MacroGenics at Citizens JMP Life Sciences Conference: Strategic Pipeline Insights

On Thursday, 08 May 2025, MacroGenics (NASDAQ:MGNX) presented at The Citizens JMP Life Sciences Conference 2025, detailing its strategic focus on a diversified R&D pipeline and financial stability. The presentation highlighted both the promising developments in bispecific and ADC programs and the ongoing search for a new CEO. While the company’s financial runway appears secure, the success of upcoming clinical data readouts will be crucial.

Key Takeaways

• MacroGenics is focusing on developing and licensing innovative drug candidates, with four assets currently in the clinic.
• The company has a cash runway extending into the second half of 2026, supported by $475 million in non-dilutive funding over the past three years.
• Upcoming data readouts for Lorigirilimab and ADC programs are anticipated, with potential implications for prostate and ovarian cancer treatments.
• A nationwide search for a new CEO is underway, with Scott Koenig continuing as CEO until a successor is appointed.

Financial Results

• MacroGenics ended 2024 with $200 million in cash.
• The company has prioritized non-dilutive funding, securing $475 million in the last three years.
• No formal marketed offering has occurred since February 2019.
• The cash runway is projected to extend into the second half of 2026.

Operational Updates

• Four clinical assets are in development, including Lorigirilimab, an anti-PD-1/CTLA-4 bispecific, with upcoming data expected.
• The ADC programs, including MGC-026, utilize a topo-one based drug linker from Cinefix.
• The MGD024 program, in collaboration with Gilead, is in phase one dose escalation, targeting hematologic malignancies.

Future Outlook

• Clinical data readouts for Lorigirilimab and ADC programs are expected later this year.
• The company aims to extend its cash runway through strategic partnerships and licensing deals.
• MacroGenics is focusing on a portfolio approach, seeking to differentiate its assets in competitive areas.

Q&A Highlights

• The LORA KEET study for prostate cancer combines Lorigirilimab with docetaxel, aiming for improved median PFS.
• MGC-026, targeting B7-H3, shows potential across various solid tumors.
• MGD024, developed with Gilead, targets hematologic malignancies, with a focus on improved administration and tolerability.

In conclusion, MacroGenics’ presentation at The Citizens JMP Life Sciences Conference 2025 underscores its commitment to advancing its R&D pipeline and securing financial stability. For further details, refer to the full transcript below.

Full transcript - The Citizens JMP Life Sciences Conference 2025:

Silvan Turkan, Senior Analyst, Citizens: Alright. Welcome back. My name is Silvan Turkan. I’m a senior analyst at Citizens covering precision medicines.

Thanks so much for joining us at our healthcare conference. And now it’s my pleasure to host MacroGenics. With me is Eric Rissen, COO of MacroGenics. Thank you so much.

Eric Rissen, COO, MacroGenics: Great. Thank you, and appreciate the opportunity to present here today at the conference and talk about MacroGenics and all the milestones and upcoming events for the company over the course of this year.

Silvan Turkan, Senior Analyst, Citizens: Yeah. Great. No. Looking forward. Maybe can you provide us some background of how you’re redirecting MacroGenics now after, you know, the r and d engine, specifically after the, vobo duo?

Eric Rissen, COO, MacroGenics: So I think the operative word there is r and d engine. You know, we’ve had a history of being a very prolific drug discoverer developer. We actually have four assets in the clinic, which were all homegrown assets, some cases leveraging platform technology that we developed internally. But we’ve also licensed in for our ADC portfolio some proprietary drug linker chemistry. So four assets in the clinic actually spanning three different mechanisms.

We’re very excited about the prospects of each of these. The lead asset in that portfolio is Lorigirlimab, which is a bispecific molecule that blocks both PD-one and CTLA-four. We actually fully enrolled a randomized phase two study, we’ll have some data coming up latter part of this year on that program. We also have two ADC programs leveraging a topo-one based drug linker that we licensed from Cinefix. Those are in the clinic in phase one going through dose escalation.

