MacroGenics, Inc. (MGNX) CEO Scott Canning on Q4 2021 Results - Earnings Call Transcript

Feb. 24, 2022 8:54 PM ETMacroGenics, Inc. (MGNX)
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MacroGenics, Inc. (NASDAQ:MGNX) Q4 2021 Results Conference Call February 24, 2022 4:30 PM ET

Company Participants

Christopher James - Vice President of Investor Relations and Corporate Communications

Scott Canning - President and Chief Executive Officer

James Karrels - Senior Vice President and Chief Financial Office

Conference Call Participants

Kaveri Pohlman - BTIG

Etzer Darout - BMO Capital Markets

Asha Babaric - Citi

Charles Zhu - Guggenheim

Jonathan Miller - Evercore ISI

Stephen Willey - Stifel

Silvan Tuerkcan - JMP

Peter Lawson - Barclays

David Dai - SMBC Nikko Securities America, Inc.


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.

Christopher James

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 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 Statement 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.

Scott Canning

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.

James Karrels

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 revenue from collaborative agreements, was $77.4 million for the year ended December 31, 2021, compared to total revenue 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 30, 2021, compared to 193.2 million for the year ended December 31, 2020.

The increase was primarily rated related to increased clinical trial and development costs related to and 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, Incyte he decrease clinical costs and BLA support for margetuximab compared to the prior year.

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 $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.

Scott Canning

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 prioritize the advancement of MGC018 and enoblituzumab our two programs targeting B7-H3 that are taking additional steps to operationalize all aspects of these programs. This included planning for the advancement towards the registration, directed study of MGC018 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 frequent activities to fuel our pipeline of investigational product candidates to the potential treatment of cancer.

With that backdrop, let me use this time to walk you through updates on a portfolio of investigational clinic molecules. Starting with a molecules targeting B7-H3, a member of B7 family molecules involved in immune regulation. We are developing two molecules that target B7-H3 through complementary mechanisms of action that take advantage of this antigens broad expression across multiple solid tumor types.

MGC018 is our investigational antibody drug conjugates designed to deliver alkylating duocarmycin cytotoxic payload consumers express B7-H3. Because September we presented an encouraging update of critical data from our ongoing study of MGC018 in patients with advanced solid tumors that has come out.

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 today, we intend to modify the dose and administration of MGC018 potentially including a slightly reduced dose and increasingly interval 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 for the 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 exists 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. Relevance 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 CR with complete resolution of this disease and normal PSA after treatment with larger elements.

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 CR with a normal PSA. Netscape has created a profile of this patient within a video they produce regarding bispecific checkpoint molecules.

Stories like to tell why we as a company and the industry developed 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 a various solid tumors including prostate cancer.

As I mentioned earlier, we expect to initiate a combination study of MGC018, a 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 over expression B7-H3 in solid tumors is enoblituzumab. And Fc-engineered antibody created using 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 base bispecific molecules designed to provide further differentiation from existing PD-L1 base options and to enable a broad set of combination options across our portfolio. Lorigerlimab is an investigational bispecific touch a balanced, dark 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 ID 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 are investigational bispecific PD-L1 by LAG-3 DART. Tebotelimab with evaluated in a Phase 1/2 dose expansion study in several tumor types, is currently being studied in combination with enoblituzumab and squamous cell carcinoma the head and nick. We are formulating plans for potential future development of tebotelimab and expect to provide an update in the second half of 2022.

MacroGenics partner in Greater China’s Zai Lab recently informed the company that is decided to discontinue development of tebotelimab for indications. It was enrolling in its territory and is evaluating future development plans in other indications.

Next up, let me discuss our efforts to advance treatment of patients with CD123 positive hematologic malignancies. We have prioritized development of MGD024 our next generation by specific 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 the 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 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.

Least I will provide an update on margetuximab. As a reminder, MARGENZA would 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 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 about the clinical data and the changing treatment landscape.

Recall in November 2021, we announced that decision to discontinue enrollment of Module A of MAHOGANY study. With regard to Zai’s effort in breast cancer, they announced last month that the China and [NPA] (Ph) 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 through throughout 2022. We would now be happy to open the call for questions. Operator.

Question-and-Answer Session


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

Unidentified Analyst

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

Scott Canning

Thanks very much for the question. After we discuss the results are data at ESMO and continue 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, as well as Cmax associated with both responses, as well as side effect profiles. From that we derived a valuation of one modifications we could do 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, two side effects, we want to further mitigate that side effects are given the bothersome nature of that effect.

We have incorporated that in a plan going forward and have included that in a briefing document to the FDA. We will be discussing that plan going forward at that meeting. And after we have feedback, we will provide further insights on how the modification of dose, both initial dose, and increasing the time between doses might be implemented.

