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

Good morning, everyone. My name is Ray Wang, and I am a member of the JPMorgan Health Care Investment Banking team. Thank you all for coming here this morning. And just wanted to let you know the breakout room will be in the Olympic room outside to the left. And now it is my pleasure to introduce Michael Richman, President and CEO of NextCure.

Thank you very much, Raymond. And I'd like to thank the JPMorgan staff for giving us the opportunity to present today. This is our first time at JPMorgan, and it's a pleasure to be here to introduce NextCure to all of you. We started NextCure 4 years ago with the mission to develop these next-generation immuno medicines, and that's what we'll be walking through today. I'd just like to introduce our forward-looking statement slide. But let me tell you about NextCure and some of the highlights that we've been focused on and that we've achieved over the last 4 years. We call these our 3 Ps: Our pipeline; our platform; and our people. I'll walk you through our platform. This is our lead program, NC318, it's a humanized IgG1 monoclonal antibody targeting Siglec-15, S15. This was discovered using an early version of our FIND-IO platform, and it's clearly different than many of the other targets that you may be reading about today, based on its unique expression profile both on the tumor as well as the infiltrating M2 macrophages. It also has this nonoverlapping expression to PD-L1. So it opens up the opportunity to treat those 60% to 70% of patients that would not respond to a PD-1 or PD-L1 treatment. I'll walk you through some of the Phase I data that Tony Tolcher, our collaborator; and Kevin Heller, our CMO, that presented at SITC in November of last year, where we saw a single-agent activity on this novel target. Our second program, NC410, we'll be filing the IND first quarter of this year. This focuses on the LAIR pathway. This is an IgG1 FC fusion protein that works through a novel decoy mechanism to activate T cells and dendritic cells to restore immune function. And then finally, we're a fully integrated organization. We have our own GMP manufacturing facility. We have 1,000 liters of capacity in Beltsville, Maryland, which enables us to advance and accelerate many of the novel targets in our pipeline in a much more expeditious and capital-efficient manner. The second PR platform, we call this FIND-IO. This is an acronym for Functional, Integrated, NextCure Discovery. Using an early version of this platform, our founder, Dr. Lieping Chen, known for his discovery of PD-L1, actually discovered Siglec-15 among many other targets that people are working on today. It's this platform that plays into the development of novel targets to build our pipeline and to build value for patients and shareholders alike. And then finally, our people. We have an experienced team that has been doing this for a long time with respect to building companies in the mid-Atlantic region, focused on biologics and focused on taking novel technology and strong immunology moving forward. We have a multiyear, multimillion dollar-sponsored research agreement with our founder, Dr. Lieping Chen, who, as I mentioned, discovered PD-L1 and is responsible for many of the targets people are working on today. So why did we start NextCure? Well, we woke up one day, and we felt that half the world that become immunologists overnight, all focused on PD-1 and PD-L1, we thought we needed to do a better job. So we decided that we were going to build an organization focused on novel targets, novel science and new biology to address those nonresponders. Those 60% to 70% of patients that don't currently address or not addressed with PD-1 and PD-L1 therapies, not to mention those individuals that progress on standard of care and furthermore, the limited treatments available for many of the tumor types facing patients today. So we have to come up with new solutions and then that's exactly what NextCure is doing in Beltsville, Maryland with respect to developing new therapeutic options for patients, driving clinical responses and improving the quality of life for individuals that what we hope will ultimately benefit from the treatments under development. We call this our immunological wheel. We're agnostic with respect to discovery. We're driven by the science and we're driven by the biology. You'll learn today NC318 at 1:00 works through unique mechanism of action on myeloid cells and M2 macrophages. At 3:00 p.m., our second program, NC410, which we'll be learning more about later this year, activates T cells and dendritic cells to restore immune function. We've also identified many other novel targets that impact one or more different types of immune cells within the tumor microenvironment to restore immune function. This sort of pipeline -- again, this is a pipeline to put it in the context that was developed over just a 4-year period. Again, NC318 is currently in Phase II. This is a humanized monoclonal antibody targeting Siglec-15, expressed both on the tumors and the macrophages. We reported the top line Phase I data at Citi last year. We initiated the Phase II in October of last year, and that's currently enrolling. We'll be reporting top line Phase II data by the end of this year. Aligned with this strategy to advance and accelerate NC318 to patients much more quickly, our clinical team is embarking on a combination style -- combination