MacroGenics, Inc. Aktie

All right. Thanks for joining, everyone. I'm Jordan Becker, SMID-Cap Biotech Associate at Barclays. And let's get started with our next session.

So it's my great pleasure to have with me Eric Risser, President and Chief Executive Officer for MacroGenics. So Eric, there's been a lot of exciting news recently, but maybe we can start for people who aren't familiar with the story, just a brief overview of MacroGenics and kind of where you are today.

Sure. So thanks, Jordan. I appreciate the introduction. Excited to be here at your conference today. MacroGenics has been around for over 20 years, really focused on next-generation antibody therapeutics for the treatment of cancer.

We have 3 core modalities that we leverage, which help drive our proprietary pipeline, includes our ADC portfolio, where we leverage third-party drug linker chemistries, primarily from Synaffix, which is now part of Lonza and integrate that with some of our really world-class antibody engineering capability to deliver what are either first-in-class or best-in-class molecules. We actually have 3 ADC programs in the current portfolio that we've disclosed.

We also have capabilities around next-gen T cell engagers, have actually a very broad partnership with Gilead that now encompasses 3 separate molecules that are all T cell-related constructs led by a clinical program that we've disclosed targeting CD123 and CD3, and then 2 other undisclosed programs that are still in preclinical development, one based on a TRIDENT construct that's our proprietary trivalent format, and the other one is another DART program. And then the third modality is our dual checkpoint approach, led by our lorigerlimab program, which is a bispecific blocking both PD-1 and CTLA-4.

So very broad portfolio. And as you alluded to, we have a pretty catalyst-rich year ahead of us and a lot of excitement within the company to really drive this portfolio forward.

Amazing. So let's kind of double-click on your ADC pipeline first, and then we'll get into lorigerlimab. So maybe on 026, that's your B7-H3 ADC. Maybe we can start -- you talked about your novel payload. We can start kind of talking about that and how it's differentiated from other payloads in the space?

Sure. Yes. So MGC026, this is our anti-B7-H3 ADC. We're an early pioneer generating therapeutics against this target. And if you think about the ADCs, this really is a system that comprises the antibody, the linker, the payload. We think we've optimized all 3 components with a very attractive B7-H3 binder, which has a very robust internalization.

We've done comparative testing, for instance, against the Daiichi Sankyo specificity, see more efficient internalization with our antibody, also has very good differential expression profile given the epitope that we bind to, which limits the normal tissue liabilities.

The linker, which is a proprietary construct licensed from Synaffix called the GlycoConnect system. This enables binding to the native glycan of the antibody. It's a site-specific approach, one of the very few ADCs against B7-H3 that leverages a site-specific linker, which enables much more uniform species of DAR4.

And then the payload is an exatecan-based payload. So exatecan is about two to fivefold more potent than deruxtecan, which is the operative payload in the Daiichi Sankyo ADC, also has shown to have better bystander killing effect and is also less susceptible to multidrug resistance. So very potent payload. And this program is now progressing into dose expansion. We completed the dose escalation late last year, and we will have initial clinical results presented middle of this year.

Yes. And then I guess on the Phase I trial, is there anything more you'd like to say in terms of the trial design, kind of updates we should expect in mid-2026?

So this will be our first kind of showcase of the clinical data. The only thing that we've guided, and this was in our earnings release on Monday, is across our now 2 clinical programs, 026 and 028, we've not seen any evidence of ILD, which could be an important differentiator given that many of the other assets in this class have shown ILD, including the Daiichi program that had actually a partial clinical hold because of some fatal events associated with ILD.

We attribute that potentially to the -- that linker by, again, binding to the native glycan. We aggregate any of the Fc gamma receptor binding. And we believe that, that can actually contribute to some of the nonspecific uptake of alveolar macrophages. And actually, that was work that Daiichi published in the context of their an HER2 program where they, again, attributed some of the ILD that they saw for in HER2 to that Fc gamma receptor binding.

So no ILD observed so far of any grade for 026 and 028. We have seen also RECIST responses across both of these programs. So I think we're very well positioned with a target that also we believe is going to be a real disruptor, probably one of the most exciting targets in oncology over the last 5 years. One of the unique features, unlike many of the other ADCs that tend to be more lineage specific, so PSMA in prostate cancer, folate receptor in ovarian cancer, B7-H3 has utility across a number of solid tumors.

