MacroGenics at Goldman Sachs Conference: Strategic Pipeline Expansion

On Tuesday, 10 June 2025, MacroGenics (NASDAQ:MGNX) presented a strategic overview at the Goldman Sachs 46th Annual Global Healthcare Conference 2025. The company highlighted its robust pipeline and financial health, underscoring its commitment to developing innovative cancer treatments. Despite a challenging market environment, MacroGenics showcased its ability to secure non-dilutive financing and maintain a strong cash position.

Key Takeaways

• MacroGenics reported a solid cash runway extending through the first half of 2027, supported by $154 million in cash and cash equivalents as of March 31.
• A significant $70 million transaction with Saggart Health Care Partners was announced, enhancing the commercial prospects of Zynas.
• The company is advancing four clinical-stage programs with distinct mechanisms of action, including promising ADC and bispecific molecule developments.
• MacroGenics has successfully raised over $550 million through partnerships and milestones over the past three years.

Financial Results

• Cash Position:

- $154 million in cash and cash equivalents as of March 31.

- Cash runway projected through the first half of 2027.

• Saggart Health Care Partners Transaction:

- $70 million upfront payment received for Zynas, with tiered royalty rates from 15% to 24%.

- Royalties revert to MacroGenics once Saggart achieves a $140 million return.

• Non-Dilutive Financing:

- Over $550 million raised from partnerships and milestones in the last three years.

• Revenue Generation:

- Emphasis on managing financial burn and extending cash runway.

Operational Updates

• Pipeline Progress:

- Lorigirlimab: Clinical update expected later this year.

- MGC026 and MGC028: Progressing in Phase 1 studies; expansion cohorts for MGC026 planned for later this year.

- MGC030: IND submission targeted for 2026.

• Partner Programs:

- Zynas: Additional approvals in frontline anal cancer.

- TZEALD: Potential regulatory decisions for new indications, including early onset type one diabetes, expected later this year.

• LORRAKEET Study:

- Phase 2 study in prostate cancer, fully enrolled with 150 patients.

- Continuation recommended by independent data monitoring committee.

• LANNETT Study:

- Monotherapy study in ovarian cancer and clear cell gynecologic malignancies.

• MGD024 (T cell engager):

- Under agreement with Gilead, currently in dose escalation phase.

Future Outlook

• Data Updates:

- Anticipated clinical update on Lorigirlimab later this year.

• Regulatory Decisions:

- Potential regulatory decisions for TZEALD expected in the latter half of the year.

• Continued Financing:

- Plans to sustain financing through non-dilutive capital sources.

• Expansion Cohorts:

- Initiation of expansion cohorts in selected solid tumor indications for MGC026 expected later this year.

For more detailed insights, refer to the full transcript below.

Full transcript - Goldman Sachs 46th Annual Global Healthcare Conference 2025:

Eric Ritzer, Chief Operating Officer, MacroGenics: All right. Good morning, everyone. My pleasure to kick things off this morning. My name is Eric Ritzer. I’m the chief operating officer at MacroGenics, and I’m joined by my colleague Jim Carrolls, our chief financial officer.

Moving to the next slide here, I’m just going to quickly note that I’ll be making some forward looking statements today. Please refer to our SEC filings for additional details on risk factors that will impact our business. So for those of you that don’t know MacroGenics, I’m going to quickly provide some overview of the company, then I’m going to dive into a little bit more detail on five of our specific programs. So MacroGenics is a developer of next generation antibody therapeutics. We’re committed to discovering, developing and delivering to patients what can be life changing medicines for various cancer indications.

We have a promising pipeline that comprises four clinical stage programs And these four programs actually span three distinct mechanisms of action. We incorporate external drug linker chemistries that we’ve licensed to support our ADC pipeline. We also have a homegrown platform for delivering bispecific and trispecific molecules. That’s referred to as our DART and Trident platforms. These have actually been applied in a couple different modalities including T cell engagers but also enable co blockade of different immune checkpoint molecules.

