All right, so let's get started. Thanks, everyone, for joining us for this session. My name is Paul Jeng. I'm a member of the biotech research team at Guggenheim. And our next presenting company is MacroGenics. And I'm very pleased to welcome Eric Risser, COO. Eric, welcome. Great, thank you, and I appreciate the invitation to the conference. Great. So maybe let's just start with a pretty brief overview of where MacroGenics is as a clinical stage biotech and where you're sort of orienting your antibody pipeline. Sure, yeah. We're very excited about 2025. We have a number of important clinical inflection points, potential milestone events tied around our clinical pipeline. As a company, we're focused on next-generation antibody therapeutics directed against cancer. There's kind of three key thematic buckets in the portfolio. One is around our B7-H3 targeting ADCs, which encompass actually two separate assets with different drug linker payloads incorporated. One is the Vobra Duo asset, which recently completed the TAMARACK study, which we can talk about some more. The other one is initiating phase I. It's an asset called MGC026, which has the same antibody but a different drug linker based on a topo I-based toxin. The second kind of thematic bucket is our bispecific checkpoint molecule, which we call lorigerlimab, that enables blockade of both PD-1 and CTLA-4, has some really nice differentiating features from some of the other bispecific checkpoint molecules that are out there. And then really the third thematic bucket is our innovative next-gen ADC pipeline. We have a very prolific R&D organization, which in the last couple of years have advanced about one new IND a year. The most recent introduction to the pipeline into the clinical portfolio is a product called MGC028, a first-in-class asset directed against a target called ADAM9, which also has a very broad expression profile across a number of solid tumors. Great. Thanks for the introduction. So perhaps starting with the TAMARACK study. So you reported clinical data from the phase II TAMARACK trial of Vobra Duo in prostate cancer earlier this year. Can you walk us through some of the key clinical learnings from that data, including what you recently presented at ESMO? Yeah, so in the context of this program, we initiated our early phase I experience. We saw some early provocative signals of activity in CRPC population. The original dose that we had selected for that phase I expansion was a 3-mg per-kg dose given on an every three-week treatment interval. The TAMARACK study was really designed to build on the learnings of that phase I experience. We did lower the doses in that study. And that actually explored two separate dose regimens. One was a 2.0 mg/kg dose administered on an every four-week cycle. And then there was a 2.7 mg dose also on a four-week cycle. The hope there was to provide a little bit more recovery time with a longer treatment interval and see if we could curb some of the toxicities that we saw in the phase I experience, which did actually limit the treatment duration on patients in that earlier study. Some of those goals were achieved, not all of them. We did see significant improvement in overall safety experience. For instance, in that phase I study, we had about three-quarters of the patients that had grade 3 treatment-related AEs. That dropped to about 50% of the patients, irrespective of the dose arms that we were looking at. With regard to treatment-related SAEs, that also fell from about 50% to closer to a quarter of the patients. Of note, some of the hematologic toxicities, those were significantly improved based on the lower dosing schedule, things like thrombocytopenia, neutropenia, anemia. Those dropped significantly. Also, hand-foot syndrome or palmar-plantar erythrodysesthesia. We had some more significant observations in the phase I study. About 45% of the patients actually had some grade of PPE in that early phase I experience. And that actually dropped dramatically with the reduced dosing, actually below 20%. And the severity of those patients were, for the most part, grade one, which is typically some reddening around the palms or the soles of the feet, but not the pain that really could potentially create quality of life issues for the patients. We also were able to extend the duration of treatment from a median of four cycles of treatment in the phase I experience to now six cycles, and again, with a prolonged interval of four weeks versus three weeks. We did have a median PFS that we did report at the ESMO conference. That's not yet mature, though. Only about 35% of the patients on the study actually had a PFS event that was reported, so we will be actually providing additional updates on the final median PFS early 2025. OK, then just following up on that, so with that mature efficacy data coming in early next year, yeah, what do we expect to see in the data? Is it just the updated sort of PFS data? And are you ultimately going to sort of make a go, no-go decision around that time? So we'll do an integrated look at the whole safety profile, efficacy data, namely the updated rPFS results. And then obviously looking at any subsets of data from the trial. About half the patients were previously treated with chemotherapy. About half the patients were chemo-naive. And then based on that, we'll make some recommendations in terms of go-forward development planning. We are trying to be vigilant in terms of resourcing and focus on the program in the near term. So we did actually announce on our recent earnings call that we had an ongoing study looking at combination with Vobra Duo and lorigerlimab, which we paused. There was also some exploration of other tumor types beyond CRPC, which we've also paused to really focus the effort to understand that