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. We have with us today CEO Scott Koenig. Thanks for joining us. Let's get started. Jonathan, always a pleasure. Nice to be invited. Maybe just for a little bit of an introduction of the company for those who are new to the MacroGenics story or have not been following for a while. As you know, we are a fully integrated immune therapeutics company focused on developing first-in-class, best-in-class molecules for treating cancer. With our fully integrated platform, we do everything from early target and platform discovery to late-stage clinical development, including the manufacture of marketed products, as well as the clinical assets that we are testing and those of partners at our commercial facility in Rockville, Maryland. Historically, three of the molecules that emerged from our pipeline have been approved by the FDA or are currently marketed. To get just a good snapshot of where the company is right now, three molecules with our three core platforms are Fc-engineered, our DART bispecific, and our ADC platform are being pursued for treatments for various lines of therapy for prostate cancer. We have three clinical assets that are antibody-drug conjugates. We have three assets that use our DART bispecific technology that have either finished clinical testing in phase I or are continuing studies in phase I to development. Ultimately, we have a very good cash position. As we announced on our third quarter earnings call, we had $200 million pro forma and $240 million in cash, which we said would be able to take us into 2026 with our current plans for our program. As you know, we have been very successful bringing a lot of non-dilutive capital into the company. In the last little more than two and a half years, we've borne $475 million through various partnerships and milestones from our programs. Just for this coming year, we should keep focused on our partnership with Incyte on the retifanlimab coming up for an sBLA has been filed for anal cancer there. Opportunities there where we have 15%-24% milestones. It's been approved already in Merkel cell, and there's been a successful study in lung cancer. Our relationship with Sanofi on the Tzield molecule for Type 1 diabetes. They have three regulatory anticipated responses in the second half of this year, which would potentially come with additional milestones. Good partnership with Gilead on our CD3 x CD123 program and working on some research programs with them as well. The prospects look really good despite the stock price. The company is in really good shape. It's, I would say, in the history of the company. I'm very pleased to say we're in a great position for a lot of readouts this year and the next six, 12, and 18 months. Great. Thanks for the introductory remarks. Maybe first question, can you give us the latest status of the ongoing CEO search? Yes. As you know, last year it was announced that a search would be ongoing for my successor. It was anticipated when announced last year that the process would be completed by the end of February. Unfortunately, the process has not been completed. They are still doing interviews, and they had asked me to continue in the role of CEO, and I have been thrilled to continue to work. The expectation is over the course of the next couple of months, hopefully a successor will be identified. Understood. Can you discuss the latest status and progress with Vobra duo? Yes. As you know, Vobra duo is our ADC, first of actually four molecules that we've developed that target B7-H3 ADC, the first ADC in the clinic. It is an ADC that uses a linker toxin called duocarmycin, which is a DNA alkylating agent. We provided the latest update at ESMO in September on the landmark endpoints for that trial, as well as an update on the safety of the program. We were very pleased that this study called TAMARACK was designed to look at two lower doses of Vobra duo as compared to the dose we used in the phase I study of 3 mg per kg on a Q3 weekly basis. We were testing 2 and 2.7 every four weeks. The landmark data showed that we achieved what we were going after in the context that more doses were able to be delivered for patients longer. Second is the rPFS at landmark was superior to what we saw with the phase I data. The comparison at the six-month landmark was approximately eight, eight and a half months for each of those lower doses compared to 5.5 with a 3 mg dose. We saw significant reductions in a lot of the safety parameters, particularly hand-foot syndrome would drop by 50% or more, reduction in neutropenias. As we were continuing to give the drug longer, we also saw some new observations of the pleural effusions were coming a little later. Where we are right now is that the last patients were dosed in July. The study was designed to follow these patients six more months for endpoints. We have reached that point. What we have said is that we will analyze the totality of the data with regard to efficacy and safety. As important, looking at what is the activity of this molecule versus things in our own portfolio, what the competitive landscape is in terms of other things that are in experimental development. Ultimately, given our broad portfolio, it would be important for us to, if we were to take this forward, to do this with a partner. Get a better understanding of what are the opportunities for partnerships for further phase II through development in prostate cancer. What we will plan to do is provide an update very shortly about some of those decisions around this molecule. Got it. Maybe if we could just double-click on that last point. What are the key considerations that will help you inform what the next steps? I would say if you put it in the context on the efficacy side, given where the standard of care, for instance, in the chemo-naive population is around eight, 8.3 months. In the chemo-experienced population, it may be around eight as well. Although real-world data suggests that both in the pre-chemo and post-chemo, it's probably shorter, but let's use that as the parameter. Thus, we've already achieved eight and eight and a half at the landmark with expectations that we will see prolongation of the median PFS here. I would say that for us to be just able to take a risk on doing this, we should be in double-digit median PFS. Of course, any survival benefit would be a complete change for the market. As you know, PSMAfore, which looked at Pluvicto, did not meet the criteria in the pre-chemo nor in the post-chemo setting. There really is no curative treatment for