Good afternoon, everyone, and thank you for joining us at the 4th day of the Needham Healthc are Conference. My name is Gil Blum. I'm a Senior Biotech Analyst here at Needham & Company, covering the immune oncology space. It is my pleasure to have with me today Michael Richman, the President and CEO of NextCure. He will walk us through recent developments of the company and its pipeline. With that, Michael, you have the stage. Great. Well, thank you so much, Gil. It's a pleasure to be participating in the 23rd Annual Needham Healthc are Conference. We greatly appreciate all the support you've provided NextCure over the years. This is a forward-looking statement, but let's quickly jump into the two promising programs that NextCure has prioritized and that we're currently focused on. The first program we'll walk through today is our NC410 combination. This is a LAIR-2 fusion protein being combined with Merck's Pembro, their anti-PD-1. We've happily seen some very interesting early clinical responses in two different tumor types, so ovarian cancer and colorectal cancer. We'll have additional clinical data to share mid-term this year, as well as the end of this year. Our second program is in the hot space of ADCs, antibody-drug conjugates. This program is LNCB74. It's a differentiated and potentially fast follower and best in class, B7-H4 ADC. We're developing this in collaboration with our partner, LigaChem Biosciences. We've just completed the antibody intermediate production, working through talks, and we'll be filing the IND the end of this year. From a financial perspective, the end of last year we ended up with $108 million on the balance sheet, which provides us a nice runway through the H2 of 2026 to support these two key programs. This next slide outlines our pipeline. Again, the NC410 is the LAIR-2 fusion being combined with Merck's Pembro, where they're kindly providing us drug to support this study. We're developing this in two specific indications and clear areas of unmet medical need. The first is in ovarian cancer. We're currently enrolling additional patients within the phase I-B, and we'll be providing an update on this specific tumor type in the H2 of this year. More closely to news flow will be the data coming out of the colorectal cancer cohort. We reported on some initial early clinical responses we've observed in CRC. And we've also added additional studies to support this phase I-B study, and we'll be presenting an update on this disease cohort at ASCO in early June. And then finally, the LNCB74 we were just talking about is our unique proprietary approach to developing a B7-H4 ADC. In collaboration with our partner LigaChem. And we're currently focused on a number of different tumor types, predominantly looking at breast cancer, ovarian, endometrial, and we'll be filing the IND in the Q4 of this year. First, let me talk about our NC410 combination study. As I mentioned, this is being pursued in two indications. Both with news flow in 2024. The colorectal cancer data will be reported at ASCO in June, and then later this year we'll follow up with the data generated in the ovarian cancer cohort. A little bit about the mechanism of NC410. NC410 is a LAIR-2 fusion. LAIR-2 is kind of a unique molecule that actually binds collagen within the extracellular matrix of the tumor. Through this interaction with collagen, it's able to break down collagen within the tumor. Open up the barrier of resistance to allow T cells to infiltrate and kill the tumor. That's exactly what we're doing with the NC410 combination approach. We're breaking up collagen with respect to the applications of NC410. We're combining it with an anti-PD-1 to activate T cells to infiltrate the tumors and to kill them. Some of the early data that we've generated has been in colorectal cancer. We've been focused on looking at PD-L1-naive subjects. More specifically, MSS, MSI-low individuals and those without liver mets. We've reported on the 19 patients that we've dosed historically where we saw two partial responses out of those 19 patients. But quite interestingly, we've seen a fairly long median PFS of 8.1 months. Based on this data that we generated earlier this year, we decided to add an additional 20 patients to the cohort, and these will be some of the subjects we'll be reporting on at ASCO in June. In addition to the colorectal cancer data that we've generated, quite interestingly, we've also been able to find or see objective responses in the ovarian cancer cohort. So fewer patients, but out of the seven evaluable patients, we saw three partial responses, one at 200 mg and two at 100 mg. Based on this data, which we thought was very exciting and quite timely, we're in the process of adding an additional 18-20 subjects. And those patients will soon be treated, and the expected data readout will be later this year. So both colorectal cancer and ovarian cancer within the NC410 combination will have data readouts in 2024. What's really exciting is the complementary biomarker studies that we've undertaken within the ovarian cancer cohort. So in three independent biomarker readouts, we've been able to complement the mechanism of action of NC410 p lus anti-PD-1 and