trial, middle of this year where we'll take NC318, and we'll be combining a combination of chemotherapeutic agents. We'll be looking at pemetrexed/carboplatinum in one line and also we'll be looking at docetaxel. And as I mentioned, NC410, we're in the process of finalizing the submission of the IND to the FDA, which will happen first quarter of this year. But next year is much more than that. We have other targets that you'll be hearing about as we build the organization with respect to multiple programs based on novel targets and new biology as well as those being developed in our FIND-IO discovery platform. So let me tell you a little bit about NC318, our lead program. This is targeting Siglec-15. We often refer to it as S15. It has this duality of expression, both on the tumors and the macrophages. And S15 biologically has been hijacked by the tumors to create an immunosuppressive condition to allow the tumors to grow. We've spent a lot of time over the last couple of years trying to understand the mechanism and biology of Siglec-15, and the result of many of these findings in collaboration with our founder, Dr. Lieping Chen, were published in Nature Medicine earlier last year. So on the left-hand panel, you'll see the Siglec-15, again, has this duality of expression on the tumor that we can measure as well as these infiltrating macrophages, we call TAMs. And it's this expression profile, that creates this immunosuppressive condition within the tumor of microenvironment that allows the tumor to grow. But more interestingly, went through many of our immunohistochemistry studies in collaboration with Dr. David Rimm at Yale, we were able to identify this unique nonoverlapping mutually exclusive expression profile to PD-L1. So how does that look? So in this particular illustration, as we've all learned in early math education, we finally get to put Venn diagrams to use. So you're either PD-L1 positive. And in that event, you'll be subject to nivo or Keytruda, but many of those patients are Siglec-15 negative. And if you're S15 positive, you're PD-L1 negative. So again, this opens up a unique segment of the population that would not respond to PD-1 or PD-L1 therapy that may be suited for NC318 treatment. Let me tell you a little bit about the mechanism of action on Siglec15. As we mentioned, as expressed on the tumors in the M2 macrophages, it creates the differentiation of survival of these myeloid cells, and it's these myeloid cells that release these pro-inflammatory, pro-tumorigenic cytokines that inactivate the T cell and allows the tumor to grow. And what we've done in NextCure is we've created NC318 designated by these orange y-shaped illustrations, where we could counteract the differentiation and survival of the myeloid cells, we could stop the production of these pro-tumorigenic cytokines, which enables us to activate the T cells to restore immune function. And this is shown in some of our in vitro findings. Again, we were -- in the first box, we're here, we're able to inhibit these myeloid cells when NC318 is added to these assays. Secondly, we can decrease the inflammatory cytokines such as IL-1beta, IL-6, TNF alpha. And then finally, and most importantly, we could activate the T cells, produce interferon gamma to kill the tumor. We've spent a lot of time studying this in vitro and in vivo, but most importantly, we're using the most important model, human beings. This slide shows the Phase I data that we reported at SITC in November of last year. This demonstrates -- this was a safety and tolerability study. We enrolled 49 patients, over 7 dose cohorts, 15 different tumor types where each of these individuals were very highly pretreated. We looked at all-comers in this trial. From a safety perspective, we saw no DLTs up through the 800 mg dose cohort. We did see a pneumonitis at 1,600 mgs. And more importantly, we saw many common immune-related adverse events such as diarrhea, rashes, vitiligo that you often see in developing immunomodulators. And this is an important effect, where as we went in -- as we increased in dose cohorts, we show -- which demonstrated an increase in frequency and severity of these immune-related adverse events, such as vitiligo, uveitis, pneumonitis. These are non-observations seen in normal cancer progression. These are pathologies observed when the immune system is being modulated. Most interestingly, the clinical responses that our clinical team and our investigators observed as part of the trial. These evaluations of these patients were done every 8 weeks. We saw a CR. And this individual has been on drug for over a year now. We also saw a PR, where the individual has been on drug for over 6 months. And then we saw many people, many patients that had stable disease. In this particular slide, we show the swim plot of the 49 patients that were administered drug in the trial. The color coding shows the various dose cohorts. Again, these were heavily pretreated individuals. And most importantly, the reason for presenting the data this way is showing the durability of response. Many of these patients, including our CR and PR, the 14 stable diseases we observed, still kind of remain on drug as of the data we reported at SITC in November. This is zooming in on a partial segment of the data. About 1/4 of the patients enrolled in the 49-patient Phase I safety and tolerability study were non-small cell lung cancer patients. These were PD-1 refractory patients. And