signal in the monotherapy setting in CRPC. And then that would inform, again, subsequent development decisions. Gotcha. OK, so just to clarify, I guess will the final decision on where to move the program come at the same time as the data next year? We'll have visibility in terms of the PFS. We're obviously doing a lot of work internally, also trying to look at the PK and PD exposure relationship on patients. That will be assessed in early 2025. Then the subsequent disclosure plans will provide guidance on that subsequently. Got it. Makes sense. OK, so you're also evaluating, as you mentioned, MGC026, which is another B7-H3 ADC in a phase I. Can you talk about how that program compares with Vobra Duo in terms of all the parameters of ADCs, linker, payload, DAR, other characteristics that you might expect to impact the clinical profile? Yeah, so we're extremely excited about the profile of this asset, MGC026. It incorporates the drug linker chemistries that we had licensed from Synaffix. We were actually a relatively early adopter of that technology back in late 2022. Subsequently, there's been a lot of interest from both pharma and biotech trying to access that technology. Some of the salient advantages and interesting features of this platform are it does recognize a site has a site-specific conjugation approach, a term at the GlycoConnect, which enables a much more homogeneous material, all DAR4 for this construct. It also has a HydraSpace polar spacer that enables conjugation to exatecan. A lot of people in the field are obviously tracking the Merck Daiichi molecule called I-DXd. That does also use a topoisomerase I-based payload. But that payload called deruxtecan is two- to five-fold less potent than the exatecan. They're also employing a DAR4 construct in their molecule. What we've also seen, exatecan has shown much better cell permeability, a better bystander killing effect. This is all based on preclinical characterization and also less susceptible to efflux and other multi-drug resistance mechanisms. So we're very excited about the profile of the asset. Preclinically, we've obviously done a lot of benchmarking. We've also done the comparative look of our antibody with the Synaffix technology versus a DXd conjugation approach and we see superior activity in some of those preclinical models. That asset is in phase I dose escalation now. We expect next year we'll be able to provide some additional updates on the status of the project as we hopefully move into expansion cohorts. OK, and then maybe on that point, what are some of the solid tumor types that are in focus for this asset? To what extent can you leverage learnings from Vobra Duo or perhaps just the prostate cancer space? In the dose escalation, it really is an all-comer solid tumor population, which encompasses a range of tumor types, some of which are being studied by the other TOP1 molecules targeting B7-H3. But some of them could be potentially outside the scope there. We're still making the decision on what those specific expansion cohorts will be. Some of that may be actually informed based on the early clinical data coming out of dose escalation. But we haven't yet provided public guidance on where we're going to prioritize in terms of those expansion cohorts. OK, and then would you ultimately just advance one of either this or Vobra Duo? Could you advance both? What's your thinking there? These are actually quite distinct mechanisms. The Vobra Duo asset has the very potent DNA alkylator. Even in the interim PFS data, we reported 7.5-8.5 months of rPFS, and that, again, was based on the immature data set. That actually significantly exceeds the early data that Daiichi Sankyo presented, which was closer to 5.3 months, so we know in some indications, one payload may work better than others, and that, I think, we're going to have to drive empirically based on the data and see where we're seeing the effect. There's also a potential logic that these could be used in combination or in sequence, depending on which agent is used in the earlier lines of therapy. Makes sense. OK, great. So then maybe shifting gears a little bit to the rest of the pipeline, starting with the PD-1, CTLA-4 bispecific. This is a strategy that's been attempted by others. What makes your approach unique? Yeah, so obviously, checkpoint molecules have been in vogue, out of vogue. It kind of has oscillated over the last couple of years. Summit Therapeutics with some of their pretty compelling data with the PD-1, VEGF has kind of, I think, reopened interest in this category. We're very excited about the profile of our lorigerlimab program. It is a tetravalent structure, which is actually akin to what Akeso has. And they actually have two molecules in their pipeline. There's the PD-1, VEGF, but they also have a PD-1, CTLA-4 molecule that encompass the tetravalent format, where you have two binding moieties for PD-1 and two binding moieties for CTLA-4. There are a few other groups, Xencor and AstraZeneca, both have bispecific molecules. Each of them is, though, relying on a bivalent structure with monovalent engagement of each target. We do believe that the tetravalent approach and the additional benefit of that avidity enables better anchoring onto these double positive TILs, which, again, enables you to really localize the effect in the tumor microenvironment and avoid some of the toxicities that have plagued just cocktails of separate antibody constructs, and that's been clearly seen with, for instance, the Ipi-Nivo constructs. They do see some additive effect when combined, but they also have shown synergistic toxicity. Our agent, right now, we reported ASCO GU 2023. We had some very provocative signals in a late line CRPC population. These are patients who have been on prior ARAT therapy, prior