Q4 2021 MacroGenics Inc Earnings Call

Operator: Good afternoon. We'll begin the MacroGenics 2021 4th Quarter Corporate Progress and Financial Results Conference call in just a moment. All participants are in listen-only mode at the moment and we will conduct a question and answer session at the conclusion of the call. At this point, I will turn the call over to Chris James, Vice President of Investor Relations and Corporate Communications of MacroGenics. Thank you, operator.

Good afternoon, we will begin the Macrogenics 2021 fourth quarter corporate progress and financial results conference call in just a moment.

All participants are in 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.

Chris James: Good afternoon, and welcome to MacroGenics conference call to discuss our fourth quarter and full year 2021 financial and operational, For anyone who has not had the chance to review these results, we issued a press release this afternoon outlining today's announcement, which is available under the Investors tab on our website at macrogenics.com. You may also listen to this conference call via our webcast on our website, where it will be archived for 30 days beginning approximately two hours after the call is completed.

Thank you operator, good afternoon, and welcome to Macrogenics conference call to discuss our fourth quarter and full year of 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 todays announcements, which is available under the investors tab on our website at Macrogenics Dot Com you.

You May also listen to this conference call will be webcast on our website, where it will be archived for 30 days beginning approximately two hours. After the call is completed.

Chris James: I'd 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 1994. 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 SBA.

I'd like to alert listeners that todays 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 1095.

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.

Chris James: 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. Thank you, Chris.

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, <unk>, President and Chief Executive Officer of Macrogenics.

Scott Koenig: I'd like to welcome everyone participating via conference call and webcast today. This afternoon I will provide key updates from our clinical programs, but before I do so, let me first turn the call to Jim Karrels, our Chief Financial Officer, who will review our financial results. Thank you, Scott.

Thank you, Chris I would like to welcome everyone participating via conference call and webcast today.

Afternoon, I will provide key updates from our clinical programs, but before I do so let me first turn the call to Jim Carroll, Our Chief Financial Officer, who will review our financial results.

Jim Karrels: This afternoon, MacroGenics reported financial results for the year ended December 31, 2021, which highlight our financial position as well as our recent progress. As described in our press release this afternoon, MacroGenics total revenue, consisting primarily of revenue from collaborative agreements, was $77.4 million for the year ended December 31, 2021, compared to total revenue of $104.9 million for the year ended December 31, 2020. Revenue for the year ended December 31, 2021 included $12.3 million net sales of Margenza, which was launched in March.

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.

Scribed in our press release. This afternoon Macrogenics total revenue consisting primarily of revenue from collaborative agreements with $77 4 million for the year ended December 31 2021.

Compared to total revenue of $104 9 million for the year ended December 31 2020.

Revenue for the year ended December 31, 2021 included $12 $3 million net sales of margins, which was launched in March.

Jim Karrels: 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 related to increased clinical trial and development costs related to MDCO-18, as well as other preclinical molecules and increased clinical expenses related to inoblituzumab and loragirlumab. These increases were partially offset by decreased development and manufacturing costs related to retifamilumab for Insight and decreased clinical costs and VLA support for margituximab 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.

Our research and development expenses were $214 6 million for the year ended December 32021, compared to $193 2 million for the year ended December 31, 2020. The increase was primarily rated it related to increased clinical trial and development costs related to <unk>.

As well as other preclinical molecules and increased clinical expenses related to <unk> map and Laura Gerald amount. These increases were partially offset by decreased development and manufacturing costs related to <unk>, Sam amount insight decreased decreased clinical costs and BLA support for margin tucked Matt.

To the prior year selling.

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.

Jim Karrels: This increase was primarily related to the Mergenza launch, as well as labor-related costs and legal expenses. Our net loss was $202.1 million for the year ended December 31, 2021, compared to a net loss of $129.7 million for the year ended December 31, 2020. 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 MgCO18 in prostate cancer or further expansion of studies currently ongoing. And now, I'll turn the call back to Scott. Thank you, Jim.

This increase was primarily related to the margins at launch as well as labor related costs and legal expenses.

Net loss was $202 $1 million for the year ended December 31, 2021, compared to a net loss of $129 7 million for the year ended December 31 2020.

Our cash cash equivalents in marketable securities balance as of December 31, 2021, with $243 6 million compared to $272 5 million as of December .

Remember 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 or.

Our guidance does not reflect expenditures related to the potential late stage development of <unk> and prostate cancer for further expansion of studies currently.

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

Scott Koenig: I'm encouraged by the progress made during the fourth quarter and our development plans for our B7H3 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, MgCO18, we have prioritized the advancement of MgCO18 and Enobosuzumab, our two programs targeting B7H3, and are taking additional steps to operationalize all aspects of these programs. This included planning for the advancement towards a registration-directed study of MgC-018 in metastatic prostate cancer later this year.

Thank you Jim I'm encouraged by the progress made during the fourth quarter and our development plans for our <unk> III 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 <unk>, we have prioritized the advancement of <unk> and <unk> are two programs targeting <unk> <unk> III and are taking additional steps to operational.

Slide all aspects of these programs.

This included planning for the advancement towards a registration.

<unk> study of MDC <unk> metastatic prostate cancer later this year.

Scott Koenig: Outside of these product candidates, we are moving closer to dosing the first patient with MgD-024, 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 Tevotelumab, a PD-1 by LAG-3 by-specific DART molecule. Beyond these programs, we have significant ongoing preclinical activities to fuel our pipeline of investigational product candidates for the potential treatment of cancer. With that backdrop, let me use this time to walk you through updates on our portfolio of investigational clinical molecules, starting with our molecules targeting B7H3, a member of the B7 family of molecules involved in immune regulation. We are developing two molecules that target B7H3 through complementary mechanisms of action that take advantage of this antigen's broad expression across multiple solid tumor types.

Outside of these product candidates, we are moving closer to dosing the first patients with Mgd <unk> 24, a next generation CD 123 by <unk> Dart molecule for patients with CD 123 positive hematologic malignancies, and working with investigators on the next steps in the development of tableau teller.

<unk>, our PD, one by lag three Bispecific dart molecule.

Beyond these programs, we have significant ongoing preclinical activities to fuel our pipeline of investigational product candidates for the potential treatment of cancer.

With that backdrop, let me use this time to walk you through updates on our portfolio of investigational clinical.

Starting with our molecules targeting <unk> 780, <unk> III, a member of the <unk> family of molecules involved in immune regulation.

We are developing two molecules that target would be 780, <unk> III through complementary mechanisms of action that take advantage of this antigens broad expression across multiple solid tumor types.

Scott Koenig: MGCO-18 is our investigational antibody drug conjugate designed to deliver DNA-oscillating durocomycin cytotoxic payload to tumors expressing B7H3. Recall, in September, we presented an encouraging update of clinical data from our ongoing study of MgCO18 in patients with advanced solid tumors and asthma. We are currently developing plans for a registration-directed study of MGCO-18 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 I-II study data to date, we intend to modify the dose and administration of MGCO-18, potentially including a slightly reduced dose and increasing the 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.

