Hello, everyone. Thanks for joining us. My name is Jonathan Chang. I'm part of the Leerink Partners equity research team. It's my pleasure to host the management team of MacroGenics, and we have with us today, CEO Eric Risser. Thank you very much for coming. Thanks, Jonathan. My pleasure to be here. I'm also joined by my colleague, James Karrels, our CFO at the conference, looking forward to the conversation. Great. Thanks. Would you like to first take a few minutes to introduce the company? Sure. Yeah. The company's been around for almost 25 years, so relatively long tenure. I stepped in as CEO last year and really excited about, you know, the go-forward prospects for the company. Always been grounded in tremendous science, really committed to delivering what could be life-changing medicines for patients. We have three core pillars across our product development pipeline. Our ADC programs, where we're leveraging third-party drug linker chemistries that we've brought in. We now have three ADC programs in our portfolio, either best in class or potentially first in class molecules. We also have a commitment to leveraging our proprietary bispecific platform to enabling dual blockade of two different immune checkpoints and have a Phase 2 program called lorigerlimab that's on a partial clinical hold right now, but working closely with the FDA to resolve that. We are also committed to next generation T-cell engagers and have a number of programs. A lead asset directed against CD123 and CD3 that's partnered with Gilead, and actually Gilead has now stepped in with a second molecule back in 2023 and then a third molecule this past November. You know, very broad relationship with them. A lot on our plate and working hard this year to really start delivering on some important value inflection points as we progress all these programs forward. Great. Thank you for the intro. Maybe first question would be what's new, different or the same with you as CEO since August? I think what's the same is, you know, commitment to really tremendous science. We've always been grounded as a science-based organization in how do we again deliver these compelling medicines for patients, and I think that shared kind of vision for the company, you know, the employees have. I think what's new is probably a heightened sense of urgency and a heightened focus in terms of we can't do everything, so we're not gonna try to boil the ocean, but really identify what are gonna be foundational value drivers for the company over the next couple of years and go deep in a few of those. I think that focus has obviously also translated into our burn, where we try to be operating as a leaner, meaner kind of footprint, and our kind of very focused view of how do we generate a return on investment for investors. How we deploy capital, I think we've been even more judicious in thinking about making those investment decisions and also in some cases making calls to make a quick kill. You know, our lorigerlimab program, we had an early study in prostate cancer. It was a randomized study. We looked at some of the emerging data, decided this wasn't gonna be a program and a profile that was gonna be competitive, and we made that decision relatively early in my tenure to really stop that asset in prostate cancer and shunt those resources into other parts of the pipeline. Got it. Let's start with lorigerlimab. Can you discuss the latest status of the LINNET study? What led to the partial clinical hold and what are next steps and timelines from here? Yeah. This is an asset we've obviously had a lot of development experience with the program, both early monotherapy experience. We've done combination studies, both with docetaxel and prednisone, as well as actually another earlier ADC program that we were developing, which was based on this very potent pyrrolobenzodiazepine. A lot of experience, probably over 300 patients in aggregate. We did see some serious AE events, specifically 4 Grade 4 events, 2 of which were Grade 4 thrombocytopenia. 1 was a Grade 4 myocarditis, and then the 4th was a Grade 4 neutropenia with a concurrent Grade 4 septic shock. That patient ultimately succumbed and died, so that ended being a Grade 5 event. We had been very proactive in terms of obviously assessing safety, had also engaged with the data monitoring committee, had also on our own decided to cease enrollment in terms of new patients as we were continuing to observe these events. Ultimately, the FDA did put us on a partial clinical hold, meaning we're not gonna continue to enroll subjects on the study, but for those patients that were already on the study, they would continue to receive lorigerlimab therapy. We're in the process of working closely with the FDA, trying to resolve this, and then the hope would be we would be able to resume enrollment of that study, which to date had enrolled about 41 patients prior to the pause in the enrollment. Got it. How should we think about timelines for next steps? You know, in terms of the timing of that enrollment pause, if you look at the actual design of the