Good afternoon, we will begin the MacroGenics 2021 First Quarter Corporate Progress and Financial Results conference call in just a moment. All participants are in listen-only mode at the moment, and we will conduct a question-and-answer session at the conclusion of the call. At this point, I will turn the call over to Jim Karrel, Senior Vice President, Chief Financial Officer of MacroGenics.

Thank you, Operator. Good afternoon and welcome to MacroGenics' Conference Call to discuss our First Quarter 2021 Financial and Operational Results. For anyone who has not had the chance to review these results, we issued a press release this afternoon, outlining today's announcements, which is available under the Investors tab in our website at macrogenics.com. You may you may also listen to this conference calls via webcast on our website where it will be archived for 30 days beginning approximately two hours after the call is completed. I would like to alert listeners that today's discussion will include statements about the company's future expectations, plans and prospects that constitute forward-looking statements for purposes of the Safe Harbor Provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factors section of our annual, quarterly and current report files with the SEC. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views changed except to the extent required by applicable law. And now I'd like to turn the call over to Dr. Scott Koenig, President and Chief Executive Officer of MacroGenics.

Thank you, Jim. I'd like to welcome everyone participating via conference call and webcast today. This afternoon, I will provide key highlights from our clinical programs. But before I do so, let me first turn the call back to Jim, who will review our financial results for the first quarter.

Thank you, Scott. This afternoon, MacroGenics reported financial results for the quarter ended March 31, 2021, which highlight our financial position as well as our recent progress. As described in our release this afternoon, MacroGenics' total revenue consisting primarily of revenue from collaborative agreements was $16.9 million for the quarter ended March 31, 2021, including $0.9 million net sales of MARGENZA, which launched in mid-March, compared to total revenue of $13.7 million for the quarter ended March 31, 2020. Revenue recognized during the quarter ended March 31, 2021 included a $10 million milestone related to development progress of Retifanlimab outside the U.S. under our exclusive global collaboration and license agreement with Incyte. Our research and development expenses were $53.1 million for the quarter ended March 31, 2021, compared to $48.9 million for the quarter ended March 31, 2020. This increase is primarily due to higher expenses related to Flotetuzumab, MGC018, MGD019, and preclinical projects partially offset by a decrease in development and manufacturing costs for Retifanlimab. Our selling, general, and administrative expenses were $15 million for the quarter ended March 31, 2021 compared to $10.2 million for the quarter ended March 31, 2020. This increase was primarily due to MacroGenics' 50% share of sales and marketing costs related to MARGENZA prelaunch and launch activities as per our agreement with EVERSANA. Our net loss was $51.3 million for the quarter ended March 31, 2021, compared to a net loss of $44.7 million for the quarter ended March 31, 2020. Our cash, cash equivalents and marketable securities balance as of March 31, 2021 was $343.2 million compared to $272.5 million as of December 31, 2020. During the quarter ended March 31, 2021 we sold 3.62 million shares through our at-the-market or ATM facility at an average price per share of $27.60, raising net proceeds of $98.2 million. As is fully depleted our previously filed $100 million ATM facility, today we refresh the ATM by filing a $200 million prospectus supplement to our shelf registration statement. Finally, in terms of our cash runway, I will remind listeners that there are two PDUFA target action date scheduled for July of this year relating BLAs for both Retifanlimab and Teplizumab. For cash budgeting purposes, we continue to discount both milestones as we have no control over them. Even with this discounting, we anticipate that our cash, cash equivalents, and marketable securities as of March 31, 2021 combined with anticipated and potential collaboration payments should enable us to fund our operations through 2023, assuming the company's programs and collaborations advance as currently contemplated. And now, I'll turn the call back to Scott.

Thank you, Jim. With the recent launch and commercialization of MARGENZA, we are delivering on our vision to provide potentially life-changing therapeutics to patients with cancer. We are well-positioned to advance this mission as the growing body of data emerges from our deep pipeline of clinical and preclinical product candidates. We are particularly excited about the multiple ongoing registrational or potentially registration-enabling studies, including Flotetuzumab in AML, and margetuximab in gastric cancer. These are in addition to two PDUFA outcomes related to Teplizumab and Retifanlimab in July. And finally, we know many of you are eagerly awaiting clinical data for multiple dose expansion or proof-of-concept studies, including from MGC018, Tebotelimab, and MGD019. With that backdrop, let me use this time to walk you through updates on our portfolio of eight clinical molecules. First, let me provide an update on margetuximab. As Jim and I both mentioned, MARGENZA was launched in mid-March in coordination with our commercial partner EVERSANA. As a reminder, MARGENZA is approved in combination with chemotherapy for the treatment of adult patients with metastatic HER-2-positive breast cancer where we received two or more prior anti-HER-2 regimens, at least one of which was for metastatic disease. MARGENZA was recently included in NCCN guidelines. As I mentioned on our last quarterly call, we have modest expectations for MARGENZA sales, given competitive realities that have taken place in the HER-2-positive breast cancer market, including multiple new approvals, which is great for patients. Owing to these recent changes in the market and abbreviated sales history, we don't expect to provide MARGENZA sales guidance until later this year when we have a better sense of uptake by oncologists. Finally, with regard to margetuximab for metastatic breast cancer, as you may recall, the Phase 3 Sofia trial is still ongoing for overall survival. Based…

