TAMARACK study and our perspective on the path forward for vobra duo based on these results. As a reminder, vobramitamab duocarmazine, or vobra duo, as we call it, is an ADC molecule designed to deliver a DNA alkylating duocarmazine cytotoxic payload to tumors expressing B7-H3. B7-H3 is a member of the B7 family of molecules involved in immune regulation, and is broadly expressed on multiple tumor types. A key pillar of our clinical development strategy is centered on our view and the industry's view that B7-H3 has the attributes of a promising cancer treatment target, and we are pursuing multiple candidates, including vobra duo, MGC026, and enoblituzumab, that are all designed to take advantage of this antigen's expression. The TAMARACK phase II study of vobra duo is being conducted in patients with metastatic castration-resistant prostate cancer, or mCRPC, who were previously treated with one prior androgen receptor axis-targeted therapy, or ARAT. Participants may have received up to one prior taxane-containing regimen, but no other chemotherapy agents. As shown on slide 7, the TAMARACK study is designed to evaluate vobra duo at two different doses, 2.0 mg/kg or 2.7 milligrams per kilogram every four weeks. MacroGenics completed enrollment of the TAMARACK study in the Q4 of 2023, and the study has reached its landmark primary endpoint of six-month radiographic progression-free survival rate. While the mCRPC study participants are no longer being dosed in the study, participants continue to be monitored for adverse events, disease progression, and survival. All data in the poster were based on data cutoff date of 9 July 2024. We expect to have mature efficacy findings, including median rPFS, no later than early 2025. Our current intent is to present such data at a subsequent medical conference. Now on to the data. As detailed when we announced earlier interim data in May, we enrolled a total of 181 patients in the TAMARACK trial. However, we're reporting only on those 176 patients who received at least one dose of vobra duo. As you can see on slide eight or figure three of the poster, in the 2.0 milligram per kilogram cohort, there was approximately a 50/50 split between RECIST-evaluable patients with measurable disease at baseline and those with non-measurable disease, with 45 RECIST-evaluable patients in this cohort. In the 2.7 mg/kg cohort, despite randomization, fewer patients had measurable than non-measurable disease, with 32 RECIST-evaluable patients. As of the data cutoff, 23 and 16 patients remained on treatment in the 2.0 milligram per kilogram and 2.7 mg/kg cohorts, respectively. Slide 9, or Table 1 of the poster, provides several baseline characteristics. Except for ECOG status, which is a fairly subjective measure, both arms were well-balanced. On ECOG status, the 2.7 mg/kg arm very slightly favors ECOG 1 over ECOG 0. In terms of having prior taxane or not, the split was close to 50/50 across both dose cohorts. Also recall that mCRPC patients had to have prior ARAT for study entry. As you can see, nine patients in the 2.0 milligram per kilogram and six patients in the 2.7 mg/kg cohort received more than one ARAT, as a second ARAT regimen of less than 60 days was permitted as a bridging agent to PLUVICTO. With that, let me now review the efficacy of vobra duo, beginning with the protocol-specified primary endpoint of six-month landmark radiographic PFS rate, as shown on slide 10 or figure 6 of the poster. For those not familiar with the six-month landmark PFS rate, this is the percentage of study participants who remain free from disease progression or death after six months from the start of treatment. In the intent-to-treat population, the six-month landmark radiographic PFS rate was 69% for the 2.0 mg per kilogram arm and 70% for the 2.7 mg per kilogram dosing arm. The median radiographic progression-free survival data shared in the poster and on slide 10 is immature, and with only 35.9% of the PFS events having occurred as of the data cutoff date, the median radiographic progression-free survival at this early date was approximately 8.5 months for the 2.0 milligram per kilogram cohort and 7.5 months for the 2.7 mg/kg cohort. For reference, in the phase I mCRPC expansion cohort, the median final radiographic progression-free survival was 5.5 months. We look forward to seeing the final median rPFS data from the TAMARACK trial no later than early next year. I'll turn to the tumor response rates, which are summarized on slide 11 or table three in the poster. Waterfall plot showing best percentage change in target lesions from baseline per investigator based on RECIST response evaluable population with measurable disease are shown on slide 12 or figure four of the poster. In the 2.0 milligram per kilogram dosing cohort, among the 45 RECIST evaluable patients, the confirmed objective response rate, or ORR, was 20%. With the inclusion of the unconfirmed CRs and PRs, the overall response rate was 26.7%. Overall, these results are consistent with the interim data reported in May. In the 2.7 mg/kg dosing cohort, among the 32 RECIST evaluable patients, the confirmed ORR was 40.6%, a significant uptake from the 25% confirmed ORR observed in our earlier data cut. With the inclusion of unconfirmed partial and complete responses, the ORR was 46.9%. Overall, while treatment with 2.7 milligrams per kilogram yielded a nominally higher ORR than 2.0 mg/kg, we are seeing ORRs across both dosing regimens that indicate durable efficacy. Coupled with the early, albeit immature, median rPFSs, we look forward to seeing how the data evolves as more events are reported. Now I'll review updated safety and tolerability findings for TAMARACK as of the data cutoff, beginning with some observations on dose reductions and discontinuations. As you can see on slide 13 or table two in the poster, in the 2.0 mg/kg cohort, as of the 9 July 2024 data cutoff, 25.6% or 23 out of 90 dosed patients remained on study drug. The median number of doses received was six, and the median dose intensity, calculated as percentage of total planned dose that was administered, was 92.6%. In the 2.7 mg/kg cohort, 