Good afternoon, everyone. My name is Ted Tenthoff. I'm a senior biotech analyst at Piper Sandler. And before I begin, I am required to point out certain disclosures regarding the relationship between Piper and NextCure, which are posted at the back of the room and also at the registration desk. And also, I think it's noon. I believe they're serving lunches, so if you want to grab a lunch and come in and join us, feel free. So NextCure is developing a rich early-stage pipeline with multiple clinical updates coming this year. The company just announced today an IND for LNCB74, which is a B7-H4 antibody-drug conjugate. So we're going to mostly focus on that, but there's also quite a few partnering opportunities at NextCure that we might touch on. So here from the company, it's my good friend Mike Richman, President and CEO. Mike, thanks for being with us. Thanks for having us, Ted. Great to be here. So I just mentioned, but your lead asset now is this B7-H4 antibody-drug conjugate, and you just filed the IND today. Congratulations. Before we get into sort of clinical plans, tell us about this target and why it's a good target for an ADC. Great. Well, again, thanks for having us. So yeah, the LNCB74 program is an antibody-drug conjugate targeting B7-H4, and B7-H4 is a really interesting target because it's overexpressed on a number of different tumor types. You see B7-H4 expressed predominantly on women's health cancers in breast cancer, ovarian cancer, endometrial cancer. Quite interestingly, we could also use B7-H4 with respect to selecting patients that have certain levels of B7-H4 expression, which hopefully indicates that they'll be most responsive to therapy. We think B7-H4 is a great target. We've developed a humanized monoclonal antibody that has high affinity to B7-H4. It's well internalized, and the candidate has been designed with a novel linker system called beta-glucuronidase. We're working very closely with our co-development partner, LCB, where we've taken a high affinity antibody, linked it up to beta-glucuronidase, and then added a payload such as MMAE with a DAR4 construct. We believe this candidate will be very unique and differentiated in positioning this candidate in a number of different tumor types. That's really great. And tell us about the partnership with Ligaken. So they brought this novel linker. Tell us about sort of the retained ownership and kind of all of those things around the partnership. Right. So the partnership with Ligaken is a 50/50 co-development partnership. I guess in the most simplistic terms, we bring the biology, they bring the chemistry. The beta-glucuronidase linker system is proprietary to them and is already subject to a number of other ongoing studies in HER2 and TROP2. And the B7-H4 program will be kind of next in line, utilizing this unique linker system. So why is the linker system important and why did we go with Ligaken as a partner? It's It's that anytime you're developing a chemotherapeutic agent for cancer patients, you're going to see some toxicity. The nice thing about the linker is it gives you a stable construct to navigate through the blood and get to the cancer or the tumor itself. Once the ADC construct is within the tumor, that's where you have the enzyme to cleave the beta-glucuronidase, release the toxin, and to kill the tumor, so we think this approach will give us a much greater safety profile. We won't see some of the off-target toxicities, such as neuropathies or other types of neutropenias that others have seen with other constructs, and we also hope, because of its safety, we'll have a greater therapeutic index where we may be able to dose higher and see a much greater clinical benefit for patients. Great. So Mike, tell us about your phase one study plan. The phase one study hopefully will start soon once we get the safe-to-proceed letter from the agency. It's been designed pretty much like many cancer clinical trial designs. We'll be focusing on three patient types: in breast cancer, in ovarian cancer, and in endometrial cancer. It will have a number of different dose cohorts. We think midway through that phase one dose escalation study, we hope to see safety. Hopefully we'll see safety all along. We hope to see efficacy. Also, once we define the recommended dose that we plan to proceed forward, the trial is designed also to look at adding additional patients. What we'll be doing is a number of what we call backfills. We'll have a safety backfill, and we'll also have a biomarker backfill. These two streams of adding additional patients within a given dose range will enable us to really kind of tease out which patients do we think will be most responsive. In the safety backfill and the biomarker backfill, we'll also be looking at B7-H4 expression profiles. That will enable us to titrate that segment of the patient population that has a certain level of B7-H4 expression that we think will be most responsive to LNCB74. And then would you do expansion work in those individual cancers, so in breast, ovarian, and endometrial, if you see activity? Correct. So assuming we see activity and we have a dose that we're comfortable with, we'll then move into what we call a part one B component of the trial. We'll focus predominantly maybe on two tumor types and may look at two doses with respect to alignment with the agency's thoughts on Optimus Prime. And then we'll obviously be well prepared, hopefully to, in 2026, advance into a phase two study, mainly focused on one of these indications. But we're also exploring preclinically other tumor types where B7-H4 is also expressed and may give us a differentiated approach to position this drug versus what others are doing in the field. And you mentioned some of the expression work that you're going to be doing. Is that going to be in preparation for a companion diagnostic? And do you view that this is something that will be required ultimately to really find patient cutoff levels? Yeah, very good question. So a lot of folks may not realize, but we actually took a naked B7-H4 antibody into the clinic a few years ago called NC762. And during that process, we had developed a CLIA-validated immunohistochemistry test to select those individuals that had various B7-H4 expression levels. So we're able to take, we're able to look at either archival or historical biopsies, or we can look at fresh biopsies. And based on the B7-H4 expression levels, as you point out, we can define certain cutoffs that we think will kind of maximize the probability of the greatest chance of clinical effect. That's really helpful. Now, obviously, we're hoping to see monotherapy activity. That's going to be the goal in these early studies. From some of the preclinical work that you're doing, are there combinations that make sense, especially as you get into the phase 2 study? You know, would you consider a phase combination in breast or ovarian or endometrial, depending on sort of where you're seeing the greatest activity? Yeah, very good question again. So obviously, you know, companies will be leapfrogging over one another as it relates to new technologies, such as new payloads, dual payloads, bispecifics, and as you point out, combinations. So yeah, there are a number of combinations