Hello, everyone, and thank you for joining us for another session of H.C. Wainwright 's 27th Global Investment Conference. My name is Eduardo Martinez, and I'm a Biotechnology Equity Research Associate at Wainwright It is my pleasure to introduce Mr. Eric Risser, CEO of MacroGenics.
Thanks, Eduardo. I appreciate the chance to speak at this year's H.C. Wainwright conference. I'll be making some forward-looking statements during the course of the presentation, so I urge all of you to refer to our SEC filings for a more complete account of our various risk factors that might impact the business, so I'm going to 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 Synaffix platform, two of which are in the clinic. One will be entering the clinic next year. We also are an 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 CD3-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'd like to highlight 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: Margenza for late-line HER2-positive breast cancer, Tzield, the CD3 partial agonist that's approved for type 1 diabetes, and then ZYNYZ, which is a PD-1 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 first half of 2027.
This includes cash and marketable securities of about $177 million. 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 million of capital. This cash runway guidance also takes into account future projected and anticipated payments from the company's various partners. This is an 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. Lorigerlimab is our PD-1 CTLA-4 bispecific molecule, which is being developed in two indications. The so-called LORIKEET study is looking at a castration-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.
Then we also have a study in ovarian cancer and clear cell gynecologic cancer called the LINNET 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 Synaffix. They have a proprietary drug linker that enables both site-specific conjugation and also enables conjugation with a very potent TOPO1 payload called exatecan. 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 B7-H3-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. MGC028 and MGC030, these are both first-in-class approaches, one targeting ADAM9, a target that, again, is broadly expressed across a number of solid tumors, including GI cancers and non-small cell lung cancer. And then 030 is still an undisclosed target. We are targeting an IND submission next year. And as we get closer to that event, we'll provide additional disclosure on this program. The partnered programs I alluded to: Margenza, ZYNYZ, and Tzield.
You can see the collaborators, TerSera, Incyte, and Sanofi, respectively. We do have a number of milestones and additional economics tied into these, which, again, afford future non-dilutive capital coming into the company. And then MGD024 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. Lorigerlimab, again, is a tetravalent molecule where you have two binding moieties for PD-1, two binding moieties for CTLA-4. Our lead indication here is castration-resistant prostate cancer.
I mentioned we also are developing it in the LINNET study for various GYN indications. The early phase I experience was highlighted at ASCO- GU. I'll talk about that a little bit more as we get through the subsequent slides. But there we did see a provocative indication of activity in a tumor type that historically has not been responsive to immune checkpoints. We had dosed 127 patients in the phase I experience overall. About 42 were in the prostate cohort. And again, we saw a confirmed ORR of 26% with PSA response rate of about 29%. That compares very favorable compared to traditional PD-1 agents that have shown only single-digit response rates. So this is, again, some of that phase I data. Again, 42 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 95% 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 PD-1 and CTLA-4, 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 650 study, there typically the Ipi regimen was only administered for two or three cycles.
Even with that short exposure, they had pretty serious adverse events, including Grade 5 colitis and pneumonitis that was reported in that CheckMate 650 study. In terms of the efficacy profile from that ASCO- GU presentation, you can see on the left those patients with measurable disease counted for about 35 patients, and we had a 26% 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. You can see the PSA reductions highlighted on the right panel. That includes, again, all the patients in this cohort, the 42 patients. We saw meaningful reduction in a number of the patients. Safety profile is highlighted here. You can see on the right-hand panel, AE profile, 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, one of the hallmark toxicities that is typically associated with CTLA-4 blockade is colitis, and now the 120 patients or so in the overall safety population, which encompassed both prostate cancer, but some other solid tumors, we only saw one or two incidents of Grade 3 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 PD-1 and CTLA-4 and avoid some of that systemic toxicity that is seen with just independent administration of a CTLA-4 agent. The design of the LORIKEET study is highlighted on this slide. It's a robust study with 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 lorigerlimab plus docetaxel to docetaxel monotherapy. This study was fully enrolled as of late 2024, and we are continuing to accrue events. It's a time-to-event endpoint with radiographic progression-free survival as a primary endpoint. We are expecting to provide a clinical update on this program later part of this year. The second clinical program for lorigerlimab 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 40 