18.6%, or 16 out of 86 dosed patients, remained on study drug at cutoff. The mean number of doses received was six. The mean dose intensity was 81.7%. Encouragingly, these results indicate an improvement in the duration of therapy for vobra duo compared to that of the phase I mCRPC expansion cohort, which received a median of four doses, the median dose intensity at 66.4%. As of the data cutoff, as shown on slide 14 or table 4 in the poster, a total of eight fatal treatment-related adverse events occurred in the TAMARACK study, five in the 2.0 mg/kg cohort and three in the 2.7 mg/kg cohort. These include three events of pneumonitis and one event each of cardiac failure, stress cardiomyopathy, ventricular fibrillation, pleural effusion, and gastrointestinal hemorrhage. The specific treatment emergent adverse events with incidence greater than or equal to 10% in either TAMARACK arm are presented visually in the butterfly plot shown on slide 15 or figure seven in the poster. In both dosing cohorts, the five most common treatment emergent adverse events of any grade included asthenia, peripheral edema, nausea, decreased appetite, and pleural effusion. As you can see, the vast majority of treatment-emergent adverse events with a 10% or greater incidence rate in either arm was limited to either grade one or grade two events, consistent with our safety observations from the prior data cutoff disclosed in May. As a reminder, one of our goals with the TAMARACK was to demonstrate a reduction in incidence and severity of pleural effusion, pericardial effusion, and palmar-plantar erythrodysesthesia, or PPE, also known as hand-foot syndrome, compared to the rates seen in the mCRPC expansion cohort of the phase one trial. The detailed incidence rates for these select treatment-emergent adverse events across both TAMARACK dosing cohorts and the phase one study are shown on slide 16 or figure eight in the poster. Overall, we observed lower rates of pleural effusion and PPE syndrome for both arms of the TAMARACK study compared to the rates observed in the phase I study mCRPC cohort, despite an increased number of doses of vobra duo. Additionally, we observed lower overall rates of pleural effusion and PPE syndrome in the 2.0 milligram per kilogram arm versus the 2.7 mg/kg arm, with most of these adverse events occurring as grade one or two. Lastly, the rates of treatment emergent adverse events and treatment-related adverse events, both including all grades and grade three or greater serious adverse events and treatment-related serious adverse events, were similar between taxane naive and taxane pretreated patients. In conclusion, we continue to observe significant antitumor activity to date in TAMARACK, as demonstrated by the ORR, PSA response rate, and six-month landmark rPFS rate findings. Overall, we believe we have a much better understanding of vobra duo's overall safety and tolerability and are considering ways to further improve molecule safety. We are particularly encouraged by the events of neutropenia, anemia, thrombocytopenia, pleural effusion, and PPE syndrome improved with dose reduction, and that safety was improved compared to the phase I trial, allowing us to keep patients on treatment longer. We are potentially exploring whether the adverse events associated with prolonged exposure to vobra duo could potentially be mitigated by further increasing the dosing interval, such as every six weeks or utilizing a loading dose strategy. This is an area that may deserve further exploration once maturation of the PFS is complete, and we are able to review the final efficacy data. With that, I'll turn it back over to Scott to walk through the rest of our pipeline. Scott? Thank you, Stephen. As I noted earlier, we look forward to assessing the final mature efficacy and safety data from the TAMARACK study. We will take into consideration a competitive assessment of the treatment landscape, resource allocation across our clinical portfolio, as well as potential partnering opportunities, and we will be thoughtful and disciplined in our approach with respect to future steps for this program. Beyond vobra duo, we have continued to advance our proprietary pipeline of product candidates, and we have made significant progress. Over the years, we have leveraged our deep antibody engineering capabilities to build a broad, multimodal portfolio that gives us multiple near to midterm opportunities to target highly relevant oncologic therapeutic areas. We believe we are well-positioned to unlock long-term value across our pipeline. Let me briefly walk you through our strategy to maximize our shots on goal for success and the key programs that underpin this approach. First, we continue to pursue additional development programs that target B7-H3, including enoblituzumab and MGC026, an investigational ADC incorporating SYNtecan, a novel topoisomerase one inhibitor-based linker payload licensed from Synaffix. As a reminder, we believe MGC026 offers a complementary approach to vobra duo for targeting B7-H3, given its distinct mechanism of action with vobra duo's DNA alkylating payload and MGC026's topoisomerase inhibitor payload. Preclinical data generated on the molecule to date has indicated potentially greater potency and improved safety compared to direct SYNtecan conjugated ADCs. And our toxicology study demonstrated an encouraging tolerability profile across all dose levels tested and approximate dose proportional pharmacokinetics in several animal models. We are on track to disclose initial data from our ongoing phase I dose escalation study of MGC026 in the first half of 2025. Regarding enoblituzumab, an Fc-optimized antibody that targets B7-H3, our academic collaborators are enrolling the HEAT study, an investigator-sponsored, randomized, translationally intense phase II investigator-sponsored trial of this molecule in up to 219 men with prostate cancer. This study is evaluating the activity of neoadjuvant enoblituzumab, given prior to radical prostatectomy in men with high-risk localized prostate cancer. Eligible patients will undergo a pretreatment prostate biopsy and conventional imaging, including