Thank you. [Operator Instructions] Our first question will come from line of Jonathan Chang of SVB Leerink. You may begin.

Hi, guys. Thanks for taking my questions. First question, can you provide your latest thoughts and hopes at expectations as it pertains to the upcoming MGC018 update at ASCO? You provided some color on the prostate expansion cohort, maybe to follow up on that, should we expect to see any lung cancer expansion cohort data at ASCO?

Jonathan, thanks very much for your question. At this point, we're not expecting updates on the long cohort given the very early nature of that study. As I have indicated previously, patients did not start enrolling in that study till after the beginning of this year. We haven't actually looked at the full data set available. We are devising the poster very shortly. But as of now I don't expect the lung cancer patients to be included in the update.

Got it. Thank you. And one clarifying question. I think I heard this but I just want to double-check. Are both the MGC018 expansion cohorts and head and neck cancer and melanoma evaluating the same 3mg/kg dose level and regimen as the other ongoing expansion cohorts?

That's correct. The new expansion cohorts in head and neck and melanoma are at 3mg/kg, q 3 weekly.

Got it. And just one final question from me. What are your latest thoughts in potential 018 updates beyond ASCO this year?

So we intend to provide updates at future scientific meetings this year. We are considering a submission to ESMO. Obviously, the data has not come up yet, but that is in the planning stage.

Got it. Thanks for taking the questions.

Our next question will come from Peter Lawson from Barclays. You may begin.

Hey. Thanks for taking my questions. Just as we think about the ASCO data for B7-H3, I guess two parts really kind of how much prostate data should we expect to see and would we see any other indications with triple negative breast cancer or in in the earlier data?

Thanks, Peter. So with regard to the quantity, as I said, we're doing a cut off this past week in terms of the data update. I haven't seen the actual data yet as we devise the poster. My expectation is you'll have in the new expansion cohort of prostate patients. There will be a double-digit number of patients included. As I said on the call today, we have treated over 20 patients. So, given that we are looking at PSA results on a Q3 weekly basis and looking at scans on every nine-week basis, it is possible that we'll have significant number of patients having at least some initial PSA evaluations in that prostate cohort. With regard to the triple negative breast, as I indicated that is enrolling slower than the prostate and lung cancer patients and don't expect the completed enrollment of the 20 patients of that cohort till the second half of this year. So, we will not include that at the ASCO meeting. However, as we have indicated today, we have data from the 4mg/kg q 3 week dosing in the dose expansion, which, as I noted today on the call will include three melanoma patients. We had historically said we had two prostate patients and there will be another patient with another indication included in this study.

Good. And the reason to add head and neck, was that influenced by [indiscernible] trial, or just the PDX model?

As we commented today, the latter with regard to the PDX model was obviously very reassuring, but even before we had the PDX model data, as you recall, two and-a-half years ago, we presented very compelling data of Enoblituzumab, combined with [indiscernible] head and neck patients with 33% overall response rate with a lot of durability of those responses. As you know, frontline head and neck cancer treatment is pembrolizumab plus chemotherapy. So, the ability now potentially treating a frontline population with two different checkpoints based on PD-L1 status, plus Enoblituzumab was very encouraging to us, and we thought that was very natural then to add an MGC018 in late-line patients as well.

Got you. Just a final question, would we get durability data in the abstract? Would we have to wait for the presentation?

With regard to the abstract, again, as discussed today, the cutoff date was January. The abstract was on February 17. So, very little data, but for the comments on the 4mg/kg cohort group is included in that abstract. Having said that, as I have noted on earlier calls in the past month, I know there's at least one of the 4mg/kg patients that's still on therapy. So again, we'll have to wait for the actual data to hear the update.

