Good afternoon. We will begin the MacroGenics 2024 first quarter corporate progress and financial results conference call in just a moment. All participants are in listen-only mode at the moment, and we will conduct a question-and-answer session at the conclusion of the call. At this point, I will turn the call over to Jim Karrels, Senior Vice President, Chief Financial Officer of MacroGenics. Thank you, operator. Good afternoon, and welcome to MacroGenics' conference call to discuss our first quarter 2024 financial and operational results. For anyone who has not had the chance to review these results, we issued a press release this afternoon outlining today's announcements. This release is available under the Investors tab on our website at macrogenics.com. You may also listen to this conference call via webcast on our website, where it will be archived for 30 days, beginning approximately 2- hours after the call is completed. I would like to alert listeners that today's discussion will include statements about the company's future expectations, plans, and prospects that constitute forward-looking statements for purposes of the Safe Harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factors section of our annual, quarterly, and current reports filed with the SEC. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change, except to the extent required by applicable law. Now I'd like to turn the call over to Dr. Scott Koenig, President and Chief Executive Officer of MacroGenics. Thank you, Jim. I'd like to welcome everyone participating via conference call and webcast today. I will provide key updates on our clinical programs, including an important interim data update on our TAMARACK Phase II study this afternoon. But before I do so, let me first turn the call back to Jim, who will review our financial results. Thank you, Scott. This afternoon, MacroGenics reported financial results for the quarter ended March 31, 2024, which highlight our financial position. As described in a release this afternoon, MacroGenics' total revenue was $9.1 million for the quarter ended March 31, 2024, compared to total revenue of $24.5 million for the quarter ended March 31, 2023. This decrease was primarily due to a decrease in revenue from collaborative and other agreements, including a $15 million milestone received from Incyte in the quarter ended March 31, 2023. Our research and development expenses were $46 million for the quarter ended March 31, 2024, compared to $45.9 million for the quarter ended March 31, 2023. Our selling, general, and administrative expenses were $14.7 million for the quarter ended March 31, 2024, compared to $13.5 million for the quarter ended March 31, 2023. The increase was primarily related to increased stock-based compensation expense and consulting fees. Our net loss was $52.2 million for the quarter ended March 31, 2024, compared to a net loss of $38 million for the quarter ended March 31, 2023. Our cash, cash equivalents, and marketable securities balance as of March 31, 2024, was $184.2 million, compared to $229.8 million as of December 31, 2023. Finally, in terms of our cash runway, consistent with our prior guidance, we anticipate that our cash, cash equivalents, and marketable securities balance of $184.2 million as of March 31, 2024, in addition to projected and anticipated future payments from partners and product revenues, should provide a cash runway into 2026. Our anticipated funding requirements reflect expected expenditures related to the ongoing Phase II TAMARACK and LORIKEET studies, as well as our other ongoing clinical and preclinical studies. Now I'll turn the call back to Scott. Thank you, Jim. We continue to believe our proprietary pipeline of product candidates has great promise, and I will walk you through each of our key programs, including disclosure of new safety and efficacy data from the TAMARACK study of vobramitamab duocarmazine in patients with metastatic castration-resistant prostate cancer. We have lots to cover today, so let's jump in. Vobramitamab duocarmazine, or vobra duo, is our ADC 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. Vobra duo is designed to take advantage of this antigen's broad expression across multiple solid tumor types. As you know, we believe B7-H3 has the attributes of an ideal cancer target. The TAMARACK study is being conducted in mCRPC patients who have previously received an androgen receptor axis-targeted agent, or ARAT, and up to one prior taxane-containing regimen, but no other chemotherapy agents. The study is designed to evaluate vobra duo in patients across two experimental arms of either 2 mg/kg or 2.7 mg/kg every four weeks, with radiographic progression-free survival, or rPFS, as the study's primary endpoint. We recently generated an updated, expanded interim data set based on a data cut-off date of April 12, 2024, which is the basis for all of the TAMARACK data we are sharing with you today. Feel free to download the slide set that highlights this data from the Events and Presentations page under the Investor Relations section of our website. Or you can find a direct link to the document provided in today's earnings press release. Flip ahead to Slide 4, and you will note we have enrolled a total of 181 patients, although a few patients were on the original control arm and are thus not counted in the safety population of 176 patients who received vobra duo. This is one less than the 177 we mentioned in an earlier press release, as one patient never fully completed the informed consent form process. As you can see on this slide, we've broken out the number of patients with evaluable PSA and baseline target lesions by dosing cohort. Slide 5 provides several baseline characteristics. Both arms are well-balanced, with the exception of ECOG status, as the 2.7 mg per kg arm very slightly favors ECOG 1 over ECOG 0. Keep in mind that this is a fairly subjective