MacroGenics, Inc.

Thank you. Good afternoon and welcome to Macrogenics conference call to discuss our third quarter 2020 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 factor section of our annual, quarterly, and current reports filed with the SEC. In addition, any forward-looking statements that represent our views only as of today, it 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, 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 quarter.

Thank you, Scott. This afternoon, Macrogenics reported financial results for the quarter ended September 30, 2020, which highlight our financial position as well as our recent progress. As described in our release this afternoon, Macrogenic's total revenue, consisting primarily of revenue from collaborative arrangements, was $18.2 million for the quarter ended September 30, 2020, compared to $18.7 million for the quarter ended September 30, 2019. Revenue recognized during the quarter ended September 30, 2020, included a $15 million milestone from Insight. Our research and development expenses were $44.7 million for the quarter ended September 30, 2020, compared to $44.9 million for the quarter ended September 30, 2019. General and administrative expenses were $9.7 million for the quarter ended September 30, 2020, compared to $11.8 million for the quarter ended September 30, 2019. This decrease is primarily due to a reduction in external expenses, including consulting costs. Macrogenic's net loss was $36 million for the quarter ended September 30, 2020, compared to a net loss of $44.6 million for the quarter ended September 30, 2019. Our cash, cash equivalents, and markable securities as of September 30, 2020 were $280.7 million compared to $215.8 million as of December 31, 2019. During the quarter ended September 30, 2020, we received $75.7 million in gross proceeds from the sale of approximately 2.55 million shares of our common stock pursuant to an at-the-market, or ATM, offering at an average sale price per share of $29.67. With the sale of these shares, we fully exhausted the dollar amount of shares that were available for sale under the ATM. As you may have seen, we filed a new one this afternoon in the amount of $100 million as a matter of financial housekeeping. We believe that it is prudent to have this financing vehicle in place for potential future use. Let me also point out that the $15 million milestone from Insight was received after September 30, 2020, and was therefore reflected on our balance sheet as a receivable. Finally, there is no adjustment necessary to our previously disclosed cash guidance. And to remind listeners, we anticipate that our cash, cash equivalents, and markable securities as of September 30, 2020, combined with anticipated and potential collaboration payments, should enable us to fund our operations into 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 continue to be excited about the momentum we have built to date in 2020 as well as the events we are anticipating during the remainder of the year and into 2021. We are particularly excited about the multiple registrational or potentially registration enabling studies currently underway that involve macrogenics O molecules or those we have partnered. First, we await the near-term PDUFA date decision by the U.S. FDA regarding margituximab in late-line HER2-positive metastatic breast cancer. Next, we announced earlier this year our ongoing registrational trial of flotituzumab in the treatment of primary induction failure refractory AML. Third, Prevention Bio recently completed the rolling submission of their BLA for teplizumab for the delay or prevention of clinical type 1 diabetes in at-risk individuals. You'll recall that we had earlier developed and sold teplizumab to them in 2018. If approved, we would receive a $60 million milestone as well as royalties on sales. Finally, INSIGHT has multiple ongoing potentially registration-enabling studies for retofanilamab, which we licensed to them in 2017. We are advancing our other internal and partner programs with a goal of evaluating additional patients across multiple indications in order to potentially define the next set of registrational studies. I'd like to use this time to walk you through the updates on our portfolio of eight clinical molecules. I will start with Plotituzumab, an investigational bispecific CD123 by CD3 DART molecule, and our most recent product candidate to enter a registration study. During the third quarter, two manuscripts were published in Blood and Blood Advances, both publications of the American Society of Hematology. The first reported on clinical results as of November 2019, while the most recent one reported on the role of Flotituzumab in the immunotherapy of TP53-positive acute myeloid leukemia. In addition, we are very excited that six Flotituzumab and AML abstracts, including two orals and four posters, were accepted for presentation at the upcoming ASH annual meeting. My understanding is that these abstracts will be released by ASH tomorrow morning. We look forward to presenting additional data on this molecule next