Thank you. Our next question will come from line of Jonathan Miller from Evercore ISI. Your line is open.

Yes, thanks for taking the questions, guys. I think let's start within one more about the ASCO data. Are we expecting to see any color at all on those other cohorts [indiscernible] cohorts' mid-year? Or should we have to wait as well to see anything on the activity side from those cohorts? Secondly, you said -- I thought I heard that you said the PSA responses, you were happy with PSA responses in the mCRPC cohort. Did I hear you correctly? Is it fair to say that those rates are holding in? And then maybe switching gears a little bit -- let me hear these answers first before I inundate you. Thanks.

Yes. Thanks, Jon. So with regard to the other cohorts and the timing, all I can project right now is obviously what we're going to do at ASCO. We typically like to present these data, scientific meetings, and time it appropriately. So, my sense is that is most likely presented at one or more scientific meetings in the second half of the year. With regard to the PSA, in the expansion cohorts, I'll just keep it general that the biological activity is trending favorably in the data they looked at literally a week ago. And I won't say more than that. Obviously, we'll have some additional numbers coming this week. But from what I've seen so far, I'm very pleased. What I'm seeing with regard to bioactivity, safety profile we've described historically and with the new patients, and then additional data that we're getting from the 4mg/kg expansion cohort.

Thanks. I guess now we can switch gears maybe. I noticed the new CD123 x CD3 moving forward there. How should we think about that in the context of potentially registrational cohort for Flotetuzumab and your plans for updates on that data set?

Totally independent. The enrollment of the registration study of Flotetuzumab and the primary induction failure early relapse patient is continuing. We anticipate providing updates by the end of the year on that study. As I've highlighted before, we're very excited about the prospects of advancing our platform technologies. So, with regard to this CD123 x CD3, this contains a slightly altered CD3 molecule that should dramatically reduce cytokine release but preserve the anti-tumor effects we have seen with Flotetuzumab, plus the ability of having intermittent dosing of those patients based on the incorporation of an FC domain. So, we're very excited, as this is one of several molecules in our preclinic portfolio that's emerging on this, advancing our platform technology.

Makes sense. And just one last one. On new expansion cohorts for MGD019, what's giving you confidence in prostate? I think melanoma makes sense for these sorts of targets, but prostate is a little bit different. Can you talk a little bit about what's driving you into that indication?

So, there are a couple of things that's driving -- obviously with our strong interest in prostate cancer, we're looking at opportunities to advance multiple molecules in that indication. As you probably remember, one of the patients that had an objective response, in fact a complete response in our dose escalation study, was a patient with castration resistant prostate cancer, which again, was quite remarkable. And that patient is still in remission and I think that's coming on close to two years now. I know it's at least a year and-a-half. So, we're very pleased about that. Also, as you know, studies that were conducted with epinebo [ph] in prostate cancer show the responses that were quite favorable. Although they did not meet the objectives of the study for approval. The idea here are being able to use a safer and potentially safer and very active molecule like MGD019, gives us a lot of enthusiasm. And finally, as you know, one of our missions in our company is the combined ability of our molecules and so as we develop these molecules individually, in a particular indication, we look for the opportunity to combine them in mechanisms that are orthogonal to each other to get to an even better response. Our preclinical data for instance, combining MGC018 and checkpoint molecules, it's been shown to be quite favorable. And so, do not be surprised at future studies, maybe designed to ask those questions in indications that we are pursuing as monotherapy.

Our next question will come from the line of Stephen Willey from Stifel. You may begin.

Yes, good afternoon. Thanks for taking the question and I'm going to ask you a couple of 01A [ph] questions, if you don't mind. But I guess there seems to be a lot of emphasis around this notion of whether or not we're going to see some resistor variable prostate cancer patients at ASCO, even though this is I believe, the minority of most refractory prostate cancer patients. Is there anything that you can say, just with respect to I guess the double digit patients that may be included in the presentation? Of what proportion of those do you think we may actually be able to see some resuscitate in?

Thanks, Steve. So with regard to the expansion cohort, with regard to resistor variable patients, I haven't looked over the latest list of patients with regard to whether they had measurable disease. What I've noted on previous looks, they seem to be following the normal composition of patients that have bony-only [ph] disease, which are a little bit more than 50% and then patients that have either lymph node, or visceral disease that is measurable, which is a little less than 50%. So, I'm assuming that we have a pretty normal distribution. I think that the issue becomes is whether we have any valuable scans at the time because as I said, most of these patients came in 2021 and we're only getting scans every nine weeks. So, if we don't have anything that's valuable by ASCO, we certainly will have it at valuable in the second half of this year. So, it's not that we're holding back anything, the patients have to have time to be evaluated.