measure. I'll point out that despite randomizations, fewer patients in the 2.7 mg per kg cohort had measurable disease than non-measurable, whereas there was roughly 50/50 split in the 2 mg per kg cohort. In terms of having a prior taxane versus not, the split was close to 60/40 across both dose cohorts. Also recall that mCRPC patients had to have a prior androgen receptor axis-targeted agent for study entry, and as you can see, a few had more than one. Next, let's re-review biological activity. On Slide 6, we show the PSA50 responses for 153 patients, which represents all subjects who had received at least one dose of vobra duo, had a baseline PSA greater than 2 nanograms per mL, and had at least one post-baseline PSA measurement. For the 2 mg per kg dosing cohort, 50% of the 82 evaluable patients experienced a greater than 50% reduction in their PSA, while 43.9% of patients had a confirmed greater than 50% PSA reduction. In the 2.7 mg per kg dosing cohort, 50.7% of 71 evaluable patients experienced a greater than 50% reduction in their PSA, while 36.6% of patients had a confirmed greater than 50% PSA reduction. Happily, these PSA50 results are generally well aligned with the PSA50 expectations we laid out before the study commenced. Turning to the summary of two responses, as summarized in Slide 7, among the 45 patients with baseline target lesion measurements in the 2 mg per kg dosing cohort, 41 or 91.1% achieved disease control, as measured by sum of confirmed, complete, and partial responses for stable disease, while the confirmed objective response rate, as measured by sum of complete and partial responses, was 17.8%. With the inclusion of unconfirmed CRs and PRs, the unconfirmed ORR was 24.4%. Among the 32 patients with baseline target lesion measurements in the 2.7 mg per kg dosing cohort, the disease control rate was 87.5%. The confirmed ORR was 25%, and with the inclusion of unconfirmed PRs and a CR, the unconfirmed ORR was 43.8%. Let's review the PSA waterfall plots next. Slide 8 shows the PSA waterfall plot for the 2 mg per kg cohort. As you can see, 41 of the 82 patients had a 50% or greater decrease in PSA, with 36 or 43.9% of these patients achieving a confirmed PSA50 response. 48 of these patients, or 58.5%, remained on therapy as of the data cutoff. Also, based on the archival biopsy, the B7-H3 membrane H scores shown on the plot, it does not appear that there are B7-H3 expression thresholds required for reducing PSA. We are still reviewing this interim data. At this point, the implication is that a B7-H3 biomarker diagnostic will likely not be required. Slide 9 shows the PSA waterfall plot for the 2.7 mg per kg cohort. Here, 36 of the 71 patients had a 50% or greater decrease in PSA, with 26 or 36.6% of these patients achieving a confirmed PSA50 response. As of the data cutoff, 39 patients or 54.9% of patients remained on therapy. Next, I will review investigator-assessed tumor size waterfall plots. On Slide 10, which shows the 2 mg per kg cohort, of the 45 patients with measurable disease, one did not have a post-baseline tumor assessment. As I mentioned earlier, the disease control rate for this group was 91.1%, with all but three patients having either a partial response or stable disease. The confirmed ORR was 17.8%, while the unconfirmed ORR was 24.4%. Slide 11 shows tumor response for the 2.7 mg per kg cohort. Here, of the 32 patients with measurable disease, two did not have a post-baseline tumor assessment. The disease control rate for this group was 87.5%. The confirmed ORR was 25%, while the unconfirmed ORR was 43.8%. Next, I will review the swimmer plots for the tumor response, which will hopefully convey a sense of durability of vobra duo in the mCRPC setting. Slide 12 shows the interim results for the 2 mg per kg cohort. Here you can see that of the 45 tumor response evaluable patients, eight or 17.8% had confirmed responses. With the inclusion of the three unconfirmed responses, the unconfirmed ORR is 24.4%. 23 of the 45 patients, or 51.1%, were still on therapy as of the data cutoff. In the 2.7 mg per kg dosing cohort shown on Slide 13, eight patients, or 25%, had confirmed objective responses. With these six unconfirmed responses, the unconfirmed ORR is 43.8%. 20 of the 32 patients, or 62.5%, remained on therapy as of the data cutoff. Next, I will review interim safety in the TAMARACK study as of the data cutoff. Slide 14 shows the overall summary of adverse events in the study to date. I'll point out a few parameters by dosing cohort. Of the 90 patients who received vobra duo at 2 mg per kg, 89 or 98.9%, experienced a study treatment-emergent adverse event of any grade. 49 or 54.4% of the patients had a Grade 3 or greater TEAE, and 10 patients, or 11.1%, had an adverse event leading to study drug discontinuation. Of the 86 patients who received vobra duo at 2.7 mg per kg, 86 or 100% experienced a TEAE of any grade. 44 or 51.2% of patients had a Grade 3 or greater TEAE, and 13 patients, or 15.1%, had an AE leading to study drug discontinuation. Also, as noted on Slide 14, as of the data cutoff date, a total of five fatal events occurred as follows: one grade five fatal event occurred in the 2 mg per kg dosing cohort, an acute myocardial infarction, which was not classified as treatment-related. Four Grade 5 events occurred in the 2.7 mg per kg dosing cohort, which included one cardiac arrest, not classified as treatment-related, and two cases of pneumonitis, which are still being investigated and initially assessed as possibly treatment-related. In addition, a patient in the 2.7 mg per kg dosing cohort had a Grade 3 pleural effusion and subsequently died. In terms of specific treatment-emergent adverse events, those with incidents greater than or equal to 10% are shown on Slide 15. For the 2 mg per kg dosing cohort, the five most common TEAEs of any grade in this dosing cohort included asthenia, nausea, peripheral