MacroGenics, Inc.

Good afternoon. We will begin the Macrogenics 2024 third quarter corporate progress and financial results conference call in just a moment. All participants on our list are in 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 Carroll, Senior Vice President, Chief Financial Officer of Microgenics.

Thank you, operator. Good afternoon and welcome to Macrogenics conference call to discuss our third quarter 2024 financial and operational results. For anyone who has not had the chance to review these results, we should have 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'd like to alert listeners that today's discussion will include statements about the company's future expectations, plans and prospects that constitute for 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 for looking statements as a result of various important factors, including those discussed in the risk factor section of our annual quarterly and current reports filed with the SEC. In addition, any for looking statements represent our views only as of today. It should not be relied upon as representing our views as of any subsequent date. While we may elect to update these for 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 quarter end of September 30, 2024, which highlight our financial position. As described in a release this afternoon, Macrogenics total revenue was $110.7 million for the quarter end of September 30, 2024, compared to total revenue of 10.4 million for the quarter end of September 30, 2023. The increase was primarily due to $100 million in milestones received from Insight in August related to Reddit FamilyMap. Our research and development expenses were $40.5 million for the quarter end of September 30, 2024, compared to 30.1 million for the quarter end of September 30, 2023. The increase was primarily due to increased research and development costs related to the company's preclinical ADC pipeline, Vograd Duo, and the Tamarack clinical trial. Our selling general administrative expenses were $14.1 million for the quarter end of September 30, 2024, compared to 12.4 million for the quarter end of September 30, 2023. The increase was primarily due to increased stock-based compensation expense and professional fees. Our net income was $56.3 million for the quarter end of September 30, 2024, compared to net income of 17.6 million for the quarter end of September 30, 2023. Net income for the quarter end of September 30, 2024 included the aforementioned $100 million in milestones from Insight. Net income for the quarter end of September 30, 2023 included a $50 million milestone payment from Sanofi related to the previously disclosed achievement of a primary endpoint in a TZL clinical study, which was recorded in other income. Our cash, cash equivalents, and marketable securities balance as of September 30, 2024 was $200.4 million, compared to $229.8 million as of December 31, 2023. The balance of September 30, 2024 did not include the $40 million upfront payment anticipated from the closing of the Mergenza transaction or the $8 million amendment fee we plan to pay our current commercialization partner. Finally, in terms of our cash runway, consistent with our prior guidance, we anticipate that our cash, cash equivalents, and marketable securities balance of $200.4 million as of September 30, 2024, plus the $40 million upfront payment anticipated from Tercera related to the Mergenza transaction less an $8 million amendment fee we expect to pay our current commercialization partner. In addition to projected and anticipated future payments from partners should provide a cash runway into 2026. Our anticipated funding requirements reflect expected expenditures related to the ongoing phase two Tamarack and Lorekeep studies, 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 I will walk you through each of our key programs. Vobor Minimab Duocarmosine, or Vobor Duo, is our ADC designed to deliver a DNA alkylating Duocarmosine cytotoxic payload to tumors expressing B7H3. B7H3 is a member of the B7 family of molecules involved in immune regulation. Vobor Duo is designed to take advantage of this antigen's broad expression across multiple solid tumor types. We continue to believe B7H3 has the attributes of an ideal cancer target. The Tamarack phase two study is being conducted in MCRPC patients who have previously received an androgen receptor access targeted agent and up to one prior taxing containing regimen, but no other chemotherapy. While study participants are no longer being dosed in the trial, participants continue to be monitored for adverse events, disease progression, and survival. The study's primary endpoint is radiographic progression-free survival, or RPFS. Given that only 65 PSF events, or 35.9%, had accrued as of the July 9th, 2024 data cutoff, the interim median RPFS estimates presented at the ESMO Congress in September were immature. And because these results were immature, we believe they are likely to change as additional events accrue. We expect to have mature median RPFS in hand no later than early 2025. Assessment of future development alternatives for Vobor Duo will be based on several factors, including the final Tamarack safety and efficacy data in MCRPC, a review of the competitive treatment landscape for MCRPC, resource allocation across our clinical portfolio, as well as potential partnering opportunities for Vobor Duo. Until we complete our assessment of the monotherapy development opportunity in MCRPC, we have paused our other development