MacroGenics, Inc. (MGNX) Earnings Call Transcript & Summary

Good afternoon. We will begin the MacroGenics Fourth Quarter and Full Year 2024 Corporate Progress and Financial Results Conference Call in just a moment. [Operator Instructions] At this point, I will turn the call over to Jim Karrels, Senior Vice President and Chief Financial Officer of MacroGenics. Please proceed.

Thank you, operator. Good afternoon, and welcome to MacroGenics conference call to discuss our fourth quarter and full year 2024 financial and operational results. For anyone who's not had the chance to review these results, we've 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'd like to alert listeners that today's discussion will include statements about the company's future expectations, plans and prospects that constitute forward-looking statements for purposes of the safe harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our annual, quarterly and current reports filed with the SEC. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change, except to the extent required by applicable law. During today's call, I will be joined by Dr. Scott Koenig, President and Chief Executive Officer of MacroGenics; and Dr. Stephen Eck, our Senior Vice President, Clinical Development and Chief Medical Officer. And now I'd like to turn the call over to Scott.

Thank you, Jim. I'd like to welcome everyone participating via conference call and webcast today. 2024 was an important year for MacroGenics as we achieved several significant clinical development milestones and are well positioned to build upon that momentum in 2025. We have a diverse and promising clinical portfolio, and we look forward to a year of continued progress. On today's call, we will provide key updates on our business and clinical programs. I'll now turn it over to Stephen to discuss those clinical update.

Thank you, Scott. We made meaningful advancements in 2024 and look forward to continued execution as we develop and grow our portfolio of antibody-based cancer treatments in 2025. First, from our proprietary investigational pipeline, I will talk about lorigerlimab, our bispecific tetravalent DART molecule designed to enable blockade of PD-1 and CTLA-4 with potentially enhanced CTLA-4 blockade on T-cells co-expressing these immune checkpoint molecules that are highly enriched in the tumor microenvironment. I'm pleased to share that enrollment is complete in the ongoing LORIKEET Phase 2 trial, a 150-patient randomized study of lorigerlimab in combination with docetaxel versus docetaxel alone in second-line chemotherapy-naive patients with metastatic castrate-resistant prostate cancer. The current trial design includes a primary study endpoint of radiographic progression-free survival. Given that this endpoint is an event-driven, the availability and subsequent presentation of final rPFS data will depend on the eventual rPFS event accrual rate. We anticipate providing a clinical update for LORIKEET in the second half of this year. Based on our cumulative experience to date from our Phase 1 and Phase 2 studies of lorigerlimab, including in metastatic castrate-resistant prostate cancer, a tumor setting historically insensitive to checkpoint inhibition, we plan to initiate the LINNET Phase 2 study. This clinical trial will evaluate lorigerlimab monotherapy in patients with either Platinum-Resistant Ovarian Cancer, PROC, or Clear Cell Gynecologic Cancer, CCGC. Both represent unmet need and historically have been relatively insensitive to checkpoint inhibitor therapy. The study's primary endpoint is ORR with multiple secondary endpoints to be explored. The company anticipates enrolling up to 40 patients with PROC and up to 20 patients with CCGC in LINNET, which is expected to commence by mid-2025. Next, I'm very excited to update you on our emerging ADC portfolio. We have 3 antibody drug conjugate molecules, 2 in clinical development, 1 in preclinical studies that each incorporate a novel, glycan-linked topoisomerase inhibitor-based payload, which are developed by our collaboration partner, Synaffix, a Lonza Company. I will now walk you through these 3 candidates. First is MGC026, which is a TOPO1 inhibitor-based ADC that targets B7-H3, an antigen with broad expression across multiple solid tumors and a member of the B7 family of molecules involved in immune regulation. We are excited about the potential for MGC026 given the molecule was constructed using a clinically active variable domain also contained in vobra duo as well as the use of Synaffix's TOPO1 inhibitor linker payload, which has shown potentially superior preclinical profile compared to that of other topoisomerase 1 inhibitors. MGC026 is currently being evaluated in a Phase 1 dose escalation study in patients with advanced solid tumors. We anticipate dose expansion in selected indications will initiate in 2025. We plan to disclose these indications at a later date. Second is MGC028, a TOPO1 inhibitor-based ADC that targets ADAM9, a member of the ADAM family of multifunctional type 1 transmembrane proteins that play a role in tumor genesis and cancer progression and are overexpressed in multiple cancers such as pancreatic, gastric, adenocarcinoma of the lung and squamous cell lung cancer, among others. As a reminder, we previously presented preclinical data showing antitumor activity of MGC028 in, in vivo models. Also, in a nonhuman primate study, MGC028 was well tolerated at high dose levels with mild reversible side effects and no ocular toxicity, which is often a concern with tubulin-inhibitor-based ADCs. The IND for MGC028 was cleared by the FDA early this year, and the first patient was recently dosed in a Phase 1 study in patients with advanced solid tumors. And third is MGC030, a preclinical TOPO1 inhibitor-based ADC that targets an undisclosed antigen expressed across several solid tumors. There are currently no approved therapies to this target. We anticipate submitting an investigational new drug or IND application for MGC030 in 2026, further expanding our already deep clinical pipeline. In terms of our T-cell engagers, recall that MGD024 is our next-generation bispecific CD123 x CD3 DART molecule that incorporates a CD3 component designed to minimize cytokine release syndrome. 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. Gilead has the option to license MGD024 at predefined decision points during the Phase 1 study. Finally, I'll update you on vobramitamab duocarmycin or vobra duo, which is our ADC designed to deliver DNA-alkylating duocarmycin cytotoxic payload to tumors expressing B7-H3. We announced today results from the TAMARACK Phase 2 study of vobra duo in patients with mCRPC who were previously treated with 1 prior androgen receptor access targeted therapy. Study participants may have received up to 1 prior taxane-containing regimen, but no other chemotherapy agents. These results, based on a data cutoff of February 21, 2025, showed a mature median rPFS of 9.5 months for the 2.0 milligrams per kilogram cohort and 10.0 months for the 2.7 milligrams per kilogram cohort in patients with mCRPC. Safety data from the study remained consistent with our prior data disclosures. Based on our internal review and assessment of TAMARACK efficacy and safety to date, we have decided not to pursue further internal development of vobra duo and are exploring potential alternatives for partnering the program. We believe the B7-H3 target continues to have potential and are pleased with the progress being made with our alternative anti-B7-H3 ADC, MGC026. As you can see, there are several upcoming milestones expected across our portfolio in 2025. We're excited about the progress we made in 2024 to advance our programs and look forward to providing further updates in 2025. And now I'll turn the call over to Joe.