One thing that I like to reference is that we’re not just a technology boutique, we are really committed to developing innovative medicines and take them all the way through the development process so we can translate these early research insights into very robust product candidates. They navigate all the complexities of regulatory CMC issues to get actually drugs on the market. We’ve had three assets that originated in our early development efforts that are now on the market in The US. Margemza for late line HER2 positive breast cancer, TZEAL for type one diabetes, and Zynas which is an anti PD-one antibody that was actually approved last month in frontline anal cancer. These three assets are being commercialized by party pharma partners and especially pharma companies, but we still maintain a residual economic interest in all three of these assets.

We’re very well resourced to execute against our plan with a cash runway that now extends through the first half of twenty twenty seven. That includes the 154,000,000 in cash and cash equivalents that we had as of March 31, also includes anticipated and projected milestones from projected partners, additional savings from some ongoing cost reduction initiatives. And notably, this morning, we announced the transaction with Saggart Health Care Partners that brought in an additional $70,000,000 That transaction is highlighted on this slide. So Zynas is an asset that was originally approved in Merkel cell carcinoma in 2023. But as I mentioned last month, it also garnered approvals in frontline anal cancer.

The asset was originally licensed to Insight in October 2017. You can see we have had meaningful economics realized through that partnership. And through the SAGGARD transaction, now recognize an additional $70,000,000 of consideration that we’ve already received. We’ll be paying royalties to SAGGARD on future global net sales of the assets. You can see the royalty rates are tiered 15% to 24%.

And once SAGARD realizes a 2x multiple on their investment, so $140,000,000 any residual royalties would revert back to MacroGenics. So in terms of our pipeline, we have a host of proprietary programs where we retain global commercial rights. That includes Lorigirlimab, the PD-one CTLA-four bispecific molecule. We’re very excited about this molecule and actually developing it in two different indications, both prostate cancer in combination with docetaxel as well as in ovarian cancer and various clear cell gynecologic cancers. We have three ADC programs behind that, and these employ the Cinefix platform.

This is a Dutch company that was acquired by Lonza. We were an early adopter of the platform and actually got broad access to support multiple development programs, including the three that are listed here. O two six is a potential best in class molecule targeting b seven h three and, again, leverages a topo one based payload and their site specific linker technology. B7 history is a very exciting target. Even the recent ASCO presentation, a number of companies have highlighted its broad potential across many different solid tumors.

Twenty eight and thirty, these are both potentially in class molecules. 28 is in phase one dose escalation and again it targets ADAM9 which is also expressed across a number of solid tumors including several GI cancers as well as lung cancer. 30 is an undisclosed target. We’re looking to take this to IND in 2026, and we’ll have additional disclosures as we get closer to that event. A number of partner programs including the three commercial assets I mentioned, and we also have a T cell engager molecule called MGD024, which is subject to an exclusive option agreement with Gilead, which was in October of twenty two.

And again, about a year after that partnership was announced, feel it expanded the relationship with MacroGenics and added a bispecific molecule which is listed here on the bottom. Again, a bispecific that is being developed for multiple solid tumor indications. So to drill into a little bit more detail, I’ll start with Lorigirilimab program. So this is our bispecific immune checkpoint. It has a two by two configuration where there are two binding moieties for PD-one, two binding moieties for CTLA-four.

Really excited about the potential of this product to be almost a pipeline within a product where it has very broad utility across many different indications. We’ve already started exploring utility in prostate cancer, the ovarian cancer study that we’ve recently initiated, we have some ISTs that are also initiated including one in cervical cancer. This can be an agent that potentially could be used both as a monotherapy but also the backbone therapy to support combination opportunities. Some of the early clinical results that we presented at ASCO GU in 2023 was the monotherapy experience in castrate resistant prostate cancer. We saw a very provocative signal in this study, both encouraging safety profile that meaningfully differentiates from what ipinivo combinations have shown in the past and also saw very provocative efficacy with a confirmed ORR of twenty six percent and PSA 50 reductions in about twenty nine percent of the patients.