<unk> is our investigational antibody drug conjugate designed to deliver DNA alkylating <unk> cytotoxic payload to tumors expressing <unk> <unk> three.

Recall in September we presented an encouraging update of clinical data from our ongoing study of <unk> in patients with advanced solid tumors at ESMO.

We're currently developing plans for our registration directed study of <unk> 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 <unk> study data to date, we intend to modify the dosing administration of <unk> <unk>.

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.

Scott Koenig: In addition to these next steps for MGCO-18, our Phase I-II 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 further matures. Beyond the ongoing monotherapy study, I am pleased to share that we plan to initiate a combination study of MGC018 and loroduralumab, formerly known as MGD019, in the coming week.

In addition to these next steps for <unk>, our phase <unk> 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 further mature.

Beyond the ongoing monotherapy study I am pleased to share that we plan to initiate a combination study of <unk> and Laura Gerald <unk>, formerly known as <unk> 19 in the coming weeks.

Scott Koenig: The scientific rationale for undertaking this trial is supported by our preclinical data, which suggests that anti-tumor activity with MGCO-18 may be significantly enhanced by combination with an anti-PD-1 agent without meaningful overlapping toxicity. As further support for this combo study, we have seen some interesting initial data from our loroduralimab dose escalation study, of Relevance to the Imminent Combination Study with MGCO-18, I'll share an exciting anecdote on one of the prostate cancer patients from our Dose Escalation Study of Laura Gerlimeth. A patient with metastatic castration-resistant prostate cancer had been on six prior lines of systemic therapy, including chemotherapy, abiriterone, enzalidomide, and cabotetaxel.

The scientific rationale for undertaking this trial is supported by our preclinical data, which suggests that antitumor activity with <unk> may be significantly enhanced like combination with an anti PD, one agent without meaningful overlapping toxicity.

As further support for this combo study we have seen some interesting initial data from our large Laura <unk> dose.

<unk> study.

Our relevance to the imminent combination study with <unk> ill share an exciting anecdote on one of the prostate cancer patients from our dose escalation study of large allomap.

Scott Koenig: 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 his disease and normal PSA after treatment with lorigerolimab. He began treatment with oral gerilimab in December 2019 for 24 weeks, then every six weeks thereafter for a total of just over one year as per protocol. He received his last dose of lorigerlumab in January 2021, and based on a recent update from the investigator, remained in CR with a normal PSA. Medscape has created a profile of this patient within a video they produced regarding bispecific checkpoint molecules. Stories like this tell why we as a company and the industry develop drugs.

A patient with metastatic castration resistant prostate cancer had been on six prior lines of systemic therapy, including chemotherapy aberrant around and <unk> and <unk>.

While patients with metastatic castration resistant prostate cancer has not been particularly responsive to checkpoint inhibition. This individual achieved a confirmed PR with complete resolution of this disease and normal PSA after treatment with larger Allomap Hebei.

He began treatment with larger Allomap in December 2019 for 24 weeks. Then every six weeks thereafter for a total of just over one year as per protocol.

He received his last dose of Lora Gerald <unk> in January 2021, and based on our recent update from the investigator remained in CR with a normal Psa.

Netscape has created a profile this pacing within the video they produced regarding by specific checkpoint molecule.

Stories like this tell why we as a company and the industry develop drugs.

Scott Koenig: Although only a single patient experienced, this patient's story underscores part of our rationale for wanting to study the combination of loroduralumab and MGCO-18 in various solid tumors including prostate cancer. As I mentioned earlier, we expect to initiate a combination study of MGCO-18 and lorogerolimab in patients with solid tumors, including renal cell carcinoma, pancreatic cancer, ovarian cancer, hepatocellular carcinoma, metastatic castration-resistant prostate cancer, and melanoma in the coming weeks. Another of our investigational molecules exploiting the overexpression of B7H3 in solid tumors is inoblituzumab, an FC-engineered antibody created using our FC optimization platform.

Although only a single patient experience. This patient story underscores part of our rationale for wanting to study the combination of lower <unk> and <unk> in various solid tumors, including prostate cancer.

As I mentioned earlier, we expect to initiate a combination study of <unk> and Laura <unk> in patients with solid tumors, including renal cell carcinoma pancreatic cancer ovarian cancer, the <unk> cellular carcinoma, metastatic castration resistant prostate cancer and melanoma in the coming.

<unk>.

Another of our investigational molecules exploiting the overexpression of <unk> III in solid tumors is another to them that an FC engineered antibody created using our FC optimization platform.

Scott Koenig: In March 2021, we initiated a combination study of anoblatuzumab in a chemotherapy-free regimen in frontline squamous cell carcinoma of the head and neck with either tebotelumab for patients who are PD-L1 negative or retifanilumab in patients who are PD-L1 positive.

In March 2021, we initiated a combination study of <unk> and a chemotherapy free regimen in frontline squamous cell carcinoma of the head and neck with either tebo telematics for patients who are PD lone negative.

Red <unk> in patients who are PD lone positive.

Scott Koenig: We expect a 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, our partner in Greater China, announced in December that the Center for Drug Evaluation of China's National Medical Products Administration approved its IND submission for the initiation of a Phase II trial in China for inoblituzumab in combination with pembrolizumab in patients with solid tumors, including non-small cell lung cancer, urothelial carcinoma, and other selected cancers.

We expect to complete enrollment of the PD lone positive patient cohort during the first half of this year and provide an update on this cohort during the second half of the year.

I Mab, our partner in greater China announced in December that the center for drug evaluation of China's National Medical products Administration approved this IND submission for the initiation of a phase II trial in China for a notebook to the Nab in combination with <unk> in patients with solid tumors.

Including non small cell lung cancer, urothelium carcinoma, and other selected cancers.

Scott Koenig: I'll next walk you through our PD-1 based bispecific molecules designed to provide further differentiation from existing PD-1 based options and to enable a broad set of combination options across our portfolio. Lauradrolumab is an investigational bispecific tetravalent dark molecule designed to enable simultaneous and or independent blockade of PD-1 and CTLA-4. We are currently evaluating loroduralimab in a 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 6 mg per kg and expect to provide an update on this study this year. Tebotelumab is our investigational bispecific PD-1-by-LAG-3-DART molecule.

I'll now walk you through our PD, one based bispecific molecules designed to provide further differentiation from existing <unk>.

<unk> PD, one based options and to enable a broad set of combination options across our portfolio.

Laura <unk> is an investigational bispecific tetravalent dart molecule designed to enable simultaneous <unk> independent blockade of PD, one and <unk> four.

We are currently evaluating lora jerald on that in a phase <unk> dose expansion study in patients with microsatellite stable colorectal cancer metastatic castration resistant prostate cancer melanoma and checkpoint naive non small cell lung cancer at a dose of six migs per kid and expect to provide an update.

This study this year.

<unk> is our investigational bispecific PD, one by lag three dart molecule.