Thank you, Stephen. This afternoon, MacroGenics reported financial results for the year-ended December 31, 2024, which highlight our financial position. As described in the release this afternoon, MacroGenics total revenue was $150 million for the year-ended December 31, 2024, compared to total revenue of $58.7 million for the year-ended December 31, 2023. The increase was primarily due to a net increase of $85 million in revenue recognized from milestones achieved under the Incyte license agreement. Our revenue for the year-ended December 31, 2024, included $118.9 million in revenue from collaborative and other agreements, MARGENZA net sales of $16.4 million and contract manufacturing revenue of $13.1 million. Our research and development expenses were $177.2 million for the year-ended December 31, 2024, compared to $166.6 million for the year-ended December 31, 2023. The increase was primarily due to increased research, development, manufacturing and clinical costs related to MGC028, our preclinical ADC pipeline and lorigerlimab, offset by decreased development and clinical trial costs related to our previously discontinued projects and margetuximab. Our selling, general and administrative expenses were $71 million for the year-ended December 31, 2024, compared to $52.2 million for the year-ended December 31, 2023. The increase was due to an $8 million amendment fee we paid to our former commercial partner pursuant to the asset sale of MARGENZA to TerSera Therapeutics, which closed in the fourth quarter of 2024 as well as increased noncash stock-based compensation and accrued severance expenses related to the separation agreement with our Chief Executive Officer. During the year-ended December 31, 2024, other income reflected a $36.3 million gain recognized on our sale of MARGENZA to TerSera. Our net loss was $67 million for the year-ended December 31, 2024, compared to net loss of $9.1 million for the year-ended December 31, 2023. Our cash, cash equivalents and marketable securities balance as of December 31, 2024, was $201.7 million compared to $229.8 million as of December 31, 2023. Finally, in terms of our cash runway, we anticipate that our cash, cash equivalents and marketable securities balance of $201.7 million as of December 31, 2024, plus additional projected and anticipated future payments from partners should extend our cash runway into the second half of 2026. Our anticipated funding requirements reflect expected expenditures related to the ongoing Phase 2 LORIKEET study of lorigerlimab in metastatic castration-resistant prostate cancer as well as our other clinical and preclinical studies currently ongoing. And now I will turn the call back to Scott.

