Q1 2022 MacroGenics Inc Earnings Call

Good afternoon, we will begin the Macrogenics 2022 first quarter corporate.

Operator: Good afternoon. We will begin the MacroGenics 2022 First Quarter Corporate Progress and Financial Results Conference Call in just a moment. All participants are in a listen-only mode at this moment, and we will conduct a question and answer session at the conclusion of the call. At this point, I'll turn the call over to Chris James, Vice President of Investor Relations and Corporate Communications at MacroGenics. Thank you, operator.

Progress and financial results conference call in just a moment all participants are in a listen only mode. At this moment and we will conduct a question and answer session at the conclusion of the call at this point I'll turn the call over to Christine <unk>, Vice President of Investor Relations and corporate communications of Macrogenics.

Thank you operator, good afternoon, and welcome to Macrogenics conference call to discuss our first quarter 2022.

Chris James: Good afternoon, and welcome to MacroGenics' conference call to discuss our first quarter 2022 financial and operational results. For anyone who has not had the chance to review these results, we issued a press release this afternoon outlining today's 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 was made.

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 announcement, which is available under the investors tab on our website at Macrogenics Dot Com you May also listen to this conference call via webcast on our website, where it will be archived 30 days beginning approximately two hours after the call is complete.

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.

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 State Harbor Provision under the Private Securities Litigation Reform Act of 1996. 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.

The safe Harbor provision under the private Securities Litigation Reform Act of 1095, and 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.

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.

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 over to Jim Karrels, our chief financial officer, who will review our financial results.

I'd like to welcome everyone participating via conference call and webcast today.

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

Thank you Scott This afternoon Macrogenics reported financial results for the quarter ended March 31, 2022, which highlight our financial position as well as our recent progress.

Jim Karrels: Thank you, Scott. This afternoon, MacroGenics reported financial results for the quarter ended March 31, 2022, which highlight our financial position as well as our recent progress. As described in a release this afternoon, MacroGenics' total revenue, consisting primarily of revenue from collaborative agreements, was $11.1 million for the quarter ended March 31, 2022, compared to total revenue of $16.9 million for the quarter ended March 31, 2021. Revenue for the quarter ended March 31, 2022, including 3.6 million net sales of Margenza.

Jim Karrels: Our research and development expenses were $61.4 million for the quarter ended March 31, 2022, compared to $53.1 million for the quarter ended March 31, 2021. The increase was primarily related to development, manufacturing, and clinical trial costs related to the MgCoA team, development of discovery projects and preclinical molecules, and increased clinical expenses related to loragerlimab. These increases were partially offset by decreased development, manufacturing, and clinical trial costs related to flotatuzumab, for which development has been discontinued, decreased margitoxibab manufacturing costs related to the Xylab agreement, and decreased retifalamab manufacturing costs for Insight. Selling general and administrative expenses were $16.3 million for the quarter ended March 31, 2022, compared to $15 million for the quarter ended March 31, 2021.

As described in our release this afternoon Macrogenics total revenue consisting primarily of revenue from collaborative agreements was $11 $1 million for the quarter ended March 31, 2022, compared to total revenue of $16 9 million for the quarter ended March 31 2021.

Jim Karrels: The increase was primarily related to Margenza selling costs, as well as stock-based compensation and consulting expenses. Our net loss was $66.4 million for the quarter ended March 31, 2022, compared to a net loss of $51.3 million for the quarter ended March 31, 2021, and our cash equivalents and marketable securities balance as of March 31, 2022 was $184 million, compared to $243.6 million as of December 31, 2021. And in terms of our cash runway, we anticipate that our cash, cash equivalents, and marketable securities as of March 31, 2022, in addition to anticipated and potential collaboration payments, should enable us to fund operations through 2023.

Revenue for the quarter ended March 31, 2022 included 3.6 million net sales of Mark gender.

Our research and development expenses were $61.4 million for the quarter ended March 31, 2022, compared to $53 1 million for the quarter ended March 31, 2021.

The increase was primarily related to development manufacturing and clinical trial costs related to M. D. C. O a teen development of discovery projects in preclinical molecules and increased clinical expenses related to large roll them out.

These increases were partially offset by decreased development manufacturing and clinical trial costs related to flooding Tusa Mab, which development has been discontinued decreased March it talks about manufacturing costs related to the XI lab agreement and decreased read a fallow mab manufacturing costs for inside.

Selling general and administrative expenses were $16 $3 million for the quarter ended March 31, 2022 compared to $15 million for the quarter ended March 31, 2021.

The increase was primarily related to March and the selling costs as well as stock based compensation and consulting expenses.

