Good afternoon. We will start the MacroGenics 2023 Fourth Quarter Corporate Progress and Financial Results Conference Call shortly. I will now hand 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 fourth quarter 2023 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 reviews change, except to the extent required by applicable law. And 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 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 year ended December 31, 2023, which highlight our financial position. As described in the release this afternoon, MacroGenics total revenue was $58.7 million for the year ended December 31, 2023, compared to total revenue of $151.9 million for the year ended December 31, 2022. Revenue for the year ended December 31, 2023, included $29 million in revenue from collaborative and other agreements, MARGENZA net sales of $17.9 million, and $9.8 million in contract manufacturing revenue. Our research and development expenses were $166.6 million for the year ended December 31, 2023, compared to $207 million for the year ended December 31, 2022. This decrease was primarily due to decreased manufacturing-related costs for vobra duo, decreased development and clinical trial costs related to margetuximab, and decreased costs related to discontinued studies, partially offset by increased expenses related to MGC026 and MGC028 development. Our selling, general, and administrative expenses were $52.2 million for the year ended December 31, 2023, compared to $58.9 million for the year ended December 31, 2022. The decrease was primarily related to decreased selling costs for MARGENZA. During the year ended December 31, 2023, MacroGenics received $100 million proceeds from the sale of our single-digit royalty interest on global net sales of TZIELD to DRI Healthcare Acquisitions LP. In addition, we received a $50 million milestone payment from Sanofi related to the achievement of a primary endpoint in a TZIELD clinical study. Under GAAP guidelines and pursuant to Financial Accounting Standards Board’s Accounting Standards Codification or ASC 470, this combined $150 million was included in Other Income as a 'Gain on royalty monetization arrangement' in 2023. Our net loss was $9.1 million for the year ended December 31, 2023, compared to a net loss of $119.8 million for the year ended December 31, 2022. Our cash, cash equivalents, and marketable securities balance as of December 31, 2023, was $229.8 million compared to $154.3 million as of December 31, 2022. Finally, in terms of our cash runway. Consistent with our prior guidance, we anticipate that our cash, cash equivalents, and marketable securities balance of $229.8 million as of December 31, 2023, in addition to projected and anticipated future payments from partners and product revenues should extend our cash runway into 2026. Our anticipated funding requirements reflect expected expenditures related to the Phase 2 TAMARACK clinical trial, the Phase 2 LORIKEET study of lorigerlimab in mCRPC, as well as our other ongoing clinical and preclinical studies. And 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 we'll walk you through each of our key programs, including newly disclosed molecules momentarily, as well as tell you about our plans for upcoming clinical programs. But before I do that and building on what Jim said, I'll quickly remind you that since mid-2022, through our business development efforts as well as milestone achievement, we have received $335 million of non-dilutive capital. This includes $215 million from Provention, DRI, and Sanofi in connection with TZIELD, $75 million from Gilead, and $45 million from Incyte in connection with ZYNYZ. Okay, on to our pipeline. Vobramitamab duocarmazine or vobra duo is our ADC designed to deliver DNA-alkylating duocarmycin cytotoxic payload to tumors expressing B7-H3. B7-H3 is a member of the B7 family of molecules involved in immune regulation. Vobra duo was designed to take advantage of this antigen’s broad expression across multiple solid tumor types. As you know, we believe that this has the attributes of an ideal cancer target. We began enrolling the TAMARACK Phase 2 study of vobra duo under a modified study protocol during the second quarter of 2023 and completed enrollment of this study in November months ahead of schedule. In fact, 177 patients received vobra duo in the study, exceeding the study design goal of 100 participants. As a reminder, TAMARACK is being conducted in patients with metastatic castration-resistant prostate cancer or mCRPC, who have previously been treated with one prior antigen receptor access targeted therapy. Participants may have received up to one prior taxing containing regimen but no other chemotherapy agents. This study is being conducted to evaluate vobra duo in patients across two experimental arms of either 2 mg/kg or 2.7 mg/kg every 4 weeks. In January, the TAMARACK Independent Data Safety Monitoring Committee recommended continuing the study based on a protocol-specified interim analysis. Also, in early February, we submitted an abstract to ASCO that included safety data from the January data cutoff. We anticipate providing an expanded more mature clinical update, including initial efficacy data in the second quarter of 2024 at this meeting. In addition, we anticipate providing updated clinical data, including radiographic progression-free survival, or rPFS, the study's primary endpoint at a conference during the second half of 2024. We plan to expand the tumor types being evaluated in the TAMARACK trial and will 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. 