And again, we’re excited about prospects of where those studies might be, later in the year. And then we also have a bispecific molecule which is predicated on a T cell engager mechanism. So CD3 by CD123 that is part of an option based deal with Gilead. And that’s also going through phase one dose escalation. And then in our earlier research labs, we continue to innovate and advance additional molecules.

The first of which will be now in the clinic next year. That’s another ADC program called MGC030. So a lot of activity in the portfolio, multiple mechanisms, many of which are actually quite complementary with one another. So we think we’ve never been really reliant on a one asset kind of investment thesis. It’s really been a portfolio approach, and we think the portfolio will do very well over the course of this year.

Silvan Turkan, Senior Analyst, Citizens: Mhmm. Great. No. Thanks for this overview. And, obviously, maybe I’d like to start with the bispecifics because, you know, it is obviously a very growing or hot topic right now, and and, you know, we’re awaiting some very important readouts, I think, from from some and and others the the summer generally in that space.

Can you just give us an overview of lugrelimab and and, you know, how how you came up with what you designed the molecule for and then how it fits, what data we’ve seen and how it fits in the prostate cancer.

Eric Rissen, COO, MacroGenics: Yeah, so we’re very excited about that molecule. Obviously, whole field checkpoint inhibition has gone through a little bit of an evolution with the first introduction of pembro and evo about eleven years ago, a flurry of interest in alternate checkpoint molecules, which in some areas did disappoint. But we have seen in a reemergence, particularly in the context of bispecific formats and actually working on validated targets. So PD-one VEGF obviously has restored some excitement in the category. Our PD-one CTLA-four molecule we’re also very excited about.

The promise of that was initially highlighted at ASCO GU when we had some monotherapy data, and that was highlighting, experience in a late line castrate resistant prostate cancer population, where historically immune checkpoints have not worked. This has been more of a immunologically inert indication. Pembrolizumab in some of their early studies only had single digit response rates. And in that study, we actually reported, twenty six percent confirmed ORR. We also had pretty meaningful PSA reductions, you know, about twenty nine percent and actually there was also very good correlation with PSA 90 as well as the responders in that study.

So great that we had early induction of response but was equally important as we actually had pretty long durable responses with in some cases patients staying on study for over two years. And that is really unprecedented when you think about some of the prior experience, for instance with ipinivo, when those molecules were combined, the toxicity really required them to limit the ipilimumab dose to only two or three cycles. So the fact that we can get continuous blockade of PD-one and CTLA-four in some cases going out two years plus is pretty provocative. And that really led us to kick off the LORA KEET study, which is a randomized phase two. It’s a 150 patients study with two to one randomization.

And there we’ll be actually combining on top of docetaxel as kind of the prevailing standard of care in a second line population and then doing it against Dozy as a monotherapy. So that was fully enrolled, late last year, and it is a, event based endpoint with, medium PFS is really the lead endpoint. So we’re obviously continuing to accrue events and hope to have some updates on that program, later this year.

Silvan Turkan, Senior Analyst, Citizens: Great. And maybe just to clarify, your monotherapy data, that was post chemo, right? Or a significant amount of patients?

Eric Rissen, COO, MacroGenics: That was a late line population. You know, vast majority had both ARAT as well as docetaxel primarily probably third, fourth line, but actually we had about a quarter of those patients that were, you know, at least four plus prior lines of therapy. So pretty late line population and again, provocative early signals and now we’re building on that with what would be primarily a second line population. So in the Lorikeet study, where we’re combining it with docetaxel, these are patients who’ve progressed on prior ARAT therapy and they’re all by definition chemotherapy naive, so potentially a little bit more, responsive patients especially for immunological intervention where earlier lines sometimes can drive an even more pronounced benefit. Great.

Silvan Turkan, Senior Analyst, Citizens: Maybe can you outline a little bit, kind of, I mean, I guess what we’ll see in the data? I think you alluded to some PFS or or at least what we’ll see in terms of durability in this data. And then kinda what the bar is. Obviously, prostate cancer is evolving quickly, right? So so we got the the radio treatments coming in here, cabozantinib, is trying to find its space there.

