Good morning. Welcome to Barclays Global Health Care Conference in Miami. You raise your hand or email me if you have questions. My name is Peter Lawson. I'm one of the mid-cap biotech analysts at Barclays. Really delighted to host President, CEO of MacroGenics. With that, I'd just, I guess, love to start the questions on your B7-H3 and I guess clinical trial for phase 2, kind of how's that enrolling and, you know, when should we- Sure. expect that to be enrolled? Yeah. First of all, Peter, thanks so much for the invitation today. Many of you know we've been pursuing multiple molecules towards B7-H3 with a lead molecule called Vobramitamab Duocarmazine. We sort of note this in short as vobra duo. It was used be called MGC018. This is a antibody to a particular epitope of B7-H3 with a cleavable linker, duo called Duocarmycin. When taken up into the cell, the linker gets cleaved and the toxin alkylates DNA, promotes apoptosis, gets released, and kills local cells in the microenvironment, which are both the dividing tumor cells as well as the vasculature and Treg cells in that environment. The study TAMARACK, we have continued to initiate sites in the U.S. It's still in early phase of the study. We have approval in four countries, and we'll be expanding the number of countries where we will be enrolling sites. The plan is to enroll in this phase 2 portion of the study, which is being testing two doses slightly lower than that was used in the expansion cohort at 2.7 mgs per kg on a Q4 weekly basis and two mgs per kg on a Q4 weekly basis. The plan is to hope to enroll a majority of those patients this year and obviously into 2024, and we're targeting in the second half of 2024 to be able to have some data available. Perfect. Thank you. Then maybe just as we think about the trial design, I know we've done K-one calls and they've kind of talked through what they would like to see additional ads. Just your thoughts around why use a androgen receptor axis targeted agent versus a CAR T cell? Yeah. Again, when we first designed this study, as many of you know, we were focused on prostate cancer. The landscape is continuously changing in terms of treatment paradigm both for metastatic castration and prostate cancer as well as actually hormone-sensitive arm of the study. It's we're really in a major shift this year and next year. Obviously, Pluvicto got approved last year. There's been obviously some difficult uptake because of a lack of enough drug. There are obviously some studies with PARP inhibitors that do not have DNA repair issue. What we have always said is that we would continue to evaluate what the appropriate standard of care would be at the time we complete the phase 2 study and then pick the right control group at that time, which again, as we say, is likely to be in the second half of next year. At the time, we had decided on taking an androgen receptor axis targeting agent as a control. There were multiple other studies using this as a control and as historically have been done. As all advances in patient care proceed, you have to adjust appropriately for that. We will be looking towards next year at picking the right control group when we move into a phase 3 study. Gotcha. That's something you'd need FDA sign-off on? Well, yeah. We had already told the FDA in the design of this TAMARACK study that we would go back to them after we had the phase 2 data to tell them which dose we were moving forward with and what we would do with regard to the control population. They, you know, again, they had listened to us about that. They didn't have any better suggestion about a control when we discussed the use of ARAD at that point. Gotcha. Would that switch in any way kind of delay the trial readout? No, it shouldn't. Again, we'll have to see where we are at that time. Perfect. Thank you. Then what does success look like for you in that portion of the trial? Well, again, we don't know how the landscape might change, vis-a-vis, Pluvicto come the end of next year. You know, are these patients gonna be further beaten up because, as you know, there is certainly some effects on the, on the bone marrow compartment? If we have those patients who have seen Pluvicto versus those who don't, we'll have to make an assessment. We would be looking clearly at a radiograph PFS improvement. You know, historically, the controls have been somewhere around 4 months or greater. Clearly, you know, for instance, the CARD study for cabazitaxel, we were able to get to eight months of our PFS in those. We would look at obviously, that range for improvement, with this drug at least. Gotcha. I guess the most obvious competitor there is Daiichi molecule. Kind of what should we take from their data? What kind of feeds into yours? Kind of how should we compare or contrast that dataset, those datasets? Well, I think we have to be encouraged. I mean, as you recall when we've had conversations historically, we were the only company working on B7-H3 at the time. People say, "Why are you working on it? on it? Nobody else is." Now that you have a party like Daiichi that has had very good data, they have indicated, particularly, moving forward in small cell lung cancer. They got some very nice data in a small subgroup. They've also had confirmed some nice data in prostate cancer. Although, you know, what we had observed and reported was that we were having PSA 50 reductions about half of patients, as were about a quarter of the patients. We were fairing a little bit better with regard to PSA 