MacroGenics at TD Cowen Conference: Strategic Innovations in Immunotherapy

On Wednesday, March 5, 2025, MacroGenics Inc. (NASDAQ: MGNX) presented at the TD Cowen 45th Annual Healthcare Conference. The discussion, led by CEO Scott Koenig, focused on the company’s robust pipeline of immunotherapeutic products, highlighting both achievements and challenges. MacroGenics emphasized its strategic direction in drug development, financial health, and the potential for future growth.

Key Takeaways

• MacroGenics has secured $475 million in non-dilutive capital over the past few years, supporting its programs until 2026.
• The company is advancing several promising molecules, including VOBRADUO, lorozirlimab, and MGCO26.
• Strategic focus is on combination therapies and targeting specific patient subpopulations.
• MacroGenics retains significant royalty rights on partnered programs like ZYNUS and TZL molecules.
• Future milestones include clinical trial updates and potential new partnerships.

Financial Results

• Cash Position:

- MacroGenics reported $200 million in cash, expected to support ongoing programs into 2026.

• Non-Dilutive Capital:

- Secured $475 million through partnerships and milestone payments.

• Sale of Margenza:

- Received $40 million from TECERRA, with potential for additional milestone payments.

• ZYNUS Molecule (Incyte Partnership):

- $365 million received to date, with potential for further milestones and a 15% to 24% royalty.

• TZL Molecule (Sanofi Partnership):

- Potential for significant milestone payments.

Operational Updates

• Pipeline Expansion:

- Three ADCs in clinical development, multiple preclinical ADC molecules targeting novel targets.

- Three bispecific DART molecules showing promising activity in various tumors.

• VOBRADUO (B7H3 ADC):

- Updated data presented at ESMO, focusing on final median PFS and safety profile.

• Lorozirlimab (PD-1/CTLA-4 Bispecific):

- Enrollment completed in a 150-patient Phase II study, with data readout expected later this year.

• MGCO26 (Next-Generation B7H3 ADC):

- Currently in dose escalation phase, with updates expected later this year.

• MGD024 (CD123/CD3 Bispecific):

- Collaboration with Gilead, in dose escalation for AML and other CD123-bearing tumors.

Future Outlook

• VOBRADUO Decision:

- Evaluating development and potential partnerships based on efficacy and safety data.

• Lorozirlimab Potential:

- Anticipating results from the LORIKATE trial, exploring use in earlier therapy lines.

• MGCO26 Development:

- Focus on completing dose escalation and identifying specific tumor types for further trials.

• Preclinical Pipeline:

- Updates expected on next-generation technologies and new targets in late 2025-2026.

• Partnership Opportunities:

- Exploring additional revenue from business development activities and partnerships.

Q&A Highlights

• VOBRADUO Update:

- Focus on doing right for patients and investors, evaluating efficacy and safety.

• B7H3 Strategy:

- Selected a TOPO1 payload for MGCO26 due to broad B7H3 expression.

• Lorozirlimab Expectations:

- High hopes for the LORIKATE trial readout, aiming for OS benefit and subpopulation targeting.

• Pipeline Priorities:

- Excitement about next-generation technologies and new targets in the preclinical pipeline.

• Patient Selection:

- Emphasis on understanding histological and mechanistic bases for targeting therapies.

In conclusion, MacroGenics remains committed to innovation and strategic growth in the immunotherapy landscape. For further insights, refer to the full conference call transcript.

Full transcript - TD Cowen 45th Annual Healthcare Conference:

Tara Bancroft, Senior Analyst, TD Cowan: Good morning, everyone. And thank you for joining us for TD Cowan’s forty fifth annual healthcare conference. I’m Tara Bancroft, one of the senior analysts here.

And for our next session, we have a presentation that will follow with Q and A with MacroGenics. And from MacroGenics, we have the CEO, Scott Koenig. And so Scott, thank you so much for joining us. So you could take it away with the presentation whenever you’re ready.

Scott Koenig, CEO, MacroGenics: Sure. And as you know, this is just a brief presentation to sort of introduce the company. And Tara and Nick, thanks so much for the invitation today. So as you know, I’ll be making forward looking statements during the course of this presentation. So please refer to our SEC filings to understand the risks associated with an investment in MacroGenics.

So let’s start. For those of you who do not know MacroGenics and or those who have not been following us for a while, We are a fully integrated immunotherapeutics company focused on the development of first in class and best in class therapeutics for the treatment of cancer. We do everything from early research discovery to late stage clinical development, including the production of marketed products as well as our molecules and clinical development for ourselves, as well as our partners at our commercial manufacturing facility. We have been in business now twenty five years. And so if I to give you a little bit of a snapshot of where the company is now, I’ve sort of arranged these pillars in groups of three.

