Okay, so just gone live. My name's Peter Lawson. I'm one of the biotech analysts at Barclays. I cover SMID cap, predominantly SMID cap oncology-focused companies, and have the pleasure of covering MacroGenics for a number of years. I've on stage with me Scott Koenig, the President and CEO of MacroGenics. First questions I've been asking companies have just been more kind of macro, just with the various movements that have happened with the new administration. Just something that always concerns me, I guess, from COVID was just like if there are any supply chain issues that we should be thinking about as we think about tariffs kicking in or cranking up. Yeah, I would put it in the perspective of going back to COVID and even before, one of the strategies that MacroGenics has set out is really to do as much as we can internally. Going back to 2005, we initiated our own manufacturing facility and now have a commercial manufacturing facility. In that context, to be able to control the production of not only our own molecules, which include all the molecules in clinical development, we also make two commercial products and molecules for other organizations that are in clinical research. We have to always be ahead of the game in terms of supply chain issues and be there, but you never know when a particular component is going to be challenging to get, especially if they're not sourced within the U.S. I could tell you, for instance, during the summer, for one of the control products that were being used in the clinical trial, there was some shortage that we ultimately resolved. It was resolved within a few weeks, that is always a concern. You've heard about shortages of antibiotics, for instance, that occur. At this point, I think we're in very good shape in terms of anticipating our needs over the next couple of years, but we'll have to see how the environment evolves. Gotcha. Thank you. Just as we think about the FDA with proposed and, I guess, current cuts, have you seen any slowdown in communication patterns, or do you anticipate any slowdown in? I think it's too early to tell. Obviously, there's a lot of disruption, as we all are encountering in government, and particularly within the HHS and FDA. Patrizia Cavazzoni leaving and senior members of the FDA leaving often presents challenges in the operation. I'm a little bit anxious to see how this gets all played out. I guess this week we've heard that employees that are supported by the fees from companies via PDUFA are not at risk. I could tell you there is a lot of anxiety, given that we are located in Rockville and very close to the FDA. We do hear of a lot of FDA and NIH people looking for jobs. We'll have to see how that all evolves. Okay, thank you. I guess the other component is just like if there's any worry about restrictions over biologicals manufacturing, and whether it's here or overseas and partnerships and any cross-border licensing agreement worries. I think that as we've built MacroGenics, it's a fully integrated discovery to commercialization, but including the manufacturing, we are trying to control our needs for our own programs as our primary objective. We do have, obviously, contracts for some CRO work on a more limited basis. Currently, right now, for instance, the ADC molecules, we have vendors that we've had good relationships with in the US to do the conjugation. At any time, that could be impactful, I think, more to others than us. We have to be aware of those challenges going forward. Gotcha. Thank you. Final question just around NIH cuts. I mean, clearly, I assume that's a terrible thing long term. And just your view on the near to midterm, kind of how that could impact innovation. I am very concerned about that. Having grown up within the academic and government infrastructure, training in universities, being at the NIH for over six years, and then going to industry, it takes a long time for the organizations to build themselves into a mass. Given so many challenges in our healthcare system, any disruption of the infrastructure there, I think, will have very long-term impacts. In particular, as we've heard of funding cuts, as of a couple of years ago, individuals were not getting their first R01 grants till they were 42 years of age. Now if your pay line is being cut even worse, there is no incentive for people to build out academic careers there, which will have a horrible impact on the basic research infrastructure. I think a lot of the, if this continues, I think a lot of the burden for both basic as well as translational work will fall on the biotech and pharmaceutical industry going forward. Gotcha. No, that's kind of frightening change. As we get back to your platform and B7-H3, ADC, kind of what do you want to see to move that forward? It's been really encouraging data that's been safety signals, and you've kind of tried to mitigate some of those, but just what are the particular metrics you want to hit, whether it's rPFS or other components? Yeah, let me put it in a little broader context. As you know, MacroGenics has been the leader in developing B7-H3 targeted molecules in the history of the company. We were the first to put a therapeutic in testing. We've had historically four different molecules targeting B7-H3. Three are currently in clinical testing. I think right now you're alluding to the vobramitamab duocarmazine molecule, which is an ADC molecule with a linker toxin called duocarmycin that the mechanism is based as a DNA alkylating agent. As we recently reported at ESMO, we provided six-month landmark endpoint in September of a TAMARACK study, which was looking at two lower doses of the molecule in