Unidentified Analyst

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?

Scott Canning

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 by-specific 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 had conducted a study of looking at combinations with the Nivo in the setting of metastatic prostate cancer, and while though they did not meet their objective endpoints for that study, there were 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, extensive study with Lord Joe men 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 the CR and today providers follow-up on that patient, where more than a year after stopping therapy is still in CR 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 a CTLA-4 axis as well.

Unidentified Analyst

Got it. thank you so much.

Christopher James

Operator could we have the next question please.


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

Kaveri Pohlman

For enoblituzumab just loss of CD16 expression play any role in efficacy, and any thoughts on combining this with cytokines like IL15 or maybe NK cell therapies?

Scott Canning

Thank you very much for that question, Kaveri. So, clearly, enoblituzumab was designed to enhance finding to CD16 with a reduced finding to CD32B, like we have characterized for MARGENZA in our approved product. We have observed that the FC modification we have incorporated in the enoblituzumab by engaging CD16 on various immune cells drives, over-expression of gamma interferon associated genes. And this results as a consequence in upregulation of various cytokines beyond gamma interferon, but also upregulation of various checkpoint molecules.

With regard to the use of cytokines, in addition, that certainly could be explored. And in addition, there has been interest of combining enoblituzumab with various NK cells both in vivo and ex-vivo, in other settings. And we are having certain discussions with other parties regarding that possibility. So thank you very much for the question Kaveri.

Kaveri Pohlman

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

Scott Canning

Thanks again for that question. And as you know, quite well, we had very encouraging early data in very late stage of patients with DLBCL, including those who had received various cell therapies.

And 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.

With regard to the PD-L1 you are absolutely correct. They have not - the blockers have nothing particularly effective in DLBCL treatments. I think this is an opportunity by blockading on multiple pathways that are involved in exhaustion of cells, one might get a additional beneficial effects in various lymphomas. And so that is some of the rationale of why we are looking at this not only DLBCL, but combinations such in solid tumors as well

Kaveri Pohlman

Appreciate it.


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

Etzer Darout

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 see if you had the chance to kind of 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? Thank you.

Scott Canning

Etzer thanks so much for the questions. And certainly as we consider the opportunities of combining a checkpoint with MGC018. One of the things paramount in our view was in addition driving better efficacy was understanding the potential for a safety signal beyond that what we have seen to-date.

From what we are observing, both in terms of our clinical experiences, with PD-L1 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 side effects seen to-date.

However, one note and predict that one might appear in a clinical trial. So in the way we are designing this trial, and we will get more into this very surely once the trial get started. We have fixed the dose of lorigerlimab at the current 6 mgs per kg, but starting at a lower dose of the MGC018, and then 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 we expect that to get started in the next few weeks.

With regard to flotetuzumab, we do think that we will get some advantage in terms of reduction of R&D spend. I can’t comment the specifics right now. We are obviously just giving - providing that information to investigators. So patients are still on the study right now. And we will continues some spend in the near-term, but we do expect some savings as a result of discontinuing natural.

Etzer Darout

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


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

Asha Babaric

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 that may have contributed? Or was it just the emerging profile for MGD024?

Scott Canning

So, thank you very much for the question. As we pointed out we believe, as you stated, the superior profile of MGD024 with regard to flotetuzumab for the long-term treatment of patients with hematological malignancies.

Certain comments in the following is that number one, the flotetuzumab molecule as you know, has given us continuous infusion required initial hospitalization of patients during the first two weeks before they can go to an outpatient setting.

With the design of an FC incorporated molecule, plus with the next generation version of the CD3 components in this molecule, we believe that this drug can be given more easily, intermittently on an outpatient basis technically, but as important, we expect to have a significant reduction in cytokine release syndrome as a result of treatments.

On top of that, as you know, when we started out this study a couple of years ago, the treatment regimens for AML were established with some new molecules, but that landscape is constantly changing.

And since we are now conducting a single arm study, we think that there may be additional risks, given the changing landscape with a final readout here, which will require obviously significant more investment in this current study. But on top of that, if we want proper European approval, that will certainly require a controlled study.

So all-in-all, given the superior profile of this molecule plus as we pointed out in the announcement today, based on data that we have shown at the recent asked meeting, that combination of MGD024 plus some standard of care can extend the use of this in early lines of therapy for AML potentially, plus extend beyond to other CD123 tumors, we think that our decision was the right one that given these various aspects as I described to you.

Asha Babaric

Okay, thank you. If I could sneak in one more? Could you provide any color to wise, I love to discontinue development with flotetuzumab here is that you can share any additional details?

