Perfect. So good morning. My name is Peter Lawson. I'm one of the biotech analysts at Barclays. Welcome to Miami, Barclays Global Healthcare Conference, and really pleased to have up on stage with us management from MacroGenics. We've got Scott Koenig, President and CEO, and, you know, first questions are gonna clearly be dominated by B7-H3. So I wonder if you can kind of talk through what we should expect to see in the full data set versus abstract, and kind of what, what you what you can potentially squeeze into that abstract and what you can focus on. Yeah. So let me just sort of set up the set situation, which I know a lot of people are quite aware of. We're moving forward in finishing up a phase 2 study called for vobramitamab duocarmazine. This is our ADC molecule targeting B7-H3 with a DNA-alkylating agent, called duocarmycin. This study is looking to compare two different lower doses than what we used previously in a chemo-experienced population in our metastatic castration-resistant prostate setting. We're looking in this study of comparing dosing at 2.7 mg/kg every 4 weeks compared to 2 mg/kg every 4 weeks. Historically, we were testing this late-line population at 3 mg/kg q3 weeks. As we have said, this study got accelerated because we had a very vigorous enrollment trajectory, particularly in the last half of the year. Two-thirds of the patients came in between a time period of the second half of the third quarter and first half of the fourth quarter. And we ultimately dosed 177 patients in the study despite the fact that originally we were planning on 100 patients in the study. As we announced on our earnings call, we had a DSMB look at the study, futility analysis, obviously looking at safety and the activity that was available at the time, and the recommendation for the DSMB was to continue the study going forward. So back to your question with regard to disclosure of information, an abstract was put together which was due early in February. It took the data that was evaluated by the DSMB to put it in the abstract. As we announced on our earnings call, this is safety data, which obviously was one of the primary objectives of the study is to improve upon the historical safety profile we had seen in the higher-dose regimen. We believe that, as we announced also is that the presentation, oh, if accepted, will be at ASCO. And, again, we don't know the nature of that. Our, you know, our expectation is probably to be a post-discussion 'cause we the abstract was safety, but we don't know that at this point. But we'll have to make it obviously a cutoff date prior to when that presentation is due, which is probably sometime early, mid-May. We'll have to do a cutoff date ahead of that time to be able to do as much cleanup of the data and to obviously incorporate it in the study, whatever we have to present. So given that, what we have said is we'll provide data on all the patients that are dosed. We'll look at, obviously, everything from who's still on drugs, any discontinuation rates, any changes in dosing. We'll look at PSA 50 reduction or PSA reductions in the whole population as well as percentages that ultimately achieved the PSA 50, and overall response rates. But it is unlikely that we'll have a sufficient number of patients that have been dosed long enough to get a mean, median, rPFS value that is noteworthy. So what we indicated on our earnings call is that likely that we would update data in a scientific meeting later in the year, and as you know, there are a number of different cancer conferences later in the year. So I just wanted to set our expectations about that. We'll be obviously transparent about the data and see what it is. You know, as you know, I've kind of put out for the various metrics before we even had that study enrolled. I've put out based on our own experiences what Daiichi has put out on their DS-7300 at ESMO last year, what I think would be, you know, fair ranges for given responses across the board there. And, you know, we're not changing it vis-à-vis the data as it goes along. We'll see what it is and what ultimately the study turns out. But if we obviously clearly meet the objectives of the study, which is improved safety tolerability and activity that meets our goals, then we would then plan a phase 3 study and likely to do that, sort of in the mid-year time. Obviously, we'd have to wait probably to later summer to get the rPFS, but ultimately be in a position so that we could start a phase 3 controlled study, sometime in the first half of 2025. Okay. Perfect. Thank you so much. A lot of detail there. For safety in the abstract, would we get discontinuation rates? Yes. You should be able to see all that as of that particular cutoff, obviously. Yeah. Okay. And And then hand-foot syndrome, pleural effusion, kind of the issues. You'll see, yeah. You'll see. To be frank, I don't remember what was ultimately in the detail in the abstract, but there was certainly a lot of detail there. But you'll get the quality and quantitation on a lot of these side effects that were being particularly looked at in that study and of concern. Gotcha. How long would the median follow-up be, I guess, when we think about the second half data for those 177 patients? I don't know the actual number there, Peter. I would say that it depends on the exact time of the cutoff. Is it gonna be sometime in March? Is it gonna be sometime in April? You know, and as I said, two-thirds of the patients came in the latter part of the year. So somewhere between four and six months would be my guess at this point. But I don't wanna give you a number now and just say that's what you said. I wanna see what the data looks like at that particular time. Okay. But if that second half data said you're gonna try and. Yeah, yeah. I mean, it's. Obscure it. We're trying to basically the final data to make a decision whether we wanna. Yeah. Pursue a prostate indication, whether it be in the chemo-naive or the chemo-experienced. But as we did indicate on our earnings call is that, with obviously the DSMB telling us to move forward, there was some certain degree of confidence that the dose, either one