Q4 2019 Earnings Call
Good afternoon, we will begin the Macrogenics 2019 fourth quarter corporate progress and financial results conference call in just a moment.
Operator: Good afternoon, we will begin the MacroGenics 2019 fourth quarter corporate progress and financial results conference call in just a moment. All participants are in a listen-only mode at this point, 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 Krasovsky, Vice President, Investor Relations and Corporate Communications, MacroGenics. Thank you.
All participants are in listen only mode at the moment and we will conduct a question and answer session at the conclusion tall.
At this point I will turn the call overtime and I saw Scott.
Vice President Investor Relations and corporate Communications Macrogenics.
Thank you good afternoon, and welcome to Macrogenics His conference call to discuss our fourth quarter 2019 financial and operational results for anyone who has not had a chance to review our results we issued a press release.
Unknown Executive: Good afternoon, and welcome to MacroGenics' conference call to discuss our fourth quarter 2019 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 announcements, which is available under the Investors tab on our website at macrogenics.com. You may also listen to this conference call via webcast on our website, where it will be archived for 30 days, beginning approximately two hours after the call is completed.
This afternoon outlining today's announcement, which is available under the investors tab on our website at Macrogenics Dot Com you May also listen to this conference call bio webcast on our website, where it will be archived for 30 days beginning approximately two hours after the call. This completed I.
Unknown Executive: 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.
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 provisions under the private Securities Litigation Reform Act of 1995 actual results may differ materially from those.
Indicated by these forward looking statements as a result of various important factors, including those discussed in the risk factor section of our annual or quarterly current reports filed with the FCC. 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 something like 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 changed except to the extent of required by applicable law.
Now I'd like to turn the call over to doctors about Keening, President and Chief Executive Officer Macrogenics.
Scott Koenig: Thank you, Anna. I'd like to welcome everyone participating via conference call and webcast today. Thank you for joining us. This afternoon, I will provide an update on our clinical programs and the progress 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 year.
Thank you right now I'd like to welcome everyone participating via conference call and webcast today. Thank you for joining on.
This afternoon, I will provide an update on our clinical program and these balances expected during the year, but before I do so let me first turn the call over to Jim Carol Senior Vice President Chief Financial Officer.
Review, our financial results for the year. Thank you Scott. This afternoon Macrogenics reported financial results for the year ended December 31, 2019, which highlight our financial position as well as our recent progress.
James Karrels: Thank you, Scott. This afternoon, MacroGenics reported financial results for the year ended December 31, 2019, which highlight our financial position as well as our recent progress. As described in our release, MacroGenics had research and development expenses of $195.3 million for the year ended December 31, 2019, compared to $190.8 million for the year ended December 31, 2018. This increase was primarily due to continued enrollment across our multiple ongoing clinical trials. We had general and administrative expenses of $46.1 million for the year ended December 31, 2019, compared to $40.5 million for the year ended December 31, 2018. This increase was primarily due to an increase in consulting costs related to market research and other commercial preparation activities. Consistent with our prior communications, we have no intention to build out a sales force at this time, as our strategy remains to partner the commercialization of margitoxin ad. Nonetheless, there is a modest preparatory investment in pre-commercial efforts that we believe may be necessary.
As described in our release Macrogenics had research and development expenses of $195.3 million for the year ended December 31, 2019 compared to 190.8 million.
The year. It at December 31, 2018. This increase was primarily due to the continued enrollment across our multiple ongoing clinical trials.
We had general and administrative expenses, a $46.1 billion for the year ended December 31, 2019, compared to 40.5 million for the year ended December 31, 2018. This increase was primarily due to an increase in consulting costs related market research and other commercial preparation activities.
System with our prior communications, we have no intention to build out of Salesforce at this time as our strategy remains to partner the commercialization of March talks man. Nonetheless, there was a modest compared to our investment in pre commercial effort that we believe maybe necessary.
James Karrels: We recorded total revenue consisting primarily of revenue from collaborative agreements of $64.2 million for the year end of December 31, 2019, compared to $60.1 million for the year end of December 31, 2018. This increase was primarily due to the timing of revenue recognition under our collaborative agreements. Included in our 2019 total revenue was $24.3 million recognized under various supply agreements with our collaboration partners, including Insight Corporation and Xylab, with regard to our development and manufacturing activities that support the supply of partnered product candidate drug material. I will also point out that of the $25.4 million in other income we recognized for the year ended December 31, 2019, approximately $20 million related to both the revaluation of warrants we received as consideration under license and purchase agreements with Prevention Bio and the gain on sale of the underlying 1.95 million shares of Prevention Bio, mostly during the fourth quarter.
We recorded total revenue consisting primarily of revenue from collaborative agreements of $64.2 million for the year ended December 31, 2019, compared to 60.1 million for the year ends December Decemberthirty one 2018.
This increase was primarily due to the timing a revenue recognition under our collaborative agreements.
Included in our 2019 total revenue was $24.3 million recognized under various supply agreements with our collaboration partners, including Incyte Corporation, and so I lab with regard to our development and manufacturing activities. That's important supply partnered product candidate drug material.
I will also point out that of the $25.4 million in other income we recognized for the year ended December 31, 2019 approximate $20 million related to both the revaluation of warrants we received as consideration under license in purchase agreements with prevention bio and the gain on.
The underlying 1.95 million shares of prevention bio mostly during the fourth quarter.
We had a net loss of $151.8 million for the year ended December 31, 2019, compared to net loss of 171.5 million for the year ended December 31 2018.
James Karrels: We had a net loss of $151.8 million for the year-end of December 31, 2019, compared to a net loss of $171.5 million for the year-end of December 31, 2018. And finally, our cash, cash equivalents, and marketable securities as of December 31, 2019 were $215.8 million, compared to $232.9 million as of December 31, 2018. We anticipate that our cash equivalents and marketable securities as of December 31, 2019, combined with anticipated and potential collaboration payments, will enable us to fund our operations into 2021, assuming our programs and collaborations advance as currently contemplated. Through the prioritization of programs and ongoing realignment of resources, we are focused on extending our cash runway into 2022. And now, I'll turn the call back to Scott.
Finally, our cash cash equivalents and marketable securities as of December 31, 2019.
Were $215.8 million compared to 232.9 million as of December 31, 2018.
We anticipate we anticipate that our cash cash equivalents and marketable securities as of December 31, 2019, combined with anticipated and potential collaboration payments will enable us to fund our operations into 2021.
I mean, our programs and collaborations advances currently contemplated.
Through the prioritization of programs and ongoing realignment of resources, we are focused on extending our cash runway into 2022, and now I'll turn the call back to Scott.
Thank you Jim as we outlined in January as the product candidates in our pipeline advance towards later stage trials. We are prior prioritizing those program, we believe the highest scientific and commercial merit as well as potential to achieve regulatory approval.
As I will describe later in more detail, we took several actions to prioritize and focus.
We just continued development of two clinical stage molecule MGT 007, and MDD 009.
Scott Koenig: Thank you, Jim. As we outlined in January, as the product candidates in our pipeline advance towards later stage trials, we are prioritizing those programs that we believe have the highest scientific and commercial merit, as well as the potential to achieve regulatory approval. As I will describe later in more detail, we took several actions to prioritize and focus. We discontinued development of two clinical stage molecules, MgD007 and MgD009. Going forward, we expect to pursue only focused-dose expansion cohorts in one or two tumor types for each molecule currently in Phase I dose escalation. We prioritized Module A of the Phase II-III Mahogany Study, and we modified the design of the planned Phase II-III Registration-Directed Study of Enobotuzumab. Let's begin with Marjah Tuktamat, our investigational, FDA-engineered anti-HER2 antibody.