edema, decreased appetite, and fatigue. Of note, the incidence of pleural effusion in this cohort was Grade 1 of 8.9% and Grade 2 of 8.9%. There were no Grade 3 or greater events. Also, the incidence of palmar-plantar erythrodysesthesia syndrome in this cohort was grade 1 of 11.1% and grade 2 of 4.4%. There were no Grade 3 or greater events. The five most common TEAEs of any grade in the 2.7 mg/kg dosing cohort included asthenia, decreased appetite, peripheral edema, nausea, and pleural effusion. Of note, the incidence of pleural effusion in this cohort was grade 1 of 14.0%, Grade 2 of 14.0%, and Grade 3 of 1.2%. Also, the incidence of palmar-plantar erythrodysesthesia syndrome in this cohort was Grade 1 of 12.8%, Grade 2 of 9.3%, and Grade 3 of 1.2%. As visually represented in the butterfly plot on Slide 16, all the TEAEs of greater than or equal to 10% are overwhelmingly limited to either Grade 1 or 2. Overall, we believe these doses are tolerable with side effects that are manageable. Also, we are very pleased with the biological activity observed in the study as of April 12, 2024, data cutoff, with the interim data being well aligned with the parameters for success that we laid out at the onset of the study. We achieved our goal of reducing the incidence and severity of both palmar-plantar erythrodysesthesia and pleural effusion in comparison as of the most recent data cutoff to what we saw in the Phase I dose expansion study. We will continue to evaluate the totality of the data, including future radiographic progression-free survival or rPFS, the study's primary endpoint, as we consider dose selection of either 2 or 2.7 mg/kg. To that end, we are currently undertaking the necessary initial steps to prepare for the potential initiation of a Phase III study in mCRPC in 2025. Looking ahead, we plan to share updated TAMARACK data, safety, efficacy, and durability data, including rPFS, in the second half of 2024 based on a future data cutoff. Also, as mentioned on our prior earnings call, we plan to expand the tumor types being evaluated in the TAMARACK trial and expect to enroll additional patients with non-small cell lung cancer, small cell lung cancer, melanoma, squamous cell carcinoma of the head and neck, and anal cancer. We expect to initiate dosing in these additional cohorts in mid-2024. Recall that we have two other clinical molecules that target B7-H3. The first, MGC026, is an investigational ADC incorporating a novel topoisomerase 1 inhibitor-based linker payload, SYNtecan E, which we licensed from Synaffix. Our second additional B7-H3-targeted molecule is enoblituzumab, an investigational Fc-optimized monoclonal antibody. I'll walk you through both of these molecules next. MGC026 incorporates a linker payload based on exatecan, a clinically validated and potent camptothecin that readily combines with Synaffix's HydraSpace technology. MGC026 preclinical data was presented recently at the American Association for Cancer Research annual meeting. In preclinical studies, MGC026 was shown to have greater potency than B7-H3-directed antibodies conjugated to deruxtecan or DXd, a topoisomerase-based payload utilized in other ADCs. In addition, the MGC026 payload has been shown to be less susceptible to multidrug-resistant mechanisms than DXd and SN-38. Also, a toxicology study conducted in cynomolgus monkeys showed that MGC026 was well tolerated at all dose levels tested. Finally, MGC026 displayed approximate dose proportional pharmacokinetics in the animal models tested, indicating predictable behavior conducive to further clinical development. We recently initiated a Phase I dose-escalation study of MGC026. The variable domain of the molecule targeting B7-H3 for MGC026 is the same sequence contained in vobra duo. We view MGC026 as a complementary approach to vobra duo for targeting B7-H3. More specifically, we believe that having distinct mechanisms of action, vobra duo and MGC026, may address different cancers, tumor stages, or be used in combination with alternate agents or potentially with one another to enhance their clinical utility. We remain confident in the potential of targeting the B7-H3 pathway, viewing our topo1 inhibitor strategy as an additional valuable tool in our therapeutic repertoire. Regarding enoblituzumab, our academic collaborators are enrolling an investigator-sponsored, randomized, translationally intense, Phase II investigator-sponsored study of this molecule in up to 219 patients with prostate cancer. The HEAT 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. Next, I'll update you on lorigerlimab, our bispecific tetravalent PD-1 by CTLA-4 DART molecule. We designed lorigerlimab to have preferential blockade on dual PD-1 CTLA-4 expressing cells, such as tumor-infiltrating lymphocytes, which are most abundant in the tumor microenvironment. We are enrolling the LORIKEET study, a randomized Phase II clinical trial of lorigerlimab in combination with docetaxel versus docetaxel alone in second-line chemotherapy-naive mCRPC patients. A total of 150 patients are planned to be treated in a 2:1 randomized study. The current study design includes the primary study endpoint of rPFS. We anticipate completing enrollment of the study this year and expect to provide a LORIKEET clinical data update in the first half of 2025. In addition, we continue to enroll patients in the Phase I/II dose-escalation study of vobra duo in combination with lorigerlimab in patients with advanced solid tumors. We anticipate commencing a dose expansion study of this combination in mCRPC and at least one additional indication in 2024. Next up, MGD024 is our next-generation bispecific CD123 by CD3 DART molecule that incorporates a CD3 component designed to minimize cytokine release syndrome while maintaining antitumor cytolytic activity and permitting intermittent dosing through a longer half-life. Our Phase I dose-escalation study of MGD024 