50s. We'll see. What I see is a confirmation not only of Daiichi pursuing B7-H3, and now a whole host of other companies in preclinical or early phase 1 studies, pursuing other technologies with H3. I think people have come around to recognize what we had seen very early on the value of this, both in terms of its expression pattern and a very deep opportunity, because it's expressed in most solid tumors. Gotcha. How should we think about kind of how that market breaks up with Daiichi? Is it kind of winner takes all or? Well, I definitely do not see that being a winner take all. Number one is that as I point out, again, almost all solid tumors express that. The ability for multiple technologies working in different tumor types, different lines of therapy, different combinations, different linker toxins, all offer opportunities for better patient care across the board. I think this is one of those unusual situations that there could be multiple winners here going forward. In that vein, as you know, we are building other B7-H3 molecules with other technologies. We have the Fc-engineered and Inotuzumab molecule. There was some very good data that was presented last year by our academic colleagues at Johns Hopkins in the use of Inotuzumab or Fc-engineered B7-H3 targeted molecule. Different epitopes than vobra duo, that showed in neoadjuvant setting a beautiful infiltration, into the prostate of patients before they had their prostate taken out, but treated with Inotuzumab. In a number of these patients, their Gleason score had reduced at the time when the prostate was taken out. We're actually in discussions with them, on the plans for a study going forward, a phase 2 study, a controlled study, potentially, using Inotuzumab in a neoadjuvant setting. Nothing definitive yet, but something we're in discussions with. Gotcha. Thank you. You think would prostate be the first approval for you? How far behind Daiichi could you be? Well, I think prostate is certainly what we're focused on. As we had set out from a corporate standpoint, is we wanna both manage the cash going forward and prioritize programs. As many of you know, we have a very deep preclinical and clinical pipeline now. So we had to make some choices, both in terms of which molecules we would prioritize, number one, and then which indications going forward. It takes nothing away from what we see as a very broad opportunity for the molecules we've already talked about going to other tumor indications, which we will intend to do when we have enough capital moving forward. Gotcha. Thank you. Maybe because the next molecule, we kinda think about PD-1 and CTLA-4, kind of what should we expect there for the combination. Yeah. -B7-H3 this year? As you know. Sorry. Sorry. Yeah. Yeah. Supposedly this year we get an update. What should we expect to see? We are very excited about the opportunity here. As many of you know, we just recently presented data at ASCO GU on the activity of Lorigerlimab, which is constructed as a Tetravalent Bispecific two binding sites to PD-1, two binding sites to CTLA-4. This is put on a backbone of an IgG4. The idea here is that you would get a high avidity of that molecule to co-express cells of PD-1, CTLA-4, maintain all the PD-1 blockade activity as well as CTLA-4, but avoid the destruction of CTLA-4-bearing cells alone that are a marker for Treg cells, which we felt was contributing to the particularly colitis that one sees in ipilimumab combinations that have been tested requiring Ipi to be reduced to one mg per kg. The data was, we believe, was quite remarkable. What we showed at ASCO GU is a PSA 50 reduction of approximately 29%. This is in a cohort of 42 patients. Of the 35 evaluable patients, we had nine patients with confirmed PRs. All those patients, nine out of nine, had PSA 90s or greater. Four of the patients who are still on therapy are on for over a year now. We have both longevity of response. Yeah, I mean, you just don't see that great correlation with PSA 90 and the objective responses, and with a safety profile that we see as looking like a PD-1 blockade. Actually we have an earnings call tomorrow. We'll provide updates, which we promised, by the end of this quarter of next study going forward of, a phase 2 study, of Lorigerlimab. We will outline, what that study will look like tomorrow. Good. Any details on the call or... Uh. Just an update. There'll be a lot of information on the call, so I think it's worth your time listening to. Okay. Perfect. Thank you. Then kind of as we think about data this year, is that something we'll kind of get on the earnings call of like how much data we're gonna see? You know what we've said is that we have an ongoing study of the two molecules I just described to you, or two of the three molecules I just described to you, which was the vobra duo combination with Lorigerlimab. We're still in dose finding. Whether we see data later this year or next year is still to be determined. We still have to figure out what that combination dose looks like. You know, with regard to the call, it won't be a lot of opportunities that you'll see unfolding for the company over the course of the next year going forward. Gotcha. You mentioned the low colitis with your combination. Just kind of what's an acceptable safety profile look like when you combine B7-H3 with your [C 4- PS 81]? Well, clearly what we've seen from the individual drugs alone, they don't seem to have much in terms of overall toxicity. What we're looking for is a profile that is