Going forward, we expect to pursue only focus dose expansion cohorts in one or two tumor types for each molecule currently in phase one dose escalation.
We prioritize module way of the phase two three mahogany study.
And we modified the design of the planned phase three registration directed study I went over to the Matt.
Let's begin with merger talks about our investigational, that's the engineered and the Urdu antibody.
In December 29 team, we submitted a biologics license application of delay the yesterday for the treatment of patients with metastatic hertwo positive breast cancer in combination with chemotherapy.
The safety efficacy results provided the B.L.A., primarily from the pivotal phase three Sophia study, which is evaluating margin talks about plus chemotherapy compared to try to choose a map plus chemotherapy in patients with her two positive metastatic breast cancer, where we see priority hurt you therapies.
Okay that results from this study were presented at the San Antonio breast cancers Symposium in December 2090.
Recently, the be away was accepted for review by the FDA.
Scott Koenig: In December 2019, we submitted a biologics license application (BLA) to the FDA for the treatment of patients with metastatic HER2-positive breast cancer in combination with chemotherapy. The safety and efficacy results provided in the BLA are primarily from the pivotal Phase 3 SOFIA study, which is evaluating margin toxomath plus chemotherapy compared to trastuzumab plus chemotherapy in patients with HER2-positive metastatic breast cancer who have received Updated results from the study were presented at the San Antonio Breast Cancer Symposium in December 2019. Recently, the BLA was accepted for review by the FDA. Accordingly, we expect a standard review process with an anticipated Prescription Drug User Fee Act, or PDUFA, date by the end of 2020.
Accordingly, we expect the standard review process with an anticipated prescription drug user fee act or PDUFA date by the end of 2020.
We also expect that the dust it will require an oncologic drugs Advisory committee or ODAC meeting in the second half of 2020.
Separately in February 2020, a regional partner in greater China, ZAR lab, and now that they initiated a bridging study to support the potential registration in greater China of margin talks about plus chemotherapy for the treatment of patients with metastatic hertwo positive breast cancer.
Beyond breast cancer, we have initiated a phase two three mahogany study in first line patients with advanced Hertwo positive gastric gastroesophageal junction cancer.
Initially mahogany is evaluating merger talks about mgo 12, our investigational anti PD, one antibody license inside in patients with her to our age Cdthree positive and PDL one several positive disease.
The single arm part of the mahogany study, which we referred to as module way is designed to support a potential accelerated approval of margin talks about plus mgo 12 in the United States based on a primary efficacy endpoint of objective response rate.
Scott Koenig: We also expect that the FDA will require an Oncologic Drugs Advisory Committee or ODAC meeting in the second half of 2020. Additionally, in February 2020, a regional partner in Greater China, Xylab, announced that they initiated a bridging study to support the potential registration in Greater China of margituximab plus chemotherapy for the treatment of patients with metastatic HER2-positive breast cancer. Beyond breast cancer, we have initiated the Phase 2-3 Mahogany Study in first-line patients with advanced HER2-positive gastric or gastroesophageal junction cancer. Initially, Mahogany is evaluating margituximab plus MGAO-12, our investigational anti-PD-1 antibody, licensed to InSight in patients with HER2, IHC3 positive, and PD-L1 double positive disease. This single-arm part of the mahogany study, which we refer to as Module A, is designed to support a potential accelerated approval of margitoximab plus MgAO12 in the United States based on a primary efficacy endpoint of objective response rate. We believe that this chemo-free regimen, which engages both innate and adaptive immunity, may be a significant opportunity to change the treatment paradigm for patients living with advanced In the second half of 2020, we expect to assess initial safety and efficacy data from the ongoing Mahogany Module A trial to inform a go-no-go decision on further enrollment.
We believe that this chemo free regimen, which engages both innate and adaptive immunity may be significant opportunity to change the treatment paradigm, where patients living with advanced her two positive gastric cancer.
And the second half of 2020 with respect to it says initial safety and efficacy data of the ongoing mahogany margin way to inform a go no go decision a further enrollment.
As a reference a response rate of 47% with the median overall survival of 13.1 month was reported from the told this study that evaluated chemotherapy and Trastuzumab in first line advanced her two positive gastric cancer.
At ESMO in September 29, gene, we presented data from our second line Phase two study of merger talks about plus pembrolizumab.
We observed a median overall survival 20.5 month and a response rate of approximately 50% among patients whose tumors are hurt too I see three positive NPV O one double positive.
Notably the safety profile that margin talks about and herbalism that observed in our study in which grade three or greater treatment related adverse events were reported in approximately 20%. The patients was comparable to the historically observed with pembro isn't that one of the therapy.
We believe this compares favorably against 68% grade three treatment related adverse event rate reported in the Toby regimen.
The second component of the mahogany study, which we referred to as module B is designed as a randomized controlled trial to evaluate the combination of margin talks about would chemotherapy plus either in jail 12, or NGL 13, our PD one by lag three dart molecule compared to try.
Isn't that big chemotherapy in a broader population of patients with advanced Hertwo positive gastric cancer.
Scott Koenig: As a reference, a response rate of 47% with a median overall survival of 13.1 months was reported from the TOGA study that evaluated chemotherapy and trastuzumab in first-line advanced HER2-positive gastric cancer. At ESMO, in September 2019, we presented data from our second-line Phase II study of Moduletuximab plus Pembrolizumab. We observed a median overall survival of 20.5 months and a response rate of approximately 50% among patients whose tumors are HER2, IHC3 positive, and PD-L1 double positive. Notably, the safety profile of margituximab and pembrolizumab observed in our study, in which grade three or greater treatment-related adverse events were reported in approximately 20% of patients, was comparable to the safety profile observed with pembrolizuma We believe this compares favorably with a 68% grade 3 treatment-related adverse event rate reported in the TOGA register.
The study is designed to evaluate overall survival as the primary endpoint.
We expect design lab to lead the initiation of the module will be in greater China. The second half of 2020.
The next program I will discuss this lot it isn't that our investigational by specific dart molecule that recognizes both CB 123 and Cdthree.
At the American Society of Hematology or Ash annual meeting in December 2019, we presented updated results from the patients with A.M.L., who are refractory to induction therapy in the ongoing phase one two dose expansion study.
Oh, the approximately 20000 patients diagnosed with A.M.L. in the United States annually at least 30% sale to achieve a CR with intensive induction therapy.
These patients represent an extremely challenging population to treat where based on our data. We believe there may be an opportunity to address this unmet need.
We intend to define a potential registration path for platoons amount in the United States in the first half of 2020 pending continue discussions with the FDA.
We have also initiated outside the United States, a combination study of flow the to the map and Mgo 12 in relapsed or refractory AML patients as a potential means the bode well what late in the duration of response or they M.L. pages uploaded to isn't that the combination is supported by a strong side.
Did the Brashly now based on data that we have previously reported.
Let me next turn to Mgo 12, our investigational anti PD, one antibody, which is exclusively licensed to Incyte Corporation globally, although we retain the rights to develop our pipeline product candidates in combination with this molecule.
Scott Koenig: The second component of the mahogany study, which we refer to as Module B, is designed as a randomized controlled trial to evaluate the combination of margituximab with chemotherapy plus either MgAO12 or MgDO13, our PD-1 bilag-3-DART molecule, compared to trastuzumab in chemotherapy in a broader population of patients with advanced HER2-positive gastric cancer. The study is designed to evaluate overall survival at primary, and we expect XyLab to lead the initiation of module B in Greater China in the second half of 2020. The next program I will discuss is flotatizumab, our investigational bispecific THAR molecule that recognizes both CD123 and CD3. At the American Society of Hematology, or ASH, annual meeting in December 2019, we presented updated results from patients with AML who are refractory to induction therapy in the ongoing phase 1-2 dose expansion study. Of the approximately 20,000 patients diagnosed with AML in the United States annually, at least 30% fail to achieve CR with intensive induction therapy.