is ongoing in patients with CD123-positive relapse or refractory hematologic malignancies, including acute myeloid leukemia and myelodysplastic syndromes. Recall that Gilead has the option to license MGD024 at predefined decision points during the Phase I study. In terms of preclinical projects, MGC028 is 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, a 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 recently presented MGC028 preclinical data at the AACR Annual Meeting in April. In addition, in a non-human primate study, MGC028 was well tolerated at high dose levels with mild reversible side effects and no ocular toxicity, which is often a concern with tubulin inhibitor-based ADCs. These promising preclinical results support the continued investigation of MGC028 as a therapeutic option for treating ADAM9-expressing solid tumors. We are currently anticipating submitting an investigational new drug or IND application for MGC028 by the end of this year. Beyond MGC028, we're exploring additional molecules for potential future IND submission. I look forward to telling you more about these additional molecules on future calls. To conclude, 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? If you'd like to ask a question at this time, please press star one one on your touchtone telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Tara Bancroft with TD Cowen. Hi, good afternoon. So, lots of questions here, I'm sure. But, so looking at the safety, it does look somewhat similar to the Phase I now with these two extra cycles versus the abstract. So could you elaborate more on what it is that you're seeing as improved on in terms of safety with these doses? Or is it what you're referring to more on the efficacy side? And how this looks like quite different from the abstract with these just two more median cycles. So could you describe more what happened there? Well, actually, Tara, let me sort of go through the safety. First of all, the safety data cut was in January, and now we're in April, greater than three months since the January cutoff. First of all, compared to the Phase I data, we are now exceeding the mean number of doses that were achieved in the Phase I study. And then second, third is, if you look at the butterfly plot of the AEs, the side effects are overwhelmingly Grade 1 or 2, manageable, with a smattering of Grade 3s. No concerning new type of side effects is propped up, as you see on the figure or on the listings, in this interim data set. And as you note on both the PSA figures as well as the figures we included on the targeted lesion figures, the majority of these individuals are still on study, where clearly in the Phase I, they were coming off study. We did a head-to-head analysis at 16 weeks of all patients that are on TAMARACK and compared it to the prostate patients on the Phase I study, also at 16 weeks, and the results in TAMARACK are dramatically improved. For example, specifically, we had half the amount of Grade 3s in TAMARACK as compared to the Phase I prostate group. One half to one third of the total of discontinuations, and about half of the reductions in TAMARACK as compared to the Phase I, and only one third to one half of drug interruptions. So as we have laid out in terms of achieving this vis-a-vis the Phase I study, we have accomplished what we wanted to achieve. Furthermore, we did some key comparisons to other prostate studies. For example, in our discontinuation rates at the 11% at the 2 mgs or the 15% of the 2.7 mgs, this compares well to a number of other studies. For example, in the CARD study, cabazitaxel, there was a discontinuation rate of 19.8%. In KEYNOTE-921, the docetaxel arm was 22.4%, and similarly, the combo arm with pembro was 29.2%. And then in TRITON3, for the doci arm, it was 32.4%. So as you see, we're doing quite well there with regard to discontinuations, vis-à-vis others. And similarly for Grade 3s, you know, we can compare what we're seeing here, for instance, in the docetaxel arm in TRITON3, 61%, KEYNOTE-921, 36%. And then if you even look at experimental Phase I studies in prostate, some new targets, if you look at Amgen's STEAP1 by CD3, it was 55%, and in Daiichi 7300, it was 47% in their prostate. So all in all, again, as I've pointed out, while the safety data has accumulated more safety side effects, as the-- we believe that these are extremely manageable. You know, in discussions with investigators, they are very comfortable with managing these patients and are very encouraged by both the safety and obviously the activity data they've seen to date. Okay, thank you. That's super helpful. Thanks. Our next question comes from the line of Jonathan Chang with Leerink Partners. Hi, guys. Thanks for taking my questions. I guess I'm also just trying to better understand the evolution in the tolerability profile versus the previously submitted abstract. Is there a time dependency to the AEs, or does this evolution reflect something else? And then second question, can you provide any additional color on the patient deaths and whether or not they were treatment related? Thank you. Yes, thanks so much for the point. So again, as I started off with a question from Tara, the cutoff from, and the safety was of, as of January, beginning of January. And, as we did a comparison, between the original, Phase I prostate data, and that of the data that we had as of the January cutoff, we looked at the 95 patients that had reached the 12 weeks. So that was a head-to-head comparison, of where the safety was at that point versus that of, of the Phase I's study. And so, as I said before, this, the, you know, data will continue to accumulate. We now have, data, safety data on the entire population over now, greater than three more months of data that's accumulated. But again, as I reiterate, look at the, look at the, B7-H3 part where we have a very, safety data that's limited to Phase I, II, quite