MacroGenics at H.C. Wainwright Conference: Strategic Antibody Advances

On Monday, 08 September 2025, MacroGenics Inc. (NASDAQ:MGNX) presented at the H.C. Wainwright 27th Annual Global Investment Conference, outlining its strategic focus on developing next-generation antibodies for cancer treatment. The company emphasized its robust pipeline and strong financial position, although challenges remain in the competitive landscape of oncology.

Key Takeaways

• MacroGenics has a cash runway extending through 2027, supported by a recent $70 million royalty monetization deal.
• The company is advancing five key pipeline assets, with Lorigirlimab showing promising results in prostate cancer.
• MacroGenics secured $550 million in non-dilutive funding over the past three years.
• The company plans to submit an IND for MGC-030 next year and continue exploring corporate partnerships.
• Lorigirlimab demonstrated a 26% overall response rate in prostate cancer, surpassing traditional PD-1 agents.

Financial Results

MacroGenics reported a strong financial position with $177 million in cash and marketable securities, ensuring a cash runway through 2027. The company has successfully secured $550 million in non-dilutive funding over the past three years, including a $70 million deal with Sagard in June. Future payments are anticipated from partnered programs, including milestone payments and royalties from collaborations with Gilead and others.

Operational Updates

Lorigirlimab, a PD-1/CTLA-4 bispecific molecule, is in development for castrate-resistant prostate cancer and gynecological cancers. The Lorikeet study is fully enrolled, with a clinical update expected later this year, while the Lennet study is actively enrolling patients. MacroGenics is also advancing its ADC portfolio, with MGC-026 and MGC-028 in Phase 1 trials and MGC-030 slated for IND submission next year.

Future Outlook

MacroGenics aims to provide additional clarity on the development path for Lorigirlimab and establish clinical proof-of-concept for its ADC portfolio. The company plans to submit an IND for MGC-030 next year and advance other first-in-class molecules from its research portfolio, with new INDs expected every 12-18 months. Corporate partnerships remain a strategic priority to enhance financial stability.

Q&A Highlights

During the Q&A session, CEO Eric Risser highlighted the significance of Lorigirlimab’s 26% overall response rate in prostate cancer, comparing it favorably to the single-digit response rates of traditional PD-1 agents. The company’s innovative technologies and strategic partnerships were emphasized as key drivers of future growth.

Readers are encouraged to refer to the full transcript for a detailed overview of MacroGenics’ presentation and strategic initiatives.

Full transcript - H.C. Wainwright 27th Annual Global Investment Conference:

Eduardo Martinez, Biotechnology Equity Research Associate, HC Wainwright: Hello, everyone. Thank you for joining us for another session of HC Wainwright’s twenty seventh global investment conference. My name is Eduardo Martinez, and I’m a biotechnology equity research associate at Wainwright. And it is my pleasure to introduce mister Eric Risser, CEO of MacroGenics.

Eric Risser, CEO, MacroGenics: Thanks, Eduardo. Appreciate the chance to speak at this year’s, Wainwright, conference. I’ll be making some forward looking statements during the course of their presentation, so I urge all of you to refer to our, SEC filings for more complete account of our, various risk factors that might impact the business. So I’m gonna kick it off with a little bit of overview on the company for those of you that may not have followed the story as closely, and then I’ll spend a little bit of time going through each of five feature projects in our core pipeline. And then I’ll recap on some of our key strategic priorities for 2025 and 2026, which I introduced on our last earnings release a few weeks ago.

So MacroGenics is a company focused on developing next generation antibodies for the treatment of cancer. We have a promising pipeline that encompasses four clinical stage programs. These four programs actually span three different modalities. One of them, is around ADC technology where we leverage third party drug linker chemistries that we’ve licensed in. We actually have three molecules leveraging the Cinefix platform, two of which are in the clinic.

One will be entering the clinic next year. We also are a innovator around multi specific platforms, and we actually have our own homegrown DART and Trident platforms that we’ve applied for a number of different modalities, including, t cell engagers, where we have a c d three based molecule in the clinic. That’s a molecule that’s been partnered with, Gilead. And then we also have applied the bispecifics to enable co blockade of two different immune checkpoints in a single recombinant molecule. One thing I like to highlight is is we have a lot of technology, but we don’t think of ourselves as a technology boutique per se.

We have a world class development team spanning clinical, regulatory, CMC, and have actually been able to take molecules from our early development efforts and bridge them all the way through an approval milestone. And you can see on this slide three examples of molecules that came out of our early development efforts that are now approved and commercialized. Margemza for late line, her two positive breast cancer, TZeal, the c d three partial agonist that’s approved for a type one diabetes, and then Zyniz, which is a p d one asset, that is being now sold for both, anal cancer as well as Merkel cell carcinoma. We are well resourced and ready to deliver on the plan that we’ve outlined with a cash runway that extends through the 2027. This includes cash and marketable securities of about 177,000,000.