Inside as initially pursuing development of LNG, IL 12, monotherapy to potentially registration, enabling studies in anal cancer, Amazon, Hi, endometrial cancer, and Merkel cell carcinoma with David you know cancer anticipated in the second half of 2020.
In addition, we expect inside to initiate two phase three study of NGL, it's well known as podium 301 and podium Rio for patients with advanced or metastatic non small cell lung cancer.
You know there are currently six registration directed clinical study ongoing or planned 2020 across a broad range of tumor types.
Our second checkpoint molecules NGL 13, a first in class investigational by specific dart molecule targeting PD, one and lack three.
Mgo 13 is being evaluated in the phase one dose expansion study, which we are selecting one or more indications for further development.
In addition, we have submitted data from select cohorts in the ongoing study for presentation and the scientific conference in the first half of 2020.
Separately in February 2020, Macrogenics regional partner in greater China, Xylem, and now announced it the initiation of a phase one study well then video 13 in combination with Niraparib, a PARP inhibitor for the treatment of patients with advanced gastric what gastroesophageal junction.
Scott Koenig: These patients represent an extremely challenging population to treat, and based on our data, we believe there may be an opportunity to address this unmet need. We intend to define a potential registration path for claudituzumab in the United States in the first half of 2020, pending continued discussions with the FDA. We have also initiated, outside the United States, a combination study of flotatuzumab and MgAO-12 in relapsed or refractory AML patients as a potential means to both broaden and lengthen the duration of response of AML patients on flotatuzumab. This combination is supported by a strong scientific rationale based on data that we have previously reported.
Yes.
Let me now briefly discuss ennobled Susan that our investigational FC engineered MPB seven Athree monoclonal antibody.
To further inform the development of the notes isn't that we decided to modify the previously planned phase two three study and take the opportunity to tell us whether we could achieve greater anti tumor activity by combining a noble choosing that with dual PD one leg, we checkpoint blockade.
We therefore plans to initiate ALLEVYN module to evaluate the activity of both the noble twos that lets him jailed flow and a novel to the math plus mgo 13 as chemotherapy free regimen in first line patients with recurrence and metastatic head neck cancer before proceeding with one of these costs.
Combinations in the future phase two three study.
Finally in 2020, we anticipate completing phase one dose escalation of M.D.C.O. 18, or antibody drug conjugates targeting the seven athree as well as for Mgo 19 applied specific dart molecule targeting PD, one and seats you like floor, we play.
Scott Koenig: Let me next turn to MgAO-12, our investigational anti-PD-1 antibody, which is exclusively licensed to Insight Corporation globally, although we retain the rights to develop our pipeline product candidates in combination with this molecule. InSight is initially pursuing development of MgAO-12 monotherapy through potentially registration-enabling studies in anal cancer, MSI-high endometrial cancer, and Merkel cell carcinoma, with data in anal cancer anticipated in the second half In addition, we expect Insight to initiate two Phase 3 studies of MgAO-12, known as Podium 301 and Podium 304, in patients with advanced or metastatic non-small cell lung cancer. In all, there are currently six registration-directed clinical studies ongoing or planned in 2020 across a broad range of tumor types. Our second checkpoint molecule is MgdO13, a first-in-class investigational bi-specific DART molecule targeting PD-1 and LAG-3.
That's the data from the dose escalation cohorts for both molecules for presentation at scientific conferences, its wanting to Arnie.
In addition, once we complete dose escalation, we're planning to initiate a focused dose expansion study for each molecule in one or more select tumor types.
Well the initial data sets are small we are encouraged by the progress and these studies to date and we look forward to sharing data from both of these programs in 2020.
In summary, 2019 wasn't importantly year for Macrogenics with the submission of our be delayed for merger talks about for her two positive breast cancer.
Margin talks about is also being evaluated in combination with checkpoint blockade in a registration directed clinical study in advance hertwo positive gastric cancer.
During 2020, we anticipate additional key events, we intend to supply the registration PAREXEL potency isn't that refractory ml pending further discussion with the FDA.
We also look forward to presenting initial clinical data from several of our phase one program, including Mgo 13, Mgo 19, and then D. C O 18.
Scott Koenig: MgDL-13 is being evaluated in the Phase I Dose Expansion Study, from which we will select one or more indications for further development. In addition, we have submitted data from select cohorts in the ongoing study for presentation at a scientific conference in the first half of 2020. In February 2020, MacroGenics' regional partner in Greater China, Xilab, announced the initiation of a Phase I study of MgdO13 in combination with norepirib, a PARP inhibitor, for the treatment of patients with advanced gastric or gastroesophageal junction cancer. Let me now briefly discuss Enobotuzumab, our investigational ST-engineered anti-B7H3 monoclonal antibody. To further inform the development of inoblituzumab, we decided to modify the previously planned Phase 2-3 study and take the opportunity to test whether we could achieve greater anti-tumor activity by combining inoblituzumab with dual PD-1 and LAG-3 checkpoint blockade. We therefore plan to initiate a lead-in module to evaluate the activity of both anoblatuzumab plus MgAO12 and anoblatuzumab plus MgDO13 as chemotherapy-free regimens in first-line patients with recurrent and metastatic head and neck cancer before proceeding with one of these combinations in a future Phase II-III study.
With these milestones we anticipate a productive year ahead and look forward to continued progress.
We would now be happy to address any questions that callers may have operator.
Yes. Good question, please touch star one.
The first question comes from damaging try to patio of H.C. Wainwright. Your line is open.
Good afternoon, guys. A this is really cool and edge. It can you hear me.
Yes, Yes, Hi, Earl.
Hey, so.
Couple of questions My mind, the first is on M.D.A. they'll one three.
When should we expect that data that morning, HCR or ask all things and additionally, what threshold of activity do you think is both compelling and convincing from single arm study.
Second question, we have is regarding.
The big step in and.
You know you guys you mentioned something about the commercial launch and wanted to know.
How do you see this adoption of March and Oh, Yes, the 201 world.
And if we could squeeze one more it's regarding located to them that.
Any further updates on the regulatory dialogue and it's the plan still single arm expansion Court and primary fabry patients.
The registration study. Thank you so much.
Scott Koenig: Finally, in 2020, we anticipate completing phase one dose escalation of MGC018, our antibody drug conjugate targeting B7H3, as well as for MGD019, a biospecific DART molecule targeting PD-1 and CTLA-4. We plan to submit data from the dose escalation cohorts for both molecules for presentation at scientific conferences in 2020. In addition, once we complete dose escalation, we are planning to initiate a focused dose expansion study for each molecule in one or more select tumor types. While the initial data sets are small, we are encouraged by the progress in these studies to date, and we look forward to sharing data from both of these programs in 2020. In summary, 2019 was an important year for macrogenics with the submission of our BLA-fomargine toxin map for HER2-positive breast cancer.
Well. Thanks, so much girl, so M.D.D.O. 13, the PD one by lag three we submitted abstracts to ask go obviously, we'll have to wait to hear the response, but given.
The content, we have placed in the abstract which included.
The dose escalation.
Of the molecule as well as expansion into a.
Multiple cohorts composed of nine different tumor types that where we've treated over 150 patients. We expect obviously our opportunity inform the present that data with regard to the specific threshold that we would expect to be acceptable it varies greatly from tumor <unk>.
Tumor well, what we've incorporated in this study.
Our.
To a patient that have Oh, we see previous checkpoint ones that were naive to a checkpoint treatment in some cases, we've also had.