Our net loss was $66.4 million for the quarter ended March 31, 2022, compared to a net loss of $51.3 million for the quarter ended March 31, 2021 and.

Our cash cash equivalents in marketable securities balance as of March 31, 2022.

Was $184 million compared to $243 6 million as of December 31, 2021, and in terms of our cash runway, we anticipate that our cash cash equivalents in marketable securities as of March 31, 2022. In addition to anticipated and potential collaboration payments.

Should enable us to fund operations through 2023. This cash runway guidance does not reflect anticipated expenditures related to the full phase three development of M. D. C. O 18 in prostate cancer anticipated to begin by year end 2022 or further expansion of other studies currently ongoing however.

Jim Karrels: This cash runway guidance does not reflect anticipated expenditures related to the full Phase 2.3 development of MGCO-18 and prostate cancer anticipated to begin by the year 2022 or further expansion of other studies currently ongoing. However, the company believes that it can reasonably obtain funding for the planned Phase 2.0 portion of the MGCO-18 study through a combination of existing financial resources, a variety of external funding or potential revenue sources, and project prioritization. And now I'll turn the call back to Scott. Thank you, Jim.

The company believes that it can reasonably obtained funding for the planned phase II portion of the M. D. C. O 18 study through a combination of existing financial resources, a variety of external funding or potential revenue sources and project prioritization and now I'll turn the call back to Scott.

Scott Koenig: I'm delighted by the progress made during the first quarter. I'm especially pleased with the outcome of our recent meeting with the U.S. Food and Drug Administration regarding the advancement of MGCO-18, our B7H3-directed antibody drug conjugate, in patients with metastatic castration-resistant prostate cancer. Our Phase 2-3 clinical plan for MGCO-18 underscores our productive dialogue with the FDA and feedback received on key elements of the program, and we are advancing toward the initiation of the Phase 2-3 study by year-end.

Thank you Jim I'm delighted by the progress made during the first quarter.

I'm, especially pleased with the outcome of our recent meeting with the U S food and drug administration regarding the advancements of M. D. C O a T. R. B seven H three directed antibody drug conjugate in patients with metastatic castration resistant prostate cancer.

Our phase two three clinical plan for M. D. C. O 18, underscores a productive dialogue with the FDA and feedback received on key elements of the program and we are advancing towards the initiation of the phase two three study by year end.

Another exciting development was the initiation of a phase one dose escalation study of M. D. C. O 18 combination with Laura Gerald <unk>, a bi specific dart molecule targeting PD, one and see Chile four in advanced solid tumors.

Scott Koenig: Another exciting development was the initiation of a phase one dose escalation study of MgCO18 in combination with loriduralimab, a bi-specific DART molecule targeting PD-1 and CTLA-4 in advanced solid tumors. I'm also happy to announce that FDA has cleared the IND for MgDO24, our next generation CD123 by CD3-DART molecule. We look forward to initiating a Phase I study of MgD O24 and CD123 positive hematologic malignancies in mid-2022.

I'm also happy to announce that F. D. A has cleared the I N E. R. M. D. D. O 24, our next generation C. D. One twenty-three by CD three dart molecule.

We look forward to initiating a phase one study of M. G. D O 24, and CD 123 positive hematologic malignancy malignancies in mid 2022.

Scott Koenig: In addition to these programs, we and our partners continue to progress our other clinical and preclinical candidates and expect to provide further updates over the course of this year. With that in mind, 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. As a reminder, 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. MGC018 is our investigational antibody drug conjugate designed to deliver a DNA-alkylating duocomycin cytotoxic payload to tumors expressing B7H3.

In addition to these programs, we and our partners continue to progress our other clinical and preclinical candidates and expect to provide further updates over the course of this year.

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 B seven age three a member of the B seven family of molecules involved in immune regulation.

As a reminder, we are developing two molecules that target be 783 through complementary mechanisms of action. They take advantage of this antigens broad expression across multiple solid tumor types.

M. D. C. O 18 is our investigational antibody drug conjugate designed to deliver a DNA alkylating door from ice inside of toxic payload to tumors expressing b 783.

Scott Koenig: We recently finalized our plans to conduct a registration path phase 2-3 study of MgCO18 in MCRPC. Based on our analysis of dose expansion study data to date, we plan to modify the dose and administration of MGCO-18 in the upcoming registrational study, including a reduced dose and increased interval between doses, which we believe will help to achieve the maximum therapeutic effect and reduce potential side effects. The Phase 2-3 study will enroll patients with MCRPC who have had prior exposure to a taxane and at least one androgen receptor axis targeted or ARAT agent such as apiridurone, enzalidomide, or apalidomide and a HAARP inhibitor, if appropriate.