Scott Koenig: Tabotelumab was evaluated in a Phase 1-2 dose expansion study in several tumor types and is currently being studied in combination with Enobotuzumab and squamous cell carcinoma of the head and neck. We are formulating plans for potential future development of Tebotelumab and expect to provide an update in the second half of 2022. MacroGenics partner in Greater China, Xi Lab, recently informed the company that it has decided to discontinue development of Tebotelumab for indications it was enrolling in its territory and is evaluating future development plans in other indications.

<unk> was evaluated in a phase one two dose expansion study in several tumor types and is currently being studied in combination with another two the mab and squamous cell carcinoma of the head and neck.

We are formulating plans for potential future development of Tebo telematics and expect to provide an update in the second half of 2022.

Macrogenics partner in Greater China XI lab recently informed the company that has decided to discontinue development of <unk> for indications. It was enrolling in its territory and is evaluating future development plans in other indications.

Scott Koenig: Next up, let me discuss our efforts to advance treatment of patients with CD123-positive hematologic malignancy. We have prioritized the development of MgDO24, our next generation bi-specific CD123 by CD3 DART molecule, which will replace our flow-to-tuzumab development program. MGD024 incorporates a CD3 component designed to minimize cytokine release syndrome while maintaining anti-tumor cytolytic activity and permitting intermittent dosing through a longer half-life.

Next up let me discuss our efforts to advance treatment of patients with CD 123 positive hematologic malignancies.

We have prioritized the development of <unk> for our next generation bi specific CD 123 by CD, three dart molecule, which will replace our floated to the map development program.

<unk> hundred 24 incorporates a CD three component designed to minimize cytokine release syndrome, while maintaining antitumor side of lytic activity and permitting intermittent dosing through a longer half life.

Scott Koenig: At the ASH meeting in December, we presented encouraging preclinical data demonstrating the enhancement of antitumor activity with MgdO24 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 MGD-024 and we expect to begin to enroll patients with relapsed or refractory hematologic malignancies in a Phase I dose escalation study pending IND clearance by the FDA. In a single study evaluating flotatuzumab, our first generation continuous infusion CD123 by CD3DART molecule, in AML patients who are refractory to induction therapy, the interim efficacy analysis threshold was met with manageable safety.

At the Ash meeting in December we presented encouraging preclinical data demonstrating the enhancement of antitumor activity with <unk> 24 in combination with cytarabine and <unk> to standard of care agents used to treat patients with AML.

We announced in November the submission of the IND application for <unk> 24, and we expect to begin to enroll patients with relapsed or refractory hematologic malignancies in the phase one dose escalation study pending IND clearance by the FDA.

And a single study evaluating floated to the mab or first generation continuous infusion CD 123 by CD three dart molecule.

In AML patients, who are refractory to induction therapy. The interim efficacy analysis threshold was met with manageable safety.

Scott Koenig: Nonetheless, we recently made the decision to discontinue the flotatuzumab to prioritize MgDO24, which we believe may have a superior profile. Next, I will provide an update of our product candidates being developed by our collaboration partners for which we have retained certain economic rights. Our second investigational ADC, IMGC0936, which targets ADAM9, a cell surface protein overexpressed in several solid tumor types, is being advanced under a co-development agreement with immunogen.

Nonetheless, we recently made the decision to discontinue the product to the mab to prioritize Mgd <unk> 24, which we believe may have a superior profile.

Next I will provide an update.

Candidates being developed by our collaboration partners for which we retain certain economic right.

Our second investigational ADC <unk> hundred six which targets Adam nine a cell surface protein over expressed in several solid tumor types is being advanced under our co development agreement with immunogen.

Scott Koenig: Under our 50-50 collaboration, Immunogen is leading clinical development, and they have indicated that they anticipate disclosing initial data from a Phase I study in multiple solid tumor types in 2022. Suplizumab is an anti-CD3 monoclonal antibody that was acquired from us by Prevention Bio in 2018. Prevention is developing teplizumab for the treatment of type 1 diabetes. In July 2021, the FDA issued a complete response letter for teplizumab DLA for the delay of clinical type 1 diabetes in at-risk individuals.

Under a 50 50 collaboration Immunogen is leading clinical development and they have indicated that they anticipate disclosing initial data from our phase one study in multiple solid tumor types in 2022.

<unk> is an anti <unk> three monoclonal antibody that was acquired from us by prevention bio in 2018.

Prevention is developing <unk> for the treatment of type one diabetes.

In July 2021, the FDA issued a complete response letter for <unk> BLA for the delay of clinical type one diabetes in at risk individuals.

Scott Koenig: Earlier this week, Prevention announced that they had resubmitted the BLA for teplizumab for the same indication. The BLA resubmission followed Prevention's Type B meeting with the FDA earlier this year. Last, I will provide an update on margituximab. As a reminder, Margenza was launched in the U.S. in March 2021 in coordination with our commercial partner, Eversana.

Earlier, this week prevention announced that they had resubmitted the BLA for <unk> for the same indication.

The BLA Resubmission, followed prevention type B meeting with the FDA earlier this year.

Last I will provide an update on margin toxin that.

As a reminder, my gender was launched in the U S. In March 2021 in coordination with our commercial partner ever sauna.

Scott Koenig: 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 ARGENZA as another marketed metastatic breast cancer therapy option. As reported, net sales were $12.3 million for Margenza in 2021.

Our agenda is approved in combination with chemotherapy for the treatment of adult patients with metastatic <unk> positive breast cancer, who have received two or more prior anti <unk> two regimen at least one of which was for metastatic disease.

We continue to believe patients may benefit from our agenda as another marketed metastatic breast cancer therapy option.

As reported net sales were $12 $3 million for margins in 2021.

Scott Koenig: 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 our margituximab partner in Greater China, Xylab recently informed us that they have decided to discontinue enrollment of Module B of the mahogany study based on their review of both the clinical data and the changing treatment landscape. Recall in November 2021, we announced our decision to discontinue enrollment of Module A of the Mahogany Study.

Given the competitive realities that have taken place in the her two positive breast cancer market, including multiple new approvals, we continue to have modest expectations for margins itself.

In terms of our margin from that partner in Greater China XI lab recently informed us that they have decided to discontinue enrollment of 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 our decision to discontinue enrollment of module a of the mahogany study.

Scott Koenig: With regard to Xi's effort in breast cancer, they announced last month that the China NMPA had accepted the NDA for margituximab in combination with chemotherapy for certain patients with breast cancer. Finally, we look forward to continuing to build momentum and advancing our pipeline of innovative product candidates and sharing our progress with you throughout 2022. We would now be happy to open the call for questions. Operator. If you'd like to ask a question, please press star then 1 on your touchtone telephone. If your question hasn't been answered and you'd like to remove yourself from the queue, press the pound key.

With regard to size the effort in breast cancer, They announced last month that the China and MPA had accepted the NDA for margin tuck the mab 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.

If you'd like to ask a question. Please press Star then one on your Touchstone telephone. If your question has been answered and you'd like to remove yourself from the queue press. The pound key we ask that you. Please limit yourselves to two questions.

Operator: We ask that you please limit yourselves to two questions. Our first question comes from Jonathan Chang with SVB Larynx. Your line is open. Hi guys, this is Faisal Khurshid, I'm for Jonathan, I just wanted to follow up on what you mentioned on MDC 018 and the dosing strategy. Is there any color you provide there?