Scott Koenig: Marjorie Tuckson-Ab is also being evaluated in combination with checkpoint blockade in a registration-directed clinical study in advanced HER2-positive gastric cancer. During 2020, we anticipate additional key events. We intend to define a registration path for protozumab in refractory AML pending further discussion with the FDA. We also look forward to presenting initial clinical data from several of our Phase I programs, including MGD-013, MGD-019, and MGC-018. With these milestones, we anticipate a productive year ahead and look forward to continued progress. We would now be happy to address any questions that callers may have. Operator.
I'm limited studies in combination therapy. So it varies from 200 tumor type and so you'll have to wait until the meeting who says that data set.
With regard to the second question.
The BLE accepted them and commercial launch.
And how you think that's how we think this will be adopted a in the post 82 or one world.
As we have shown previously and and discuss the merits of the merger talks and that we're actually very excited for the opportunity for patients to have access to a molecule like margin talks about obviously if it gets.
Approved by the F.D.A. first of all this is the only head to head study than it's ever been tested.
Again tries to the map and the having shown successfully in a statistically significant matter.
Operator: To ask a question, please touch star 1. The first question comes from Debjee Tadipadhyay of HC Wayne.
PFS benefit of this molecule and trending.
In the West benefited a merger talks about over of of March that's not all but try to the Matt We think again, the oh well to patients and the treating physician a great opportunity tool to give the patient.
Unknown Caller: Your line is open. Good afternoon, guys. This is Erroll DeHoover at Skagegit. Can you hear me? Yes, yes. Hi, Errol.
Unknown Caller: Hey, so a couple of questions from our end. The first is on MGA 013. When should we expect that data? Is that more at AACR or ASCO events? And additionally, what threshold of activity do you think is both compelling and convincing from single-arm studies? The second question we have is regarding BLA acceptance, and you guys mentioned something about the commercial launch and wanted to know... How do you see this adoption of Marge in the post-DSA201 world? And if we could squeeze one more question in, it's regarding Lote Thusimath. Any further updates on the regulatory dialogue, and is the plan still a single-arm expansion core in primary factory patients as a registration study? Thank you so much.
A better treatment selection in particular given that this was tested in four different the in combination with four different chemotherapy.
Depending on the historical treatment regimens. These patients every seat it gives optionality or where they may not have it under other conditions and we expect <unk> I'm in the case of 82 or one while the <unk>. The response of patients was quite remarkable.
Fortunately many of these patients will progress on.
Their treatment and as a result will need additional options.
With regard to uploaded to the mab and updates in the regulatory dialogue as we had previously noted we had the interaction with the FDA. This past September we discuss the opportunity to the devised a clinical.
Scott Koenig: Thanks so much, Errol. So, MGD013, the PD-1 biological 3, we submitted abstracts to ASCO. Obviously, we'll have to wait to hear the response, but given the content we included in the abstract, which included the dose escalation of the molecule as well as expansion into multiple cohorts composed of nine different tumor types, where we've treated over 150 patients, we expect, obviously, an opportunity in a forum to present that data. With regard to the specific threshold that we would expect to be acceptable, it varies greatly from tumor to tumor.
Plan.
Focused on the refractory population.
The F.D.A. a agreed with US that this is a population where there is a clear need they had asked us for additional data, which were supplying to them expect to have some additional dialogue in the first half of this here and our plan is to be able to update.
Everyone by mid year on those discussions and next steps going forward in the interim we are continuing to enroll patients I'm using a the dosing regimen that we discussed at ash in December to increase.
Scott Koenig: What we've incorporated in this study are patients that have received previous checkpoints, ones that were naive to checkpoint treatment. In some cases, we've also had some limited studies in combination therapy, so it varies from tumor to tumor type. And so you'll have to wait until the meeting to assess that data set.
The number of patients that could potentially benefit from floated to isn't that with regard to the design of the specific.
Study clearly a a single arm study would be optimal given that these patients have failed multiple lines of a high dose chemotherapy and hypomethylating agent treatment as well as directed therapy, but again this will be a part of the conversation we.
Scott Koenig: With regard to the second question, the BLA acceptance and commercial launch and how you think this, how we think this will be adopted in the post-8201 world. As we have discussed previously and discussed the merits of margituximab, we're actually very excited for the opportunity for patients to have access to a molecule like margituximab, obviously, if it gets approved by the FDA. First of all, this is the only head-to-head study that has ever been tested against trastuzumab, and having shown successfully in a statistically significant manner a PFS benefit of this molecule and trending in the OS benefit of margituximab over trastuzumab, we think it gives both the patient and the treating physician a great opportunity to give the patient a better treatment selection.
With the FDA and the ultimate design of the molecule.
Thank you so much huh.
[noise]. Thank your next question comes from more of Cantor Fitzgerald.
I'm sorry.
Hey, good evening, everyone and thanks for taking the questions. It's focused on lot it to the map.
Any regulatory discussion ongoing around safety profile and specifically around the leading dosing strategy. Scott if you can provide some color.
So there is you know been multiple conversations over the years, a with regarding the dosing strategy and clearly as you have seen the evolution of this molecule. We have evolve this strategy. So that we've optimized the lead and adult.
Singing up in the first week of of treatment to achieve the targeted dose of 500 nanograms per gig in subsequent treatment during the three weeks of the first cycle of therapy.
Scott Koenig: In particular, given that this was tested in four different combinations, in combination with four different chemotherapies, depending on the historical treatment regimens these patients had received, it gives patients optionality where they may not have it under other conditions. And we expect, in the case of 8201, while the response of patients was quite remarkable, unfortunately, many of these patients will progress on their treatment and, as a result, will need additional options. With regard to Aflodituzumab and updates in the regulatory dialogue, as we have previously noted, we had an interaction with the FDA this past September. We discussed the opportunity to devise a clinical plan focused on the refractory population. The FDA agreed with us that this is a population where there is a clear need.
We've also implemented in the subsequent cycles of therapy continue dosing of the drugs. We have found that if you do not interrupt dosing of the likelihood of having any further cytokine release associated with drug is dramatically reduced.
And then what we said we have seen that a this is a very favorable profile for the drug.
So so far we will nothing further to discuss with regard to the safety profile. We are continuing to provide additional data which includes the safety analysis of patients that have been treated historically and an hour on going treatment.
We expect obviously to the has that as part of our updated discussion with the up the shortly.
Thank you Scott and I wanted to follow up on 013, and a PD one lakh three program.
You know given to target a PD, one and lack of three.
I just wanted to understand if there will be supporting data at the conference or when you put it ended up you know the initial data, which can potentially highlight contribution coming from PD, one or lack suite.
Scott Koenig: They asked us for additional data, which we're supplying to them. We expect to have some additional dialogue in the first half of this year, and our plan is to be able to update everyone by midyear on those discussions and next steps going forward. In the interim, we are continuing to enroll patients using the dosing regimens that we discussed at ASH in December to increase the number of patients that could potentially benefit from Aflodituzumab. With regard to the design of the specific study, clearly, a single-arm study would be optimal given that these patients have failed multiple lines of high-dose chemotherapy and hypermethylating agent treatments as well as directed therapy. But, again, this will be a part of the conversation we have with the FDA in the ultimate design of the molecule.
So in that regard you know we don't have obviously as separate lag three anti body. This is a a composite molecule. We're evaluating these both in.
Checkpoint or anti PD, one or anti PD L. One experienced patients as well as naive patients well, we will try to do and you know I don't know by the time at school occurred what do we have a full comprehensive data is that we are analyzing.
Specimens for bearing lag levels of black three expression in patients treated and we'll try to obviously come to some conclusions.
With the value of either threshold level, the blackberry expression or or ultimate percentage of like three expression in the tumors and its association with ultimate responsiveness I think that's probably the best we'll be able to provide in this timeframe.
