MacroGenics' (MGNX) CEO Scott Koenig on Q1 2020 Results - Earnings Call Transcript

MacroGenics, Inc. (NASDAQ:MGNX) Q1 2020 Earnings Conference Call May 5, 2020 4:30 PM ET

Company Participants

Anna Krassowska - VP, IR and Corporate Communications

Scott Koenig - President and CEO

Jim Karrels - SVP, CFO and Secretary

Conference Call Participants

Christopher Marai - Nomura

Debjit Chattopadhyay - H.C. Wainwright

David Lebowitz - Morgan Stanley

Jonathan Miller - Evercore ISI

Stephen Willey - Stifel

Etzer Darout - Guggenheim

John Barrett - Leerink Partners

Tom Shrader - BTIG

Evan Seigerman - Credit Suisse

Operator

Good afternoon. We will begin the MacroGenics 2020 First 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 Anna Krassowska, Vice President, Investor Relations and Corporate Communications of MacroGenics.

Anna Krassowska

Thank you. Good afternoon and welcome to MacroGenics’ conference call to discuss our first quarter 2020 financial and operational results. For anyone who has not had a chance to review our 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’d like to turn the call over to Dr. Scott Koenig, President and Chief Executive Officer of MacroGenics. Scott?

Scott Koenig

Thank you, Anna. I’d like to welcome everyone participating via conference call and webcast today. Given the ongoing COVID-19 pandemic, it goes without saying that I hope all of you as well as your family members are safe. Thank you for joining us. This afternoon I will provide an update on our clinical programs and the data expected during the year.

But before I do so, let me first turn the call over to Jim Karrels, Senior Vice President and Chief Financial Officer who will review our financial results for the quarter.

Jim Karrels

Thank you, Scott. This afternoon, MacroGenics reported financial results for the quarter ended March 31, 2020, which highlight our financial position as well as our recent progress.

As described in our release, MacroGenics had research and development expenses of $48.9 million for the quarter ended March 31, 2020 compared to $47.1 million for the quarter ended March 31, 2019. This increase was primarily due to an increase in development and clinical trial costs for multiple programs.

We had general and administrative expenses of $10.2 million for the quarter ended March 31, 2020 compared to the same amount for the quarter ended March 31, 2019. We recorded total revenue consisting primarily revenue from collaborative agreements of $13.7 million for the quarter ended March 31, 2020 compared to $9.7 million for the quarter ended March 31, 2019. This increase was primarily due to revenue recognized for manufacturing services under the clinical supply agreements with Incyte and Zai Lab, as well as milestone payments under the Zai Lab agreement for clinical trial initiations in Greater China.

We recorded net loss of $44.7 million for the quarter ended March 31, 2020 compared to a net loss of $45 million for the quarter ended March 31, 2019. And finally, our cash, cash equivalents, and marketable securities as of March 31st, 2020 were $170.8 million compared to $215.8 million as of December 31st 2019.

We anticipate that our cash, cash equivalents, and marketable securities as of March 31, 2020, combined with anticipated and potential collaboration payments, should now enable us to fund our operations into 2022 assuming our programs and collaborations advances currently contemplated. We've previously guided into 2021 this extension was made possible through several factors including our program prioritization efforts.

And now I'll turn the call back to Scott.

Scott Koenig

Thank you, Jim. We are encouraged by the progress and clinical activity that we continue to observe across our broad portfolio of certain anti-body based product candidate and anticipate presenting clinical data from all these molecules this year.

While we expect some near-term impact on clinical trials site initiation and patient enrollment, due to the unprecedented challenges posed by the COVID-19 pandemic, we have not changed our guidelines for the timing of key anticipated 2020 clinical data readouts of regulatory events.

I will start with flotetuzumab, our investigational bispecific CD123 x CD3 DART molecule. During a plenary session at the Virtual AACR Annual Meeting held last week, Dr. Sergio Rutella present the translational data suggesting that TP53 mutated acute myeloid leukemia or AML was correlated with an immune infiltrated tumor microenvironment in the bone marrow, which as previously reported, predicts and was in fact, associated with response to flotetuzumab.

This new analysis stills our prior data by Dr. Rutella presented at ASH last year showing the same immune signature was associated with a lack of response to chemotherapy or the response to flotetuzumab immunotherapy and the ongoing Phase 1/2 dose expansion study.

Separately, we are scheduled to meet with the FDA in the coming weeks to gain feedback on our planned registration test in the U.S. for flotetuzumab for the treatment of patients with AML were refractory to induction treatment, defined as primary induction failure or PIF patients and patients who relapsed within six months of initial response.

We intend to share these plans with you before the end of the second quarter. Of the approximately 20,000 patients diagnosed with AML in the U.S. annually, at least 30% fail to achieve a complete response with intensive induction therapy. These AML patients have a poor prognosis with limited options to treat this particularly challenging disease. We expect to present updated data from the ongoing expansion study of flotetuzumab in this AML population in the second half of 2020.

Separately, we stopped enrollment in an ex-U.S. Phase 1/2 study combining flotetuzumab with retifanlimab, an anti-PD-1 molecule also known as MGA012 in patients with relapsed or refractory AML. This decision followed the successful completion of the first planned dose escalation cohort of 300 nanograms per kg per day flotetuzumab, plus three mgs per kg of retifanlimab, and with not any safety finding or lack of activity. We plan to resume the study at U.S. sites in the future.