castration-resistant prostate patients. These are ones who have been both naive to chemotherapy as well as experiencing chemotherapy. We were, in a sense, trying to compare it to our historical dosing in the phase I study at 3 mg per Q3 testing versus in the TAMARACK study of either 2Q4 or 2.7Q4. The landmark data was very encouraging. We had established that at the six-month landmark endpoint of these two lower doses, already a better PFS profile, where we were already at eight to eight and a half months for those two doses. We had seen dramatic improvement in some of the safety parameters going forward. In July of last year, we stopped dosing the patients who had not progressed or were off study and said we would continue to follow those patients for another six months. That was actually the study design and the endpoint. As we've described this early part of this year, we would provide an update both on the final median PFS as well as the safety profile as final evaluation. In a broader context, we're looking at that response in the whole development plan for any drug for prostate cancer. How good is the efficacy? Is the safety manageable to move forward? What is the competitive landscape? What else do we have in our clinical pipeline in the prostate setting? Ultimately, given our broad pipeline and so many active drugs, ask the question for doing a phase III study, do we want to devote it to this molecule or to other molecules? I think the general conclusion, which we have expressed previously, is that for us to go forward with all the other success, if we're successful in all those other parameters, we would want to have a partner to take forward, given the cost of doing a large phase III study. We will provide updates very shortly about the opportunity on vobramitamab duocarmazine and probably at a later time, later this year, present a more wholesome full data set for the entire program so people get an appreciation of what was done in the TAMARACK study. Gotcha. The idea of a partner for kind of a large phase III study, would that also capture both vobramitamab duocarmazine and also the next generation or the Topo I labeled? As you know, Peter, we have been very successful in the whole history of the company of doing partnerships. We are very open to different strategies on partnering molecules. I would say that it would be more likely just to focus on a vobramitamab duocarmazine opportunity with a partner, but we never discount that if somebody wants to have a broader relationship, given that, as I already alluded to, we have multiple B7-H3 targeted molecules, that we might possibly include that. Never excluded, but I would say the inclination would be to focus on just the vobramitamab duocarmazine as an opportunity. Gotcha. Do you think vobramitamab duocarmazine versus 026? Do you think there's a difference in the different indications that could go out? Oh, absolutely. Again, if you recall, the strategy which we set out a number of years ago was that experiences, as everyone is well aware, is that different tumors will respond to different chemotherapies and mechanisms of action. We had an excellent variable domain antibody for targeting B7-H3. And so we started out with the duocarmycin as the first toxin, but as more data came in on the potential of Topo I inhibitors to treat lots of different tumors and our relationship with Synaffix identifying what we think is a superior Topo I inhibitor platform, we said it would be, I think, a smart idea for us to develop two parallel molecules. In the context, for instance, we're talking about prostate cancer, it may be vobramitamab duocarmazine may be better than a Topo I inhibitor. We just don't have enough data right now on MGC026 to address that at this point. Gotcha. Okay, perfect. Thank you. The efficacy from, or the difference in efficacy you get from a Topo I payload, is that depth of response? Is it durability? I think it could be all depending on the tumors. As you know, a lot of competitive molecules out there right now targeting B7-H3 has shown very good efficacy, for instance, in small cell lung cancer. Depending on which study you look at, probably about half the patients have had objective responses. In the end, it's what line of therapy you're going to give it, are you giving this as a single agent or in combination? What is standard of care of this? I think, as I have highlighted for the ultimate treatment for prostate cancer, the drugs on the market are not curative. They're palliative. Ultimately, doing combination therapy with orthogonal mechanisms, I think will be the best way to go to hopefully get to a cure for prostate cancer. Which if, thank you, I was going to open it for you. With 026 and vobramitamab duocarmazine, when you look at that versus Daiichi Sankyo's molecule, which are more similar and. I would declare without the data that we have a superior molecule. But all joking aside, there is some rationale to that opinion. First of all, on the antibody side, we think we have a better variable domain than the Daiichi molecule. We have actually made what we believe to be a copy of their molecule. And we know that we have excellent tumor to normal tissue binding ratios and an excellent incorporation of linker toxins into cells and seems to be superior to the variable domain that they are using in their lead molecule. I secondly would argue that based on the Synaffix preclinical data and even some clinical data that's out there with their linker toxin for Topo I exatecan, it has a profile that could be quite superior to the direct exatecan basis for the Daiichi Merck molecule. In particular, data has been shown that it's more