Just checking that it's still morning. Good morning, everyone, and thank you for joining us for TD Cowen's 45th Annual Healthcare Conference. I'm Tara Bancroft, one of the senior analysts here, and for our next session, we have a presentation that will follow with Q&A with MacroGenics, and from MacroGenics, we have the CEO, Scott Koenig. Scott, thank you so much for joining us. You could take it away with the presentation whenever you're ready. Sure, and as you know, this is just a brief presentation to sort of introduce the company and Tara. And Nick, thanks so much for the invitation today. As you know, I'll be making forward-looking statements during the course of this presentation, so please refer to our SEC filings to understand the risks associated with an investment in MacroGenics. Let's start. For those of you who do not know MacroGenics, and/or those who have not been following us for a while, we are a fully integrated immunotherapeutics company focused on the development of first-in-class and best-in-class therapeutics for the treatment of cancer. We do everything from early research discovery to late-stage clinical development, including the production of marketed products, as well as our molecules and clinical development for ourselves, as well as our partners at our commercial manufacturing facility. We have been in business now 25 years. If I give you a little bit of a snapshot of where the company is now, I've sort of arranged these pillars in groups of three. In the history of the company, we've had three monoclonal antibodies that have been approved by the FDA and are currently being marketed. We have three molecules in the development of prostate cancer using our three proprietary technologies: Fc engineering, our bispecific DART technology, as well as our ADC molecules. We have ADCs, three ADCs using different linker toxin technologies in clinical development for different indications. Plus, we have a number of preclinical molecules, ADC molecules, targeting new and novel targets, and I would expect over the coming years, at least three of these will get into clinical development. Sticking with the threes, we actually have three bispecific DART molecules that are either completed clinical development with good activity in a number of tumors or proceed in further clinical development using either combination checkpoints or redirected T-cell mechanisms. Finally, our third quarter earnings report, we had $200 million in cash with plans for continued support of our programs into 2026. This is the listing of our current pipeline molecules where we retain commercial rights. As you see, as I pointed out, we have three ADC molecules here: vobramitamab duocarmazine and MGC026, which are targeted B7-H3, and the ADAM9 molecule, MGC028. Two of the three bispecific DART molecules, lorigerlimab and tebotelimab, and then the Fc engineered molecule, which is being pursued in an IST in over 200 patients in patients with newly diagnosed high-risk prostate cancer. Oops. With regard to additional programs, our partner programs where we could anticipate future cash flow and further platform validation, just to give you a little perspective, in the past two and a half to three years, we have brought in $475 million of non-dilutive capital, either coming from partnerships or milestone payments. We anticipate additional money coming in from such activities, BD activities and milestones. Examples of this are included in that recently, in the end of 2024, we brought in $40 million from the sale of Margenza to TerSera. We have potential for additional milestones there. With regard to the Zynyz molecule, the molecule that we had sold to Incyte in 2017 when it was just starting phase one studies, we have brought in $365 million to date. This is now approved in Merkel cell cancer, as Incyte presented at ESMO last year, had a successful phase three practice-changing study in anal cancer. They have filed an sBLA for this and anticipate approval in 2025. They also had a successful phase three study in frontline non-small cell lung cancer, and I anticipate they would likely file that as well. There we have significant hundreds of million dollars of potential milestones there, and we retain a 15%-24% royalty there, which allows us both to opportunely clip a coupon or potentially monetize that through the royalties. With regard to the Tzield molecule, the CD3 molecule that we developed years ago for type 1 diabetes, which ultimately we sold to Provention Bio, which was then acquired for $2.9 billion from Sanofi, we retain significant hundreds of millions of dollars of potential milestone payments. They have filed both in Europe as well as the U.S. for additional indications, the new onset indication for type 1 diabetes. We will await the results of that to see that going forward. We have a very significant collaboration with Gilead around CD123 and CD3, which is in dose escalation, continues in dose escalation, and we have collaborations around additional research programs with them. While I will not be able to discuss the specific programs today, we're very excited about the activity of these research programs. Let me touch on individual molecules quickly. You heard a lot about vobramitamab duocarmazine. This is the ADC molecule using a linker toxin, duocarmycin, which is a DNA alkylator. We presented data at ESMO, which updated the landmark six-month endpoint of rPFS. We have presented updates on the safety profile of this molecule, and what we