this is a snapshot showing the durability of response as well as the CR and PR that was demonstrated in this trial. Looking at the responses a little bit more closely, NC318 demonstrated single-agent activity. We saw a durability of responses and stable disease. We saw immune-related adverse events, but most importantly was this complete response. This was in the 56-year-old non-small cell lung cancer woman that had multiple target lesions, 2 in particular at 10 millimeters based on RECIST criteria. She had 3 prior chemo treatments, then came on to nivo. She progressed, where she saw -- where multiple nontarget lesions came into the mix. And over time, being treated with NC318, those target lesions disappeared and those nontarget lesions also disappeared, which ultimately -- she was designated as a CR. In similar vein, our PR individual was a 74-year-old gentleman, also non-small cell lung cancer. He had a PD-L1 TPS score less than 50%, similar to our CR patient. He decided not to go on chemo, but was involved in a Phase I clinical trial, looking at a LAG-3, PD-1 combination, ultimately progressed, had 2 big, fairly large target lesions, approximately 2.5 centimeters each. And during week 16, we saw a significant decrease in those target lesions. So on the conclusions from the Phase I portion of the Phase I/II study of NC318, we demonstrated that the drug was very well tolerated over multiple dose levels. We saw an adverse event profile consistent with what others have seen in immunotherapies, looking at these immune-related adverse events. We have a predictable PK profile efficacy, looking at the CR, the PR and the 3 stable disease in non-small cell lung cancer. We also saw a stable disease in other tumor types such as endometrial and Merkel. And as I mentioned, we initiated the Phase II component of this Phase I/II trial in October of last year. So let's quickly review the Phase II trial that was initiated. We decided to focus on 4 tumor types: non-small cell lung cancer; head and neck; ovarian; and triple negative breast. These tumor types were chosen based on not only into the data from the Phase I, but based on some of our preclinical immunohistochemistry studies where we saw S15 positivity, I mean, in tumor micro arrays in many of these different types of tumors. The design of the trial is focused on requesting pre biopsies. These individuals will have a PD-L1 score -- of TPS score less than 50%. And we'll be evaluating S15 expression retrospectively based on the tumor samples that have been collected as part of their biopsies. We'll be doing extensive biomarker evaluations. This is a monotherapy trial, and we'll be working through the -- with our recommended Phase II dose of 400 mgs every 2 weeks. So in summary, we have a fairly good understanding on the mechanism of Siglec-15, and what it's doing biologically, both naturally and within the tumor microenvironment. We've completed and reported data on the Phase I clinical trial at SITC. We've initiated the Phase II monotherapies trial. And midyear, we'll be doing this Phase II combination study in chemo in non-small cell lung cancer. So let me segue into our second program. We're not just a Siglec-15 company, we are an organization, building a pipeline for patients and shareholders alike. So let me tell you about NC410. This is a fusion protein that works through a natural decoy mechanism to restore immune function, and it targets leucocyte associated immunoglobulin like receptor, that's why we call it LAIR, LAIR-1. It focuses at both on T cells and dendritic cells. And what LAIR does naturally, it promotes this activity, and we're developing it for a number of both solid tumors and perhaps liquid tumors alike. Talking a little bit about the LAIR biology. LAIR-1 is a co-inhibitory receptor, like many of the molecules that others are investigating today. It's membrane bound, both on T cells and dendritic cells. And it binds 1 of 2 collagen -- 1 of 2 ligands, collagen or C1q for the complement pathway. It's through these interactions where LAIR-1 expression and negative signaling creates an immunosuppressive environment that allows the tumor to grow. So how does mother nature regulate this? Well, somewhere along the evolutionary pathway, she duplicated the LAIR-1 gene, we call it LAIR-2 and it's different in 2 respects. Although it's 70% homologous to LAIR-1, it's not membrane bound, it's soluble, but it has higher affinity for the ligands, both collagen and C1q. So LAIR-2 enables you to restore immune homeostasis by activating T cells and dendritic cells to restore immune function. So what did we do at NextCure? Well, we're not really that smart. We just copy mother nature. And what we created in NC410 was a bio-mimic. So this is a molecule that walks and talks like LAIR-2, but with greater avidity and affinity for the collagen and the C1q ligands. This enables you to outcompete the negative signals from LAIR-1, activate the T cells and dendritic cells to restore immune function and to ultimately kill the tumor. We've demonstrated a tremendous amount of biological information in understanding this enhanced T cell expansion and this alleviation of immune suppression. So some of the data on the left in a dose responsive way, we've demonstrated that you could block this immunosuppression by measuring T cells. And similarly on the right, we've demonstrated a decrease of tumor volume also in a dose responsive way. So you'll be hearing a lot