We recently finalized our plans to conduct a registration path phase two three study of M. D. C. O 18 in M. C. R. P C.

Based on our analysis of dose expansion study data to date, we plan to modify the dosing administration of M. D. C O <unk> in the upcoming Registrational study, including a reduced dose and increase the interval between doses, which we believe will help to achieve the maximum therapeutic effect and reduce potential.

Side effects.

The phase two three study will enroll patients with M. C. R. P C who have had prior exposure to a taxane and at least one androgen receptor axis targeted or eight rat, aged such as abiraterone and solidified our Apple legitimized.

PARP inhibitor if appropriate.

During the phase two portion of this study approximately 150 patients will be randomized one to one to one to receive either two megs per kid or 2.7, Vicksburg Kid of M. D. C. O 18 every four weeks in the experimental groups or physician's choice of in a red agent not previously received.

Scott Koenig: During the Phase 2 portion of the study, approximately 150 patients will be randomized one-to-one-to-one to receive either 2 mg per kg or 2.7 mg per kg of MgCO18 every four weeks in the experimental groups or physician's choice of an ARAT agent not previously received in the control group. Following completion of the phase two portion of the study, analysis of the data will be performed to further inform the phase three portion, in which we plan to randomize additional patients one-to-one to receive either MGCO-18 at the recommended dose or an ARAT agent as the control group.

And the control group.

Following completion of the phase two portion of the study and the analysis of the data will be performed to further inform the phase III portion, which we plan to randomize additional patients one to one to receive either M. D. C O a team at the recommended dose or in a rat agent for the control group.

In recognition of the current cost of capital environment inclusion of an end of phase two interim analysis to evaluate the two ends M. D. C. O 18 dose levels will allow us to further assess safety tolerability and futility and select the best dose before proceeding to the phase III portion of the <unk>.

Scott Koenig: In recognition of the current cost of capital environment, including an end-of-Phase II interim analysis to evaluate the two MGC018 dose levels will allow us to further assess safety, tolerability, and futility and select the best dose before proceeding to the Phase III portion of the study. Finally, for the Phase 2-3 study, we will utilize radiographic progression-free survival as the primary endpoint, an objective response rate, and overall survival as a secondary key endpoint. This study design was discussed during a constructive meeting with the FDA in March. We expect to begin enrollment in the fourth quarter of 2022.

Study.

Finally, with a phase two three study we will utilize radiographic progression free survival as the primary endpoint and objective response rate and overall survival as the secondary key endpoint.

This study design was discussed story and constructive meeting with the FDA in March.

We expect to begin enrollment in the fourth quarter of 2022.

Let me provide a few more details about how we arrived at the modified dose and dosing interval with a planned phase two three study.

Scott Koenig: Let me provide a few more details about how we arrived at the modified dose and dosing interval for the planned Phase 2-3 study. To determine these lower doses and longer dosing interval, we performed modeling and simulation of patient pharmacokinetic and safety data from the Phase 1-2 study to evaluate the relationship between MGCO-18 exposure and dose modification, including dose reductions and dose delays and key indices of tolerability. The doses of 2 versus 2.7 mg per kg every 4 weeks we plan to evaluate in the phase 2 portion of the study compare with a starting dose of 3 mg per kg every 3 weeks with any subsequent reductions evaluated in the phase 1 dose expansion study.

To determine these lower doses and longer dosing interval, we pro form modeling and simulation of patient pharmacokinetic and safety data from the phase one two study to evaluate the relationship between N. G. C O 18 exposure and dose modification, including dose reductions and dose delays and key indices.

A tolerability.

At doses of two versus 2.7 mixed breed kick every four weeks, we plan to evaluate in the phase II portion of the study.

Pair with a starting dose of three Meg per kg every three weeks with any subsequent reductions evaluated in the phase one dose expansion study.

We expect a slightly lower doses will decrease adverse events and potentially improve the efficacy by allowing patients to stay on therapy longer.

Regarding our ongoing phase <unk> dose expansion study of M. D. C. O. A T. We are encouraged by initial clinical activity observed in patients with melanoma and plan to recruit 20 additional melanoma patients.

Scott Koenig: We expect that slightly lower doses will decrease adverse events and potentially improve efficacy by allowing patients to stay on therapy longer. Regarding our ongoing Phase 1-2 Dose Expansion Study of MGCO-18, we are encouraged by the initial clinical activity observed in patients with melanoma and plan to recruit 20 additional melanoma patients to evaluate a dose of 2.7 mg per kg administered every four weeks. Again, this dose compares to the starting dose of 3 mg per kg administered every 3 weeks with any subsequent reductions during dose expansion.