align that with the overall responses that we've observed in the ovarian cancer subjects. So the first was a decrease of granzyme B. So granzyme B is associated with the actual breakdown of collagen within the extracellular matrix. So this demonstrates that NC410 is remodeling collagen, based on its mechanism of action. In addition, we've been able to show a decrease in suppressive myeloid-derived suppressor cells. So by reducing these suppressor effects, we're demonstrating activity within the immune system. And then finally, we've been able to see a decrease in the chemokine CCR7 CD4+ T cells. And this induces chemokine-guided migration. So collectively, the biomarker study has been very supportive of the 3 PRs we've observed in the ovarian cancer cohort to date. So in summary, the LAIR-2 fusion combination study is a differentiated approach. We're looking at remodeling the tumor architecture. So this is really getting back to the basics of biology and looking at structure function relationships. Where we're changing the structure of the tumor while activating the T cells with Pembro so that they can, those T cells can infiltrate the tumor and allow killing them. We're focused on large unmet medical needs in ovarian cancer and colorectal cancer where Pembro has not been successful historically. We have a deep understanding of LAIR biology and understanding the extracellular matrix as it relates to tumor resistance. This will potentially be first in class with respect to a LAIR-based approach in treating cancer. Our second program is in the hot area of ADCs. This is our LNCB74 program. We'll be filing an IND later this year. Currently we're focused on a number of different tumor types, breast cancer, ovarian, and endometrial. However, B7-H4 is expressed on a number of different tumor types, which allows for a pan cancer effect in treating patients. So this program actually builds on our deep expertise in B7-H4. We historically had a program looking at a naked antibody. Based on the data generated where we saw some stable disease and very good safety, we decided to pivot into what we believe would be a more productive antibody drug conjugate. But we've been working in the B7-H4 space for a fairly long time, and we're highly published in this area. And the beauty of this is we have a lot of the tools in-house, both in vitro and in vivo, to understand B7-H4 biology. And now the antibody drug conjugate. We're working closely with our partner LigaChem. This was a co-development agreement that we signed in 2022. They've had significant success in the antibody drug space based on their proprietary and differentiated linker technology. And in addition to the B7-H4 ADC, we also have the option under our agreement to add in additional targets, which are currently under discussion. So let's talk a little bit about the construct. There are a number of different B7-H4 ADCs out there. They all march to the beat of a different drum based on the antibody. It's affinity. It's ability to permeate tumor cells. The payloads differ in many of the constructs. And then quite importantly, the linker system differs in many of the approaches people are taking. Working very closely with our partner, LCB, we've been able to develop a construct. Using a linker based on the enzyme glucuronidase. So glucuronidase is a cleavable linker. That most of the cleavage is done within the tumor itself. It's proven to be extremely stable. And selective, and we think we'll potentially have a much greater safety effect as well as hopefully a superior, efficacious effect also. We're looking at an MMAE payload with a DAR 4. Which we also believe will help in demonstrating improved safety and improved efficacy in the dispersement of the payload. So this slide's a little bit busy, but I can walk you through it. So the reason we're so excited about glucuronidase as a linker, it already has a proven history based on LCB's applications and looking at other targets. Glucuronidase, unlike some of the other linkers that some of our peers are working on, seems to be extremely stable. You don't see the target, or I'm sorry, the payload coming off and the serum. So that stability enables you to avoid any off-target toxicity and get the antibody and the payload to the tumor where it needs to be, then the toxin is then cleaved in a fairly high concentration and where we can see a bystander effect in killing tumors. This slide just shows some of the many in vivo models that we've conducted here at NextCure, looking at the tumor types that we've been investigating. These studies represent both CDX and PDX models and looking at breast, ovarian, and triple negative breast cancer models. And as you can see, the molecule is extremely potent with respect to reducing tumor volume and killing those tumors. This slide just kind of highlights some of the recent reports. Coming out of ESMO last year from both Seagen and now Pfizer and then Hansoh, who's recently partnered with GSK, looking at B7-H4 as a validated target. The nice thing about this is that they've both been able to demonstrate both safety and clinical responses in a number of different tumor types. And this alone gives us confidence that B7-H4 