potent, meaning the Synaffix platform. It has lower ability to induce multi-drug resistance. And by the nature of the fact that the linker toxin is hooked onto an engineered glycan within the Fc domain, if you go back to the data that Daiichi has presented with regard to interstitial lung disease, they account for both in HER2 as well as the B7-H3 interstitial lung disease to be secondary to the binding of the Fc domain of their linker toxin to alveolar macrophages and other granulocytes which are in the lung. Because the Synaffix platform knocks out Fc receptor binding by virtue of the binding to the glycan site, one would expect that the likelihood of interstitial lung disease should be reduced. Now, this is theoretical, but that'd be another reason. So great antibody looks like great linker toxin. I would also point out that the same linker toxin has been licensed for other targets. For instance, Innovent is now doing a phase III study with a Claudin 18.2 based on very good phase II data. We think we have a nice combination here of a superior variable domain and a superior Topo I linker toxin that should bode well for the future development. Perfect. Thank you. Daiichi is not pursuing prostate cancer. Is there suspicion why or why not? I would, again, speculation. I don't live in the bowels of Merck or Daiichi. If you go back to the original phase I data, which had about 50 patients in late stage prostate cancer, their rPFS value was 5.3. Not very encouraging. Already, as we have pointed out for vobramitamab duocarmazine, we were at eight, eight and a half. We are hoping the final data will be even higher. It may be that they do not feel that their molecule or Topo I is sufficient to address prostate cancer and the prospects for other tumor types may be better for them. Gotcha. Thank you. I guess as we think about 026, can that be accelerated quickly? Just Just because based on your prior experience, does that help you with kind of dose escalation or prioritization of various indications? I think we have tremendous experience and insights on this target and the whole development process here. I would say that the phase I study is going exceptionally well. A lot of investigators who participate in the study are clamoring for additional slots in our trial. I would say that we're in a dose range that is maybe actually the dose we ultimately select or within one dose away. I think by the second half of the year, we should be in a good position to select a dose and have once we get the pharmacokinetic feedback from our data set back and obviously a little more experience with additional patients. With regard to particular indications, my expectation is that we will select a few to move forward into expansion into phase II development. Gotcha. Thank you. Are you currently enrolling in all comers or do you? I would say that it's a very wide range of tumors. There are a few exclusionary tumor types that we have that are not participating, but it's a very wide set of tumor types. They're not tested for B7-H3? No, this is irrespective of B7-H3 expression. Do you get a sense if there is kind of a threshold level or if there's a? Our experience in both on the 26 molecule on vobramitamab duocarmazine and our previous molecules so far has not identified a direct association of density of expression with responsiveness. Clearly, there are certainly tumors that have higher H- scores and higher percentages of cells, but we just do not have enough data to say whether there is a particular cutoff value for responsiveness. Gotcha. Thank you. When we see the data, kind of how much data should we expect to see? What is it? You know, it's a typical phase I study. I can't give you the ultimate final numbers on these. I mean, these are usual cohorts of three patients going up. I would say it could be anywhere from 20-50 or 60 patients from that initial phase I. We have designed the study that you can do little mini cohort expansions. I don't know what the ultimate final data set's going to show. Maybe just on lorigerlimab, just kind of when we could see the initial top line kind of PFS number. We're very excited about lorigerlimab, which is the tetravalent PD-1 x CTLA-4 bispecific. The LORIKEET study, which is a 150-patient study, two-to-one randomization in patients who had castration-resistant prostate cancer that are naive to chemotherapy. One hundred patients are getting standard of care dosing of docetaxel plus lorigerlimab versus 50 patients getting docetaxel alone. We finished enrollment of that study in December. Given the historical time for progression for the control group, which could be anywhere on the average or median of about five, six, seven, or eight months in that range, I think we'll be in a good position in the second half of this year to know where the study is going. This is an open study, so there are interim looks on the data, but it's an event-driven readout here of PFS. I can't give you precision about this, but I think given where the enrollment was completed, my projection would be second half of this year, we'd be in a good position to say, hey, is the study moving in the right direction? Where are we going with next steps with lorigerlimab going forward for prostate cancer? I should also note that we will announce very shortly another tumor indication that we are going to proceed with lorigerlimab. We are encouraged by what we have seen historically in the dose escalation of lorigerlimab, our expansion studies, the LORIKEET s tudy to date to move forward with another tumor indication. Perfect. Thank you so much. Always a pleasure. Always a pleasure. Thank you Peter. Thank you. Thanks Thanks a lot.