Sally waiting a dose of 2.7 mix per kg administered every four weeks.

Again this dose compares to the starting dose of three Meg per kg administered every three weeks with any subsequent reductions during dose expansion.

Scott Koenig: As for the other tumor types enrolled in the expansion study, we are evaluating possible next steps for treating additional patients with non-small cell lung cancer and continue to enroll patients in the squamous cell carcinoma of the head and neck expansion cohort. However, we do not plan to proceed with advancing the study in patients with triple negative breast cancer at this time. We intend to provide an update on clinical data from Phase I-II dose expansion cohorts in the second half of 2022 as the data further matures.

As for the other tumor types enrolled in the expansion study we are evaluating possible next steps for treating additional patients with non small cell lung cancer and continue to enroll patients with squamous cell carcinoma of the head and neck expansion cohort.

We do not plan to proceed with advancing the study in patients with triple negative breast cancer at this time.

We intend to provide an update on clinical data from phase one to dose expansion cohorts in the second half of 2022 as the data matures.

In addition, we recently dosed the first patient in the dose escalation study of M. D. C. O 18 in combination with Laura <unk>, our PD one by <unk> four by specific in patients with advanced solid tumors, including renal cell carcinoma pancreatic cancer ovarian cancer.

Scott Koenig: In addition, we recently dosed the first patient in the Dose Escalation Study of MGCO-18 in combination with loroduralumab, our PD-1 bis CTLA-4 bispecific, in patients with advanced solid tumors, including renal cell carcinoma, pancreatic cancer, ovarian cancer, pedocellular carcinoma, MCRPC, and melanoma. The scientific rationale for undertaking this trial is supported by our preclinical data, which suggest the anti-tumor activity of MGCO-18 may be enhanced by combination therapy with an anti-PD-1 agent without meaningful incremental toxicity.

Sir.

Cellular carcinoma M C RPC and melanoma.

The scientific rationale for undertaking this trial is supported by our preclinical data, which exists suggest the antitumor activity with M. D. C. O. A T may be enhanced by combination therapy with an anti PD, one agent without meaningful incremental toxicity.

Lastly in April we presented a poster titled targeting B seven H Street in prostate cancer preclinical proof of concept with M. D. C. O 18, an investigational anti B 783 antibody drug conjugate at the American Association for cancer Research annual meeting.

Scott Koenig: Lastly, in April, we presented a poster titled Targeting B7H3 in Prostate Cancer, Preclinical Proof of Concept with MGCO-18, an Investigational Anti-B7H3 Antibody Drug Conjugate, at the American Association for Cancer Research Annual Meeting. MGCO-18 demonstrated anti-tumor effects on prostate cancer cell lines and enhanced activity in some lines when combined with PARP or androgen receptor inhibitors in the preclin

M D C O I team demonstrated antitumor effects on prostate cancer cell lines and enhanced activity in some lines when combined with PARP or androgen receptor inhibitors in the preclinical study.

Scott Koenig: We believe these data lend further support for advancing MGCO-18 in patients with prostate cancer, and we look forward to potentially evaluating MGCO-18 in combination with these agents in future studies. 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. We are recruiting patients in a Phase II study of enoblatuzumab in front-line patients with squamous cell carcinoma of the head and neck, in which PD-L1-positive patients receive combination therapy with retifanilamab, an anti-PD-1 antibody, and PD-L1-negative patients receive combination therapy with tibotelumab, a PD-1 by LAG-3 D

We believe these data will further support for advanced the M. D. C O a T in patients with prostate cancer, and we look forward to potentially evaluating M. D. C. O 18 in combination with these agents in future studies.

Another of our investigational molecule is exploring the overexpression of <unk> seven AC in solid tumors is a novel to the Mad an FC engineered antibody created using our FC optimization platform.

We are recruiting patients in a phase II study of a novel Susan that in frontline patients with squamous cell carcinoma of the head and neck in which PDL one positive patients receive combination therapy would rather fine law mab and anti PD, one antibody and PDL, one negative patients receive combination therapy with <unk>.

Tell him that are PD, one by lag three dart molecule.

Scott Koenig: We expect to complete enrollment in 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. In April, the results from a Phase I study of the combination of inoblituzumab and pembrolizumab in advanced B7H3-expressing cellular tumors were published in the Journal for Immunotherapy of Cancer.

We expect it to.

To complete enrollment of the PDL, one positive patient cohort during the first half of this year and provide an update on this cohort during the second half of the year.

In April the results from a phase one study of the combination of a novel Susan that and pemble isn't that an advanced b cell and age three expressing solid tumors were published in the journal for immunotherapy of cancer.