metastatic castration-resistant prostate cancer. Anything that would prolong survival would be seen as an attribute here. That is, I would say, the parameters we would look on efficacy. With regard to the safety, what we would want to see is a pathway forward. We have certain hypotheses on what we would do to improve the safety, particularly the pleural effusions. Again, if we move forward with a partner on this, we would design that into the study. Understood. You also mentioned the comparison between this program and other things in your pipeline. Can you discuss your second B7-H3 ADC program, MGC026? Yep. How is this differentiated from Vobra duo? Quite in a way, we are taking the learning curve and almost the best of all worlds. First of all, we know the variable domain of this molecule in 26 is identical to the one we have in Vobra duo. We did that purposely because we knew how good an antibody this was. A, high tumor to normal tissue binding properties. B, it is targeted to a domain within B7-H3 that is inhibitory for this molecule. That could be another attribute. C, for an ADC, this is exceptionally well incorporated with a linker toxin into a cell. We actually have done some side-to-side comparisons with other competitive antibodies that we believe, based on sequencing, shows that our molecule has these added benefits and features. We have a good variable domain. Now we add a linker toxin, which is a Topo I inhibitor. We're using the Synaffix technology, which has an active exatecan molecule. This, again, with work that Synaffix has done and what we have done as well, suggests as compared to other topo I inhibitors, have features that appear to be superior. Some of the parameters, for instance, are it seems to be more potent on a head-to-head comparison. Again, compared to DXd, the deruxtecan that the Daiichi Merck molecule is using, it seems to be better than SN38, which is in Trodelvy, another topo I inhibitor. It has a lower multi-drug resistance profile. Because it is linked to the glycan site within the Fc region, as many of you know, topo I inhibitors, one of their main toxicities is the potential interstitial lung disease. Because you knock out binding to Fc receptors, which are expressed on alveolar macrophages and other granulocytes, there's a good chance that you would have less chance to have interstitial lung disease as a result of using this particular linker toxin. Where we are in this development plan, having what we think is a good antibody, a good linker toxin, obviously a lot of data now that says this is a good target, we think we're in a good position to move this forward. We're finishing out the phase I study. We expect to have that complete in the second half of this year. In the way this is designed in dose escalation, if we see activity in a particular tumor type, we have the ability to put little mini cohorts there. Our expectation is to be able to provide an update later this year about the status of that program and then hopefully be able to give you an idea of which particular tumor types we would expand into in phase II development. Got it. How would you characterize how the study has progressed so far? Exceptionally well. There is a lot of we have a lot of people clawing to get into the study. As you know, it becomes a competition among investigators, can I get my patient in there? You only have a certain number of slots there. There has been we are moving this as quickly as possible to get to an answer. Do you think you have enough from the 026 phase I study to help inform your decision-making on Vobra duo at this point? I would say that we certainly don't have the breadth of comparison, particularly for prostate cancer. No, that would be, and I wouldn't say that necessarily 026 would be positioned to go after prostate cancer because of the wide expression pattern of 026. While prostate would be one of the considerations, there are a number of other tumor types that we are likely to explore with 026. Understood. If you think about how your two B7-H3 programs, how would you say they compare versus other things in the competitive landscape? I think we'd have to look at this again in the context of prostate cancer line of therapy and then other tumor types as well. Let's just start with the prostate story. As you know, we're developing lorigerlimab, the PD-1 x CTLA-4 molecule, and being tested right now in the LORIKEET study in chemo-naive metastatic castration-resistant prostate patients. It is an unusual opportunity for us with this molecule for prostate cancer, given that no checkpoint molecule has been approved for prostate cancer. Actually, there is no competition out there that we know of in the checkpoint space in prostate cancer. Specifically, the only other company that was working on a PD-1 x CTLA-4 was Zai Lab recently, who has announced that they're stopping their PD-1 x CTLA-4 program, where they were only looking at a subpopulation of prostate cancer with DNA repair deficit. If we're able to succeed here in combination with docetaxel in a chemo-naive population, we have a beautiful way of developing this not only for prostate cancer, but also for potentially other indications. As many of you know, we had presented data about two and a half years ago in late-stage castration-resistant prostate cancer, where we saw a very nice outsized response, overall response rates, as well as PSA 50 reductions as compared to Ipinivo tested in similar settings as compared to Pembro tested in similar settings. Again, we have finished enrollment of 150 patients' study in December. One hundred patients getting docetaxel plus lorigerlimab versus docetaxel alone. As we know in the chemo-naive population, as I stated before, the median PFS is about eight months at best on the comparative other studies. If we see obviously an improvement on that combination or a nice subpopulation that is having a long prolonged response or improvement of OS, this is a terrific opportunity to develop this not only as a combination with docetaxel, but then the thought is you can combine this with other agents that are orthogonal to the checkpoint activity of this molecule. Got it. I was going to touch on that anyways, but actually my prior question was with regards to your two B7-H3 ADC programs. And how do those compare? Oh, to other programs. Versus the competitive ones. Oh, okay. Obviously, I would say that the Vobra duo data to date is better than any other ADC in prostate cancer. The biggest data set we have out there to compare to was the Daiichi molecule, which in their phase I