I would like to turn to the clinical abstracts that have been selected for presentation at the upcoming ASCO Annual Meeting that will be held virtually at the end of May. The first is an oral presentation covering dose escalation and select expansion cohorts from the ongoing Phase 1 study of MGD013, our investigational bispecific PD-1 x LAG-3 DART molecule.

The overall safety profile of MGD013 as it relates to immune-mediated toxicity is generally consistent with anti-PD-1 molecules with respect to event type and frequency. We have not identified the maximum tolerated dose.

Tumor-specific expansion cohort have been treated at a flat dose of 600 milligrams once every two weeks. Among the valuable patients we are observing activity of MGD013 across expansion cohort in several tumor types, including after anti-PD-1 therapy, which warrants further investigation.

While expression of LAG-3 PD-1 were not criteria for study entering high lag three expression on archival biopsy tissue seems to associate with response to MGD013 monotherapy. We are also conducting further translational work into other potential correlative biomarkers.

The course we noted that margetuximab are investigational, Fc-engineered monoclonal antibody targeting HER2 enhances LAG-3 on effector cells. We initiated an expansion cohort recombination with MGD013. Most notably, and as you will hear more about at ASCO, in a cohort of over a dozen valuable patients with advanced HER2-positive tumors treated with a combination of MGD013 and margetuximab, we observe confirmed and unconfirmed objective responses in excess of 40%.

All responders remain on therapy. We are very encouraged by this observation that we believe represents synergistic activity of the two molecules based on our results in monotherapy studies.

For additional context, published data indicate that responses among HER2-positive breast cancer patients treated with trastuzumab plus anti-PD-1 or anti-PDL-1 antibodies are 0% among PDL-1 negative patients and 15% among PDL-1 positive patient.

Given the strong early efficacy signal and favorable safety profile, we expect to prioritize the combination of MGD013 and margetuximab for further development. We believe that the combination of Fc-engineering and dual checkpoint blockade engages both innate and adaptive immune responses against a broad range of tumors with very tumor micro environments.

Separately, Zai Lab, our regional partner in Greater China is continuing to explore MGD013 in combination with their pipeline assets, including niraparib, a PARP inhibitor and patients with advanced gastric cancer and brivanib, a dual tyrosine kinase inhibitor of the VEGF, FGF receptors in patients with hepatocellular carcinoma.

The second presentation of clinical results at ASCO will be a poster covering initial dose escalation data from the ongoing Phase 1 study of MGC018, our investigational anti-body drug conjugate, targeting B7-H3.

Dose escalation study is ongoing. Among enrolled patients, the safety profile, which includes hematologic and skin toxicity, as expected, has been manageable. In dose escalation, we have also observed early evidence of clinical activity, especially in patients with metastatic castration-resistant prostate cancer, or mCRPC, with reductions in PSA levels of 50% or more in five of seven patients treated including one with sustained regression of bone disease. Based on these encouraging observations, we are planning a dose expansion in patients with metastatic CRPC once the dose escalation is completed.

The third and final of our clinical presentations at ASCO will be a poster results stratified by chemotherapy in the Phase 3 SOFIA study of margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy in patients with HER2-positve metastatic breast cancer.

A note regarding the timing of the final analysis of overall survival in SOFIA. We continue to anticipate reporting final OS results in the second half of 2020 pending the accrual of death events needed per the protocol to conduct the analysis.

Separately, as a reminder, the FDA has indicated its plan to schedule an Oncologic Drug Advisory Committee or ODAC Meeting in the second half of 2020 and has a prescription drug user fee of PDAFU target action date for margetuximab for the treatment of HER2-positive metastatic breast cancer in December 2020.

While we are discussing margetuximab, beyond breast cancer, we are opening clinical sites globally to enroll patients in the Phase 2/3 MAHOGANY study, evaluating the combination of margetuximab and checkpoint blockade as a frontline treatment for advanced gastric and gastroesophageal junction cancer.

Initially, MAHOGANY is evaluating margetuximab plus retifanlimab, our investigational anti-PD-1 antibody licensed to Incyte in patients with HER2 IHC 3+ and PDL-1 positive disease. The single ARM part of the MAHOGANY study which we refer to as Module A is designed to support potential accelerated approval of margetuximab plus retifanlimab in the U.S. based on a primary efficacy endpoint of objective response rate.

I can comment on our initial observations. We have observed the objective responses in the first three to four valuable patients treated on the study with a schema-free regimen. These are very early observations but supporter optimism around possibilities for margetuximab in this indication.

As you all recall, we observe responses in approximately 50% of second line patients with HER2 IHC 3+ and PDL-1 positive disease in the study of margetuximab and enoblituzumab, we expect to report initial data from MAHOGANY Module A in the second half of 2020.

The second component MAHOGANY study, which we refer to as Module B, is designed as a randomized control trial to evaluate the combination of margetuximab with chemotherapy, retifanlimab or MDG013 compared to trastuzumab and chemotherapy in a broader population of patients with advanced HER2-positive gastric cancer. We expect to first initiate Module B in Greater China in collaboration with our regional partner, Zai Lab in the second half of 2020.