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 or TILs, which are most abundant in the tumor microenvironment. We are enrolling the LORIKEET study of randomized Phase 2 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 the 2:1 randomized study. The current study design includes a primary study endpoint of rPFS. We anticipate providing a trial update in the second half of this year. In addition, we continue to enroll patients in the Phase 1/2 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 another 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 anti-tumor cytolytic activity, and permitting intermittent dosing through a longer half-life. Our Phase 1 dose escalation study of MGD024 is ongoing in patients with CD123 positive relapsed 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 1 study. Next, I'm very excited to tell you about our growing ADC portfolio, which now includes an additional product candidate in the clinic. As I've mentioned on prior calls, we have been developing preclinical ADC molecules utilizing linker payload technologies we licensed from Synaffix. The first of these is MGC026, a clinical ADC incorporating a B7-H3-targeting antibody and a novel topoisomerase 1 inhibitor based linker payload SYNtecan E. This cleavable linker payload is based on exatecan, a clinically validated and potent cancer agent that readily combines with Synaffix hydrospace technology. We believe Synaffix's approach potentially provides advantages compared to other topoisomerase 1 inhibitor-based ADCs. In fact, exatecan appears to be more potent and less susceptible to multidrug-resistance mechanisms than other type 1 inhibitors, such as SN-38 and deruxitecan. Additionally, site-specific conjugation of SYNtecan to the normally glycosylated amino acid in the FC domain abolishes FC gamma receptor and mannose receptor binding, which contribute to nontargeted uptake of ADCs in our alveolar macrophages and is reported to be associated with lung toxicity, and therefore, may provide a safety benefit for patients. The variable domain of the molecule targeting B7-H3 is the same sequence contained in vobra duo. We recently initiated a Phase I dose escalation study of MGC026. 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 Topo 1 inhibitor strategy as an additional valuable tool in our therapeutic repertoire. We plan to present preclinical data for MGC026 at the upcoming American Association for Cancer Research or AACR Annual Meeting next month. Here is a preview of what you'll see. In preclinical studies, MGC026 exhibited a favorable profile with potent in vivo activity to our B7-H3 expressing tumor xenografts representing a range of cancer indications. MGC026 was tolerated in cinemalogous monkeys, a relevant toxicology model at exposure levels exceeding those required for antitumor activity. We look forward to showing you the data at next month. In addition, we are readying a second topoisomerase 1 inhibitor based ADC, MGC028 for which we currently expect to submit an IND later this year. MGC028 is a preclinical ADC incorporating an ADAM9 targeting antibody and the second of our ADC molecules incorporating Synaffix's novel linker payload. ADAM9 or disintegrin and metalloprotease domain 9 is a member of the ADAM family of multifunctional Type 1 transmembrane proteins that play a role in tumor genesis and cancer progression and is overexpressed in multiple cancers, making it an attractive target for cancer treatment. MGC028 is the second ADAM9 target ADC that we have pursued. The first was IMGC936, a molecule with a maytansinoid payload that was advanced under a co-development arrangement with ImmunoGen, Inc., now part of AbbVie. Under the 50-50 collaboration, ImmunoGen led clinical development of IMGC936. Neither MacroGenics nor AbbVie intends to further pursue development of IMGC936 as the molecule did not receive our pre-established clinical safety and efficacy benchmarks. We plan to present preclinical MGC028 data at the upcoming AACR annual meeting in April. As a preview, MGC028 exhibited specific dose-dependent in vivo antitumor activity toward ADAM9 positive CDx and PDX models, including in gastric, lung, pancreatic, colorectal, and head and neck cancers. MGC028 was well tolerated in a repeat dose nonhuman primate toxicology study up to 55 milligrams per kg, the highest dose level tested. Of note, ocular toxicities that are typically seen with maytansinoid payloads, and which we observed in our IMGC936 cinemalogous toxicology study, were not observed in the MGC028 pilot toxicology study. We plan to present more preclinical data on this asset at AACR. We currently anticipate submitting an investigational new drug or IND application for MGC028 by the end of 2024. In addition, beyond MGC026 and MGC028, we are exploring additional molecules for potential future IND submission. Stay tuned. Finally, enoblituzumab is an Fc-optimized monoclonal antibody that targets B7-H3. Our academic collaborators have initiated an investigator-sponsored randomized translationally intense Phase II investigator-sponsored study of enoblituzumab in up to 219 men with prostate cancer. The HEAT study will evaluate the activity of neoblituzumab, given prior to radical prostatectomy in men with high-risk localized prostate cancer. Eligible patients will undergo a pretreatment prostate biopsy and conventional imaging, both CT and bone scan, as well as PSMA PET and optional prostate MRI as per institutional preferences. To conclude, we believe we have 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.