is a validated target. And opens up a unique opportunity for us to take our glucuronidase linker system and develop an improved molecule where we think we'll be able to avoid or reduce toxicity. And also hopefully have a much greater therapeutic index and efficacious profile. And again, the IND will be filed Q4 of this year. Our tox studies are underway. We've already done some dose ranging tox studies in cynomolgus monkeys. We have not seen any major concerns from a safety or toxicity perspective. And on the manufacturing side, we're well underway with respect to producing. We just completed our 1,000-L production run of the antibody intermediate. The material has been sent to Shanghai, currently being conjugated. Which will then come back to the United States to file the IND and to initiate first in human studies. This is just kind of a brief outline of the synopsis that we're developing in the phase I-A dose escalation study. Again, we'll be looking at breast cancer and a number of other gynecological indications. Our first segment into the clinical studies will be a traditional dose escalation where we'll be looking at five dose cohorts every three weeks. We'll look at about 15-45 subjects based on backfilling in some of those cohorts, and we'll be evaluating scans every six weeks. We'll then segue rapidly into a dose expansion, narrowing down the focus on into two dose cohorts and two tumor types where we'll be adding an additional patients and evaluating them further. So again, the B7-H4 ADC program in summary is clearly a differentiated approach. It's got a unique antibody linker strategy. We have an impressive co-development partnership with LCB. That really kind of helps us merge the chemistry and the biology and what we're trying to achieve. Based on our historical work, we actually have a CLIA validated immunohistochemistry test that enables us to take biopsies from subjects and evaluate their B7-H4 expression levels. And we believe this test, along with the repertoire of biomarker tools we've developed, will be really important in selecting those patients that we think will be most responsive to LNCB74. We also have deep expertise in the B7-H4 scientific arena. And I think this, this experience, coupled with the new approach we're taking, will be fairly significant in putting this on a path forward towards success. So finally, these are our anticipated milestones for 2024. You know, as we talked about the NC410 combination, the LAIR-2 anti-PD-1 approach, we'll have multiple data readouts in 2024. So we will have a phase I-B data readout coming out at ASCO for colorectal cancer. And we're currently enrolling in the ovarian cohort. Excuse me, and should have a data readout by the end of this year. And then quite excitingly, we're moving forward with the LNCB74 B7-H4 ADC that we've been co-developing with LigaChem. We're on track to file that IND by year-end. And hopefully getting clearance from the FDA will start clinical trials soon thereafter. So hopefully, you've gotten a feeling for NextCure. This has been a little bit of a more focused strategy for us, but definitely built on solid clinical data as well as potential excitement into the B7-H4 ADC space. So thank you very much for listening, and Gil, happy to take any questions. Thank you for that, Mike. And you know, the floor is now open for questions from the audience, but maybe a good place to start. One of the founding principles for your company was going after targets that no one else has. Has that changed over time or are you guys still preferring to be, you know, not just best but first? Yeah, that's a great question. So, I guess we'd always want to be first. And in the absence of being first, being best is a nice position to be in. But when we started the company, we had a platform where we were screening really the human proteome. Looking for novel targets that we thought would have applications in modulating the immune system. I'm happy to say quite nicely that we had generated dozens and dozens of those targets. They've all been validated in different ways, looking at expression profiles and functionality. And quite interestingly, not all, but a lot of those targets actually make antibody drug conjugate candidates. So we're currently in discussions with a lot of partners that have that are rich in chemistry and understanding payloads. They're rich in understanding their respective linker systems. But they've kind of exhausted the inventory of targets. We have to get beyond HER2, EGFR. So I think this next wave, and we know this based on our discussions with many different groups, people are starting to focus on new ADCs, new targets. Based on specificity of expression within tumors. And then obviously aligning that with the right payloads and the right linker systems. So yeah, I'm sure you'll be hearing more about that from NextCure in the years to come. Okay, so focusing on NC410 in combination with Pembro and and colorectal cancer. First of all, I don't know if this was on the slide, but are these microsatellite stable patients? Yeah, so in the colorectal cancer, yeah, these are all PD-L1 naive as well as MSS, MSI low, and then liver met minus. So all of the patients