more about NC410 as we continue to advance this program, but we've demonstrated an understanding of its mechanism of action. We've also been very active at completing our IND-enabling studies including tox studies. We already have completed our GMP manufacturing campaign where we have clinical material in the freezer ready to go, and we'll be filing that IND this quarter. So beyond our 2 lead programs, I'd like to talk a little bit about our platform, we call it FIND-IO. That's an acronym for Functional, Integrated, NextCure Discovery in Immuno-Oncology. This is really different science. This is really different discovery. We use a cube as a metaphor to look at the inputs and the outputs of the system. The inputs of our target libraries were up to almost 10,000 genes where we're walking through the human proteome on a gene-by-gene basis to determine whether or not a given protein impacts the immune system. And if so, is this stimulatory or inhibitory? The beauty of the system is we can dial in different cell types. So in the case of cancer, we can look at myeloid cells, lymphoid cells, various tumor cell lines. But most importantly and the real value driver here are the functional readouts. We're doing a tremendous amount of functional analysis in trying to understand how these proteins impact the immune system. So how does this work? So the methodology is quite simple. On the left-hand side, we actually transpect each gene on an individual basis into a host cell. Moving to the top right, that gene is expressed on the surface of that cell, where we then combine it with an immune cell that's been engineered with a reporter signal linked to a fluorometric tag, in this case, green fluorescent protein. We've also engineered a transfected cell with RFP, red fluorescent protein. So now we can look at bidirectional signaling on a gene-by-gene basis to determine whether or not a given protein might impact the immune system. And this is some of the work our scientist see in the laboratory. On the right-hand side, you always see some vector control and looking at green fluorescent protein readout, but what we're looking for is increase in the GFP landscape, which is indicative of a co-stimulatory function that may alter the immune system. Conversely, you may see little or no GFP representative of a co-inhibitory molecule. On the left-hand side, we call this our cloud. Each dot represents a known protein in our database. Doing comparative analysis, both on a functional basis and aligning that with bioinformatic studies, we could determine whether or not a given protein might, again, be stimulatory or inhibitory. Once we've demonstrate a functional response, we put it through the 3 Rs on the bottom. We spend a lot of time looking at the reproducibility of our findings. And then the heavy lifting begins and looking at the robustness. This is the validation where our targets go through an extensive amount of work to demonstrate whether or not these are druggable targets. And then third and final R is relevancy, in this case, as it relates to cancer. So the platform has a lot of versatility. So imagine not dialing in certain myeloid cells, but imagine dialing T regulatory cells and looking at functional readouts such as cytokines. This enables you to now identify targets that may have applications in various autoimmune diseases to address those 30% to 40% of patients that don't respond to Humira and other anti-TNF therapies. So now we're going beyond FIND-IO into what we call FIND-AI, not artificial intelligence, but autoimmunity and inflammation. So now we can leverage the same platform using the same gene libraries, dialing in different cell types and looking at different functional readouts to determine whether or not a given protein may have applications in another therapeutic area. And then finally, FIND-MIND, where we're finding a lot of these targets have overlap from an evolutionary perspective. FIND-MIND enables us to look at novel CNS targets, nerve regeneration, nerve degeneration. And what we find in a lot of our screens is many of the targets that impact the immune system have evolutionary routes in skeletal systems and neurological systems. And so we're understanding a lot of the biology, which we believe will set the stage for building these new -- building our pipeline moving forward. So our anticipated milestones moving forward, we'll -- we have initiated the Phase II trial for NC318. We'll be reporting that top line data end of this year. We'll be initiating a combination study in chemotherapy in non-small cell lung cancer midyear. Also midyear, you'll be getting an update on the biomarker readouts, and then an update on the Phase I patients that we reported on at SITC. We'll be filing the IND for NC410 first quarter, and you'll continue to hear over time some of the targets that we're advancing through our discovery and validation. So in summary, hopefully, we've given you overview of kind of what a NextCure looks like. Again, over the last 4 years, we've built a fully integrated organization with a very focused approach on immunology. We've demonstrated significant momentum in building our pipeline, advancing candidates through manufacturing and getting them into the clinic. We're leveraging our innovative platform around FIND-IO. And we have the team to deliver on many of our objectives moving forward with respect to the future deliverables of the organization. So thank you very much.