To briefly discuss retifanlimab, Incyte plans to present data in the second half of 2020 from their potentially registration enabling monotherapy study in patients with anal cancer, which is now fully enrolled. Two other monotherapy studies are retifanlimab are also ongoing in MSI high endometrial cancer and Merkel cell carcinoma and could potentially support registration.

In addition, we expect Incyte to initiate a Phase 3 study known as POD1UM-304 in patients with metastatic non-small cell lung cancer in 2020. In all, there are currently five registration directives clinical studies ongoing are planned in 2020 by either company across a broad range of tumor types.

Let me next turn to MGD019, an investigational bispecific PD-1 x CTLA-4 DART molecule. The dose escalation is ongoing in all cover population with advanced cancers. We have not restricted the study to tumor types that are known to respond to checkpoint inhibitors.

We are currently enrolling patients in additional dose escalation cohorts with no dose limiting toxicities observed. Of the 13 of valuable patients treated at doses of three milligrams per kilogram or greater, we have observed four patients across different tumor types with three confirmed and one unconfirmed objective response. We are encouraged by these admittedly very early data and plan to submit results from the dose escalation presentation at scientific conferences later this year.

Finally, let me discuss enoblituzumab, our investigational Fc-engineered, anti-B7-H3 monoclonal antibody. In consideration of the current global and domestic COVID-19 pandemic, the planned Phase 2 study initiation of enoblituzumab in combination with checkpoint blockade as chemotherapy-free treatment of patients with advanced head and neck cancer will be delayed.

We expect to provide an update on the timing for initiating the study in the second half of 2020. The delay to the study does not reflect the lack of enthusiasm for this molecule.

As you can see, despite the current global crisis, we continue to expect 2020 to be a data and catalyst-rich for MacroGenics.

We would now be happy to address any questions that callers may have. Operator?

Question-and-Answer Session

Operator

[Operator Instructions]

And our first question comes from the line of Christopher Marai with Nomura. Your line is open.

Christopher Marai

Hey, good afternoon, everybody. Thank you for the update. Scott, quite extensive. I guess maybe just to begin with MGC018, you'd highlight that -- highlighted that the hem in the skin tox was as expected and manageable, could you just elaborate is that tox caused by B7-H3 engagement or is that separate from your payload on the ATC? Thank you.

Scott Koenig

Thank you very much, Jackson [ph] for the question. Obviously, details will be presented at a poster session at ASCO. The expectations with regard to the hematological was related to the toxin and the skin observations were either due to the toxin or due to the targeting of B7-H3. Right now it's unclear. But as I noted, they are manageable toxicities.

Christopher Marai

Okay, great. And then with respect to SOFIA's final book, it sounds like that's going to hit before PDUFA decision. How should we think about sort of that FDA has expressed to you for -- our understanding is that they've expressed to you that an LS result is not necessary, in your view, how should we think about the potential for outcomes on the SOFIA's final result with respect to any approval decision?

Scott Koenig

Jackson, thanks for the question. Right now, we're continuing to monitor the number of events of death, as I've indicated, this is still anticipated in the second half of this year. It's very hard to predict with precision of when this will occur, my expectation, it will be later in this year, and obviously, there has to be some data cleaning. So, it may be very close, even to PDUFA date when that date would be ready to present. So at this point, our plan is to take the second interim analysis for OS and use that as the basis which has obviously been already provided to the FDA and the BLA filing for evaluation. If any changes occur, we will obviously update everyone at that appropriate time.

Christopher Marai

Great. And then just sticking with margetuximab at MAHOGANY progress looks really exciting, but your observed responses in three or four valuable patients. I was just wondering if you can comment what level of number durability we expect to see, in terms of these responses? How durable are they? How much time have you have you observed them for? And how much will be available at ASCO? And then two, I think previously, the you had discussed that this could be potentially registrational worthy the Module A, with a response rate and an endpoint in this patient population. So just maybe, if you could remind us of your plans with respect to that, and maybe what the hurdle might be in terms of, I suppose, adding more patients to the expansion part of that Module A? Thank you.

Scott Koenig

So, that's a couple of questions. So with regard to the length of duration of response, if it's still these patients are still on treatments. So it's still too early to predict, even on these fewer – few patients, what the target PFS or OS would be just to give you a little context. The median PFS for first line therapy for flotetuzumab is 6.7 months and the OS was 13.1 months. So our hope is that, this will far exceed that with regard to PFS and OS.

With regard to overall response rate, which is the target is endpoint for the single arm study. Just again to recall toggle was 47%. Our hope is that this will be a north of 50% and use that as a basis for decision. As we pointed out previously, we have said that, we should have a sufficient number of data from the initial patient to make a decision whether we are achieving the targeted range that would then encourage us to finish out completing enrollment. And we will plan to update everyone later this year, assuming if we continue to enroll with the rate we have been doing at this point.

Christopher Marai

Okay, great. Thank you very much. Congratulations.

Scott Koenig

Yes. Thanks very much. And sorry, I thought – the volume is very low. Are you there Chris?

Christopher Marai

It’s me. Yeah. You sitting down the questions were easier.

Scott Koenig

I am sorry. Thank you so much.

Operator

Thank you. And our next question comes from the Debjit Chattopadhyay with H.C. Wainwright. Your line is open.