And you're already seeing some promising early clinical data in small cell lung cancer, castrate-resistant prostate cancer, sarcoma, head and neck, ovarian, cervical, sarcoma. I mean the list is kind of going on and on. So it's a very intriguing target, and we think we have a very intriguing molecule. And even though there are a number of competitors, I think there's enough white space here that we're going to be able to have a meaningful presence in this category.

Very interesting. So you mentioned 2 things, and I want to click on both of those. So obviously, B7-H3 ADCs have shown activity in multiple tumor types. Can you give us a sense -- so are you rolling evenly across these tumor types in this basket trial? Or are you kind of just enrolling into [indiscernible]?

It's a dose escalation that would be a mix of different histologies. And then as we move into expansion cohort, which we've defined, we have 2 ongoing expansion cohorts in tumor-specific indications. Again, we've selected a dose now that we're enrolling those 2 expansion cohorts. We have not yet disclosed the specific tumor types that we're pursuing in those expansion cohorts.

And I mean, given the competition, are you kind of interested in going after already validated tumor types? Or are you interested in going in kind of your own way where there hasn't been.

We haven't guided specifically. But again, the notion is likely we're not going to be going into areas where others are already standing up advanced Phase III programs with small cell lung cancer. You have a number of groups already well into Phase III, in some cases, already running multiple trials, trying to get even to earlier line populations. So that's less likely. It's probably going to be less of that very crowded categories, but areas that are more still emerging.

And then I guess, lastly, on the B7-H3 space, you mentioned that there's a lot of competition, BioNTech, Merck. Can you kind of speak to how you're thinking about development within the space? If you're thinking about doing this alone or your kind of not there yet or how you're thinking about this?

At this point, we're obviously focused on execution on the program. Longer term, we've always been open to partnering. We've had a very prolific history in terms of consummating high-value corporate partnerships. In fact, every year for the last decade, we've done at least one, if not multiple corporate partnerships, and we have very good relationships within all the top 50 pharma companies.

So partnering is definitely something we would consider, especially for a target that has such broad utility. We're not going to be in a position to stand up 6 Phase III studies of our own. So partnering definitely would make sense, although it's a question of timing and partner and what's the shape of that relationship going to look like.

Amazing. Okay. So now let's shift to 028. This is your ADAM9 ADC. Maybe we can talk about kind of the target specifically, the history of the target, your history with the target and then go for kind of like what is differentiated about 028.

Yes. So similar to B7-H3, where we were an early innovator with that target, ADAM9 was a target that we were one of the very first groups to mobilize an ADC development effort. We did have a first-generation molecule targeting ADAM9, which was previously part of a co-development alliance with ImmunoGen. In that context, we had identified the target, had a panel of antibodies. They had their drug linker chemistries.

In that case, it was a emtansine-based construct, and we took that into the clinic, saw some early evidence of antitumor activity, although never got to the target therapeutic dose levels, primarily because of ocular toxicity that we observed in that early study. And that's a well-known payload-related toxicity, which we saw even in the preclinical setting, but thought we might be able to manage it in the clinic with some supportive care measures and thinking about things like fractionated dosing.

Ultimately, that didn't yield the result. We discontinued the program, but we'll apply the learnings from that early effort to our second-gen molecule, which is an ADAM9 binder, one of the most efficient internalizers from all the antibodies that we've screened. And we're leveraging again the Synaffix platform. So it's that same system with a site-specific linker binding to the native glycan, potent exatecan warhead.

And this started Phase I about a year after 026, but we'll have data presented second half of this year. So we're kind of closing the gap there. It's a target that's also started to capture the interest of other groups. We've seen at least 1 or 2 others that are now mobilizing early Phase I efforts. But at this point, we're first-in-class and very aggressively moving the program forward.

No, that's great for context. And in terms of the data that's coming up, you guided to second half 2026. Can you give us a sense of what we should expect? And given the history of the molecule, kind of what you're looking for in terms of safety and maybe any efficacy?

So that will be somewhat of a tumor-specific assessment in terms of efficacy thresholds that we'd be targeting. We know the target has a broad expression profile across a number of solid tumors, including a number of GI indications, things like colon cancer, gastric cancer, pancreatic cancer, lung, triple-negative breast and others. So we'll do that assessment on an indication-by-indication basis.

