Hello everyone, and welcome to day three of the 2021 Bank of America Healthcare Conference. Thank you for joining this session with NextCure. My name is Alec Stranahan, and I'm the analyst covering NextCure here at BofA. I'm pleased to be joined by Michael Richman, the President and Chief Executive Officer of NextCure, and I believe Michael is going to run through some slides to start, and then we can jump into Q&A if there's time for that. Michael, over to you. Great. Well, thank you very much, Alec, and thank you very much for the opportunity to speak at the BofA Securities Conference. It's a pleasure to give you a quick update on NextCure. Hopefully everyone has the slides in front of them. The first slide really addresses the key vision for the organization, and this involves developing next-generation immuno medicines. On Slide two is our forward-looking statement. On S lide three, these are NextCure's highlights. We call these the three Ps, our pipeline, our platform, and people. I'll walk you through quickly our pipeline. We're very proud of it. Over the last five years, we've introduced three INDs, taken two products into the clinic, NC318, which is currently in phase II, NC410, currently in phase I, and our recently announced IND filing of NC762. In addition to the pipeline, we have a discovery platform we call FIND-IO. This stands for Functional, Integrated, NextCure Discovery in Immuno-Oncology, this enables us to discover and validate novel targets that we hope will impact those patients in need and addressing unmet medical need. Finally, our people. We have a fully integrated GMP manufacturing that's to produce clinical material to support our pipeline. We've recently announced earlier this year the hiring of Dr. Han Myint as our CMO. Finally, as many of you may recall, the company was founded about five years ago, by Dr. Lieping Chen, who discovered PD-L1 and remains fairly active with the company as both a founder, consultant, and head of our scientific advisory board. Slide four is a high-level overview of our product development pipeline. NC318 is a humanized monoclonal antibody against Siglec-15. We're currently in phase II in monotherapy. We've also recently announced a combination with PD-1 with our founding institution at Yale University. Thirdly, we're pursuing a phase I clinical trial. This is a dose escalation safety tolerability study with NC410 or LAIR-2 decoy program. Finally, NC762, which we'll be initiating clinical trials shortly. In addition to that, we have multiple programs working their way through the pipeline, and you'll be hearing much more about those in the coming years. Just to point out, NextCure owns full worldwide rights to each of its programs. Slide five, let's briefly talk about NC318. This is a humanized monoclonal antibody targeting Siglec-15. Siglec-15 was in fact discovered by Lieping Chen at Yale University. It's got a unique expression profile, unlike many other IO targets, since it's expressed both on the tumors and the infiltrating M2 macrophages. This unique expression profiles creates an immunosuppressive environment, and we've developed NC318 to counteract that suppression and to activate the immune cells to kill the tumor. We'll briefly talk about an update on the program with respect to our newly developed CLIA-validated immunohistochemistry test that we'll be using for selecting patients. We recently announced our collaboration with our founding institution, with Yale University to return to lung with respect to looking at both monotherapy and combination with an anti-PD-1. We'll be applying a lot of the lessons we've learned with respect to patient selection. We're looking at combinations and also addressing an extensive biomarker analysis with our future programs. Just to kind of recap for those that have been following the company, you may recall NC31's history in phase I, where we conducted a dose escalation study, 49 patients, 15 different tumor types. We looked at all comers at the time. At that time, about 25% of those patients were non-small cell lung cancer. We had one CR, we had one PR, and three stable disease. Happy to say that the CR and PR subjects remain on therapy. Our phase II, which is ongoing, the recommended phase II dose at 400 mg every two weeks. We're conducting biopsies, and we've announced in the past that we have two PRs, one in head and neck, one in triple-negative breast, both in which we've advanced to stage 2 of the Simon 2-stage study. Moving forward, we'll be selecting for S15-positive patients. As mentioned earlier, we're also conducting a study with Roy Herbst and Scott Gettinger at Yale. These are leading lung cancer oncologists, and we're very fortunate to have the opportunity with them, coupled with the supply of pembro by Merck. This is a three-arm study, a mono study looking at S15-positive patients in a PD-1 refractory setting. Quite