efforts in alternative tumor types, as well as the phase one two dose combination study of Vobor Duo plus Lauradurumab. Recall that we have two other clinical molecules that target B7H3. The first, MGCO26, is an investigational ADC incorporating a novel Tobol isomerase I inhibitor-based linker payload, -TKAN-E, which we licensed from Cinefix. Our second additional B7H3-directed molecule is Anoblutuzumab, the investigational FC-optimized monoclonal antibody. MGCO26 incorporates a linker payload based on X-TKAN, a clinically validated and potent Camtothecan that readily combines with Cinefix's hydrospace technology. We initiated a phase one dose escalation study of MGCO26 early this year in patients with advanced solid tumors. The variable domain of the molecule targeting B7H3 for MGCO26 is the same sequence contained in Vobor Duo. We view the MGCO26 as a complementary approach to Vobor Duo for targeting B7H3. More specifically, we believe that having distinct mechanisms of action and potentially different safety and efficacy profiles, Vobor Duo and MGCO26 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 regardless of the mechanism of action or payload. Regarding imoldotuzumab, our academic collaborators are enrolling the HEAT study and investigator sponsored randomized phase two study of this molecule in up to 219 men with prostate cancer. Next, I'll update you on loragilumab, our bi-specific tetravalent PD-1 by C-PLA4 dark molecule. We designed loragilumab to have preferential blockade on dual PD-1 C-PLA4 expressing cells such as tumor infiltrating lymphocytes or TILs which are most abundant in the tumor microenvironment. We are enrolling the LORAKHEAT study, a randomized phase two clinical trial of loragilumab in combination with docetaxel versus docetaxel alone in second line chemotherapy naive MCRPC patients. The current study design includes a primary study endpoint of RPFS. A total of 150 patients are planned to be treated in a two to one randomized study with more than 100 study participants enrolled to date. We anticipate completing enrollment of the study late this year or early 2025 and providing a clinical data update on the study in the first half of 2025. MGD-024 is our next generation bi-specific CD-123 by CD3 dark 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 one dose escalation study of MGD-024 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 MGD-024 at predefined decision points during the phase one study. MGD-028 is our second topoisomerase one inhibitor based ADC incorporating Cinefix's novel linker payload and an ADDM9 targeting antibody. ADDM9 is a member of the ADDM family of multifunctional type one transmembrane proteins that play a role in tumor genesis and cancer progression and is overexpressed in multiple cancers, making it an attractive type of antibody target for cancer treatment. We recently submitted an investigational new drug application for MGC-028 to the US FDA. Beyond MGC-028, we are exploring additional molecules for potential future IND submission. I look forward to telling you more about these additional molecules on future call. Finally, after quarter end, we sold global rights to Margetuximab, which is marketed as Margenza, to Tesserra Therapeutics LLC, a privately held biopharmaceutical company pursuant to an agreement announced a few weeks ago. Tesserra is expected to pay us $40 million at closing and we may receive additional sales milestone payments of up to an aggregate of $35 million. The transaction is expected to close in the fourth quarter of 2024, subject to customary closing conditions. We expect to pay an $8 million in amendment fee to our current commercialization partner during the fourth quarter of 2024 and will manufacture Margenza drug substance on behalf of Tesserra going forward. The pending Margetuximab transaction, as well as the recently received $100 million in milestones from Insight, further strengthen our financial position, enabling us to sharpen our focus on our key priorities of advancing our clinical stage assets while researching and developing the next wave of early stage product candidates. Thank you all for joining today. As you know, we announced last week that I will be stepping down as president and CEO early next year. After nearly 25 years with Macrogenics, it's truly a milestone for me personally and professionally. Together we've transformed ideas into treatments, building a fully integrated biotech company dedicated to helping patients. I'm immensely proud of what we've achieved, particularly the impact of the COVID-19 pandemic and the advancement of therapeutics like Margenza, Zinus, and T-Zil to FDA approval and our robust pipeline of antibody-based treatments. This transition comes at a time when Macrogenics is strongly positioned with a diverse and promising development portfolio and a solid financial foundation. The board has initiated a thoughtful search for my successor, and I am committed to supporting the company during this period to ensure a seamless transition. Looking ahead, I am confident in Macrogenics' future. Our near-term goals remain unchanged, advancing our pipeline, expanding partnerships, and creating value for patients and shareholders alike. I want to thank the Macrogenics team, our board, our shareholders, and our partners for their dedication. I look forward to continuing my support as an advisor and shareholder, and I'm excited to see all that Macrogenics will accomplish in its next chapter. We would now be happy to open the call for questions. Operator?

