Han?

Yes.

All right. Good. Keep me real.

Good answer.

Your next question comes from the line of Asthika Goonewardene from Truist Securities.

Han, good to meet you. So 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, would the Yale study be recruiting enough patients to delineate between primary progresses and subsequent failures? I'm just wondering if there's any sort of updated thinking on that interplay between PD-L1 and S15 in this particular group. And then I've 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 2 to 4 patient type per month that they will see. So that's what they were looking at to come on to the study. We haven't stratified as far as I recall in the primary numbers that you get from the very beginning or the one that already failed. I think that's why I think we had the arm called naive population. But currently, they have other studies ongoing, that these are going to wrap up. Once those studies wrap up, and there are -- you can predict, right, from some of the base on -- especially with the pembro, with the MSI-high and what have you. And they could have easily predict those. And that in future will be used in the naive population. But right now, I think they're concentrating on the failure population first.

Got it. Okay. And then in terms of the B7-H4, 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?

Yes, that's a great question. So I think how we differentiate that when we look at product development, we look at targets, we look at candidate and then we look at patient population. So we've always felt B7-H4 is a really important target. And I think your earlier question, people were -- someone was asking about autoimmunity, and it potentially does have applications in looking at autoimmune diseases. But in -- 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. And when we talk about function or mechanism of action, NC762 is clearly different. And 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 to read it but also ascertain how best to position this for when Han would join us in and to move it into the clinic. Tim, anything else you'd like to add?

No, that's exactly the answer.

Great. And then lastly, on NC410, are you able to give us any update on where you are on the dosing, dose escalation? And -- or if you complete -- or how far you are from completing recruitment?

Yes. So 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, and as Han mentioned, we'll be reporting an update on that trial later this year.

Your next question comes from the line of Tony Butler from ROTH Capital.

I appreciate the update. Just a very simple -- 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? And 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. And 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.

So 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 quantitate, I think, 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. But 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, Han, any thoughts on the naive versus the refractory population and the impact that might have on S15 expression. Not sure we know that.

No, I don't think we have -- we know that. I mean 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? MSIs 1 and then there's many other markers that they'll be looking at. They're looking at out any mistake and so on. There are so many ways that they've been determining. So 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, the way you frame it, I don't think we know the answer.

Yes. So as we talked about today, on 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 refractory patients. So we'll be learning a lot, and we'll be looking at both S15 expression and PD-L1 expressions.

Your next question comes from the line of Ren Benjamin from JMP Securities.

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 seated in both the head and neck trial the triple-negative study? And how many do you plan on enrolling after the protocol amendments? And have you -- I know you mentioned the PD-L1 staining, at least for the head and neck patients, but any color you can give us regarding the Siglec-15 and expression or staining from these patients that are responding?

Yes. So 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. And 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 in the -- after the protocol amendment has taken place for the...

Right. Yes, 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 2 of that Simon 2-stage study.

Got you. And 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 I and Phase II trials will look at about 100 -- or I'm sorry, our Phase II trial will look at about 100 patients in total.

Correct.

Got it. Okay. And just switching gears for to NC410. It seems like a big component, and I think you mentioned it before is, of course, biomarker development. Can you give us kind of sense as to how you might be looking at biomarker development for the NC410 asset?

Yes. Boy, how much time do you have? I love talking about NC410 biomarkers. Yes so as Han walked you through, so NC410 is a fusion protein of LAIR2, which works through a decoy mechanism to basically stimulate T cells in dendritic cells to restore immune function. But LAIR1 and LAIR2, bind 2 key ligands, collagen, and this is monomeric collagen expressed on the tumor that impact the extracellular matrix in the architecture of the tumor and the CME. It also binds C1q, which is also an important part of the complement system and impacts the immune system. So what we've done is, wow, we -- our team has been, I think, going a little overboard on developing the tools from a biomarker perspective. So we can look at LAIR1. We could look at LAIR2. We're looking at collagen and college degradation products. We're looking at C1q. So 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 population and help the individual to give us the ability to do some comparative analysis. So independent of the traditional PK and PD analysis that we would do, in looking at immunophenotyping, looking at cytokines and chemokines, NanoString, so many of the biomarkers that most people are familiar with in immuno-oncology, we've added on to that with respect to LAIR1, LAIR2, collagen and C1q, and I'm sure, by tomorrow, there may be a few more. Sure thing.

Got it. And 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 B7-H4, and that did not come out of FIND-IO. Now historically, Dr. Chen has worked on the B7-H4 program, and that would have been before the advent of the precursor of FIND-IO. So it's a homegrown product candidate.

Your next question comes from the line of Aydin Huseynov from Benchmark.

Congrats on the progress. The first question I have is about the Phase I mono study. So initially, you planned lung, had another TNBC and ovarian, so lung essentially stopped. Head and neck got a 1 response, TNBC 1 response. But did you see any responses in ovarian cancer?

Yes. So we did not see any responses in ovarian cancer. We also didn't generate the number of biopsies that we had hoped to. So 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. And for non-small cell lung cancer for the 2 responses that you have, 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 CR/PR, were in our Phase I dose escalation study, where biopsies weren't collected at that time. So that's most unfortunate. But fortunately, both patients are still around today.

Right, yes. And for B7-H4, do you see -- for NC763 assets, do you see any potential synergies with PD-L1 or any targeted therapies in the future?

So our research folks are doing in vivo comparative studies. I mean, that's something that comes to mind, maybe PD-1 or PD-L1, but there may be some other molecules like CARB inhibitors that are already approved and being used in gynecological cancer applications. So network is still in research, but 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.

Thanks.

Okay. And 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.

Yes. So we haven't provided any guidance with respect to any specific partnerships that might be consummated. But you are correct that we have a very proactive business development team that Tim leads, and we're constantly and consistently engaged in multiple discussions on multiple fronts. So we remain opportunistic, but no defined guidance at this time.

Here, we have a follow-up question comes from Tony Butler from ROTH Capital.

Sorry for the follow-up, but this is brief. The dosing of the Siglec-15 is every other week, if I recall correctly from, I guess, the deck. But importantly, how do you do the trial, or how do you think about doing the trial in conjunction with PD-1 given -- or at least pembro, given its dosing, which is clearly different?

Tony, I think the pembros have been dosed at every 3 weeks and the -- our drug has been given every 2 weeks. That's the current design. But 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, but right now, that's how they designed it.

And there are no questions on 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 discussion. Have a nice evening.

Thank you very much.

This concludes today's conference call. You may now disconnect.