interestingly, looking at the combo with pembro, both in PD-1 refractory and PD-1 naive patients. I think one of the more important updates, and something many of you know we've been working on for a long time, is a CLIA-validated immunohistochemistry test. This is a highly specific sensitive monoclonal antibody that helps us detect S15 expression in patients both on the tumor and within the stroma. We'll be taking tumor biopsies from patients, we'll be validating those with our CLIA-validated test and enriching for selection for S15-positive patients moving forward. We'll be reporting an update on this trial by the end of this year. Let me transition into NC410, our second program. This works through a decoy mechanism involving LAIR-1 and LAIR-2. LAIR-1 is a co-inhibitory molecule expressed on dendritic cells and T cells that creates this negative signaling and immunosuppressive condition. What we've tapped into is what Mother Nature does naturally. She created a second gene called LAIR-2, which is much more specific to the ligands than LAIR-1. It shuts down that inhibitory response that enables one to restore immune function. Quite interestingly, the mechanism of action works through the extracellular matrix. We believe this interaction is having an impact on changing the architecture of the ECM moving forward, which will hopefully restore immune function and treat patients. At SITC last year, we had two posters with respect to the mechanism of action in NC410, and also looking at combination therapies in three independent preclinical experimental works with respect to looking at PD-1 and PD-L1 combinations. We'll have an upcoming poster at ASCO with respect to kind of an in-trial and progress. Mechanistically, LAIR-1 and LAIR-2 bind one of two ligands, both collagen on the tumor as well as C1q, which is part of the complement pathway. LAIR-2 competes with LAIR-1 to restore immune function. What we've done is we've just basically taken what we've learned from mother nature. We've created a biomimic of LAIR-2, which enables us to outcompete LAIR-1 binding to activate T cells and dendritic cells to kill the tumor. As mentioned earlier, we're currently in the phase I portion of a phase I/II human study. This is a dose escalation of safety and tolerability study. We're looking at multiple advanced and metastatic solid tumors. Most of these tumors are fairly collagenous based, since LAIR-1 and LAIR-2 bind collagen within the extracellular matrix. We're looking at lung, ovarian, and pancreatic, as well as other tumor types. We'll be providing an update on the phase I trial by year-end. Transitioning into our third program, again within five years, is NC762. This is a humanized monoclonal antibody against B7H4. We screened and evaluated many antibodies to develop this particular candidate that has a unique mechanism of action in directly killing tumors that is independent of T cells. NK cells have been shown to enhance this tumor activity, and our plan is to look at a number of gynecological cancers as well as lung cancer moving forward, where we know B7H4 is heavily expressed. The IND is filed, unique mechanism of action. Many lessons learned from NC318. We will have an assay, as we will with NC410, to select those patients that express the target that we believe will be most responsive to treatment. We'll be evaluating extensively biomarkers. I'd like to just touch base on our manufacturing. It's not something we often talk about, but a critical and competitive advantage, especially during the time of COVID, where it's difficult to get biologics manufacturing capacity. We had 1,000 L of capacity during COVID over the last year. We doubled that capacity by adding another bioreactor. This provides an efficiency that enables us to produce clinical material much more quickly than outsourcing that others might do. Also provides us a lot of flexibility in scheduling, efficiency from an operation and capital use perspective, and then also managing the quality of the clinical material that we produce. All three of our trials will be using clinical material produced here at NextCure. Finally, we have our platform. Again, this is FIND-IO, Functional Integrated NextCure Discovery. This is a platform that we industrialized, automated, and roboticized from what Lieping Chen originally developed and how we discovered PD-L1. We're applying these screens and these validation tools to develop this whole next generation. You'll be hearing about a lot of these targets working their way through the pipeline. Independent of oncology, there are opportunities to diversify into other areas such as autoimmunity and inflammation and also neuro as it relates to the targets that we've been discovered. Anticipated near-term milestones on Slide 15. As mentioned earlier, we'll provide an update by year-end on both the NC318 phase II trial as well as the NC410 