Macrogenics Inc Q4 FY2021 Earnings Call

Good afternoon. We will begin the MacroGenics’ 2021 Fourth 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 fourth quarter and full-year 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 announcement, 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 would like to turn the call over to Dr. Scott Canning, President and Chief Executive Officer of MacroGenics.

Thank you, Chris. I would 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 to Jim Karrels, our Chief Financial Officer, who will review our financial results.

Thank you, Scott. This afternoon, MacroGenics reported financial results for the year ended December 31, 2021, which highlight our financial position as well as our recent progress. As described in our press release this afternoon, MacroGenics’ total revenue, consisting primarily of revenue from collaborative agreements, was $77.4 million for the year ended December 31, 2021, compared to total revenue of $104.9 million for the year ended December 31, 2020. Revenue for the year ended December 31, 2021, included $12.3 million net sales of MARGENZA, which was launched in March. Our research and development expenses were $214.6 million for the year ended December 31, 2021, compared to $193.2 million for the year ended December 31, 2020. The increase was primarily related to increased clinical trial and development costs related to MGC018, as well as other preclinical molecules and increased clinical expenses related to enoblituzumab and lorigerlimab. These increases were partially offset by decreased development and manufacturing costs related to retifanlimab. Selling, general, and administrative expenses were $63 million for the year ended December 31, 2021, compared to $42.7 million for the year ended December 31, 2020. This increase was primarily related to the MARGENZA launch, as well as labor-related costs and legal expenses. Our net loss was $202.1 million for the year ended December 31, 2021, compared to a net loss of $129.7 million for the year ended December 31, 2020. Our cash, cash equivalents, and marketable securities balance as of December 31, 2021, was $243.6 million, compared to $272.5 million as of December 31, 2020. Finally, in terms of our cash runway, we anticipate that our cash, cash equivalents and marketable securities as of December 31, 2021, in addition to anticipated and potential collaboration payments, should enable us to fund operations through 2023. Our guidance does not reflect expenditures related to the potential late-stage development of MGC018 from prostate cancer or further expansion of studies currently ongoing. Now I will turn the call back to Scott.