docetaxel. Many of them also had cabazitaxel or PARP inhibitors, and we had seen a 26% confirmed overall response rate. That is significantly higher than what traditional PD-1 agents have shown. We've also seen that we can keep patients on therapy for a relatively long duration, in some cases well over a year, with continuous blockade of both PD-1 and CTLA-4. If you look at, for instance, in CheckMate 650, where Ipi-Nivo were combined, you can only have Ipi administered for a median of two cycles of therapy. And that's some of the toxicity associated with that. So we're feeling pretty good about the profile of the asset. We've actually now initiated, and we've almost fully enrolled the LORIKEET study, which is going to be a randomized study against docetaxel versus the combination of lorigerlimab plus docetaxel. That's going to be a 150-patient study, so relatively large sizing, and again, a controlled study, which will give us some real insights in terms of that asset and future development options. Great. So on that study, I think you've guided to an initial clinical update in the first half of next year. What can we expect to see in that update? And how do you think about sort of the benchmark for success? I mean, ultimately, what we're going to be looking at is durability and likely PFS as an important proxy in terms of long-term durable effect. If you look at some of the published data of other docetaxel-based studies, there is the KEYNOTE-921 study, which was Pembro plus docetaxel in the control arm with docetaxel. And that was a sizable study, about 1,000 patients. They saw about an eight-month PFS. So again, we'll see where we end up with our study. Doing the cross-trial comparisons is always challenging, which is why we want to have a control arm embedded in there. But we would want to see something meaningfully better than that in our study. Based on timing, obviously, the early surrogates for activity and efficacy will be PSA response as well as ORR. Obviously, the durability question will be something that will be more readily available later in 2025. Good. Gotcha. OK, all right, then maybe taking a view on some of the earlier assets in your pipeline. So you've guided to a phase I study for your ADAM9 asset, MGC028. First of all, can you just talk a little bit about the targets? What's the opportunity for the target? And why is the asset sort of positioned to address it? Yeah, so ADAM9, it's a target we're very excited about, potentially a first-in-class opportunity for the company. It also employs the Synaffix platform. So it's actually the same drug linker that is in 026 is being incorporated in 028. The target, and there's been actually a lot of literature published in the recent years suggesting that there's correlation of target expression with disease severity and outcomes. We do see overexpression in a number of solid tumors, including a number of GI malignancies, such as pancreatic cancer, gastric cancer. Non-small cell lung cancer has high overexpression of the target. So it does afford us many different potential development opportunities. We have had experience with this target with a prior asset, which was actually part of a co-development relationship with ImmunoGen. That asset was called IMGC936. We took that into phase I studies. We actually did not see any on-target related toxicities. The challenge with that program was ocular tox, which we ascribed to the payload, which in that setting was a second-gen maytansinoid, which is, again, as a class, has been reported. Ocular toxicities are pretty frequently observed. We did see some early evidence of activity, and actually, we had a poster presentation at the Triple Meeting in Barcelona highlighting the first-generation profile, so there have been some learnings around the target. Potential areas that we want to focus on will be kicking off the phase I early next year, and we reported on our recent earnings call that IND has already been submitted. Maybe just on learnings on the ADAM9 target, anything that you've gathered about, perhaps like a receptor or expression density that drives efficacy in certain tumor types versus others, distribution of the target, that's something of a consideration for other ADCs. Anything that you've learned from that first asset? Learnings on the target, but also around the platform. The Synaffix platform, which is now being broadly incorporated by a number of other groups. One of the collaborators on Synaffix is Innovent, which has a couple of molecules they're pursuing. One of the lead assets is a Claudin 18.2 directed program, which they actually had presented some very encouraging data at ASCO and at ESMO GI earlier this year and are now initiating a phase III study in gastric cancer. They also showed some early but provocative signals of activity with, I think it was about 30% response rate in pancreatic cancer. That gives us some sense that with regard to the payload and being able to induce a response in that indication, there's some element of validation. We've also done our own comparative look at ADAM9 expression patterns and how that compares to other targets, including Claudin 18.2, and we do see indications that it has a broader expression profile and a higher level of expression in those samples. That's based on tissue microarray data that we've done in-house. OK, very interesting. So all right, then another program that you have in your pipeline is the MGD024 and CD123 hematologic cancer. So can you just update on the status of this program? How should we think about any clinical benchmarks for success here? Yeah, so that is part of our T cell engager portfolio. Actually, that is also a second-generation molecule leveraging some of the learnings of an asset called flotetuzumab. That was a first-gen molecule. What