improved by that combination. Remember, mechanistically, because they're working by different arms of the immune system, potentially, there is maybe the opportunity for both lowering doses to get a additive or synergistic effect. There's always the possibility of toxicities unfolding with that combination that we could not foresee. We'll have to see, you know, as we move forward with this. Gotcha. Okay. I guess before we get to the end, I definitely wanna ask your exposure to SVB and also regional banks and I guess non-bank lenders as well, and kind of the worry there. You know, knock on wood, obviously we're sorry to see, the issues unfolding with regard to SVB and as well as, the smaller regional banks. We have no exposure at all. We have no money with them, nor with other regional banks. Gotcha. Okay. Just as we think about the financing deal you did as well, how does that extend cash runway, I guess with your anti-CD3? We are, have been very successful at bringing non-dilutive capital to the company. We've highlighted that over the course, since our IPO 9.5 years ago. We have brought over $1 billion of non-dilutive capital into the company through various partnership deals and government contracts. Overall, just to refresh your memory, in the second half of last year, we brought in $150 million of non-dilutive capital. Last week we talked about a deal with CRI to monetize royalty that we have from the prevention asset purchase of the [Prism Labs]. We announced that we had $100 million cash that will be in the bank probably later today. In addition, another $100 million on that deal with CRI with particular milestones to be achieved. Now that the, there was an announcement yesterday of the purchase by Sanofi of Prevention, Milestones that both in terms of DRI that I just described, additional $100 million. There's also a topper on that where if a certain sales point is achieved above that, we will share in the residual royalties on additional sales there from the DRI side. As you might remember from our deal with Prevention, we had additional milestones, both clinical regulatory and commercial milestones, which together on the, on the just the Prevention side, is $335 million between the regulatory and commercial. You take the $335 million, the $100 million I just talked about potential in DRI, that's $435 million. Then there's a potential topper on that as I described to you with regard to particular sales. Given that now Sanofi has just paid $2.9 billion for Prevention, they clearly have great expectations on sales. I think a lot of these milestones could be achieved for all these potential markets, no longer fire bucks for us. These are really potentially achievable milestones. If you just think about the Prevention side and the DRI side of our portfolio from a future cash basis of somewhere $400 million or $500 million coming in, I think the world could take it. Have you changed, I guess will you change cash flow guidance? We will talk that tomorrow. Okay. Yep. What we have said as of at JP Morgan, we said our current cash position of the ones I just described with the full DRI, took us through. We will obviously extend that on our call tomorrow. Okay. I guess with the potential change in cash guidance, will you think about accelerating payments as well? I think that this will provide opportunities to expand some of the work we're doing. What you might not have noticed this morning, there was an announcement by Synaffix. Remember last year we did a deal with them for three slots for linker toxins. What I announced to JP Morgan was that, of those three slots we plan to have an option B for a new ADCs molecule at the end of this year, and then actually, 2nd one next year. Today's deal with the expansion of that collaboration where we have now 4 new slots. That's seven slots for ADC molecules coming from our preclinical portfolio. You know, we have been always ambitious, but we would not have taken on this opportunity if we did not know, where we wanted to go with this, both in terms of potential, targets to pursue. Would things like B7-H3, would that be included in? Oh, well, that is certainly a possibility on the table. Okay ... for us to pursue other linker toxins for B7. Perfect. If I can go back briefly to B7-H3, just with the data for Daiichi in small cell lung cancer, Is that something that would influence an expansion of? Obviously that's an important indication, although a small indication. When we did an evaluation of H-scores across all the tissues we looked at, SCLC was not one of the highest ones going forward. It's very nice to see that they've had some very good data in that regard. In our own studies, we only had one patient at a lower dose in dose escalation. I happen to say that that patient did very well. Our patient with small cell lung cancer. That patient, if I recall, was on two mgs per kg on a weekly basis in dose escalation. That patient had tumor reduction, did not get an objective response, but actually had been on therapy for over six months, which for patients with small cell lung cancer is quite remarkable. With regards to small cell lung cancer, we have a investigator who is interested in working with us on enrolling some of those patients right now. We don't have any near-term plans to have a controlled study for that indication. We have other tumor types that we have interests to present. Perfect. We've good to end. I'd love to end it, thank you so much. Okay, Peter. Absolutely. Thanks for the question and answers.