Thank you, Jim. I’m encouraged by the progress made during the fourth quarter and our development plans for our B7-H3-directed programs in 2022. Since our presentation at the European Society of Medical Oncology or ESMO meeting in September, in which we showed promising data for our lead molecule MGC018, we are prioritizing the advancement of MGC018 and enoblituzumab, our two programs targeting B7-H3, and are taking additional steps to operationalize all aspects of these programs. This included planning for the advancement towards the registration-directed study of MGC018 in metastatic prostate cancer later this year. Outside of these product candidates, we are moving closer to dosing the first patient with MGD024, a next-generation CD123 by CD3 DART molecule for patients with CD123 positive hematologic malignancies, and working with investigators on the next steps in the development of tebotelimab or PD-1 by LAG-3 bispecific DART molecules. Beyond these programs, we have significant ongoing activities to fuel our pipeline of investigational product candidates for the potential treatment of cancer. With that backdrop, let me use this time to walk you through updates on a portfolio of investigational clinical molecules. Starting with molecules targeting B7-H3, a member of the B7 family of molecules involved in immune regulation. We are developing two molecules that target B7-H3 through complementary mechanisms of action that take advantage of this antigen's broad expression across multiple solid tumor types. MGC018 is our investigational antibody-drug conjugate designed to deliver alkylating duocarmycin cytotoxic payload to consumers expressing B7-H3. Since September, we presented an encouraging update of critical data from our ongoing study of MGC018 in patients with advanced solid tumors. We are currently developing plans for a registration-directed study of MGC018 in metastatic castration-resistant prostate cancer and plan to meet with the FDA later this quarter to discuss these plans. Based on our analysis of phase 1/2 study data to date, we intend to modify the dose and administration of MGC018, potentially including a slightly reduced dose and increased intervals between doses, which we believe will help to achieve the maximum therapeutic effect while aiming to reduce potential side effects. In parallel, we are advancing various operational aspects of the program. In addition to these next steps for MGC018, our phase 1/2 dose expansion study is fully enrolled for patients with metastatic castration-resistant prostate cancer, non-small cell lung cancer, melanoma, and triple-negative breast cancer, while enrollment continues in patients with squamous cell carcinoma of the head and neck. We expect to provide an update from this study during the second half of the year as the data mature. Beyond the ongoing monotherapy study, I’m pleased to share that we plan to initiate a combination study of MGC018 and lorigerlimab, formerly known as MGD019, in the coming weeks. The scientific rationale for undertaking this trial is supported by our preclinical data, which suggests that anti-tumor activity with MGC018 may be significantly enhanced by combination with an anti-PD-1 agent without meaningful overlapping toxicities. As further support for this combo study, we have seen some interesting initial data from our lorigerlimab dose escalation study. Relevant to the imminent combination study with MGC018, I will share an exciting anecdote on one of the prostate cancer patients from our dose escalation study of lorigerlimab. A patient with metastatic castration-resistant prostate cancer had been on six prior lines of systemic therapy, including chemotherapy, Abiraterone, enzalutamide, and Cabazitaxel. While patients with metastatic castration-resistant prostate cancer have not been particularly responsive to checkpoint inhibition, this individual achieved a confirmed complete response with complete resolution of this disease and normal PSA after treatment with lorigerlimab. We began treatment with lorigerlimab in December 2019 for 24 weeks, then every six weeks thereafter, for a total of just over one year as per protocol. We received his last dose of lorigerlimab in January 2021 and based on a recent update from the investigator remained in complete response with a normal PSA. Netscape has created a profile of this patient within a video they produced regarding bispecific checkpoint molecules. Stories like these illustrate why we as a company and the industry develop drugs. Although only a single patient experience, this patient’s story underscores part of our rationale for wanting to study the combination of lorigerlimab and MGC018 in various solid tumors, including prostate cancer. As I mentioned earlier, we expect to initiate a combination study of MGC018 and lorigerlimab in patients with solid tumors, including renal cell carcinoma, pancreatic cancer, ovarian cancer, urothelial carcinoma, metastatic castration-resistant prostate cancer, and melanoma in the coming weeks. Another of our investigational molecules exploiting the overexpression of B7-H3 in solid tumors is enoblituzumab, an Fc-engineered antibody created using the Fc-optimization platform. In March 2021, we initiated a combination study of enoblituzumab in a chemotherapy-free regimen in frontline squamous cell carcinoma of the head and neck with either tebotelimab for patients who are PD-L1 negative or with retifanlimab in patients who are PD-L1 positive. We expect to complete enrollment of the PD-L1 positive patient cohort during the first half of this year and provide an update on