we've changed with this asset is we've detuned the CD3 binder and changed the kinetics of the binding pattern to attenuate some of the cytokine release that we observed with the first-generation asset. It is also an Fc-bearing construct, which enables intermittent dosing, whereas the first-generation asset required continuous IV infusion. So this is in phase I. It is part of an exclusive option relationship with Gilead. So they're ultimately going to be driving some of the downstream development decisions there. But what I can say is based on the first-gen molecule, we published some of that data at ASH, we did see some very encouraging signs of activity, including CR rates in an AML-MDS population that were about 20%. So the hope is we can recapitulate some of the efficacy advantages, potentially get a better safety profile that then also enables moving into earlier lines of therapy, as well as potentially positioning it as a combination agent with other agents for AML and MDS. OK, so if you do get encouraging efficacy data, what would be the most likely, I guess, next steps? That will likely be driven by Gilead, assuming they want to advance the program. I'm not in a position to really comment on their downstream development plans for that asset. OK, great. So then perhaps just touching a bit on recent news. So the company recently partnered Margenza out. Can you just talk a little bit about the terms of that partnership and how you plan to, I guess, deploy the capital that you've gotten from that? Yeah, so obviously gearing up for 2025, we have a number of exciting inflection points, milestones that we are looking to hit with some of those clinical assets. We've made the decision to really focus the resources of the company in the context of Vobra Duo. I mentioned we're only going to look exclusively at Tamarack in the near term. We're not investing in some of the other ancillary studies for that program. Margenza, it is our only commercial asset, although pretty modest sales potential, and we realized we really want to monetize that asset. We partner with TerSera, which is a US-based specialty pharma company. Actually, we just closed that deal today. So we recognize the $40 million of proceeds. We can obviously redeploy some of the internal human capital onto the other pipeline assets that we're focused on. That really gives us an opportunity to really focus the operation going into 2025. Great. And what's your general strategy towards partnerships going forward, perhaps in the next year? We've had a very productive, I'd say successful BD operation at the company. Actually, over the last two and a half years, we brought in about $475 million of non-dilutive capital. So it's obviously been a great vehicle for bringing in funding for the business. We have four existing partnerships, which have the potential to create additional annuities of cash flows. Those are around our PD-1 asset called Zynyz that we've partnered with Incyte about six years ago. They also actually presented some nice data at ESMO, which was highlighted in the Presidential Symposium suggesting in frontline anal cancer, they may have a practice-changing new therapy available, the only PD-1 approved in that setting. We also have a type 1 diabetes program called Tzield that Sanofi is commercializing in the U.S. and are potentially looking at additional expansion of geography and indications in the coming years. And then we have the Gilead relationship. I referred to it, and TerSera is the newest addition to that partner portfolio. So we'll continue to be active looking at partnerships that both bring in capital, but also, I think, thinking more strategically around how can partnerships enable us to accelerate and expand development on some of our assets going forward. Great, so I think maybe with our last minute, could you just remind us of your catalyst lineup for the next 12 months or so? Near-term catalysts are really around those four assets that I mentioned. Vobra Duo, we'll have an update on that final median PFS number in early 2025, and we'll be able to then disclose that subsequently. The LORIKEET study for lorigerlimab, which will be fully enrolled around the end of this year, we'll have the ability to provide updates in early 2025 on that asset. MGC026, the other B7-H3 directed ADC, will be moving into dose expansion phases next year. And again, we'll have updates to provide on that asset. One of the attractive features of obviously ADCs is in many cases early on in that clinical experience, you'll have an understanding of both safety and efficacy that will guide your future development. So that could be an additional milestone for the company. And then 028 will really just get rolling with its phase I execution. So all those will be potential catalysts. And then obviously on the partnered portfolio, we're expecting next year to unlock a number of different milestones. Incyte has guided that the BLA for frontline anal cancer will likely go in this year, potentially approval in kind of 2025-2026 timeline. Similarly, they have a frontline lung study that had a positive readout, which they're guiding could potentially also enable an approval over the next two years or so. And then Gilead, we're continuing to mobilize resource on that collaboration. That's been a very productive relationship. First asset was 024, which was the CD123, CD3 program. About a year after entering that partnership, they actually expanded to add an additional research program that also leverages our DART program. So that's progressing nicely as well. Awesome. So 2025 is looking to be a pretty exciting year for us. Yeah, very busy year coming ahead. But we're up on our time. So I want to thank you, Eric, for joining us. And thank you all for tuning in. Great. Thanks so much.