First question comes from Jonathan Chang with SBB Leerink. Your line is open.

Hi, guys. This is Chris on for Jonathan.

Wanted to follow up on what you meant.

<unk> and <unk> and the dosing strategy is there any color you can provide there like are these lower doses or schedules already being evaluated or something that needs to be done and also how does this factor into your regulatory strategy.

Scott Koenig: Like are these lower doses or schedules already being evaluated or something that needs to be done? And also how does this factor into the regulatory strategy? Thanks very much for the question. After we discussed the results of our data at ESMO and continued to follow the patients, both in prostate cancer as well as the other indications, we did an evaluation of the response rate side effect profile and various pharmacokinetics, both looking at the area under the curve as well as CMAX associated with both responses as well as side effect profiles.

Thanks very much for the question.

After we did.

Discuss the results of our data at ESMO.

And continue to follow the patients both in prostate cancer as well as the other indications we didn't have valuation.

Response rates side effect profile and various pharmacokinetics, both looking at the area under the curve as well as C. Max associated with both responses as well as side effect profiles from that we derived a evaluation of what modifications, we could do with the Doe.

Scott Koenig: From that, we derived an evaluation of what 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-foot syndrome where while we saw most of those patients had grade 1, 2 side effects, we wanted to further mitigate that side effect given the bothersome nature of that effect.

<unk> to maximize the therapeutic response and to minimize the side effect profile in particular, we were interested in the hand foot syndrome, where we saw most of those patients had grade one two side effects. We wanted to further mitigate.

That side effect, given the positive nature.

That effect.

Scott Koenig: We've 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. Thank you so much. That's super helpful. And then if I could just squeeze in one on the combination strategy with larger LIMAB.

We have incorporated that in our plan going forward.

<unk> included that in a briefing document to the FDA.

We will be discussing that plan going forward.

That meeting and after we have a feedback we will provide further insights on how the modification of dose both initial dose and increasing the time between doses.

Might be implemented.

Got it. Thank you so much that's super helpful. And then if I could just squeeze in one on the combination strategy with large orders on that.

What do you see as the benefits of that approach versus pursuing a combo with something like <unk> or an approved checkpoint inhibitor.

Scott Koenig: I guess what do you see as the benefits of that approach versus pursuing a combo with something like a retifan LIMAB or an approved checkpoint inhibitor? First of all, thank you very much for that question. And as we did our analysis of combining MgCl18, the ADC, with anti-PD-1s, including renifanlamab, or alternatively with a combination of our bispecific checkpoint molecules, we saw additional benefit in this particular case of adding the anti-PD-1 and the CTLA-4 blockade.

First of all thank you very much for that question and as we did our analysis of combining <unk> ADC.

Anti PD ones, including where the fan or a mab or alternatively with a combination of our bi specific checkpoint molecules. We saw additional benefit in this particular case of adding the anti PD, one and <unk> four blockade.

Scott Koenig: I should refresh your memory that Bristol-Myers had conducted a study of looking at combinations of epinevo in the setting of metastatic prostate cancer. And while they did not meet their objective endpoints for that study, there was some evidence that the combination of blockade of those two molecules could provide some benefit to patients with metastatic prostate cancer.

I should refresh your memory that Chris.

Bristol Myers has conducted study of looking at combinations of Athene Evo in the setting of metastatic prostate cancer and while though they did not meet their objective endpoint for that study there was some evidence that the combination of blockade of those two molecule.

<unk>.

Could provide some benefit to patients.

With metastatic prostate cancer given that.

Scott Koenig: Given that, and, you know, as you know, we are currently doing a monotherapy study, expansion study, with Laura Gerlman currently right now. As we discussed in this particular call, while very anecdotal of single patient, as you recall, in our dose escalation study, we highlighted one of the patients who achieved a CR, and today provided 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 benefit beyond just an anti-PD-1 blocker to incorporate something that blocks a CTLA-4 axis as well. Got it.

And.

Operator: Thank you so much. Operator, can we have the next question please? Our next question comes from Kaveri Pohlman. BTIG, your line is open. Yeah, good afternoon.

As you know we are currently doing a monotherapy study expansion study.

With larger <unk> currently right now.

As we discussed in this particular call.

While very anecdotal a single patient as you recall in our dose escalation study.

<unk> highlighted one of the patients who achieved a CR and today provide a follow up on that patients were 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 as anti PD one blocker.

To incorporate something that block.

<unk> four.

Accidents as well.

Got it thank you so much.

Yeah.

Operator can we have the next question please.

Our next question comes from cap requirement.

<unk> Your line is open.

Scott Koenig: Thanks for taking my question. For an altitude map, does loss of CD16 expression play any role in its efficacy? And any thoughts on combining this with cytokines like IL-15 or maybe NK cell therapy? Thank you very much for that question, Catherine. So clearly, inovutuzumab was designed to enhance binding to CD16 with a reduced binding to CD32B, like we have characterized for margenza in our approved product. We've observed that the FC modification we've incorporated in inovutuzumab, by engaging CD16 on various immune cells, drives overexpression of gametopheron-associated genes.

Well good afternoon, thanks for taking my question.

And how much of a mob.

That 16 inch expression play any role in its efficacy and any thoughts on combining with cytokines like IL 15, or maybe NK cell therapies.

Scott Koenig: And this results, as a consequence, in upregulation of various cytokines beyond gametopheron, but also upregulation of various checkpoint molecules. Um... And with regard to the use of cytokines in addition, that certainly could be explored. And in addition, there has been interest of combining anoblatuzumab 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. That's helpful, thank you.

Thank you very much for that question together.

Clearly no.

With two the Mab was designed to enhance binding to <unk> 16, with a reduced binding to CD 30 to be likely have characterized for mark gender.

A proved product we've observed that the FC modification, we've incorporated in the nobu to demand.

By engaging CD 16 on various immune cells drive over expression of gamma interferon in associated genes and all results.

As a consequence in upregulation of various cytokines.

Beyond gamma interferon, but also upregulation of various checkpoint molecules.

Yeah.

With regard to.

The use of cytokines in addition.

That certainly could be explored and in addition, there.

There has been interest of combining a.

<unk> done that with our various NK cells, both in vivo and ex vivo.

Other settings, and we are having certain discussions with other parties regarding that possibility. So thank you very much for the question because there.

That's helpful. Thank you and <unk> with Cowen.

Scott Koenig: And for Teva Kalamab, just curious to know your plans for DLBCL and generally I just wanted to get your thoughts on role of PD-1 for this tumor type because there aren't a lot of checkpoint inhibitors in this phase. Thanks again for that question. And as you know quite well, we had very encouraging early data in very late stage 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.

Yes.

<unk> D L Bcl and in generally I just wanted to get your thoughts on Golar PD, one tumor type because there arent a lot of checkpoint inhibitors in this space.

Scott Koenig: As noted today, we should be able to provide updates on the next steps for new trials in potentially the hematologic and solid tumor indications in the second half of this year. With regard to the PD-1, you are absolutely correct. The blockers have not been particularly effective in DLBCL treatments.