Debjit Chattopadhyay

Hey, good afternoon. Lot of data drop here, so I probably have missed a few. So based on the activity with MGD013, do you expect to develop a companion diagnostic or the trend that you alluded to regarding correlation of responses, but LAG-3 expression is mostly a trend and you don't have anything concrete yet. And you know, because it’s a PD-1 LAG-3, you're getting a pretty holistic kind of response?

Scott Koenig

Rather than me commenting on that, why don't you stay and wait for the ASCO presentation. There may be merit of developing a diagnostic associated with this to select patients that would most benefit from this. But again, wait for the ASCO presentations to hear the details.

Debjit Chattopadhyay

Okay. Then, just a clarification here for the upcoming data with the MGD013, you mentioned responses in multiple different tumor types in the post PD-1 setting. So are these patients primary refractory patients or patients who progressed after an initial response?

Scott Koenig

You know, we had cohorts of approximately 16 in some of these expansion groups. And so there is a mixed histories on these patients. And I can't specify off the top of my head for the particular populations. We will show at the meeting, where they fall, but we can follow up with you afterwards.

Debjit Chattopadhyay

Great. And just one quick follow-up on 018. Did you reach the recommended Phase 2 dose and the 50% PSA reductions in five out of seven with bone regression? Is this at the RP2D or is the dose escalation still ongoing?

Scott Koenig

The dose escalation is still ongoing. These were actually at lower doses and on previous calls. I had indicated, we were very encouraged by the data we're seeing, even in this lower doses range. So we're actually moved the dose up. We're right now enrolling patients and what we believe would be the top cells to establish a maximum tolerated dose, whether we achieve that with its highest dose, we do not intend to go higher. And we will select based on the response rate and pharmacokinetics and obviously, the safety profile of the preferred dose going forward. But the fact that we're seeing a such a high response rate across multiple doses is obviously very exciting for us.

Debjit Chattopadhyay

Perfect. I will hop back in the queue. I have a few more. I'll come back later. Thank you.

Scott Koenig

Thank you.

Operator

Thank you. And our next question comes from David Lebowitz with Morgan Stanley. Your line is open.

David Lebowitz

Thank you very much for taking my question. When you meet with the –

Scott Koenig

David, David, we can’t hear you. Can you talk closer to the phone?

David Lebowitz

When you meet later with the FDA on flotetuzumab, what are the range of possible outcomes you think on the registration or path forward?

Scott Koenig

If I heard your question, when you were very soft - in on our end, is what is the outcome of our expected outcome with a meeting with the FDA later this month. As I previously indicated, we had met with the FDA last September to discuss the design of a registration study in the refractory population. They agreed that this was a population that was very suitable and addressable and necessary given the current state of affairs for this population. Obviously, we can't predict what an outcome of any meeting with the FDA is. But we're very highly encouraged based on the last meeting, we have with them. With some of the open questions, we were going to provide them which we have already done, some additional data on new patients that have been enrolled at the targeted doses, both with regard to safety and response rate.

And as I have previously indicated, they were very interested in the historical data, a patient with so called refractory disease, and their response rate, as reported in the published literature over the last 30 years. And we provided them with all that data. So our goal right now is mainly to – to come up with some final designs on this trial and some certain understanding of what a target successful outcome would be for this study. So right now, we're very optimistic, but until we have that meeting, we can't give you any more clarity about the outcomes.

David Lebowitz

That make sense. And I might have missed this when you mentioned on the call. But on the Phase 1/2 combination with formerly named MGA012 that was halted. What was the primary reason? Was it halted? Is this COVID-19 related or what?

Scott Koenig

So what happens is, is that enrollment slowed down, because this was an ex-U.S. study in three countries, including Spain, which basically all the sites shut down, Australia sites were shutting down, and Israel sites was shutting down. And basically, with very poor enrollment and incurring very significant costs, just to maintaining a CRL, we said, it doesn't make sense to continue paying these huge fees. And so we said, let the COVID-19 pandemic slow down, and we will resume the study in the U.S.

David Lebowitz

Make sense. Thanks for taking my question.

Scott Koenig

Thank you, David.

Operator

Thank you. And our next question comes from the line of [Indiscernible] with Citi. Your line is now open.

Unidentified Analyst

Hi, this is [Indiscernible]. Thanks very much for taking our questions. On SOPHIA for the potential ODAC meeting for margetuximab, what questions do you believe you need to be prepared to answer clearly in order to generate a successful outcome? I'm sure that as you're expecting ODAC meeting, you are actively preparing for that ahead of time. Just curious is there any thoughts there?

Scott Koenig

Yeah. I think probably the biggest questions that are looming and which has been publicly aired in many different settings is the value clinically of the molecule in the intensity population with regard to the PFS data that we presented. As you know, when we saw a hazard ratio and the intensity population of a reduction of 24% compared to the control population, but a very short actual value in terms of months with regard to the improvement in that market F allele population. I think the second question is related to the F allele population, which as you know was a targeted exploratory population that was predefined, but did not allocate any output in the analysis. And given that, which we have shown quite clearly, most of the therapeutic benefits is related to that F allele population which represents 85% of the overall population. How the FDA views that population and further includes there. I think those are probably the two major questions. Oh, looming

Unidentified Analyst

Great, thank you. That's very helpful. And then you mentioned in your prepared remarks that you were going to open an expansion cohort for of MGD013 and margetuximab. I wonder if you could give a bit more context for the study you quoted as a comp Herceptin combined with PD-1 therapy is that a 0% response rate for PDL-1 negative? What line of therapy was that study conducted in? And in the data that you're going to be presenting for MGD013 and margetuximab, I think you said 40% responders, how many of those are PDL-1 negative, just trying to get a clear picture of how those two studies compare?