Obviously, we we had some difficulties with the control arm here. Right? So we don’t know if it’s it’s gonna be filed or not. You have a chemo control arm. Would you think you’re coming a little bit later with respect to those new treatments or maybe at the same

Eric Rissen, COO, MacroGenics: It is a very heterogeneous population. It’s also a very competitive category, which is also why we really were adamant to make sure we had a control arm in that study. If you look at some of the historical efforts with docetaxel, for instance, the KEYNOTE-nine 21 study, which was pembro plus docetaxel versus docetaxel, In that control arm, they had about an eight month PFS value. That’s a little bit higher than what has been reported when we look at real world evidence and there were some features of that study where it was again immunotherapy based, where some of the investigators were potentially treating even beyond initial study progression. So, we’ll see where we end up with that, but we do have that control arm to really give us a clear, benchmark that we’re going to look to beat and see if we can meaningfully extend PFS there and also have overall acceptable safety tolerability profile.

Silvan Turkan, Senior Analyst, Citizens: Okay. That’s very helpful.

Eric Rissen, COO, MacroGenics: But it would tee us up for potentially a future registration path that would likely be again recapitulating that regimen and that would be primarily a second line, population.

Silvan Turkan, Senior Analyst, Citizens: Okay, great. You also have another study, the Lynette study, in ovarian cancer and other gynecological cancers. Could you just tell us about what motivated this trial, and where you are with it, and when we could see, I guess you’re just ramping it up, but when could we see data?

Eric Rissen, COO, MacroGenics: Yes, so really excited about this program. It’s in some ways a little bit of the same playbook as prostate cancer, another indication that has been historically not very sensitive to immune therapy. Again, the benchmarks there for traditional PD-one monotherapy were single digit response rates. Checkpoint therapy has had limited success, although there have been evidence that PD one plus CTLA four combo has actually meaningfully raised the bar there and they’ve generated twenty five, thirty percent response rates in some of the studies that have reported. But again, the safety liabilities are are always a challenge there, and that’s where we think our approach, which is the tetravalent format enabled co engagement of these double positive TILs.

You really localize the effect, potentially have a better overall safety profile. We think that could be a real, differentiator. And we also know that ovarian cancer in these later line, settings, chemotherapy is only driving ten to fifteen percent response rate. So the hope is we can show meaningful, activity both in terms of the response rate, but also durability. And that again is an opportunity to really differentiate, is really driving much more extended efficacy benefits for patients.

It’s also one of the shortcomings with some of the ADC approaches in this area. So there’s obviously been a big surge of interest across lots of different targets. You’ve seen the folate receptors, you’ve seen the B7H4, you’ve seen cadherin six. So a lot of ADCs that are targeting ovarian cancer, many of which are, relying on topo-one based payloads. The Mirvetuximab asset was based on metanzanoate based platform.

They do have pretty good potential to induce rapid, tumor reduction, but the PFS in those studies in that late line population has only been five months or so in terms of median PFS. So that’s also an opportunity longer term is, you know, see where the monotherapy signal pans out, but opportunities longer term to think about a whole life cycle strategy that could be both monotherapy, but also combination.

Silvan Turkan, Senior Analyst, Citizens: Okay, that makes sense. So for now, study, the Lannett should have plenty of failures of these ADCs enrolling, right?

Eric Rissen, COO, MacroGenics: Could be, mean the only one that is approved right now is mirvetuximab, so there may be some of those, this will be primarily patients with one to three prior lines of therapy and it actually is two populations that are embedded in this study, which is about a sixty patient study overall. One is the platinum resistant ovarian cancer patients, which is the population where mirvetuximab is approved, although they’re only approved for a subset that have high folate receptor expression. The other part of the study is actually looking at clear cell gynecologic malignancies. So that’s a subset that historically has not been very chemo sensitive and actually the checkpoint therapies, although not approved, have seen a little bit more encouraging activity. So it’s a smaller disease, but potentially an opportunity to really show an outsized signal with a novel immune checkpoint approach.