Yes, thanks again for that.

And as you know quite well we had very encouraging early data in very late stage patients with <unk>, including those who had.

Received.

<unk> cell therapies.

And as a result, we are exploring the possibility of developing this in at the <unk> line of therapy.

As well as in solid tumors as noted today, we should be able to provide updates on the next steps for for new trials.

Potentially the hematologic and solid tumor indications in the second half of this year with regard to the PD, one you're absolutely correct.

They have not the blockers have not been particularly effective in <unk>.

In the <unk> treatment.

Scott Koenig: I think this is an opportunity by blockading multiple pathways that are involved in exhaustion of cells, one might get an additional beneficial effect in various lymphomas. And so that's some of the rationale of why we're looking at this, not only in DLBCL, but combinations of such in solid tumors as well. Appreciate it. Our next question comes from Etzer Darout with BMO Capital Markets. Your line is open.

I think this is an opportunity by blockading multiple pathways that are involved in exhaustion of cells when it might get a an additional beneficial effect.

In.

Various lymphomas.

And so that's some of the rationale of why we're looking at this not only in <unk>, but combinations of such in solid tumors as well.

I appreciate it.

Our next question comes from Ed said, they're out with BMO capital markets. Your line is open.

Scott Koenig: Great. Thanks for taking the question. The first one for me on the PD-1 CTLA-4 study with MGC-018, just wondered if you had an opportunity to look at that combination preclinically from a tolerability standpoint, given sort of, you know, I think the efficacy argument is clear. Just wanted to know if you had the chance to kind of look at that from a tolerability standpoint.

Great. Thanks for taking the question. The first one for me on the PD one <unk> four study with <unk> just wondered if you had an opportunity to look at that combination pre clinically from a tolerability standpoint, and given sort of weird.

I think the efficacy argument as clear just wanted to know if you've 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 Florida Tusa map just continuation on R&D spend in 2022. Thank you.

Scott Koenig: And then the second question, unrelated, but any meaningful impact of the Flotatuzumab discontinuation on R&D spent in 2022. Thank you. And so thanks so much for the questions. And certainly, as we considered the opportunities of combining a checkpoint with MGCO 18, one of the things paramount in our in our view was, in addition, driving better efficacy was understanding the potential for a safety signal beyond that which we have seen today. From what we are observing, both in terms of our clinical experiences with PD-1, CTLF-4, Lerner-Gerlach as monotherapy, as well as the monotherapy we're getting for MGC018, we see very modest opportunities for the additive or worsening of side effect profiles based on side effects seen to date.

Thanks, so much for the questions and certainly as we considered the opportunities of combining a checkpoint with <unk> one of the things are paramount in our in our view.

<unk> 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, one <unk> journal NAV as monotherapy as well as the monotherapy, we're getting for <unk>, we see very modest.

Opportunities for the.

The additive or <unk> or worsening of side effect profiles based on side effects seen to date. However, one never can predict that one Mike.

Appear in a clinical trial so in a way we are designing this trial and we will get more into this very shortly once the trial get started we have fixed adults.

Scott Koenig: However, one never can predict that one might appear in a clinical trial. So in the way we are designing this trial, and we'll get more into this very shortly once the trial gets started, we have fixed the dose of loriduralumab at the current 6 mg per kg, but starting at a lower dose of the MGC018.

Our general and that at the core.

Six megs per kid, but starting at a lower dose of the <unk> and then we'll dose escalate in a three plus three design for that study to mitigate any.

Scott Koenig: And then we'll dose escalate in a 3 plus 3 design for that study to mitigate any unexpected side effect profiles for the drug. But again, right now, we're hoping that that goes smoothly, and we expect that study to get started in the next few weeks. With regard to flotatuzumab, 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.

Unexpected side effect profiles for the drug, but again right now, we're hoping that that goes smoothly.

And we expect that study to get started in the next few weeks with regard to Florida to the map. We do think that we will get some advantage in terms of reduction of R&D spend.

Scott Koenig: We're obviously just providing that information to investigators, so patients are still on the study right now and will continue some spend in the near term, but we do expect some savings as a result of discontinuing that trial. Great, thank you and thank you for the update today. Our next question comes from Yigal Nochomovitz with Citi. Your line is open. All right, this is Ashik Mubarak, on for you all.

Comment the specifics right now we're obviously just.

Given gathering that information to our investigators so patients are still on the study right now.

And we will continue some spend in the near term, but we do expect some savings as a result of discontinuing that trial.

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

Our next question comes from Yigal <unk> with Citi. Your line is open.

Alright.

Eric on for Yigal, Thanks for taking my questions.

Scott Koenig: Thanks for taking my questions. Can you comment on what drove the decision to discontinue Fluta-Tuzumab? Was there something in the interim analysis that may have contributed, or was it just the emerging profile for MgD024? So, thank you very much for the question, and as we pointed out, we believe, as you've stated, the superior profile of MGD-024 with regard to flotatuzumab for the long-term treatment of patients with hematological malignancies. Certain comments of the following is that, number one, the flotatizumab molecule, as you know, is given as continuous infusion, requires initial hospitalization of patients during the first two weeks before they can go to an outpatient setting.

Can you comment on what drove the decision to discontinue it was there was there something in the interim analysis that that may have contributed or was it just the emerging profile for <unk> four.

So thank.

Thank you very much for the question.

As we pointed out we believe.

As you've stated.

Superior profile of MGE deal.

024, with regard to Florida, Florida Tuesday.

With the long term.

Treatment of patients with Hematological malignancies.

Certain comments following is that number one.

The qualities of that molecule as you know has given us continuous infusion.

Acquired initial hospitalization of patients during the first two weeks before they can go to an outpatient setting.

Scott Koenig: With the design of an FCE-incorporated molecule, plus with the next-generation version of the CD3 component 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 treatment.

With the design of NFC incorporated molecule plus with the next generation version of the CD three components in this molecule.

We believe that this drug can be given more easily intermittently on an outpatient basis technically.

As important.

We expect to have a significant reduction in cytokine release syndrome is a result of treatment on top of that as you know when we started out this study a couple of years ago.

Scott Koenig: 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 risk given the changing landscape, with the final readout here, which will require, obviously, more investment in this current study. But on top of that, if we want to file for European approval, that will certainly require a controlled study.

The treatment regimens.

For AML.

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 the final readout here, which will require obviously significant more investment in this in this current study but on top of that.

If we want to file for European approval that will certainly required a controlled study. So all in all given the superior profile of this molecule plus as we pointed out in the announcement today.

Scott Koenig: 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 ASH meeting, that combinations of MgDL24 plus some standard of care can expand the use of this in early lines of therapy for AML, potentially, plus expanding beyond to other CD123 tumors, we think that our decision was the right one now, given these various aspects, as I described to you. Okay, thank you. If I could sneak in one more.

On data that we have shown at the recent ash meeting that combinations of <unk> 24, plus some standard of care can expand the use of this in earlier lines of therapy for AML potentially plus expanding beyond two other <unk>.