Scott Koenig

I think it would be premature for me to state this at this call. So please attend or listen to the meeting at ASCO. We will have clarity about all those aspects with regard to line of therapy, specific tumors, the PDL-1 expression pattern, but it would be inappropriate for me to comment on this now before the ASCO presentation.

Unidentified Analyst

Okay. Got it. Understand and we'll certainly be tuning into that. If one more question for me, maybe a bit of a bigger picture question. We're going to see, obviously that a meaningful data set for MGD013 at ASCO, and you're still in dose escalation for MGDO19, but we should get initial data for them the second half. Given that these are both assets that are by specifics with a PD-1 arm, I guess, I'm just wondering how you're thinking that both of these assets are going to finish the treatment landscape together. Are there certain tumor types or even potentially drug combinations where you think each of these assets may be better suited?

Scott Koenig

I think what you will see which relates to both molecule is the value of this by specific and enhancing responses in populations with regard to both PD-1 -- PDL-1, expression and prior treatment with anti PD-1 PDL-1 therapies. What we envisioned for both these molecules is that they will be easily combinable with other assets. I wish showed you the illustration today of March plus 13. As you know, we are on the ongoing gastric study as well planned for March 13.But one of the big goals for the 2019 study was to achieve the synergy that one sees for combining an anti-PD-1 with anti-CCR4 without getting the toxicity that has been previously observed with if you need both combination. Just to correct a statement, we have completed the dose escalation part of 19. We will share that with you later this year. As I said, I'd have a follow up conference.

But what I have indicated previously, we are far above the dose that the typical in epi-evo combination as you know, epi has been used historically, mostly in the clinic originally at three minutes per kid, and currently in current studies that one day per kid, and we're far above that dose. And as indicated here, with a toxicity profile that is quite favorable with regard to observations with respect to typical anti PD-1 treatment associated effects. Just to give you a historical refreshment, when we did the monkey study with MGD019, we went up to doses of 100 Meg's per kid without associated significant toxicities. And remember, at much lower doses, if niebo caused those animals to die with very severe diarrhea and dehydration. So the enhanced ability to activate T cells without the associated toxicity is one of the things that will I think, be important for the value of this asset.

Unidentified Analyst

Okay, great. Thank you so much, and appreciate all the color there.

Operator

Thank you. And our next question comes from Peter Lawson. Your line is open.

Unidentified Analyst

Hi there. This is Mitch, on for Peter. Thank you for taking our questions. The first one is going into the December PDUFA can you get as an update on how you are prepared for potential launch of margetuximab?

Scott Koenig

So we've previously mentioned, earlier in the year, we have done our marketing assessments. One of the things obviously with monitoring is the watches of other drugs that have been recently approved in a third and late line therapies. So we are doing our homework for both on the marketing side and other aspects of the drug. We have engagement obviously before COVID-19 with our MSLs in the community, to educate them with regard to FC engineering. The value potentially of immune mediated effects that are associated with molecules like margetuximab. Our plan, as I said previously, is to open up discussions again with additional partners who can be in a position to help commercialize this molecule.

Unidentified Analyst

Thank you. And then just one more. Just wanted to get your thoughts on you are thinking about the release of data and kind of a social distancing world. Is this not a -- do you think about waiting for UN conferences, for better reception from the medical community, or that's something we didn't thought to?

Scott Koenig

So, again, if you saw today, we were very transparent with trying to provide as much data recognizing that there's been much -- there are a lot of challenges that occur currently and we expect will continue throughout the year for access. So our goal is to be as open with ongoing studies as we can. We're not planning to give patient by patient updates. But we will provide as much data as we can in sizable numbers, so that you can be aware. One of the things that we're very excited about, as I have said previously, also than our clinical molecules are active, and right now our goal in the course of this year next year is to have multiple registration studies ongoing and to build on the prospects of these molecules to get them to patients as quickly as possible.

Operator

Thank you. And our next question comes from Jon Miller. Your line is open.

Jonathan Miller

Hi, guys. Thanks for taking my question and congrats on all of the progress. I guess after the ACR presentation on flotetuzumab and the TP53 genotyping observations you made there. Are you still focused on the refractory population? Or is there a space for a genotype defined population? Is it is it better? Can you get a larger population by going for TP53 mutant patients as opposed to simply refractory population?

Scott Koenig

Great question, John. As has been pointed out, TP53 is about 10% overall, the population. As I pointed out today, there is a subset of refractory patients is probably the most refractory and given that we saw in our study so far, as reported about 40% response rate in this particular population, we're very excited that even in the most refractory population, we're seeing a good response. So, our goal is to actually treat the entire refractory population, which we think at the minimum is at least 30% and could be as much as 50% of the overall AML population, so that, in fact, we will not select based on genotype going into the study.

Jonathan Miller

Absolutely understood. I guess, another follow up then for your cash runway, which now reaches into 22. Could you provide any more color on what had to get prioritized out in order to extend the runway?

