MacroGenics, Inc.

We will begin the Macrogenics 2023 Fourth 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 Carrolls, Senior Vice President, Chief Financial Officer of Macrogenics.

Thank you, Operator. Good afternoon and welcome to the 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 two 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 this 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. It should not be relied upon as representative 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. 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 a 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, margins and 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 end of December 31, 2022. This decrease was primarily due to decreased manufacturing-related costs for VOGR Duo, decreased development and clinical trial costs related to margituximab, and decreased costs related to discontinued studies, partially offset by increased expenses related to MGC 026 and MGC 028 development. Scott will tell you about these two ADC product candidates in a few minutes. 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 March. In addition, we received a $50 million milestone payment from Sanofi related to the achievement of a primary endpoint in a TZILD clinical study. Under GAAP guidelines and pursuant to Financial Accounting Standards Board Accounting Standards Qualification, or ASC 470, this combined $150 million was included in other income as a, quote, gain on royalty monetization arrangement, unquote, in 2023. Our net loss was $9.1 million for the year end of December 31, 2023, compared to a net loss of $119.8 million for the year end of December 31, 2022. Our cash equivalence 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 II lorikeet study of lorigerlumab 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. I will 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-volutive capital. This includes $215 million from prevention, DRI, Sanofi, in connection with T-ZEAL, $75 million from Gilead, and $45 million from Insight in connection with Zinus. Okay, on to our pipeline. Boverimidimab duocarmazine, or Bover Duo, is our ADC designed to deliver DNA-alkylating durocomycin cytotoxic payload to tumors expressing B7H3. B7H3 is a member of the B7 family of molecules involved in immune regulation. Bover 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 II study of VOBRDUO under a modified study protocol during the second quarter of 2023 and completed enrollment of the study in November, months ahead of the schedule. In fact, 177 patients received VOBRDUO in this study exceeding the study design goal of 100 participants. As a reminder, Tamarac 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. Participants may have received up to one prior taxane-containing regimen, but no other chemotherapy agents. This study is being conducted to evaluate VOBRDUO in patients across two experimental arms of either 2 mg per kg or 2.7 mg per kg every four 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 lorigerolimab, our bispecific tetravalent PD-1 by CTLA-4 DART molecule. We designed lorajerolimab 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 Lorakeet study, a randomized phase two clinical trial of lorajerolimab 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 two-to-one 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 a VOBRDUO in combination with lorajerolimab 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 an anti-tumor cytolytic activity and permitting intermittent dosing through a longer half-life. Our phase one dose escalation study of MGD024 is ongoing in patients with CD123 positive relapse or refractory immunologic malignancies, including acute myeloid leukemia and myelodysplastic syndromes. Recall that Gilead has the option to license MGD-024 at predefined decision points during the Phase I 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 mentioned on prior calls, we have been developing preclinical ADC molecules utilizing linker payload technologies we licensed from Cinefix. The first of these is MGC026, a clinical ADC incorporating a B7H3 targeting antibody and a novel topoisomerase-1 inhibitor-based linker payload, Syntecan-E. This cleavable linker payload is based on Exotecan, a clinically validated and potent cancer thecan that readily combines with Synefex hydrospace technology. We believe Synefix's approach potentially provides advantages vis-a-vis other topoisomerase-1 inhibitor-based ADCs. In fact, Exotecan appears to be more potent and less susceptible to multi-drug resistance mechanisms than other TOP1 inhibitors, such as SN38 and Durexatecan. Additionally, site-specific conjugation of Synefix to the normally glycosylated amino acid in the FC domain abolishes FC gamma receptor and MANOS receptor binding, which contribute to non-targeted uptake of ADCs in alveolar macrophages and reported to be associated with lung toxicity and therefore may provide a safety benefit for patients. The variable domain of the molecule targeting B7H3 is the same sequence contained in VOBRDUO. We recently initiated a phase one dose escalation study of MGC026. We view MGC026 as a complementary approach to VOBRDUO for targeting B7H3. More specifically, we believe that having distinct mechanisms of action, VOBRDUO 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 B7H3 pathway, viewing our Topo1 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's a preview of what you'll see. In preclinical studies, MGC026 exhibited a favorable profile with potent in vivo activity toward B7H3 expressing tumor xenografts representing a range of cancer indications. MGC026 was tolerated in cinnamologous monkeys, a relevant toxicology model, at exposure levels exceeding those required for antitumor activity. We look forward to showing you the data set next month. In addition, we are readying a second toboisomerase 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 Cinefix's novel linker payload. Atom 9, or disintegrin and metalloproteinase domain 9, is a member of the atom family of multifunctional type 1 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. MGC028 is the second ADAM9 target ADC that we have pursued. The first was IMGC936, a molecule with a metansenoid payload that was advanced under 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 IMGC 936 as the molecule did not achieve our pre-established clinical safety and efficacy benchmarks. We plan to present preclinical MGC 028 data at the upcoming AACR annual meeting in April. As a preview, MGC 028 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. MGC-028 was well-tolerated in a repeat dose non-human primate toxicology study up to 55 milligrams per kg, the highest dose level tested. Of note, ocular toxicities that are typically seen when the tansanoid payloads and which we observed in our IMGC-936 cinnamologous toxicology study were not observed in the MGC 028 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 MGC 028 by the end of 2024. In addition, beyond MGC 026 and MGC 028, we are exploring additional molecules for potential future IND submission. Stay tuned. Finally, inoblituzumab is an FC-optimized monoclonal antibody that targets B7H3. Our academic collaborators have initiated an investigator-sponsored, randomized, translationally intense, Phase II investigator-sponsored study of inoblituzumab in up to 219 men with prostate cancer. The HEAT study will evaluate the activity of neoadjuvant nobutuzumab 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. Operator?

To ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster.

Our first question comes from Jonathan Chang with Levering Partners.

Your line's now open.

Hi, guys. Thanks for taking my questions. First question, can you help set expectations for the preliminary TAMRAC data coming up at ASCO? And then second question, can you discuss the rationale behind expanding the TAMRAC 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 the 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 Obra 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 Migs Q4 as compared to historical treatment with the 3 Migs Q3. As a result, we expect the PSA50 to be in a similar range, somewhere between 40 and 60 percent 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 is 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 this study, and a very important one in terms of obviously 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 six or greater in terms of RPFS going forward. Now, with regard to the specific tumor types we have selected for 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 B7H3 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 behind 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. Obviously, given the experience in small cell, for instance, where both Daiichi and Hanso have seen very nice activity in small cell cancer, we have not had that opportunity to test it in patients with small cell cancer. So this became a very obvious one to include among the five. I would say the others were based on our own experiences, as well as preclinical work that we had done against these targets. But again, we're not even limiting it to these five. We are also considering others, which would be very good opportunities for looking at the value of Oberduo.

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

Oh, 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 so much, Kelsey. Because of the timing, and I'll discuss enrollment in a second, so it became quite obvious. As I pointed out, we had to do a cutoff date in January. for the data submission in early February at ASCO. And as a result, we primarily relied on safety data to be included in the abstract, but also noting that our plan was to present obviously the clinical efficacy data as we were able to accumulate additional data closer to the time of ASCO. Again, to give you a sense of why these decisions were made in terms of the presentations, with the amendment of the original Tamarack study, we began to enroll a few patients in the end of the second quarter. But as it turns out, two-thirds of the patients, of the 177 patients, were enrolled between the second half of the third quarter and the first half of the fourth quarter. So not sufficient time was allowed to accumulate data regarding efficacy. And so that's why the decision was made to primarily include the safety data in the abstract.

Perfect. Thank you so much.

Thank you. One moment for our next question. Our next question comes from Steven Willie with Stifel.

Your line's now open.

Yeah, good afternoon. Thanks for taking the question. Maybe just to follow up on the enrollment kinetics you just referenced, Scott, can you just, I guess, speak or characterize as to whether or not those that bolus of patients that came in second half 3Q, first half 4Q, was that primarily across newly opened sites or were those across sites where the treating investigator had had sufficient experience with the drug?

Thanks for the question, Steve. So as we have spoken about it before, the initial sites with the new amendment that were opened were in the U.S., but the number of sites in the U.S. were small. The greatest number of sites were in Europe. And so with the approval of the amendments in the European sites later in the year, this created an opportunity for initiating enrollment in a large number of sites. And as we've discussed before, the rapidity of enrollment was far beyond what we expected. And in fact, we ended up probably, and don't hold me to the exact number, approximately a third of the sites that we intended to open were never opened because of the fast enrollment later in the year on these newly opened sites. U.S. sites continued to enroll, but just because of the proportion that were in Europe compared to Asia and the U.S., the majority got enrolled in Europe in that bolus 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?

Well, again, remember the regulatory timing for getting the amendment through was after that of the U.S. So it occurred after the U.S. started to enroll these patients. The majority came in in Europe. It was just the sheer numbers of sites 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?

You know, 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 to the, after the mid-year. 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'll be a decision that we will arrive at by mid-year.

Okay. And 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 mid-year.