month. I'll quickly remind listeners that Macrogenics continues to enroll a single arm registrational clinical study to evaluate flow-to-tube demand in up to 200 AML patients with primary induction failure or early relapse AML with complete remission and CR with partial hematological recovery as the primary endpoint. I'll next discuss MGC018, our investigational antibody drug conjugate designed to deliver a DNA-alkylating duochromycin cytotoxic payload to cells that express B7H3. Post-ASCO, we selected 3 milligrams per kilogram as the recommended dose for expansion. We recently commenced the enrollment of patients with metastatic castration-resistant prostate cancer, triple negative breast cancer, and non-small cell lung cancer in the dose expansion portion of the Phase I clinical study. The rationale for selecting metastatic castration-resistant prostate cancer patients is based on promising activity in dose escalation, which we previously presented at ASCO. Moreover, through our own IHC analysis of over 1,500 tumor tissue samples to date, we know that many solid tumors express B7H3 with several tumor types at exuberant levels. We selected triple negative breast cancer as a second dose expansion cohort based on its B7H3 expression coupled with unmet medical need. Finally, we selected non-small cell lung cancer not only due to its high degree of B7H3 expression, but also because of the results previously reported at SITC 2018 regarding the activity of inoblituzumab, our B7H3 monoclonal antibody, in combination with an anti-PD-1 in the non-small cell lung cancer setting. We are focused on execution of the MGC018 study and expect to provide an update on it next year. Next, I would like to turn to tebotelemab, our investigational bispecific PD-1 by LAD3 DART molecule, previously known as MGD013. Recall that we previously reported that LAG3 expression on immune effector cells was enhanced by margituximab, our investigational FC-engineered monoclonal antibody targeting HER2. Given the early efficacy signal and acceptable safety profile observed in an initial small expansion cohort of patients, We are evaluating the combination of tebotelemab and margituximab in three subgroups of patients with HER2-positive tumors, one with gastric or gastroesophageal junction cancer, another with breast cancer, as well as a basket of other HER2-positive cancer types with 30 patients initially targeted for each group. We believe that combining SC engineering and checkpoint blockade has the potential to engage both innate and adaptive immune responses against a broad range of tumors with varied tumor microenvironments. We plan to present the poster on the ongoing phase one dose expansion study of tebatellumab in combination with margituximab in a cohort of patients with advanced HER2 positive tumors at the upcoming Society for Immunotherapy of Cancer annual meeting. I believe that ASTRAX will be officially released by SITC next week. In addition, we will have a poster presentation at ASH next month regarding tebotelemab and DLBCL. Also, based on early association of biomarkers with clinical responsiveness to tebotelemab that we first reported at ASCO, we are completing an assessment of biomarkers that can be used to screen and select patients who would have a greater likelihood to respond to treatment including patients with DLBCL and solid tumors. We look forward to providing these updates. Speaking of tebotelemab, I'd like to tell you about a study combining this molecule with another of our FC-engineered antibodies. In the first quarter of 2021, we are planning to initiate a combination study of inoblutuzumab, which targets B7H3 in a chemo-free regimen in frontline squamous cell carcinoma of the head and neck with either tebatellumab for patients who are PD-L1 negative or with retifalumab in patients who are PD-L1 positive. Blockade of the PD-L1-PD-1 inhibitory axis with retifanilamide is ideally suited for tumors with an underlying inflammatory response, as indicated by the positive PD-L1 score at baseline. In contrast, PD-L1-negative tumors, or those tumors lacking a T-cell infiltrate, may benefit from an FC-engineered antibody like a novituzumab. Novituzumab has been shown to induce an inflammatory T cell response in tumors in a neoadjuvant clinical study of patients with newly diagnosed prostate cancer. It has also been shown to enhance expression of checkpoint molecules, including both PD-L1 and LAG-3, and therefore patients may benefit by the concomitant treatment with tebotelemab through the combinatorial blockade of the PD-1 and LAG-3 axes. Moving on to margituximab, the PDUFA target action date for our BLA in metastatic HER2-positive breast cancer is December 18, 2020. In early October, we had our late cycle meeting with the US FDA. Based on the current accrual rate of the overall survival events in the Phase III SOFIA study, MacroGenX now anticipates accrual of the 385th OS event, which triggers the final OS analysis to take place in the second half of 2021. FDA has stated that they intend to meet their PDUFA date obligation on the basis of the SOFIA study's