Scott Koenig

Sure. So, I think, we tried to give you a lot of detail here about obviously, specific programs here. And I think that the ability to decide at various trigger points, when to advance a program. One of the points we have made previously and as part of our analysis, historically, we would typically look at four or five or six different tumor types for a given indication. As I pointed out today, for instance, for NGC team, we've got to focus in initially on the prostate population, with then the ability to expand further. So, again, by narrowing down many of our programs to one or two indications, we were able to actually project considerable savings going forward. That's in part on the way we were getting to 2022. But there are other things that contributed to that analysis.

Jonathan Miller

That makes perfect sense. And I guess when -- more last one, then I noticed that unlike many of your peers, and perhaps admirably you have been pretty, you've neglected to do any work on COVID yourself, you left that to others. What's been driving your decision making there? And do you think that your technology could be useful in the ongoing pandemic?

Scott Koenig

That was a very difficult decision for us. Obviously, we have expertise. Historically, if you go back into the history of the company, we had worked on many different infectious diseases. As you know, we have an ongoing HIV trial with our dark eyes Pacific. So it was it was quite easy for us to jump into the development side of things. But given with such a broad, cancer focused program, we didn't want to remove all the infrastructure and obviously the costs that we've now allocated to the seven clinical and multiple preclinical programs to then move it into the COVID-19 initiative, particularly for treat -- towards development of antibodies or by specific molecules, particularly given that we saw that there was an immediate response for very large pharmaceutical companies who had a lot more assets than we did.

However, we have reached out to academic investigators who we've worked with in the past. And I've indicated to them if they have very unusual molecules that could actually contribute because of our infrastructure with regard to development and manufacturing. We could provide some help down the road, but right now we're prioritizing moving forward with our cancer molecules.

Jonathan Miller

Got it. Thank you very much.

Operator

Thank you. And our next question comes from the line Stephen Willey with Stifel. Your line is open.

Stephen Willey

Yeah. Good afternoon. Thanks for taking the questions. I guess Scott, maybe just kind of given some of the enthusiasm embedded within your commentary around margin, MGD013; just curious if that at all makes you rethink the design of module B. I guess specifically, just given that you're looking at the, the inside PD-1 there. And the BI specific and obviously, you're, I guess favorably leveraged from an economic perspective to the BI specific here, so, just curious as to what your thoughts there. And could you also maybe just talk a little bit about LAG-3 expression within gastric cancer?

Scott Koenig

Yeah, so, with regard to the design of module B, remember the complexity of mahogany. The single arm study was intended -- a single arm study intended for subpopulation for accelerated approval and with our agreement with the FDA, part of the design of the module B was going to be confirmatory to have -- the 012 was just read a file of that particular exam and then as a second study, even though it was designed with chemotherapy, for confirmation. So right now the plan is to continue with the module v enrollment, as you said, Zai is moving forward for enrolling in China later this year, we will then follow up with that.

As we get more experience with combinations of 13. Remember, as I said, we just have a little over a dozen patients with a combination, which costs multiple different tumor types. And again, wait for ASCO to see the specifics there. I think there is an opportunity both to execute on the mahogany study, and do a very focused, well designed study of MGD013 in March in board a number of indications. So, right now we're still in the discussion phase on how we would move forward and obviously we'd like to see additional data. Clearly, we want to see how long these responses lasts, but the initial data is very encouraging to us.

Stephen Willey

Is there anything you can say about LAG-3 expression on gastric cancer?

Scott Koenig

Yeah, it is. It's not the highest, but there's a significant. I don't recall the exact numbers. I think our data was a higher in the subset of specimens we've looked at compared to what's been out in the literature. But it was significantly over 50% of the population.

Stephen Willey

Okay. That's helpful. And then just lastly, you just talk a little bit about some of the privatization that's been taken here in an effort to extend cash runway. Can you maybe just speak a little bit to the assumptions regarding the underlying collaborative payments that are embedded within the runway guidance, I guess, specifically as to whether or not that includes some kind of regulatory payment from inside as a result of MGA012 approval? Thank you.

Scott Koenig

So, we can't give you the granularity of the timing of payments and the type of payments. And obviously, we've imposed A, what I think is a very conservative about valuation of expectations with regard to that. Just to give you again, context, to refresh your memory, just the regulatory and approval milestones amount of $405 million. That's obviously across several indications in different territory. But given where I know the programs are, as I pointed out today, that the NL study is fully enrolled. There are as I said five registration enabling studies ongoing. We think that we expect some significant milestones coming from that. That’s part of our calculation. But that's not by itself the decider on how we got to 2022.

Stephen Willey

Got it. Got it. Thanks for taking the question.

Jim Karrels

Hey, this is Jim. Keep in mind also that our -- with Provention Bio enables us to achieve a $60 million milestone upon the potential BLA approval of trastuzumab. Now in our -- and by the way, that molecule has breakthrough designation status, and they expect to complete the submission of the BLA sometime this year, I think in the fourth quarter of this year.

Now we take that $60 million and we have cut that and I think you'll find that we have cut that fairly significantly just reflect some risk. So we try to do this very conservatively and we -- we're constantly updating the probabilities assigned to the various milestones across the portfolio just to get a real-time sense of where the numbers might be.