this cohort during the second half of the year. IMAB, a partner in Greater China, announced in December that the Center for Drug Evaluation of China’s National Medical Product Administration approved its IND submission for the initiation of a Phase 2 trial in China for enoblituzumab in combination with pembrolizumab in patients with solid tumors, including non-small cell lung cancer, urothelial carcinoma, and other selected cancers. I will next walk you through our PD-L1 based bispecific molecules designed to provide further differentiation from existing PD-L1-based options and to enable a broad set of combination options across our portfolio. Lorigerlimab is an investigational bispecific molecule designed to enable simultaneous and/or independent blockade of PD-L1 and CTLA-4. We are currently evaluating lorigerlimab in the Phase 1/2 dose expansion study in patients with microsatellite stable colorectal cancer, metastatic castration-resistant prostate cancer, melanoma, and checkpoint inhibitor-resistant non-small cell lung cancer at a dose of 60 mg per kg, and expect to provide an update on this study this year. Tebotelimab is our investigational bispecific PD-L1 by LAG-3 DART. Tebotelimab, which is being evaluated in a Phase 1/2 dose expansion study in several tumor types, is currently being studied in combination with enoblituzumab in squamous cell carcinoma of the head and neck. We are formulating plans for the potential future development of tebotelimab and expect to provide an update in the second half of 2022. MacroGenics’ partner in Greater China, Zai Lab, recently informed the company that it has decided to discontinue development of tebotelimab for indications it was enrolling in its territory and is evaluating future development plans in other indications. Next, let me discuss our efforts to advance treatment for patients with CD123 positive hematologic malignancies. We have prioritized the development of MGD024, our next-generation bispecific CD123 by CD3 DART molecule, which will replace our flotetuzumab development program. MGD024 incorporates the CD3 components designed to minimize cytokine-release syndrome while maintaining anti-tumor cytolytic activity and permitting intermittent dosing through a longer half-life. At the ASH meeting in December, we presented encouraging preclinical data demonstrating the enhancement of anti-tumor activity with MGD024 in combination with cytarabine and Venetoclax, two standard of care agents used to treat patients with AML. We announced in November the submission of the IND application for MGD024 and we expect to begin to enroll patients with relapsed or refractory hematologic malignancies in the phase 1 dose escalation study pending IND clearance by the FDA. In a single study evaluating flotetuzumab, our first-generation continuous infusion CD123 by CD3 DART molecule in AML patients who are refractory to induction therapy, the interim efficacy analysis threshold was met with manageable safety. Nonetheless, we recently made the decision to discontinue flotetuzumab to prioritize MGD024, which we believe may have a superior profile. Next, I will provide an update of product candidates being developed by our collaboration partners for which we retain certain economic rights. Our second investigational ADC, IMGC0936, which targets ADAM9, a cell surface protein over-expressed in several solid tumor types, is being advanced under a co-development agreement with ImmunoGen. Under our 50/50 collaborations, ImmunoGen is leading clinical development, and they have indicated that they anticipate disclosing initial data from a phase 1 study in multiple solid tumor types in 2022. Teplizumab is an anti-CD3 monoclonal antibody that was acquired from us by Provention Bio in 2018. Provention is developing teplizumab for the treatment of type 1 diabetes. In July 2021, the FDA issued a complete response letter for teplizumab BLA for the delay of clinical type 1 diabetes in average individuals. Earlier this week, Provention announced that they had resubmitted the BLA for teplizumab for the same indication. The BLA resubmissions followed Provention’s type B meeting with the FDA earlier this year. Lastly, I will provide an update on margetuximab. As a reminder, MARGENZA was launched in the U.S. in March 2021 in coordination with our commercial partner Eversana. MARGENZA is approved in combination with chemotherapy for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. We continue to believe patients may benefit from MARGENZA as another market in metastatic breast cancer therapy options. As reported, net sales were $12.3 million from our agenda in 2021. Given the competitive realities that have taken place in the HER2-positive breast cancer market, including multiple new approvals, we continue to have modest expectations for MARGENZA sales. In terms of Margetuximab's partner in Greater China, Zai Lab recently informed us that they have decided to discontinue enrollment in Module B of the MAHOGANY study based on their review of the clinical data and the changing treatment landscape. Recall in November 2021, we announced that decision to discontinue enrollment of Module A of the MAHOGANY study. With regard to Zai’s effort in breast cancer, they announced last month that the Chinese NMPA had accepted the NDA for Margetuximab in combination with chemotherapy for certain patients with breast cancer. Finally, we look forward to continuing to build momentum and advancing our pipeline of innovative product candidates and sharing our progress with you throughout 2022. We would now be happy to open the call for questions.