data, they showed about 50 patients with a PFS of 5.3 months. Already when I described our landmark endpoint of six months of being already eight, eight and a half, we're superior to that. Now with further follow-up, we expect that to be even higher. At least in the terms of activity, I think in prostate we have a superior opportunity there, although we have a different safety profile that we would have to contend with. Now with regard to other indications, a lot of the other B7-H3 molecules, including the Daiichi, the MediLink, and Hansoh molecules with GSK, have shown nice activity in small cell lung cancer. As you know, many of them are moving forward to phase III development in that indication. There are other, depending on the company, being pursued for other things. With regard to 026, we are certainly behind time-wise, but given the broad expression of this, I think we can find our competitive indication where we can move quickly ahead if the phase I data turns out as we expect. Understood. Maybe switching over to MGC028, can you tell us about this next-gen ADAM9 program? Yes. How is this program differentiated from, I guess, a past ADAM9 program that you guys previously had partnered with ImmunoGen? Yeah. This is a great opportunity. One of the things that if you look at the history of MacroGenics, we like to have the balance between going after both validated targets as well as novel targets. B7-H3 was a good example. We were the first company to make any molecule to that target. The same story is true for ADAM9. This is a target that is a metalloproteinase by activity, although the doses we're using here is not to inhibit the metalloproteinase activity. This is a target that's highly overexpressed in a lot of different tumor types, lung cancer, a lot of GI cancers, including pancreatic, colorectal, cholangiocarcinoma, gastric. It's also found in a subset of prostate and triple negative breast. We have published and presented at AACR last year the preclinical data on this molecule showing terrific activity in vitro and in vivo against a lot of different tumor types. Jonathan, as you've alluded to, we jumped into the clinic with this target with a collaboration with ImmunoGen a couple of years ago using their sort of next generation maytansinoid called DM21. We took that through phase I development. It was a 50-50 partnership. ImmunoGen was acquired by AbbVie. AbbVie presented the data on the phase I at a meeting, which showed that we could not achieve the targeted dose that we were hoping because of the associated eye toxicity that is characteristic of maytansinoid toxins. We both agreed that that 936 molecule would not move forward. Because we had such good preclinical data on the variable domain, and we owned that, and we developed that variable domain, we decided to make a new molecule, which contains the exact same variable domain we used in 936. Now we're using what I previously described, the Synaffix linker toxin linked to the glycan in the FC domain, which is active moiety is exatecan. Again, good experiences with the variable domain. There's a good track record so far with the linker toxin. We are started phase I development there for this molecule. We're again the only one in the clinic with this target. Understood. How should we think about timelines for that clinical? You know what we decided to do is instead of having it open to every tumor type, we are focused on a subset of the tumors that should be responsive so that we're hoping to get to a signal both in terms of activity and safety in a shorter period of time. This is just starting. I would anticipate by 2026 we would have enough data to be able to provide some update on the program. Understood. How are you thinking about business development opportunities for your programs and platform? We're very excited about that. Again, as you know, historically we've been very active in business development and taking advantage of the broad platforms and targets and that has attracted a lot of capital to the company both through partnerships, but ultimately even in the clinic and approval. As I alluded to before, we have in 2025 opportunities from the Incyte and Sanofi partnerships that we would potentially see more capital coming in in the cases of both of those in terms of milestones. In the case of Incyte, particularly we have a 15%-24% royalty on that. If it gets approved in a larger indication like anal cancer, we could expect more money coming in from sales of that. Also, it's a potential for monetization if we decide to go that route for the royalties. In addition, we have the partnership with Gilead, which I alluded to before. There is the dose escalation study for the 123 x CD3. They have an option by the end of phase I. We have a second program, a research program that is proceeding very well on another DART molecule. We are actually exploring some work on a third molecule with them. Opportunities are there in terms of both milestones and other payments from that partnership. Even beyond that, people are very interested in other things in our portfolio, both clinically and preclinically. We will just wait for later in the year to describe those opportunities. Just again, to put this in context, we have brought in hundreds of millions of dollars from these various opportunities in the past couple of years. I think we will continue to follow that pathway forward. Understood. Let me check to see if there are any questions from the audience. All right. Maybe just last question for me. Can you highlight the key 2025 catalysts and milestones that the investors should be looking forward to this year? Yeah. For 2025, I alluded to some of these things. Obviously, very soon update status of Vobra duo, where we expect to go with that. Second is bring you up to date on the lorigerlimab, LORIKEET study, probably second half of this year with regard to the clinical outcomes on that program. I should also point out, based on our phase I dose escalation data with lorigerlimab, plus the activity we've seen in both phase I and now phase II in LORIKEET in prostate cancer, we will announce another tumor type, which we will be pursuing for lorigerlimab. Stay tuned for that very shortly. Obviously, progress on the ADAM9 program this year. Second half of this year, certainly an update on MGC026 going forward. Likelihood of business development announcements during the course of the year. Understood. Thank you very much for joining us. Thank you so much for the invitation. All right. Thank you. All right. Thank you. Good to see you. Thank you.