Our first question comes from Jonathan Chang with Leerink Partners. Your line is now open.

Hi guys, thanks for taking my questions. First question, can you help set expectations for the preliminary TAMARACK data coming up at ASCO? And then second question, can you discuss the rationale behind expanding the TAMARACK study to include patients with non-small cell lung cancer, small cell melanoma, head and neck and anal cancer, what is informing this decision? Thank you.

Thank you so much, Jonathan. As you've heard me previously, we had taken an evaluation of our own data that published recently by Daiichi on the 7300 molecule at ESMO this past fall and other data that was out there with regard to activity against prostate cancer. And with that, as I have noted and which we have not changed the ranges that we were seeing, just to recall, we saw about half the patients in our 3 mg per kg of Q3 weekly dosing of vobra duo in our expanded approximately 40-patient cohort of about half those patients reducing PSA50 from baseline. Given the dosings right now of 2.7 Q4 and 2 Q4 and with expectations if the safety is improved as we expect, we should be actually delivering as much or more of the 2.7 mg Q4 as compared to historical treatment with the 3 mg Q3. As a result, we expect the PSA50 to be in a similar range somewhere between 40% and 60% PSA50 reduction. With regard to overall response rate, again, as we had previously presented, approximately a quarter of the patients achieved both confirmed and unconfirmed responses, and this was similar to that, which was reported by Daiichi of 25%. So our expectation is we should be 25% or greater. With regard to rPFS, which is the primary endpoint of the study and a very important one in terms of prolonging both the life and the quality of life of these patients. Daiichi reported 5.3 months of rPFS. And what we have said is that we expect to have at least 6 or greater in terms of rPFS going forward. Now with regard to the specific tumor types, we have selected four study in these expansions, again taking advantage of our own experiences of treatment of patients with a subset of these tumors as well as the histology and expression of B7-H3 on these tumor types, we think these are very promising tumors to pursue. I should also point out, while we are expanding into five different tumors now, we are also considering additional tumors in the future to conduct studies.

Understood. Maybe just a clarifying question on that. So the decision expanding the study to include these other tumor types, this is based on your own internal data or data you're seeing in the competitive landscape or both?

I would say both. Clearly, based on our experience in small cell cancer, where both Daiichi and other companies have observed significant activity, we recognized the need to include this type of cancer. We haven't had the chance to test it in patients with small cell cancer yet, making it an obvious choice to add to our list. The other types were selected based on our own experiences and preclinical research we conducted on these targets. However, we're not strictly limited to just these five; we are also exploring additional opportunities where vobra duo could add value.

Thank you. One moment for our next question. Our next question comes from Kelsey Goodwin with Guggenheim. Your line is now open.

Hey, guys. Thanks for taking my question. First, regarding the ASCO abstract, what should we expect to be included in there? Will it just be safety? Or will preliminary efficacy data also be in the abstract? And then secondly, could you just remind us how patient enrollment tracked throughout 2023 and how we should think about follow-up on the 177 patients in the full ASCO presentation? Thank you.

Thank you, Kelsey. Due to timing, and I will talk about enrollment shortly, it became clear that we needed a cut-off date in January for data submission in early February at ASCO. Consequently, we mainly depended on safety data for the abstract, while also planning to present clinical efficacy data as we gathered more information closer to ASCO. To clarify why these decisions regarding the presentations were made, with the amendment of the original TAMARACK study, we started enrolling a few patients at the end of the second quarter. However, it turns out that two thirds of the 177 patients were enrolled between the latter half of the third quarter and the first half of the fourth quarter. Therefore, there wasn't enough time to gather data on efficacy, which is why we decided to focus on safety data in the abstract.