In the history of the company, we’ve had three monoclonal antibodies that have been approved by the FDA and are currently being marketed. We have three molecules in the development of prostate cancer using our three proprietary technologies, FC engineering, our bispecific DART technology, as well as our ADC molecules. We have ADCs, three ADCs using different linker toxin technologies in clinical development for different indications. Plus, we have a number of preclinical molecules, ADC molecules targeting new and novel targets. And I would expect over the coming years, at least three of these will get into clinical development.

Sticking with the 3s, we actually have three bispecific DART molecules that have either completed clinical development with good activity in a number of tumors or proceeds in further clinical development using either combination checkpoints or redirected T cell mechanisms. And then finally, our third quarter earnings report, we had $200,000,000 of cash with plans for continued support of our programs into 2026. So this is the listing of our current pipeline molecules where we retain commercial rights. So as you see, as I pointed out, we have three ADC molecules here, VOBRADUO and O26, which are targeted B7H3 and the ADAM9 molecule MGC O28. Two of the three bispecific DAR molecules, lorodirimab and tivotalumab and then the Fc Engineered molecule, which is being pursued in an IST in over two hundred patients, in patients with newly diagnosed high risk prostate cancer.

With regard to additional programs, our partnered programs where we could anticipate future cash flow and further platform validation. Just to give you a little perspective, in the past two point five to three years, we have brought in $475,000,000 of non dilutive capital either coming from partnerships or milestone payments. And we anticipate additional money coming in from such activities, BD activities and milestones. Examples of this are included is that recently in the end of ’twenty four, we brought in $40,000,000 from the sale of Margenza to TECERRA. We have potential for additional milestones there.

With regard to the ZYNUS molecule, the molecule that we had sold to Incyte in 2017 when it was just starting Phase one studies, we have brought in $365,000,000 to date. This is now approved in Merkel cell cancer as Incyte presented at ESMO last year had a successful Phase III practice changing study in anal cancer. They have filed an SPLA for this and anticipate approval in 2025. They also had a successful Phase III study in frontline non small cell lung cancer, and I anticipate they would likely file that as well. There we have significant hundreds of million dollars of potential milestones there and we retain a 15% to 24% royalty there, which allows us both to obviously clip a coupon or potentially monetize that through the royalties.

With regard to the TZL molecule, the CD3 molecule that we developed years ago for Type one diabetes, which ultimately we sold to Prevention Bio, which was then acquired for $2,900,000,000 from by Sanofi, we retained significant hundreds of millions of dollars of potential milestone payments They have filed both in Europe as well as The U. S. For additional indications, the new onset indication for Type one diabetes. So we will await the results of that to see that going forward. And then we have a very significant collaboration with Gilead around CD123 and CD3, which is in dose escalation, continues in dose escalation.

And we have collaborations around additional research programs with them. And then while I will not be able to discuss the specific programs today, we’re very excited about the activity of these research programs. So let me touch on individual molecules quickly. You heard a lot about VOBER DUO. This is the ADC molecule using a linker toxin, dura komycin, which is a DNA alkylator.

We presented data at ESMO, which updated the landmark six month endpoint of RPFS. We have presented updates on the safety profile of this molecule and what we promised is an update early this year with regard to the prospects for this molecule, which we will do in a very short order. As we’ve described, the goal for this molecule is to assess what the final median PFS is, what is the safety profile of this molecule, what is the competitive landscape, what else is in our pipeline and what do potential partners view this molecule going forward. And that’s all I’ll say today and I’m sure you’ll have some questions about that in which we can follow-up. We’re very excited about lorazirlimab.

This is the PD-one CTLA4 molecule, which we designed to have as good or better activity for combinations of anti PD-1s and CTLA4, zippinivo as the prime example. As you know, the historical basis of that combination is the toxicity associated in combinations where they’ve had to limit it and the ipi dose to one mgkg and giving a maximum of four doses. As you know, there has been no checkpoint molecule that has been approved in prostate cancer. We showed very exciting data two point five years ago at ASCO GU demonstrating twenty nine percent PSA50 reductions in late stage metastatic castration resistant prostate patients with a twenty six percent overall response rate with all the patients with ORRs having PSA 90s or greater. This led us to design a lower key study.