Safety, obviously, is what I alluded to earlier, no ILD has been seen to date on 026 or 028. And again, we've been looking for a favorable safety profile, which is pretty consistent with what others have seen for the class, which is important because it does give you the ability to move into earlier line populations and also explore combinations if you have a very strong safety profile. So that's something we're going to be obviously keenly looking for, for both 026 and 028.

Okay. And no ocular safety side effects or anything?

Yes. That really is less of a concern with this molecule given that TOPO1, really that's less of a liability. And again, that was a predictable tox, which we've never seen any issues with ocular tox in the GLP tox work and now in the clinic, that's not really been an issue.

Okay. And so we've gone over 026. We've gone over 028, which I would say you've guided to data in 2026. And you ended kind of this year with around $190 million in cash. Can you kind of give us a sense of how you're prioritizing these programs and what you look for to kind of decide strategically how to move these programs forward?

Yes. And there's a third one in that lineup, 026, 028 and then the next emerging clinical program is 030 with an IND in Q3. Yes, we're well capitalized, and we've had a history of continuing to bring in nondilutive capital in the last 3.5 years alone, we've brought in over $600 million in non-dilutive capital. So the goal will be continue to extend that cash runway. And at this point, we have these programs fully financed to drive them to a PoC inflection point.

Incredible. And you mentioned 030, but let's talk more about that. You have an INDs in third quarter of 2026. So maybe I mean, give us as much as you can kind of an overview of how you're thinking about this third ADC program?

The third ADC, which we have not yet disclosed the target. It is currently positioned as a first-in-class TOPO1 ADC, also has very strong compelling preclinical data package based on the GLP tox, PDX animal modeling and is also a target that has expression across a number of solid tumors, including ones where we think there's still high unmet clinical need.

So by design, we've not disclosed the target because we know that it is a very competitive arena, and we have a lot of eyes on us in terms of target selection, but we'll be progressing that one and are excited about the potential of that asset as well.

And can you give us any sense of when we will know the target or any updated information on that?

We'll probably hold off on that as long as we can. So -- probably at the point we get into the clinic, that's probably when we'll have obviously additional information on that program.

Amazing. And so now let's shift to lorigerlimab. Maybe you can give us kind of a history of the molecule and where it is today?

So lorigerlimab, this is our dual checkpoint molecule blocking both PD-1 and CTLA-4. We had actually dosed probably 300 patients plus to date across our monotherapy experience, our combination studies. We are excited about the profile of this molecule that enables, again, co-blockade of the 2 checkpoints. We are able to localize the effect to double-positive TILs, which also potentially helps with the overall safety profile.

Based on the early Phase I data, we had patients that had continuous treatment for over 2 years. And in that early clinical experience actually only saw 1 or 2 colitis events, which is unheard of when you think about the ipilimumab plus nivo experience where ipi is typically only administered for 2 or 3 cycles. And even with that short course, there's pretty profound AEs.

More recently, on our LINNET study, and this is our gynecologic cancer study that includes 2 populations. One is serious ovarian cancer. These are platinum-resistant ovarian cancer patients. Other cohort was clear cell gynecologic cancer. We've enrolled about 41 patients. We have seen some unanticipated AEs, specifically 4 patients that had grade 4 events. In one case, the patient actually died. It ultimately was classified as a grade 5 event.

Those included 2 cases of thrombocytopenia, one case of myocarditis. These are, again, toxicities that you do typically see with checkpoints. And then the fourth case was a grade 4 neutropenia. It's a very complicated case, had concurrent septic shock. Ultimately, that patient was the one that died.

So in an abundance of caution, looking at that data, confirming with the DMC, we decided to pause enrollment of the study. FDA subsequently concurred and put us on a partial clinical hold, meaning that we're not going to continue to enroll patients, but we will continue to dose those patients that are still on study. And right now, we're actively working with the FDA, trying to coordinate and address their questions and hope to resume enrollment as quickly as possible.

And so you guided to updates on that conversation around mid-2026?

Mid-'26, we'll have a holistic update on the program, which could include regulatory status. Obviously, we've talked a little bit about AEs and safety, have not talked about efficacy results to date. So obviously, risk benefit is something you always got to look at in tandem. And then obviously, some early thoughts on go-forward development strategy. So that will be part of our mid-'26 update.

And then one more on, lorigerlimab. Given the safety signals that you've seen, are you considering experimenting with maybe different dosing schedules, anything like that? Like how are you thinking about that moving forward?