study, it was a two-arm study. One population was a serous platinum-resistant ovarian cancer population. The other was a clear cell gynecologic cohort. Both of these were designed to be roughly 20 patients in terms of sizing with the option to kind of based on hitting a predefined efficacy threshold with the PROC cohort that we would add another 20 patients. Based on the 41 patients we enrolled, it was kind of a natural point to really assess the overall, both safety and efficacy profile. Obviously, we did not expect some of these safety events, but we're in the process of, you know, looking at the overall data, both risk and benefit, and we are continuing to commit to a mid-2026 clinical update on the program, which will be, I think, a pretty comprehensive assessment of, you know, the profile of the asset, these two indications, and go-forward planning for these indications. Got it. How do you see the opportunity for lorigerlimab in those two settings you just mentioned, so platinum-resistant ovarian cancer and in clear cell gynecologic cancer? You know, again, back to the history of the program, you know, we have explored a fairly broad swath of indications, even in the early Phase 1 experience, encompassing both indications that are more referred to as cold tumors that are more checkpoint refractory. Those would include things like prostate cancer and then also indications like melanoma, where we had, you know, some patients, some of these were all prior checkpoint therapy, and lung was another indication that we had in our Phase 1. The utility of a bispecific checkpoint could potentially span both. Our early experience where we took a much larger study forward was in a prostate population, but we combined it with systemic chemo and prednisone. In this study, we actually have two populations embedded. The PROC population historically is also viewed as more of a checkpoint-insensitive tumor. If you look at the prior benchmark data with traditional PD-1 monotherapy, single-digit response rates, so, you know, relatively limited activity. But again, that's with just single blockade of a PD-1. Clear cell is an indication. It's a smaller disease in terms of prevalence, but it is one that tends to be more susceptible to immune checkpoint intervention, and it's also an indication that has historically been fairly refractory to conventional platinum-based chemo. So that could again be an opportunity to explore. So we're looking at both these populations, and again, we'll have an update middle of this year based on the overall assessment of efficacy, safety, and obviously always thinking about competitive dynamics in the market as well as long-term lifecycle planning. You know, is this gonna be a monotherapy? Is this better positioned as a combination agent? Those are all things that we'll be looking at. Understood. The update mid-year, will it just be for investors? Will we just see the clinical data, disclosure, or will you also be ready potentially to make some calls, on the development path for the program? We haven't parsed out exactly what that disclosure is, but it will be kind of a holistic assessment of both, you know, evolving data as well as a little bit of the development strategy going forward. Understood. Maybe switching over to the ADC efforts, how is your ADC technology positioned versus other ADC constructs using a topoisomerase I inhibitor? Our platform, which has been our go-to for the three molecules in the portfolio, MGC026, MGC028, and MGC030 are all through a licensing arrangement with Synaffix, which is now part of Lonza. We were a fairly early adopter of that technology, so we actually negotiated broad access at, you know, relatively favorable terms. We've been very happy with the performance of the platform. Again, there's a lot of different ADCs out there. I was in China about a month ago, and obviously, there's a proliferation of companies and platforms that are out there. I always think of it as almost a system when you talk about the ADC. It starts with the target, you know, what's the target, and is there a nice differential expression profile in tumor versus normal? The antibody is also an essential component of that mix, and we've done some benchmarking, for instance, on the MGC026 asset relative to the DXd program from Daiichi, where we believe our antibody is a more efficient internalizer, which again enables uptake of the cytotoxic into the cell. The linker is a critical variable there. Synaffix relies on a site-specific conjugation approach. If you look at the other kind of leading B7-H3 ADCs in the space, most, I think all of them are really leveraging cysteine-based chemistry, so it's more of a random conjugation approach where you get more of a distribution of DAR. We have very uniform DAR four species in our program. The other nice feature of the site-specific conjugation is we bind to the native glycan on the antibody, so you don't need any re-engineering of the antibody, and you also render the Fc domain inert, so it's kind of a silenced Fc. That means you don't have binding to, you know, some