CT and bone scan, as well as PSMA PET, and optional prostate MRI as per institutional preferences. We recognize the potential applicability of our B7-H3 franchise across a variety of cancer settings, tumor stages, or in combination with alternate agents, or even with one another, to enhance their clinical utility. Our assets that target the B7-H3 pathway remain key drivers of our long-term pipeline strategy, and we look forward to advancing MGC026 and our other novel product candidates towards key development milestones. We also continue to pursue additional opportunities in mCRPC outside of vobra duo as monotherapy. In particular, I'd like to highlight our ongoing progress with lorigerlimab, our lead checkpoint inhibitor candidate, designed as a bispecific tetravalent PD-1 and CTLA-4 DART molecule. Recall that in our phase I study of lorigerlimab in patients with mCRPC, we saw a confirmed ORR of 26%, with a PSA50 response of 29%, and the majority of those patients, in fact, attaining PSA90 responses. As we've highlighted in the past, some patients ended up remaining on therapy for more than two years or greater than 30 cycles, indicating the possibility for durable responses in mCRPC patients. These results show the potential of lorigerlimab to be differentiated from other checkpoint inhibitor-based molecules, including anti-PD-1 and anti-CTLA-4 molecules that have been studied in mCRPC patients. And we continue to explore the use of this asset as both a monotherapy and in combination with other agents, including vobra duo. We have two ongoing clinical trials for lorigerlimab that are both on track and progressing. The first is our LORIKEET study, a randomized phase II clinical trial, which is evaluating lorigerlimab in combination with docetaxel versus docetaxel alone in second-line chemotherapy-naive mCRPC patients. To date, we have enrolled more than half of the 150 anticipated participants in this study, and we expect completing enrollment by late 2024 or early 2025 to support an initial data readout in the first half of next year. In addition, we continue to advance our strategy of evaluating lorigerlimab in combination with vobra duo with our phase I/II dose-escalating study in patients with advanced solid tumors ongoing. We see this study as an opportunity to exploit both molecules' orthogonal mechanisms of action, supported by growing clinical validation around the benefits of combining ADCs with immune checkpoints, including evidence generated by our preclinical model that have shown enhanced antitumor activity and immunological memory with a vobra duo anti-PD-1 combination. We anticipate being well-positioned to leverage findings from our dose-escalating study to initiate a dose expansion study of vobra duo and lorigerlimab later this year. Looking beyond mCRPC, I'd like to spend the next few minutes discussing our programs aimed at targeting additional oncologic indications. MGD024 is our next-generation bispecific CD123 by CD3 DART molecule being developed through an ongoing collaboration with Gilead that leverages our significant expertise in developing CD3-directed bispecifics. MGD024 incorporates a CD3 component designed to minimize cytokine release syndrome while maintaining antitumor cytolytic activity and permitting intermittent dosing through a longer half-life. We are progressing a phase I dose-escalation study in patients with CD123-positive, relapsed, or refractory hematologic malignancies, including acute myeloid leukemia and myelodysplastic syndromes. As a reminder, Gilead has the option to license MGD024 at predefined decision points during the phase I study. On the preclinical side, we are pursuing development of MGC028, our second topoisomerase 1 inhibitor-based ADC, incorporating Synaffix's novel linker payload and an ADAM9-targeting antibody. ADAM9 is a member of the ADAM family of multifunctional type I transmembrane proteins that play a role in tumorigenesis and cancer progression and is overexpressed in multiple cancers, making it an attractive target for cancer treatment. We have generated what we believe is a compelling body of preclinical evidence demonstrating specific antitumor activity with MGC028 in in vivo models representing gastric, lung, pancreatic, colorectal cancer, squamous cell carcinoma of the head and neck, and cholangiocarcinoma. In addition, in the non-human primate study, MGC028 was well tolerated up to 55 mg/kg every two weeks, with mild reversible side effects and no ocular toxicity, which is often a concern with tubulin inhibitor-based ADCs. Based on these promising preclinical results, we believe MGC028 holds potential as a treatment option for ADAM9-expressing solid tumors, and we currently anticipate submitting an investigational new drug application by the end of this year and initiating a phase I clinical study in early 2025. Beyond MGC028, we are exploring additional molecules for future IND submission, including filling the additional ADC slots available through our partnership with Synaffix, which has already yielded us with two successful product candidates. We will continue to bolster our early-stage pipeline to fuel future growth and innovation in MacroGenics, and I look forward to providing additional updates on this front in future calls. In conclusion, we believe we have a promising strategy in place to continue delivering value to patients, physicians, and our shareholders, enabled by our deep pipeline and leading R&D capabilities. We look forward to seeing the mature median rPFS for TAMARACK, as well as data from MGC026 and the combination of vobra duo and lorigerlimab. Many of you are familiar with our established track record of success in discovering and advancing first-in-best-in-class molecules through the clinic. Our broad drug conjugate development capabilities, powerful proprietary multispecific platforms, and modality-agnostic approaches have enabled us to pursue a diverse and comprehensive program to target multiple tumor types, and we believe we are well-positioned for long-term growth as a result of our unique strategy. Over the next few quarters, we expect to reach multiple catalysts that will