The LORRAKEET study, which is the name of our randomized phase two study in prostate cancer, fully enrolled late last year and I’ll talk a little bit more about the design of that study. We did have through the independent data monitoring committee, the recommendation continue to proceed based on an early futility analysis in February of twenty five and we expect to provide a clinical update on this program latter part of this year. We also recently initiated the Lannett study, which is the name of our monotherapy study in ovarian cancer as well as clear cell gynecologic malignancies. So the early phase one experience I alluded to that we presented at ASCO GU is highlighted here. We had forty two patients that were treated.

These were typically a late line population. Actually fifty percent of the patients fell into what was either fourth or fifth line therapy. The vast majority of these patients had prior exposure to both docetaxel as well as AR inhibitor and you can see they had extensive tumor burden with ninety five percent of the patients actually having bone metastasis. On the right, you can see in the swimmer’s plot that we had very good durability with some patients having continuous treatment over two years. So that’s really remarkable, especially when you consider their early experience with ipinivo in the CheckMate six fifty study.

In that case, ipi was only delivered for two or three cycles. And even with that short duration, they saw profound toxicity with both grade five events with colitis and pneumonitis. Again, we haven’t seen any grade five events and notably only one or two episodes of grade three colitis in our entire safety population, is over one hundred and twenty patients. So very good that we can see continuous blockade of both PD-one and CTLA-four, and in some cases that extending for over two years. The efficacy profile is shown here with the left panel showing those patients with measurable disease, about thirty five patients where you saw a confirmed ORR of twenty six percent.

On the right panel, see those patients with PSA reductions. So here we profiled the full cohort of forty two patients and what we saw also interestingly was that all the patients with an objective response had a deep PSA declines of over ninety percent reduction. Next slide is just reiterating some of the safety and this is again in the broader population that includes both prostate cancer but also some other solid tumors. Overall, typical kind of AE profile that you see with immune checkpoints, there are some immune mediated events but the most frequent AEs were more of these constitutional symptoms, fatigue, rash, pruritus, and as I mentioned earlier, things like colitis which tends to be a hallmark of anti CTLA-four therapy, we really saw very low incidence there with only one or two grade three events reported in this phase one population. What we also had done in this study, we incorporated a number of pharmacodynamic markers again to underscore the utility and activity of this agent.

We saw a very good blockade of PD-one at our recommended phase two dose which is six mgs per kg on an every three week regimen. We also saw good evidence of Ki67 activation, which is a marker for T cell proliferation. And we also saw ICOS upregulation, which is a marker for CTLA-four blockade. So we’re excited to see that the mechanism here is really driven by this combinatorial approach and the fact that we can actually localize the activity to these double positive TILs and again avoid some of that systemic toxicity, which is again reflected here with a very encouraging safety profile. So the two trials I alluded to earlier are shown here in a little bit additional detail.

So LORAKEEP, this was a randomized study with 150 patients. It’s a two to one randomization schema for delivering loradirlimab in combination with docetaxel, which is a standard of care, especially in patients that have already progressed on a prior ARAT therapy. And then the control arm here is docetaxel monotherapy. Study fully enrolled late last year and the primary endpoint is radiographic progression free survival. So it is a time to event endpoint and we’re continuing to accrue those events and hope to provide an update on the status of this study later this year.

The study that I alluded to is the Lannett study. The study actually has two arms, one focused on high grade serous ovarian carcinoma. That includes up to forty patients and will be administering Loradirlimab as a monotherapy. The arm is focused in clear cell gynecologic cancer and that’s, we’re exploring a subset about twenty patients. That’s a rare form of cancer and it actually is typically much more aggressive form of disease with worse prognosis for patients.

And it’s also a disease that typically is less susceptible to platinum based chemo and potentially more susceptible to immune therapy. So we’re very excited to see if we could see an early and provocative signal in that population that could potentially support a accelerated approval path. So switching gears, I’ll talk a little bit about the ADC portfolio. Again, the three molecules that I’ll describe are all leveraging the Sinefix drug linker technology. The asset is MGC026, and that’s directed against B7H3.