That has actually increased from our last quarter based on some additional transactions that were announced, namely the royalty monetization deal with Sagard that was announced in June, brought in $70,000,000 of capital. And this cash runway guidance also takes into account future projected and anticipated payments from the company’s various partners. This is a encapsulation of our portfolio, which includes both proprietary pipeline programs where we retain full commercial rights as well as some partnered, programs which are on the bottom panel of the slide. Lorigirlimab is our p d one CTLA four bispecific molecule, which is being developed in two indications. The so called Lorikeet study is looking at a castrate resistant prostate cancer population.

This is a randomized study. I’ll talk about the specific design, components of that study as I go through the remainder of the presentation. And then we also have a a study in ovarian cancer and clear cell gynecologic cancer called the Lennet study that’s actively enrolling. This is a molecule that has the promise to almost, afford a pipeline within a product where it can be applied across a number of different tumors as well as monotherapy and combination regimens. The next three assets that are listed are all ADCs, and they all employ a platform that was licensed from Cinefix.

They have a proprietary drug linker that enables both site specific conjugation and also enables conjugation with a very potent topo one payload called exoticon. We were an early adopter of this technology. They’ve subsequently had a number of major pharma alliances that they’ve announced. By virtue of being an early adopter, we actually have broad access to the platform. Again, we’ve applied it for all three of these, molecules, and the original deal actually enabled us to pursue up to seven different molecules leveraging their platform.

The first asset listed is a b seven h three directed program. This is an exciting target that has actually had broad clinical validation across a number of solid tumor targets. We think there are some differentiating features both in terms of the technology, but also our development strategy for this molecule, MGC o two eight and MGC o 30. These are both first in class, approaches. One targeting ADAM nine, target that again is broadly expressed across a number of solid tumors, including GI cancers and, non small cell lung cancer.

And then o 30 is still a undisclosed target. We are targeting an IND submission next year. And as we get close to that event, we’ll provide additional disclosure on this program. The partner programs, I I alluded to Margemza, Zioniz, and TZILD. You can see the collaborators, Tercera, Insight, and Sanofi, respectively.

We do have a number of milestones and initial economics tied into these, which again afford future nondilutive capital coming into the company. And then MGD o two four was the molecule that I mentioned that’s partnered under an exclusive option agreement with Gilead that was entered into in October 2022. And about a year after that original alliance, they, decided to expand and add an additional molecule, which is listed here. We haven’t disclosed the targets, but, again, it’s a bispecific being developed for multiple solid tumor indications. So I’ll dig a little bit deeper into each of our five, kind of feature, pipeline assets.

Lorigirlimab, again, is a tetravalent molecule where you have two binding moieties for p d one, two binding moieties for c t l a four. Our lead indication here is castrate resistant prostate cancer, and I mentioned we also are developing it in, the Lannett study for various gyne indications. The early, phase one experience was highlighted at ASCO GU. I’ll talk about that a little bit more as we get through the the subsequent slides. But there, we did see, you know, provocative indication of activity in a tumor type that historically has not been responsive to immune checkpoints.

We had dosed a hundred and twenty seven patients in the phase one experience overall. About forty two were in the prostate cohort. And, again, we saw confirmed ORR of twenty six percent with PSA response rate of about twenty nine percent. That compares compares very favorable compared to traditional p d one agents that have shown only single digit response rates. So this is, again, some of that phase one data.

Again, forty two patients, you can see the baseline characteristics on the left panel. These are heavily pretreated, patients. About half of the patients, in fact, were fourth, fifth line patients with prior exposure to both docetaxel and AR inhibitors in the majority, and you can also see there was extensive, tumor burden in these patients with ninety five percent having bone involvement and many also having liver mets or lung metastases. On the right hand side, you see what is pretty impressive in terms of the durability of response, which again for checkpoints, that is the salient feature you’re always looking at. And the fact that we can have continuous blockade of both p d one and c t l a four, in some cases, going out now two years is pretty unprecedented.

If you look at some of the benchmark data, for instance, with the ipi nivo combos, the so called CheckMate six fifty study, there, typically, the ipi regimen was only administered for two or three cycles. And even with that short exposure, they had pretty serious adverse events, including grade five colitis and pneumonitis that was reported in that CheckMate six fifty study. In terms of the efficacy profile from that ASCO GU presentation, you can see on the left those patients with measurable disease accounted for about thirty five patients, and we had a twenty six percent confirmed response rate. What was also interesting was that all the patients that had an objective response also had greater than 90% reduction in their PSA value from baseline, and you can see the PSA reductions highlighted on the right panel. And that includes, again, all the, patients in this cohort, the forty two patients, and we saw, you know, meaningful reduction in a number of the, the patients.

