Good afternoon. We will begin the MacroGenics 2021 Second Quarter Corporate Progress and Financial Results Conference Call in just a moment. All participants are in a 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 Chris James, Vice President of Investor Relations and Corporate Communications of MacroGenics.

Thank you, operator. Good afternoon and welcome to MacroGenics’ conference call to discuss our second 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 on our website at macrogenics.com. You may also listen to this conference call 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 reports filed 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 change, 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, Chris. I’d like to welcome everyone participating via conference call and webcast today. So those who have not yet met Chris James, he recently joined MacroGenics as our VP of Investor Relations and Corporate Communications. We are delighted to have him on board. This afternoon I will provide key highlights from our clinical programs, but before I do so, let me first turn the call to Jim Karrels, our Chief Financial Officer, who will review our financial results for the second quarter.

Thank you, Scott, and welcome, Chris. This afternoon, MacroGenics reported financial results for the quarter ended June 30, 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 $30.8 million for the quarter ended June 30, 2021, including $3.2 million net sales of MARGENZA, which launched in mid-March. The $30.8 million compared to total revenue of $20.3 million for the quarter ended June 30, 2020. Revenue recognized during the ended June 30, 2021 included $14.4 million from Zai Lab related to the recent June 2021 collaboration announcement and a $5 million milestone related to development progress of retifanlimab under our exclusive global collaboration and license agreement with Incyte. Our research and development expenses were $55.8 million for the quarter ended June 30, 2021 compared to $57.4 million for the quarter ended June 30, 2020. Selling, general and administrative expenses were $15.2 million for the quarter ended June 30, 2021, compared to $10.2 million for the quarter ended June 30, 2020. This increase was primarily due to MacroGenics’ 50% share of sales and marketing costs related to MARGENZA launch activities as per our agreement with EVERSANA. MacroGenics net loss was $39.9 million for the quarter ended June 30, 2021 compared to a net loss of $46.9 million for the quarter ended June 30, 2020. Our cash, cash equivalents and marketable securities balance as of June 30, 2021 was $297.3 million compared to $272.5 million as of December 31, 2020. Our June 30, 2021 cash position did not include $55 million received from Zai Lab in July related to our broad strategic collaboration to develop and commercialize preclinical bispecific antibodies in oncology. This collaboration was announced on June 16, 2021. The $55 million consistent of a $25 million upfront payment and a $30 million equity investment as consideration for the execution of the collaboration agreement. Finally, in terms of our cash runway, we anticipate that our cash, cash equivalents and marketable securities as of June 30, 2021, combined with funds subsequently received in addition to 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. We are excited by our continued progress towards our goal of providing multiple potentially life-changing therapeutics to patients with cancer. In March, we launched MARGENZA for the treatment of HER2-positive metastatic breast cancer. More recently at ASCO, we presented encouraging preliminary clinical data from a Phase 1 study of MGC018, our anti-B7-H3 antibody drug conjugate. We plan to present updated clinical data from the MGC018 Phase 1 study, as well as our Module A of the MAHOGANY study of margetuximab in gastric cancer at ESMO in September. With that backdrop, let me use this time to walk you through the updates on our portfolio of clinical molecules. When we first discussed MGC018, our investigational antibody drug conjugate designed to deliver a DNA alkylating duocarmycin cytotoxic payload to cells that express B7-H3. MacroGenics presented an update of clinical data from the ongoing Phase 1 study of MGC018 in patients with advanced solid tumors at ASCO in June of this year and held a conference call and webcast with external guest presenters to discuss the results. As of the May 3, 2021 data cutoff, the study demonstrated anti-tumor activity in all three melanoma patients from the 4 mg/kg dose escalation cohort were enrolled subsequent to the 2020 ASCO poster presentation, including one with a confirmed partial response. As presented, preliminary results in the metastatic castration resistant prostate cancer cohort expansion demonstrated 11 of 22 or 50% of the patients had a PSA reduction of 50% or greater. Anti-tumor activity was observed in four of seven of these patients with measurable disease who had their first nine-week imaging results available, including one unconfirmed partial response. The adverse events continued to be manageable and include hematologic and skin toxicities as well as pleural and pericardial effusions. Overall, we’re encouraged by the…

Thank you. [Operator Instructions] And we have a question from the line of Yigal Nochomovitz with Citi. Your line is open.