Perfect. Thank you so much.

Thank you. One moment for our next question. Our next question comes from Stephen Willey with Stifel. Your line is now open.

Good afternoon. Thank you for taking my question. I would like to follow up on the enrollment dynamics you just mentioned, Scott. Can you clarify whether the influx of patients in the second half of 2023 came mainly from newly opened sites or from sites where the treating investigator had ample experience with the drug?

Thank you for the question, Steve. As we've discussed previously, the initial sites with the new amendment were in the U.S., but those were few, while most sites were in Europe. With the amendments approved for European sites later in the year, we had the chance to begin enrollment at many locations. The speed of enrollment exceeded our expectations, and we ended up with about a third of the intended number of sites never opening due to the rapid enrollment at the newly opened sites. Although U.S. sites are still enrolling, the majority of enrollments occurred in Europe during that surge in the second half of the year.

Okay. So just to clarify, these were new sites that came online in Europe? Or were these sites that had already enrolled...

No, the regulatory timing for getting the amendment approved was after that of the U.S. As a result, it happened after the U.S. began enrolling these patients, with the majority coming from Europe due to the large number of sites available there.

Okay. Understood. And then I guess, in kind of baking off the 2.7 and 2.0 q4W doses, I mean, I know you just referenced 2.7%. Is it safe to say that you guys have settled on a go-forward dose at this point? And would there be any need to evaluate both dosing regimens as you expand into some of these additional tumor types?

I think it's too early to have a final answer on that. Clearly, we want to continue to follow the safety as well as the ultimate activity. And as I alluded to in my earlier remarks, the expectation, for instance rPFS won't occur until after the midyear. So I think we will have to see the totality of data to be definitive about which one goes forward. But as pointed out in the comments earlier, the data safety monitoring committee in January looking at the safety at the time and the activity at the time that was available in January concluded that both doses should continue. So I think it will be a decision that we will arrive at by midyear.

Okay. And then last question, is the maturity of that rPFS statistic rate limiting to your ability then to initiate these additional dose expansion cohorts?

No, no. That will not slow that down at all. We are working both from a regulatory advantage and operationalizing this so that we can get going by midyear.

Thank you. One moment for our next question. Our next question comes from Etzer Darout with BMO Capital Markets. Your line is now open.

Great. Thanks for taking the question. Just a couple for me here, too. Just thinking about the monotherapy vobra duo study. Just if you can maybe start just describing what your thoughts around sort of the pivotal path for development for that in terms of monotherapy or in combination based on what you're observing from TAMARACK so far? And whether or not any of sort of the recent data sets that have come out in prostate sort of maybe changes the dynamic of how you're thinking about pivotal development of vobra duo? Thanks.

Thanks, Etzer. Again, I won't comment on the activity from the TAMARACK study that will come out at ASCO. But obviously, looking at the landscape, what is necessary to get a high confidence for a regulatory approval, I think we are in a fortunate position now that with the 177 patients dosed, and what I have commented on earlier that we had a sizable number of patients that were both chemotherapy experienced, as well as chemotherapy naive in this study. So while we entered into the study with the idea that any Phase III study would likely to be done in a post-chemo experience population, we have now changed that view that, clearly, in a chemo-naive population if both the efficacy and the safety warranted, that seems to be a very suitable population, an early along population to pursue. And we can also pursue the late line as well. So we still have everything open at this point. But until we have the more mature data, we won't make that decision.

Thank you. One moment for our next question. Our next question comes from Yigal Nochomovitz with Citigroup. Your line is now open.

Hi, Scott and Jim. Thank you. Just to clarify. So for the ASCO abstract, it seems like you're just going to be focused on the safety, but in the presentation at the conference itself, should we expect to see any initial radiographic PFS data or not?