primary PFS endpoint. With the PDUFA date right around the corner, we are planning for the commercialization of margituximab if it is approved. As we have previously discussed, we do not currently intend to develop an internal sales force. Instead, we are evaluating a number of arrangements with third parties, including providers of sales, marketing, distribution, and logistics services, as well as potential biopharmaceutical commercial partners who may assist us with the potential launch of margituximab. Beyond breast cancer, the Phase 2-3 mahogany study is evaluating margituximab and checkpoint blockade as a frontline treatment for advanced gastric and gastroesophageal junction cancer. Module A, the single arm part of the mahogany study of margituximab and retifanilamab, an investigational anti-PD-1 antibody, is enrolling and we expect to submit data on a subset of the initially targeted 40 patients for presentation at a scientific conference in the first half of 2021. Macrogenic's partner in greater China, Xylab, recently announced dosing of the first patient in that region for Module B, the randomized component of mahogany that will evaluate margituximab plus chemotherapy versus margituximab plus chemotherapy plus either retifanilamab or tibotelimab versus standard of care, which is trastuzumab plus chemotherapy. Let me next discuss MGD019, our investigational bispecific checkpoint DART molecule that targets PD-1 and CTLA-4. At the ESMO virtual congress in September, data from our phase one dose escalation study of MGD019 was reported via oral presentation. MGD019 was well tolerated in patients who received less than 10 mgs per kilogram. Of note, dose-dependent upregulation of the inducible co-stimulator or ICOS molecule was evident in treated patients, including those who responded to MGDO-19 therapy, as well as T-cell expansion. And based on activity that was reported, we are expanding the study initially in patients with microsatellite stable colorectal cancer and checkpoint naive non-small cell lung cancer at the recommended phase two dose of six milligrams per kilogram. Let me next turn to retifanilamab, previously known as MGA012 and INC MGA0012. the investigational anti-PD1 antibody that we licensed to Insight. Macrogenics and Insight have each established multiple development programs for this molecule, evaluated either as monotherapy or in combination with other agents. Insight is conducting clinical trials that are potentially registration-enabling for patients with metastatic non-small-cell lung cancer, squamous cells, carcinoma of the anal canal, MSI high endometrial cancer, and Merkel cell carcinoma, while Macrogenics is conducting the potentially registration-enabling study in HER2-positive gastric cancer, as I mentioned previously. At the ESMO virtual congress in September, data from INSIGHT's Merkel cell carcinoma and anal cancer monotherapy studies were presented. Initial safety and activity data appear to be comparable to that of approved anti-PD-1 monoclonal antibodies. During the third quarter, INSIGHT initiated the Phase III Podium 304 clinical trial, which is evaluating the efficacy and safety of retifanilamab with platinum-based chemotherapy in patients with metastatic squamous and non-squamous non-small cell lung cancer. This triggered our $15 million milestone payment to Macrogenics. We expect Insight to initiate Podium 303 in patients with anal cancer in the coming months. In October, we entered into a commercial supply agreement with Insight, as contemplated by our collaboration and license agreement, pursuant to which we are entitled to manufacture a portion of the global commercial supply needs for Retifanlimab. We plan to manufacture commercial retofanilamab at our 5 by 2,000 liter scale GMP facility in Rockville, Maryland. I will remind listeners that under our collaboration agreement with Insight, we are eligible to receive up to a total of $390 million in potential remaining development and regulatory milestones and up to $330 million in potential commercial milestones. If retifanilamab is approved and commercialized, macrogenics would be eligible to receive royalties tiered from 15% to 24% on future worldwide net sales of the molecule. And finally, we expect our second antibody drug conjugate, IMGC936, an ADC targeting ADAM9 that is being advanced under a co-development agreement with Immunogen to enter clinical testing in the near term. Under our 50-50 collaboration, Immunogen is leading clinical development and they are currently screening patients for the phase one dose escalation study in patients with select advanced solid tumors. As we hope you can see, we continue to build momentum and advance our pipeline of innovative product candidates. We would now be happy to open the call for questions. Operator, before you release the talk here for questions, I'd like to add that the seven abstracts accepted for ASH were prematurely released today, and as such, we released a press release earlier today noting the titles and times of the presentation at ASH. With that, Operator, let's open the call for questions.