Scott Koenig: Thank you. Our next question comes from Varun Kumar of Cantor Fitzgerald. Your line is open. First, on Float It to the Map, are there any regulatory discussions ongoing around the safety profile and specifically around the lead-in dosing strategy? Scott, if you can provide some color.
On thank you very much God and maybe last one if I may on the financial guidance.
You know you talked about the cash runway could go into 2022.
You know going forward should we expect any advanced program to be impacted by.
Scott Koenig: So, there's, you know, been multiple conversations over the years with regard to the dosing strategy. And clearly, as you have seen the evolution of this molecule, we have evolved this strategy so that we've optimized the lead-in dosing in the first week of treatment to achieve the targeted dose of 500 nanograms per kg in subsequent treatment during the three weeks of the first cycle of therapy. We've also implemented continued dosing of the drug in subsequent cycles of therapy. We have found that if you do not interrupt dosing, the likelihood of having any further cytokine release associated with the drug is dramatically reduced. And we have seen that this is a very favorable profile for the drug. So far, we will have nothing further to discuss with regard to the safety profile. We are continuing to provide additional data, which includes the safety analysis of patients that have been treated historically and our ongoing treatment, but we expect, obviously, to have that as part of our updated discussion with the FDA shortly.
Reprioritizing in different programs to extend the cash runway.
Well again, obviously, we can anticipate everything in the future, but I think as we've laid out just before the JP Morgan me I'm eating a prioritization and the program taking into account.
Timing for the enrollment rates for the various programs as I think we've highlighted they focus on the module a in the gastric study and a delay in the phase three study for no Bluetooth Susan that has afforded us.
Additional cash to continue on without program.
As Jim has pointed out through 2021 and as we're hoping.
As we analyze the the spend over the course of the next few months that this may allow us to get into 2022. So at this point, we don't see any further need to modify the plans for the the studies going forward.
Thank you very much Scott and come back on the progress.
Thank you.
Thank you. Our next question comes from Jonathan Miller Evercore. Your line is open.
Scott Koenig: Thank you, Scott. And I wanted to follow up on 013, the PD-1 LAC-3 program. You know, given two top
Hi, guys. Thanks, so much for taking my question and congrats on the recent progress.
Scott Koenig: to target PD-1 and LAG-3.
I would like to focus first on the mahogany trial, you said initial data second half. This year is your expectation that that potentially registration little our artisan assuming module a is as good as you hope it is would be get that potentially registration lower aren't second half this year or some other I'm not sure update a then I'd like to ask about the PD.
Scott Koenig: I just wanted to understand if there will be supporting data at the conference when you present the initial data, which can potentially highlight contributions coming from PD-1 or LAC-3?
Scott Koenig: So in that regard, you know, we don't obviously have a separate LAG-3 antibody. This is a composite molecule.
One CTO like four by specific which I think it's an interesting one that seems to be down your list of priorities <unk> priorities. What's your what's the next steps there and is it possible, we'll see that just escalation data maybe at ASCO. This year alongside the PD one lag three by specific.
Scott Koenig: We're evaluating these both in checkpoint or anti-PD-1 or anti-PD-L1-experienced patients, as well as naive patients. What we will try to do, and, you know, I don't know by the time ASCO occurs whether we will have a full comprehensive data set, but we are analyzing specimens for varying levels of LAG-3 expression in patients treated, and we'll try to obviously come to some conclusions about the value of either threshold levels of LAG-3 expression or ultimate percentage of LAG-3 expression in the tumors and its association with ultimate responsiveness. I think that's probably the best we'll be able to provide in this time frame.
Last thing I guess I'll ask for is a any other plans and the flooded using that PD. One combo, you've mentioned you're doing that study ex U.S., but that you had said on the Q3 called <unk> that could potentially expanding and become a larger programs or what are your next steps with fluid combos, a as we look forward to.
Scott Koenig: Thank you very much, Scott. And maybe last one, if I may, on the financial guidance. You talked about the cash runway that could go into 2022. Going forward, should we expect any advanced programs to be impacted by reprioritizing different programs to extend the cash runway?
FDA meeting for the monotherapy.
Thanks to those questions John So with regard to mahogany you know, we just began late last year to enroll in that study.
We are selecting is as you note in that module a is the her two or three plus by I'd see PDL, one positive one 1% or greater obviously, there's some degree of screening failures, we're expanding the number of sites going forward.
Scott Koenig: Well, again, obviously, we can't anticipate everything in the future, but I think, as we laid out just before the J.P. Morgan meeting, a prioritization of the program, taking into account timing for enrollment rates for the various programs. As I think we've highlighted, the focus on Module A in the gastric study and a delay in the Phase II-III study for enoblituzumab has afforded us additional cash to continue with our programs, as Jim has pointed out, through 2021, and as we're hoping, as we analyze the spend over the course of the next few months, that this may allow us to get into 2022. So, at this point, we don't see any further need to modify the plans for the studies going forward.
As noted in our various briefing books. Our initial goal that we had laid out was to enroll up to 40 patients to be able to be making assessment or whether we're hitting the target of overall response and what we have put out.
Previously is that we like the obviously hit what the Togo is in terms of overall response rate or greater just to refresh your memory was about 47% in the telco regimen and obviously you have a better safety profile, we think that with less than 40 patients will be able to make.
The assessment.
Whether the response rate is adequate enough to try to accelerate the can continued enrollment.
Scott Koenig: Thank you very much, Scott. And congrats on the problem solved. Thank you.
Through 2021, if we hit those milestones.
Operator: Thank you. Our next question comes from Jonathan Miller of Evercore. Your line is open.
We feel that we can get that fully enrolled them by the end of a a 2021, but clearly 'em we walked through a good start a this year. It obviously takes time to continue to evaluate the patient and it observed them. So clearly the hope is is that in the first half this year, we will enroll enough.
Jonathan Miller: Hi guys, thanks so much for taking my question and congrats on the recent progress. I would like to focus first on the mahogany trial. You said initial data would be second half this year. Is your expectation that that potentially registrational ORR, I'm assuming module A is as good as you hope it is, would we get that potentially registrational ORR in the second half this year or some other lesser update? Then I'd like to ask about the PD-1 CTLA-4 bi-specific, which I think is an interesting one that seems to be down your list of priorities. What are your next steps in that regard?
Patients to be able to make that decision in the second half of this year.
With regard to the PD, one C.P. delay for.
Priorities and dose escalation and are we gonna presented at.
At ASCO, what I mentioned, just before JP Morgan meeting we had.
Done a dose escalation of the molecule our targeted top dose was 10 megs per keurig, we achieved that a quite successfully we've seen objective responses in a multiple tumor types and so with a very good.
Scott Koenig: And if possible, we'll see that dose escalation data maybe at ASCO this year alongside the PD-1 lag-3 bi-specific. The last thing I guess I'll ask for is any other plans for the floated PD-1 combo. You've mentioned you're doing that study at QS, but you had said on the Q3 call that that could potentially expand and become a larger program. What are your next steps with floatated combos as we look forward to the FDA meeting for monotherapy?
Good safety profile now that seems quite comparable to single anti PD. One therapies, we obviously want to get a broader experience now with this molecule in ER and or at the higher those we're also exploring a different.
Scott Koenig: Thanks for those questions, John. So with regard to mahogany, you know, we just began late last year to enroll in that study. You know, what we are selecting is, as you note in that module A, the HER2 3 plus by IHC PD-L1 positive 1% or greater. Obviously, there's some degree of screening failures. We are expanding the number of sites going forward. As noted in our various briefing books, our initial goal that we had laid out was to enroll up to 40 patients to be able to make an assessment of whether we're hitting the target of overall response. And what we have put out previously is that we like to obviously hit what TOGA is in terms of overall response rate or greater. And just to refresh your memory, it was about 47% in the TOGA regimen and obviously has a better safety profile.