Thank you. Ladies and gentlemen, to ask a question, you will need to press -1-1 on your telephone and wait for your name to be announced. To withdraw your question, simply press -1-1 again. Please stand by while we compile the Q&A roster. Now, first question coming from the line of Tara Bancroft with CityCow, and the line is now open.

Hey, guys, this is Nick on for Tara. Thanks for taking our question. Just one for me, but I understand the parameters factoring into your decision will be multi-fold for this, but what do you need to specifically see from the data next year to make a decision about going forward or not for Vodafone Duo, and do you have any updated thoughts on a potential dose at this point?

Thanks. Thank you very much, Nick. As you said, we are close to getting the final data. As we've noted, we continued the observation of these patients post the last dosing, which occurred in July. The patients will be followed no longer than six more months. As I pointed out, there are a number of parameters to look at, obviously looking at the final RPFS, looking at the safety profile of the drug, looking at the competitive landscape, and assessing this in the context of other things we have in our portfolio, which is just too early at this point to give the specific parameters which will determine next steps forward. So be patient, and we should be able to provide some insights in the coming months.

Thank you very much.

Thank you. And our next question coming from the line of Jonathan Cheng with Learing Partners, the line is now open.

Hi, guys. Thanks for taking my questions, and of course, best wishes to Scott. First question, on that point, can you provide any color around the search process for the next CEO and how he should be thinking about timelines for the transition? And then second question on MGC026, your second B7H3 ADC program, can you discuss how the Phase I dose escalation is progressing, and when could investors see initial clinical data from that program? Thank you.

First, Jonathan, thank you very much. It's always been a pleasure working with you. In terms of the search process, as the announcement occurred last week, there is a subgroup of the board that has been selected to initiate the process. We're going to have a search committee that's going to be working with an outside firm, and that process is just getting started. The expectations, as I said, is that I will stay on. We're going to continue with the strategy we have adopted and move the programs forward until the new CEO is selected. It's anticipated, obviously, these things take a few months. I will stay on until the new CEO is selected, so there should be a smooth handoff to anyone when that person comes on board. With regard to the 026 study, we're in the middle of dose escalation. The study is going quite well. We're getting into ranges right now where one might anticipate the beginning of We're not sure of the causiveness. The expectation here is that we would begin, we would complete the study in 25 and be able to report the data out in 25.

Understood. Thanks for taking the questions.

Thank you. Our next question coming from the line up, Yigal Nukomovitz with Citi. Yelena is now open.

Hi, this is Rena for Yigal. Thanks for taking my question. I just wanted to ask what kind of triggered the decision to halt the combo now versus earlier when the decision was to stop dosing patients in Tamarack, and if you could provide any more details on the color on pausing the Lurker Lab combo with Volgra, how many patients were dosed, were there any E's reminiscent of what was seen in the Volgra monotherapy, or just any additional color you might have there?

Yeah, thank you very much for the question. As you know, we had proceeded with the combo study to the point where we were very comfortable with the doses that were achieved in the populations we were examining with the individual Lourker Lab and Volgra in combination. However, as we pointed out, is that we are looking at the final data for Tamarack coming up in the next couple of months. We would look at the possibility of exploring additional studies in Volgra to fine-tune that if appropriate. And therefore, rather than continue moving forward in expansions with the doses that we had already tested in combination, we wanted to get that final assessment of the appropriate Volgra dose before we would then explore combinations going forward. So it's a judgment that we want to ultimately have the best dose going forward if we continue combination studies.