have promised is an update early this year with regard to the prospects for this molecule, which we will do in very short order. As we've described, the goal for this molecule is to assess with the final median PFSs what is the safety profile of this molecule, what is the competitive landscape, what else is in our pipeline, and what do potential partners view this molecule going forward. That is about all I'll say today, and I'm sure you'll have some questions about that, which we can follow up. We're very excited about lorigerlimab. This is the PD-1 CTLA-4 molecule, which we designed to have as good or better activity for combinations of anti-PD-1s and CTLA-4s, ipilimumab as the prime example. As you know, the historical basis of that combination is the toxicity associated in combinations where they've had to limit the Ipi dose to 1 mg per kg, giving a maximum of four doses. As you know, there has been no checkpoint molecule that has been approved in prostate cancer. We showed very exciting data two and a half years ago at ASCO GU demonstrating 29% PSA50 reductions in late-stage metastatic castration-resistant prostate patients with a 26% overall response rate, with all the patients with ORRs having PSA90s or greater. This led us to design a LORIKEET study. This is a 150-patient study, two-to-one randomization for combination of docetaxel in chemo-naïve patients who have progressed on an anti-androgen receptor targeting agent in combination with lorigerlimab, 50 patients getting control arm. We finished enrollment of this study in December. As you know, the historical data on the control group there is about eight months at best. We should see what the control group will be doing this year, and therefore we'll have a readout of this molecule going forward. What we have also promised with the excitement about this molecule is we're looking at the potential for other tumors, and we will announce very shortly what additional tumor type or types we will pursue. MGC026, which is called our next-generation B7-H3 ADC molecule, we saw this as a parallel development to vobramitamab duocarmazine. I think we have it all designed appropriately here. We're using a variable domain, which is the exact same one we have in vobramitamab duocarmazine. We know this is a very good binder to tumors versus normal tissues. We know this gets incorporated into the cells quite efficiently. We've done our comparison of this variable domain against what we believe to be the Daiichi molecule in terms of incorporation, and we see superiority of this variable domain. It also targets the inhibitory receptor that is deemed to be associated with inhibition of T-cell responses targeting B7-H3. On the linker toxin side, instead of the duocarmycin molecule, we're using the linker toxin from Synaffix, which ultimately is an exatecan, a topo I inhibitor. As you see here, it has a DAR of four. It is binding to an engineered portion, the glycan found in the Fc domain, and this is a big advantage because by knocking out the Fc activity of this molecule, therefore it does not bind to FcRs. The theoretical basis of what interstitial lung disease is caused by the Enhertu molecule and the DXd platform and that of SN38, you avoid the binding to Fc receptors expressed on alveolar macrophages and other granulocytes, and therefore in theory should have a reduced opportunity to develop interstitial lung disease. In addition, Synaffix and work we've done ourselves suggest that this is superior to DXd and the SN38 platforms. It has lower multidrug resistance. It has enhanced potency as compared to those platforms as demonstrated in published data. Where we are on this molecule, we're in the middle of dose escalation. We should finish out dose escalation this year. Should be able to report updates on this phase one study later this year. Designed in this study is the ability to do mini expansion cohorts once we see responses. We are very excited about the prospects of this molecule. The next one is our ADAM9 molecule. Excuse me. One second. This is using an antibody that we developed originally in a collaboration with ImmunoGen. This targets a metalloprotease ADAM9, which is overexpressed in a lot of different tumors: GI tumors, pancreatic, colorectal, gastric, lung cancer, cholangiocarcinoma, triple-negative breast, prostate. Again, we're using the Synaffix technology here, the exact same linker technology which I just described for O26. This is starting phase one study this year. Obviously, no data this year, more likely next year. The MGD024 is the molecule I alluded to before as a collaboration with Gilead at CD123 x CD3, middle of dose escalation in AML and other 123-bearing tumors. This is an option-based deal with Gilead, and they have the opportunity to complete the licensing by the end of phase one. I think that's all I planned for today, and it's up to you for additional questions. Perfect. Okay. Yeah. Thanks so much for that very detailed presentation. It's good to get a level set, the foundation and everything that you guys have going on because it is a lot. You can come get comfortable, have a seat with us. I guess my first question would be on the vobramitamab duocarmazine update that's expected pretty much imminently because you got it to this quarter. What do you need to see from this dataset to continue development of it, or is that still the goal to continue developing it or switching to MGC026? Our goal is to do right for the patients, do right for the molecule, and