Great. Hi, this is Carly on for Yigal. Thank you so much for taking our questions. On MGC018, can you comment at all on if the anti-tumor activity observed in four out of seven prostate cancer patients who had measurable disease is deepening over time and relatively, if the one unconfirmed PR has since been confirmed? And then similarly for the melanoma dose escalation patients, have you seen any evidence of anti-tumor activity deepening over time there? Thank you.

Carly, thanks for the question. This is Jim Karrels. I think Scott – we have a thunderstorm here and I think Scott’s line in the office dropped. So you’re going to have to repeat that question in just a moment. You’re on? Okay.

I have my cell phone. We had a thunderstorm here and it cutoff.

Carly, would you mind – Scott, did you hear the question? If not, maybe Carly, would you mind repeating it?

No.

Okay. Okay, sure. I can repeat it. Yes. I was just asking about sort of an update to what you had shown at ASCO, if you’ve seen any evidence of anti-tumor activity deepening over time in the four out of seven prostate cancer patients with measurable disease and whether that one unconfirmed PR has been confirmed. And if you had any similar comments on the melanoma dose escalation cohort in terms of deepening of tumor responses over time, that would be really helpful.

Yes. Thank you very much for the question. Obviously, we’re very excited about providing updates at the upcoming ESMO meeting. And so we don’t want to preview this ahead of that meeting. As we’ve said on the call today, we’re going to try to provide an update of the data as late as possible and still meet the obligations of the poster session. My expectation is that we will have at least three months of additional data so that we’ll include following the original 22 patients we discussed with regard to PSA 50% reduction, and then additional patients in the study. In that regard, we have recently completed the full enrollment of the castration resistant prostate cohort, which was consisted of 40 patients. In addition, we had completed enrollment of the 20 patients in the metastatic lung cancer cohort. So we’re very happy with the strong interest of investigators and patients to participate in this study. We should be able to provide obviously updates of the data with regard to both PSA, as well as the scans on the original four or actually the original 13 patients that we had identified that had at least one scan at a time at ASCO. Further follow ups on those patients plus additional patients that have come in over the last few months. While we will not have a full dataset on all 40 patients, my expectation is that we should have approximately 30 or so patients included in that dataset, of which we expect probably around half of those patients to be ones with measurable disease based on disease within this row, lymph nodes. With regard to the melanoma patients, as you recall in the 4 mg/kg cohort, we had three patients with a significant reduction in tumor size. We noted on the call that one of those patients had a partial response, which was confirmed. I’m pleased to say that the patient continues as of last week as I know of the last cuts of data to continue on the study and continued to do well. So, well, again, we’re very encouraged by that. We should also note that we have enrolled some patients in the new identified melanoma cohort and hope to continue progress to the planned 20 patients over the course of this year and maybe into early next year.

Thank you. Our next question is from Jonathan Chang with SVB Leerink.

Hi, guys. Thanks for taking my questions. First question, it looks like there’ll be data from a competing B7-H3 ADC program coming up at ESMO. How are you thinking about the competitive landscape for 018? And what are the key things that you’ll be looking to learn from the competitor dataset?

Thank you, Jonathan. As you know, we are aware of competing data from Daiichi being presented at ESMO. Obviously, we’re very encouraged by the fact that they at least anecdotally reported that they’ve seen responses in a couple of tumor types to which we have yet to enroll in our study. That’s very encouraging that in terms of having an outside organization validate the target and the approach, obviously they’re using a different antibody drug conjugate going forward. Overall, we feel that it’s, again, always in the best interest of patients that have opportunities with different mechanisms of action and look forward to reviewing their data. But we’re very encouraged as I say, with the data we’ve seen to-date and we intend to continue to expand our plans for this program.

Got it. Thank you. And second question. What do you view as the appropriate efficacy benchmarks for 018 in non-small cell lung cancer?

In prostate, I assume. In lung and prostate, or just lung, Jonathan?

Yes, about lung.

For lung, okay. Well, the answer is it’s too early to deem what’s the appropriate response rate. I mean, the only thing that I can comment on from equivalent mechanisms of action at ASCO, as I am aware Trodelvy reported results in non-small cell lung cancer late-stage patients with response rates approximately 25%. But clearly, we would like to see the best response there. And given that this will be an early cutoff data, while present, we will continue to follow these patients through the course of the year. So it’s just too early to benchmark the responses at this time.

Understood. Thank you.

Our next question is from Jonathan Miller with Evercore ISI.