Got it. That's very helpful. And I know in the literature, there's this suggestion that the correlation between, a PSA50 response and the resist response is pretty high. But do you think that correlation differs on a target-by-target basis in terms of just modality of therapy? Or do you think that that's just a correlation that broadly holds across the treatment landscape?

I think the full answer is not in yet. I think that the recent data suggests a pretty good correlation. As you know, many of the agents that are approved for treatment are part of the AR inhibitor family. And so I suspect that the effects on TSA and then ultimate prediction there may be different than, say, an ADC molecule with cytotoxic effects. I think we'll just need some more time to evaluate this. I think that in the case here, where you're using an ADC, the only thing that I can truly ascribe to the reduction PSA is actually a reduction in tumor. That's the only mechanism that I can see here either by direct cytotoxic effects or possibly by secondary immunological mechanisms. So, we'll have to see whether that correlation also -- I should also know that for patients that particularly late stage patients that have continually rising PSAs, the ability to shut that off that doubling time, should be also seen as quite favorable. Because ultimately, we're not curing late stage patients, we're looking at both improving the morbidity and mortality of these patients and prolonging their life. So, I think again, we're going to need more time to ultimately come out with a conclusion here. But as I said, we were very excited last year by the initial data, we continue to see the current data in a positive light.

That's helpful and just lastly, Scott, you mentioned the possibility of combining MGC018 with PD-1 inhibitor. I know that the protocol for the MGC018 a trial calls for I guess, with or without Retifanlimab. Have you started dose escalation with Retifanlimab? And I guess, did some of the PD-1 plus chemo data that we've seen in the refractory setting kind of accelerate those development timelines? Especially now that you've settled on a recommended basis [ph]? Thanks.

Excellent question, Steve. So, when we were starting the dose escalation, we expected to quickly go over and flip to the combo study with Retifanlimab. However, we were obviously pleasantly surprised with the robustness of data we saw with the PSA reduction. And so rather than continue on with that part of the protocol, as you know, we didn't even finish out the dose escalation, we went to the expansion. Now that we have so much more data with both Tebotelimab, the PD-1 x LAG-3 and with MGD019, PD-1 and CTLA-4, in addition to Retifanlimab, we have a lot of different opportunities now and don't necessarily have to resort to just using Retifanlimab. And so, we're right now in discussions of next steps in designing those combinations studies, and so I would not necessarily assume that it's going to be Retifanlimab.

Our next question will come from line of Yigal Nochomovitz from Citigroup. You may begin.

Hi, Scott and Jim, thank you for taking the questions. Could you just clarify why you're combining Enoblituzumab with Tebotelimab in the PD-L1 negative head neck patients, given that Tebotelimab targets PD-1?

Yes. This goes back to the observations we made and described last year at ASCO with regard to our FC engineering and combination with Tebotelimab. As you recall, we presented a very exciting data margetuximab with Tebotelimab in patients that were HER-2-positive in late line patients who the majority or many of these had very low checkpoint like an expression. So, very low PD-L1, very low LAG-3. In fact, many of the patients were PD-L10. At the same time we were conducting the preclinical studies with that combination, we were also conducting Enoblituzumab in combination studies, with Tebotelimab and demonstrated as we have discussed before, the ability to drive up innate and specific community as a result of treating with the FC engineered Enoblituzumab, and by up-regulating both LAG-3 and PD-L1. We see that as an opportunity of now getting a much more dramatic therapeutic effect when added to Tebotelimab. So again, this is a Phase 1 study in the Enoblituzumab with PD-L1 negative, but our assumption is the same that's the engineering that's in March where we said positive clinical results would translate the same way for the PD-L1 negative patients when given this FC engineering plus Tebotelimab. And as you know, the historical data from Merck with pembro, or from [indiscernible]; and head neck with PD-L1 negative was very poor. So, any way to increase the expression here we think will be having salutary effects.

Okay, got it. And then could you just comment on the rationale for expanding the Phase 1 MGC018 study into melanoma? I'm just wondering if you also had mouse PDX data for melanoma as you did for head and neck.