That could definitely be -- I mean, right now, we're in the fact timing stage. Again, the concentration of these AEs in this specific study population was a little bit unanticipated. So trying to understand, is there something unique about this population. We know they were all platinum-experienced patients, which typically -- that's a fairly harsh regimen that depletes the bone marrow and potentially could drive some of these AEs.

But we're looking at measures in terms of safety monitoring, how do we screen patients at baseline to make sure they're appropriate candidates for the study. You mentioned dosing that could be, again, one of the areas that we could look at. This study was dosed at 6 mgs per kg every 3 weeks. We know from our Phase I data that even with doses as low as 1 mg per kg, we actually had full P1 receptor occupancy. So there may be an opportunity to explore alternate dosing as well.

Okay. Amazing. And so now let's shift to your partnered programs. I guess, first, kind of high level, you mentioned that you're very well capitalized through these kind of important inflection points for your ADC pipeline. Maybe just briefly talk about the nondilutive capital you get from these partnerships and how that -- how you're using that to kind of finance the development of your own internal pipeline and how you think about prioritizing both of those?

Yes. So I mentioned we brought in lots of nondilutive capital. There still are quite a number of kind of latent milestone payments that could be paid to MacroGenics that encompasses the Gilead relationship, where across the 3 molecules I described, there's $1.6 billion of future potential milestones. Again, some of these are going to be more the bio bugs that might be more challenging, but some of these we think are going to be more likely near-term prospects.

Incyte, we partnered with them several years back on our ZYNYZ program. That's now the approved PD-1 asset that they're commercializing globally. We've seen some very encouraging regulatory updates on that program, including an approval in Japan in December.

And then just last week, they garnered an EU approval in frontline anal cancer. So that program continues to grow, and we have $540 million of potential milestones. There's also a royalty embedded in the ZYNYZ program.

We monetized some of that last year with Sagard Health through a cap structure. So they paid us $70 million, have an opportunity to earn 2x that investment, but then all the residual royalties would revert back to MacroGenics. And those are, as described publicly, 15%-to-24%-tiered royalty rates.

And then Sanofi has another MacroGenics originated asset called TZIELD, also an approved asset for type 1 diabetes, and they're pursuing global commercialization for that program. And we have $330 million of residual milestone payments that could get paid out there. That also has a royalty embedded in it, although we did monetize a component of that with DRI capital previously, but that also has a -- what I would call a soft cap mechanism that after they achieve a certain threshold of revenue, additional -- a portion of the additional royalties would revert back to MacroGenics.

So that gives us great optionality in terms of securing additional capital. And then obviously, there's always the opportunity to consummate new BD partnerships.

Incredible. It's very impressive kind of the nondilutive capital that you can bring in to kind of finance everything else that's going on.

Okay. So before we wrap up, this has been great. Thank you for coming. Is there anything you would like to leave us with?

I think 2026 was going to be an important year for the company. I stepped into the CEO role last August. The team has really rallied. There's a lot of excitement within the company in terms of these product candidates that we're developing, the promise to really create -- really transformative medicines for patients, and the team is really looking to deliver for shareholders in 2026.

Amazing. Well, thank you, Eric.

Thank you.

All right, good morning, everyone. My pleasure to kick things off this morning. My name is Eric Risser. I'm the Chief Operating Officer at MacroGenics, and I'm joined by my colleague, Jim Karrels, 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 5 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 4 clinical stage programs, and these 4 programs actually span 3 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. And these have actually been applied in a couple of different modalities, including T-cell engagers, but also enable co-blockade of different immune checkpoint molecules.

One thing that I'd 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. It's a very robust product candidates, they navigate all the complexities of regulatory CMC issues to get actually drugs on the market. We have had 3 assets that originated in our early development efforts that are now on the market in the U.S. MARGENZA for late-line HER2-positive breast cancer, TZIELD for type 1 diabetes and ZYNYZ, which is an anti-PD-1 antibody that was actually approved last month in frontline anal cancer. These 3 assets are being commercialized by third-party pharma partners and specialty pharma companies, but we still maintain a residual economic interest in all 3 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 2027. That includes the $154 million 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 Sagard Healthcare Partners that brought in an additional $70 million that transaction is highlighted on this slide. So ZYNYZ 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 Incyte in October 2017. You can see we have had meaningful economics realized through that partnership. And through the Sagard transaction, we now recognize an additional $70 million of consideration that we've already received [Technical Difficulty] will be paying royalties to Sagard on future global net sales of the asset. You can see the royalty rates are tiered, 15% to 24%. And once Sagard realizes a 2x multiple on their investments, so $140 million. 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 includes lorigerlimab, the PD-1 CTLA-4 bispecific molecule, we're very excited about this molecule. We're actually developing it in 2 different indications, both prostate cancer in combination with docetaxel as well as in ovarian cancer and various clear cell gynecologic cancers. We have 3 ADC programs behind that. These employ the Synaffix’ 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 3 that are listed here.