Biomarkers that may give us insights on further future activity of this molecule. Our plan is is completing out this dose escalation study a with expansion with multiple tumor types or sort of an all commerce study and then starts.
Secondly, pick one or a maximum of two tumor types that we will expand into.
We did not submit a abstract at ASCO for this but we are planning up probably in the second half of the year, providing at a scientific meeting other data that we've generated to date and we'll continue to generate over the next few months.
With regard to floated to the map the ongoing study with anti PD, one is ongoing and a three countries. It's a in Australia, Spain and Israel, we are in various dose escalation of phase.
Scott Koenig: We think that with less than 40 patients, we'll be able to make an assessment of whether the response rate is adequate enough to try to accelerate continued enrollment through 2021. If we hit those milestones, we feel that we can get that fully enrolled by the end of 2021. But clearly, we're off to a good start this year. It obviously takes time to continue to evaluate the patient and observe them. So clearly, the hope is that in the first half of this year, we will enroll enough patients to be able to make that decision in the second half of this year.
Is that study, we started out with a little lower doses.
To make sure that we didn't see a increase safety signal, which we haven't seen today I plan is to continue to expand in those countries and it is our plan also to eventually get U.S. sites involved as well.
Scott Koenig: With regard to the PD-1 CTLA-4 priorities and dose escalation, and whether we are going to present it at ASCO, as I mentioned just before the JP Morgan meeting, we had done a dose escalation of the molecule. Our targeted top dose was 10 mg per kg, and we achieved that quite successfully.
Some something or that we intend to do it in this year. So that's kind of where we are would that molecule.
Great. Thank you very much.
[noise]. Thank you My next question comes from Christopher.
<unk>.
Your line is open.
Hey, Thanks for taking my question just one for me here on N. G. T O 18, you're a or B seven age Threeeighty see I'm. Just wondering if you could tell you will further elaborate on the type of data that we might see here from the initial dose escalation obviously safety.
Scott Koenig: We've seen objective responses in multiple tumor types, and so with a very good safety profile now that seems quite comparable to single anti-PD-1 therapies, we obviously want to get broader experience now with this molecule at the highest dose. We're also exploring different biomarkers that may give us insights into further future activity of this molecule. Our plan is to complete this dose escalation study with expansion with multiple tumor types, sort of an all-comer study, and then subsequently pick one or a maximum of two tumor types that we will expand into. We did not submit an abstract to ASCO for this, but we are planning, probably in the second half of the year, to present at a scientific meeting the data that we've generated to date and will continue to generate over the next few months.
And then maybe the potential chance for efficacy data.
With regard to safety could you also perhaps help us understand.
The toxicities you might expect from the the pay though the anything there.
And.
And try to help set up my expectations around that thank you.
Thanks, Chris.
So with regard to where we are on this molecule as I had outlined previously in January.
We went through what we are in the middle of dose escalation.
We are in and the in mics per kilo dosing range, which was the expected range, where we would begin to see biological activity, which I had indicated we have observed in a different tumor types second is.
Scott Koenig: With regard to flotatuzumab, the ongoing study with anti-PD-1 is ongoing in three countries. It's in Australia, Spain, and Israel. In various dose escalation phases of that study, we start out with lower doses to make sure that we don't see an increased safety signal, which we haven't seen to date. Our plan is to continue to expand in those countries, and it is our plan also to eventually get U.S. sites involved as well. It's something that we intend to do this year. So that's kind of where we are with that molecule.
With the safety that we've seen to date again with a limited number of patients it appears to be quite acceptable and tolerable.
The intended toxicity is already it's possible expected toxicities that one sees with this particular payload or the door for myosin, which is a incorporated in a another molecule that since on developing for her to therapy.
Scott Koenig: Great, thank you very much. Thank you. Our next question comes from Christopher Mirai of the Nomura Institute. Your line is... Hey, thanks for taking the question. Just one for me here on MGC018, your B7H3ADC. I was wondering if you could, you know, further elaborate on the type of data that we might see here from the initial dose escalation, obviously, some safety, and then maybe the potential chance for efficacy data. But with regard to safety, could you also perhaps help us understand the toxicities you might expect from the payload that you're using there and sort of help set expectations around that? Thank you.
Their major toxicity that was observed was orphan reported for other 80 sees which was I toxicity car types and such I have to say, we haven't seen much in terms of a problems with ER I today and so again.
Our experiences on a limited number of patients we will a plan to provide an update 'em a mid year to the second half of this year on this study and because this is an 80 see molecule single agent activity should be expected and we would.
Scott Koenig: Thanks, Chris. So, with regard to where we are on this molecule, as I had outlined previously in January, we went through, while we were in the middle of dose escalation, we are in the mixed-per-kig dosing range, which was the expected range where we would begin to see biological activity, which I have indicated we have observed in different tumor types. Second, with the safety that we've seen to date, again, with a limited number of patients, it appears to be quite acceptable and tolerable. The intended toxicities, or the possible expected toxicities, that one sees with this particular payload, duochromycin, which is incorporated in another molecule that Synthon is developing for HER2 therapy, their major toxicity that was observed was often reported for other ADCs, which was eye toxicity, keratitis, and such.
I didn't tend to advance this forward, though likely in one major tumor type or possibly too.
Okay, and then regarding the tumor types that you're looking at did you do just sort of like a tumors that that express piece at an age three highly I know many too are there any there that that macrogenics is looking at to prioritize development.
Pending data thank you.
Rather then opening up and revealing at this point, whereas we have our priority list, but I think it's still too early to be definitive about this we will update. This later this year.
Thank you.
Thank you My next question comes from.
Some of it.
Citi. Your line is open.
Scott Koenig: I have to say, we haven't seen much in terms of problems with the eye to date. And so, again, our experience is with a limited number of patients. We will plan to provide an update mid-year to the second half of this year on this study. And because this is an ADC molecule, single-agent activity should be expected, and we would intend to advance this forward likely in one major tumor type or possibly two.
I see a call. Thanks very much for taking my question and decision 10 men that you know, but isn't that child to include a they didn't tell her combination I am GT, one screen NMG D O one tail.
I Wonder if you could elaborate more it's not everything you believe engine deal I'm pretty may potentially be better combo with you know buttress the mom and is it known what expression of Blackberry is among patients with head and neck cancer.
Scott Koenig: Okay, and then regarding the tumor types that you're looking at, did you sort of look at tumors that express B7H3 highly? I know many do. Are there any there that MacroGenics is looking at to prioritize development in, you know, pending data? Thank you.
[noise]. So yes. Thank you very much without question you know that's why we're doing this lead in a module testing them. We had seen as we've indicated activity cause a number of tumor types, including head and neck cancer.
Scott Koenig: Rather than opening up and revealing at this point, we have our priority list, but I think it's still too early to be definitive about this. We will update this later this year.
We had analyzed our own a set of specimens and there was also reported the published a work on legs, we expression in head and neck cancers, and it turns out to have expression that in a in a sizable portion of the population. So.
Yigal Dov Nochomovitz: Thank you. Thank you. Our next question comes from Yigal Nochomovitz of Citi. Your line is open. Thanks very much for taking our questions. On the decision to amend the enoblatuzumab trial to include leading cohorts for combination with MgD-013 and MgD-012, I wonder if you could elaborate more on some of the reasons that you believe MgD-013 may potentially be a better combination with enoblatuzumab, and is it known what the expression of LAG-3 is among patients with head and neck
Rather than diving in with the the old one too given the advancement of the on one three program, we thought rather than.
Doing a phase two three study and kicking ourselves afterwards, so not a testing on one three we thought it would be I'm much more effective.