do right for the company and investors. There may be different decisions that then preclude us to any final answer to that, and I'm not going to share it with you today. As I've pointed out, first we want to see the efficacy activity. As we presented at the ESMO presentation at the six-month landmark endpoint, we had already improved the efficacy from the phase one 3 mg per kg Q3 from a median PFS of the 41, 42 patients we had in that study of 5.5 months, and we were already at eight, eight and a half on the doses that we were taking. Now we were continuing to follow these patients. The expectations that will be even longer now, and the question is how much longer is enough. As I've alluded to you before, given the competitive landscape, it would have to be in the double-digit range or higher, and clearly more is better in that regard. The second is on the safety. As we achieved our goals of, if you recall, what TAMARACK was designed to do by giving lower doses, we got better efficacy, but we also improved the safety. If you recall, the biggest issues on the safety was hand-foot syndrome. We dropped that by 50% or more. We dropped the neutropenia. As we continued to be able to dose these patients longer, we were seeing similar rates of pleural effusions occurring later. The question then becomes, can we address this going forward with further designs of this study? The answer is, I think so. I think we have a hypothesis. We're not going to articulate it today, but that will come into the decision-making process. In addition, we have to say what is out there, what's the competitive landscape, where can this molecule make a difference? I'll give you one example. As you know, the majority of the competitive molecules are targeting PSMA. As you know, as the disease progresses in patients, PSMA levels drop, and actually a lot of patients with late-stage castration-resistant prostate cancer don't express PSMA anymore. B7-H3 actually is maintained or goes up. It is a great opportunity now that if in fact the efficacy data and the safety data bears out, that could be a subpopulation. I also, we showed at ESMO that in the pre-chemo population, it's working pretty well as well. That will be important. As I've illustrated, we have a great portfolio of clinical and the preclinical ones I haven't even talked about. I'm excited about it as well. We have to make the decision, can this be partnered and what can be done? Those are the decisions we'll be confronting. Okay. Staying on the topic of B7-H3, you have O26, which looks promising. It has a different payload. Can you tell us a little bit more about why you wanted to select a topo payload and kind of separately, since we're talking about the strategy of why this, why you selected this, why the payload, what made you decide to keep an ADC instead of maybe going for an antibody, T-cell engager, or any other modality? Curious your thoughts on that. Both can be true. Let's start with where we were. As I noted before, we had a great variable domain, but an ADC is not any different than a targeted chemotherapeutic. We know in the spectrum of B7-H3 expression across a large number of different tumors, every tumor will respond to different classes of molecules. In fact, if you look at the history of prostate cancer, one would not have anticipated a DNA alkylating agent necessarily would work in prostate cancer. The same thing would be said about topo I inhibitors for a number of different tumor types. It was obvious that Enhertu was a home run there in the topo I space. This was even before Daiichi Sankyo developed a similar linker DXd for B7-H3. We already had decided that we wanted to go to topo I. I illustrated the reasons why we like the Synaffix linker toxin platform. We think that it has many of these features that mechanistically would make it a superior molecule there. In our business, it is very rare to have an antigen that is overexpressed in so many different tumor types with relatively limited expression in normal tissues. It is important to pick the right variable domain and the epitope to that. We felt we had the right thing. That was why we pursued that there. I should also point, if you've heard me endlessly over the years, single drugs rarely cure cancers. It is always a combination story. Our goal has been, as you know, from the get-go, is can we take orthogonal mechanisms and put that together? What you've heard and illustrated here is we're working on combination checkpoints. We're working on ADCs. We're Fc engineered. We'd like to see the evolution of these molecules come together and meet where you show activity of the individual molecules and show superiority going forward. I'll give you a good illustration. At ASCO GU just recently on Pluvicto, which is obviously an exciting molecule in the radiopharmaceutical space, an Australian group presented data on giving limited doses of Pluvicto in combination with PD-1 and show prolongation of our PFS going forward. There's no reason that we can't do the same thing with our molecules as well. What indications beyond MCRPC could you use a B7-H3 for? Are Are you exploring? It's pretty broad here. Obviously, as you know, a lot of the competitive molecules are going after small cell lung cancer. It's not something given where we are in the case of O26 that we're going to jump in to go after that indication. It's overexpressed in lung cancer, both non-small cell and lung cancer. It's expressed in other large indications. It's in