026 is a potential best-in-class molecule targeting B7-H3, and again leverages TOPO1-based payload and their site-specific linker technology. B7-H3 is a very exciting target. Even the recent ASCO presentation, a number of companies have highlighted its broad potential across many different solid tumors. 028 and 030, these are both potentially first-in-class molecules. 028 is in Phase I 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. O30 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 partnered programs, including the 3 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 [Technical Difficulty] in October of '22. And again, about a year after that partnership was announced, Gilead expanded the relationship with MacroGenics and added a second 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 lorigerlimab program. This is our bispecific immune checkpoint. It has a 2x2 configuration where they for -- PD-1 to binding moieties for PD-1, two binding moieties for CTLA-4. Really excited about the potential, this probably could be almost a pipeline within a product where it has very broad utility across many different indications. We've already started exploring utility and 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 age 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 Ipi/Nivo combinations have shown in the past and also saw a very provocative efficacy with a confirmed ORR of 26% and PSA50 reductions in about 29% of the patients.

The LORIKEET study, which is the name of our randomized Phase II 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, a recommendation continue to proceed based on an early futility analysis in February of '25, and we expect to provide a clinical update on this program in the latter part of this year. We also recently initiated the LINNET study, which is the name of our monotherapy study in ovarian cancer as well as clear cell gynecologic malignancies.

So the early Phase I experience I alluded to that we presented at ASCO GU, was highlighted here. We had 42 patients that were treated, these were typically a late-line population. Actually, 50% 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 95% of the patients actually having bone metastasis.

On the right, you can see in the swimmers plot that we had very good durability with some patients having continuous treatment over 2 years. So that's really remarkable, especially when you consider the early experience with Ipi/Nivo in the CheckMate 650 study. In that case, [ Ipi ] was only delivered for 2 or 3 cycles. And even with that short duration, they saw a profound toxicity with both grade 5 events with colitis and pneumonitis. Again, we haven't seen any Grade 5 events and notably only 1 or 2 episodes of Grade 3 colitis in our entire safety population which is over 120 patients. So very good that we can see continuous blockade of both PD-1 and CTLA-4 and in some cases, that extending for over 2 years.

The efficacy profile is shown here with the left panel showing those patients with measurable disease, so about 35 patients where you saw a confirmed ORR of 26%. On the right panel, you see those patients with PSA reductions. So here we profiled the full cohort of 42 patients. And what we saw also interestingly was that all the patients with an objective response had a deep PSA declines of over 90% 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 a 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-4 therapy, we really saw very low incidents there with only 1 or 2 Grade 3 events reported in this Phase I population.

What we also had done in this study, we incorporated a number of pharmacodynamic markers again, to underscore the utility and the activity of this agent. We saw very good blockade of PD-1 at our recommended Phase II dose, which is 6 mgs per kg on an every 3-week regimen. We also saw good evidence of Ki-67 activation, which is a marker for T-cell proliferation. And we also saw ICOS upregulation, which is a marker for CTLA-4 blockade. So we're very 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 the very encouraging safety profile.

So the 2 trials I alluded to earlier are shown here in a little bit additional detail. So LORIKEET this was a randomized study with 150 patients, it's a 2:1 randomization schema where we're delivering lorigerlimab 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 end point, and we're continuing to accrue those events and hope to provide an update on the status of this study later this year.

The second study that I alluded to is the LINNET study. This study actually has 2 arms, one focused on high-grade serous ovarian carcinoma. That includes up to 40 patients, and we'll be administering lorigerlimab as a monotherapy. The second arm is focused in clear cell gynecologic cancer, and that's -- we're exploring a subset of about 20 patients. That's a rare form of gyn 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 can see an early and provocative signal in that population that could potentially support an accelerated approval path.