enable us to strengthen our conviction for directed approaches to B7-H3-expressing cancers, broaden our clinical footprint in prostate cancer and other oncologic indications, further validate our platforms through our partnered programs, and continue advancing our wholly owned pipeline of innovative therapies. Lastly, just a moment on cash and our cash runway. As announced early last month, our cash, cash equivalents, and marketable securities balance was $140.4 million as of 30 June 2024, with an additional $100 million in milestones subsequently received from Incyte following the positive phase III top-line results from registrational studies of retifanlimab in both anal and lung cancer. I'll remind listeners that in just over the past two years, we have generated $435 million in non-dilutive capital from partnering activities related to TZIELD from Sanofi, ZYNYZ from Incyte, and from Gilead. We expect that our current cash and marketable securities balance, plus projected and anticipated future payments from partners and product revenues, should support our cash runway into 2026. Our expected funding requirements reflect anticipated expenditures related to the phase II TAMARACK clinical trial, the phase II LORIKEET study, as well as our other ongoing clinical and preclinical studies. We're excited to share our continued progress in the coming months. We believe MacroGenics has the technical development and clinical expertise, as well as financial resources, to support our vision of developing and delivering life-changing medicines to cancer patients. We would now be happy to open the call for questions. Operator? Thank you. One moment before we go into the Q&A session. We are aware that there was a technical glitch for some reason at the beginning of the call, in which Mr. Karrels covered the company's cautionary note on forward-looking statements, and Dr. Koenig made some introductory remarks. To hear these sections in their entirety, listeners should be able to listen to the recorded webcast via the link on MacroGenics' website. If you would like to ask a question, please press star one one on your telephone. You will then hear an automated message that your hand is raised. We also ask that you wait for your name and company to be announced before you proceed with your question. One moment while we compile the Q&A roster. Our first question for the day will be coming from Tara Bancroft of TD Cowen. Please go ahead with your question. Hi, good morning, and thanks for taking the questions. F irst for Scott, can you tell us what feedback you've received from KOLs that are at ESMO and have seen the data? And then maybe more so for Jim, does this at all change your capital allocation plans, like acceleration of the next gen asset or, or anything like that? Thank you. Thank you so much, Tara. I'm going to leave it to the various study physicians to express their individual views. I n general, for those we have engaged, they have noted significant activity of the drug in a very hard-to-treat setting. They also have commented, as we have also commented, there is potentially more to do to improve the safety profile, and as we have discussed today, some ways we may address this as we get to the mature data in the next few months. Thanks for that question, Tara. Regarding capital allocation, this data does not change our allocation of resources. As you recall, our cash runway is into 2026. This does not reflect a phase III study as any such study, you know, we wouldn't make the determination as to whether to move forward with such a study until we have the final rPFS in hand, no later than early 2025. Okay, great. Thank you. Thank you. One moment for the next question, and our next question for the day will be coming from Mayank Mamtani of B. Riley Securities. Your line is open. Good morning, team. Thanks for taking my questions, and appreciate the detailed review of the updated TAMARACK results. Just curious about the rPFS analysis that we'll see early part of next year. You know, we know that the enrollment had really bumped up Q4 last year, and assuming a lot of the early progressors may have now been captured, you're still not having patients receive additional doses. How should we think about where you know you're thinking of planning for that final rPFS analysis? J ust maybe a quick data question. The breakdown of two and two point seven mg per kg in a post-vaccine setting, you know, if you're able to comment on you know ORR and rPFS there. I was just curious that the high dose, you know, did exceed ORR of 41% in post-vaccine, but that, you know, 2x delta relative to low dose was not observed when you did the pre and post-vaccine subanalysis. I f you could clarify that, that would be helpful. This is Stephen Alcorn. I'd be happy to address both those questions. First of all, as you know, the radiographic progression-free survival is an event-driven rate, and so you ideally would want to capture all of an event from every patient enrolled. Now, that's not possible because we lose some patients. They stop for adverse events before having an event, or they might start another therapy. T he data we're reporting, as was noted, is quite immature, with, you know, approximately only a third of the patients giving you an event. We'd like to see somewhere greater than 50% of the patients receiving event. Now, the study will time out because we will follow the patients into January, and that's why we can be confident that we'll know the median PFS rate in early 2025. With regard to the ORR, overall response rates, and I believe you were asking about the differential between the two arms. I wouldn't put a tremendous amount of weight on that. Obviously, we like the ORR because it shows the drug is active, and it's an early measure of drug activity. We know that within a few months. The determining factor, of course, is going to be the median PFS rate, because that will determine what we will use as our competitor. Thank you. J ust if I could squeeze in a safety question, the eight fatal AEs seemed a little higher than what you reported in prior cutoff. Could you clarify if that contributed to