Hi guys. Thanks so much for taking my question. First, I guess the KOLs in your ASCO webinar talked about pleural effusion and hand and foot syndrome is potentially concerning for the 018 and prostate data. But it seems like you had a different take there. With a little more follow-up, how are those signals evolving and where are those KOLs? At the time, you also mentioned optionality on dosing and schedule. And I would love to check in on how those efforts at this point are evolving and how you balance the need to advance the molecule with the desire to fully explore the dosing space?

Jonathan, thank you very much for the question. As we have noted consistently, we have found the side effect profile, which as we stated today, including the skin toxicities, which include hand-foot syndrome and the pleural effusions as noted to be manageable. We don’t – aren’t deviating from that observation. Patients are continuing on studies even in many of these patients who have experienced these side effects. As we have pointed out, we have included in the study design, the ability to hold doses or reduce doses going forward as some of the side effects profiles emerge. As we have taken our strategy forward, we felt it was more important to get a larger patient base experience at the 3 mg/kg every three weeks, and then make the alterations during the study. To then do an evaluation when the 40 patients in the prostate study are completed, we will then be able to come up with a decision moving forward what is the appropriate dose based on both the safety profile and the efficacy we observed. As we have noted before, some of the things under consideration would be to increase or decrease the frequency of giving a drug. We feel that most of the side effects are an area under the curve associated effect. And so the longer exposure to the drug we think will be more beneficial to the patient. The other alternatives are low – we reduce doses going forward and some other alterations. We have not come up with the conclusion, but all I can say is, is that based on enrollment, the treatment paradigm right now I think things are going as planned.

Thanks so much. I guess the second question, the Incyte CRL obviously sits back that program and I recognize that they’re leading the development for retifanlimab, but does this impact your ability to use this molecule as a backbone for combos? Does it impact your – delay any of your combo plans or your expectations for milestones associated with that advance? And how relevant those are for your cash runway?

So with regard to the use of retifanlimab in any of our studies, has no effect at all in either ongoing studies or other studies we might want to use this, or in fact, any partnership that we developed in which we want to include retifanlimab as part of the opportunity to combine this with other party’s molecule. So all that is the same. With regard to the cash runway, again, we risk adjusted the opportunity for milestones from this payment. And as noted on today, there is no change in projected cash runway even with no anticipated milestones coming from an approval due to the CRL.

Okay. Thank you very much.

Our next question is from Tom Shrader with BTIG.

Hi, this is [indiscernible] on for Tom. Thanks for taking our questions, and thanks for the updates. My first question is for the Module A MAHOGANY study. Has the bar for a go and no-go decision changed for this study after the data released from the KEYNOTE-811 trial?

That’s a very good question. Thank you very much for asking us. As many of you know, Merck announced and the FDA approved on an accelerated basis in frontline gastric cancer, the use of Herceptin plus chemotherapy plus pembrolizumab in patients with newly diagnosed gastric or gastroesophageal cancer. In that study, there was a controlled study. They saw in the controlled population approximately 54% overall response rate; in the treated population with pembrolizumab, it was 71%. As noted historically, as we pointed out the baseline data prior to the study was about a 47% overall response rate based on the previous approval of chemotherapy and Herceptin in this indication. So what we have always indicated while not giving the specific number that we hope to exceed, it was greater than 50% based on conversations that we had with the FDA. I think the questions that we need to decide is if we do not achieve 71% of greater response, can this drug still be used in a chemo-free setting in this population; meaning somewhere between 50% and 71%. And that’s something we don’t have the data yet because the data will be analyzed in the coming by with results from central review of the study. If that does occur, we will certainly think about what’s the appropriate next steps are, and we will certainly seek advice from the FDA on what is the appropriate way to continue with the study to get it available for patients, but still yet to determined.

Got it. And for the Module B of MAHOGANY study, you were evaluating combinations with both PD-1 and PD-1 x LAG-3. Do you expect to screen patients for LAG-3 level based on the emerging data?

So at this point we are not – that would obviously be a huge impediment in getting enrollment of a trial of that size. As you know, from the RELATIVITY-047 study, there was no difference in terms of responsiveness of patients based on LAG-3. And so we still do believe that based on our own results, particularly in solid tumor populations, there is potentially a role for screening patients based on LAG-3. But at this point we have not changed plans going forward with regard to screening and we would then do this retrospectively and analyze based on clinical results as well as biomarker expression patterns.

Thank you. Our next question is from Stephen Willey with Stifel.

Yes, good afternoon. Thanks for taking the questions. Can you maybe just provide a little bit more granularity around when you completed enrollment into the prostate and lung expansion cohorts? And then I guess, how should we be thinking about any potential disclosure coming out of the triple-negative cohort? This is for MGD – MGC018. And just whether or not there’s an opportunity to maybe either sneak that into ESMO or maybe more likely into a San Antonio presentation.