Thank you, Jim. As I previously mentioned, 2024 was a year of strong execution and important progress for MacroGenics. We are excited about our innovative and proprietary pipeline of product candidates, including lorigerlimab, MGC026 and MGC028, and we look forward to continuing to advance these candidates and sharing our progress with you. Our development efforts are complemented by our continued business development focus, and we were very pleased to complete the sale of MARGENZA to TerSera Therapeutics in the fourth quarter. The nondilutive capital from this deal, along with $100 million received from Incyte during the year has allowed us to continue to invest in our clinical pipeline and R&D efforts. Lastly, the Board continues its diligent search for my successor, and I remain committed to supporting the company during the transition period. We look forward to providing you with updates when available. In closing, 2025 looks to be an exciting year for MacroGenics as we work to advance our pipeline, expand our partnerships and drive value for both patients and our shareholders. We would now be happy to open the call for questions. Operator?

[Operator Instructions] And it comes from the line of Peter Lawson with Barclays.

On the LINNET study, what are the gating factors to starting? And then on the B7-H3 TOPO1 ADC, where are you for the -- in the dose expansion?

Yes, I'm happy to answer that. So with regard to LINNET as you know, the standard of care for -- in later line ovarian cancer is quite low. We typically see overall response rates of 10% to 15% with anti-PD-1s in the experimental therapy setting. Some selected experimental trials of ADCs in combination checkpoint inhibitors have demonstrated ORRs size of about 30%. This is a small study, but it is a well-selected patient population, which I think we will be able to inform us about whether we can further develop in these indications. And then you had a question about the MGC026 Phase 1 study. So that study has enrolled quite well. We're very pleased with the progress we've made. We're well into a very nice dosing range, and we should be selecting a dose for further expansion sometime later this year.

Comes from the line of Jonathan Chang with Leerink Partners.

First question, can you discuss the rationale behind developing lorigerlimab in ovarian and clear cell gynecologic cancers? And second question on MGC026, when could we see initial clinical data for that program?

Yes. This is Stephen. So I'll answer the second question first. We probably won't get to show you data until the latter half of this year probably '26. With regard to lorigerlimab in ovarian cancer and clear cell gynecologic cancers, we take that indication because it's basically untreated area as far as checkpoint inhibitors are concerned. The checkpoint inhibitors that are currently available have not shown as much promise as one. We think our checkpoint inhibitor, lorigerlimab differentiates well because we specifically target the T-cells that are already in the tumor microenvironment and that co-express both PD-1 and CTLA-4. And in doing so, largely, but not completely fair the T regulatory cells that are in the periphery that give rise to the classic toxicities that you see with the available CTLA-4 inhibitors.

Jonathan, this is Scott. I'll just add on the other note, looking at open spaces for treating combination checkpoint molecules, our encouraging data that we have seen both in reported late-stage castration-resistant prostate cancer and the ongoing LORIKEET study, which is, as you know, an indication in which is considered a coldest tumor has not successfully been treated with checkpoints before. We think ovarian is another case here where the similar mechanisms might prevail on the value and the side effects of lorigerlimab.

Our next question is from Tara Bancroft with TD Cowen.

This is [ Nick ] on for Tara. The first one for me is, given the rPFS data that you guys just reported for vobra duo, how does this help clarify the path forward for MGC026? For example, do you plan to move this forward in pre-chemo or post-chemo patients, assuming that mCRPC is still an indication of interest? And then the second question is for the ORR data that's coming in the second half of the year, should we expect to see any RPFS data from that? Or is this primarily just going to be ORR?