Stephen Willey

Understood. Appreciate the extra color Jim. Thanks.

Operator

Thank you. And our next question comes from the line of Etzer Darout with Guggenheim. Your line is open.

Etzer Darout

Great. Thanks for taking the question. Just a couple. I guess, my first question is even -- so in the expansion cohort of -- for 019 patients on prior therapy with combinations of PD-1 CTLA-4, looks like they're being excluded. I guess based on the data that you're seeing. Do you see this is more positioned for PD-1 naive or PD-1 sort of refractory population?

And I guess -- and second question, any read on whether or not you started to see some additivity for flotetuzumab PD-1 at the 300 milligrams per kg dose on the under study that was sort of stopped?

Scott Koenig

Yeah. So with regard to whether we're targeting the naive or refractory population, the patients that were included in the study included both. So I think that in fact MGD019 could be addressable for both populations. Obviously, we need a lot more experience in large numbers, because all we have right now is a limited data set without a significant -- without expansion in a particular tumor types. But again, we'll provide more data later this year on this molecule, but at this point, we think both populations could be serviced by this as a monotherapy, bispecific or in combination with other drugs to enhance immune reactivity.

With regard to the combination of flotetuzumab plus retifanlimab, we have just had too few patients that were enrolled in the study to come to any conclusion. When you see enhanced responses in a single or two patients, it's hard to interpret. So, just too early to say.

I would say though, that our analysis historically, with regard to the up-regulation of PDL-1 in patients treated with a single cycle flotetuzumab is been quite consistent. I also should note that the study by Sergio Rutella given that the immune environment favors that of treatment with flotetuzumab, which includes activation of checkpoint molecules. It seems quite natural that some combination of this would benefit certainly a subset of patients. So we will continue to explore that combination in the future, as I noted.

Etzer Darout

Got it. Thanks, Scott.

Operator

Thank you. And our next question comes from the line of Jonathan Chang. Your line is now open.

John Barrett

Hello, team. This is John Barrett on for Jonathan. My first question is, you mentioned that you have not reached a maximum tolerated dose for MGD013 yet. How did you choose the dose that you're treating with and what confidence do you have that it is the correct dose, given the high dosing -- the high levels of dose that you're able to achieve?

Scott Koenig

So thanks for that question. And we obviously -- as for many checkpoint molecules, often you don't reach a maximum tolerated dose. So what we look for is pharmacokinetics occupancy of various receptors and we picked the dose based on that and obviously have integrated the safety profile as well.

So, what I can say is as pointed out earlier, this is a well behaving molecule. It has a very nice pharmacokinetics and a -- again a good safety profile, comparable to that of anti PD-1 treatments. So, that's how we're picking the dose.

John Barrett

Got it. And MGC018, you mentioned the interest in moving forward in prostate cancer. Could you just remind us the expression levels of B7-H3 in prostate cancer and any potential strategy to select for biomarker expression in that patient population?

Scott Koenig

As we know, as we pointed out previously, B7-H3 is highly expressed on most solid tumors and in particular prostate, almost all prostate specimens of primary tumors as well as metastatic tumors have very high levels of B7-H3. So, we do not expect the need, particularly for prostate cancer to actually require any diagnostic.

Obviously, we will analyze that mostly retrospectively one patient during this in the study to see if there is any gradation based on relative levels of expression, but you don't expect that to be an impediment. As you know, we have -- had a collaboration on another B7-H3 molecule flotetuzumab as a neoadjuvant treatment in a ISG study with Johns Hopkins, who have previously shown that giving an enoblituzumab patient with primary prostate cancer before they have resection of their prostate has a very nice localization of enoblituzumab in the tumor. And this was also associated with an increase of inflammatory cells in a tumor, which is typically very cold. So we could believe that both molecules may have opportunities to be used in various settings for prostate and other tumor types.

John Barrett

Great. Thank you. And one more, if you don't mind. Of course, the data for the overall survival of margetuximab is still coming in. But do you have an expectation of what setting you might like to present the final overall survival data be at a conference or press release?

Scott Koenig

Well, we obviously this is an important event for the company. So we will certainly press release when the data is available. But certainly we will present the final data at a conference. It all depends on when the data comes in. It probably is -- would be too early for San Antonio Breast. It's possible, but more likely some scientific are conference next year.

John Barrett

Got it. Thank you.

Operator

Thank you. And our next question comes from Tom Shrader. Your line is open.

Tom Shrader

Good afternoon. Thanks for all the details. Back to the ODAC panel, so do you expect the driving force there is the small subset of patients that have seen who have done worse. And also, and I apologize, this was asked if you in fact get the hint that you're going to get approved for a subset. But that changed your launch timing.

Scott Koenig

With regard to the second -- no, that doesn't change anything in that regard. As we have indicated before, we think that having a least a research based diagnostic for selecting patients based on their CD16 allele would be valuable for selecting patients and maybe best help by the drug.

I wouldn't actually characterize this is a driving subset being worse, which is the 15% of the VV population. As we've pointed out this numerous times, we think that the worse response in that population may be a combination of differences. One is that it was a very small subset. So just from the randomization, patients were not selected based on a CT16 allele and so as we have pointed out -- and was pointed out by [Indiscernible] at the San Antonio Breast Meeting, many of the characteristics for randomizations seem to favor the trastuzumab of the population compared to the margetuximab population. And that's just the randomization that goes with a very small population.