of those doses could be used to look at other indications going forward. And as we said that, we are going to advance into five new additional indications besides prostate cancer, probably starting mid-year. Thank you. Then the patient mix that we see for the phase 2, kind of if you can talk through anything about, you know, who's seen prior dosing, who haven't, who are naive? Yeah. So, again, we when we loosened up the excuse me, entry criteria and allowed for patients up to 1 docetaxel/taxane exposure, that gave the opportunity for patients who either were not eligible for chemo or did not wanna be on chemo to enter into this study. And so, while I don't have the exact numbers among the 177 patients, as I recall, approximately half were chemo-naive and half were chemo-experienced. So there'll be sizable numbers in those groups to independently analyze them for both safety and activity to see if there's any differences there. And that could that will obviously guide us ultimately, if successful, which population to pursue for a phase 3 study. Gotcha. Then for ARAT exposure, kind of how should we be thinking about that for enrollment criteria? How many? Yeah. So, again, that was another criteria we modified, in the amendment. Originally, as we were thinking about a true control registration study, there was a request from the regulators to only enroll patients who had experienced successful treatment with an ARAT of at least 12 months. When we took off the control arm of the study and didn't make it registrational, we then loosened up that criteria and only required to be on an ARAT but did not require a full 12 months of exposure. So, you know, clearly there'll be patients that couldn't continue for varying reasons, progression of disease or side effects or whatever. But as long as they've been on for some period of time, they were allowed in the study as well. Gotcha. And And what colored that change? It was slow enrollment, or was it? Well, I think the original change on the amendment was when we saw pushback on using a second ARAT as control from particular investigators. We were fearful that the time to enroll in the study would take too long, and it was more important to us to get an answer, do we can we identify a dose that was acceptable to move forward not only for prostate cancer but for other indications. And so, you know, looking where we are right now, that clearly was the right decision for us, because of obviously the speed of enrollment and the enthusiasm to participate in the study. Yeah. So should we think about most of those patients have been on an ARAT for less than one year? I would assume, but I don't know the answer to that. So I have no idea exactly what the mean or median or how many fell into the grades up. But I would presume that. Sorry. But they did that, yeah, for a year. But we'll have to update you in the future time on that. Gotcha. There's a washout period. Well, there was a washout for all drugs. So they and I, again, each one of them have some requirement that they wash out on drug. You know, for instance, a radiopharmaceutical or an ARAT or whatever. Yeah. Good. Good. I guess at one time point you're gonna show us kind of an immature rPFS, and would it be kind of landmark PFS data that we should be thinking about seeing? Well, I think, ultimately it will be a landmark, whether ASCO or after ASCO. You know, again, we'll see when the cutoff is and how much the mature data. I won't comment on exactly when that happens. Gotcha. And then how low do you think the hand-foot syndrome, and is there any feedback from physicians about whether that's manageable? Well, I'm not commenting on the conduct of the study. Clearly, it's a situation where we want the incidence to reduce and then, in those that do, ultimately show signs and symptoms of hand-foot syndrome, reducing the grade. As I pointed out, the majority of the patients were grade one too. But once they get grade two, that's when they experience the pain in the extremities, particularly the feet, which is most problematic. You know, I want to sort of set the setting for these type of patients being in that age group. Elderly men, although I'm not androgen suppressed, but androgen suppressed elderly men actually are more feeble than a lot of populations. And so, you know, having the discomfort of pains in the feet to walking and daily living can be quite problematic. If we can reduce grade as well as incidence for that, that would be the objective here. Gotcha. Is pleural effusion, I guess, that was the. That was another side effect again, looking to see a reduction in incidence there. Is that more serious for at least the treating physician? Well, I mean, the fact if it's a situation where you have an effusion that is not creating any issues with respiratory functions, perception of shortness of breath, etc., and it turns out to be an incidental finding, then it's not a problem. Obviously, if it gets to the point when it impacts their ability to exchange oxygen, that you have to do a procedure to eliminate that fluid. That's where it only becomes problematic. So, if they, you know, you wanna minimize the number of patients you'd have to get a thoracentesis to get the fluid removed. Gotcha. Thank you. And the registration trial, if you will, what would that look like? Again, it'd be dependent upon the effect size in the population. So, we'll have to see what the data is in the chemo-naive versus the chemo-experienced population. Presumably, it'll be a controlled trial, either 2-to-1 or 1-to-1 randomization. Again, we'll have to see what the effect size is from the current study to then determine the size of the study, the controlled groups. There are a lot of options here. We are engaging KOLs around the world for their advice. So, if you look at the controlled groups that are still used despite the fact there has been some pushback, often using second androgen receptor targeting agents as a control. It may not be the most optimal one, but certainly still acceptable, at least to some of the regulators at this point. We'll see how this sort of evolves over time. Likely, we include a chemo as a