Well, we certainly will see -- let me answer the second question first, Nick. We certainly will see ORR. The -- whether we see rPFS or not event-driven. And so we just have to wait and see how the cards fall and how quickly we progress. So I can't speculate beyond that. Now your first question with regard to 026 and how that differentiates. 026 is considerably different than of overdue 018. They have a different -- slightly different linker and a completely different payload. So we think there's opportunity for activity beyond what we saw with 18. And also, it's unlikely we will see and so far haven't seen the -- some of the toxicities you saw with overdue, most notably the portal fusions.

And Nick, this is Scott. I just want to add, your question alluded to the fact of comparing that in the prostate setting. We have not decided at this point on 026 and which indications. We'll let the clinical data guide us, obviously, the competitive landscape and what we see in prostate and other tumors to decide what particular tumor types will prioritize for further expansion.

Our next question is from the line of Jon Miller with Evercore.

I'm going to build on the other Jonathan's question on the LINNET indications. I noticed that you're not including any of the indications where AstraZeneca is developing their PD-1 x CTLA-4 bispecific. Can you speak to any plans you might have in those more traditionally hot tumors or places where we already know that there is a good potential for PD-1 x CTLA-4 combinations? And then secondly, speaking of combinations, if LINNET really does have a superior tox profile relative to CTLA-4s, are there places where you might proactively be targeting combinations of LINNET with non-IO agents in those indications?

Jon, thanks so much for your question. With regard to the pathway we are going to proceed, obviously, we have to prioritize our studies. And given the open space in ovarian, we figured that this was an opportunity for us to take advantage of, but we have not excluded the opportunities for other tumors as well. We'll see how the lorigerlimab LORIKEET study comes out. We'll see how the LINNET proceeds. And then clearly, we are certainly open to looking at other indications in a timely manner. With regard to combinations, you hit the nail on the head. If, in fact, by completing the LORIKEET study and now demonstrating that we can combine with a chemotherapeutic like docetaxel, which by itself has its own toxicities, we will look at other combinations in the future as we get the final results on LORIKEET. Given particularly the mechanisms by which LORIKEET is working, the ability to combine this with other ADCs, TKIs and other therapeutics is certainly a plan for the future.

Our next question is from Stephen Willey with Stifel.

I guess in the context of potentially getting an update of LORIKEET that maybe does not include our rPFS before the end of this year. Is there just anything that you can say? I know it's really early at this point, but is there anything that you can say just about how the event rate appears to be accruing at this point? Is it in line with expectations? Is it going a little bit slower than expected? I know the randomization scheme here is 2:1 in favor of LORI. So just curious.

Yes. It's a 2:1 randomization study, a study designed for 150 patients. We're very pleased with how quickly it enrolled. We started in the later part of 2023 and closed that enrollment at the end of 2024. So, the study is fully enrolled, and we're just waiting for events. I think it's too early to comment on the event rate. So beyond that, we just have to wait and see. It's just too early to know.

Just in addition, we had a sizable number of patients who were enrolled early in '24 as well. And given what the expected control population would progress, it would not be unreasonable to think that having a PFS event rate in the second half of the year is possible. But as Stephen commented on, until we achieve the actual numbers, we won't discuss it.

Okay. And I think maybe the question was asked; I might have missed the answer, but could there be some data that's disclosed here in the back half of the year from LORIKEET, whether that's a response rate data point to PFS?

Yes, there certainly could. We just don't know. There are 2 factors. One, you don't know well how the control arm performs. There's a good bit of variability in how docetaxel performs in the clinical setting, and varies from trial to trial. So there's that factor. And then you have the experimental arm. So we'll have to see how much added benefit we have if it's going to cut down the effect size. And the bigger the effect size, the sooner you find out.

Okay. I guess the question is just whether or not there's disclosable data in the absence of having that rPFS trigger.

Yes. The ORR is something we can look at, and we would expect both agents could contribute to ORR. So you could see differentiation on ORR alone. And that's not as event-driven. There is act time that it takes to get an ORR sometimes.