As I alluded to earlier, a lot of excitement around this target. There are a number of groups that are also developing ADCs. And actually to date, there’s been clinical validation established by some of these competing programs across six or seven indications, including small cell lung cancer, non small cell lung cancer, prostate cancer, sarcoma, esophageal, nasopharyngeal cancer, and actually the list has continued to grow. We see this market as one where there won’t be a winner take all, but there probably will be multiple groups that can establish a beachhead just given the expansive nature of the indications that overexpress B7 H3. We do think there are some differentiating features with our drug linker approach that we licensed including the glyco connect linker that enables you to bind the native glycan.

By doing that, you essentially have no Fc gamma receptor binding and one thing that has been noted in the literature and there was a study published back in 2020 in Cancer Science which looked at trastuzumab deruxytkin and noted that some of the lung toxicities that were observed were associated with non targeted uptake in the alveolar macrophages and that was mediated by Fc gamma receptor binding. And again, this case, because it binds that native glycan, it really abrogates any binding to the Fc receptors. We also incorporate this hydrospace linker that enables us to bind to more hydrophobic payloads, which would include exatecan. And then the payload itself, as I mentioned, is exatecan, which does have some salient points of differentiation when compared with diruxetiquin, which is the payload that is incorporated in the Daiichi Sankyo molecule. it’s more potent.

So we’ve seen in the in vitro models, two to five fold higher potency. It’s less susceptible to EFLA escape mechanisms as well as multidrug resistance and also has superior cell permeability that potentially affords better bystander killing. This molecule is in the phase one dose escalation. We’ll be kicking off several expansion cohorts in selected solid tumor indications latter part of this year. This slide just highlights again some of the comparative advantages that I noted.

So exoticon relative to SN38, which is the payload employed by Trodelvy, and then doruxeticon, which is again the workhorse payload that is used in many of the Daiichi Sankyo molecules against a number of different targets including B7 H3. And as I noted, better potency, the linker which binds to the native glycan and the benefits of potentially avoiding multidrug resistance. There’s been a number of preclinical studies showing the of Cintiqin E relative to a drug Cintiqin and what’s shown here on the bottom is some data generated by Cinefix that was presented at World ADC in 2023, which shows that we can outperform with the Cintiqin E payload at trastuzumab doroxetine molecule even one that has a higher DAR. So in this case, it was a DAR eight molecule employing the drug cetecin payload versus a DAR four molecule with exotecin. This is some of our own data, so some in vivo models, both a lung model shown on the top panel and a melanoma model.

Both of these are relatively high expressor cell lines for B7 H3. You can see with a single dose, very good control over tumor growth and reduction and again, of dose proportional increase in control. What we’ve also done is actually profiled some of the other antibodies including the Daiichi Sankyo antibody have shown that our binder has better internalization properties versus some of these other molecules. So we’re very excited about both the antibodies, the linker, and the payload, and ultimately obviously we’re hoping that we’ll be able to see encouraging activity in the clinic as we move into these expansion cohorts. The molecule I’ll highlight is called MGC028.

So this is a molecule that targets ADAM9, a disintegrin and metalloprotease nine. This is a type one transmembrane protein and there’s been a lot of literature suggesting that dysregulation of ADAM-nine is associated with tumor progression and metastasis. It’s also been shown that there’s overexpression of this target across a number of solid tumors and that there’s association of overexpression with both severity of the disease as well as overall outcomes. Same overall drug linker that I just highlighted for ’26, again a DARFOR construct with the same linker, the same hydrospace polar spacer, and the same exatecan payload. This is a molecule that actually follows on the heels of a generation molecule that was called IMGC936.

Also was taken into the clinic. We did see some early evidence of activity in patients but there were some dose limiting toxicities related to ocular tox which we attributed to the platform. That generation molecule was based on a metanzine based payload and then again, that’s a well known class toxicity. We haven’t seen any ocular events in any of our preclinical models and again, that was a toxicity that was in fact predictable based on the early synode data with our generation molecule. So we’re very encouraged by this overall molecule.

