MacroGenics at Leerink’s Conference: Strategic Pipeline Insights

On Tuesday, 11 March 2025, MacroGenics (NASDAQ: MGNX) presented at Leerink’s Global Healthcare Conference 2025. The company showcased its robust pipeline of cancer therapeutics and strategic partnerships, highlighting both achievements and challenges. While financial stability and promising clinical data were underscored, ongoing concerns such as treatment side effects were also addressed.

Key Takeaways

• MacroGenics has a strong cash position of $240 million, projected to last into 2026.
• The company secured $475 million in non-dilutive capital over the past 2.5 years.
• VOBERDUO showed improved RPFS in trials, with reduced side effects.
• The CEO search is ongoing, with completion expected in the coming months.
• Strategic partnerships with Incyte, Sanofi, and Gilead are progressing with potential milestone payments.

Financial Results

Cash Position:

• MacroGenics holds $240 million in cash, sufficient to fund operations through 2026.

Non-Dilutive Capital:

• The company has secured $475 million from partnerships and milestones over the last 2.5 years.

Upcoming Milestones:

• Potential milestone payments from partnerships with Incyte (retofemumab) and Sanofi (TZL molecule) are anticipated.

Operational Updates

VOBERDUO (B7H3 ADC):

• Landmark data showed improved RPFS at six months (8-8.5 months) compared to Phase 1 (5.5 months).
• Hand-foot syndrome was reduced by 50% or more, but pleural effusions were noted later.

MGC-026 (Second B7H3 ADC):

• Utilizes the same variable domain as VOBERDUO with a TOPO1 inhibitor linker toxin.
• Phase 1 study completion is expected in the second half of the year.

MGC-028 (Next-Gen ADAM9 Program):

• Phase 1 development underway, with data updates expected in 2026.

Lorazirlimab (PD-1 CTLA-4 Molecule):

• Enrollment for the LORIKETE study is complete, with outcomes expected in the second half of the year.

Future Outlook

Key Catalysts and Milestones (2025):

• Updates on VOBERDUO and its development plans are forthcoming.
• Clinical outcomes from the loradirlimab LORIKETE study are anticipated in the second half of the year.
• Progress updates on the ADAM9 program and MGC-026 are expected later this year.

Strategic Focus:

• MacroGenics aims to continue pursuing partnerships and non-dilutive funding.
• The company is focused on advancing clinical programs and exploring new indications for existing molecules.

Q&A Highlights

VOBERDUO Next Steps:

• Future development will focus on achieving a double-digit median PFS and improving safety.

Comparison to Competition:

• VOBERDUO’s data surpasses other ADCs in prostate cancer, with a PFS of 8-8.5 months compared to Daiichi’s 5.3 months.

MGC-026 Strategy:

• Likely to target tumor types other than prostate cancer due to B7-H3’s wide expression in various cancers.

In conclusion, MacroGenics’ presentation at Leerink’s Global Healthcare Conference provided insights into its strategic direction and ongoing projects. Readers can refer to the full transcript for more detailed information.

Full transcript - Leerink’s Global Healthcare Conference 2025:

Jonathan Chang, Equity Research Team, Leerink Partners: Hello, everyone.

Thanks for joining us. My name is Jonathan Chang. I’m part of the Leerink Partners equity research team. It’s my pleasure to host the management team of MacroGenics. We have with us today CEO, Scott Koenig.

Thanks for joining us. And let’s just start.

Scott Koenig, CEO, MacroGenics: Always a pleasure. Nice to be invited. Maybe just for a little bit of introduction of the company for those who are new to the MacroGenics story or haven’t been following for a while. As you know, we are a fully integrated immune therapeutics company focused on developing first in class, best in class molecules to for treating cancer. We with our fully integrated platform, we do everything from early target and platform discovery to late stage clinical development, including the manufacturer of marketed products, as well as the clinical assets that we’re testing and those of partners at our commercial facility in Rockville, Maryland.