Thank you. Ladies and gentlemen, as a reminder to ask the question, you will need to press star then one on your telephone. To withdraw your question, press the pound key. Again, that's star one to ask the question. Please stand by while we compile the Q&A roster. Our first question comes from the line of view. No trouble with the city group. Your line is open.

Great. Thank you very much for taking the questions. Congrats on the progress. It was interesting in comparing the Flutatuzumab ASH abstract that was just released versus the 2019 ASH slides. It looks like the incremental response rate was quite good, 7 out of 10. I just wondered if there was anything specific or different about those patients that led to the 70% incremental response rate. as compared with the initial 9 out of 28 response rate that we've seen in the 2019 data.

Thank you, Gal, for the question. So, you know, the presentation at last ASH was approximately 30 patients. What happened is that we treated a very large group of patients subsequent to the ASH meeting. And the only patients that were presented in the 38 that were in the abstract were those that were limited to fewer lines of therapy as we have outlined with the FCA in our plans for our registration study. So we had eliminated some of the patients or a significant number of those patients that we presented last year. So more than half the patients that you're going to see at the upcoming ASH meeting are newly treated patients that have been enrolled in this study under the little more restrictive criteria. But you're absolutely right. We are seeing improved response rates even compared to the data from last year.

Okay, great. And then I was just wondering on MGD019, You know, you've announced plans for the expansion cohorts in MSS, CRC, and non-small cell lung cancer, but you did have a complete response, as I understand it, in a metastatic castrate-resistant prostate cancer patient. Any particular reason you've chosen not to do an expansion cohort in MCRPC? Okay.

Excellent question. Obviously, we're very excited about the activity of this molecule. We had to make some decisions in terms of priority, and given the need for treating patients with MS-stable colorectal cancer and seeing both patients that had objective responses as well as tumors that shrunk, We thought it would be worthwhile to expand that study to see how profound that signal was in colorectal cancer. For our look at the non-small cell lung cancer, clearly there has been a lot of work on ipinivo combinations, and we therefore want to establish how MGD019 was performing compared to the large database that's already available for ipinivo. But we have not lost sight of the value of using MGD019 in castration-resistant prostate cancer. As you recall, there has been activity that's been tested for ipinivo combinations in that indication, and while Bristol did not succeed in that trial, there was some activity in that combination. Given that, we also have explored the use of inoblituzumab, our other B7H3 molecule, targeting prostate cancer in collaboration with the group at Johns Hopkins in an IST, and what we saw as patients with single-agent activity in this, we are considering moving forward with MGD-019, possibly even in combination with inoblituzumab, but right now that's on the drawing board, and nothing has been definitely decided yet.

Thank you. Our next question comes from the line of Evan Sigelman with Credit Suisse. Your line is open.

Thank you. Thanks, operator. Hey, Scott, thank you so much for taking my question. Really congrats on the progress this year. So I know you had started alluding to some plans for commercializing margituximab. You had mentioned either kind of doing it, I don't want to say in-house, but kind of getting a contract sales organization or partnering it out. Do you want to see the data from mahogany module A before you make that decision? I'm just trying to get a sense as to when we could potentially start to see commercial sales of margituximab. And any other thoughts around how you would position the asset in the breast cancer space? Thank you.

Yes, Evan, thanks so much for your comments and your question. So we, as you point out and as we stated today, we are exploring different avenues for commercialization, both looking at potential contracting relations so that we'd have drug available if the FDA approves it by the PDUFA date in the early part of next year. And we're also in discussions with certain companies who might also serve to commercialize this drug for us in the U.S. We expect that again, if it's approved by the end of the year, we should be in a position to be making an announcement about our plans for commercialization sometime around December or early next year. With regard to the decision around Module A, that is totally independent. Clearly, the opportunity to expand into a gastric setting in the front line would be great, but the data still has to mature. We're still enrolling in that part of the study. With regard to positioning this asset for other breast cancer indications, There is an IST that has been initiated in patients with newly diagnosed breast cancer, testing it compared to standard of care in a neoadjuvant setting. And as we pointed out, the activity we're seeing in late line HER2 positive tumors in combination with TIBO, which include breast cancer patients, we're continuing to expand that cohort. And hopefully that may, if successful, provide an avenue to further develop margituximab in a chemo-free regimen. So we're very excited about the prospects, obviously, and wait to hear from the FDA by the PDUFA date.

And just one follow-up on MGC018. So I know we had some really interesting data at ASCO, and you plan to provide a data update in the first half of 2021. I guess Any thoughts as to what tumor types you want to pursue this in, or is this more of a tumor agnostic setting, you know, for a potential pivotal trial, assuming that the Phase I data update is positive next year?

Well, on the NGC 018, as we've previously announced, We're right now screening patients now for expansion in the metastatic castration-resistant prostate cancer patients. We're hoping to enroll up to 40 patients to confirm the signal and extend it. We've also announced that we're enrolling two smaller cohorts, one in triple negative breast cancer and one in non-small cell lung cancer, and those two will begin screening patients very shortly with that. So those are the three initial indications we are pursuing, but that doesn't limit it just to those three. As you know, we have shown quite nicely that B7H3 is highly overexpressed in both common and solid tumors. And if, in fact, we are producing successful data in these indications, we clearly will look at additional indications, both as monotherapy, but of course also in combination with other drugs. And there's opportunities to expand that soon in combination therapy as we have gotten a lot of positive feedback of interest to look at different orthogonal ways of addressing tumor control.

Excellent. Thanks so much, Scott, for the color on both of those questions. I'm sure we'll speak soon. Thanks.

Thank you. Our next question comes from the line of Tom Schrader with BTIG. Your line is open.

Hi, this is Kaveri for Tom. Thanks for taking our question. For the Module B of mahogany study, you're evaluating combinations with both PD-1 and PD-1-LAG-3. Can you tell us how do they fit into the treatment landscape?