Okay, that makes sense. Thanks for taking my question.

Thank you. And our next question coming from the line of Esadar with BMO Capital Markets. Your line is now open.

Thanks for taking the question. Just one question for me on MGC 026. Just wonder, given now you've evaluated Volgra Duo preclinically and in the clinic, you've gotten a preclinical assessment of MGC 026. If you're seeing any notable differences in the profiles for those two ADCs from a safety perspective and how that profile could be differentiated from Volgra on sort of safety, thank you.

Thanks, Esadar. One would expect that obviously with Volgra being a DNA-alkylating agent and the 026 being a TOPA-1 inhibitor, one will see distinct safety profiles. As I said, we want to get the final safety. We obviously achieved much with the Tamar-X study with lowering the doses there. But at this point, being only in the middle of dose escalation on 026, I can't give you a -by-side comparison of the two. There will be distinct differences in safety, but it's just too early to spell out the specifics at this point.

Thank you.

Thank you. Our next question coming from Delina. John Miller with Evacor ISI. Your line is now open.

Hi, guys. Thanks for taking the question, and I'll echo my respect for Scott. As we've heard before, great to work with you for all these years. I'd also like to ask about the Volgra-Lori combo that you're pausing. How many patients have you dosed there? How much data do you have? And is there any chance we could see that data maybe around the same time that Lora is coming out or in the near term at any rate? And maybe from a Lora perspective, how do you view the landscape for Lora combinations going forward from here, whether it's with OverDuo or with other ATCs in prostate?

Yeah, thanks so much, John. I really appreciate the personal comments. It's a pleasure working with you and your colleagues as well. With regard to the number of patients, we did many. And the actual specific numbers, I can't answer to you off the top of my head. But in the double digits in terms of looking at multiple doses, this was a 3 plus 3 assessment at various combinations. But of course, because we were enrolling patients with different tumor types, the representation of any particular tumor type was quite small. So at this point, we haven't assessed the form of presenting the data we have there. It's more likely that, as I said earlier, we want to assess the final results of Tamarack, make some decisions whether we need further alterations of the Vobor dosing if we continue with the combination studies going forward. With regard to the opportunity with Laura Gerlemapp, as you know, we are doing the Laura Keats study in combination with DOCETaxel. And as I noted earlier, that study will completely enroll by the end of the year or very early in 2025. So we'll have data in 2025 on that. And we are looking at opportunities of combining Laura Gerlemapp in other clinical settings, not only in prostate cancer with other agents, but it's again too early to assess that until we have the final data on the Laura Keats study.

Let me just add to that just in case it wasn't completely clear to listeners. So with regard to Vobor plus Laura, that combination, we've only studied that in dose escalation. We had thought we would move into dose expansion later this year. Obviously, we did not do that. So all of our data comes from dose escalation. The dose expansion study was never actually commenced.

Yeah, as Jim is pointing out again, it was a 3 plus 3 design in looking at that.

Thank you.

And our next question coming from the line of Kelsey Goodwin with Guggenheim Partners.

Yeah,

thanks very much with regard to the Laura Keats study. You were a little soft on the sound here. I just want to make sure everybody understood what the question was. Clearly, we're looking here at a chemo-naive population. As you know, if you look at the standard of care of dosetaxel alone, if you look at the last three studies where dosetaxel was tested, it's approximately 8 to 8.6 months of RPFS benefit. Clearly, we would like to see a significant increase both in RPFS and then ultimately, obviously, have a benefit seen in OS, the actual number. We are not in a position to declare at this point, but certainly would be in a, for RPFS, would be certainly in a double digit month of improvement.

Thank you.

And our next question coming from the line of Sylvain Drekken with CitizensJMP. Yolana Soppen.