This is a 150 patient study, two:one randomization for combination of docetaxel in chemoine patients who have progressed on a angiogen receptor targeting agent in combination with loraginalumab, fifty patients getting control arm. We finished enrollment of this study in December. So as you know, the historical data on the control group there is about eight months at best. So we should see what the control group will be doing this year and therefore, we’ll have a readout of this molecule going forward. And what we have also promised with the excitement about this molecule is we’re looking at the potential for other tumors and we will announce very shortly what additional tumor type or types we will pursue.

MGCO26, which is called our next generation B7H3 ADC molecule, we saw this as a parallel development to voberduo. I think we have it all designed appropriately here. We’re using a variable domain, which is the exact same one we have in vomerduo. We know this is a very good binder to tumors versus normal tissues. We know this gets incorporated the cells quite efficiently.

We’ve done our comparison of this variable domain against what we believe to be the Daiichi molecule in terms of incorporation, and we see superiority of this variable domain. And it also targets the inhibitory receptor that is deemed to be associated with inhibition of T cell responses targeting B7H3. On the linker toxin side, instead of the duercomycin molecule, we’re using the linker toxin from SINIFIX, which ultimately is an exotecan, a TOPO1 inhibitor. As you see here, it has a DAR of four. It is binding to an engineered portion, the glycan found in the Fc domain.

And this is a big advantage because by knocking out the Fc activity of this molecule, therefore, it does not bind to FcRs. The theoretical basis of what interstitial lung disease is caused by the, in HER2 molecule and the DXT platform and that of SN38, you avoid the binding to Fc receptors expressed on alveolar macrophages and other granulocytes and therefore, in theory, should have a reduced opportunity to develop interstitial lung disease. In addition, Sinefix and work we’ve done ourselves suggest that this is superior to DXD and the SN38 platforms. It has lower multi drug resistance. It has enhanced potency as compared to those platforms as demonstrated in published data.

So where we are in this molecule, we’re in the middle of dose escalation. We should finish out dose escalation this year, should be able to report updates on this Phase I study later this year. And designed in this study is the ability to do mini expansion cohorts once we see responses. So we are very excited about the prospects of this molecule. The next one is our ADAM9 molecule.

Excuse me. One second. So this is using a antibody that we developed originally in a collaboration with ImmunoGen and this targets a metalloproteinase ADAM9, which is over expressed in a lot of different tumors, GI tumors, pancreatic, colorectal, gastric, lung cancer, cholangiocarcinoma, triple negative breast, prostate. Again, we’re using the SINIFIX technology here, exact same link of technology, which I just described for ’26. This is starting Phase one study this year.

Obviously, no data this year, more likely next year. The MGD024 is the molecule I alluded to before as collaboration with Gilead at CD123 by CD3, middle dose escalation in AML and other 123 bearing tumors. This is an option based deal with Gilead and they have the opportunity to complete the licensing by the end of Phase one. So I think that’s all I plan for today. And it’s up to you for additional questions.

Tara Bancroft, Senior Analyst, TD Cowan: Perfect. Okay. Yeah. Thanks so much for that very detailed presentation. It’s good to get a level set the foundation and everything that you guys have going on because it is a lot.

And so you can you can come get comfortable, have a seat with us. So I guess my first question would be on the VOBRA DUO up update that’s expected pretty much imminently because you got you got into this quarter. What what do you need to see from this dataset to continue development of it? Or is that is that still the goal to continue developing it or switching to o two six?

Scott Koenig, CEO, MacroGenics: Our goal is to what’s to do right for the patients, do right for the molecule and do right for the company and investors. And there may be different decisions that then precludes to any final answer to that. And I’m not going to share it with you today. As I’ve pointed out is first, we want to see the efficacy activity. As you we presented at the ESMO presentation at the six month landmark endpoint, we had already improved the efficacy from the Phase one three mg per kg Q3 from a median PFS of the forty one, forty two patients we had in that study of five point five months and we were already at eight, eight point five on the doses that we are taking.

So now we were continuing to follow these patients. The expectation is that will be even longer now. And the question is, how much longer is enough? And as I’ve alluded to you before, is that given the competitive landscape, it would have to be in the double digit range or higher and then clearly more is better in that regard. The second is on the safety.

As we achieved our goals of if you recall what Tamarac was designed to do by giving lower doses, we got better efficacy, but we also improved the safety. If you recall, the biggest issues on the safety was hand foot syndrome. We dropped that by 50% or more. We dropped the neutropenia. But as we continue to be able to dose these patients longer, we were seeing similar rates of pleural fusions occurring later.