Scott Koenig: So, yes, thank you very much for that question. You know, that's why we're doing this lead-in module testing. We have seen, as we've indicated, activity across a number of tumor types, including head and neck cancer. We have analyzed our own set of specimens, and there is also published work on LAG-3 expression in head and neck cancers, and it turns out to have expression in a sizable portion of the population.
Testing on one versus the other and the other point is is that Oh, one too as you know is partner with inside where except for China rights 'em, we own a one three so again, a being able to combine the two a barrel Myles.
Scott Koenig: So rather than diving in with the O1-2, given the progress of the O1-3 program, we thought rather than do a phase 2-3 study and kicking ourselves afterwards for not testing O1-3, we thought it would be much more effective to test one versus the other. And the other point is that O1-2, as you know, is partnered with Insight, where, except for Chinese rights, we own O1-3. So again, being able to combine two of our own molecules together if the efficacy and safety look more favorable than O1-2 would make the most sense to us.
Fuel together, if the efficacy and safety looks a more favorable than a one to would make the most and stuff.
Thanks, that's very helpful. And then it came to MGT on screen without revealing the types of tumors that you have on your priority list I Wonder if you could just gives me the color on what your thought process was for what Chuck E. tumor type you will be advancing.
What's the threshold.
Hi, broadly and is that potential for monotherapy only or would you advancing somebody's tumor type at the potential combination as well.
Scott Koenig: Thanks. That's very helpful. And then sticking to MGD-013, without, you know, revealing the types of tumors that you have on your priority list, I wonder if you could just give maybe a bit more color on what your thought process was for which of the tumor types you would be advancing. You know, what was the threshold that you had broadly, and is there potential for monotherapy only, or would you advance some of these tumor types as a potential combination?
Thanks for the question. So again, we had gone to the literature to look at levels with expression.
Have a lag three across all solid tumor types as well as a lymphomas.
And obviously the reported literature had varying grades of expression, we did our own pathology work in house to evaluate a very large number of tumor said and I know in large part many of them were or similar to what had been previously reported.
Scott Koenig: Thanks for the question. Again, we went to the literature to look at levels of expression of LAG-3 across all solid tumor types, as well as lymphomas. And obviously, the reported literature had varying grades of expression. We did our own pathology work in-house to evaluate a very large number of tumor sets, and in a large part, many of them were similar to what had been previously reported.
What should be a interest it what is also interesting just as a set aside.
In addition to all Upregulation of lack the expression on immune cells, which include T cells and and NK cells. There are certain tumor types that also upregulate lead free expression and so again without giving you any guidance right now we'll have to wait to data.
Presented at ASCO, we plan to focus on a specific tumors, where we've seen a responsiveness and correlate that with the Biomarkers that we are I'm working on in terms of I T X expression patterns.
Scott Koenig: What should be interesting...what is also interesting, just as an aside, in addition to upregulation of LAG-3 expression on immune cells, which include T cells and NK cells, And so, again, without giving you any guidance right now, we'll have to wait until data presented at ASCO. We plan to focus on specific tumors where we've seen responsiveness and correlate that with the biomarkers that we are working on in terms of IHC expression patterns. With regard to how we will proceed with this, we look at this both as monotherapy in certain tumor types, but we have also explored in a more limited fashion the combination of O13 with other molecules in our portfolio. And clearly, the opportunity here is to combine it with other modes of therapy, which can include both immune therapeutics, chemotherapy, and targeted agents as well.
With regard to on how we will proceed with US we look at this both as monotherapy in certain tumor type, but we have also explore to know more limited fashion. The combination of one three a with the other molecules in our portfolio and I'm clearly the.
The opportunity here is to combine it with other modes, the therapy, which and can include both immune therapeutics chemotherapy and targeted agents as well.
Thanks very much question.
Thank you. Your next question comes from.
Your line is open.
Thank you congrats on the progress last year in thank you for taking my questions. I know you touched on this level of that before but can you just help me better understand how you view the commercial opportunity for March and breast cancer and what are you going to plan when do you plan on kind of.
Scott Koenig: Thank you. Hi guys.
Unknown Caller: Thank you. Congratulations on the progress last year, and thank you for taking the time to answer my questions. I know you touched on this a little bit before, but can you just help me better understand the commercial opportunity for MARGE and breast cancer and when are you planning on kind of giving us more details as to how you're thinking about partnering that out? And then, as a follow-up on the MARGE question, can you provide us with any color as to why FDA is requiring the panel ahead of your PDUFA date?
Give me just more details as to how you're thinking about partnering that out and then a follow up on the margin question I'm can you provide us with any color as to why it is requiring the panel I had of your for you for date.
So with regard to the commercial opportunity, we haven't given any guidance with respect to the specific targeted value or and market. Oh. This molecule, obviously with a changing landscape now with 82 and one just launch the likelihood of a tick.
Scott Koenig: So, with regard to the commercial opportunity, we haven't given any guidance with respect to the specific targeted value and market of this molecule. Obviously, with the changing landscape now with 8201 just launched, and the likelihood of Ticatnip being launched sometime in the middle of this year, we obviously have to assess the opportunities here. We have done our own marketing analysis.
Well I'm being launched done sometime middle of this year, we obviously have to assess what the opportunities here. We have done around marketing analysis I have to say, it's a quite favorable from my perspective as a company now that would be selling its a or abhi.
The finding a partner to sell the first molecule. So I can't give you any more guidance on that and I think though as the market evolve. This here for the other competing late line drugs will get a better sense of things with regard to details on partnering we had established I'm contacts.
Scott Koenig: I have to say it's quite favorable from our perspective as a company now that would be selling its, or obviously finding a partner to sell the first molecule. So I can't give you any more guidance on that, and I think as the market evolves this year for the other competing late-line drugs, we'll get a better sense of things. With regard to details on partnering, we have established contacts and interactions with a number of companies that have shown interest in margituximab. I would say that given the acceleration of the launch of the competitive molecules and, right now, given the timeliness of the regulatory review of that, I think most of them would want to see the outcomes of both those things before establishing a firm commitment to partner with us.
And interactions with the number of companies that had showed interest in in March we talked about I would say that given the acceleration of the launching of the competitor molecules and right now given the.
Timeliness of the regulatory review of that I think most of them would want to see or the outcomes of both those things up before establishing a a firm commitment to partner with us. So as I've said previously we still engaged.
Scott Koenig: So, as I have said previously, we still engage partners from time to time on this, but we see this as the second half of the year post-ODAC review when we would get more engaged with partnering activity. As Jim pointed out earlier, we've done our homework regarding the marketing of this drug going forward, so whatever partner we end up with, we will be able to provide them with a very significant package with regard to the opportunity. As regard to the FDA panel, it's the FDA's choice to ask whatever questions they want. If I were to speculate on this, it would clearly be that we're still in a...we've achieved a PFS benefit. We still have a...we're in the...haven't received the final OS evaluation for the drug, which will occur at 385 events.
Partners from time to time on is but we see this as a second half for the year post ODAC every view when we would get more engaged with the partnering activity as I as Jim pointed out earlier, we've done our homework with regarding the the marketing Oh this drug.
Going forward so.
Or whatever partner, we end up with 'em, we will be able to provide them with a very significant a package with regard to the opportunity as regards the FDA panel. It's the FDA choice to a asked to whatever question. They want if I want to speculate on this is.
The clearly we're still in a we've achieved a PFS benefit are we still have a we're in the haven't we see the final or west evaluation.
For the drug which will occur at 385 events as you know 'em, we had a pre planned exploratory analysis.
Scott Koenig: As you know, we had a pre-planned exploratory analysis of the epithelial population. If I were to speculate, I think that would be something that the FDA might want to query with regard to the value of following that population or even limiting the drug to use in that epithelial population. I have no insight specifically on what they would query of the ODAC.