Historically, three of the molecules that emerge from our pipeline have been approved by the FDA, are currently marketed. And to get just a good snapshot of where the company is right now, three molecules with our three core platforms, our FC engineered, our DART bispecific and our ADC platform are being pursued for treatments for various lines of therapy for prostate cancer. We have three clinical assets that are antibody drug conjugates. We have three assets that use our DART bispecific technology that have either finished clinical testing in Phase I or are continuing studies in Phase III development. And ultimately, we have a very good cash position.

As we announced on our third quarter earnings call, we had $200,000,000 pro form a, $240,000,000 in cash, which said we would be able to take us into 2026 with our current plans for our program. As you know, we have been very successful bringing a lot of non dilutive capital into the company. In the last little more than two point five years, we brought in $475,000,000 to various partnerships and milestones from our programs. And just for this coming year, we should keep focused on our partnership with Incyte on retofemumab coming up for and SBLA has been filed for anal cancer there. So opportunities there where we have fifteen percent to twenty four percent milestones has been approved already in Merkel cell and there’s been a successful study in lung cancer.

And then our relationship with Sanofi on the TZL molecule for type one diabetes, they have three three regulatory anticipated responses in the second half of this year, which would potentially come with additional milestones. Good partnership with Gilead on our CD3 three by CD 123 program and working on some research programs with them as well. So the prospects look really good, despite the stock price. The company is in really good shape, as I would say, in the history of the company. I’m very pleased to say we’re in a great position for a lot of readouts this year in the next six, twelve and eighteen months.

Jonathan Chang, Equity Research Team, Leerink Partners: Great. Thanks for the introductory remarks. Maybe first question, can you give us the latest status of the CEO ongoing CEO search?

Scott Koenig, CEO, MacroGenics: Yes. And as you know, last year, it was announced that a search would be ongoing for my successor. It was anticipated when announced last year that the process would be completed by the February. Unfortunately, the process has not been thrilled to continue to work. So the expectation is over the course of the next couple of months, hopefully, a success will be identified.

Jonathan Chang, Equity Research Team, Leerink Partners: Understood. Can you discuss the latest status and progress with VOBER DOUO?

Scott Koenig, CEO, MacroGenics: Yes. As you know, VOBRADUO is our ADC first of actually four molecules that we’ve developed that target B7H3 ADC, first ADC in the clinic. It is an ADC that uses a linker toxin called durocamycin, which is a DNA alkylating agent. We provided the latest update at ESMO in September on the landmark endpoints for that trial, as well as an update on the safety of the program. We were very pleased that this study called Tamarac was designed to look at two lower doses of VOBERDU as compared to the dose we used in the Phase one study of three mgs per kg on a Q3 weekly basis, we were testing two and two point seven every four weeks.

The landmark data showed that we achieved what we were going after in the context that more doses were able to be delivered for patients longer. Second is the RPFS at landmark was superior to what we saw with the Phase one data. The comparison at the six month landmark was approximately eight to eight point five months for each of those lower doses compared to five point five with a three mg dose. And we saw significant reductions in a lot of the safety parameters, particularly hand foot syndrome would drop by fifty percent or more reduction in neutropenias. But as we were continuing to give the drug longer, we also saw some new observations of the pleural fusions were coming a little later.

And so where we are right now is that the last patients were dosed in July. The study was designed to follow these patients six more months for endpoints. So we’ve reached that point. What we have said is that we will analyze the totality of the data with regard to efficacy and safety. But as important, looking at what is the activity of this molecule versus things in our own portfolio, what the competitive landscape is in terms of other things that are in experimental development.

And then ultimately, given our broad portfolio, it would be important for us to, if we were to take this forward, to do this with a partner. So get a better understanding of what are the opportunities for partnerships for further Phase twothree development in prostate cancer. What we will plan to do is provide an update very shortly about some of those decisions around this molecule.

Jonathan Chang, Equity Research Team, Leerink Partners: Got it. Maybe if we could just double click on that last point. What are the key considerations that will help inform what the next steps?