Thanks, Steve, for the question. Both – as you recall quite vividly, the guidance has always been to have both cohorts enrolled by mid-year prostate and lung, and that was achieved and that was achieved quite recently. So while enrollment of prostate began late in last year, almost all the patients got enrolled since February on prostate and since March on lung. So as you can imagine some of these patients came in quite recently and therefore would not have data. So again, to reiterate my guidance to what I’ve said is it’s likely we should have for ESMO by then the next data cut 30 or so patients in prostate to be able to describe in some with regard to PSA, and some of the scans that will continue obviously as patients continue on treatment, and on lung we’re hoping to provide updates on about half of those patients. So by the end of the year, we certainly will have a lot more data on the full cohort of both those groups. With regard to triple-negative breast, we’re continuing to enroll as I’ve indicated that we will should complete in the second half of this year. But I can’t give you specific commitments of time of updates of that data.

Okay. That’s helpful. And maybe you can just speak a little bit with respect to where you are with MGD019 dose escalation. And I guess specifically – or not dose escalation, with dose expansion. And I guess, specifically within the prostate cohort, I think if I remember correctly, you had seen if there was a PR or CR within dose escalation and in prostate. And I’m just kind of wondering if that expansion data within prostate is going to serve as kind of the decision-making point for whether or not you pursue 018 combo with that asset rather than say something like retifanlimab.

Yes. Steve, thanks very much for both, the suggestions and the questions. With regard to the dose expansion, if you recall, we initially started with colorectal – in a stable colorectal and with lung. Particularly lung that proceeded slowly because of our interest in enrolling patients who are naive to anti-PD-1 therapies. So that has picked up lately mostly obviously in Europe from those patients. The new prostate and the new melanoma cohorts for 019 were only recently added. And while we have had some patients enrolled, there are very few at this point. With regard to future combinations of checkpoints, as I indicated on our call at ASCO, we are very incredible at preclinical data that combining checkpoint does increase the anti-tumor effect 018. And so certainly 019 would be one of those under consideration to combine. And as you pointed out, especially with the fact that we source CR in the original dose escalation study of a patient with late-stage prostate cancer, we’re very encouraged as one of the – as that as one of the leading candidates.

Okay. And maybe just one quick logistical question for Jim. Are the outgoing payments to EVERSANA, are those realized in real time, i.e., the quarter in which they happen, or is there a look back or a true payment that’s made at some point towards the end of the year?

It’s not the end of the year, it’s on a quarterly basis.

Okay. Thank you for taking the questions.

Our next question is from Etzer Darout with Guggenheim Securities.

Great. Thanks for taking the question. Just wanted to get a sense from you, Scott, if you have any updates on the number of evaluable patients, we may see for lung cancer with 018. And then the follow-up, I guess, to earlier question just around sort of the benchmark question. When we think back to sort of the TROP2 ADC from Daiichi and the 21% to 25% response we saw in lung and monotherapy, I guess in sort of a second-line plus setting, is that kind of a fair benchmark, if you will, in terms of what we would consider as encouraging results? We know different mechanisms, but just wanted to kind of get a sense of your sense, I guess, of the landscape, given those datasets. Thanks.

Yes. Thanks, Etzer. So you may have missed my comments and some questions, both of these came up. What I said with regards to the lung we’ve recently completed the enrollment of the 20 lung patients. Obviously, some of them came in more recently, we’re going to do the data cut likely sometime in August. So given these scans are done every nine weeks, I think – well, I can’t give you the exact number of patients will report on the lung, I think it’ll be about 10 of the 20. Don’t hold me to the specific number, but we’ll obviously try to include as many as possible. With regard to the benchmark, with regard to reported at ASCO on Trodelvy of 25%, I commented before obviously higher is better, but I noticed the same observation. So certainly it would be nice to be in that 20% to 30% range and then potentially higher, but I have no sense right now exactly what it’s going to be. And certainly this will be just a cut off data and we’re going to be continuing to follow many of these patients through the rest of the year. So given that they presented the data of a completed study, we are going to be presenting data of an ongoing study.

Great. Thank you.

Our next question is from Boris Peaker with Cowen.

Hi, this is Cynthia on for Boris. Thinking through MGD024, how do you think about the development of that DART alongside flotetuzumab? And then just thinking, I guess pre-clinically, how do those two DART molecules stack up with regards to safety and anti-tumor activity?