manageable going forward. And as I was pointing out earlier, this is not that different from what has been seen, with other ADCs, as well as other agents that have been approved in, prostate cancer. So, you know, that's, that's a summary there. With regard to the patient deaths, as pointed out, a cardiac death and a, a cardiac arrest were not deemed to be, associated with the drug, unrelated. The additional, cases, two cases of pneumonitis, are being investigated. These are sort of real-time, observations in the 2.7 mg/kg cohort. What we can say is that particularly one of these cases was very complicated with other confounding matters, medical matters with this patient, but it's being further investigated right now, so I don't have a further decision with regard to cause and effect with regard to to drug. And similarly, the patient that was deemed with a pleural effusion, the occurrence of that death occurred more than three months later, and again, is being investigated at this time. Got it. Thanks for taking my questions. Our next question comes from the line of Yigal Nochomovitz with Citi. Hi, guys, this is Ashiq Mubarack on for Yigal. Thanks for taking my questions. A few from me. I guess on the grade five pneumonitis event, were you surprised that these occurred? I can't quite recall if pneumonitis had been observed as a signal previously. And to that end, is there B7-H3 expression in the lungs, and are you considering maybe integrating some type of steroid prophylaxis to help prevent pneumonitis moving forward? Well, again, as I was indicating, these are still being investigated, so the cause and effect with regard to the drug is still under investigation. And we have not, and in fact, we have not seen, in the large number of patients here, any association with pneumonitis in that patient. So that, again, raises, you know, questions of what is the ultimate cause of these patients' deaths associated with the pneumonitis. And with regard to- Okay. Okay, got it. And then- Let me just finish. I'm sorry, I didn't finish your second question, which was expression of the B7-H3 in the lung. Not normally seen in the lung. We had no lung findings in the cynomolgus monkey toxicology studies. Clearly, with certain activation, you can have certain cells that may have expression of B7-H3, but it's not a normal occurrence. Okay. Okay, got it. And then maybe another question. I mean, choose... How are you thinking about choosing the dose moving forward into Phase III? I know it's a little, it seems a little confounding. It seems like efficacy is balanced on PSA50, but RRs are a little bit higher at the higher dose, but maybe the safety is a little better at the lower dose. So how are you thinking about that? Well, I think that's exactly the point here, is that we're seeing a nice gradation. We see. We believe that we have picked the correct dosing range to evaluate what will be the optimal dose. And so this will be determined, you know, when we achieve the rPFS values and the disease control rate values, which we expect to happen, you know, towards later in the midyear. So, you know, stay tuned for that. But, as we view the data right now, both doses are potentially usable and further developable going forward with this interim data. Got it. Thanks very much. Our next question comes from a line of Kaveri Pohlman with BTIG. Hi, yes, good evening. Thanks for taking my questions. Can you comment on how the efficacy and safety look like in chemo pre-treated versus chemo-naive patients, if you saw any notable differences there? Thank you, Kaveri, for that question. I'm not gonna comment on that, but what I would say at this point is that both populations, both the chemo-naive and the chemo-experienced populations are under consideration for development, if we go forward into the Phase III study. Nothing unexpected was observed with regard to either populations in terms of overall responses. Got it. And then, is there any feedback you received from physicians regarding dose reduction, interruption rates, the reduced level of doses you, that were used and their potential to impact durability? Well, again, as I, you know, we've shown very nicely, and we wanted to illustrate that on the swimmer's plot, these patients had sustained responses and continued even under circumstances when doses had been modified and reduced. You know, as you looked on some of the longer treated patients, we had, as you saw on patients with 2.7 mg per kg and a patient on the 2 mg per kg that were over 30 weeks of treatment, there was some dose reductions there, and again, patients are doing quite well. So they are very comfortable and with experiences in using other chemotherapies, for example, on doing dose modification. We have seen that this is has not led to any mitigation or reduction in the responses so far as of the interim data. Got it. That's helpful. And maybe a last one. Any thoughts on why there is no correlation between efficacy and B7-H3 expression? Well, you know, that was something we pointed out on the Phase I study. We did not see that either. We were observing responses even in patients that had lower H scores, although this may be a situation that it's a threshold effect, where you if you have a modest number of expression B7-H3, that's sufficient to provide entry of the toxin of the linker toxin into the cell. So we see that as actually as a positive result here. The caveat is of course these are archival specimens, and you know, there may be some differences if you do fresh biopsies. Helpful. Thanks for taking my question. Our next question comes from the line of Stephen Willey with Stifel. Yeah, good afternoon. Thanks for taking the questions. Just with respect to the pneumonitis, I know that this is typically something that needs to be proactively looked for, whether it's via chest X-ray or CT. And just, I'm curious if that was kind of a routine screening