Scott Koenig, CEO, MacroGenics: So I would say if you put it in the context on the efficacy side, given where the standard of care, for instance, in the chemo naive population is around eight point three months. In the chemo experienced population, it may be around eight as well, although real world data suggests that both in the pre chemo and post chemo, it’s probably shorter, but let’s use that as the parameter. Thus, we’ve already achieved 8.5 at the landmark with expectations that we will see prolongation of the median PFS here. I would say that for us to be just able to take a risk on doing this, we should be in double digit median PFS. Then of course, any survival benefit would be a complete change for the market.

As you know, PSMA4, which looked at Plavicto, did not meet the criteria in the pre chemo nor in the post chemo setting. So there really is no curative treatment for metastatic castration resistant prostate cancer. And So anything that would prolong survival would be seen as an attribute here. So that’s, I would say, the parameters we would look on efficacy. With regard to the safety, what we would want to see is a pathway forward.

We have certain hypothesis on what we would do to improve the safety, particularly the pleural effusions. And again, if we move forward with a partner on this, we would design that into this study.

Jonathan Chang, Equity Research Team, Leerink Partners: Understood. And you also mentioned the comparison between this program and other things in your pipeline. Can you discuss your second B7 H3 ADC program, MGC026? Yes. And how is this differentiated from VORBADU?

Scott Koenig, CEO, MacroGenics: Well, quite, in a way, we are taking the learning curve and almost the best of all worlds. First of all, we know the variable domain of this molecule 126 is identical to the one we have in vograduo. And we did that purposely because we knew how good an antibody this was, A, high tumor to normal tissue binding properties, B, it is targeted to a domain within B7H3 that is inhibitory for this molecule. So that could be another attribute. And see, for an ADC, this is exceptionally well incorporated with the linker toxin into a cell.

And we actually have done some side to side comparisons with other competitive antibodies that we believe, based on sequencing, shows that our molecule has these added benefits and features. So we have a good variable domain. And now we add a linker toxin, which is a TOPO1 inhibitor. And we’re using the SINIFIX technology, which has an active exotecan molecule. This, again, would work that SINIFIX has done and what we have done as well, suggests as compared to other topo one inhibitors have features that appear to be superior.

Some of the parameters, for instance, are it seems to be more potent on a head to head comparison, again, compared to DXD, the deuxetican that the Daichi’s Merck molecule is using. It seems to be better than SN38, which is in Tridelby, another TOPO1 inhibitor. It has a lower multi drug resistance profile. And because it is linked to the glycan site within the Fc region, as many of you know, TOPO1 inhibitors, one of their main toxicities is the potential interstitial lung disease because you knock out binding to Fc receptors, which are expressed on alveolar macrophages and other granular sites, there’s a good chance that you would have less chance to have interstitial lung disease as a result of using this particular linker toxin. So where we are in this development plan having what we think is a good antibody, a good link or toxin, obviously, a lot of data now that says this is a good target.

We think we’re in a good position to move this forward. So we’re finishing out the phase one study, we expect to have that complete in the second half of this year. In the way this is designed in dose escalation, if we see activity in a particular tumor type, we have the ability to put little mini cohorts there. And so our expectation is to be able to provide an update later this year about the status of that program and then hopefully be able to give you an idea of which particular tumor types we would expand into in Phase II development.

Jonathan Chang, Equity Research Team, Leerink Partners: Got it. How would you characterize how the study has progressed so far?

Scott Koenig, CEO, MacroGenics: It’s exceptionally well. There is a lot of we have a lot of people clawing to get into the study. And as you know, it becomes a competition among investigators. Can I get my patient in there? And you only have a certain number of slots there.

So there’s been we’re moving this as quickly as possible to get to an answer.

Jonathan Chang, Equity Research Team, Leerink Partners: Do you think you have enough from the zero to six Phase I study to help inform your decision making on VORBADUO at this point?

Scott Koenig, CEO, MacroGenics: I would say we don’t certainly don’t have the breadth of comparison, particularly for prostate cancer. So no, that would be and I wouldn’t say that necessarily O2-six would be positioned to go after prostate cancer because of the wide While prostate would be one of the considerations, there are a number of other tumor types that we were likely to explore with O26.

Jonathan Chang, Equity Research Team, Leerink Partners: Understood. And if you think about how your two B7 H3 programs, how would you say they compare versus other things in the competitive landscape?