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

Great. Thanks for taking a question. Just a couple for me here, too. Just thinking about the monotherapy, what we're doing, study, just you can maybe start just describing what your thoughts around sort of the pivotal path or 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, you know, sort of maybe changes the dynamic of how you're thinking about, you know, pivotal development of overduo. Thanks.

Thanks, Ed, sir. 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 dose, the bill 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-experienced population, we have now changed that view that, clearly, in a chemo-naive population, both the efficacy and the safety warranted, that seems to be a very suitable population, an early aligned 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.

Great. Thank you.

Thank you. One moment for our next question.

Our next question comes from Yagal Nakamovitz with Citigroup. Your line's now open.

Yeah, hi, Scott and team. 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 TFS data or not?

So thank you very much, Igal. So clearly we will show as much efficacy data as possible at the cutoff time. You know, 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 or 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 PSA 50 reductions, would look at overall response rates, you know, a full data set, obviously a full data set with safety. With regard to 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 six months 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, cabezotaxel and clovicto, respectively, As we know, those were slightly higher around eight and eight and a half months. Are those reasonable expectations or not for what one should expect for Tamarack?

Yeah, and again, it'll depend on whether we go into the chemo-naive population or chemo experience 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, You know, it obviously will depend on what the controlled drug is. The typical ones, for instance, for in the chemo-naive population was docetaxel for around eight months. And similarly in the activity for the CARD study was about eight months. So, yeah, I think that, again, which population you ultimately look at would require, more than just six, it would be eight or higher. And certainly, I just don't want to limit what this drug could potentially treat. 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 six months.

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

Hi, guys. Thanks for taking the question. I would love to ask about those additional indications that you're moving Vover Duo into in the Tamarack study. Do you have any additional data from any of those indications in the Phase 1 expansion that we haven't seen at this point? Obviously, we've seen a lot of interest in these indications with B7H3 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 after 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 B7H3 ADC. from the other TOCO1 payload ADCs against the same target 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 two years ago, we were intending to do an expansion, a further expansion 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 VOBR duo. And small cell was as 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 drug longer to have potentially good outcomes. And that's why we're looking to expand into those indications. Now, with regard to 026, 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 VOBR duo in its activity and what we believe to potentially be a superior TOBO1 inhibitor payload based on the Cinefix profile. And as I pointed out, from various vantage points, including increased activity, potency, a less susceptibility to efflux multidrug resistance, a better cell permeability bystander effect. And the fact, as Daiichi has pointed out, many of the interstitial lung disease complications, they are ascribing to binding to alveolar macrophages. And by the fact that this Cinefix platform eliminates the binding through FC receptors as well as mannose receptors, one should potentially have the ability to reduce a ILD effect with a topo-1 inhibitor. So, from all these vantage points and from all the things that I described earlier, looking at the ability to treat with VOBRDUO, looking at potential combinations with O26 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 one before you put those on hold?

We have not. Yeah, 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 Pullman with BTIG. Your line is now open.

Yeah, good evening. Thanks for taking my questions. For the upcoming readout, you will have OBRA 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 three trial?

Well, a good question, Kaveri. You know, 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 data set to make a final decision, but I think by mid-year we'll know quite well if we're on track for moving forward to a of phase three 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 mid-year.

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

So with regard to 024, as I was commenting, we are in the middle of dose escalation. As you know, for T cell redirected killing mechanisms for bispecifics, the regulatory agencies have been very strict on the rate in which one can do the dose escalation. And so that's really been what the most limiting factor here. So I can't tell you what the end will be. We are through many cohorts of groups and continuing up as quickly as possible. With that, Gilead hasn't, you know, until a short period of time after we present the full phase one data to them to opt in on the program. So, clearly, there's still time. And clearly, if during the dose escalation, if they decide they want to opt in, they have the right to do so.

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

Hi. Good afternoon. So I understand the rationale for potentially enabling broad development of Ogaduro with the inclusion of pre-taxane patients. But I'm curious what details you will give us in the presentation about baseline characteristics. And in particular, will you include time to progression on initial therapy? And I have Depending on your answer, a follow-up on that.

So, you know, we will clearly try to provide as detailed 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. Yeah, 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 six-month versus eight-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 brushstrokes on that. on understanding the patients, rapid progressives 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 removed 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 course to any treatment. So that is why we have gotten actually also feedback from KOLs that having a baseline of six 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 Kowalski with Barclays. Your line's now open.

Hey, this is Pete Lawson from Barclays. So just a couple of questions. Firstly, in the abstract, will we see safety that's broken out by discontinuation rate and or side effects such as hand foot, pleural effusion, and have we got a follow-up?

Peter, you will have the discontinuation rates as of that cut of 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'll have to get back to you on that.