control. Again, we'll have to find a therapy to determine which one, and whether it's a single control drug or a physician's choice among a couple still gets determined. Gotcha. Is there anything that we should be watching that could help inform what a trial would look like based upon other readouts? Seems to be this pushback for the second ARAT is becoming more prominent here. Well, I mean, there is a lot of talk. But as we've seen, you know, Merck just started a study that the second ARAT control in their new drug, PSMAfore had that as a control. CONTACT-2 had it as a control. So the bottom line is, despite the fact we've heard a lot of discomfort about using that, it's still being used in trials. So we'll have to see how, you know, the feedback from both investigators, advice, and regulators are. We'll have to see what the effect size is and determine what's the most appropriate for the study. Gotcha. Were patients who've been exposed or how many patients would have been exposed to a radiopharmaceutical? I presume very small numbers there. And that, you know, you know, clearly there are two approved on the market as, radium and obviously Pluvicto, with regard to the latter. The number of sites, that we had in the U.S. was small compared to the number of sites in Europe. And, at the time we enrolled the study, there the availability of drug was, very sparse in, Europe. And the patients who oh, there was also a limitation even in the U.S. But, for those who were on drug, not enough time elapsed, from, discontinuation, to be on the study. So my expectation is that there will be some, but, but probably very few. Gotcha. Do you think you'll be first-to-market in prostate with B7-H3 or first-to-market generally for B7-H3? Well, of course, we are hoping that's where we'll be. We have no knowledge of other competitors targeting B7-H3 that have advanced programs further than we have in that regard. So, again, it's a lot dependent on the quality of the data that comes out will determine how quickly we're in a very good position to start a phase 3 study, as I said, in the first half of 2025. I don't know if others, I mean, clearly the one competitor that's most advanced has not announced any indication that they are starting a more advanced study in prostate cancer, namely Daiichi and Merck. Gotcha. And you've got a broad development program for B7-H3 ADC, first-generation ADC. Why, why take that approach? Was, you know, why so broad? Why not kind of pick one indication? Well, I think that we are blessed with an opportunity now that we were the first company to develop any molecule for B7-H3. This goes back now 16 years ago. And you know, we have now three molecules in the clinic targeting B7-H3. We had a fourth one, which we pulled out of clinic even though there was activity, that was one of our prior bispecifics. And we're looking at even other opportunities here. There are very few targets that have such a broad exposure across the board in solid tumors in terms of expression pattern and combined with a relatively low expression in normal tissues, especially if you are discriminate on which epitope and variable domain you go after. Having a large number of antibodies to B7-H3, we were able to select ones with different profiles that could take advantage of different mechanisms to limit tumor growth. So, for instance, enoblituzumab, our Fc-engineered anti-B7-H3 molecule, was selected again for a good tumor-to-normal tissue ratio, but was able to sit on the surface of molecules much longer than the variable domain we selected for vobramitamab duocarmazine, which gets to incorporate quicker. And so, as you know, a study called HEAT just started, as an IST, led by Johns Hopkins and three other major institutions, looking at the neoadjuvant use of this as a neoadjuvant treatment for high-grade Gleason 8-10 local newly diagnosed patients who will ultimately develop metastatic disease based on the data that they had tested in the original 32 patients. So different mechanism of action, different profile of that drug, looks historically very safe. It's been in over 400 patients, with evidence of anti-tumor activity, good T-cell activating properties. The vobramitamab duocarmazine gives us opportunity, obviously, now in sort of mid-stage castration-resistant prostate cancer based on the activity and the safety profile. As we just recently announced, and I hope folks get to see our AACR poster, we have just started a clinical study with a variable domain that was identical to the one in vobramitamab duocarmazine but now has a linker toxin that inhibits TOPO-1. It's a TOPO-1 inhibitor. But based on the preclinical data that Synaffix has presented to us in their studies, it could have a superior clinical profile to other TOPO-1 inhibitors, particularly the TOPO-1 inhibitor that's in Trodelvy, SN-38, and deruxtecan, which is obviously in 7300 and HER2. So if, in fact, by being able to have a very good controlled experiment now where we have good target, same antibody but now a different toxin, we'll be able to look across different studies, our own experience, and Daiichi's experience. If that turns out to be a superior TOPO-1 inhibitor, all of a sudden, that toxin can now be used in multiple other targets and other variable domains. Perfect. Thank you. We've got 30 seconds on the clock. I guess final question, just as we think about the LORIKEET study, so your PD-1 bispecific CTLA-4, is that a similar population as TAMARACK? So it's similar to the subpopulation that are chemo-naive. So from that vantage point, these patients have progressed on an androgen receptor targeting agent but have not seen chemotherapy. So as you know, that's a 150-patient study, 2-to-1 randomization. In this case, instead of single-agent therapy, we're looking at the combination of lorigerlimab, the PD-1 CTLA-4 bispecific with a standard of care, which is docetaxel, in 100 patients versus docetaxel alone. We expect that study to complete enrollment this year and then provide an update on that data. Perfect. We're getting the hook today, but unfortunately, we can't. Okay. Thank you so much, Scott. That was. Oh, thanks, Peter. As always.