So good morning. And thank you very much for taking the time to listen to the NextCure presentation. We're honored to be here and address your questions. Again, I'm Michael Richman, President and CEO and honored to be here with our -- some of the members of our leadership team. I'll let them introduce themselves.

Tim Mayer, Chief Operating Officer.

I'm Kevin Heller, the Chief Medical Officer.

Steven Cobourn, the Chief Financial Officer.

So we have all the Chiefs up here. So happy to address any questions.

Yes. Michael, so I asked this question before. So regarding your CR, so something was -- passing whether there is really a CR or is a delayed response for everyone there?

Sure. Well, thank you for the question. So the question was the CR, which was seen in our non-small cell lung cancer patient at the 8 mg dose. And let me have Kevin address that since he is the one leading the clinical trial.

Right. Thank you for the question. So the complete response that we observed at the 8-milligram dose. This was a 56-year-old woman with non-small cell lung cancer. And the question was really focusing on whether or not it was legitimate CR because the patient had prior PD-1. So I'd like to point out that, that patient had a PD-L1 TPS score between 1% and 50%. So that's someone who is not necessarily a good candidate to have clinical benefit to a PD-1-directed therapy. Also she had failed 3 prior lines of chemotherapy. And while she was then ultimately put on nivolumab, she developed multiple new lesions while she was receiving nivolumab after 7 months of stable disease. So the fact that she developed new lesions while she was receiving nivolumab so late into the treatment, the probability of her ultimately having clinical benefit 8 weeks later and on to our clinical trial is extremely unlikely. And I would like to also point out that the patient who had 2 target lesions that met the RECIST criteria being 10 millimeters each, they did shrink over time by 40% at the first scan, 80% at the second scan. And then ultimately, she also had resolution of a bony metastasis, which are actually very hard to clear even with very good immunotherapies. And she was declared a complete response based on the PET scans. So there was no minimal residual disease. The fact that her clinical vignette improved, the longer she was on NC318 and the further she was from the last PD-1 dose also significantly supports that this was a direct result of NC318.

Thank you. Any other questions?

Can you resummarize the LAIR2 programs had in the clinic at this point?

Right. So the question was, can we resummarize the LAIR program, which we refer to as NC410.

And whether it's in the clinic?

Yes. So it's currently not in clinic, but we will be in the clinic soon. We're in the process of preparing and filing the IND, which will be first quarter. Once we get to 30-day clearance from the FDA, we have clinical material ready to go. We've identified the clinical sites, and we'll be moving forward to initiating that trial on patients. So I would assume, definitely by the first half of this year, we'll have embarked on dosing patients.

Would that be the same type of patients as your first drug?

Yes. So the question is, would that include the same types of patients as our first drug where we did all-comers in the Phase I. Kevin, you've designed the trial.

Right. So with -- again, the question regarding what type of patients will be -- will we be examining for the NC410, the LAIR program? For a first-in-human study, we always have to balance quickness and efficiency of enrollment with also trying to get as much data as possible. So while it will focus on solid tumors, much like the NC318 program, part of what we're doing right now and my colleagues back at NextCure and the labs are evaluating more data with regard to tumor types that might be more suitable for response. So we can easily address as we move into the Phase II component of the NC410 trial and focus on patients that might have T cells or dendritic cells that are expressing LAIR-1 and perhaps a little bit more responsive. And if I may extrapolate, this is very much like how we handle the NC318 program that as emerging data presented itself, we shifted what tumor types to evaluate in the Phase II program. So when we say that we follow the science, it's not lip service. We genuinely are always evaluating our options. Our Phase II component for NC318, which actually began enrolling right around SITC back in October of 2019. We are focusing on tumor types that demonstrated Siglec-15 expression. So you can imagine we're going to take that same scientific approach of what makes the most rational sense and moving from there.

Thank you. Well, maybe we could ask you folks some questions. Yes?