Silvan Turkan, Senior Analyst, Citizens: Nice. Maybe moving on to B7 H3, obviously you’re still very excited about that target, and and, you know, you’re a leader in that space, having pioneered already in ADC here. You now have MGC o 26, which uses a topo one payload. Can you just talk about, you know, that, let’s call it the next generation ADC for b seven h three, and and how that fits in?

Eric Rissen, COO, MacroGenics: Yeah. So, that molecule, which is called MGC zero two six or MacroGenics conjugate zero two six, as well as actually the the two succeeding molecules, o two eight and o 30, all leverage the Sinefix based platform. We were an early adopter of that platform, and we’re really excited about the potential, the promise, also the potential to differentiate from other topo ones. I think it’s fair to say that not all topo one ADCs are the same, and you can think about both the payload where we are relying on an exoticon based approach. Daiichi Sankyo, which is probably the furthest along with, topo-one based ADCs, theirs is predicated on diruxatecan.

And again, there’s been a lot of work published suggesting that exoticon is two to five fold more potent than diruxatecan. It supports better cell permeability and better bystander killing versus doroxetine, and it’s actually less susceptible to, multidrug resistance and efflux pump escape mechanisms. So a lot of points of differentiation on the payload. They’ve been able to use one of their proprietary, polar spacers to enable conjugation to exatecan. This payload tends to be a little bit more hydrophobic, so that’s really the challenge in terms of how do you enable conjugation.

We believe we’ve kind of addressed that concern. And then the other differentiating feature with our approach is we do actually rely on a site specific conjugation approach. This is called the glyco connect, where we can actually engage the native glycan. So the benefits there is you do get a much more homogenous, material. So it’s really DAR4 specific, potentially improves the therapeutic, window and, overall tolerability of the agent.

And by virtue of binding to the native glycan, you’ve essentially knocked out, Fc receptor function and potential liabilities of ADCC. And what has also been reported and published is that these Fc gamma receptors can in some cases, enable non specific uptake of these alveolar macrophages which in some cases could also contribute to lung toxicity, which is something that everyone is always watching with regard to TOPA one. So again, we’ll have to see how this all plays out Mhmm. In the clinical setting, but I think there’s a lot of, you know, reasons for optimism in terms of where this agent will play. And then obviously, the other point beyond the technology advantages, you know, what is the development strategy?

Where do we wanna position? And we’ll have, you know, some additional updates on that later in the year. We haven’t yet disclosed which specific expansion courts we’re gonna be pursuing. But the hope is that would, you know, start panning out later part of this year.

Silvan Turkan, Senior Analyst, Citizens: Okay. Yeah. Maybe I’m going to try to poke around that a little bit, obviously Daichi, think correct me if I’m wrong, was still very focused on small cell lung cancer and and you obviously have experience with vobaduo with a different payload in prostate cancer. What other tissues make sense for TOPO-one B7 H3?

Eric Rissen, COO, MacroGenics: Well B7 H3 is a target and this is why there is such broad interest in this target. Has a very broad expression pattern across a number of different solid tumors. The ones that have really advanced now to pivotal studies, Daiichi Sankyo and others have, targeted small cell lung cancer as a priority indication that’s both in late line settings, but also starting to move into earlier lines of therapy, also combinations with standard of care. Esophageal cancer has been a tumor where there’s been pretty interesting data published and some late stage studies ramping up. Then actually prostate cancer, Dietrich Zanko recently announced that they’re standing up a large, I think a 1,400 patient phase three study in that indication, but there’s actually a number of others.

There’s probably a dozen or so tumor types spanning GI cancers, gynecologic cancers, thoracic cancers. So it’s still, I think, a wide open arena. Obviously, lot of competition, but I think this is an area you’re going to have not just winner take all, but there’ll be you know, a few groups that will be able to carve out a meaningful market opportunity for themselves.

Silvan Turkan, Senior Analyst, Citizens: Yeah. No. That’s right. Remember Daichi making several comments about how big they they view b c n seven h three as an opportunity for themselves.