So thank you very much, Yigal. So clearly, we will show as much efficacy data as possible at the cutoff time. Likely this is going to be a month, a month and a half before the submission is ready for presentation. So as you know, the meeting itself is the end of May, I would presume that they will require us to have the material prepared by mid-May. So my expectation would be that there would be a cutoff date sort of late March, early April. With that, we will clearly have a lot of data available on patients that have been dosed for many months. So that would include, obviously, PSA50 reductions. We will look at overall response rates, a full dataset, obviously, a full dataset with safety. With regard to our rPFS, we'll have to see how many patients have been dosed for how long to see if we can do some at least preliminary cuts on rPFS. It may require us to wait until the next meeting in the early fall to update that. But we certainly will provide as much data as we can.

Okay. Thanks. And then a moment ago, you referenced the PFS of at least 6 months, this would be the expectation. I'm just wondering for some of these other comps out there, which we're all familiar with the CARD trial and the VISION trial for cabazitaxel and pluvicto, respectively. As you know, those were slightly higher around 8 and 8.5 months. Are those reasonable expectations or not for what one should expect for TAMARACK?

Yes. And again, it will depend on whether we go into the chemo-naive population or chemo-experienced and how late line we would do those studies. So that's why it's a little broad. If you look at the controls for the studies that you described, it obviously will depend on what the controlled drug is. The typical ones, for instance, for in the chemo-naive population were docetaxel for around 8 months. And similarly, in the activity for the CARD study was about 8 months. So yes, I think that, again, which population you ultimately look at would require more than just 6, it would be 8 or higher. And certainly, I just don't want to limit what this drug could potentially achieve. We just don't know the answer yet. I was just pointing out the base minimum particularly on a later line population would be at least 6 months.

Thank you. One moment for our next question. Our next question comes from John Miller with Evercore. Your line is now open.

Hi, guys. Thanks for taking the question. I would love to ask about those additional indications that you're moving vobra duo into in the TAMARACK study. Do you have any additional data from any of those indications in the Phase I expansion that we haven't seen at this point? And obviously, we've seen a lot of interest in these indications with B7-H3 more broadly. But previously, you had said you were prioritizing prostate for bandwidth reasons and to sort of competitively be in white space there. So can you talk us through a little bit about what changed and why your decision to chase out for those indications coming now? And then secondly, I'd love if you could go in a little bit deeper into your differentiation of the new 026 B7-H3 ADC from the other topo1 payload ADCs against the same targets that are in development?

Thanks so much, John. Yes. So as you well know, while we've been focusing on prostate cancer because of bandwidth, which is correct. As you may recall, about 2 years ago, we were intending to do an expansion as further expansion in melanoma but had to cut back because of cash at that time. So that was clearly a population that we had a strong interest in. We also had seen in the expansion studies, very good activity in other indications. So things like non-small cell lung cancer became a great opportunity to us, activity in head and neck cancer as well. We have not had any experience with anal cancer with the vobra duo and small cell is obvious as I alluded to before, based on others' experience there. So those are the initial reasoning behind going after this. And we believe that with the improved potential safety profile of the new dosing regimen, these patients with these other cancers will be able to stay on the drug longer to have potentially good outcomes. And that's why we're looking to expand into those indications. Now with regard to MGC026, as I pointed out, this is a great opportunity for us to really take an important answer important questions and a great opportunity for treating a wide range of cancers. As you are well aware, different chemotherapies work in different tumors and combination chemotherapy as well as combinations with other modalities is the typical standard of treatment for cancer. And so given that we've had wonderful experience with the variable domain of vobra duo in its activity and what we believe to potentially be a superior topo1 inhibitor payload based on the Synaffix profile. And as I pointed out from various vantage points, including increased activity, potency, less susceptibility to efflux multidrug resistance, better cell permeability by standard effect. And the fact, as Daiichi has pointed out, many of the institutional lung disease complications they are ascribing to binding to alveolar macrophages and by the fact that this Synaffix platform eliminates the binding through Fc receptors, as well as mannose receptors, one shouldn't potentially have the ability to reduce an ILD effect with a topo1 inhibitor. So from all these vantage points and from all the things that I described earlier, looking at the ability to treat with vobra duo, looking at potential combinations with MGC026 down the line, looking at treatment of different tumors, I think this provides us with a great opportunity.

Thanks, Scott. Have we seen all of the data from the various other indications that you were looking at in Phase 1 before you put those on hold?

Yes, we have not. And at a future date, we will put all that data together for publication. So yes, at a future time. But there is data yet to be presented.

Thank you. One moment for our next question. Our next question comes from Kaveri Pohlman with BTIG. Your line is now open.