Scott Koenig, CEO, MacroGenics: Well, I think we have to look at this again in the context of prostate cancer line of therapy and then other tumor types as well. So let’s just start with the prostate story. As you know, we’re developing lorazirlimab, the PD-one CTLA-four molecule and being tested right now in the LORIKETE study in chemo naive metastatic castration resistant prostate patients. It is an unusual opportunity for us with this molecule for prostate cancer given that no checkpoint molecule has been approved for prostate cancer. And actually, there is no competition out there that we know of in the checkpoint space in prostate cancer.

And specifically, the only other company that was working on a PD-one CTLA-four was Zencor recently, who has announced that they’re stopping their PD-one CTLA-four program where they were only looking at a subpopulation of prostate cancer with DNA repair deficit. So if we’re able to succeed here in combination with docetaxel in a chemo naive population, we have As many of you know, we had presented data about two and a half years ago in late state castration, which is in the prostate cancer, where we saw a very nice outsized response, overall response rates, as well as PSA50 reductions as compared to ipinivo tested in similar settings as compared to pembro tested in similar settings. And so again, we have finished enrollment of one hundred and fifty patient study in December. So one hundred patients getting docetaxel plus loradirlimab versus docetaxel alone. As we know in the chemo naive population, as I stated before, the median PFS is about eight months at best on the comparatives other studies.

So if we see a obviously an improvement on that combination or a nice subpopulation that is having a long prolonged response or improvement of OS, This is a terrific opportunity to develop this not only as a combination with DOSY, but then the thought is you can combine this with other agents that are orthogonal to the checkpoint activity of this molecule.

Jonathan Chang, Equity Research Team, Leerink Partners: Got it. I was going to touch on that anyways, but actually my prior question was with regards to your 2B7H3 ADC programs and how do those compare, you

Scott Koenig, CEO, MacroGenics: think, versus competitive ones? Oh, okay. So obviously, I would say that the VOBR Duo data to date is better than any other ADC in prostate cancer. The biggest data set we have out there to compare to was the Daiichi molecule, which in their Phase one data, they showed about fifty patients with a PFS of 5.3 months. So already when I described our landmark endpoint of six months of being already eight, eight point five, we’re superior to that.

And now with further follow-up, we expect that to be even higher. So at least in the terms of activity, I think in prostate, we have a superior opportunity there, although we have a different safety profile that we would have to contend with. Now with regard to other indications, a lot of the other B7 HD molecules, including the Daiichi, the MEDI link and hand cell molecules with GSK have shown nice activity in small cell lung cancer. As you know, many of them are moving forward to Phase III development in that indication, and there are other depending on the company being pursued for other things. So with regard to O26, we are certainly behind time wise.

But given the broad expression of this, I think we can find our competitive indication where we can move quickly ahead if the Phase one data turns out as we expect.

Jonathan Chang, Equity Research Team, Leerink Partners: Understood. Maybe switching over to MGC-twenty eight, can you tell us about this next gen ADAM9 program?

Scott Koenig, CEO, MacroGenics: Yes.

Jonathan Chang, Equity Research Team, Leerink Partners: And how is this program differentiated from, I guess, the past ADAM9 program that you guys previously have partnered with ImmunoGen?

Scott Koenig, CEO, MacroGenics: Yes. So this is a great opportunity. One of the things that, if you look at the history of MacroGenics, we like to have the balance between going after both validated targets as well as novel targets. B7 H3 was a good example. We were the first company to make any molecule to that target.

And the same story is true for ADAM9. This is a target that is a metalloproteinase by activity, although the doses we’re using here is not to inhibit the metalloproteinase activity. This is a target that’s highly overexpressed in a lot of different tumor types, lung cancer, a lot of GI cancers, including pancreatic, colorectal, cholangiocarcinoma, gastric. It’s also found in a subset of prostate and triple negative breast. We have published and presented at AACR last year the preclinical data on this molecule showing terrific activity in vitro and in vivo against a lot of different tumor types.