Well, you know, again, we're excited about this. As you noted, as we've noted, that enrollment has just started through our partners, iLab, and we will plan to begin enrolling in that portion of the study next year. The goal there was obviously to build on the FC optimization technology where, as we have noted, activation of both innate and specific immunity is achieved through that FC optimization. The question then becomes in patients that are, for instance, PD-L1 positive, it may be sufficient to treat patients only with an anti-PD-1 to get the enhanced therapeutic benefit, but in those patients who are PD-L1 negative, What we had previously observed, that FC optimization can also enhance other checkpoint molecules like LAG3. So using a molecule like tebotelemab, the PD-1-LAG3 bispecific in combination, could give a further improvement of responses. And so that was the rationale to design that molecule going forward. Having said that, I would put my bets on probably the combo with a tebotelumab, but, you know, we don't have the data yet. We'll have to see as it comes along.

That's useful. And do you expect to screen patients for lag-free levels based on the emerging data?

So that's an excellent question. With regard to Module B, there's no plans to screen those patients. Clearly, we had the opportunity to retrospectively analyze that in the context of the gastric study. What we are doing, and again, wait for the presentation at SITC on the combination of MARCH and TiVo in the late HER2 positive populations, As well as the data we've already presented with regard to the association of LAG3 expression and responsiveness in our monotherapy cohorts, we are planning by the end of the year or early next year to be in a position to give a little bit more disclosure on our plans for biomarker screening. And at this point, we think LAG3 expression, either through IHC or through transcript levels, could be one very valuable biomarker, but there may be others that we might add to this as part of a screening procedure for enriching for populations that should respond or hopefully would respond to Teva-Telemab.

That makes sense. And does a cohort combining PD-1-CPLA-4 make sense before starting a large cohort?

So the PD-1-CPLA-4, can you amplify what specific indications are you talking about? Hello?

Operator, can you bring it back?

She's out of the queue. If she can press star 1 again.

You'll have to come back and give me a little more details of what you're looking for there, and I'll be happy to answer you.

Thank you. Our next question comes from the line of Jonathan Miller with Evercore.

Hey, guys. Thanks so much for taking my question, and congrats on all the progress. One thing I noticed, it seems like there was a meaningful rave through the ATM facility, but you didn't give an update to guidance. So was that amount of cash that you were getting contemplated in your previous guidance, or are you spending against it? And if so, what are you adding that's new that you weren't thinking about before? Secondly, I wanted to ask about the PD-1 LAG-3 plus MARGE combo expansion in gastric that you're adding to that phase one that you discussed in the 01, I'd say the 013 section of your talk. Is that phase one expansion cohort potentially going to be available prior to mahogany part B data? And if so, does that inform your plans for HER2 plus the bispecific combos in the controlled trial? And then thirdly, I just wanted to congratulate you on using the word exuberance to describe expression levels of B7H3 and multiple supertests.

Well, thank you very much, John, for those comments, including the use of the word exuberance. Let me go, I'll go back to the second question and then I or Jim can comment on the ATM. With regard to the PD-Lag3 in combination with MARG in late line patients, so these are progressed most likely on HER2 and other therapies. We are not waiting for that expansion cohort, which we have characterized to enroll up to 30 patients there. We obviously had several patients, as you saw in our earlier presentation, that responded to that. But given that we're looking at Module B in a front-line setting, we see that as two independent pathways. And clearly with Module B, as you know, we're adding chemotherapy there. Here we're looking in the late-line setting in the absence of chemotherapy. So two completely different plans with regard to the use of tabetalumab in that. With regard to the ATM, just a comment on that was, this is obviously gives opportunities to extend our runway into 2023, but the use of proceeds that have not been assigned to any particular program. But Jim, you want to make additional comments?

Yeah, really quickly, Jonathan. The ATM obviously extended our runway a bit, you know, further into 2023. At this point, we're not providing the granularity with regard to, you know, exactly how far along it takes us. Recall that we do stand to potentially receive up to, I guess, what remains 390 million of milestones from InSight, as well as Scott mentioned, the $60 million from Prevention Bio related to the BLA should it be approved from the Teplizumab program. And so all that together, you know, the runway does take us out a little bit further, but at this point, we're not really going to, you know, be precise about how far into 23 it takes us.

Okay, that makes sense. Thanks a lot. I guess the one follow-up I have then is in discussing your CPI-naive NSL, the non-small cell cohort for 019. I assume, given that you want to directly compare or at least do cross-trial comparison to the ipinevo combos, that you're primarily interested in first line. But can you comment on, you know, exactly what sorts of patients you're going to get and if the possibility exists for you to get later line of therapy patients who are still somehow checkpoint naive into that expansion cohort and how would you think about making that comparison in that case?