Safety profile is highlighted here. You can see on the right hand panel, you know, AE profile, you know, similar to what other immune checkpoints have shown. We do see some evidence of immune mediated events, although the most frequent AEs that were reported include more constitutional symptoms around fatigue, rash, pruritus. As I mentioned, you know, one of the hallmark toxicities that is typically associated with CTLA-four blockade is colitis, and now the one hundred and twenty, patients or so in the overall safety population, which encompass both prostate cancer but some other solid tumors, we only saw one or two, incidents of grade three colitis in that population, which we attribute to the fact that in this bispecific approach, we can localize the effect to TILs that are double positive for both p d one and c tally four and avoid some of that systemic toxicity that is seen with, you know, just independent, administration of a c tally four agent. The design of the Lorikeet study is highlighted on this slide.

It’s a robust study with a 150 patients overall. It’s a two to one randomization schema. All these patients are chemo naive, and we’re basically comparing the doublet therapy of loradirlimab plus docetaxel to docetaxel monotherapy. This study was fully enrolled as of the, late, 2024, and we are continuing to accrue events. It’s a time to event endpoint with radiographic progression free survival as the primary endpoint.

We are expecting to provide a clinical update on this program latter part of this year. The second clinical program for Loradrelimab that has been initiated in May is the Linnet study, and here we are looking at two populations. One is a high grade serous ovarian carcinoma population where we’ll be looking at up to forty patients. This is a Simon two stage design with 20 patients in the first stage, and then assuming we hit some threshold of activity, we progress to the second stage of the study. We are also looking at a cohort focused on clear cell gynecologic, cancers.

This encompasses about twenty patients. This is a a population that typically has pretty, you know, limited treatment options. Platinum based chemotherapy is less effective in the clear cell population, and they tend to be more responsive to immune checkpoint therapy, which is why we’re excited about the promise of this, albeit it is a smaller indication, but it might afford us a more rapid, path to registration. So to switch gears a little bit, I’m gonna talk about our ADC portfolio. Again, all of these molecules leverage the Cinefix platform.

First molecule is called m g c o two six. Again, this is a DAR four construct as is with the other molecules, and a few salient features of the Cinefix platform. It does enable conjugation to the native glycan in a site specific, manner. We do think that that abrogates some of the lung toxicities that have been demonstrated with other topo one agents, which and, there’s been data published, in cancer research that shows that the Fc gamma receptor binding actually in some cases, enables nonspecific uptake of alveolar macrophages, and that drives some of that lung toxicity. The hope here is that that may limit that and also creates a much more homogenous species of just star four construct.

We have a, highly polar spacer technology called the HydraSpace that’s also employed that enables conjugation to more hydrophobic payloads, including exoticon. And then the the payload itself, exoticon, we have, again, observed in some of the in vitro characterization that it is much more potent than doruxoticon. Again, that’s the topo one that is being leveraged by Daiichi Sankyo in their, pipeline programs, about two to five fold higher potency. It’s also less susceptible to efflux pump escape mechanisms and other, forms of multidrug resistance and also has shown in some of the in vitro, characterization better bystander killing effects. This molecule is in a phase one dose escalation study, and we’re on the cusp of kicking off some dose expansion in some tumor specific cohorts latter part of this year.

This is a target that obviously has drive driven a lot of interest, within the marketplace. There are a number of other companies developing ADCs against this target, and you can see now there’s been clinical validation from five or six tumor types, including small cell lung cancer, non small cell lung cancer, sarcoma, esophageal cancer, nasopharyngeal cancer. But I also think that this is not a winner take all market dynamic. There’s an opportunity to really find a beachhead here given that this target has such a vast expression profile in a number of solid tumors. We haven’t yet disclosed which tumors we’ve prioritized, and that is partly due to some of the competitive dynamics of this market.

This slide, I just kind of enunciates, again, why we’re excited about exoticon as the operative payload, and we compare it to s n thirty eight, which is the topo one that approach used in Trodelvy as well as diruxoticon, which is employed in the Daiichi Sankyo Topo one portfolio, and you can see what I highlighted in terms of higher potency, a very stable linker that also enables a consistent DAR four species by conjugation of of the native glycan. That also means that we don’t have to do any, engineering to introduce a a specific conjugation handle, which also kind of decreases cycle time for developing these programs, And again, less sensitive to efflux and MDR. On the bottom panel, and there’s been a lot of data now published with Cinefix technology. This was some data presented at the World ADC conference in 2023, which compares a trastuzumab deruxtecan construct, relative to trastuzumab with a Cintecan e platform from Cinefix. And you can see compares very favorably with these two doses administered, and that’s despite having a DAR four with the Syntykin construct versus a DAR eight of a drug Syntykin.