of the immune effector cells. One population is these alveolar macrophages, which we know, at least based on some published data from Daiichi, that that could be attributed to some of the higher rates of ILD or interstitial lung disease that you see with some of the topo ones. What I am also happy to report, and we made that comment on our earnings release earlier in the week, is to date, we've actually seen no ILD of any severity across both the MGC026 and MGC028 assets. The linker we think is great, both, again, very uniform DAR four species, great CMC properties, and potentially some safety advantages. The payload is the last element of this system, and not all topo ones are the same, and we're leveraging exatecan, which is a relatively potent flavor of topo one. Deruxtecan or DXD is the operative payload for Daiichi, and based on some preclinical benchmarking, again, we're about 2- to 5-fold more potent. We've shown better bystander killing effects and again, less susceptibility to multi-drug resistance. Hansoh Pharma/GSK is another, you know, program which is also more biased towards the lower kind of potency, and they're also not a site-specific approach. I believe both Daiichi and Hansoh Pharma/GSK have, you know, active Fc domains that still have Fc gamma receptor binding. Then two of the other programs which are more kind of newcomers are also two Chinese innovators, DualityBio, which is partnered with BioNTech, and then, MediLink, which has a partnership with, Roche. You know, they're a little bit more aggressive with the DAR 6 and DAR 8 construct for those latter two. A lot of differences, and again, it's tough to, you know, make any conclusive determinations of how one will compete against another. I don't think this is gonna be a winner-take-all kind of market dynamic, and I think, we're still in the early innings of the B7H3 ADC horse race. I think one of the really attractive features of this target, and I would argue it's probably one of the most exciting new targets in oncology for quite some time, is just the breadth of expression pattern. You're seeing people standing up late-stage development efforts in prostate cancer and small cell lung cancer and esophageal cancer and sarcoma. I think there's gonna be an expanding list of development opportunities that people will pursue, both in late line settings where that might be more guided towards a monotherapy development path, but also early line settings, given the more favorable safety profile with some of these agents, that these could be, you know, more readily combinable with other agents. Understood. Let's go to MGC026, since, you know, you touched on B7H3 already, so this is your B7H3 ADC. How has the Phase 1 study progressed? Are you talking about 026 or 028? Uh... Oh two eight is the ADAM9- Yeah, 026. MGC026 is the first molecule against B7-H3. We finished the dose escalation. We started expansion cohorts latter part of last year, and we will be also providing a clinical update on the program in mid-2026. That was again, you know, as part of our disclosure early this week. We try to lay out kind of a roadmap to help guide investors of what disclosures are coming up this year, and that will be a relatively near-term one, you know, again, mid this year for MGC026. Got it. Can you help set expectations for what investors might learn in the update? What's completed to date is the dose escalation, and we're obviously now initiating expansion cohorts in a couple different indications. You'll hear a little bit more about overall safety and efficacy. Obviously, ORR will be something we'll have some representative rates based on the dose escalation, and we'll obviously continue to see how the enrollment continues over the next few months and, you know, getting scans in and ideally confirmatory scans. One of the things that is always going to be critical is durability of response, and that may take a little bit more time. I think you'll have a good representative data set that you'll be able to assess, you know, how's this, you know, asset looking, both in terms of safety and efficacy. You know, we'll start also layering a little bit more disclosure over the course of this year on our longer term development strategy and indications that we're gonna likely prioritize that hopefully will enable us to have a differentiated development path going forward. Got it. Maybe just on that last point, just given the expression profile B7H3, that there are a lot of different ways that you could take this. If you look at the competitive landscape of B7H3 ADCs, a lot of them have sort of overlapped in terms of places that they're looking to advance this. How do you see the positioning of your B7H3 ADC, and as you consider the directions you could take this? Yeah. I think all four of the groups I mentioned earlier are actively exploring small cell lung cancer, and many of them are already well into pivotal study designs. That's less likely the kind of indication that we'd wanna compete in at this point. Rather, you know, thinking about where can we, you know, still have a