the decision to terminate further dosing? Y ou know, if you're able to comment on any regulatory correspondence, you know, you may have around these events. Lastly, any geographical differences, you know, observed in how these AE dose reductions or interruptions are managed. T he taxane naives, you're seeing a higher number of dose reduction interruptions. J ust curious if that also contributed to efficacy in some way that, you know, once you optimize dosing further, you could improve upon. Thanks again for taking my question. Certainly. F irst of all, with regard to your question about the term terminating this dosing, we meet regularly with our external data safety monitoring committee and provide them updates on the safety. In July, with most of the patients no longer being dosed and only a handful of patients still eligible for another dose, we presented the totality of our safety data, and we had, at that point, already met our primary endpoint of six months PFS rate. I t's looking at the totality of the safety data that we decided that we would not continue dosing patients beyond that point. You know, and, and maybe I will comment on the few increases in the deaths that were noted, which is found on the poster. As you know, there's a very complex relationship between study treatment and deaths. Some are likely related, possibly avoidable, with greater attention to early onset or delayed delivery. Some likely unrelated because of comorbidities and other medications, and others more difficult to assess because they occur very late after the last drug delivery. W ith regard, as we noted in the poster, there were a couple of patients at the time of the deaths that were assessed by the investigator to be possibly related to pneumonitis, for example, but all the other ones were single events across different causes. W hen we followed up as the sponsor, fewer of those cases were deemed related. A gain, we think that we have a very good idea on how going forward for future studies to get better management for these things, without any new side effects or deaths from things that we have noted previously from our phase one experiences. Thank you. Our next question will be coming from Yigal Nochomovitz of Citigroup. Your line is open. Hi, thanks for taking the question. Just again, with regard to the fatality risk, I'm just wondering if you could comment as to whether you see that rate of grade five events as in line with other pivotal studies in mCRPC that led to approval? S econdly, what do you believe you would need to see on the final rPFS early next year to justify the clinical benefit risk profile in light of the grade five event rate? Thanks. This is Stephen Eck. Let me comment on the grade five events. As Scott has noted, some of them aren't, we don't think related to drug exposure. Our study population is a group of men of an advanced age, many with other comorbidities, and some of the deaths are occurring far removed from drug exposure, and also in the setting of prior events in the patient's medical history, which would predispose them such as myocardial infarction or something. Overall, I think while the death rate is unfortunate, we're happy to you know, we're pretty happy with the safety profile in this population. With regard to comparisons to other studies, obviously, we would like the median PFS rate to be as high as possible, but ultimately, that will determine what our comparator would be, should we take it forward into a phase three registrational study. Just to, this is Scott, Yigal, and you know, in addition, as we had noted on our last call, with just very few more deaths that we noted here, and as we had commented earlier, we are not, as you look at other studies where drugs have been approved for mCRPC, we are not out of the ranges which were reported in these other phase III studies. O bviously, this is all a caveat that studies will have different populations that are being enrolled in these studies. I t's a little bit difficult to be definitive in that comparison. Thanks. Also, I was just curious on the ORR to PFS translation. Were you at all surprised that despite the approximate doubling of the ORR to 2.7 versus two, that on the PFS side of things, it was much more balanced? That's not totally unexpected. Depending on the disease state, response rate may translate well into PFS and in other diseases not so much. I t's a good reliable. The ORR is a good reliable indicator of drug activity at the beginning, you know, early on in your study. U ltimately, what you wanna see in a palliative setting is that patients are free from disease progression or death. Thanks. J ust one more on the safety. When you were comparing the three mg per kg to the newer, lower doses, I appreciate that the rates went down on pleural effusion, though, the grades were a little bit higher in the two mg per kg. Just wondering if you could comment on that and how you would reconcile those two profiles, given the overall higher event rate in the pleural effusion at the higher dose, but some higher grades at the lower dose. Thanks. We've spent a lot of time looking at the pleural effusion, pericardial effusion rates, because those are adverse events that are somewhat unusual. They have been seen previously in other studies with this ADC using this toxin, so it's not totally new. A part of the reason that the pleural effusion rate doesn't come down as much as one might like is because you're continuing to dose the patient, so their time at risk goes up. W e're pleased to see that, you know, certainly at the lower dose, that the rate of pleural effusion, despite having more time at risk, did come down, and certainly we did see a marked reduction in the PPE as well. Not as big a decrement for the pericardial effusions. Thank you. One moment for the next question. O ur next question is coming from Jonathan Miller of Evercore. Your line is open. Hi, guys. Thanks for taking the question. I guess I would love to ask about what the possible next steps are here. O bviously, you haven't decided fully on what that's gonna be, yet I understand that. I f, you know, suppose you do see rPFS results