[Operator Instructions] Our first question comes from Jonathan Chang with SVB Leerink. Your line is open.

Hi guys, this is [indiscernible] on for Jonathan. Just wanted to follow-up on what you mentioned about MGC018 and the dosing strategy. Is there any color you could provide like are these lower doses or schedules already being evaluated or is that something that needs to be done and also has this factored into the regulatory strategy?

Thanks very much for the question. After we discussed the results of our data at ESMO and continued to follow the patients both in prostate cancer as well as the other indications, we did an evaluation of the response rate, side effect profile, and various pharmacokinetics, both looking at the area under the curve and Cmax associated with both responses as well as side effect profiles. From that, we derived a set of modifications we could implement with the dosing to maximize the therapeutic response and to minimize the side effect profile. In particular, we were interested in the hand and foot syndrome, where while we saw most of those patients had grade one or two side effects, we want to further mitigate those side effects given the bothersome nature of that issue. We have incorporated that into the plan going forward and have included that in a briefing document to the FDA. We will be discussing that plan moving forward at that meeting. After we have feedback, we will provide further insights on how the modification of the dose, both initial dose and increasing the time between doses might be implemented.

And then if I can just squeeze in one on the combination strategy with lorigerlimab. I guess what do you see as the benefits of that approach versus pursuing a combo with something like a retifanlimab or an approved checkpoint inhibitor?

First of all, thank you very much for that question. And as we did our analysis of combining MGC018 ADC with anti-PD-1 including enoblituzumab, or alternatively with a combination of our bispecific checkpoint molecules, we saw additional benefits in this particular case of adding the anti-PD-1 and CTLA-4 blockade. I should refresh your memory that Bristol Myers conducted a study looking at combinations with the Nivo in the setting of metastatic prostate cancer, and while they did not meet their objective endpoints for that study, there was some evidence that the combination of blockade of those two molecules could provide some benefits to patients with metastatic prostate cancer. Given that and as you know, we are currently doing a monotherapy study, an extensive study with lorigerlimab. Currently right now, as we discussed in this particular call, while very anecdotal, a single patient, as you recall, in our dose escalation study, we highlighted one of the patients who achieved complete response, and today providers follow up on that patient, where more than a year after stopping therapy is still in complete response with a normal PSA. So we think that mechanistically, there may be additional benefits beyond just an anti-PD-1 blocker to incorporate something that blocks the CTLA-4 axis as well.

Got it. Thank you so much.

Operator, could we have the next question please.

Our next question comes from Kaveri Pohlman with BTIG. Your line is open.

For enoblituzumab, does loss of CD16 expression play any role in efficacy, and do you have any thoughts on combining this with cytokines like IL-15 or maybe NK cell therapies?

Thank you very much for that question, Kaveri. So, clearly, enoblituzumab was designed to enhance binding to CD16 with a reduced binding to CD32B, like we have characterized for MARGENZA in our approved product. We have observed that the Fc modification we have incorporated in enoblituzumab by engaging CD16 on various immune cells drives upregulation of gamma interferon-associated genes. And there is a resulting upregulation of various cytokines beyond gamma interferon, as well as upregulation of various checkpoint molecules. With regard to the use of cytokines, that certainly could be explored. Also, there has been interest in combining enoblituzumab with various NK cells both in vivo and ex vivo, in other settings. We are having certain discussions with other parties regarding that possibility. So thank you very much for the question, Kaveri.

And regarding flotetuzumab, just curious to know your plans for DLBCL and in general, I just wanted to get your thoughts on the role of PD-L1 for this tumor type, because there aren’t a lot of checkpoint inhibitors in that space?

Thanks again for that question. As you know, we had very encouraging early data in late-stage patients with DLBCL, including those who had received various cell therapies. As a result, we are exploring the possibility of developing this in a DLBCL line of therapy as well as in solid tumors. As noted today, we should be able to provide updates on the next steps for new trials and potentially the immunologic and solid tumor indications in the second half of this year. Regarding PD-L1, you are absolutely correct that the blockers were not particularly effective in DLBCL treatments. I think there is an opportunity that by blocking multiple pathways involved in exhaustion of cells, one might achieve additional beneficial effects in various lymphomas. That is some of the rationale for why we are looking at this not only in DLBCL but also in combinations in solid tumors as well.

Appreciate it.

Our next question comes from Etzer Darout with BMO Capital Markets. Your line is open.

On the first one for me on the PD-L1 and CTLA-4 study with MGC018. Just wondered if you had an opportunity to look at that combination preclinically from a tolerability standpoint, and given sort of weak, I think the efficacy argument is clear. Just wanted to know if you had the chance to look at that from a tolerability standpoint. And then the second question unrelated but any meaningful impact of the flotetuzumab discontinuation on R&D spend in 2022?