Okay, so without revealing specific data, as you noted on our call today, we had at the 4mg/kg, three patients with melanoma. That's all I'll say about those patients and wait till the ASCO presentation. But I also should put this in the context of our historical experience in melanoma. With Enoblituzumab as a single agent, we had objective responses or tumor reduction in late stage melanoma patients and the same thing was also observed in patients who were treated by specific MGD019, which is the CD-3 x B7-H3. So, we have many avenues at this point that suggests melanoma would be a good population to continue to evaluate and of course, we also have done immunohistochemistry studies with tissue specimens from melanoma patients showing high expression of B7-H3.

Okay. Thank you very much, Scott.

Our next question on the line of Brad Canino from Credit Suisse. You may begin.

Great, thank you for having me on the call. I'll just ask one and not about data expectations. But I do have a question on the product market fit for the gastric cancer module A that you're going to be reporting at ESMO. Because I understand the rationale of a chemo-free regimen to reduce toxicity, but these patients present with pretty debilitating symptoms from the tumor are likely struggling to eat and I would think they would want a fast response, which is what the chemo would provide. So, how important is the chemo-free regimen? Is this just a niche opportunity relative to your chemo triple that you'll have later? Or do you think there's really a demand here? Thank you.

That's an excellent question, Brad. Nice to meet you via phone. So again, if you recall, we had conducted studies in second line of margetuximab and pembrolizumab and actually saw -- and these are patients who have progressed on Herceptin and chemotherapy. And so in their HER-2 3-plus positive PD-L1 positive population, actually a very quick response and certainly a large number of those patients. And the additional value of that is that our overall survival of that population was dramatically better than the approved second line therapy with paclitaxel. And much better than first line therapy when you compare, of course, different studies. And so that was the rationale also, the fact is, is that when you look at the patients in the frontline setting, their HER-2 expression tends to be higher, and their PD-L1 expression tends to be higher. So, again, we are expecting or had expected and hope to be able to present the data later this year at a scientific conference addressing the question you had in terms of the rapidity of response, and the durability of that response.

Great. Thank you. Look forward to ESMO.

Our next question comes from line of Boris Peaker from Cowen. You may begin. Boris, your line is open. And our next question will come from the line of Etzer Darout from Guggenheim Securities. You may begin.

Great, thanks for taking the question. The first one, I guess is another sort of clarifying question from the introductory remarks. Just wanted to confirm that all but two patients in the sort of the prostate expansion are made on therapy and then also on the pace of enrollment and melanoma and head and neck? And then I have a second question.

So as the data that I had seen a couple of days ago -- that was that was correct, so I can tell you it change today, but as of a couple of days ago that statement is correct. With regard to the speed in which we will enroll the head, neck and melanoma patients go work. This is just opening up. The expectation is that we will enroll a significant number in the second half of this year. But again, we'll provide updates over the course of the year. how that's going.

Great. Thank you. And then one question on MGD024. I guess based on the preclinical evaluation you've done so far, how are you thinking about sort of maybe frequency of administration and that kind of relates to Flotetuzumab, once every week once every two weeks? Any thoughts around what that interval could be based on what you're saying?

Good question, Ed. So obviously, we'll have to see what happens in patients. But I think a q 2 weekly dosing regimen is certainly possible. It may reduce to q 1 or increase to q 3. We'll just have to see.

Great. Thank you.

[Operator Instructions] Our next question will come from the line of David Lebowitz from Morgan Stanley. You may begin.

Thank you very much for taking my question. On the gastrointestinal trial module A, I guess how many patients were originally expected to be presenting at ASCO versus the 40 that will be presented later this year? And what I guess is the driving factor behind the leading physician wanting to postpone presenting the data at this point, what factors are pushing, wanting to just hold off until the complete data set is ready?

Yes, thanks, David. It was very, very simple. It's that as you know, our decision to move forward based on central review of 40 patients and we only had about a little over 20 patients that had investigator review. So it was really in-between presentation. And so since there was no compelling decision and we're waiting till the full 40 patients get evaluated radiographically, we didn't see any harm on allowing the investigator to present this hopefully at ESMO, given that it was only a partial study, this was going to be a poster session. And with a much more fuller data set, there is obviously a potential for an oral presentation with this type of study.

Have any of the patients in that original abstract undergone the, I guess, radiographic assessment to this point?

So, they have all the patients 20 -- some patients have investigator evaluations. There's been some additional patients. But there's no full central review data set available at this point.

Okay. Thanks for taking my question.

Thank you. And I'm not showing any further questions in the queue. I like to turn the call back over to the speakers for any closing remarks.

Thank you, Operator, and thank you for your participation in the meeting today. We look forward to updating you on our programs in the not-too distant future. Have a wonderful afternoon.

This concludes today's conference call. Thank you for participating. You may now disconnect.