procedure for some of these patients, and could some of the higher rates of dyspnea that are observed in the 2.7 arm, including some of the grade 3+ events, could those be, I guess, maybe miscategorized as pneumonitis in the context of perhaps not proactively screening for it? I don't believe that there is a screening protocol for this, because, A, as I pointed out earlier, there was no observed increased rate of pneumonitis in the population. With regard to a patient that has dyspnea, they would normally get, as part of their treatment, although I can't comment on the specific patients here, obviously a full workup. And clearly, there are a lot of different causes of dyspnea, although again, the percentages are quite low. So again, I just reiterate the cases of pneumonitis are under investigation, and clearly there are, at least the data to date, other complicating factors of one of the patients with pneumonitis of other medical issues. And we still need to get additional information on the other patients. So, it's too early to draw any conclusions. Okay. And I'm not sure if it's in the presentation, but can you also provide us with what the median duration of follow-up is in both of these, in both of these arms at this point? We don't have it included here, and I don't know off the top of my head, but and what we did is obviously you saw on the swimmers plot, the time and, you know, a large number of these patients have, you know, exceeded the 16- 20-week time interval. The number of doses, the mean number of doses is now five, so, which is on an acute basis. And then just lastly, I know, this trial allowed for patients who had not been on, I guess, quote, unquote, stable, ARPI for 12 months. Do you know how those patients attribute out between the two treatment arms with respect to patient baselines? With regard to that population, I don't have the specific percentages in front of me, but as I recall, I believe it was about a 40%-60% split in terms of less than 12 months, greater than 12 months of a historical ARAT exposure in that regard. Thanks for taking the questions. Our next question comes from the line of Jon Miller with Evercore. Hi, guys. Thanks for taking my questions. Very interesting update here. Scott, I would love to get a little bit more confirmation. I know you said in response to an earlier question that you saw interruptions and discontinuations looking better than Phase I, but that, I want to confirm that, that you said that and what exactly, number you're pulling from. When I look at the Phase I poster, I see 15% discontinuations, 59% interruptions. That looks right in line with what we're seeing with today's update at, at 15% and 56% on the 2.7 mg per kg arm there. For hand-foot syndrome, while obviously the grading appears to be lower in this update, you're seeing, you know, 31% in the Phase I result, going to 23% in the 2.7 mg arm, today. So, you know, when you look at the tox signals versus Phase I, you know, you characterize them as being much better than they were, but I would love to see... Like, is there a place, this particular number you can point to, they say, "Look, this is where it got better. This is where docs are going to be comfortable dosing this. You know, this is the, this is the linchpin number that is going to let people stay on therapy longer than they did in Phase I? Yeah, so the, you know, again, I wanted to do compare apples to apples here, and so I'm comparing, as we did in the previous safety data reveal from the abstract. It was a comparison to the prostate cohort. I believe what you were pulling out is all different, different populations. So I'm just looking, and I have, and I know the specific data, and what I said before is absolutely correct, that in the patients in the Phase I study, whether you look at severity of Grade 3. W hether you look at drug discontinuations, whether you look at drug dose reductions, whether you look at drug interruptions, the percentage of those patients in the Phase I study was anywhere from greater than 2x of what we're seeing at the same six, at same time interval, around 16 weeks. I'm trying to as best do an apples to apples comparison from a time exposure to drug. Now, there could be some modest variations of what the ultimate drug exposure was, but, I'm clearly seeing, at least 2-3x more of the side effect profiles and severity of grades in the Phase I prostate arm versus what we're seeing here in TAMARACK. And so again, I will reiterate, the feedback we're getting from the investigators has been manageable tolerability, not concerning. And, in addition, as I pointed out earlier, we are now past of where the mean number of doses in this TAMARACK is vis-à-vis where we were in the Phase I study. And so I'm, you know, I'm feeling very encouraged and that we're on the right pathway here for delivering this, this drug. As I showed in the various swimmers plots, majority of the patients are still on treatment despite, you know, some of the dose modifications and interruption. All right. All right, I guess I understand that. Maybe on the efficacy side, I would love to. I don't see in the deck how many prior lines of therapy, what's the median prior line of therapy in this, in these cohorts? And then what are you looking at for the comps for ORR and DCR in that population? So, here, as I pointed out, the entry criteria was no more than three lines of therapy. I don't know where it ended up on with regard to the median for this study, whether it was two or three, but we'll have to get back to you on that. Again, in terms of the ORR, I mean, if you listened as you have to some of the continuous guidance I had, which I started back in November, we were seeing approximately a 25% confirmed unconfirmed rate of objective responses. And what was observed in the Daiichi 7300 in their ESMO presentation was a solid 25% as well. The point I made was that we should certainly achieve