Etzer, thanks so much for the questions. Certainly, as we consider the opportunities of combining a checkpoint with MGC018, one of the paramount considerations in our view was in addition to driving better efficacy, understanding the potential for a safety signal beyond what we have seen to date. From what we are observing, both in terms of our clinical experiences with PD-L1 and CTLA-4, lorigerlimab as monotherapy, as well as the monotherapy we are getting for MGC018, we see very modest opportunities for the additive or worsening of side effect profiles based on what we have seen thus far. However, one note I predict that one might appear in a clinical trial. In the way we are designing this trial, we have fixed the dose of lorigerlimab at the current 6 mg per kg, but starting at a lower dose of MGC018, and we will dose escalate in the three plus three design for that study to mitigate any unexpected side effect profiles for the drug. But again, right now, we are hoping that that goes smoothly and expect that to get started in the next few weeks. Regarding flotetuzumab, we do think that we will achieve some reduction in R&D spend. I can’t comment on the specifics right now. We are obviously just providing that information to investigators. So patients are still on the study right now, and we will continue with some spend in the near term, but we do expect some savings as a result of discontinuing.

Great. Thank you and thank you for the updates today.

Our next question comes from Yigal Nochomovitz with Citi. Your line is open.

Hi, this is Asha Babaric on for Yigal. Thanks for taking my questions. Can you comment on what drove the decision to discontinue flotetuzumab? Was there something in the interim analysis that might have contributed? Or was it just the emerging profile for MGD024?

Thank you very much for the question. As we pointed out, we believe, as you stated, the superior profile of MGD024 compared to flotetuzumab for the long-term treatment of patients with hematological malignancies contributed significantly to our decision. Certain comments in this regard include that the flotetuzumab molecule requires continuous infusion, which necessitates initial hospitalization of patients during the first two weeks before they can transition to an outpatient setting. With the design of an Fc incorporated molecule, plus the next-generation CD3 components in this molecule, we believe this drug can be administered more easily, intermittently, on an outpatient basis, but importantly, we expect to have a significant reduction in cytokine release syndrome as a result of treatments. Additionally, at the time we started this study a couple of years ago, the treatment regimens for AML were established with some new molecules, but that landscape is constantly changing. Since we are now conducting a single-arm study, there are additional risks given the changing landscape that would require significant investment to complete this current study. If we want proper European approval, that will certainly require a controlled study.

Okay, thank you. If I could sneak in one more? Could you provide any color on why you decided to discontinue development of flotetuzumab here? Is there any additional details you can share?

I can’t at this point, but let me emphasize. Just to continue on the current indications, they were temporary. So they are not enrolling patients in that. They are considering additional indications and may in the future as we decide to advance into additional studies to participate in such studies. It is still up to them. But as of now, it says they will not be enrolling any additional patients in the current indications that they have received.

Our next question comes from Charles Zhu with Guggenheim. Your line is open.

Hi everybody. Thanks for taking the question. I may have missed this one earlier, but it sounds like your melanoma, NSCLC cohorts are fully enrolled for MGC018. How are you evaluating go/no-go decisions for these indications that data matures, and what are some of the potential benchmarks you'll be using to make those decisions? Also, how should we think about timelines toward those kinds of points?

Sure. Thanks very much for the question. As you recall from previous calls, these cohorts beyond the prostate are much smaller. We have enrolled between 16 to 20 patients in the cohorts that have been fully enrolled, and we are continuing to follow these patients. As I have stated before, given the small size of these cohorts, it is still too early to make any decision moving forward. We want to assess the responsiveness as well as follow up on the standard of care in these late-line patients. We will also factor in the plans for prostate cancer; we want additional experience with the slightly modified dose with additional patients for the specific cohorts we want to further test. Given all this together, we like to see the data mature a little more so we can make decisions on which of these cohorts to prioritize, and we will be able to provide guidance in the second half of this year regarding that as well as once we get feedback from the FDA.

Got it, makes sense, and thanks for that color. If I need to squeeze in one more on MGC018, I want to gauge your reactions to data from diabetes DSM300 coming out of ASCO GU and how that weighs into your thinking for MGC018, especially regarding positioning?