So the question then becomes, can we address this going forward with further designs of the study? And the answer is, I think so. I think we have a hypothesis. We’re not going to articulate it today, but that will come into the decision making process. Then in addition, we have to say what is out there, what’s the competitive landscape, where can this molecule make a difference?

I’ll give you one example. As you know, the majority of the competitive molecules are targeting PSMA. As you know, as the disease progresses in patients, PSMA levels drop and actually a lot of patients with late stage castration resistant prostate cancer don’t express PSMA anymore. D7H3 actually is maintained or goes up. So it’s a great opportunity now that if in fact the efficacy data and the safety data bears out, that could be a subpopulation.

But I also we showed at ESMO that in the pre chemo population, it’s working pretty well as well. So that will be important. But in the end, as I’ve illustrated, we have a great portfolio of clinical and the preclinical ones I haven’t even talked about. I’m excited about it as well. So we have to make the decision, can this be partnered and what can be done.

So those are the decisions we’ll be confronting.

Tara Bancroft, Senior Analyst, TD Cowan: Okay. And then staying on the topic of B7H3, so you have O2-six, which looks promising. It has a different payload. Can you tell us a little bit more about why you wanted to select a topo payload and kind of separately, since we’re talking about the strategy of why this, why you selected this, why the payload, what made you decide to keep an ADC instead of maybe going for an antibody with T cell engager or any other modality? Curious your thoughts on that.

Scott Koenig, CEO, MacroGenics: So both can be true. So let’s start with where we were. As I noted before, we had a great variable domain. But an ADC is not any different than a targeted chemotherapeutic. And we know in the spectrum of B7H3 expression across a large number of different tumors, every tumor will respond to different classes of molecules.

And in fact, if you look at the history of prostate cancer, one would not have anticipated a DNA alkylating agent necessarily would work in prostate cancer. The same thing would be said about TOPO1 inhibitors for a number of different tumor types. It was obvious that INHER2 was a home run there in the TOPO1 space. This was even before Daiichi developed a similar linker DXT4 B7 H3. We already had decided that we wanted to go to TopoONE.

I illustrated the reasons why we like the Cinefix Linker Toxin platform. We think that it has many of these features that mechanistically would make it a superior molecule there. And so in our business, it is very rare to have a antigen that is over expressed in so many different tumor types with relatively limited expression in normal tissues. And it’s important to pick the right variable domain and the epitope to that. And we felt we had the right thing.

So that was why we pursued that there. I should also point if you’ve heard me endlessly over the years, single drugs rarely cure cancers. And so it’s always a combination story. And so our goal has been, as you know, from the get go is can we take orthogonal mechanisms and put that together? And what you’ve heard and illustrated here is we’re working on combination checkpoints, we’re working on ADCs, we’re FC engineered.

We’d like to see the evolution of these molecules come together and meet where you show activity of the individual molecules and show superiority going forward. I’ll give you a good illustration. At ASCO GU just recently on Plavicta, which is obviously exciting molecule in the radiopharmaceutical space, The Australian group presented data on giving limited doses of Plavicto in combination with PD-one and show prolongation of our PFS going forward. There’s no reason that we can’t do the same thing with our molecules as well.

Nick: What indications beyond mCRPC could you use a B7:H34 are you exploring?

Scott Koenig, CEO, MacroGenics: Well, it’s pretty broad here. Obviously, as you know, a lot of the competitive molecules are going after small cell lung cancer. It’s not something given where we are in the case of 26 that we’re going to jump in to go after that indication. But it’s overexpressed in lung cancer, both non small cell and lung. It’s expressed in other large indications.

It’s in renal. It’s small indications. It’s in thyroid. It’s pretty large. It’s all the GU cancers.

You’ll see it in endometrial. You can see it in a subset of ovarian. There’s a lot of possibilities here. What we will do for O26 and we have actually a wide range of tumors that are being enrolled in this study. We will identify the ones, we will look at market opportunities, we will look at what the competitors are focusing on and we’re not afraid if we think the activity is superior to compete, but we’re not stupid when somebody is doing a Phase III that we’re still in Phase I.

So we were going to pick and choose based on the activity profile we see in the Phase I, Phase II to decide on which particular tumor types to pursue.

Tara Bancroft, Senior Analyst, TD Cowan: Okay. Next, let’s move to the upcoming Phase II data from the LORIKATE trial for lardrelimab. What

Scott Koenig, CEO, MacroGenics: do

Tara Bancroft, Senior Analyst, TD Cowan: you think it could achieve here with PSA50, ORR? And what can we expect in the data? I know you mentioned a BAR already, the eight month RPFS from the CARD trial, but more so where you think it’ll end up and where you’d really like it to end up?