Can you tell us a little bit about the competitive landscape of S-15, especially in combo with [indiscernible]?

Sure. So the question was, can we discuss the competitive landscape for Siglec-15? The beauty of building an organization around novel, first-in-class proprietary targets are -- there is no competition. Historically, Siglec-15 was developed in a clinical trial for -- in osteoporosis. This was done by Daiichi Sankyo in Japan, based on the natural mechanism of Siglec-15 in bone remodeling, that did enter a trial, but they are no longer pursuing the program. So to the best of our knowledge, no company is developing an anti-Siglec-15 therapy. However, what we've learned in this business, and once the target is validated and seems to have some promise, we could reassure that some competition will come in. I think we saw that with PD-1.

And I believe the second part of the question was with regard to combining NC318 with PD-L1s or PD-1 directed therapies. So if I may address that. Because Siglec-15 is expressed typically when PD-L1 is not expressed, we do not immediately have the scientific rationale for concurrent dosing of NC318 with, say, a PD-1 like pembrolizumab or nivolumab. However, we have had multiple investigators still suggest the general concept of trying them concurrently, if not sequentially. Because perhaps, patients who relapse on a PD-1 directed therapy might have a change in their immune surveillance evasion, right, in the tumor microenvironment and therefore, it could make sense to switch between the 2 therapies. That being said, we think it's an excellent idea to still look at it from an academic perspective, and we have had investigators approach us to run investigator-sponsored trials evaluating the combination. And in the event that there is significant synergy that, I think, at the moment, I would be a little surprised, we'd be more than happy to change gears and pursue it with a partner, perhaps. Yes.

So I'm interested in your discovery platform. So just wondering what is the efficiency there , like, from early screening to only to getting a lead compound, what is the block timeline there?

So the question is our FIND-IO discovery program and the efficiency in identifying targets, and how long it might take to get lead program? So we look at a 2-year window. So we're constantly doing screens. Our libraries are now about 10,000 genes. We go through multiple screens to identify that initial functional activity. Once that's identified, that second R regarding the robustness entails a lot of validation. And that includes everything from looking at expression profiling of a particular target. It could include knockout studies in mice, significant breadth of in vitro studies based on immune activity, and then ultimately looking at in vivo models. So -- for example, in the case of Siglec-15, we took that from target to Phase I clinical trials in 2.5 years. That's pretty quick these days. But obviously, there's a certainly patients in need. So we think within a 2.5- to 3-year window, once we've demonstrated a validated target, we can then advance it forward very quickly through translational research, through development with respect to developing cell lines, manufacturing material and getting it into the clinic. The nice thing about the platform is we're parallel processing. So it's not necessarily a linear approach. There's multiple targets being validated at any given time. And these targets are being reprioritized in real-time based on our confidence of the data set and the developability from the standpoint of generating a candidate that we could ultimately advance forward. Thank you.

It's the natural ligand for S-15 is known [indiscernible]?

So the question is the natural ligand for Siglec-15. We are very active in looking for the binding partner for Siglec-15, both in NextCure and in collaboration with our founder, Professor Lieping Chen at Yale. We have identified a number of lead candidates that we think might be the binding partner. There is a possibility that there could be more than one binding partner for Siglec-15, but it's an active area of investigation within the organization. We hope to find it soon.

You're showing some of the side effects, the immune-related adverse events in the 49 patients, and there was a grade III pneumonitis, but overall, how would you characterize the side effects relative to a PD-1 or a CTLA-4 blockade? Is it higher or lower higher? It doesn't seem higher, but...

Yes. So the question relates to the adverse events that we're seeing in the Phase I, NC318 clinical trial. And then how that might compare to other immunomodulators like maybe PD-1 or CTLA-4? Kevin?