Yeah, that's a good question, John, and obviously we haven't started rolling that. Clearly, we're planning to initiate most of the recruitment of this outside the U.S. where ipinivo combinations have not been approved in the frontline setting. So, again, it's possible that we may include post-first-line patients that have been naïve to anti-PD-1 or ipi. But the majority, we hope, will be frontline patients.

Great. Thank you very much. Okay.

Thank you. We will now go back to the line of Kavir. Your line is open.

Hi. again for Tom. Just rephrasing my last question here, are there any hints in the literature or that you have uncovered as to the potential different places to use PD-1-Lact-3 versus PD-1-CTLA-4?

Oh, okay, so now that I understand. Thank you very much for that question. You know, clearly we're starting to sort that out, that mechanistically we may be talking about different T cell populations that may be addressed. As you know, the activation of T cells or inhibition induced through CTLA-4 occurs in different compartments than, say, for instance, LAG-3. Remember, as we've described, the design of these molecules were for varying reasons. In particular, for the PD-1 CTLA-4, this was designed to try to markedly reduce the toxicity profile that was observed at higher doses of ipilimumab. And by using a bispecific DART molecule, we seem to be targeting primarily to the co-expressing cells of PD-1 CTLA-4 that are found in the tumor microenvironment, as well as some that are PD-1 positive alone. So this, in fact, is a great value for the use of this in different tumor settings. With regard to the PD-1 LAG-3, it's still too early right now to define which specific indication, but given our original data that we demonstrated, we seem to be having responses, particularly in tumors like triple negative breast cancer, some ovarian cancer, lung cancer. Obviously, we're going to provide updates on DLBCL, so clearly there may be distinct populations and tumor types that are more preferable to be used with one versus the other.

That's helpful. Thank you, and congrats on the progress.

Thank you.

Thank you. Our next question comes from the line of Steve and Willie with Stiefel. Your line is open.

Yeah, thanks for taking the question. So just going back to flutuzumab for a moment, and I think Scott, you and I maybe talked about this before, but I guess just curious as to what proportion of the responding patients might be progressing to transplant? And I guess given that this is now a registrational trial, how does that potentially complicate the interpretation of duration of response just for the purposes of a potential accelerated approval?

So, you know, Steve, it's still too early to know exactly what percentage are going to go to transplant. Given that most of these patients are typically not candidates for transplant, obviously we have to understand, do they have... a potential match donor that can participate. Obviously, their underlying clinical condition, apart from the AML, their age and such, will factor into this. But we're hoping that over 50% of these patients ultimately may become candidates for transplant and go on to transplant. And right now, that seems to be the percentage right now that we are close to achieving.

Okay. And has there been any regulatory dialogue about just how that gets incorporated into the agency's consideration of duration of response, which they've traditionally held to be kind of a fairly important metric for the purposes of an accelerated approval?

Yes, we had that discussion with them on how to monitor those patients and include them in terms of survival and duration of response. There will be an analysis that's devoted to those patients who go on to transplant. It is actually part of our secondary endpoint for the study.

Understood. Got it. And then just a question on the MARGO trial. And I know this is investigator-sponsored, so I don't know to what extent you can provide some context around the trial design. But I was just kind of curious as to, you know, what's the endgame here, right? I mean, it's obviously overpowered in terms of it being kind of a proof-of-concept trial, but, you know, it's probably not sufficiently large enough for, you know, any kind of regulatory consideration. So I guess if you could just... Maybe walk us through, like, the rationale for having such a large kind of open label with an active comparator, single site, that many patients. That would be helpful.

Are we talking about the neoadjuvant study you're talking about?

Yeah, correct.

Yeah. It's not a single site. I think there will be, like, 19 sites. This was a consortium. So it's actually going to be conducted in probably some of the major breast cancer sites in the country. The goal here is actually we're looking at the epithelial population and we are again trying to take advantage of the the salutary effects of the engineering of the FC region here to get a better response. Obviously, it wasn't sized for a study for approval, but hopefully, we will see trends there with regard to benefit. So, you know, that's the intent at this point.

Okay.

Thank you. Our next question comes from the line of with Guggenheim Securities. Your line is open.

Great. Congrats on the progress and thanks for taking my question. So first question for me, maybe you can speak to the response one would expect in relapse refractory AML patients with TP53 mutations. Just to help maybe put the 60% response we're seeing with that population from prototuzumab into some sort of context? And then I have a second question.