Good evening. Thanks for taking my questions. For the upcoming readout, you will have vobra duo data for both docetaxel naive and experienced patients. But since you are not going to have mature rPFS data until second half, how are you thinking about making a decision on where to go in terms of a Phase III trial?

Well, a good question, Kaveri. Clearly, there will be other metrics that we will be looking at beyond just the rPFS, but there will be a certain number of those patients that will have advanced. We certainly would like to have the full dataset to make a final decision. But I think by midyear, we'll know quite well if we're on track for moving forward to a Phase III point. And obviously, we don't want to wait until the last minute because operationally, there's a lot to do, not the least of which is engagement with regulatory agencies to describe plans and get feedback there. So we would just want to be as aggressive as possible once we have at least a large body of data available to us by midyear.

All right. That's helpful. And then my second question is regarding MGD-024. Any color on when you expect to complete the Phase I trial? And how much time Gilead will have to make a decision to opt in once you provide the data?

With respect to MGD024, we are currently in the dose escalation phase. As you're aware, regulatory agencies have imposed strict guidelines on the pace of this escalation for bispecifics that utilize T cell redirected killing mechanisms. This has been a significant limiting factor for us. I can't predict the outcome at this stage. We have completed several cohorts and are advancing as quickly as possible. Gilead will have a short period after we deliver the complete Phase I data to opt into the program. There is still time for them, and they retain the option to opt in during the dose escalation phase if they choose to do so.

Thank you. One moment for our next question. Our next question comes from Tara Bancroft with TD Cowen. Your line is now open.

Hi, good afternoon. I understand the rationale for potentially enabling broad development of vobra duo with the inclusion of Pretaxane patients. However, I'm interested in what details you will provide in the presentation regarding baseline characteristics. Specifically, will you include the time to progression on initial therapy? I may have a follow-up question based on your answer.

So we will clearly try to provide as detailed data as possible on that population. I don't know how many of the patients we have that data in the database in terms of their time to progression. We'll have to go back and look at that and update you at a future date. I just don't know that off the top of my head of how many of those patients we have that data.

Okay. Yes, thanks. So you're not excluding rapid progressors, right? And if not, how would you expect them to affect rPFS? Like is that where your 6th month versus 8 month expectations come from are those patients?

I think you've hit the nail on the head, and that's why I'm trying to give a little bit broad brush strokes on that on understanding the patients. The rapid progressors are allowed here as we opened up, for instance, the study, the original design of the study required at least 12 months of treatment on an ARAT to be qualified for enrollment in our study. And when we remove that requirement, clearly patients who had very short courses and progressed quickly, as well as very newly diagnosed patients before they got their initial treatment presented as metastatic disease. These are the type of patients that could have a much more aggressive course and a shorter time to any treatment. So that is why we have gotten actually also feedback from key opinion leaders that having a baseline of 6 months is not unreasonable for that type of patient.

Okay. Thank you so much.

Thank you. One moment for our next question. Our next question comes from Courtney Kowalsky with Barclays. Your line is now open.

This is Pete Lawson from Barclays. I have a couple of questions. First, could you provide details on safety, specifically regarding discontinuation rates and side effects? I have a follow-up question as well.

Peter, you will have the discontinuation rates as of that cut-off January data. With regard in the abstract itself, I don't recall specifically how deep in terms of the breakdown of the AEs were? I have to get back to you on that.

Got you. Thank you.

And then in the TAMARACK study, patients have been exposed to radiopharmaceuticals such as Pluvicto.

And will you be able to break that out eventually?

Yes. Unfortunately, they are allowed in the study, but given the timing of the study, and as I pointed out, the majority of these patients came from Europe, the actual availability of vobra duo and the timing didn't work out to get those Pluvicto progressors and experienced patients there. We expect a few of them from the U.S., but very small numbers there.

Okay. And then just a quick question for Jim on the puts and takes around the cash guidance just with the expansion of the B7-H3 clinical trials kind of I guess that's a negative for cash, but what are the puts and takes we can be thinking about for you to maintain that cash guidance?

Yes. Thanks, Peter. Thanks for the question. So our guidance of cash runway into 2026 reflects the additional cohorts under the TAMARACK umbrella, the digital vobra duo cohorts. So everything we're talking about, all of these studies that we're currently running and talking about running are included as part of our guidance.