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 20 patients. This is a population that typically has pretty 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 going to talk about our ADC portfolio. Again, all of these molecules leverage the Synaffix platform. First molecule is called MGC026. Again, this is a DAR4 construct as it is with the other molecules. And a few salient features of the Synaffix 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 TOPO1 agents, which, and again, there's been data published in cancer research that shows that the Fc gamma receptor binding actually in some cases enables non-specific 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 DAR4 construct. We have a highly polar spacer technology called the HydraSpace that's also employed. That enables conjugation to more hydrophobic payloads, including exatecan. And then the payload itself, exatecan, we have, again, observed in some of the in vitro characterization that it is much more potent than deruxtecan. Again, that's the TOPO1 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 multi-drug resistance, and also has shown in some of the in vitro characterization better bystander killing effects. This molecule is in a phase I dose escalation study, and we're on the cusp of kicking off some dose expansion in some tumor-specific cohorts later part of this year. This is a target that obviously has 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 in 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 exatecan as the operative payload. And we compare it to SN-38, which is the TOPO1 approach used in TRODELVY, as well as deruxtecan, which is employed in the Daiichi Sankyo TOPO1 portfolio. And you can see what I highlighted in terms of higher potency, a very stable linker that also enables a consistent DAR4 species by conjugation of the native glycan. That also means that we don't have to do any engineering to introduce 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 Synaffix technology. This was some data presented at the World ADC Conference in 2023, which compares a trastuzumab deruxtecan construct relative to trastuzumab with a SYNtecan E platform from Synaffix. And you can see it compares very favorably with these two doses administered. And that's despite having a DAR4 with the SYNtecan construct versus a DAR8 of a deruxtecan. 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 Claudin 18.2 construct, which they presented at some of the congresses, they've now advanced that to phase III development in both gastric cancer and pancreatic cancer. So it's a nice overall validation on the drug linker.
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. You can see dose-dependent killing observed at 0.3 mg, 1 mg, and 3 mg. Again, this is with a single administration of 10 mg per single dose administration with the three doses highlighted here. We've also done some comparative testing looking at the actual antibody itself. Again, we pulled this construct from 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 028.
Again, the same overall payload. This is in a phase I dose escalation study. ADAM9 very highly expressed across a number of tumors, including some of the GI cancers 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 very nice killing with these two doses administered at 10 mg/kg. 030 is another ADC molecule, which we'll be talking more about as we move closer to IND submission next year. And then MGD024 is the partnered asset with Gilead. This is a bispecific that enables redirected T- cell killing as the operative mechanism. CD123 is a leukemic stem cell target, highly expressed in a number of hematologic malignancies, including AML, MDS. And this is in an ongoing phase I dose escalation study.
Very well capitalized in terms of the company with $177 million 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 million in non-dilutive funding, and actually, over the last 10 years, every year, we've done one and in some cases multiple deals that have brought in non-dilutive funding, and again, we will continue to be active in exploring partnering across the portfolio, both products as well as platforms, so in terms of key strategic priorities for 2025 and 2026, I've touched on many of these. You'll see additional clarity around the development path for lorigerlimab based on the two ongoing studies, the LORIKEET and LINNET trials. We'll be continuing to advance our ADC portfolio with 026 and 028, looking to establish clinical POC, IND submission for 030 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 research organization with new INDs coming out every 12- 18 months. We'll continue to be active on corporate partnering, 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.
Thank you so much. If there are any questions from the audience, I guess I'll just go quick one about the LORI programs.
In the castration-resistant prostate cancer, you look at roughly a 26% overall response rate. How does that fare generally for drugs in the phase I stage and the ones competing in that indication?
I mean, prostate cancer is a field that has evolved considerably over the last couple of 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 PD-1 agents, and there's been a number of studies, including the KEYNOTE-921 study that looked at Pembro plus chemo. And then there was prior work with just the monotherapy, which would be the relevant comparison here. Their monotherapy experience was only a single-digit response rate. So again, this is a tumor that historically has not been very responsive to checkpoints.
The 26% for us was actually very provocative early evidence of activity in a population that was also very late line and obviously had been on in many cases three or four prior rounds of treatment.
Well, thank you so much. Thank you, Mr. Risser [audio distortion].