So thank you very much. With regard to the questions on our CD123 x CD3 program, with regard 024, obviously we’re going to enter into this as a dose escalation study. And we expect that IND to be filed in the fourth quarter. As noted, clearly the initial patients that would be incorporated would be late-line patients who have progressed on other AML treatments initially. Whether we expand this into other CD123 bearing indications, we have not determined that. As of now we’ll focus initially on AML. Given that the way this drug is designed both in terms of a dramatically reduced cytokine release profile based on preclinical studies, as well as the S-T engineering, which allows us to give the drug intimately and still achieve a Cmax binding to the tumor. We are looking forward to developing this in much earlier lines of therapy than flotetuzumab. We have data both with flotetuzumab and MGD024 that we can combine this with HMA inhibitors, venetoclax and other molecules. So I think this would be a very nice addition potentially based on the preclinical data to add to the armamentarium for treating AML and other diseases that express CD123. With regard to the safety and anti-tumor responses that we’ve seen, in a xenograft model, while the actual dose required for MGD024 is higher, we achieved the maximum killing effect and achieved equivalent amounts of tumor control in xenograft model systems. And with regard to monkey studies with regard to the elimination of circulating CD123 monocytes and other granular sites that would express CD123, they were equivalent in terms of their efficiency.

Great. Thank you.

Our next question comes from Peter Lawson with Barclays.

Hey, thanks for taking my questions. Thanks for the updates. I may have missed this, but for 018, when would we see the melanoma data, Scott?

Yes. So, Peter, as you know, that was one of the recent cohorts we added after we saw those 4 mg/kg responding patients. So it’s very late added in and a lot of the sites have just gone up recently. And we’re very encouraged that we have had a number of patients enrolled. And I think this cohort will enroll quickly. But to be realistic about this, this is probably first half 2022 update. Obviously, we’ll try to get that data out as early as possible. But we are again, very encouraged to what we’ve seen to-date.

Got you. And then just, I guess, holistically, Scott, just around B7-H3 ADC. Are there particular indications where you think you get a single agent activity sufficient for pivotal trials?

Well, right now, there’s nothing to preclude us from believing that particularly in tumors where we’re seeing very effective responses in late-line patients, especially ones that have no alternative therapy, that single agents have would not be possible. It’s still too early to make that determination. We obviously want the updated data on prostate. We want the updated data on melanoma and the other cohorts. But at this point, our strategy is going to be with different intense move as fast as possible with the monotherapy, particularly towards registration if possible if the data pans out in these Phase 1/2 studies. But don’t stop looking at combinations, particularly with agents that we are developing ourselves to get even a better higher response. We think in some of those cases that may allow it to move further up quicker into earlier-line therapies, especially in tumors that, where for instance, checkpoint molecules are ineffective or checkpoint molecules and chemo have not been approved. So we’re analyzing this in terms of what’s the fastest way to get new classes of drugs of this type to market.

Got you. And just I was thinking of another question just around the PD-1 x LAG-3 update for this year, what are we going to – are we going to see data, or is it going to be kind of a strategic update of directions you compare with that?

We have a little more data from the varying studies. It doesn’t change what we have expressed at previous meetings. We are in discussions with various organizations and with key opinion leaders on what would be the fastest and best venue to develop this molecule towards registration. Ongoing discussions now is possible that we may provide data more likely to focus in on what’s the next steps with regard to particular tumor indications and how we tend to move this forward toward registration.

Okay. Perfect. Thank you so much.

Thank you.

Thank you. [Operator Instructions] We have a question from David Lebowitz with Morgan Stanley.

Well, thank you very much for taking my question. In the upcoming ESMO update, will we be able to see, I guess, a breakdown of safety and tolerability data in patients on original dosing versus those who’ve had dosing adjustments?

So, David, thank you very much for that question. We have not obviously put this poster together yet, and haven’t even planned it out specifically. We want to get the cut off the data. But we do believe it’s important to provide updates on the safety, how it’s formatted in that regard. We obviously want to get as much data out as possible. But so right now I can’t tell you how we’re going to put it out, but we certainly will add information regarding that.

Well, thanks for taking my question.

Thank you.

Thank you. And I’m not showing any further questions in the queue. I will pass it back to Scott for final remarks.

Yes. Thank you very much for participating today. Sorry for the interruption on the Q&A session due to the weather, but we look forward to a further update during the course of the year, and have a nice evening.

And with that, we conclude today’s program. Thank you for your participation and you may now disconnect.