Yeah, thank you. Thanks for taking my question. And Scott, thank you for working with us. It was great to work with you. I have a question on MGD 024. You know, you've mentioned that Gilead has some opt-in at various points throughout this trial and it's ongoing and you may or may not get data next year, but are any of those points next year, could we find out next year, Gilead's opt-in or not? Thank you.

You know, thank you very much again for your personal comments. With regard to the study, it's proceeding well. As you know, with active redirected T cell killing molecules, the FDA position is that one requires slow dose escalation. And we've been through many, many cohorts already and we are continuing to dose escalate here. So I can't at this point determine when the study will be completed. It is moving forward and nor can I determine when Gilead might make the decision with regard to opting in. They have the ability to wait until the end of the Phase 1 data. So at this point, we have a very good collaboration. We share the data with them and we expect that the study will continue.

Thank you.

And our next question coming from the line of Mayank Mamteni with B. Riley Security Sealant is now open.

Good afternoon, Dean. Thanks for taking that question and congrats to Scott for a long list of accomplishments that we missed. One big picture question. You know, you've tended to focus as an organization on prostate cancer. Could we see a bit of a strategy shift in some sort as we get to this next chapter for macrogenics? And relatedly, if you're able to give us precise guidance, Scott, on when and if at all next year we could see both CRPC and maybe lung cancer specific data for 026 to assess direct comparability to both your program and the PRB7S3 programs also getting to late stage development. And then I have a follow up.

Thank you very much. Again, for the personal comments as well. With regard to the prostate cancer, you know, we are a company that is strongly focused on developing a wide range of treatments for solid tumors. We embarked on prostate cancer a number of years ago because of the opportunities there and the lack of appropriate treatments, particularly for late stage patients. There certainly was a need there and that obviously led to the development of multiple molecules which we're pursuing. As you know, the B7H3 programs as well as Laura Gerle and we will continue with that. And I've discussed the results that we expect over the course of 2025. With regard to 026, as we've talked about with Overduos, so with 026, we're looking at the use of this drug in a lot of different tumor types. The dose escalation is open to a wide range of B7H3 positive tumors. The plan going forward is to determine patients that have responses to 026 in the dose escalation. We have built into the Phase 1 study the ability to do many expansions. And so as a result, with regard to responses in prostate for 026, we expect that we should have data in other tumor types as well. But at this point, again, as I indicated, we're only in the middle of dose escalation and it's too early to determine what specific tumor types we might pursue further.

Great. And then one specific question regarding the Tamarack learning. The efficacy of VD seems generally comparable to post-axone. I was wondering if this could be because of B7H3 expression pattern and its maintained expression pre and post-tumor, which could be different than say PSMA. And is your expectation going forward that remains the case as you intend to report the final Tamarack data?

Yeah, so we are continuing to look at obviously both the chemo-naive and the post-taxing settings for the Tamarack data. As we showed at ESMO and indicated, we're having at the landmark timeframe of six months, we're getting very good responses in both the chemo-naive as well as the chemo-experienced population. So at this point, until we have the final data, we haven't assessed if we pursue this further. Again, as I pointed out earlier, there are a lot of things that we will assess when we have the final data. But right now, it's still open to providing a potentially new paradigm for treatment both in the chemo-experienced as well as the chemo-naive population. All comes down to the degree of activity, the RPFS, as well as the safety profile.

Understood. And lastly, for the LORIC-EAT trial enrollment getting to completion here, Scott, are you able to comment on how maybe the patient baseline characteristics prior treatment exposure, the PSMS data compared relative to the doxidaxel trials that have been done in MCRPC previously? And could you just clarify if the OS results will also be available next year or would that take longer?

With regard to the characteristics of the LORIC-EAT, I would say that the population for these chemo-naive patients was quite similar to what was enrolled in the patients for Tamarack. So they obviously had progression on an antigen receptor targeting agent. And so we think that this will be a population that is very characteristic of what is normally seen there for patients who on the standard regimen would get doxidaxel. The fact that we have this as a controlled trial, we will have our own data to see what doxidaxel does alone in the 50 patients or so that are treated with that agent alone as compared to historical data. So I'm feeling pretty confident that we will have a data set that will be nicely valuable as compared to historical studies. Now, with regard to overall survival, I think it will be too early to be able to report that out in 2025. But given that, as I said, the study will be complete enrolled by the end of this year or very early in 2025. I think we'll be in very good shape to present obviously responses, PSA reductions, as well as RPFS in 2025, but OS may be a little early.