Eric Rissen, COO, MacroGenics: Exactly. And that was obviously reflected with the collaboration they with Merck. That was a major partnership, 2,000,000,000 in upfront capital committed. So they’re obviously looking to extend this across many different tumor types. I think we’re just getting started in terms of where the field is going and and where the different development opportunities are for that program.

Silvan Turkan, Senior Analyst, Citizens: Great. Maybe talking a little bit high level about MacroGenics, on the operational side. At year end ’24, you had 200,000,000 in in cash, and and the runway was into second half of twenty six. Just how are thinking about extending the runway? Would and what BD options do you have?

You know, you’ve done already a lot. And and what kind of, like what are the key catalysts, you know, that that you could use maybe to to, you know, get more diluted funding per perhaps or something like that. So so where where do you what do you think will be the highlights over the next until your cat runs out?

Eric Rissen, COO, MacroGenics: Yeah. So we’ll we’ll obviously have data coming out over the course of this year, but we’ve also had, I’d say, a pretty impressive track record in terms of our corporate deal making prowess. So over the last three years, we’ve actually brought in about $475,000,000 in non dilutive capital. We have not done a formal marketed offering since 02/2019.

Silvan Turkan, Senior Analyst, Citizens: Mhmm.

Eric Rissen, COO, MacroGenics: So we’ve been able to, you know, obviously, public markets are probably not gonna be a primary option at this point. So nondilutive sources of capital is something we’re always thinking about. Again, we’ve had a a strong track record, in executing in those areas, and we’re always, you know, exploring options for the future. And the expectation is we’ll continue to extend, you know, that runway to enable us to support these programs and carry them to important inflection points.

Silvan Turkan, Senior Analyst, Citizens: Mhmm. Great. Maybe talk about MGD o 24. Gilead has an exclusive option here to license the CD123 CD3 DART. What are some of the factors getting that option, and where are you in your phase one trial?

Eric Rissen, COO, MacroGenics: Yes. So the molecule that’s MGD024 targeting CD123 and CD3, it’s actually a follow on molecule or second gen molecule that came in the wake of flotetuzumab, which was also CD123 directed. Here we’ve actually tailored the CD3 binding domain. We’ve in some ways detuned the affinities but also changed the whole kinetics of the binding properties and what that has enabled us to do is reduce some of the cytokine release that we’ve seen with that earlier stage molecule. That’s all based on some of the early preclinical work that we have done and published.

It also is an Fc bearing construct, whereas the first generation molecule did require continuous infusion. The benefit of that first generation molecules, we have a lot of data, and empiric evidence that we can start baselining against to figure out how do we further improve the features of this molecule. So that isn’t a a dose escalation. It is part of an option based agreement with Gilead. They’re really driving the timetable in terms of data disclosure and dissemination.

It is going through dose escalation, which has been a fairly prolonged effort, that is partially for these class of molecules and based by on the direction of the FDA, they’ve taken a little bit more measured approach in terms of how we’re going through dose escalation and also the requirement to start at this Mabel dose level, which is very, very low doses. But, you know, it continues. We’re excited about the prospects of the molecule. And actually about a year after that first collaboration was announced, actually Gilead expanded the relationship with MacroGenics with a second bispecific molecule, and that is also now progressing. That’s still preclinical stage.

So, you know, very excited about that relationship. Great. What kind of patient are you enrolling, in that trial, or who’s getting dosed? So these are hematologic malignancies that are typically CD123 expressers, primarily AML, MDS would be really the prevailing tumor types. And how does it fit in AML?

So would this be post relapse? For this initial population it’ll be post relapse or a later line population, but again based on the design goals of this molecule, it creates something that’s a little bit more convenient in terms of administration, potentially a little bit more tolerable. The opportunities are also to go into earlier line and do combination based approaches and some of that work we’ve also published and there does seem to be nice complementarative mechanisms when you add into other agents.

Silvan Turkan, Senior Analyst, Citizens: Would it be it be combinable with venetoclax or or or some of the target therapies?