renal. It's small indications. It's in thyroid. It's pretty large. It's all the GU cancers. You'll see it in endometrial. You can see it in a subset of ovarian. There's a lot of possibilities here. What we will do for O26, and we have actually a wide range of tumors that are being enrolled in this study, we will identify the ones. We will look at market opportunities. We will look at what the competitors are focusing on. We're not afraid if we think the activity is superior to compete, but we're not stupid when somebody is doing a phase three that we're still in phase one. We were going to pick and choose based on the activity profile we see in the phase one, phase two to decide on which particular tumor types to pursue. Okay. Next, let's move to the upcoming phase two data from the lorigerlimab trial for lorigerlimab. What do you think it could achieve here with PSA50, ORR, and what could we expect in the data? I know you mentioned a bar already, the eight-month rPFS from the CARD trial, but more so where you think it'll end up and where you'd really like it to end up. I think right now it is, I don't know the answer. I mean, despite the fact that it is an open trial, we finished enrollment in December. Given the eight-month timeframe, you know the control is going to read out this year, and therefore you're going to look at the hazard ratio later in the year and see are the curves separating and going forward. You know, I'd clearly like to have a high double-digit rPFS number, but the bottom line is PSMA fore didn't show any OS benefit for Pluvicto. I would love to see an OS benefit as well. That obviously will take longer than this year to do that. Again, you might start seeing separation of the curves there in that regard. The bottom line for obviously checkpoint molecules, you'd like to see a subpopulation tail that would be responsible. If we have a combination of double digits and higher and better, we see some OS benefit there and a tail, we got a home run there. Is it going to be too early to show rPFS? I know that you said that enrollment completed in December, but. I don't know. It's an event-driven thing. We have our calculations of when the particular events. We'd like to see at least half the events occur. That clearly was what happened for PSMAfore in that regard. It's possible. I just don't know at this point. Maybe landmark like you did at ESMO. Possibly, yeah. Okay. Maybe you could talk about where you think this could be positioned in the marketplace, like relative to what's available out there. I mean, Pluvicto is going in earlier lines. There's still chemo. There's second ARPI. Where do you think this could go? I think it's limitless. I mean, I think that as you know, in the landscape of prostate cancer, the standard of care is changing. The recent data on the final readout of the PARP plus Enza studies suggest that those will be, that may become more standard of care, obviously. This is both in the DNA repair defect indications, BRCAs, et cetera, but also in non-mutational prostate cancers as well. I think that as I illustrated before and described the combination with Pluvicto with the PD-1, if you're having the value of a CTLA-4 there, this could be early line. It could be late line. I won't even rule out that neoadjuvant is a possibility in years to come. I'm optimistic going forward. Yeah. And maybe type of patient too, that it might be better for what, like slower progressing patients. Absolutely. There clearly is, we don't have, our understanding of prostate cancer is still evolving. When I look at the patients that are in our trials, we have some patients that don't respond to anything. They just quickly move. We got a sizable large proportion, whether it be in the early line or late line, hormone sensitive, hormone resistant, that just work their way along. As we get better understanding of the histological and the mechanistic basis for those subpopulations, I think we'll get a better idea of how to use these drugs and which lines of therapy. Yeah, that makes sense. Okay. I think we have time for one more question. Nick, do you want to ask something about the pipeline? Yeah. So beyond vobramitamab duocarmazine, beyond lorigerlimab, beyond MGC026, since we've talked about those, which is most exciting? Is it MGC028, MGD024, the LAG-3? What do you think is most exciting? I have a lens that you don't have because I know what's in our both clinical and preclinical pipeline. I would say that any one of the clinical assets that you just alluded to, except for ADAM9, because we're just starting the phase one study, we have activity. They can all be winners here. Having now a second ADAM9 molecule and trying to fix what was the problem before can be a tremendous winner. I get back to the point I made earlier. There are very few targets that have expression against a lot of tumors with limited expression in normal tissue. One should try to take advantage of them as much as one can. Having said that, you're going to have to wait to hear our preclinical pipeline. I'm really excited about some of the next generation platform things we've done and new targets we're going after. You'll have to wait for late 2025, 2026 to hear some more about those. You can disclose those if you want to. I know I can, but you know I got to keep you asking us back again. All right. We are exactly up on time, but thank you, Scott, for this great discussion, detailed presentation, for being here. Thanks everyone for listening. Thank you.