It’s in phase one. We just initiated earlier this year, progressing very nicely. We have a number of very committed investigators in this study and they’re starting to move through those early dose escalation cohorts. Here I profile some of the again salient features of the target including some IHC data on the left panel and you can see across a number of GI cancers including pancreatic cancer, gastric, colorectal cancer, very nice expression profile and then also in ADNO non small cell lung cancer, very nice expression profile. We’ve done actually some comparative testing as well, looking at ADNO-nine versus other targets that are for instance overexpressed in GI cancers and see a really encouraging profile here with very uniform staining, less heterogeneity versus some of the other targets that we’ve looked at, and actually very broad expression profile.

One example would be a target like clotting eighteen-two which is also being pursued in a number of GI cancers and we think in some of our comparative analysis, ADA nine actually stacks up very favorably. That’s also been shown in some of the PDX work on the right hand panel across a number of tumor types, colorectal cancer, pink, lung, you can see very good control over the tumor with two doses administered at ten mgs per kg. What’s also interesting in some of these PDX models, we have seen patients where they have not been responsive to prior Arena TCAM therapy but do show very profound response in these animal models when treated with MGC028. Next up is our MGC030 molecule. So again, this one we’ve not disclosed the target, also based on the Sinefix platform, an exothecin based molecule and we’re making nice progress completing some of the IND enabling studies and hope to submit an IND in 2026.

As we get closer to that, we’ll provide additional disclosure around this program. So again switching gears, I’ll talk about a modality and this is really the T cell engager. And we’ve had a number of molecules that we’ve is a CD3 based bispecific with monovalent engagement of CD3, monovalent engagement of CD123 which is broadly expressed in leukemic stem cells. We actually had an earlier generation molecule which did not have an Fc domain. So the advantage of this molecule is it does have an Fc domain which enables intermittent dosing scheme of every week or every two weeks.

And we’ve also detuned the CD three binder here, actually changed the whole kinetics of the binding of that CD three arm that also mitigates some of the cytokine release potential that we saw with some of our earlier generation molecules. So this molecule is agreement with Gilead that we entered into in late twenty twenty two. It’s going through dose escalation. And, again, given the potency of this class of molecule, we did employ MABL dosing. So starting at very low doses and slowly graduate in terms of higher doses.

So that’s ongoing and disclosure here is again subject to Gilead making a decision around this molecule. They have an exclusive opt in right which they can exercise at some predefined time points during the course of the phase one study. So a lot going on at MacroGenics, and as I mentioned, we’ll have a number of inflection points and data updates over the course of the next year or two. Loradrelimab will have our clinical update latter part of this year. And then ’26, 28 both progressing nicely in their phase one studies.

We’ll be continuing to advance additional molecules including 30, which will be our next IND. So our research teams continue to be a very prolific group with on average every twelve to eighteen months they’ve advanced one new IND. And it will have additional updates around some of our partner programs, including the two commercial assets that are highlighted here. So ZYN is really excited about the fact that they garnered additional approvals in frontline anal cancer. That was actually some data that they highlighted ESMO last year at the presidential symposium as potentially practice changing data.

And then TZEALD, which is a program that’s now partnered with Sanofi. Sanofi has guided that the latter half of this year, there’ll be multiple regulatory decisions related to additional indications, potentially moving into the early onset type one diabetes population and potentially approvals in other geographies outside The US. And as I mentioned at the beginning, we’re very well positioned with a cash runway that now extends through the first half of twenty twenty seven. That includes the $154,000,000 that was disclosed as of March 31, additional anticipated and projected payments from some of the existing partners, some additional cost savings from some ongoing cost reduction initiatives, and then the Sagger deal that was just announced this year. What I’ll also note, which is again a real tribute to our company, is the ability to continually to finance the business through non dilutive sources of capital.

And actually, over the last three years, we’ve raised over $550,000,000 from various partnerships and milestones that we recognized. So really tremendous effort from the organization. And what I’ll also say is this is actually the consecutive year that we’ve announced a transaction, at least one transaction, some cases more than one transaction, has brought in additional non dilutive capital. So extraordinary consistent effort and track record there and you can see that in terms of the revenue that has been generated and the ability to kind of manage the burn and continue to extend the cash runway. So with that, thank you for your attention and we look forward to providing additional updates on the company over the course of this year.

Thank you so much.

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