phase I study. Q2 of next year, we'll be focusing on the outcome of our collaborative work with Yale, looking at the mono and combo studies with NC318. Then second quarter of next year, we'll provide an update on the NC762 study. Thank you very much for the opportunity to give a brief update. Just in summary, NextCure has taken a very focused approach over the last five years. We have a lot of momentum, have taken three things pretty much in the clinic, leveraging our platform, and applying all this to develop next-generation immunomedicines. Thank you, Alec. Great. Thanks, Michael, for that overview. Very helpful. Now we can transition to Q&A. I have a few here, but for those dialed into the webcast to log a question, simply submit it through the Veracast platform and I'll read it off. Michael, maybe we could just start on NC318. We obviously saw some early responses from phase I, and the phase II study is ongoing. Could you maybe talk about the S15 patient selection you're planning to implement, I think starting in 2Q? Is this active already, and I guess could you just talk a little bit about the assay that you've built? Sure. It's a great question. What we've learned in developing these next generation immunomedicines is that when you're looking at novel targets and first-in-class proprietary molecules, there are three things we have to get right. The target, the candidate, and the patient. Focusing on the patient, we've realized, and there's been some learning lessons along the way, how important patient selection is. Our plan moving forward at the end of this quarter to continue with the phase II enrollment is we've developed an immunohistochemistry-based test that enables us to take biopsies from patients and look at S15 expression, both on the tumor as well as looking at the M2 macrophages within the stroma. We think this gives us a real competitive advantage to enrich for those patient cohorts that we believe will be most responsive to therapy. This was not an easy undertaking, and as many of you know, it's taken a little bit longer than anticipated. This started with the work in collaboration with David Rimm, a leading pathologist at Yale, where we screened many monoclonal antibodies, with respect to murine, rabbit, and other types of monoclonals. Through that effort, we were able to define a specific one that gave us the specificity and the sensitivity. Once that was done, we then needed to work closely with our CRO to do additional development of the assay and the validation. Long-term process, the nice thing is we've been applying the same process now for NC410 and NC762. To answer your question, the test is ready to go. We're in the process of submitting an amendment to the FDA. Hopefully, we'll hear back shortly, and we'll start screening patients and look for those S15-positive individuals. Okay, great. Maybe you could talk a little bit about the investigator-led study at Yale. It's going to be NC318 and non-small cell lung, and will test obviously monotherapy but also in combination with KEYTRUDA, I believe. Could you maybe just talk a little bit about the rationale of continuing to pursue non-small cell lung cancer given the phase I data, and sort of your thoughts around patient selection for this study in terms of prior PD-1 exposure? Yeah, thanks, Alec. Therapy exposure. Oh, thank you. There was a little bit of a delay. Yeah, with respect to the phase I study where we saw the PR and CR in three stable disease in non-small cell lung cancer, that gave us hope that moving forward, we would be able to treat this population. Unfortunately, when we enrolled lung cancer patients in the phase II component, we did not see any responses. When we went back and looked at the biopsies, we saw very few patients that were S15 positive. At that point, that led us to believe that S15 selection was going to be more important. During middle of last year, we put lung cancer on hold. We were moving forward with head and neck as well as triple-negative breast cancer, where we saw PRs in each of those indications. Through our founding institution, Yale University, where they were involved as a site in the phase I study, they remained very interested in Siglec-15 biology. We got to know Roy S. Herbst and Scott Gettinger quite well, leading lung cancer specialists, and they were interested in doing a NC318 study in combination with pembro, based on some of the preclinical data that we have generated in combination with anti-PD-1. Based on that, coupled with a very clear design that our CMO, Han Myint, and his team have been focused on in collaboration with our colleagues at Yale University, we have a real great strategy to move forward. It has a monotherapy arm where we will select for S15-positive patients. These will be PD-1 refractory patients, and then there'll be 2 arms with respect to the combination with pembro, where we'll be