Well thank you, Charles. We feel that we have the right profile to move forward with MGC018 and late-stage prostate cancer. It is clear that others are interested in that indication, as evidenced by Daiichi's plans to pursue that in this indication. The toxins that they have incorporated in their molecule are akin to our targets working through different mechanisms. I would say that I’m encouraged by the data because the data we have reported at ESMO were quite comparable to what they reported at the recent ASCO GU meeting. The PSA 50 reductions we reported seem to be better than what data they have reported to date. Overall, I would say we are seeing both companies generating very encouraging data in the treatment of prostate cancer, which provides further validation for targeting B7-H3 with this type of mechanism. I believe we are potentially in a better position now that we are going to start this combination study with our checkpoint molecules with our knowledge that Daiichi has a similar plan in place.

Sounds great. Thanks for taking the questions.

Our next question comes from Jon Miller with Evercore. Your line is open.

Hey guys, thanks for taking my question. I would like to start with maybe the ADAM9 which I know is being led by ImmunoGen. But could you give us some color on what to expect from the data release this year in terms of tumor types, dosing numbers, that sort of thing, and maybe your level of conviction in that program relative to your other internal early-stage candidates?

Thanks, Jon. Good to hear from you. With regard to ADAM9, ImmunoGen is running those clinical trials. They are still in dose finding, and they are continuing with some additional expansion which they have not selected specific indications for expansion yet. We expect that should occur in the near term, consistent with the guidance they have provided us. They do expect to have that dose and be able to announce plans for expansion into specific tumor types later this year. Regarding where this fits into our portfolio, we are very encouraged by the preclinical data until we see specific doses selected and further expansion, it is too early to comment on its overall prospects. Except for MGD024, we have a lot more data on many of our other programs and are obviously much more encouraged about the prospects for those in our portfolio going forward at this time.

And then maybe just to follow-up on some of the B7-H3 questions that have come up. Given that we know the dose is going to come down from 3 mg per kg already, how should we expect to interpret the expansion cohort data when that comes out?

In that regard, I will emphasize that the dose is more of a tweaking of our planned dosing right now with regard to slight reductions and the time interval. But remember, as I said, the way we evaluated this was actually taking real data from patients, understanding what dose modifications occurred in these patients to achieve responsiveness or side effect profiles. In fact, we do have the overall total dose that these patients received to make this decision. We would, however, obviously want additional confidence regarding the prospect of using this drug. But right now, I think this is as good as we can do to move forward in this study.

Got it. Thanks very much, guys.

Thanks, Jon.

Our next question comes from Stephen Willey with Stifel. Your line is open.

Thanks for taking the questions. Just to clarify, are you prospectively treating patients at this revised, lower, less frequent dose of MGC018 or have you just integrated this dosing regimen into existing patients that still remain on treatment?

Thanks, Steve. We have not started any additional expansions with this proposed modified dose. This will be part of our discussions with the FDA coming up this quarter. Our plan would be to incorporate that operation in the design of the registration-directed study if everything else follows through from our FDA discussion. We will also incorporate that dosing regimen in additional expansion cohorts for indications we want to pursue beyond prostate cancer.

So I guess you don’t feel the need to do any bridging work, and you’d be comfortable going right into a registrational design in the absence of clinical experience at this dose?

Well, rather than comment on that, let’s wait until we have the FDA guidance and feedback. We will come back to you regarding what we plan to do next for the various aspects of prostate and other indications. We would like to have that regulatory insight before making any definitive statements about the specific design of that prostate study.

Okay. And then, maybe just a question for Jim, but just on the cash runway guidance. I know that 018 is excluded from that, in terms of the pursuit of a later stage study. Is that just a function of needing that regulatory clarity or is there still some uncertainty regarding whether or not the tumor types are going to be prostate and/or how they can put that trial a little bit?

The intention is, thanks for your question. We do plan to move ahead. Obviously, we are waiting to have the dialogue with FDA this quarter. We have not completely priced out what the trial might look like. We would like to have a better sense of that before we know what is needed to make this happen. However, we do have adequate cash to launch a study. We just want to be in a position where we can fully fund the entire study. We have had a very active BD history at the company, bringing in north of $700 million since our IPO in 2013. We intend to continue advancing various BD dialogues with various parties forward. Where our stock is trading today, as the whole market is off, it is an option that we don't like to consider, but one that we would if necessary.

Understood. That is very helpful. Thanks for taking the questions.