Thanks again for taking a question.

Thank you. Now, next question coming from Delina Peter Lawson with Barclays Yelena Snellman.

Great. Thank you so much. I guess, as we think about your B7H3 acids, I guess your second generation molecule, how far behind is that when we see the initial data? And kind of what do you want to see in that, I guess your first generation B7H3 to kind of understand if that and how that moves forward?

Thank you very much, Peter. To comment, as you know, there are a number of other molecules that are moving forward for TOPA1 inhibitors. The data has been presented in a number of different scientific forums. Again, we see many of the virtues of the way 026 was designed with regard to having a site specific conjugation of the Cinefix exotecan with the DAR4 and with other profiles that despite the fact that we may be behind in that particular molecule development as compared to others, that we feel that the opportunity here is that this could perform quite well. And then obviously because of the broad expression of B7H3 in different tumor types, the data that's been presented to date for competing molecules has been in a limited number of tumor types. And so despite the fact there has been data that has been shown particularly in small cell cancer and in some cases modest data in other lung cancers, we feel that we can be quite competitive with the 026 molecule once we finish those escalation. And as I said earlier, we expect that data from the Phase 1 study to be available in 2025. With regard to the Vobraduo molecule, again, it's just too early to spell out the opportunity here. Clearly, we have the largest data set in prostate cancer with Vobraduo, but we will have to assess again what is necessary to achieve a go-forward plan based on the final RPFS data as well as the final safety profile and whether further tweaking will be necessary for the dosing to move forward in the future. So we're still very encouraged by the prospects of both of our B7H3 ADC molecules.

Great. Thank you so much, Scott. It's always been a pleasure talking to you over the years.

Thanks for all those

conversations.

Thank you very much. Same here. I've had the same feeling.

Thank you. And as a reminder, to ask a question, please press star 1-1 and wait for your name to be announced. Our next question coming from the line of Stephen Willey with Steve Full, your line is now open.

Yeah, good afternoon. Thanks for taking the questions. First, I just wanted to say best of luck to you, Scott. I've certainly enjoyed all the interactions over the years. And then second, just a quick question on MgCO2-8. Just curious as to whether or not the Phase 1 dose escalation program is going to be pre-specifying for specific tumor types. If I remember correctly, I think Immunogen had outlined a few different tumor types that it was interested in as it ran that Phase 1 development program. I know that you were a partner with them, obviously. But just wondering if that list of tumor types has changed just given that you've swapped the payload out. There's obviously an inherent sensitivity of different tumors to different payloads. And we'd be curious if you could just give some information as to what tumors you're thinking about. Thanks.

Yeah, thanks, Stephen. Again, a real pleasure always working with you over the years. The answer is, yes, we are going to limit the specific tumor types going forward. As you know, in particular, this based on our own preclinical data as well as IHC data, we've shown overexpression in a number of tumor types. So one among the tumors that you could expect would be obviously lung cancers and pancreatic cancer and at least another tumor type as well. So we feel that that will give us the best sense as we dose escalate to be able to see activity signals as well as obviously the safety profile of the drug. And as you know, one of the challenges on the immunogen molecule is that we were never able to achieve the targeted dose because of the itoxicity that was observed.

All right. Thanks for taking the question.

Thank you. And at this time, I see no further questions in the Q&A queue. I will now turn the call back over to Dr. Koenig for any closing remarks.

Again, thank you everyone for your kind remarks personally. And obviously, we look forward to providing updates on our own exciting programs and other company related activity on our next earnings call. And go out and vote if you haven't done it already.

Good night,

everyone. Ladies and gentlemen, that doesn't go out conference for today. Thank you for your participation. You may now disconnect.