the 25%, you know, by this end of the study. And as we see here, not only are we achieving it, it is likely we're gonna exceed this at when the final data comes out, given that, as I pointed out, many of these patients are still on study, but we have a confirmed and unconfirmed ORR in the 2.7 mg per kg of 43.8%, and in the 2.0 Q4 in a confirmed or unconfirmed 24.4%. So I, you know, I think we're doing quite well with regard to what the expectations were and what the data is as of this cut. But again, continue to expect further maturation of this data and continuing improvement. All right, makes sense. Can you talk about potential use of vobra duo in combinations, given the safety profile here? It's obviously not an innocuous molecule, and some of the toxins are overlapping with other agents that you might expect to see in prostate space. So I'm thinking about pneumonitis and neutropenia, for instance. So you know, are you looking? You know, what does this mean for potential use in combination and thereby uses in earlier lines of therapy compared to other, you know, programs that are enthusiastically pursuing larger combinations in early line therapy? Well, again, we, you know, are very much interested in looking at combinations of vobra duo with different agents. And as you know, we have initiated dose-finding studies with our lorigerlimab, PD-1 CTLA-4 DART-specific molecule. And as I commented earlier, we expect to be able to define the go-forward doses from these dose-finding studies very shortly, where we would not only look at this combination in prostate cancer, but in other tumors as well. Given that mechanistically, we believe these are very orthogonal mechanisms for controlling tumor, and as we have already shown, in addition to the vobra duo data that we described today, activity independently, single agent of lorigerlimab in late stage patients, I think this will be a very good combination to explore, and we are looking at the potential of others, as well. All right. Thank you very much. Our next question comes from the line of Etzer Darout with BMO Capital Markets. Great, thanks. Just wanted to know if you could provide a little bit more color around sort of the, the combination, with, specifically with lorigerlimab, given that you had sort of indicated that, you know, you could move into sort of, dose expansion studies with the, with vobra and lorigerlimab, in the first half, I believe. Maybe if you could comment on where you are with that program, and is that still sort of a viable plan moving forward, given, given the profile that we've seen today? Thanks. Yeah, Etzer, we are on track for moving forward with that. I think we're at the final evaluation of the dose-finding cohort for finding what the ideal doses of each one when put together to maximize both the safety and activity to explore. So I think we will be in a pretty good shape in the second half of the year to initiate enrollment in the prostate and potentially another tumor indication. So stay tuned for that. Thank you. Our next question comes from Mayank Mamtani with B. Riley Securities. Good afternoon. Thanks for taking our question. So maybe on the look-forward basis, Scott, if you could comment on your expectations for the rPFS data, and you know, how you may look to present that in the next few months, you know, based on what you're seeing on durability, median cycles. And I think importantly, how you see based on all that you know, you see this fit in the paradigm relative to PSMA, STEAP1. You know, when you think about sequencing, you think about designing your Phase III next year. Yeah, thanks very much, Mayank. Right now, you know, as I again laid out the parameters here as baseline, what we had indicated was an rPFS of at baseline of six, but greater, and obviously looking for 7, 8, 9, 10, or higher. I think that the data that we showed today and the fact that these patients are still on therapy, I think we will, you know, ultimately see the results, but there is no reason we can't meet some of the longer lived rPFS values here. So we'll have to wait to be seeing the results. The expectation is that this would be presented at a scientific conference in the second half of this year. Got it. Thank you. And maybe just one quick clarification: there weren't too many RLT or Pluvicto-exposed patients in the study. Does that try to do any kind of analysis, if you could clarify that? I'm sorry, did you say radiotherapy? Yeah, RLT or Pluvicto-exposed patients. Okay. That's true. And then as you saw on the geographic distribution of the patients, there were a very modest number of patients from the U.S. where they would have the ability to, when we initiated the study and when the enrollment occurred, to either have seen Pluvicto or have progressed on that, given the timing of the marketing of that drug in the U.S. versus Europe, where the majority of the patients came from Western Europe. So we expect small numbers of those patients in this study. Got it. Thanks for taking my question. Our next question comes from the line of Silvan Tuerkcan with Citizens JMP Securities. Yeah, good afternoon, and thanks for taking my question. First of all, when could we find out about the adjudication of the death, if they are treatment related or not? Would that be available by the time we get that presentation at a medical conference in the second half? I would presume so. Obviously, we're giving you ongoing results, as they, you know, come in. I mean, we're here in early May, and as we just did this data cut in in April. So, you know, the expectation is the teams are working very hard in finding out the details on the patient study and evaluating comorbidities and other things that may have contributed to the specific deaths. Right. But the DSMB is looking at these, right? Presumably between- Oh, absolutely. January and this data cut. Absolutely. Great. And then, what—maybe talk to