Yes. Understood. And then just on the ADC portfolio, can you just remind us what the highest non-toxic dose for 026 was in preclinical primate trials? And is there any kind of differential in that dosing threshold between 026 and 028 just as we try to think about the relative TI for each of these targets?

Steve, it's Scott. We achieved doses of 50 migs per kig in the primate studies and did not hit a toxic dose. At that point, the magnitude of the effect here, we're over 20x in terms of human dosing expected in terms of area under the curve. So at this -- what was the second part of the question?

I'm just wondering if that 50 migs per kig is both candidates or just 026.

For both.

Our next question is from Silvan Tuerkcan with Citizens.

Mine is on the bispecific MGD024, you're almost 1.5 years into the Phase 1. Can you provide any more details on when we could see data and when Gilead -- I know you mentioned that they have points where they can opt in, but are we getting close to one of these points? Could that be this year? Or would that be a next year event?

Well, hopefully, it will be this year. I mean we're locked into a relatively slow dose escalation design based on what the FDA expects. And so we're taking a very slow incremental approach to dose escalation and characterizing all of the adverse events very carefully. So it is a bit of a slow-going trial compared to your typical Phase 1 study. We knew this from the beginning just based on where we started, started very low doses and slowly worked our way up. So we're certainly getting near, but we are not at MPD yet.

It comes from Mayank Mamtani with B. Riley Securities.

Just quickly on the LORIKEET, are you able to talk to your expectations for the discontinuation rate given the CTLA-4, PD-1 experience previously? And I was also curious to learn what learnings, if any, from the Phase 2 experience informed you prioritizing the program? Just sorry if I missed that earlier.

Yes. So I think your first question has to do with the -- what do we expect in terms of discontinuation rate. We think we'll do better than some of the prior checkpoint inhibitors simply because lorigerlimab is very well tolerated and patients -- we've had patients stay on the lorigerlimab for considerable length of time in other studies. So we're not anticipating that we'll have a significant dropout from the experimental arm that is the combination of lorigerlimab with docetaxel due to intolerability. Obviously, you can have some, but we think this is a much better tolerated drug than, say, giving ipilimumab with nivolumab, for example.

Yes. And any learnings from that study that contributed to the program?

Well, I think -- I mean, obviously, they're very different programs or different indications. So the learnings are indirect, principally around what dose we want to use and what safety profile we should expect. Now the LINNET study is an open-label noncombination study. It's a single-agent study. So it's a simpler study in that respect.

And this is Scott. The totality of the data, which encourage us to go into ovarian cancer was not only based on our experience in LORIKEET, it was from the Phase 1 expansion studies in prostate, but I should also remind you that in the dose escalation study, we were seeing good tolerability. And in fact, 1 of the patients that had an objective response was a patient with a serous carcinoma of the fallopian tube, which is essentially similar to ovarian cancer. So again, all these points in aggregate and our experiences of improved tolerability of giving this combination checkpoint encourage us to seek other indications like ovarian cancer.

And just 1 more. On MGC028, are you able to comment on how far along you are in the Phase 1 study? And if there is any specific tumor type enrichment you have started doing already?

Yes. So that study has just got underway a few weeks ago. We think we have plenty of patients lined up. I think that will go in a very expeditious manner. It's too early to comment on that. With regard to the second part of your question, we're not preselecting patients with respect to the level of ADAM9 expression. I think that's what you were alluding to. We'll have a look later on and see if there is a differential effect. But for now, we're not preselecting.

But I just want to say we did limit it initially to particular tumor types where we know ADAM9 has upregulation, particularly pancreatic, lung and cholangiocarcinoma, and we have ideas by adding other tumor types subsequently. So we hope that during the dose escalation, we'll see evidence of activity as well as tolerability.

[Operator Instructions] All right. As I see no further questions in the queue, I will conclude Q&A session. I will turn it back to Scott Koenig for his final remarks.

Well, thank you. In closing, I'd like to thank everyone for joining us on this call and for continued interest in MacroGenics. A special thank you to our employees for their continued commitment, and we look forward to sharing updates on our progress during future calls. Have a good evening.

Thank you. And this concludes our program. You may now disconnect.