Three tumors, we think that our decision was the right one now.

Giving the given these various aspects as I described described to you.

Scott Koenig: Could you provide any color as to why Xylab chose to discontinue development with Teletelemat? I'm curious if you can share any additional details. I can't at this point in that regard, but let me emphasize, they're not discontinuing. They're discontinuing on the current indications that they were testing. So they're not enrolling any patients in that.

Okay. Thank you.

I could sneak in one more.

Would you provide any color.

<unk> chose to discontinue development with total them up I'm curious if you can share any additional details.

I can't at this point in that regard, but let me emphasize.

Discontinue their just continue on the current.

The indications that they were testing so theyre not enrolling any patients in that they are.

Scott Koenig: They are considering additional indications, and may in the future, as we decide to advance this into additional studies to participate in such studies. It's still up to them, but as of now, it's just that they will not be enrolling any additional patients in the current indications that they've pursued to date. Okay, thank you very much. Our next question comes from Charles Zhu with Guggenheim. Your line is open. Hi, everybody.

Sintering.

Additional indications and may in the future as we decided to advance this into additional studies to participate in such studies, it's up to them, but right now it's just that they will not be enrolling any additional patients in the current.

Indications.

That they pursue today.

Okay. Thank you very much.

Our next question comes from Charles <unk> with Guggenheim. Your line is open.

Hi, everybody. Thanks for taking the question I may have missed this one earlier, but it sounds like Youre melanoma CNBC and it fills the cohorts are fully enrolled for <unk>. How are you evaluating go no go decisions for these indications as data mature waters and what are some of the potential benchmarks on which.

Scott Koenig: Thanks for taking the question. I may have missed this one earlier, but it sounds like your Melanoma, TNBC, and NSLC cohorts are fully enrolled for MGCO-18. How are you evaluating go, no-go decisions for these indications as data mature? What are some of the potential benchmarks on which you would be able to make those decisions?

You would be able to make those decisions.

Decisions and also how should we think about timelines towards those kinds of points.

Points.

Scott Koenig: And also, how should we think about timelines towards those kinds of, you know, Charles, thanks very much for the question. As you recall, and as I've stated on previous calls, these cohorts beyond the prostate are much smaller. We've enrolled, for the ones that have completely enrolled, between 16 to 20 patients in those cohorts, and we're continuing to follow these patients. As I have stated before, given the size of these cohorts, it's still too early to make a decision going forward on which ones we will prioritize for additional, say, phase two or registrational-directed studies.

Thanks very much for the question.

As you recall and as I've stated on previous calls.

These cohorts beyond the prostate.

Are much smaller.

We've enrolled for the ones that have completely enrolled between 16 to 20 patients in those cohorts and we're continuing to follow.

These patients.

As I have stated before given the size of these cohort it's still too early to make a decision going forward.

And which ones we will.

Prioritize for additional state phase III Registrational directed studies.

Scott Koenig: What we expect to do is obviously look at what the standard of care is in these late-aligned 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'd like to see the data mature a little more.

We expect to do is obviously look at what the standard of care is in these late line patients and come to a bulk both EE and assessment of the responsiveness, but in addition and as.

As I pointed out 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 won.

To further test and so given all of this together we.

Like to see the data mature a little more.

Scott Koenig: 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's sort of the plans at this point. Got it, makes sense and thanks for that color.

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 thats sort of the plans at this moment.

Got it makes sense and thanks for that color and if I may just squeeze in one more on <unk> I also kind of wanted to gauge perhaps youll reactions.

Scott Koenig: If I may just squeeze in one more on MGC 018, I also kind of want to gauge, you know, perhaps your reactions, you know, to Daiichi's DSMB 300 data coming out of ASCO-GU and, you know, how or if at all that that weighs in on your thinking for MGC 018, especially when it comes to positioning. Well, thank you, Charles, again. Again, as you know, we feel that we have the right profile to move forward with MGCO-18 in late-stage prostate cancer.

Daiichi as DSM. These 300 data coming out of <unk>.

Or is it all that weighs in on your thinking for <unk>.

When it comes to traditional thanks.

Well, thank you again.

Again.

You know, we feel that we have the right profile to move forward with.

<unk> and late stage prostate cancer it is.

Scott Koenig: It is also nice to see that an organization like Daiichi with expertise in ADCs are interested in pursuing that in this indication. As you know, the toxins that are incorporated in their molecule 7300, as well as ours, target DNA, but are working by different mechanisms.

So nice to see that.

A organization like Daiichi with expertise in Adcs.

Are interested in pursuing that in this indication as you know the toxins that are incorporated them in their molecule suddenly 300, as well as ours target DNA, but are working by different mechanisms.

Scott Koenig: I would say that I am very encouraged by the data in the following sense. It is that the data we've reported in terms of resist criteria at 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've reported to date. And so, overall, I would say we're seeing both companies very encouraging data in the treatment of prostate cancer, which provides further validation for targeting B7H3 with this type of mechanism.

I would say that I'm very encouraged by the data in the following sense is is that.

The data we have reported in terms of the resist criteria at ESMO.

Quite comparable to what they reported at the recent <unk> meeting.

The PS a 50 reductions that we have reported.

Seem to be better than what the data that they've reported to date.

And so overall I would say.

We're seeing both companies very encouraging data in the treatment of prostate cancer, which provides further validation for targeting <unk> 780, <unk> III with this type of mechanism I would say we are also in a <unk>.

Scott Koenig: I would say we're also in a potentially better position now that we're going to start this combination study with our checkpoint molecules, without knowledge that Daiichi has a similar plan in place. So, I think, all in all, I think we will try to advance this as quickly as possible for the benefit of patients. Sounds great.

Potentially.

Better position now that we're going to start this combination study with our checkpoint molecules.

Our knowledge that Daiichi has a similar.

Our plan in place so I think all.

All in all I think we will try to advances as quickly as possible for the benefit of patients.

Scott Koenig: Thanks for taking the question. Our next question comes from John Miller with Evercore. Your line is open.

It sounds great. Thanks for taking the questions.

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

Scott Koenig: Hey guys, thanks for taking my question. I'd like to start with maybe the ADAM-9, which I know is being led by Immunogen, but maybe could you give us some color on what we ought to expect from the data release this year in terms of just tumor types, patient numbers, that sort of thing, and maybe your level of conviction on that program relative to your other internal early-stage candidates? Thanks, John.

Hey, guys. Thanks for taking my question I'd like to start with maybe the Adam nine which I know is being led by immunogen, but maybe could you give us some color on what we ought to expect from the data release. This year in terms of just tumor types patient numbers that sort of thing and maybe your level of conviction on that program relative to your other internal early stage candidates.

Scott Koenig: Good to hear from you. With regard to ADAM9, the correct immunogen is running those clinical trials. They are still in dose finding, doing some additional expansions. That continues.

Thanks, John Good to hear from you with regard to item nine correct.

Immunogen is running those clinical trials.

Scott Koenig: They have not selected a dose 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'll leave it to them and wait until then. So, with regard to where this fits into our portfolio, again, we're very encouraged by the preclinical data until we see the specific dose that's selected and further expansion. It's just too early to comment on that in terms of the prospect overall.