So, at this point, given that there is no statistical significance of that, while there was clearly a numerical trends that traz was working better in the DV population, we hope that the study gets approved on intended tree. But if the FDA does agree and -- that agrees to limit us to the F allele, we will not be unhappy and we will be prepared to provide the support via a research diagnostics at time of product launch, which would not be delayed.

Tom Shrader

Okay, great. Thanks. And then quickly on the 018 prostate cohort, are you going to try to get patients before chemo? Because I assume that's kind of where you would like an ADC to be slotted or will you have to treat later line patients in this next cohort?

Scott Koenig

Well, -- as you know Tom the beauty of such a molecule as we're describing, post-taxane and post the antigen blockers is very real -- add to those. And as a result, we actually think, to start with a very late line population, which these patients were, in fact, that population, most of these patients had extensive bone disease. I mean, in fact, all the patients had bone disease, that this might be a very good first indication, but clearly then there could be opportunities to go earlier line. And as I pointed out on an earlier question, there also is an opportunity as we pointed out and treating in neoadjuvant settings, various B7-H3 targeted the agents, which could be enoblituzumab, it could be 018, and it could be other things that we'll talk about in the future.

Tom Shrader

Yes. Got it. Okay. Thank you.

Operator

Thank you. And our next question comes from line of Evan Seigerman. Your line is open.

Evan Seigerman

Hi, Scott. Thanks for taking the question. Hope you all are well. So, just on MGD019, I know you kind of provided some really preliminary data on some responses. Can you give us any color to any thoughts on duration of those responses? And also what type of tumors are in the mix? And how advanced are these patients? I know you don't want to provide all the data, but any more color on that data would be super helpful.

Scott Koenig

So, rather than characterize detail here, let me say that on the four responses we alluded to, were four different tumor types. These were all very late stage patients. Very interesting responses in including tumor types, you would not expect not your traditional populations of renal cancer or patients with melanoma. These were distinct populations. Again, numbers are small, but this bears fruit. This is a very exciting opportunity for this drug.

Evan Seigerman

Okay. And then do you plan to dose beyond the three milligrams per kilogram? I know you said you were greater, but are we going to get -- how high do you think you'll go with that?

Scott Koenig

Again, not to -- we pointed out that we gave the results of three milligrams or higher. We got to our top dose already which is quite considerably higher. Right now based on the pharmacokinetics and again, occupancy and things that we're discussing, obviously, looking at the safety profile in the larger data sets. The -- clearly the dose will be higher than three mgs per kg, but we haven't made a decision yet what the final dose is. We should have that by the time we have a public presentation later this year.

Evan Seigerman

Okay. And then just -- can you remind us aside from head and neck, any other tumor types that can be targeted with an anti-B7-H3, like enoblituzumab?

Scott Koenig

So again, as I pointed out B7-H3 is highly express most solid tumors. If you remember the data we presented at SITC, we highlight not only the head and neck of patients; we were very excited about the prospects of combining NATB 1 one enoblituzumab in patients with lung cancer who are PD-1 negative. So again, the prospects of how such a molecule here could be pursued in other tumor types like lung cancer and others again, which we will point to going forward.

Evan Seigerman

All right. Thank you so much for the call. I appreciate it.

Operator

Thank you. And our next question comes from the line of Boris Peaker [ph]. Your line is open.

Unidentified Analyst

Hi, this is Cynthia on for Boris. Thank you for taking our questions. Just a quick one for me regarding markets, regarding margetuximab. Are there any updates around dialogues educational study in Greater China, especially in light of COVID-19 enrollment? And then can you remind us what are the studies also looking at the 158 subset population?

Scott Koenig

So the answer is that they've done a regulatory review and they are initiating studies in the various countries that they have rights to. At this point, given what we understand the circumstances are in China, things are open and there should not be any return to enrolling the study. So, as you pointed out, this will occur during the course of this year, but we don't have any details with regard to specificity of specific patients yet.

Unidentified Analyst

All right. Thank you.

Operator

Thank you. And we have a follow up question from the line of Debjit Chattopadhyay. Your line is open.

Debjit Chattopadhyay

Hey, thanks for squeezing back in. So, with regards to like the expression, I don't know if you have the answer to this or not, but have you noticed any difference between patients who are parameter refractory versus patients who have initially responded, does LAG-3 expression increase over time obviously, if it's a you know, escape offer for PD-1?

Scott Koenig

It's too early to say that I again rather than me giving you more your details. Listen to the ASCO presentation; I think you'll get a lot of new information at that at that call. But certainly, we will have to follow up on the sexiness of based on the historical treatment profiles of these patients. But you'll see, you'll see certainly, as I pointed out, the relative expression levels of LAG-3 being associated, I can say is predictive, but associated with higher expression.

Debjit Chattopadhyay

Got it. Thank you so much.

Operator

Thank you. And I'm not showing any further questions at this time.

Scott Koenig

I just like to thank everyone again for joining us this afternoon. And to let you all know that we look forward to continuing to advance our program in the coming year and providing updates on our progress. Have a nice evening.

Operator

Ladies and gentlemen, this concludes today's conference call. You may now disconnect. Everyone, have a good day.