that we've enrolled to date as part of this cohort are all MSS, MSI low. Okay. And where do you think the bar sits, for, you know, continuation with that program? I mean, you're now expanding your cohort a bit, so maybe this is a good juncture to discuss that. Yeah, so, you know, there's sadly not a lot to do for these colorectal cancer patients. So the bar is somewhat relatively low. But, you know, we would like to see kind of a somewhat over 20% response rate with some robust findings that gives us the consistency and confidence, to move into kind of a more formal phase II study. So that's kind of the rationale for why we added these additional 20 patients based on selecting the patients that we talked about. Coupled with looking at kind of a fixed dose of 100 mg at this point. And maybe going back to your phase I results, was there ever any interesting side effects for NC410 or an MTD? Anything at all? Yeah, that's a great question. Yeah, so, you know, based on the phase I-A dose escalation as well as the combo data, you know, we've seen really no side effects. It's been very safe. The feedback we've gotten from, you know, the investigators on the front line and treating patients have been very pleased with the safety. So from a safety perspective, unlike many of the antibody-drug conjugates, it's been really totally clean. So not something that we're worried about, at this point, at least with respect to the doses we're currently looking at. Okay. And, maybe kind of a more in-depth question. I'm assuming you have some tumor biopsies from patients treated with NC410. Do those look different, you know, from a mechanical perspective, morphologically? I mean, you're targeting collagen, so I would expect maybe they would have a different texture. Yeah, yeah, so what we know we're certainly exploring that further with respect to the structural changes, you know, within the tumor itself. You know, in the responses, it gets a little bit more challenging because the tumors are shrinking. So there's less tumor to actually pull out after treatment. But to the extent we could get some tissue, we're certainly interested in looking at that as well as the whole repertoire of other biomarkers. So independent of the tumor, we could actually measure what we call these CDPs, these collagen-derived products, you know, in the periphery. And we could demonstrate that, you know, we see an increase in those patients that are treated with NC410. And maybe, shifting gears to your ADC program. I mean, outside of your own data, which may take some time to generate. What do you think could drive excitement in that space? Yeah, it's a real exciting space. Well, anytime you could see clinical responses that are helping patients, you know, that's a great thing. And when you could see confirmation and validation of a target in the hands of multiple parties, even though they're taking different approaches, I think is really positive. What we're really excited about is the differentiated approach we're taking. You know, we've been looking at B7-H4 antibodies for a long, long time. We think we have a very specific high affinity permeable antibody. And then with respect to the prenylation and conjugation of the glucuronidase linker and MMAE, we think that's going to be quite unique. You know, we're privileged to not only kind of do some comparable data, internally looking at things preclinically, but also building on the significant experience that LCB has in this linker system and looking at other targeted approaches. So I think it's differentiated. I think it potentially could be much safer. We think it could be best in class and superior. And so we're looking forward to getting this into the clinic and demonstrating this, hopefully in multiple tumor indications. I know the company has become a lot more focused in recent years, but not to completely neglect Siglec-15. You did put out some interesting data regarding bone density. Is there maybe opportunities there? Yeah, so we do have another anti-Siglec-15. This is our NC605 program. That's actually has a very impressive data set and focuses on bone-related diseases. Currently we're focused on an orphan indication, osteogenesis imperfecta. This has really gotten a lot of attention based on some work Ultragenyx has done with sclerostin in the pediatric population. We're actually focused on the adult population. We think our molecule will be safer. We've been able to demonstrate in multiple animal models the ability to not only decrease bone resorption, but enhance bone formation and quality bone, both in the cortical and the trabecular space. So we're in the process of talking to a number of different groups, to see how best to advance this program. We're currently doing tox studies. Even though our focus has been on oncology, as you mentioned, a more focused effort on these two programs, hopefully with the right support, we'd love to see the bone program advance in some way also. Excellent. Well, thank you, Michael, for attending today. Well, thank you very much, Gil. I greatly appreciate the opportunity. It's always a pleasure speaking with you, and we appreciate again Needham's ongoing support. So thank you very much.