We're still in dose finding.

Doing some additional expansion.

<unk>.

That continues they have not selected the dose for expansion into other tumor types as of yet we expect that should occur in the near term.

So.

With consistent with the guidance that they have provided us.

Do expect to have that dose and be able to announce later this year plans for expansion into specific tumor types the specific types.

I have not been.

Detailed publicly so I'll leave it to them.

Until then so with regard to where this fits into our portfolio again, we're very encouraged.

By the preclinical data until we see.

The specific dose at selected and further expansion. It's just too early to comment on that in terms of the prospect overall as you see as you know except for <unk> 24, we have a lot more data on many of our other programs and have obviously much more encouraged about the prospects.

Scott Koenig: As you know, except for NGD024, we have a lot more data on many of our other programs and have obviously much more courage about the prospects for other things in our portfolio going forward at this time. Okay, and then maybe just to follow up on some of the B7H3 questions that folks have asked, I guess given that we know that the dose is going to come down from three megs a keg already, how should we expect to interpret the expansion cohort data when that does come out?

For other things in our portfolio going forward at.

At this time, Okay, and then maybe just to follow up on some of the disadvantage three questions that you've asked I guess given that we know that the dose is going to come down from $3. A keg already how should we expect to interpret the expansion cohort data when that does come out.

Scott Koenig: 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.

So in that regard.

I will emphasize that the dose is it more of a tweaking of the dose.

As planned right now with regard to slight reductions.

The time interval, but.

Remember as I said the way we evaluated this was actually picking 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 receive.

To make this decision, but surely we would obviously want.

Scott Koenig: But surely, we would obviously want additional confidence by the prospective use of this drug. But right now, I think this is as good as we can do to move forward in the study. Alright, thanks very much, Scott. Thanks. Our next question comes from Stephen Willey with Stiefel. Your line is open.

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.

Alright, thanks, very much Scott.

Thanks, John .

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

Scott Koenig: Yeah, thanks for taking the questions. So maybe just to clarify, then, are you prospectively treating patients at this revised, lower, less frequent dose of MGC 018? Or have you just, I guess, layered this, this dosing regimen into existing patients, that's the Romano treatment. Thanks, Steve.

Yes, thanks for taking the questions.

So maybe just to clarify that are you prospectively treating patients at this revised lower less frequent dosing them she sees or what eight or have you just.

Yes.

Later at this.

Dosing regimens into existing patients that still remains true.

Scott Koenig: We have not started any additional expansions with this proposed modified dose. This will be part of our discussion with the FDA coming up this quarter. And then what our plan would be is to incorporate that alteration in the design of the registration-directed study, if 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. Okay, so I guess you don't feel the need to do any, any bridging work and you'd be comfortable going right into a registrational design, in the absence of clinical experience.

Thanks, Steve we have not.

<unk> started any additional expansions with this proposed modified dose this will be part of our discussion with the FDA.

Coming up this quarter.

And then what our plan would be is to.

Incorporate.

That operation in the design of the.

<unk> directed study if all everything else.

<unk> grew from our FDA discussion and then also as I said earlier incorporate that dosing regimen is additional expansion cohorts for indications that we want to pursue beyond prostate cancer.

Okay. So I guess, you don't feel the need to do any.

Any bridging work and you'd be comfortable going right into a registrational design.

In the absence of.

Clinical experience at this dose.

Scott Koenig: Well, rather than comment on that, let's wait until we have the FDA guidance and feedback. And then we will come back to you with regard to what we will do next for the various aspects of the prostate as well as the other indications. So we'd like to have that regulatory insight before we.., more definitive about the specific design of that prostate. Okay, and then maybe just a question, I guess, I don't know for you and for Jim, but just on the on the cash on the cash runway guidance, I know that 018 is kind of, Excluded from that in terms of in terms of the pursuit of a later stage study is, is, is that just a function of needing that regulatory clarity?

Well rather than comment on that let's wait until we have the FDA guidance and feedback and then we will come back to you with regard to what we will do next.

For the various aspects of the prostate as well as the other indications so.

We'd like to have that regulatory insight before we.

More definitive about the.

The specific design of that prostate study.

Okay and then.

Just a question I guess on the numbers.

And for Jim, but just on the on the cash on the cash runway guidance I know that 018 is kind of.

Scott Koenig: Or is there still some uncertainty with respect to whether or not the tumor type is going to be prostate and or how big and what that trial is going to look like? Jim, did you want to take that?

Excluded from that in terms of 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 are going to be prostate and or how big is that.

We're going to look like.

Jim did you want to take that.

Jim Karrels: No, I mean, the intention is, thanks for that question, we do plan to move ahead. Obviously, we're waiting to have the dialogue with FDA this quarter. We've not completely, you know, priced out what the trial might look like. We'd like to have a better sense of that before we know what the nut is that we need to find to make this happen. However, we do have adequate cash to launch the study. We want to be in a position where we can fully fund. United, forward.

And the intention is.

Thanks for that question, we do plan to move ahead, obviously, we're waiting to have the dialogue with FDA this quarter.

We've not completely priced out what the trial might look like we'd.

We'd like to have a better sense of that before we know what not is that we need to.

<unk> to make this happen. However, we do have adequate cash to launch. The study we just we want to be in a position where we can fully fund.

The entire study so.

Obviously BD, we've 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.

Our word.

<unk>.

Jim Karrels: And obviously, you know, with stock is trading today, as the whole market is off, it's an option that we don't like to look at, but one that we would if we had, Understood. That's very helpful. Thanks for taking the questions. Our next question comes from Silvan Tuerkcan with J&P Securities. Your line is open. Hello, good afternoon.

And obviously with the stock is trading today as the whole market is off.

It's an option that we don't like to look at but one that we would if we had to.

Understood.

That's very helpful. Thanks for taking questions.

Sure.

Our next question comes from Silvan <unk> with JMP Securities. Your line is open.

Scott Koenig: Thanks for taking my questions and congrats on all of the progress. My question is, and I might have missed this, is the goal of the MGC 018 dosing regimen modification to reduce the side effects? And if so, which ones specifically are you trying to ameliorate?

Hello, Good afternoon, Thanks for taking my questions and congrats on all of the progress.

Scott Koenig: Or is it to keep the dose in the patient over the course of treatment as high as possible? Thank you. Silvan, I think, thanks for the question, and I would say that we're trying to probably accomplish both in that we'd like to 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-foot syndrome, and like to decrease the incidence severity of that.

My question is.

Might have missed this is the goal of the <unk>.

Dosing regimen modification to reduce the side effects and if so which one specifically are you trying to moderate or is it to keep.

Dose in the patient over the course of treatment is highest possible.

Thank you.

So when I think.

Thanks for the question and I would say that.

We're trying to properly accomplish both.

In that we'd like to mitigate some side effects as I pointed out today.

The one we feel that was most.

<unk> based on feedback from the patients.

Was the hand foot syndrome, and like to decrease the incidence.

Severity of that we feel that things like the.