Got you. And are there any additional inflows of cash you're thinking through to kind of counterbalance that? Was that always in the cash guidance?

Those cohorts are new to the guidance. There have been some savings. There's always a possibility of additional business development activities. And of course, with $1 billion milestones hanging out there related to both TZIELD and ZYNYZ, which we've handicapped significantly, we would anticipate recognition of some of those over the next couple of years.

And there were some additional revenues coming in that weren't anticipated originally that are part of this guidance. So...

Great, okay. Thank you so much. Thanks for the clarity.

Thank you. One moment for our next question. Our next question comes from Silvan Tuerkcan with Citizens JMP. Your line is now open.

Thank you for taking my question, and congratulations on the progress. Building on the previous question, what are the criteria for the safety profile in the abstract or at the ASCO presentation compared to the safety profile we've observed with the older doses? I'm particularly interested in the grade 3 or higher issues we've encountered. Can you comment on what improvements you're aiming for? Is there a standard that gives you confidence moving forward? I have a follow-up as well.

Sure, Silvan, I want to clarify that our concern wasn't with Grade 3 hand-foot syndrome, as we want to avoid that, but its occurrence was quite low. The main issue was that patients experiencing Grade 2 symptoms, such as pain, chose to discontinue treatment even though they were seeing antitumor benefits. Our top priority is to completely reduce the incidence of these issues. Additionally, our goal is to help those with reduced symptoms to prevent them from escalating from Grade 1 to Grade 2. Regarding neutropenia, it likely stems from free toxin affecting the bone marrow. However, this was primarily a laboratory finding and did not lead to an increase in infections or serious neutropenia. It's mostly managed by pausing or stopping the drug. If we can lower both the incidence and severity, that would be an improvement, but it wasn't a significant concern for the doctors treating these patients.

Thank you. And maybe about the LORIKEET study, will we get data from that study this year? And maybe how does that relate to your late-stage monotherapy plans if you get data from the combo of what we do in lorigerlimab?

We will provide an update on the study soon. The timing depends on how quickly we can enroll patients over the next two months. We might exceed our enrollment plan, or it could take longer, which would delay full enrollment until later this year. If that happens, we expect to have a more comprehensive update in early 2025. We will have more guidance later this year based on the enrollment rates. Regarding the success of the trial, we are testing it in patients who have not received chemotherapy, in combination with docetaxel. If the trial is successful, it would be beneficial if vobra duo also works in that therapy line. We are not ruling out the possibility of looking at LORIKEET and Lorigerlimab for late-stage prostate cancer, which is something we will consider. Additionally, we plan to explore Lorigerlimab outside of prostate cancer moving forward. It is too soon to make decisions on registration studies until we receive the data.

Thank you. Our next question comes from Yigal Nochomovitz with Citigroup. Your line is now open.

Thank you so much for taking the follow up. Scott, I just had a quick follow-up on TAMARACK; it's unusual that you see a trial that's 77% over-enrolled relative to the target and enrolled very quickly. Could you just comment on some of the factors that resulted in the heavy over-enrollment and as well as the speed to which it was over-enrolled. Thanks.

Yes. In deciding to allow more patients into the study, we believed it was unethical not to include those who had already passed the screening criteria. We felt compelled to proceed with this approach, especially since both the patients and the investigators had put in significant effort to identify candidates for the study. As I mentioned earlier, there was a remarkable increase in enrollment once we received approval for the amended protocol in Europe, and there was a strong motivation to participate in the study. There are likely various factors at play; some amendments allowed for patients who did not need to have 12 months of treatment on an ARAT to enter the study, enabling those who were progressing rapidly to join, especially since they might not have many alternatives available. Additionally, we found a substantial number of patients who were unable to qualify for docetaxel or chemotherapy, or who chose not to pursue those options, which helped us attract a significant number of chemo-naive patients into the study.

Thank you. I'm showing no further questions at this time. I would now like to turn it back to Scott Koenig for closing remarks.

Well, thank you very much for participating in the call today. We look forward to obviously updating you at ASCO in the near term and talk to you at future times on earnings calls and in other venues. Thank you very much.

This concludes today's conference call. Thank you for participating. You may now disconnect.