Scott Canning

I can’t at this point in that regard, but let me emphasize. Just continue with, it just continue on the current indications that they were temporary. So they are not enrolling patients and 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 that they will not be enrolling any additional patients in the current indications that they have received today.

Asha Babaric

Okay. Thank you very much.


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

Charles Zhu

Hi everybody. Thanks for taking the question. I may have missed this one earlier, but it sounds like you are melanoma CNBC and NSCLC cohorts are fully enrolled for MGC018. How are you evaluating go no go decisions for these indications that data mature and what are some of the potential benchmarks on which, you would be able to make those decisions? And also, how should we think about timelines towards those kinds of points?

Scott Canning

Sure. Thanks very much for the question. As you recall, and as I said on previous calls. These cohorts beyond the prostate, are much smaller. They, we have enrolled for the ones that have completely enrolled between 16 to 20 patients in those cohorts.

And we are continuing to follow these patients. As I have stated before, given the size of these cohorts, it is still too early to make any decision going forward. And which ones we will prioritize for additional, say Phase 2 or registrational directed studies.

What we expect to do is obviously look at what the standard of care is in these late line patients and come to both an assessment of the responsiveness. But in addition, as I pointed out for the plans for prostate cancer, we want to also have additional experience with the slightly modified dose with additional patients for the specific cohorts, we want to further test.

And so given all this together, we like to see the data mature a little more that will allow us to then make some decisions on which one of these cohorts we want to prioritize. And then we will be able to provide some guidance in the second half of this year with regard to that and also after we get the feedback from the FDA. So that is sort of the plan at this moment.

Charles Zhu

Got it, makes sense and thanks for that color. If I need to squeeze in one more on MGC018. I also kind of want to gauge perhaps your reactions to diabetes DSM300 data coming out of ASCO GU and how or it is at all that weighs in on your thinking for MGC018, especially when it comes to positioning? Thanks.

Scott Canning

Well thank you Charles again. Again, as you know, we feel that we have the right profile to move forward with MGC018 and late stage prostate cancer. It is clear there is also nice to see that a organization like Daiichi with expertise and ADC are interested in pursuing that in this indication. As you know, the toxins that are incorporated in their molecule 7300 as well as our target DNA by working by different mechanisms.

I would say that I’m very encouraged by the data in the following sense is that the data we have reported in terms of with this criteria as ESMO, were quite comparable to what they reported at the recent ASCO GU meeting. The PSA 50 reductions that we have reported, seem to be better than what the data that they reported to-date.

And so overall, I would say we are seeing both company’s very encouraging data in the treatment of prostate cancer, which is provides further validation for target B7-H3 with this type of mechanism.

I would say we are also in a potentially 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. So I think, all-in-all, I think we will try to advance it as quickly as possible to the benefit of patients.

Charles Zhu

Sounds great. Thanks for taking the questions.


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

Jonathan Miller

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

Scott Canning

Thanks Jon, good to hear from you. With regard to ADAM9, you are correct that ImmunoGenis running those clinical trials. They are still in dose finding, doing some additional expansion that continues and they have not selected adults for expansion into other tumor types as of yet. We expect that should occur in the near-term.

So consistent with the guidance that they have provided us, they do expect to have that dose and be able to announce later this year plans for expansion into specific tumor types, the specific types have not been detailed publicly. So I will leave it to them and wait till then.

So with regard to where this fits into our portfolio, again, we are very encouraged by the preclinical data until we see the specific dose that is selected and further expansion. It is just too early to comment on that in terms of the prospects overall.

As you know, except for MGD024 we have a lot more data on many of our other programs and have obviously much more encouraged about the prospects for other things our portfolio going forward at this time.

Jonathan Miller

And then maybe just to follow-up on some of the B7-H3 questions that folks have asked, I guess given that we know that 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 does come out?

Scott Canning

So in that regard, I will emphasize that the dose is more of a tweaking of a dose as planned 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 the responsiveness or side effect profile.

So, in fact, we do have the overall total dose that these patients received to make this decision. But surely, we would obviously want additional confidence by the prospect of use of this drug. But right now, I think this is as good as we can do to move forward in this study.

Jonathan Miller

Got it. Thanks very much guys.

Scott Canning

Thanks Jon.


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

Stephen Willey

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

Scott Canning

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

Stephen Willey

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

Scott Canning

Well, rather than comments on that, let’s wait until we have the FDA guidance and feedback. And then we will come back to you in regards to what we will do next for the various aspects of the prostate as well as the other indications. So we would like to have that regulatory insight before we more definitive about the specific design of that prostate study.

Stephen Willey

Okay. And then maybe just a question, I guess I will refer you and for Jim, but just on the cash runway guidance. I know that 018 is kind of 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 with respect to whether or not the tumor types going to be prostate and/or how they can put that trial a little bit?