Right. that's a good question. And I would have to say that as we began to see immune-related adverse events on those first-in-human study, it actually became more reassuring to myself as well as the investigators that we were experiencing or witnessing systemic immune activation. And that's really one of the pharmacodynamic markers of activity. One of the things that we also noticed was that there was an increase in the frequency and the severity of the immune-related adverse events as we went up in dose. So for example, the dose-limiting toxicity, which was a grade III pneumonitis was observed at the 1,600-milligram dose, but we also saw a few other immune-related adverse events, unlike diarrhea or rashes, in general, but ones that really are only seen among patients who are being exposed to an immune-modulating agent like IL-2, ipilimumab, nivo, pembro and so on. For example, vitiligo, a reactivation of memory cells in the skin, which is evidence of that immune reactivation. We saw that at 80 as well as at 400 milligrams. We also saw a patient with a grade III uveitis at 400 milligrams. That was in a patient with colorectal cancer. That's something that is obviously not part of the normal history of colorectal cancer, it is clearly secondary to an immune modulating agent. And then we also saw another patient with a grade III pneumonitis at 400. When we reported these findings at SITC, the most significant immune-related adverse events as you were suggesting, they didn't happen at a high enough frequency to make it onto our table. But likewise, that's similar to pembrolizumab and nivolumab and what has been reported there, while they are not completely rare, they are not uncommon. But we used those immune-related adverse events as part of our justification that this has systemic activity. And now the burden is on our team to find the right patient populations for where we can translate some of that systemic immuno activation to antitumor immune activation. Thank you.

Yes.

Sorry, missed your presentation, but could you guide, like, what's the next step for you guys to report based on the Phase I data or Phase II?

Sure. So the question was, if we could provide guidance on when we'll be reporting data? I'm sorry you missed the presentation. I'm happy to do it again. Yes. So what we're reporting is really 4 key messages that will be delivered in 2020 for the company, 3 revolve around NC318 and 1 around NC410. So with respect to NC318, we've initiated the Phase II trial, and we'll be reporting that top line data by the end of this year. Mid this year, we'll be reporting 2 findings. One will be an update on the biomarker readouts and the status of the Phase I patients that we reported on at SITC. So that will come out sometime midyear. And then the final midyear event will be the initiation of the combination study in non-small cell lung cancer with NC318 and chemotherapeutic agents. And then the fourth item that we'll be reporting, as we mentioned, was the initiation and submission of the NC410 IND in first quarter of this year. Any other questions? We've got 9 minutes. You got to ask some questions, otherwise they don't pay us. We're happy to lead a song. Yes, please.

Just to ask it. For the 3 '20 biomarker update, is the ASCOs were the preferred place for that or could it come earlier than that?

So the question is on the biomarker update, the forum on when we would disclose that information whether it would be at ASCO? Kevin?

Right. Well, at the ASCO, our deadline is coming up in about 4 weeks. So it's really a matter of whether or not we feel comfortable pulling all the data together and a lot of the biomarker data that we've been collecting is pharmacodynamic. So we're trying to evaluate some of the subtle changes in the peripheral blood over time. So that took us a while because the patients have been staying on study so long. But also, we're looking at paired biopsies. About 20 of the subjects will have screening as well as on treatment biopsies. And some of those analysis are, at least for the on-treatment biopsies, are starting to ramp up as we speak. ASCO would be nice. I -- and just to really temper expectations, I think that we had --- if we have it as we would expect it to be probably a poster, I think anyone looking at the poster will say, that they'll appreciate some of the trends of some of the signs that we're seeing in the peripheral blood or in the biomarkers that we're seeing in the biopsies, any changes. And then it'll just be a nice opportunity to hopefully present that most of the subjects that we're still having durable stable disease or the CR/PR will still be on study as of that time. But I think for the 318 program, the real question will be how are the Phase II patients doing? And we expect our top line data in the fourth quarter of this year.

Yes, please.

Would you elaborate your [indiscernible] future partnership strategy?

So the question is, can we elaborate on our future partnering strategy? Are you interested in partnering with us? No, thank you. We have a very active -- so I should say, proactive business development strategy. In fact, our Head of Business Development, Sebastien Maloveste, there, he's waving in the back there. So we're constantly engaged in evaluating business development opportunities around our targets, around our candidates. Obviously, we have a lot of flexibility with respect to the type of relationship we might consider if NC318 or any of our programs were to take off. Certainly, having the assistance of a partner that could enable us to advance and accelerate and expand the development aspects from a global clin reg perspective could be very useful. So we are always open to partnering. And I'm sure, over time, in building the organization based on the breadth and depth of our pipeline and discovery activities, there will certainly be more partnerships to come. God bless you. Is that a question or a sneeze? Any other questions? I am impressed with the staying power of being at JPMorgan all week and still your willingness to continue to handle this in the presentations. Okay. Well, thank you very much for those questions. Thank you for coming.

Thank you.