Scott Koenig, CEO, MacroGenics: I think right now it is I don’t know the answer. So I mean despite the fact that it is an open trial that we finished enrollment in December, given the eight month time frame, you know the control is going to read out this year. And therefore, you’re going to look at the hazard ratio as later in the year and see are the curves separating and going forward. I clearly like to have a high double digit RPFS number. But the bottom line is PSMA4 didn’t show any OS benefit for Plavicto.

So I would love to see an OS benefit as well. That obviously will take longer than this year to do that. But again, you might start seeing separation of the curves there in that regard. And then the bottom line for obviously checkpoint molecules, you’d like to see a subpopulation tail that would be responsible. If we have a combination of double digits and higher and better, we see some any OS benefit there and a tail.

We got a home run there.

Nick: So is it going to be too early to show RPFS? I know that you said that enrollment completed in December, but

Scott Koenig, CEO, MacroGenics: I don’t know. It’s an event driven things. We have our calculations of when the particular events we’d like to see at least half the events occur. That clearly was what happened for PSMA four in that regard. It’s possible.

I just don’t know at this point.

Tara Bancroft, Senior Analyst, TD Cowan: But maybe landmark like you did it?

Scott Koenig, CEO, MacroGenics: Possibly, yes.

Tara Bancroft, Senior Analyst, TD Cowan: Okay. So maybe you could talk about where you think this could be positioned in the marketplace like relative to what’s available out there? I mean, Pluvicto is going in earlier lines. There’s still chemo, there’s second ARPI. Where do you think this could go?

Scott Koenig, CEO, MacroGenics: I think it’s limitless. I mean, I think that as you know, in the landscape of prostate cancer, the standard of care is changing. The recent data on the final readout of the PARP plus ENSA studies suggest that those will be that may become more standard of care, obviously. And this is both in in the DNA repair defect indications, BRCA’s etcetera, but also in non mutational prostate cancers as well. So I think that as I illustrated before and described the combination with Plavicta with the PD-one, if you’re having the value of CTLA-four there, this could be early line.

It could be late line. I wouldn’t even rule out that neoadjuvant is a possibility in years to come. So I’m optimistic going forward.

Tara Bancroft, Senior Analyst, TD Cowan: Yes. And maybe type of patient too that it might be better for what, like slower progressing patients?

Scott Koenig, CEO, MacroGenics: Absolutely. There clearly is we don’t have our understanding of prostate cancer is still evolving. When I look at the patients that are in our trials, we have some patients that don’t respond to anything. They just quickly move. And then we got a sizable large proportion, whether it be in the early line or late line, hormone sensitive, hormone resistant that just work their way along.

And so as we get better understanding of the histological and the mechanism basis for those subpopulations, I think we’ll get a better idea of how to use these drugs and which lines of therapy.

Tara Bancroft, Senior Analyst, TD Cowan: Yeah. That makes sense. Okay. I think we have time for one more question. Nick, do you want to ask something about the pipeline?

Nick: Yeah. So beyond COPREDU, OBEON, on lorodilimab and beyond MGC zero to six since we’ve talked about those, which is most exciting? Is it zero to eight, zero to four, the LAG three? What do you think is most exciting?

Scott Koenig, CEO, MacroGenics: Well, I’m again, I have a lens that you don’t have because I know what’s in our both clinical and preclinical pipeline. I would say that any one of the clinical assets that you just alluded to, except for ADAM9 because we’re just starting the Phase one study, we have activity. And so they can all be winners here. And having now a second ADAM9 molecule and trying to fix what was the problem before can be a tremendous winner. Again, I get back to the point I made earlier.

There are very few targets that have expression against a lot of tumors with limited expression in normal tissue, so one should try to take advantage of them as much as one can. Having said that, you’re going to have to wait to hear our preclinical part, but I’m really excited about some of the next generation platform things we’ve done and new targets we’re going after. So you’ll have to wait for late twenty five, twenty six to hear some more about those.

Nick: You can disclose those if you want to.

Scott Koenig, CEO, MacroGenics: I know I can, but, you know, I gotta keep you asking us back again.

Tara Bancroft, Senior Analyst, TD Cowan: Alright. We are exactly up on time, but thank you, Scott, for this great discussion, detailed presentation, for being here, and thanks, everyone, for for listening.

Scott Koenig, CEO, MacroGenics: Thank you.

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