Yeah, as you know, this is probably one of the most difficult mutated subsets in AML where the expectation of responsiveness is less than 10%. So, the fact that we were seeing such a high response rate in this subset, we're, you know, very excited about, you know, the initial data. Obviously, we're going to expand this with additional patients and monitor this, but, you know, the data speaks for itself.

Great. Thanks for that. And then, secondly, for MGD013, I'm not sure if you really can But, you know, we know in this, you know, complete response in DLBCL, you know, that was a CD9-experienced patient. But I wondered if you could elaborate at all on the other three patients that had partial responses and whether or not those were also sort of CAR T experience. Obviously, this is sort of from the abstracts released today. Okay.

Yeah, so I wouldn't wait for the CITSE. It's coming up very shortly. In fact, we'll probably have even additional, I mean, this is at ASH. It's coming up, obviously, in about a month. you know, the specifics around those patients will be described there. And I think by that time, we should be able to include some additional valuable patients in that cohort. In the abstract, we were only at the cut-off date, had ones that had already had scans. So I think there's been a couple additional patients that will be included in that analysis. So we'll wait for that. But we're very excited about the activity we're seeing here. And again, we'll be looking at various biomarkers associated with responsiveness as well.

Thank you. Our next question comes from the line of Jonathan Chang with SBB Liebering. Your line is open.

Hi, team. This is John Barrett on for Jonathan. A couple questions on Flutatuzumab. Regarding the registrational trial now running for that molecule, what would be the overall benchmark to define a positive trial for Flutatuzumab? Based on all the translational research you've presented, are there any predefined patient subgroups for this molecule which you could seek approval if you do not meet the activity threshold in the overall population?

Thanks for the question. We are clearly not giving the definitive benchmarks. What we have guided in the past is that patients that typically fail high-dose chemotherapy in the frontline setting On the first salvage attempt, we're talking about, at best, a low double digit responsiveness, and then on subsequent failures, salvage success goes down dramatically to low single digits to zero. And so as a result, we had conducted an analysis of the literature over the last 30 years to define what we expect to be the mean and median response rate in that population based on different treatment regimens and presented that analysis to the FDA to form the basis for the design of a registrational study. Obviously, for competitive reasons, we don't want to give you the specific details there, but you can gather what range we're talking about here and given the historical success we've had with this molecule so far in these defined populations. With regard to the biomarkers that you've alluded to, You know, we had toyed with the idea of working on predefined populations based on the biomarkers, but this is still in an evolution phase right now. We want to obviously expand this data. We will do a retrospective analysis of the current patients and the current studies. But the beauty of this is, and you'll hear much more data on this at the ASH meeting, so beyond the whole P53 population, which clearly we could go after, there are other biomarkers that we can combine with the gametopheron-associated genes that were defining the response of the population. But that will be a future study and a future design.

And one more just regarding execution for that trial. Do you have any expectations on how long this trial could enroll or take to come to the end of the trial.

Yeah, so, again, we've been guiding that our aspiration is to enroll this by the end of next year. But given the whole COVID-19 situation, you know, we were hoping that there wouldn't be a flare in Europe. As you've heard, a number of countries, again, are shutting down their hospitals. Right now, we're still on target in terms of our enrollment rates, but I can't predict what's going to happen over the next few months. So, again, the hope is that we'll have this enrolled by the end of next year.

Thank you.

Thank you. Our next question comes from the line of Boris Peeker. Let's call him. Your line is open.

Hey, this is Cynthia on for Boris. Thank you for taking our questions. For the, I guess, last of the ADAM-9 ADC, can you comment about what you and Immunogen are looking for regarding patient selection? Are you planning to screen for levels of ADAM-9 expression in And finally, based on the data you have so far, are there particular tumor types that look attractive for the Phase I dose escalation? Thanks.

So thanks very much for the question. And of course, we're very excited with our partner, Immunogen, on the initiation of this trial. I expect they will also provide some update on their conference call with regard to this study. We had defined several different tumor types for enrollment in the dose escalation part of this study, but did not define this based on ADAM9 levels or expression. Clearly, this is something we can analyze retrospectively. And with regard to expansions, that will obviously be dictated on both the responsiveness and safety we see in the dose escalation phase.

Thank you. Our next question comes from the line of Peter Lawson with Barclays. Your line is open.

Hey. Thanks, Scott. Thanks for taking the question. Congrats on the progress. Firstly, just on the next update for the prostate data, so MGC018, is that in the first half or is that for the other indications, triple negative breast cancer or lung that we see?

Thanks, Peter. As I've mentioned on previous calls, you know, our goal was to enroll this as quickly as possible. As I noted earlier, we're screening these patients now. You know, we like to get as many of the 40 patients in in the first half, by the first half of next year. So our plan is to try to provide an update no later by mid-year next year.