Thank you. And then in the Temarec study, have patients been exposed to radiopharmaceuticals such as Plavicto? And will you be able to break that out eventually?

Yeah, 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 Plavicto and the timing didn't work out to get those Plavicto and experienced patients there. We expect a few of them from the U.S., but very small numbers there.

And then just a quick question for Jim on the puts and take around the cash guidance. Just with the expansion of the B7H3 clinical trials, I guess that's a negative for cash, but what are the puts and takes we should be thinking about for you to maintain that cash guidance?

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

Gotcha. Are there any additional inflows of cash you're thinking through to kind of counterbalance that? Or was that always in the cash guidance?

Peter, I'm sorry, could you repeat the question, please?

Oh, is there any additional cash inflows that you're thinking of through? Or were those cohorts always in the cash guidance?

Those cohorts are new to the guidance. There have been some savings. There's always the possibility of additional business development activities. And of course, with a billion dollars in milestones hanging out there related to both T-Zield and Zinus, of 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.

Great. Okay. Thank you so much. Thanks for the clarity.

Thank you.

One moment for our next question. Our next question comes from Sylvan Turkin with Citizens JMP.

Your line is now open.

Thank you. Thanks for taking my question and congrats on the progress. Maybe piggybacking a little bit on a previous question. What's the bar for the safety profile in the abstract or also at the ASCA presentation versus the safety profile that we've seen on the older doses? And I'm asking in particular maybe on the grade three or higher issues that we've seen with the hand-foot map signal and perhaps neutropenia. Can you just comment on what you're trying to improve? And is there any bar that makes you confident in the

future here thank you and I have a follow-up sure Sylvan I just want to correct you our concern was not grade three hand foot obviously we want to avoid that at all though the incidence of that was quite low the issue was is that patients would be the grade with grade two where they have experiencing pain would be electing to come off treatment despite the fact that that they were having anti-tumor effects. And so number one is the most important is that we can decrease the incidence totally. And then for those that have with a reduced incidence, converting or preventing them from going from grade one to grade two would be what our goal is there. With regard to the neutropenia, clearly that is something most likely due to free toxin getting to the bone marrow. But again, this is a situation where it was largely a laboratory value. It did not result in increased infections or febrile neutropenia. And so this is mostly handled by holding the drug or stopping the drug. And again, if we can reduce that both in terms of incidence and grade, I think that will be better. But that wasn't as concerning to the treating physicians in managing these patients.

Great. Thank you. And maybe about the Laurie Keat study, will we get data from that study this year? And maybe how does that relate to your late-stage monotherapy plans, you know, if you get data from the combo of what we're doing in Lugerla-Mann?

With regard to the timing of this, we'll provide, as I said earlier, an update on the study. It ultimately will depend on the speed in which we can enroll these patients. Clearly, over the next two months, will we exceed the plan or will it take longer, meaning later in the year, to get full enrollment of this study? If it's the latter, it's more likely we'll have a more fulsome update in early 25, but again, be able to give you a little bit more guidance later in the year based on enrollment rates. With regard to the success in this trial, clearly we're testing this in the chemo-naive population in combination with docetaxel. I think that if that trial is successful, it's a great problem to have if the VOBR duo pans out also in that same line of therapy. I should also say that we are not eliminating the possibility that we're going to look at laurogerolimab in later line prostate cancer. That is certainly a possibility to consider. But as I have said before, we are also going to look at laurogerolimab outside of prostate cancer going forward. It's just too early to make a decision on registration studies until we have the data.

Great, thank you.

Thank you. As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Our next question comes from Yagal Nakamovitz with Citigroup. Your line's now open.

Oh, hi. Thank you so much for taking the follow-up. Scott, I just had a quick follow-up on Tamarack. You know, 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 the speed to which it was over-enrolled? Thanks.

Yeah, so with regard to our decision on letting so many more patients into the study, is we felt it was not ethical for us to not allow these patients into the study if they had already been in screening and passed the screening requirements. And so we felt that we should do this because the patients made a, and the investigators made great efforts to find patients in the study. As I was commenting on earlier, you know, the surge of enrollment, once we had the go-aheads from the amended protocol in Europe, there was tremendous enthusiasm to join the study, and I'm sure there are a lot of different reasons. As I was pointing out, some of the amendments included the fact that we didn't require 12 months of treatment on an ARAT, and so patients who were progressing quickly were able to join the study, and they probably did not have much in terms of other alternatives. There also, it turns out, to be a large number of patients for varying reasons, whether they're not qualified to go on docetaxel or chemotherapeutic or they choose not to. I think we attracted a large number of those patients into the study that allowed us to have a very sizable subpopulation of chemo-naive patients.

Got it. Thank you very much.

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.