Definitely a population if I were to speculate I think that would be or something that the FDA might want to 'em query with regard to the value of of following that population or even limiting the a drug to use in that Oh population, but I have no inside spin.
Typically on a what they would query of the Oh that.
Scott Koenig: And then just a follow-up, I know you touched on this before, but when you talk about Module A of the Phase II-III Mahogany Study, what type of response rates do you want to be seeing to support potential approval?
And then just a follow ups I know you touched on this before but when you talk about the module and the phase two two mahogany study. What's your response rates do you want to do you see to support potential approval.
Scott Koenig: Without being specific to the precision of a single digit, clearly, we would like to achieve a response that is good or better than that of Toga, which was a 47% response rate. If you can achieve that or greater without giving a chemotherapy regimen, given the safety profile of this drug, I think that would be quite favorable. But, of course, that's again a conversation we would have with the FDA.
Without being.
Specific to the precision [laughter] other single digit.
Clearly, we would like to achieve a response, there as good or better than that of Togo, which was a a 47% response rate. If you can achieve that or greater with 'em out, giving a came a chemotherapy regiment.
Given the safety profile of this drug I think that would be quite favorable but of course, that's again a conversation we would have with the FDA.
Unknown Caller: All right, thanks so much for taking the questions. I really appreciate it and congratulations on the progress. Thank you, Thank you. Our next question comes from Stephen Willey of Stiefel. Your line is open.
Alright, thanks, so much for taking the questions I really appreciate it and congrats on the progress.
Thank you.
Thank you. Our next question comes from Stephen Willey of Stifel. Your line is open.
Stephen Douglas Willey: Yeah, good afternoon. Thanks for taking the questions. Just a couple of questions on the Xilab trial. Is the incidence of the CB16 AF allele carrier status the same in Chinese patients as it is in the U.S.? I'm guessing this is a study that's looking at efficacy as a function of intent to treat, but can you also just speak to whether or not they're also trying to carve out from a secondary endpoint perspective activity within the FLEL population specifically?
Yeah, good afternoon, and thanks for taking the questions.
Couple of questions on the xylem trial its is.
Is the incidence of the CD sixteena ethylene ill carrier status the same in Chinese patients as it is in the U.S. and.
I'm guessing. This is the study that's looking at that efficacy is a function of intend to treat but can you also just speak to whether or not there also trying to carve out from a secondary endpoint perspective.
Activity within the affiliate population specifically.
Oh, Thanks for the question Steve.
Scott Koenig: Thanks for the question, Steve. Worldwide, there is minor variation in terms of CD16 allelic variation, but we're talking about a 5% or so difference from one ethnic group to another. So what we have seen in our study, which included, as you know, patients and careers in our study, 86% had the F allele. So, you know, in reported literature, it goes from essentially around 80% to 85%, so maybe some minor local variation, but I don't expect it to deviate much. The plan really for this study, as I understand it, is a bridging study to SOFIA, so they're looking at the opportunity to treat in combination with chemotherapy and looking at response rates overall and intent to treat, but I think they also plan retrospectively to look at the F allele subsets as well. Having not seen their submission specifically, I can't give you any more definitive plans with regard to other secondary endpoints.
Worldwide, they're minor variation in terms of C.D. 16, I'm, a little variation, but we're talking about a 5% or so I'm a difference from a one ethnic group to another so what we have seen.
In our study, which included as you know patients in Korea or in our study there was 86% had the f. fulfill so you know in reported literature. It goes from a essentially around 80% or to the 85%. So maybe.
Some minor local variation, but it only expected to deviate any greatly the plan really from this study as I understand it is they a bridging study to Sofia, so they're looking at the opportunity to.
To treat in combination with chemotherapy and looking at response rates overall and intend to treat but I think they also a plan retrospectively to look at the affiliate <unk> subsets as well, having not seen their submissions specifically I can't.
Have you anymore.
Definitive plans with regard to other secondary endpoints.
Scott Koenig: Okay, and then just a quick question regarding mahogany. I guess if the module data looks favorable, and you go ahead and proceed with additional enrollment, have you guys done any work to look at extending Marge dosing out to Q4W? Just in an effort, I guess, to harmonize with MGAO-12's dosing schedule?
Okay, and then just a quick question regarding mahogany I guess, if if the module data.
It looks to be favorable and you go ahead and proceed with additional enrollment.
Have you guys don't any work to look at extending March dosing out to Q4 W. Just in an effort I guess to harmonize with Mgo 12 dosing schedule.
Scott Koenig: So, we have not looked at Q4, as I recall, in March at this point. But clearly, with regard to different dosing regimens, we have explored different dosing regimens for MgAO-12. And so I do believe it could fit the Q3 weekly dosing if necessary. But right now, I know of no data on Q4 weekly for MgAO-12.
So we have not looked at Q4 as I recall on March at this point, but clearly with regard to different dosing regimens. We are you know.
We have explored and different dosing regimens for Mgo 12, and so I do believe they could that the Q3 weekly dosing if necessary, but right now I know, who Oh no data on on.
Q4 weekly for March.
Stephen Douglas Willey: Okay, thanks for taking the questions. Thank you. Our next question comes from Etzer Darout of Guggenheim Securities. Your question, please.
Okay. Thanks, taking my questions.
Thank you. Your next question comes from answer to rule of Guggenheim Securities. Your question. Please.
[noise] tastes great. Thanks for taking my question just one quick one.
Operator: Hey, thanks for taking my question.
On the.
Etzer Darout: The combination study in gastric cancer. I just wondered if maybe
The combination study in gastric cancer, just wondered if maybe.
Scott Koenig: You can talk a little bit about the sort of PD-1 Lag-Free drug, Nurapirib.
Could talk little bit to those sort of the PD, one like free owner, operator study in China, whether or not there's an opportunity to extend this combination to patients outside of China.
Scott Koenig: whether or not there's an opportunity to extend this.
Scott Koenig: So that, you know, thanks for the question, Etzer. You know, they just filed and just started that study. Given that the rights to Nuraparib are in Xi's hands, and I believe GSK is outside of China, clearly there is opportunity there, but we don't have the ability to pursue that ourselves. So, and clearly, you know, there are other combinations that are being anticipated, other chemotherapies, and other targeted therapies, but if that data is promising, obviously, we would yield the benefit through the insight relationship from the economics there on And clearly, if there's positive data there, other PARP inhibitors could be used in combination with it as well. Great, thanks for that, and congratulations on all the updates.
[laughter], so that I I you know thanks for the question. That's there you know they just filed and just started that study given that the though the rights to know raft River, our enzyme and then I believe the GSK as.
Outside of China play there is opportunity there, but we don't have the ability to pursue that ourselves. So and clearly you know there are other combinations that are being anticipated other chemotherapy than the other targeted therapies, but.
If that data is promising obviously, we would yield the benefit or through the inside the relationship from the economics there on on the PD, one and clearly a if there's positive data there other PARP inhibitors could be using.
Combination with it as well.
Great. Thanks for that Tom and congrats on all the uptick on the progress. Thank you.
Scott Koenig: Thank you. This concludes the question and answer session. I now turn the call back to Dr. Koenig for closing remarks.
This concludes the question and answer session I now turn the call back to Dr. checks for closing remarks.
Scott Koenig: I'd just like to thank everyone again for joining us this afternoon and to let you know that we look forward to continuing to advance our programs in the coming year and providing updates on our progress. Have a nice day.
I just like to thank everyone again for joining us this afternoon and to let you know that we look forward to continuing to advance our programs in the coming here and providing updates on our progress.
Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect. BF-WATCH TV 2021
I have a nice day.
Ladies and gentlemen, this concludes todays conference call. Thank you for participating you may now disconnect.
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