Scott Canning

Jim, did you want to take that?

Jim Karrels

No, I mean, 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 the nut is that we need to define to make this happen.

However, we do have adequate cash to launch a study. We just we want to be in a position where we can fully fund the entire study. So, obviously, BD 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 to advance various BD dialogue with various parties forward. And obviously, where stock trading today, as the whole market is off, it is an option that we don’t like to look at, but one that we would if we had to.

Stephen Willey

Understood, it is very helpful. Thanks for taking the questions.

Jim Karrels



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

Silvan Tuerkcan

Hello good afternoon. thanks for taking my questions and congrats on all of that 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 is it to keep the dose in the patient over the course of treatment as highest possible? Thank you.

Scott Canning

Silvan, I think thanks for the question. And I would say that we are trying to probably accomplish both and that will mitigate some side effects. As I pointed out today, the one we feel that was most problematic based on feedback from the patients was the hand switch syndrome. And like to decrease the incidence severity of that.

We feel that things like the hemologic side effects that we were observing such as the neutropenia, were easily handled by holding dose and supplementary growth factors like GCSF. And again, also increasing the time interval between dosing should also provide some value there.

Ultimately, as you pointed out in the second comment, is that by the reduction and reducing side effects, we think that you can hopefully treat patients for a longer period of times and offer obviously greater benefit to those patients as a result. So that is the objective going forward.

Silvan Tuerkcan

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

Scott Canning

I think, at future discussion we will be able to provide some guidance in terms of the fully administered dose to the patients which we think would be most valuable for getting the best effects, but again, we will wait till after we have a discussion with the regulators.

Silvan Tuerkcan

Great. thank you so much for taking my questions.


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

Peter Lawson

Hey, Scott, thanks for taking the questions. Just on the DSP meeting in Q1. Just will you communicate that to us the outcome around the dosing and then will the combination with your PDL-1 CTLA-4, would that 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 1Q?

Scott Canning

Yes. So with regard to the meeting, as in our approaching March, the quarter ends at the end of March. So 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, and actually patients are in screening right now and it is likely that we will have first patient dose potentially even before that meeting, so that will that will start.

With regard to communication about that obviously, we will have to see what the written comments come back. So I think, more or less, the likelihood is we will be able to communicate this sometime in the second quarter.

Peter Lawson

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

Scott Canning

No, I think, Peter, the point was, we wanted the data to continue to mature on this patients that are on the 3 mg per kg Q3 regimen. And obviously with the modifications that occurred. So whatever update, we provide them, irrespective of that, for a particular indications we can plan to continue. We would then apply new dosing, and that wouldn’t start until the second half of the year so.

Peter Lawson

Great. thank you. Thank you so much.


[Operator Instructions] Our next question comes from David Dai with SMBC. Your line is open.

David Dai

Thanks for taking my question. So just couple of questions on MGC018. So regarding the dose expansion data in prostate cancer and second half this year. Could you just set the data expectation and what would be the clinical benchmark we should be expecting. And then also on MGC018 and prostate cancer could you also share with some of your thoughts on biomarker strategies to further identify responders in prostate cancer?

Scott Canning

Thanks David. So with regard to dose expansion, as you know these are very late line, a castration-resistant prostate patients. The patient line of therapy for the expansion cohorts, were third and fourth line therapy. As you know historically, these patients had based on progression, usually has several months to lay progress, I mean, obviously depending on which study they had been previously looked at.

So we are clearly looking at those markers for advancing beyond of what the historical data has, and we have reviewed our data with experts in the field and feel that we have a profile even with a limited 40 patients that could provide significant benefits to these patients going forward.

Of course, as I pointed out earlier, we are looking to even further and enhance the effect here by dosing modifications. So that will be certainly part of the analysis. And clearly we will continue to look at different populations of patients.

Today we have not specifically identified any gene markers, per se, that would predict a more favorable outcome of one patient versus another based on MGC018, but we will continue to look at that analysis.

And also continue to look at patients who have various types of diseases, those that have visceral disease and eliminated various organs, while most nodes versus those with bone disease. So again, at this point while we treated approximately 50 patients with this dose it is still limited number of patients.

The other thing we are keeping an eye on is B7-H3 expression. And to-date, that doesn’t seem to portend predictions for those patients will respond or not, we saw patients in general had very high levels by H score of B7-H3. But we did see the occasional patients with low H scores that also had evidence of activity. So at this point, at least for prostate cancer that does not seem to be the predictable marker going forward.

David Dai

Got it. very helpful. Thank you.


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

Scott Canning

I want to thank everybody 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.

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