meaningful foothold and an indication that we'll have, you know, still high unmet need and commercial viability, but also looking at indications that may have some early, you know, proof of concept based on either our preclinical work or emerging clinical data in the market. Understood. When could we learn more about the longer-term development path, do you think? Well, we'll start with middle of this year, and, you know, we'll see, you know, how much of an integrated discussion that will be, both on data and forward planning efforts. Understood. Let's talk about MGC028. Yeah the ADAM9 ADC. How has that Phase 1 dose escalation study progressed? That trial initiated about a year after 026, so it was early part of 2025. It's moved briskly. We're wrapping up the dose escalation Phase, and what we've committed to is, you know, second half of this year, we'll have a clinical update with some early emerging data on that asset. This is a first in class program. Again, we were one of the early innovators in both B7H3 but also in ADAM9, actually had a first-generation molecule several years back that we were co-developing with ImmunoGen, so a lot of learnings about the target, the expression profile, also some lessons learned of, you know, things that we might wanna fix. The principal issue with the first-gen molecule was the platform tox. It was a maytansinoid-based payload and had a lot of ocular tox, which we think we've now been able to manage with the Synaffix platform with the site-specific approach, a DAR 4, and again, a exatecan-based payload. I think it also opens up coverage on other indications that tend to be also amenable to different classes of payloads that maybe aren't just cell cycle-dependent payloads, like an auristatin or a maytansine. We're excited about this molecule. We have noticed there is some emerging interest now in the marketplace with at least one or two other groups declaring that they're intending to move their own Phase 1 programs forward. You know, we're aggressively moving that forward, and again, it's all the classic features that we'd want in an ADC with, again, the target, very nice differential expression profile. One thing we did learn from that first gen molecule is we didn't see really any other off-tumor toxicities. You know, it was really the ocular tox, which was more of a payload-driven artifact, so no, you know, normal tissue reactivity kind of watch outs. You know, good target. Again, a nice linker, same system that we're using in 026, and a payload that we think is gonna be amenable for, you know, a mix of GI cancers, which is one of the areas where ADAM9 is overexpressed. You know, lung cancer, and there's other solid tumors that we could also explore. Got it. What could we learn in the update for 028 later this year? You know, it's not gonna be dissimilar from what we've guided on 026. You know, we'll obviously have the dose escalation data and that we'll be hopefully moving into either backfills or other expansion cohorts. It's gonna be some representation of overall safety, tolerability. Ideally, also starting to align on what a likely recommended dose would be, and potentially also giving some direction in terms of development priorities in terms of where we wanna take the asset going forward. Got it. What makes ADAM9 a great target for ADCs? Or for your specific ADC? High expression profile across a number of these targets. The antibody we selected also is actually an extremely efficient internalizer. In fact, when ImmunoGen, several years back, when they went through a little bit of a restructuring effort of their own, they kept the ADAM9 program in their pipeline. You know, I think one of the features that they were really excited about is its really nice differential expression profile, very clean, and again, a very rapid internalizer, meaning you can get very efficient uptake into the cells to release the payload. Got it. Can you remind me the ADAM9 data from ImmunoGen? When were those? It was at the EORTC-NCI-AACR Symposium several years ago. It was an early experience. Ultimately, we never really got to the target dose levels. The ocular tox, which we thought we might be able to manage through supportive care measures and even explore things like fractionated dosing, but in the end, that ended up being really a dose-limiting tox. Many of the patients that even got to kind of the higher dose within that studies had reductions in place. Got it. I think it's less instructive on the efficacy side, although there were some anecdotes of anti-tumor activity in that study. You know, more gives us conviction that, you know, normal tissue looks, you know, good and obviously very compelling PDX animal modeling data that we've generated for current MGC028 construct. Understood. On MGC030, I believe the target's still undisclosed for this ADC. This is the new kid on the block, same Synaffix platform. It's an undisclosed target. What can you tell us about this new kid on the block? We're obviously excited to have this new addition to our ADC family. It's another target that does have