next year that you feel are supportive enough to continue with vobra duo, the safety profile here and the need for additional work clearly indicates that you're gonna have to do more dose optimization. Does that necessitate another phase two, potentially with multiple arms? Jim, you mentioned that your current runway doesn't include a phase three. Does it include further dose optimization in phase twos? I f so, what potential steps would need to be taken in order to facilitate those further experiments before we get into pivotal studies? Let me address the first question, and I'll let Jim answer the second question. Y ou're correct, we would like to see improvement in the safety profile. This is a palliative therapy. It's non-curative therapy, and so how the patients experiences the drug is obviously very, very important. There are a number of levers we have at our disposal. As Scott has alluded to, we can pursue further dose adjustments or simply just increase the dosing interval, as we had done from phase one into phase two, we could increase that interval yet further. We haven't yet explored, although we are considering other premedications that could make it less likely to get a pleural effusion or pericardial effusion. As you know, when other drugs were developed, such as pemetrexed or even docetaxel, which are in common use today, part of their success is the application of other adjunctive therapies that decrease the rate of side effects. Steroids in the case of docetaxel and folate supplementation in the case of ALIMTA. Jonathan, at this point, we have not allocated resources to any sort of further dose optimization of vobra duo. We do have other trials ongoing, as you know, and which Scott mentioned on the call. It's possible that we could explore. We could tuck in some elements of dose exploration in, you know, in a combination study, for example. It's yet to be determined. Fair enough, but I assume you would want to see some evidence of controlled safety before you head into a large randomized study, yes? You know, the answer is it's optimal. We will obviously assess what is necessary to do to get to the right conclusion there. One can design this obviously as small independent studies or as part of a larger study lead-in testing to establish that dosing. We're still like to see what the median PFS and the overall safety is before we draw the conclusion on what the next steps going forward. Understood. And then I guess one related question is on the potential for combination therapies, and obviously, we're all very excited to see the LORI combination whenever that data is available. But it does feel like early lines in prostate, first, second line, are going to evolve into bigger and bigger combinations. H ow do you feel the VOBRA safety profile fits into those potential areas? Do you have a good enough safety profile, or do you anticipate having a good enough safety profile even after all these dose adjustments and optimizations that will allow you to effectively combine with the sort of first and second line agents likely to be backbones in combination regimens, like ARAT, like taxane? John, that's a great question. As you know, this is an ever-changing landscape for the treatment of this disease. An s you noted in more and more patients, for instance, getting triple therapy very early, obviously, in the hormone sensitive and then even in the metastatic castration-resistant setting. As a result, as you know, here, we focused on in the metastatic castration-resistant setting, and we do believe that with further modifications of the dosing, we could achieve a safety profile and activity profile that could be used very effectively going forward. Again, depending on what we see in the mature data going forward. W e are optimistic there. Y ou point out, we have our own combinations that we're also very excited in. In the case of LORIKEET, we're combining with docetaxel our PD-1 CTLA-4 combination. We're having the ongoing study of vobra duo now with lorigerlimab. We are gotten to a dosing range, which we are deciding next steps in terms of expansion later this year, as I pointed out earlier. A s I noted earlier, we're going quite nice advancement of the MGC026 study through dose escalation. As that dose gets established and the safety and activity profile are determined, we'll be able to also potentially plan for combination studies there, noting that even at this early stage, we're seeing differences in safety profile between MGC026 and vobra duo. So again, we have a lot of opportunities here to be able to address various stages of mCRPC treatment. Thank you. One moment for the next question. O ur next question will be coming from Kelsey Goodwin of Guggenheim. Your line is open. Oh, hey, thanks for taking my question. Maybe just building on some of the prior questions. I guess, will you be taking any of the read-through from TAMARACK to modify the studies in other solid tumors? I know you mentioned increasing the dosing interval or adding in a loading dose. I guess, are those things that can be implemented, you know, ASAP, or are they things that you'll kind of wait to see the data to implement? Second, I guess, what would you really need to see in TAMARACK's mature data next year to continue advancing vobra duo and not just, you know, kind of move forward with MGC026 as kind of the sole B7-H3 asset? Thank you. Kelsey, again, I will repeat that we're obviously waiting till the mature data emerges from TAMARACK, but clearly, we would apply the lessons learned from the dosing schedule to other solid tumors going forward. On the mature data? Absolutely, when the data matures, that will give us a better idea of how we're gonna position vobra duo in terms of what line of therapy within prostate cancer. As Scott noted, we have our own internal combination studies which have been going quite well. Too early to say anything about efficacy, but from a safety perspective, we're quite happy with the safety of the combinations. Just to say, with only 36% of the events here and with where we are on the rPFS, where we know that these can change, we're very encouraged by what we're