Scott Koenig: We feel that things like the hemologic side effects that we were observing, such as 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 point out in the second comment, is that by the reduction and reducing side effects, we think that we can hopefully treat patients for a longer period of time and offer, obviously, greater benefit to those patients as a result. So that's the objective going forward. Great, thank you.

Hematologic side effects.

That we were observing such as neutropenia.

Easily handled by holding dose and supplementary.

Growth factors like G CSF.

And again also increasing.

The time interval between dosing should also provide some value there ultimately as you pointed out.

Can comment is that by.

The reduction in reducing side effects, we think that we can.

Hopefully treat patients for a longer period of time, then offer obviously greater benefit.

To those patients.

As a result, so that's the objective going forward.

Great. Thank you Ed and so at the upcoming update we get an idea of what the average dose was per patient rather than be.

Scott Koenig: And so at the upcoming update, will we get an idea of what the average dose was per patient rather than the, I guess, the labeled dose that you're administering? I think at a 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 until after we have a discussion with the regulators. Great, thank you so much for taking my question. Our next question comes from Peter Lawson with Barclays. Your line is open.

I guess the Lai.

Labeled dose.

Yeah.

I think.

<unk> 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.

Our valuable for getting the best effects, but again, we will wait till after we have a.

Discussion with the regulators.

Great. Thank you so much for taking my question.

Yes.

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

Scott Koenig: Hey, Scott, thanks for taking the questions. Just on the FDA meeting in Q1, and just, Will you communicate that to us, the outcome around the dosing? And then, will the combination.., with your PD-L1-TCLA-4. Will that start on the basis of that discussion with the FDA, or will that start sooner? kind of help us through the timing and communication in one. So, with regard to the meeting, as you know, we're 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.

Hey, Scott Thanks for taking the questions just on the FDA meeting.

Q1.

And just.

Will you communicate that to us the outcome around the dosing.

And then with the combination.

With your PD.

PD Lone <unk> four.

That stock on the basis of that discussion with the FDA.

Soon it just kind of help us through the timing and communications and <unk>.

Yeah, so with regard to the meeting as an hour.

We're 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 actually patients are in screening right now.

Scott Koenig: 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 start. With regard to communication about that, obviously we'll have to see what the written comments come back, so I think more or less the likelihood is we'll be able to communicate this sometime in the second quarter. Great, thank you. And the data for B7H3 in the second half, is that going to be with the new dosing? That's the idea versus...

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'll be able to communicate this sometime in the second quarter.

Great. Thank you the data for.

<unk> three in the second half.

Not going to be with the new dosing.

I'd versus.

Scott Koenig: Exist in patience [inaudible] No, I think, Peter, the point was, is 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 occur. So we, you know, whatever update we provide them, irrespective of that. For the particular indications we plan to continue, we would then apply new dosing and that wouldn't start until the second half of the year. Great. Okay. Thank you so much. As a reminder, to ask a question, please press star then 1. Our next question comes from David Day with SMBC. Your line is open.

Existing patients.

No I think Peter the <unk>.

<unk> was because we wanted the data to continue to mature on this.

Ah patients that are on the three Meg per kg Q Q3 regimen, and obviously with the modifications that occurred so.

Whatever update we provide them irrespective of that.

For the particular indications we plan to continue we would then apply new dosing and that wouldn't start until the second half of the year. So.

Great. Okay. Thank you so much.

As a reminder to ask a question. Please press Star then one.

Our next question comes from David Day, with SMB see your line is open.

Scott Koenig: Hi, thanks for taking my questions. So, a couple of questions on MGCO-18. So, regarding the dose expansion data in prostate cancer in the second half of this year, could you set the data expectation and what would be the clinical benchmark we should be expecting? And then also, on MGCO-18 in prostate cancer, could you also share with us some of your thoughts on biomarker strategies to further identify responders in prostate cancer? Thanks, David.

Hi, Thanks for taking my questions. So a couple questions on <unk>.

So regarding to your dose expansion data in prostate cancer in second half. This year could you just said you did expectation and what would be the clinical benchmark, we should be expecting and then also on <unk> in prostate cancer could you share with some of your thoughts on biomarker strategies to further identify responders in prostate cancer.

Scott Koenig: So with regard to dose expansion, you know, as you know, these are very late-line 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 had several months until they progressed. It obviously varied depending on which study they had been previously looked at.

So thanks, David So with regard to.

Dose expansion.

As you know the.

These are very late line castration resistant prostate patients.

The.

Patient in line of therapy for the expansion cohort towards third and fourth line.

Therapy as you know.

Historically these patients had.

Based on our progression.

Usually had several months.

Till they progressed.

It vary depending on.

Which study.

<unk> had been previously.

Scott Koenig: So we are clearly looking at those markers for advancing beyond what the historical data has. And, you know, 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, we, as I pointed out earlier, we are looking to even further enhance the effect here by dosing modifications. So that will be certainly part of the analysis.

Looked at.

So we are clearly looking at those markers for advancing beyond of what the historical data has.

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.

Slide significant benefit too.

These patients going forward of course.

As I pointed out earlier, we're looking to even further enhance the effect here by dosing modification.

So that will be certainly part of the analysis and clearly we will continue to look at different populations of patients.

Scott Koenig: 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 MGCO-18. But we will continue to look at that analysis and also continue to look at patients who have various types of disease. Those that have visceral disease that are limited to various organs or lymph nodes versus those with bony disease.

Today, we have not specifically identified any gene markers.

Per se that would predict a more favorable outcome.

One patient versus another based on <unk>, but we will continue to look at that analysis and also continue to look at patients who have various types of disease. Those that have this real disease that have limited various oregon lymph nodes versus those with bone disease.

Scott Koenig: So, again, at this point, while we've treated approximately 50 patients with this dose, it's still a limited number of patients. The other thing we are keeping an eye on is B7H3 expression. And to date, that doesn't seem to portend predictions for those patients who respond or not. We saw patients, in general, had very high levels by age scores of B7H3. But we did see the occasional patients with low age scores that also had evidence of activity.

So again.

At this point, while we've treated approximately 50 patients with this dose it's still a limited number of patients the other thing.

We are keeping an eye on is <unk> three expression and to date that doesn't seem to portend.

Predictions for those patients who respond or not we saw patients.

In general had very high levels by a or a b <unk> three but we did see the occasional patients with low H score is that also had evidence of activity. So at this point at least for prostate cancer that does not seem to be the predictable market going forward.

Scott Koenig: So at this point, at least for prostate cancer, that does not seem to be the predictable marker going forward. Very helpful. Thank you. There are no further questions. I'd like to turn the call back over to Dr. Scott Koenig for any closing remarks. 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.

Got it very helpful. Thank you.

There are no further questions I'd like to turn the call back over to Dr. Scott Koenig for any closing remarks.

I want to thank everybody for participating in the call today, obviously, we have a lot of.

Citing data that will be coming up during the course of the year and look forward to sharing with you with you at a future conference. Thank you.

Scott Koenig: Thank you. This concludes the program. You may now disconnect.

This concludes the program you may now disconnect.

Operator: . . .

Okay.

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