focused on refractory and naive patients. We think this is a very important move for the company in not giving up on lung. We still believe that both the preclinical data, all of the immunohistochemistry expression data, coupled with the phase I data that we've observed, that Siglec-15 is playing a very important role. Working through our phase II and now working with Yale, we'll be able to answer some of these key questions in monotherapy, in combination with pembro, and then also applying an extensive biomarker analysis. There's a lot of traditional work in immunophenotyping, looking at cytokines and chemokines. We'll be looking at soluble Siglec-15, which could be playing an important role in the mechanism of action. We'll be applying NanoString technology. We'll be able to look at both tissue and things within the blood to determine mechanistically, is NC318 doing what it needs to do? Okay, that makes sense. Maybe switching over to NC410. Obviously, LAIR1 is another novel target that hasn't really been pursued by many others. Could you maybe just talk about LAIR1, your rationale for going after this molecule, and sort of the preclinical observations that have supported your confidence going into the phase I study? Yeah. LAIR1's been around for a while. It was first discovered in the context of autoimmunity by Linde Meyaard, who's actually one of our collaborators at Utrecht University now. Lieping Chen and our head of discovery, Dallas Flies, actually worked on LAIR1 many years ago because it's a co-inhibitory molecule similar to other immune modulators that people are evaluating. The LAIR1 biology is quite exquisite because it's a natural process in which the tumor has hijacked the immune system to prevail. LAIR1, as we were describing earlier, is expressed on T cells and dendritic cells, and by binding one of its ligands, either collagen on the tumor or C1q, which is part of the complement pathway, you have a negative signaling effect, which creates an immunosuppressive condition in the TME, and when that allows the tumor to grow. Somewhere along the way, mother nature duplicated the LAIR1 gene to create LAIR2. It's 70% homologous to LAIR1, but it differs in two respects. It's soluble, so it's not membrane bound, and it binds to collagen and C1q with higher affinity. What we've done in creating NC410 is this biomimic that works as a decoy similar to LAIR2 to basically counteract LAIR1 binding to its ligands, enabling us to activate the T cells and dendritic cells to restore immune function. The pre-clinical data that we've generated mechanistically has demonstrated that this works exactly the way mother nature probably intended for it to do. We've generated a significant amount of in vivo data to demonstrate the biological activity and the function of NC410. I think quite interestingly is some of the combo data that we reported on at SITC last year. We presented two posters, one on the mechanism of action of NC410, then two was the collaboration we've had with NCI, where we were looking at bintra, which is a PD-L1 TGF-beta trap in combination with NC410. We saw exquisite and impressive tumor killing in those experiments. Quite interestingly, when we went back to challenge the mice, they maintained a memory immune response, and the tumors did not come back. We actually repeated the findings internally here NextCure with PD-L1, then thirdly, also with our collaborator in the Netherlands. In three independent studies seeing very important combination study of NC410 with a PD-L1 like molecule. What we believe is happening is you're changing the extracellular matrix architecture. By doing that, it may enable PD-L1 to do certain things beyond what it might be able to do on its own and seeing this synergistic effect. We're learning a lot about the biology of LAIR-1. We think NC410 has some real special properties, from a functional perspective. Now we're really excited as we work through the phase I dose escalation study. We're about midway through the cohorts, and as I mentioned, we'll be reporting an update on that trial by year-end. Okay. That makes sense. We're definitely looking forward to the data update later this year. I think you said that we may be seeing some data from NC410 at ASCO as well. I think I heard you right. Yeah. This basically will just be pretty much an update on trial and progress. We'll provide some additional pre-clinical data as well as kind of a design of the trial. This is being shared kind of in anticipation of the more focused clinical data to year-end. Okay. All right. That makes sense. Maybe switching over now to NC762, which is your newest asset. Should we assume that the phase I will be structured sort of similarly to NC318 and NC410? Obviously, you're planning to include selection maybe from the get-go in this study as well. Looking at NC762 focused on B7-H4. The trial design is pretty similar to