Eric Rissen, COO, MacroGenics: It it could be. I mean, there’s a lot of opportunities there. You know, azacitidine, you know, so there’s a a host of, agents that we’re looking at, and ultimately Gilead will likely direct that strategy in terms of where they wanna combine and and how they wanna prioritize.

Silvan Turkan, Senior Analyst, Citizens: Great. And what are the next steps on Gilead on that particular molecule? Like, would it be an opt in, or or what and when would that happen?

Eric Rissen, COO, MacroGenics: Yeah. So the way that the agreement was structured, there is an opt in decision point, and actually there’s several decision points that are hardwired into the agreement, and that would be in the context of the phase one study. Yeah. So specific timing guidance we haven’t actually provided at this point.

Silvan Turkan, Senior Analyst, Citizens: Okay. Great. May maybe ask about, your CEO search. How is that going, and and can you give us some color around, you know, what kind of candidate you’re looking for or or when that could come to an end?

Eric Rissen, COO, MacroGenics: Yeah. So late last year, you know, the board announced that we have a nationwide search that they kicked off. We don’t have any specific timetable to really disclose at this point. There is a subset of the board for members of a of a search committee, and they’re going through that, process. Scott Koenig is continuing to function as the CEO and is committed to really, you know, supporting the company and, you know, making sure there’s a, you know, good transition, you know, when that next candidate is

Silvan Turkan, Senior Analyst, Citizens: Alright. Welcome back. My name is Wilbon Turcan. I’m a senior analyst at Thank you so much.

Eric Rissen, COO, MacroGenics: Great. Thank you, and I appreciate the opportunity to present here today at the conference and talk about MacroGenics and all the milestones and upcoming events for the company over the course of this year.

Silvan Turkan, Senior Analyst, Citizens: Yeah. Great. No. Looking forward. Maybe can you provide us some background of how you’re redirecting MacroGenics now after, you know, the r and d engine, specifically after the Vova Duo?

Eric Rissen, COO, MacroGenics: So I think the operative word there is R and D engine. We’ve had a history of being a very prolific drug discoverer developer. We actually have four assets in the clinic, which were all homegrown assets, some cases leveraging platform technology that we developed internally. But we’ve also licensed in for our ADC portfolio some proprietary drug linker chemistry. So four assets in the clinic actually spanning three different mechanisms.

We’re very excited about the prospects of each of these. The lead asset in that portfolio is Lorigirilimab, which is a bispecific molecule that blocks both PD-one and CTLA-four. We actually fully enrolled a randomized phase two study, so we’ll have some data coming up latter part of this year on that program. We also have two ADC programs leveraging a Topo-one based drug linker that we licensed from Cinefix. Those are in the clinic in phase one going through dose escalation.

And again, we’re excited about prospects of where those studies might be, later in the year. And then we also have a bispecific molecule which is predicated on a T cell engager mechanism. So CD3 by CD123 that is part of an option based deal with Gilead. And that’s also going through phase one dose escalation. And then in our earlier research labs, we continue to innovate and advance additional molecules.

The first of which will be now in the clinic next year. That’s another ADC program called MGC030. So a lot of activity in portfolio, multiple mechanisms, many of which are actually quite complementary with one another. So we think we’re, you know, never been really reliant on a one asset kind of investment thesis. It’s really been a portfolio approach, and and we think the portfolio will do very well over the course of this year.

Silvan Turkan, Senior Analyst, Citizens: Mhmm. Great. No. Thanks for this overview. And, obviously, maybe I’d like to start with the bispecifics because, you know, it is obviously a very growing or hot topic right now, and and, you know, we’re awaiting some very important readouts, I think, from from Summits and and others this summer generally in that space.

Can you just give us an overview of lugrelimab and and, you know, how how you came up, what we what you designed the molecule for, and then how it fits What data we’ve seen and how it fits in the prostate cancer?

Eric Rissen, COO, MacroGenics: Yeah, we’re very excited about that molecule. Obviously, the whole field of checkpoint inhibition has gone through a little bit of an evolution with the first introduction of, you know, pembro and evo about eleven years ago, a flurry of interest in alternate checkpoint molecules, which in some areas did disappoint.

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