broad expression across a number of tumor types. Again, it's not a lineage-specific target where we're gonna only be focused on, you know, one or two indications. You know, very strong preclinical package and, you know, we're wrapping up all the IND-enabling work, including our GLP toxicology study, which is complete, and we're on track for an IND submission in Q3 of this year. Got it. All three of these ADC programs you've discussed, they use the same construct and technology? Largely the same construct. There's been some evolution in some of the chemistry on our 030, you know, partly to further improve some of the CMC features. You know, the basic construct of the GlycoConnect site-specific linker exatecan and payload is pretty much consistent across all three molecules. It's also a similar platform. In fact, it's the identical platform that 026 and 028 have that Innovent included in their ADC molecule that targets claudin 18.2. That was again same GlycoConnect linker, you know, DAR 4 species with an exatecan and payload, although in their case, a different target. You know, also have presented data that looks, you know, fairly robust, and that asset was partnered with Takeda a few months back in a fairly, you know, sizable global licensing transaction. Got it. How are you guys thinking about business development opportunities? Of course, that's historically been a big part of MacroGenics. You know, when I first joined the company 16 years ago, was brought in to lead a lot of the BD, so I've, you know, been obviously closely involved with a lot of those transactions. We've actually done at least one, in some cases, multiple partnerships every year for the last decade, and that's been a great source of non-dilutive capital. In the last three and a half years alone, we brought in over $600 million in non-dilutive funding. We will continue to be active on partnering. The most recent transaction we announced was in November with Gilead, so this was, you know, when they tripled up on a third program, which is an evolution of our T-cell engager platform. We're delighted to obviously have that broad relationship with Gilead, and we're continuing to, you know, stay very close with all the top fifty pharmas and explore opportunities, which always is a function of, you know, who's the partner, what's the molecule, and what's the right timing to really do the most, you know, meaningful transaction that's possible. Got it. What types of transactions could MacroGenics be looking for? If you look at the history of what we've done, I mean, there's definitely not a cookie-cutter approach. It's very much bespoke to who the partner is. You know, we've done regional deals. We've done global deals. Ideally, we would like to have some level of participation rights beyond just pure economic interest. Mm-hmm. Especially for some of these lead assets that we've discussed. Understood. Remind me, what is the cash position and runway? I know you guys just reported recently. Yeah. I think you know, we're feeling pretty good about the cash runway right now. Our guidance is through late 2027. Cash balance is about $190 million. You know, we do have a lot of latent milestone payments, you know, given our existing partnerships where we have Gilead. The three molecules in aggregate could bring in up to $1.6 billion. We have a Sanofi relationship on Tzield, which is a marketed program for type 1 diabetes. That's about $330 million. We have Incyte, which is another marketed program with ZYNYZ. That's about $540 million in latent milestone payments. We're obviously encouraged by the progress in some of these programs. You know, ZYNYZ, for instance, highlighted that they had a recent approval in Japan in December, also just highlighted a few weeks ago, now approved in Europe, for anal cancer. TZIELD is also Sanofi's been guiding that there's potential upcoming regulatory actions on that program as well. That, that's another way to obviously supplement the cash that we have on hand today. Understood. Just last question from me. Can you just review the catalyst and milestones that we can expect in 2026? Yeah. You know, last 6 months since I've come on board, there's been a very strong focus on execution. The team's, you know, all, you know, working hard, all rowing in the same direction. 2026, we're really hoping is gonna be an important year for the company. As we've discussed today, by mid this year, we'll have updates on the LINNET programs and the MGC026, the B7-H3 ADC. Second half of the year, we'll have our IND submission for MGC030 in Q3 and additional clinical update on the MGC028 program. What we're continuing to do is also progress additional molecules. We've had a very prolific research team with about one new IND advancing a year. Beyond 2030, we're continuing to catalyze new assets that have best in class or first in class potential. The hope is later this year, you'll hear also additional updates of what else is coming through that research pipeline. Great. Thank you very much for taking the time to chat with us today. My pleasure. Thank you so much.