what we've seen. It's pretty much a 3-by-3 design. It's a dose escalation study looking at safety and tolerability. Obviously, we'll be looking very closely at clinical samples that we could evaluate from a biomarker perspective. Mainly, we're looking at safety and a recommended phase II dose that we could then move forward with a phase II, where we will be using a CLIA-validated test to select those patients that are expressing B7-H4 and that we think will be most responsive to NC762. Okay. I guess if you look at the sort of expression patterns of B7-H4, are there any sort of tumor types that jump out that might be more amenable to treatment? I guess, sort of along those lines, I mean, B7-H4 is also expressed in some autoimmune diseases as well. Are there any plans? Maybe apply NC762 to those indications also. Yeah, that's a great question. B7-H4 is overexpressed in a number of different tumor types. People have worked on it for many years. I think our molecule has a unique mechanism of action and approach. It's overexpressed in many gynecological cancers. You see it really light up when you do the immunohistochemistry studies in breast cancer, in ovarian cancer, fallopian tube cancer, and of course, you see it in other types of cancers, such as non-small cell lung cancer. We think this has a unique opportunity. I think the mechanism of action with respect to direct tumor killing is somewhat differentiated and enables us to position this in monotherapy. With that said, we will evaluate combinations if that makes sense from a life cycle management. There are others working in the field looking at ADC types of approaches. If need be, we can certainly add a linker and a payload to it. At this point, we don't think we need this to see the clinical effects. We're obviously looking forward to starting that trial, and getting that into patients to see what clinical impact it will have. Okay. That makes sense. Maybe just wrapping up, you guys have alluded to plans to file at least one IND a year over the next few years. The early-stage pipeline is definitely not standing still. Maybe it would be great if you could provide a little bit more color on the preclinical work you guys have been doing and whether any of these INDs over the next few years could actually be maybe outside of oncology, say, from FIND-IO, or is the plan really just to go full in in cancer? We've been developing our FIND-IO platform over a number of years, and our goal is still to ultimately file one IND per year. We have a richness of assets. Each of these targets are novel, first in class, and proprietary. Each of these targets has a functional activity that impacts the immune system, so it can be stimulatory or inhibitory. When we look at these targets, many of them are overexpressed on tumors or various immune cells. We've also learned over the years that some of these targets will have applications in autoimmunity or neuro. I know, sorry, you did mention autoimmunity in the case of B7-H4, and yes, there is applicability with respect to a fusion protein that could have impact on T-cell-mediated autoimmune diseases. We're very interested in looking at the other side of the immune system, and this screening platform that we've developed enables us to look at these targets in a different way. Very similar to CTLA4, where the antibody focuses on cancer and the fusion protein, ORENCIA, focuses on arthritis. We're always looking at both sides of the pathway with respect to a ligand and a receptor, and whether we want to develop an agonist and/or antagonist to turn on the immune system or to turn it off in the case of autoimmunity. Neuro is a really interesting area. We're very interested in looking at the convergence of neuroscience and inflammatory disease. Many of the targets that we pull out of our screens, Alec, when we go back to the literature, you find out that they have roots in neuroscience or in some cases, even skeletal biology. We think this is really interesting because before we had modern-day immune systems, we had skeletal systems, and we had neuro systems. A lot of these targets that we've identified, we hope will have the opportunity to look at this next wave of unmet medical need in looking at CNS disorders, and we hope to have some of these targets play a role in that. Okay. Very interesting. I'm looking forward definitely to see the pipeline progress and the data later this year. I think we're out of time, so we'll leave it there for today. Mike, I really wanted to thank you for taking the time to participate in the conference and for the great overview of your business. Really appreciate it. Well, thank you very much, Alec. It's been a real pleasure, and thanks for sharing your great questions and giving us this opportunity. Of course. All right. Take care, and thanks to everyone on the line for your interest. All right, take care. Thanks. Bye-bye.