Jonathan, as you’ve alluded to, we jumped into the clinic with this target with a collaboration with ImmunoGen a couple of years ago using their sort of next generation metantinoid called DM21. We took that through Phase one development. It was a fiftyfifty partnership. And ImmunoGym was acquired by AbbVie, and AbbVie presented the data on the Phase one at a meeting, which showed that we could not achieve the targeted dose that we were hoping because of the associated eye toxicity that is characteristic of metancinoid toxins. And so we both agreed that that nine thirty six molecule would not move forward.

But because we had such good preclinical data on the variable domain, and we own that and we developed that variable domain, we decided to make a new molecule which contains the exact same variable domain we used in nine thirty six. But now we’re using what I previously described, the SINIFIX linker toxin linked to the glycan in the Fc domain, which is active moiety as exotecan. So again, good experiences with the variable domain. Good there’s a good track record so far with the linker toxin. And so we are starting Phase I development there for this molecule.

So we’re again the only one in the clinic with this target.

Jonathan Chang, Equity Research Team, Leerink Partners: Understood. And how should we think about timelines for that clinical?

Scott Koenig, CEO, MacroGenics: What we decided to do is instead of having an open to every tumor type, we are focused on a subset of the tumors that should be responsive so that we’re hoping to get to a signal both in terms of activity and safety in a shorter period of time. So this is just starting. I would anticipate in ’twenty by ’twenty six, we would have enough data to be able to provide some update on the program.

Jonathan Chang, Equity Research Team, Leerink Partners: Understood. And how are you thinking about business development opportunities for your programs and platform?

Scott Koenig, CEO, MacroGenics: Well, we’re very excited about that. Again, as you know, historically, we’ve been very active in business development and taking advantage of the broad platforms and targets, and that has attracted a lot of capital to the company, both through partnerships, but ultimately, even in the clinic and approval. As I alluded to before, we have N25 opportunities from the Incyte and Sanofi partnerships that we would potentially see more capital coming in, in the cases of both of those in terms of milestones. And in the case of Incyte, particularly, we have a 15% to 24% royalty on that. So if it gets approved in a larger indication like anal cancer, we could expect more money coming in from sales of that.

But also it’s a potential for modernization if we decide to go that route for the royalties. In addition, we have the partnership with Gilead, which I alluded to before. There is the dose escalation study for the one hundred and twenty three by CD3. They have an option by the end of Phase I. We have a second program, a research program that is proceeding very well on another DART molecule, and we’re actually exploring some work on a third molecule with them.

So opportunities there in terms of both milestones and other payments from that partnership. Even beyond that, people are very interested in other things in our portfolio, both clinically and pre clinically. And we’ll just wait later in the year to describe those opportunities. Just again to put this in context, we brought in hundreds of millions of dollars from these various opportunities in the past couple of years. And I think we will continue to follow that pathway forward.

Jonathan Chang, Equity Research Team, Leerink Partners: Understood. Let me check, see if there are any questions from the audience. All right. Then maybe just last question from me. Can you highlight the key 2025 catalyst and milestones that

Scott Koenig, CEO, MacroGenics: the investor should be looking forward to this year? Yes. So for ’twenty five, I alluded to some of these things. Obviously, very soon update status of OBERDUO, where we expect to go with that. Second is bring you up to date on the loragirilumab, lauriquet study, probably second half of this year with regard to the clinical outcomes on that program.

I should also point out based on our Phase one dose escalation data with lorogerumab plus the activity we’ve seen in both Phase one and now Phase two in lower key in prostate cancer, we will announce another tumor type, which we will be pursuing for lorazirlimab. So that stay tuned for that very shortly. Obviously, progress on the ADAM9 program this year and then the second half of this year, certainly an update on ’26 going forward and then likelihood of business development announcements during the course of the year.

Jonathan Chang, Equity Research Team, Leerink Partners: Understood. Well, thank you very much for joining us.

Scott Koenig, CEO, MacroGenics: Well, thank you so much for the invitation. All right.

Jonathan Chang, Equity Research Team, Leerink Partners: Thank you.

Scott Koenig, CEO, MacroGenics: We’ll see you. Thank you.

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