seeing so far. Got it. Thank you. M aybe just a quick follow-up: for, I guess, making the decision to advance vobra duo, I guess, will you wait to see the MGC026 data before ultimately making a decision, or would you plan to kind of do some of the modifications and maybe a small study, to see, you know, how vobra duo could potentially look with some changes? I think we view these as two different agents with distinctly different opportunities. Obviously, there could be some overlap, but I think we could make a decision on vobra duo with the data we have from TAMARACK, and then we make an independent decision on zero two six as its data evolves. Okay, got it. Thank you so much. Thank you. One moment for the next question. O ur next question will be coming from Matthew Kulp of Leerink Partners. Your line is open. Hi, this is Matthew Kulp on for Jonathan Miller. Thanks for taking my question. You've touched on this a bit, but with regard to the grade five events and the safety profile more broadly, are you seeing any correlation with B7-H3 expression and grade and severity? Thanks. This is Stephen Eck. No, we, we're not. We don't think this is B7-H3 related, in part because we know what to expect from a duocarmazine alkylating agent. I think some of the toxicity we're seeing, particularly the pleural effusions, pericardial effusions, and third spacing of fluid, those are consistent with a duocarmazine payload. So I don't think it's related to B7-H3. Furthermore, you know, as you noted, we have extensive experience with enoblituzumab and other molecules targeting B7-H3, and we have not seen similar side effect profiles. Got it. Thank you. Thank you. One moment for the next question. O ur next question will be coming from Alex Balcoci of Barclays. Your line is open. Hi, this is Alex on for Peter at Barclays. Can you hear me okay? Okay, great. Thank you for taking our questions. I just wanted to ask again on safety, on the pleural effusions and the pericardial effusions, and also just the PPE. s there a certain, you know, rate that KOLs want to see? I'm just trying to get a sense, you know, with more dose optimization, I guess, what are your expectations for how much you could still improve and kind of reduce the rates of these adverse events? Well, we're not, haven't taken an official poll as to what rate they'd like to see, but obviously all of us would like to see it come down significantly. It's important to note that some of the pleural effusions are grade one, which are incidental findings on CT scan, and really don't pose much of a hazard. The pericardial effusion, there is no grade one. You know, we're much more concerned about that, but it is less frequent. So we would like to see these come down. We think there are some options available to us with perhaps adjusting the pre-meds to prevent them, as I noted earlier, it's been done with other medications, or changing the dose and schedule. As to the exact number we need to get to, I can't tell you that. Okay, great. And then just on the follow on ADC, the 026 molecule, I guess, is there a biologic rationale, I guess, or your expectations that the overall safety profile could be improved? There are two bases for the safety profile being different. One is the linker itself. I mean, it's entirely plausible, although we have not established it, that the toxicity we see with vobra duo is due to a free duocarmazine, which is metabolized in cells and then re-released. With a different linker, that pharmacology could be dramatically altered. T he second part, of course, is you have a different toxin, and so that would alter your adverse event profile. I don't expect them to have similar adverse event profiles. Great. Thank you. Thank you. One moment for the next question. Our next question is coming from Stephen Willey of Stifel. Your line is open. Hey, good morning, guys. This is Julie on for Stephen Willey. W e have three questions on our end, if you don't mind. So, starting with the first one, we're wondering how informative the PFS data would be in terms of informing any potential next, developing steps, given how significantly patient censoring appears to be impacting this median and landmark analysis. Second question is kind of like follow-up on the prior questions. What have you been able to learn about the safety of those vobra duo doses, being evaluated in the durvalumab dose escalation study? If you think that there is a viable path forward for vobra duo in this metastatic CRPC, why would you I mean, wouldn't you just move forward with this combo approach? I have a follow-up on after these questions. Thank you. Let me start with the PFS. I guess your question is around the PFS of event rate and censoring. That's an ongoing process, and we'll have to see how that plays out. Right now we have a lot of censored data, as shown on the poster, and that could very well shift rightward on the graph, if you like, as patients continue to be event-free, even though they're no longer on therapy. We'll just have to wait and see how that plays out. Obviously, there is some censoring that has hardly occurred and is permanent, as you would expect, because patients leave the study for a variety of reasons. I'm not sure if I've correctly answered your question, but if not, please, please, I can get back to that, and then you ask about the safety, and particularly in regard to the combination of the vobra duo with durvalumab, so the vobra duo durvalumab combination study is ongoing, and they're still in the dose escalation phase. We haven't gone into the expansion phase yet, although we hope to do that very soon, so far, the safety profile there has proven very nice. Now, as to your question as to whether you just take the combo over the single agent, there's not enough data on it. It's an unequal data set, so we have a limited amount of data with the combo. So I'd really only be able to answer that question after we did the expansion cohorts to see what the true clinical benefit. And then you had a third question, which we hadn't gotten to yet. Yes, thank you. Thank you for the answers. And the third question is actually related to Incyte's