we've defined. Those combinations will be determined based on the clinical indication we pursue, whether it's breast, it may be one set of combinations. If it's ovarian, it could be another set of combinations. So those are all being laid out. We are doing some work preclinically. And as the field develops and as the standard of care evolves, we'll position our combination approach to kind of maximize the benefit, you know, to patients overall. That's great. That's super helpful. And I'm excited to hear more about that program. Congrats on the IND. Thanks. I'm going to just touch on sort of some of the other programs that you're working on. You guys just presented some combination data with Keytruda on NC410 for LAIR-1 targeting. You know, maybe just touch on this data. What are your plans to take this forward? Yeah, so LAIR-1 is a very exciting target. And our NC410 LAIR-2 fusion protein combined with Merck's Pembro was subject to a number of interesting studies and findings. And we focused on looking at colorectal cancer patients and ovarian cancer patients. And quite interestingly, we saw three partial responses in the colorectal cancer patient population. Those were fairly durable responses. And some of those patients are still on therapy. Even more interestingly was the ovarian cancer cohort, where we saw five PRs out of, you know, almost around 25 patients. And again, you know, seemed to have significant clinical benefit. So scientifically, there's really no reason for us not to pursue the program. It's really being driven by economics. So as a young company, we're trying to preserve our balance sheet and our financial means to get an answer on one program versus a half an answer on multiple programs. So as we talked about earlier, the prioritization and the focus of our resources will be focused on LNCB74 to get an answer from that trial. And then with the NC410, we're already in discussions with potential partners that share our interest and enthusiasm in the science, the biology, and the clinical responses. And most likely, that could be a company that has PD1 that is trying to differentiate their PD1 approach with an NC410-like asset. So those discussions are just kind of going on, and our goal is to try to keep these programs advancing, but through strategic partnerships. That makes a lot of sense. And there's a lot of other things going on at the company too that offer partnering opportunities. So I have to imagine BD is a big focus right now. Maybe you can tell us about your anti-Siglec-15 antibody NC605 for the potential to treat osteogenesis imperfecta, or a very rare disease. Maybe you can start by telling us about that disease and then the role that Siglec-15 plays. Yeah, so osteogenesis imperfecta, it's taken me a long time to learn how to pronounce that. So we just call it OI. It's also known in layman's terms as brittle bone disease. And it's an orphan disease. It's quite tragically impacts the patient population where there's an imbalance in bone remodeling. And their bones are not developed with the integrity and strength that a healthy individual would see. So many of these individuals are sadly in wheelchairs, experience bone fractures, loss of bone density. So what does anti-Siglec-15 bring to the mix? So Siglec-15 is overexpressed on osteoclasts. So there are two different types of cells in bone remodeling: the osteoclasts that absorb bone and the osteoblasts that make bone. And your body constantly has a balance with respect to bone remodeling, bone repair. So what we've developed is an antibody targeting Siglec-15 to shut down the osteoclasts and to reduce bone resorption. So if we can reduce bone resorption, our goal then is to preserve looking at bone mineral density, reduce bone fractures. And that's really the goal of this program is to go into the OI patient population using a very extensive set of bone markers and tools to look at bone mineral density readouts, fracture reduction. And others have shown this with other molecules. So this could be in the clinic as early as a year from now. But again, due to, you know, the economic conditions, we're looking to either partner this program or perhaps spin it out into a new company. Cool. And maybe there's even some kind of funding you could get from a nonprofit or something like that, at least to keep it going. So because it sounds like a really interesting program. Yeah, thanks. That's a good program. We actually, the OI Foundation is not too far from, you know, where NextCure resides in Maryland. So that is always a possibility. That's great. You also presented some preclinical data on an anti-ApoE4 antibody, NC181, I guess with potential to treat Alzheimer's disease. Maybe you can tell us about this program and what your partnering plans are here. Yeah, so five years ago, you know, we made the decision, and perhaps prematurely, to think about diversification of the organization. And we approached Dave Holtzman out of Washington University that had been developing an antibody against APOE for Alzheimer's disease. So fast forward over the last few years, we've had a very strong collaboration and have now defined an extensive preclinical data set that demonstrates that we're able to reduce various effects associated with Alzheimer's disease in mice. Quite interestingly, it also performs quite well against some of the comparative agents that people have seen recently get approved. And even more so, we do not see the side effects called ARIA, which is related to blood hemorrhaging. So where the program is right now, we're currently doing some initial tox studies. Our goal again is to look for a partner or spin this out also into a new company. The ApoE target is kind of a scientist's dream because it's a genetic marker that clearly associates individuals with that gene or a pair of those genes that could potentially succumb to Alzheimer's disease. Quite interestingly, if you look at the side effects of the current drugs that have been approved in looking at those blood hemorrhages, those are pretty much seen in the ApoE4 positive individuals. This just opens up a unique window for the NC181 program. We're looking forward to, you know, again, we're in discussions with various groups. We hope to keep this program moving for patients and then also monetize it in the context of bringing in some non-dilutional revenue. And then in non-dilutive funding, we'll just come back into advancing LNCB74. So that sounds like a really good strategy. To this point, you guys ended the third quarter with cash of around $75 million. How long does this fund the company? And what do you guys get to accomplish with that? Yeah, so as you point out, as of the end of last quarter, we have $75 million on the balance sheet. Our guidance is currently a runway into the second half of 2026. That's more than enough means to get a clear answer on LNCB74. So we're in a pretty good shape as a single product company. You know, I think our goal strategically will be now how to kind of backfill the pipeline with respect to other ADC assets that kind of fit into, you know, our overall strategy and building value for the company. Yeah. Well, great. Mike, I appreciate you being with us, and I look forward to a busy 2025. Me too.