Perfect. Thank you. Do you get a better sense of how it's working so well in prostate? Is that something to do with the tumor microenvironment, or what are your thoughts there?

Peter, as I mentioned this before, we don't think there's anything specific to prostate from the data that we presented in the phase one study. We think that that was sort of a serendipitous that one of the first patients that seemed to respond was at the two micks per kick level. And as a result, the investigators decided to add many more of the prostate patients to that two or three mix per kid because they had nothing to treat these patients with and saw it as an opportunity. I should note, as I said before, of the two patients with non-small cell lung cancer, one at 0.5 and the other at 0.5, two mgs per kg, both those patients had tumor reductions, with the patient treated at two mgs per kg had a 24% reduction of a very large lung mass. We don't see that specifically the microenvironment at this point as dictating, but we are looking at various immune markers, and that could obviously contribute as well. One of the things that you, Remember, we make comment that there seems to be immune activation as a result of using this particular epitope with the ADC. And so, if you remember, in the original design of the Phase I study, we had an arm that we had included to add retifanilamab to MGC018. But given the exuberant responses we had seen, with the prostate patients, we put that combination study on hold, but we will clearly come back to doing some combinations with either retofenilamab or one of our other checkpoint molecules.

Thanks for the update around that. Adam 9, the ADC, when can we see the initial data for that?

Well, again, the study is just starting, and it will all be dictated by, obviously, the ability to recruit patients, which I don't think will be difficult. There will be several sites open that will be enrolling patients, but clearly we'll have to, you know, obviously monitor the safety as well. So it's just too early to give you any advice about timing.

Great. And then I assume for partnering a margin tax amount, that's kind of on hold with the kind of the Lumen commercialization.

That's not what I was saying. Maybe what I said was misinterpreted. We are in discussions both looking at various vendors that can help us get the drug available to patients to use it. Obviously, there are a lot of steps on bringing a drug to market, but we're also working with groups that can fully commercialize that, including typical biopharmaceutical companies. So, as I noted earlier in this call, If we have an approval by the PDUPA date, we should be in a position around that time or soon thereafter to discuss the commercialization of that molecule. So nothing is on hold. We're actually actively discussing prospects with various partners.

Great. Okay. Thank you so much. Thanks for taking the questions.

Thank you. As a reminder, ladies and gentlemen, that's star one if you'd like to ask a question. Our next question comes from the line of . Your line is open.

Thank you so much for taking the follow-up. Just two on margituximab and one on flotatuzumab. Obviously, you mentioned the PDUCA data of December 18th. You made no mention of an adcom. Is that the interpretation that the FDA is no longer interested in an advisory committee meeting for margituximab? And then secondly, the goalposts seem to shift a bit with respect to the timing of the 385th overall survival event. Originally, it was the end of this year, and now it's the second half of next year. I'm just wondering if there's anything to be made of that in terms of a read-through in terms of the greater overall survival benefit. And then on flovituzumab, Could you just explain the comment in the abstract with respect to the outpatient dosing, given the trending down of the CRS events during the first cycle? How is it possible to do the outpatient dosing in the context of a 28-day continuous infusion for the first cycle? Thank you.

Thank you, Gal, for the follow-up. So we had announced earlier this year that the FDA had told us that an outcome was not necessary, and there's been no change in that. And again, the interaction with the FDA has been very positive. Clearly, they make the final decision, but we're on track for them to meet their PDUFA requirements, so no outcome there. With regard to the 385th event, I think you've picked up on an important point, which is the deaths overall are slowing down. And given that, again, we saw some numerical reduction in the deaths from patients treated with MARG versus TRAS, Clearly, we hope that trend continues, and we see that potentially that's very favorable that these patients are living longer. So again, all positive from our interpretation so far of the data. With regard to Flotatuzumab and outpatient dosing, remember what we have said is that the initial eight days of treatment occurs in patients, because the patients have been tolerating the drug, there is lead in dosing during that first week. And as we've noted before, it is at that timeframe it would be the greatest time where you would see any cytokine release that needed to be addressed, although as we pointed out, we have dramatically reduced risk there associated with CRS. So as a result, these patients can have a pump and a pack, which they take with them potentially home, which then they would replace every several days with a new infusion. This is not any different than is used in Blenitubumab.

Okay, got it. Thank you so much.

Thank you. I'm showing no further questions in the queue. I would now like to turn the call back over to Dr. Scott Kenick for closing remarks.

Thank you, Operator, and thanks, everybody, for participating in our call today, and we look forward to speak to you about updates at a future call. Have a nice evening.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.