Sure.

Our next question comes from Silvan Tuerkcan with JMP Securities. Your line is open.

Hello. Good afternoon. Thanks for taking my questions and congrats on all the progress. My question is, and I might have missed this, is the goal of the MGC018 dosing regimen modification to reduce the side effects? And if so, which ones specifically are you trying to ameliorate or are you trying to keep the dose in the patient over the course of treatment as high as possible?

Silvan, thank you for the question. I would say that we are trying to accomplish both: to mitigate some side effects while achieving the highest dose possible. As I pointed out today, the most problematic side effect based on patient feedback was the hand-foot syndrome, and we wish to decrease the incidence and severity of that. We feel that hemological side effects such as neutropenia were relatively manageable by holding the dose and using supplementary growth factors like GCSF. Additionally, increasing the time between doses should also provide some value there. Ultimately, as you pointed out in your second comment, by reducing side effects, we aim to treat patients for longer periods and offer greater benefits as a result.

Okay, thank you. And so at the upcoming update, will we get an idea of what the average dose was per patient rather than the label dose that you're administering?

I believe at future discussions, we will be able to provide some guidance regarding the fully administered dose to the patients, which we think would be most valuable for achieving the best effects. However, we should wait until after we have a discussion with the regulators.

Our next question comes from Peter Lawson with Barclays. Your line is open.

Hey, Scott, thanks for taking the questions. Just on the FDA meeting in Q1, will you communicate the outcome around the dosing to us and will the combination with your PD-L1 and CTLA-4 start on the basis of that discussion with the FDA or will that start sooner? Just kind of help us through the timing and communication in Q1?

Yes. Regarding the meeting, as we move into March, the quarter ends at the end of March. We will have the FDA meeting sometime within the next four weeks. The outcome of that meeting has no effect on the start of the combination study. In fact, patients are already in screening right now and it is likely that we will have the first patient dosed potentially even before that meeting. As for communication about that, obviously, we will need to see what the written comments come back, so I think the likelihood is we will communicate this sometime in the second quarter.

Great, thank you. And then regarding the data set dissemination, the second half is going to be with the new dosing. That is the idea versus existing patients?

No, I believe the point is that we wanted the data to continue to mature on these patients that are on the 3 mg per kg Q3 regimen. Whatever update we provide, irrespective of modifications, for particular indications, we plan to continue. We would then apply the new dosing, and that wouldn’t start until the second half of the year.

Our next question comes from David Dai with SMBC. Your line is open.

Thanks for taking my question. Just a couple of questions on MGC018. Regarding the dose expansion data in prostate cancer and second half of this year, could you just set the data expectations and what would be the clinical benchmark we are expecting? Also, on MGC018 and prostate cancer, could you share some of your thoughts on biomarker strategies to further identify responders in prostate cancer?

Thanks, David. Regarding dose expansion, as you know, these are very late-line castration-resistant prostate cancer patients. The patient line of therapy for the expansion cohorts was third and fourth-line therapy. Historically, these patients have had progression within several months depending on the study they were previously involved in. We are clearly looking at those markers for advancing beyond what historical data suggests, and we have reviewed our data with experts in the field. We feel that our profile, even with a limited 40 patients, could provide significant benefits to these patients moving forward. As I pointed out earlier, we are looking to enhance this effect by dosage modifications, and that will be part of our analysis. We will continue to look at different patient populations. We have not specifically identified any gene markers that would predict favorable outcome for MGC018, but we will continue to analyze that and also look at patients who have various disease types. Most nodes versus those with bone disease, at this point, while we have treated approximately 50 patients with this dose, this data is still limited. We have observed that high levels of B7-H3 expression do not seem to be predictive for those patients who would respond or not, and we have seen patients with low H scores that showed evidence of activity. So right now, for prostate cancer, that does not seem to be the predictable marker going forward.

There are no further questions. Let me turn the call back over to Dr. Scott Canning for closing remarks.

I want to thank everyone for participating in the call today. Obviously, we have a lot of exciting data that will be coming up during the course of the year and look forward to sharing with you at a future conference. Thank you.

This concludes the program. You may now disconnect.