So switching gears, I'll talk a little bit about the ADC portfolio. Again, the 3 molecules that I'll describe are all leveraging the Synaffix’ drug linker technology. The first asset is MGC026, and that's directly against B7-H3, 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 or programs across 6 or 7 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 over express B7-H3.

We are -- we do think there are some differentiating features with our drug linker approach that we licensed, including the GlycoConnect linker that enables you to bind to 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 Deruxtecan 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, in this case, because you bind that native glycan to really aggregate any binding to the Fc receptors.

We also incorporate this Hydraspace 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 deruxtecan, which is the payload that is incorporated in the Daiichi Sankyo molecule. First, it's more potent. So we've seen in some of the in vitro models, 2 to 5 fold higher potency. It's less susceptible to [indiscernible] mechanisms as well as multidrug resistance, and also has superior cell permeability that potentially affords better by standard killing. This molecule is in the Phase I 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 exatecan relative to SN-38, which is the payload employed by Trodelvy and then deruxtecan, 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 glycans and the benefits of potentially avoiding multidrug resistance. There's been a number of preclinical studies showing the [Technical Difficulty] of [ SYNtecan ] relative to deruxtecan. And what's shown here on the bottom is some data generated by Synaffix that was presented at World ADC in 2023, which shows that we can outperform with the SYNtecan epay load trastuzumab deruxtecan molecule, even one that has a higher DAR. So in this case, it was a DAR8 molecule employing the deruxtecan payload versus a DAR4 molecule with exatecan.

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. And you can see with a single dose in a very good control over tumor growth and reduction, and again, kind 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 antibody, 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 the expansion cohorts.

The second molecule I'll highlight is called MGC028. So this is a molecule that targets ADAM9, A Disintegrin and Metalloprotease 9. This is a type 1 transmembrane protein, and there's been a lot of literature suggesting that dysregulation of ADAM9 is associated with tumor progression and metastasis. It's also been shown that there's over expression of this target across a number of solid tumors, and there is association of over expression with both severity of the disease as well as overall outcomes. Same overall drug linker that I just highlighted for 026, again, a DAR4 construct with the same linker, the same Hydraspace polar spacer and the same exatecan payload. This is a molecule that actually follows on the heels of a first-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 first-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 [ cyno data ] with our first-generation molecule. So we're very encouraged by this overall molecule. It's in Phase I, 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 adeno non-small cell lung cancer, very nice expression profile. We've done actually some comparative testing as well, looking at ADAM9 versus other targets. They are, for instance, over expressed 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. So one example would be a target like CLDN18.2, which is also being pursued in a number of GI cancers. And we think in some of the comparative analysis, ADAM9 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, panc, lung, you can see very good control over the tumor with 2 doses administered 10 mg per kg. What's also interesting in some of these PDX models, we have seen patients where they have not been responsive to prior [indiscernible] 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 Synaffix platform, an exatecan-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 third modality, and this is really the T-cell engager, and we've had a number of molecules that we've [Technical Difficulty] this 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 2 weeks. And we've also detune the CD3 binder here actually changed the whole kinetics of the binding of that CD3 arm that also mitigate some of the cytokine release potential that we saw with some of our earlier first-generation molecules.

So this molecule is an option [indiscernible] agreement with Gilead that we entered into in late 2022. It's going through dose escalation, and again, given the potency of this class of molecule, we did employ naval dosing, so starting at very low doses and then 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 I 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 2. Lorigerlimab, will have our clinical update latter part of this year and then 026, 028 both progressing nicely in their Phase I studies and we'll be continuing to advance additional molecules, including 030, which will be our next IND. So our research team continues to be a very prolific group with -- on average, every 12 to 18 months, they've advanced 1 new IND. And then we'll have additional updates around some of our partner programs, including the 2 commercial assets that are highlighted here. So ZYNYZ, 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 TZIELD 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 1 diabetes population and potentially approvals in other geographies outside the U.S.

And as I mentioned at the beginning, we're very well positioned with a cash runway that now extends through the first half of 2027, that includes the $154 million that was disclosed as of March 31. Additional anticipated projected payments from some of the existing partners, some additional cost savings from some ongoing cost reduction initiatives, and then the Sagard 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 continue to finance the business through non-dilutive sources of capital. And actually, over the last 3 years, we've raised over $550 million 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 tenth consecutive year that we've announced the transaction, at least 1 transaction in some cases, more than 1 transaction that's 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.