This same drug linker that we’ve leveraged has also been now leveraged by other companies, including Innovent, which is a Chinese company that has recently disclosed that for their clot in ’20 construct, which they presented at some of the congresses, they’ve now advanced that to phase three development in both gastric cancer and pancreatic cancer. So it’s a nice overall validation on the drug linker. And, again, we’re very excited about the targets that we’re now positioning with this platform. This is some of our internally, generated, data, showing again in vivo efficacy in two cell lines. One is a lung cancer cell line in the top panel.

The bottom panel is a melanoma cell line, and you can see dose dependent killing observed at point three mgs, one mg, and three mgs. And again, this is with a single administration of ten mgs per single dose administration with the three doses highlighted here. We’ve also done some comparative testing looking at the actual antibody itself. And, again, our we pulled this construct from an probably a portfolio of 30 different antibodies. This is one of the most efficient internalizers within that panel and actually outperforms when we look at some of the comparative models with the Daiichi Sankyo antibody.

Our second molecule in this pipeline is 28. Again, the same overall payload. This is in a phase one dose escalation study. Adam nine very highly expressed across a number of tumors, including some of the GI cancer shown here. We have very encouraging activity in a number of PDX models, And, again, that’s with a range of h scores.

So in terms of the intensity level of target expression, we do see, you know, very nice, killing with these two doses administered at ten mgs per kg. O 30 is another ADC molecule, which we’ll be talking more about as we move closer to IND submission next year. And then MGD o two four is the partnered asset with Gilead. This is a bispecific that enables, redirected T cell killing as the operative mechanism. CD one twenty three is a leukemic stem cell target, highly expressed in a number of hematologic malignancies, including AML, MDS, and this is in an ongoing phase one dose escalation study.

Very well capitalized in terms of the company with a $177,000,000 on the balance sheet. We’ve also had a history of being very prolific in corporate deal making. In the last three years alone, we’ve brought in 550,000,000 in nondilutive, funding. And actually over the last ten years, every year, we’ve done one, in some cases, multiple deals that have brought in a nondilutive funding. And again, we will continue to be active in exploring partnering across the portfolio, both products and as well as platforms.

So in terms of key strategic priorities for ’25 and ’26, I’ve touched on many of these. You’ll see additional clarity around the development path for loradirlimab based on the two ongoing studies. The Lorikeet and Lannett trials will be continuing to advance our ADC portfolio with 02/06 and 02/08, looking to establish clinical POC, IND submission for o thirty coming up. We will also be continuing to advance other programs out of our research portfolio, namely first in class, molecules. We’ve had a very productive r or research organization with, you know, new INDs coming out every twelve to eighteen months.

We’ll continue to be active on corporate partner as I alluded to, and we will be even more vigilant, obviously, in this challenging macro environment of being good stewards of the capital that we have, deploying that into the assets that have the greatest promise. So we’ll continue to improve the financial position through operational efficiency initiatives as well as, corporate partnering efforts. And I think that was it. So thank you, and we look forward to providing additional updates over the next few quarters on the progress.

Eduardo Martinez, Biotechnology Equity Research Associate, HC Wainwright: Thank you so much. If there are any questions from the audience? I guess I’ll just go quick quick one about, the Lorie programs. In the castration resistant prostate cancer, you look at the roughly a twenty six percent overall response rate. How does that fare generally for drugs in the phase one stage and the ones competing in that indication?

Eric Risser, CEO, MacroGenics: I mean, prostate cancer is a field that has evolved considerably over the last couple years. There’s a lot of modalities, T cell engager approaches, radiotherapy, ADCs. If you look at it within the class of immune checkpoints, traditional p d one agents, and there’s been a number of studies including the the keynote 09/21 study that looked at pembro, plus, chemo, and then there was prior work, which is the monotherapy, which will be the the relevant comparison here. Their monotherapy experience was only single digit response rate. So, again, this is a tumor that historically has not been very responsive to checkpoints.

So the twenty six percent for us was actually very provocative early evidence of of activity in a population that was also very late line and, you know, obviously had been on, in many cases, three or four prior rounds of treatment. Yeah.

Eduardo Martinez, Biotechnology Equity Research Associate, HC Wainwright: Well, thank you so much. Thank you, mister Visser, for present

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