me, maybe if you can walk me either through the waterfall plot or... Basically, I'm trying to understand or reconcile the unconfirmed responses. There's a fair amount, especially in the high-dose arm, you know, where your confirmed response rate is 25%, but it could be with the unconfirmed as high as 43%. Are those responses the majority? Why are they not confirmed? Are they still ongoing? Did the patients didn't have that scan yet, or could you please characterize that? Well, yes. I mean, it's very, you know, if I look at the plots there of the swimmers plot, say, for the 2.7, the time fr- the timing frequency with regard to the scans is every 8 weeks. And so again, if you look at the majority of these patients, if they were still on therapy as of 16 weeks, would have had two scans. Those that had, you know, achieved 24 weeks would have had three scans, and there's at least one patient that probably had four scans. So for instance, if you look at the patient with 2.7 mg per kg Q4, the one on the top of that curve, they had initial evaluation for a PR that he achieved at eight weeks, the first scan, but it wasn't until probably the fourth scan that it was confirmed as a confirmed PR. So you know, the bottom line is that it will take longer time. I mean, there are a number of patients I see here that have, you know, one positive value and have not gotten the second scan yet to confirm it. Great. Thanks for taking my questions. Our next question comes from the line of Kelsey Goodwin with Guggenheim Partners. Oh, hey. Thanks for taking my question. I guess given the early looks at durability with the swimmer plot, for the pre-specified evaluable patients at least, I guess, do you have any update on how you're thinking about, you know, where durability may land for the fall update or just any additional color you could provide there? Thank you. Yeah, I think it's just too early to say, given that, you know, again, the majority of the patients are still on, for example, the 2.7 mg/kg, in the patients with measurable disease. We have, as noted here on the slide, 62.5% that is still ongoing treatment. So, you know, again, we feel very encouraged that, given even at this point, that, you know, we should be able to have an opportunity to treat a large number of these patients with mCRPC. Got it. Thank you. And for the non-RECIST patients, I guess, do these swimmer plots kind of are they representative for the non-RECIST patients as well? Is this a representative look at it? Yeah. Again, what we wanted to do is give you a representative feel for the various durability, and we felt that this was a good representation with regard to RECIST, with measurable disease at baseline. But I would say that our general view is that this can be extended to, you know, patients with bony disease as well, et cetera. So we're just... You know, we have this balance that we want to provide investors a look at this data as we had promised, but at the same time is having additional data that we can then present at scientific conferences. But nothing here is more selective in that regard. Got it. Okay. Thank you so much. Our next question comes from the line of Peter Lawson with Barclays. Great. Thank you. Thanks, Scott, for the update. Just wonder if you could possibly characterize what the spider plots look like, and, you know, if these, these patients are staying on, and the PSA 50 reduction or PSA reductions improving over time, or kind of the best way you could potentially characterize that? Yeah, again, what we try to do is give you a capsule summary, but I would say that the spider plots are exceptionally encouraging. As we had shown in the Phase I data, you will see initial reductions in PSAs and, you know, they seem to be sustained for long periods of time and in a time interval, at least at this interim data, going forward. Clearly, there are individual patients that, you know, will not have the continued PSA 50 responses, but I would say, as we characterize at Phase I, they do very well over a long period of time. Gotcha. Thank you. And the PSA50 reduction was higher in that lower dose. Was that driven by a lower discontinuation rate, or is there something else going on? I, I think this is just, you know, idiosyncratic. I would not overinterpret these. Even though these are nice size populations, I don't think there is anything of particular. I would say, I would more look at, I mean, the 50/50 with regard to the patients that are, that had at least one PSA 50 reduction. I think says that both populations are, are seeing a similar, even though the confirmed ones seem a little lower on the 2.7. I think it's, it's, it's just spurious in that regard, and as I pointed out, is expecting that those numbers could potentially increase over time. So I, I, I don't look at that as a definitive parameter of a difference at this point. Got you. Thank you. Then final question, whether the PSA reductions or it's, if it's ORR or disease control rate, what correlates best in your mind for this agent and PFS? My sense, it's going to be rPFS and disease control rate. As I, you know, pointed out previously, avoiding new growth of lesions is the most important thing here. And so that, obviously, if a patient has 30% or greater, it's recorded as a PR, but if a patient has 20% reduction, it'll be recorded as a stable disease. As long as there are no new lesions, I think that that is fine. But, you know, again, we'll have to see as the data continues to mature. Gotcha. Okay, thank you so much. That concludes today's question and answer session. I'd like to turn the call back to Dr. Koenig for closing remarks. Well, thank you, everybody, for your questions today, and we look forward to following up the completion of the TAMARACK study and further updates on our other programs soon. Have a good evening. This concludes today's conference call. Thank you for participating. You may now disconnect.