retifanlimab. Is there any kind of best efforts clause within the Incyte retifanlimab agreement that would require them to either to pursue approval or commercialization of that drug in the lung cancer? Thank you. There was no, as I recall, any specific tumor identified as a requirement. There obviously needs to be best commercial efforts with regard to the commercialization here. As you know, the data that was presented on the anal cancer at the current ESMO meeting was part of the presidential event, which is a practice-changing for patients with anal cancer, and as you have heard, this was received exceptionally well by the community and is expected to lead to approval in this coming year. Furthermore, that opportunity obviously opens up additional revenues for MacroGenics, given our 15% to 24% royalty that is imposed on that to us. With regard to lung, we still await to hear from that. As you know, Incyte is also conducting studies in endometrial cancer. That study is expected to complete, and we await that data. That creates additional opportunities, financially for us if that is successful. F urthermore, retifanlimab is being used in combination with other investigational and approved drugs by Incyte.T his has been a great partnership with Incyte, on the development of retifanlimab, and I should also point out, we are manufacturing that molecule for them. Thank you very much. Thank you. And one moment, we do have a follow-up question coming in. O ur follow-up question will be from Yigal Nochomovitz of Citigroup. Your line is open. Oh, thanks for taking the follow-up. I was just curious, you know, if it turns out that when you do see the mature PFS data next year, that it's basically mirroring what you've seen here, about eight months PFS, would that be sufficient to move forward? I f you know, what would that data imply in terms of how you would position vobra duo in lines of therapy in prostate cancer? Obviously, it's always the balance of safety and efficacy, you know, with the current PFS we're showing with immature data, it's clearly a very active agent. We've heard this from a number of investigators. There'd be a greater pressure to improve the safety if you were operating with a lower PFS, and it would direct you toward probably a later line of therapy, if that's what ultimately was gonna be pursued. But you really got to look at the totality of the data to make that call. Okay, thank you. Thank you. One moment for the next question. O ur next question will be coming from Silvan Tuerkcan of Citizens JMP. Your line is open. Thank you. T hanks for taking my question and thanks for the update. One question about the deaths here. Could you please confirm the 35 + 3 deaths are now treatment related? H ow do they transfer from treatment emergent to related, and how many total deaths are there? I'm talking treatment and emergent deaths that you've seen in the trial. And then I have a follow-up, please. There's a lot of background noise, so I'm not sure I got all of that. But I think part of your question is the translation of treatment-emergent to treatment-related. So the treatment-emergent is what's scored at the time the event occurs. W hether it's treatment-related is through an adjudication process where we look for additional information that may be related to that assignment. W e look and the protocol pre-specifies some of the elements that we look for. One is you know the time. You know, was the patient on drug at the time, or was this long after exposure to the drug had stopped? The other parameters we look at are, are there pre-existing comorbidities that are more likely explanations for the event that's observed? Another consideration is, have we seen the event before? Clearly, if we've seen the event before, then the weight shifts towards being treatment related. If it's a very unusual event that we haven't seen despite dosing 181 patients, and particularly if that is a late event, may, might, or will not be related. But it is a rather complex adjudication process where we gather additional information to try to figure out what is the likely relationship between the event and the exposure. Silvan, let me just add a little additional point that Stephen was making. With the treatment-related that we reported here, except for pneumonitis, which overall with regard to pneumonitis within the entire population, which was a low-frequency event, all the other treatment-related events ascribed by the investigator at the time were single events of course. A gain, the rarity of these particular causes gives us a lot more confidence that these are part of the natural situation of very advanced patients, elderly patients, that have other comorbidities. Great. Thank you for the details here. R egarding the PFS curves, and obviously, as you mentioned, they're not mature yet. N ormally a hallmark of a, you know, higher dose giving a little bit less of PFS is a hallmark of some tolerability issue. What's your confidence that that's not the case here? Thank you. The listed doses are what they start at. It's what we see is more dose reduction in the higher dose. So there is. The overall exposure to the investigational agent is not radically different between the two dosing arms. When you're looking at the PFS curve, you're looking at things that are happening late, and what we're seeing is more dose reductions in the two point seven mgs per kilogram arm than we saw in the 2.0, resulting in less dose intensity. They're getting a lower percentage of their assigned dose, and their overall exposure is not as different as you might think. Great. That's very helpful. Thank you. Thank you. I t this time, there are no more questions in the queue. I would like to turn the call back over to management for closing remarks. Please go ahead. Thank you all for participating in the call today. We obviously are very excited to be updating you in the near future on the final data of vobra duo, as well as discussing next steps forward with many of the programs we discussed today. Have a great day. This does conclude today's conference call. Thank you so much for joining, and you may all disconnect.