These data were initially presented at the society for immunotherapy of cancers 2018 annual meeting.

Scott Koenig: These data were initially presented at the Society for Immunotherapy of Cancer's 2018 annual meeting. As previously reported, objective responses occurred in 6 of 18 valuable patients, or 33.3%, with squamous cell carcinoma of the head and neck, who were checkpoint NINEVE and had previously progressed after receiving first-line platinum-based chemotherapy. Of note, in patients with squamous cell carcinoma of the head and neck, the updated data show a median overall survival of 17.4 months, with a 95% confidence interval of 9.2 to not reach.

As previously reported objective responses occurred in six of 18, evaluable patients or 33, 3% with squamous cell carcinoma of the head and neck or checkpoint naive and had previously progressed after receiving first line platinum based chemotherapy.

Of note in patients with squamous cell carcinoma of the head and neck. The updated data show a median overall survival of 17.4 months with its 95% confidence interval of 9.2 to not reached.

Scott Koenig: This compared favorably to the objective response rate of 13-16% and median OS of 7.5 months seen with single-agent use of anti-PD-1 agents previously reported in squamous cell carcinoma of the head and neck patients who had progressed after platinum-based chemotherapy. We believe the recently published data from our combination of enoblacuzumab and pembrolizumab, while from a small study, are encouraging given the historical efficacy of anti-PD-1 agents. The results demonstrated that therapy combining B7H3 and PD-1 inhibition is feasible, potentially with minimal additive toxicity beyond what would be expected with anti-PD-1 monotherapy.

This compared favorably to the objective response rate of 13% to 16% and median OS of 7.5 months seen with single agent use of anti PD. One agents previously reported in squamous cell carcinoma of the head and neck patients who had progressed after platinum based chemotherapy.

We believe the recently published data from a combination of a novel Susan that in Pan Burleson that well from a small study are encouraging given the historical advocacy with anti PD one agents.

<unk> demonstrated that therapy, combining these German age three and PD, one inhibition is feasible potentially with minimal additive toxicity beyond what would expect with anti PD one monotherapy.

Next let me update you on Lora Gerald <unk>, our investigational Bispecific tetravalent Dart molecule designed to enable blockade of PD, one and see July four.

Scott Koenig: Next, let me update you on loriderlimab, our investigational bispecific tetravalent start molecule designed to enable blockade of PD-1 and CTLA-4. As mentioned, we recently initiated a clinical study of MGCO-18 and loroduralimab in patients with advanced solid tumors. We are also evaluating lorodrolumab in a phase 1-2 dose expansion study in patients with microsatellite-stable colorectal cancer, MCR-PC, melanoma, and checkpoint nave non-small cell lung cancer at a dose of 6 mg per kg.

As mentioned, we recently initiated a clinical study of M. D. C O 18, and Laura Gerald <unk> in patients with advanced solid tumors.

We are also evaluating Lora geralyn mab in a phase <unk> dose expansion study in patients with microsatellite stable colorectal cancer.

M C. R. P C melanoma and checkpoint naive non small cell lung cancer and a dose of six migs per keg.

We expect to provide an update from this ongoing study in the second half of 2022.

Next up I'll discuss our efforts to advance treatment of patients with C. D 123 positive hematologic malignancies.

Scott Koenig: We expect to provide an update from this ongoing study in the second half of 2022. Next, I'll discuss our efforts to advance treatment of patients with CD123 positive hematologic malignancies. MgD024 is our next generation bispecific CD123 by CD3 DART molecule that 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.

M. G. D. O 24 is our next generation bi specific CD 123 by CD three dart molecule that incorporates a C. D. Three component designed to minimize cytokine release syndrome, while maintaining antitumor side of lytic activity and permitting intermittent dosing through a longer half life.

In April our R&D for M. G. D. O 24 was cleared by the FDA for evaluation in patients with hematologic malignancies.

Scott Koenig: In April, our IND for MGD-024 was cleared by the FDA for evaluation in patients with hematologic malignancies. We expect to begin enrollment in a Phase I study of MgDL24 in patients with CD123 positive neoplasms, including acute myeloid leukemia, in mid-year. Next, I will provide an update on our product candidates being developed by our collaboration partners for which we retain certain economic rights. Suplizumab is an anti-CD3 monoclonal antibody that was acquired from us by Prevention Bio under an asset purchase agreement in 2018, for which we are entitled to receive future milestone payments and royalties on net sales. Prevention is developing to plasmid for the treatment of type 1 diabetes.

We expect to begin enrollment of the phase one study of M. G. D. O 24 in patients with C. D 123 positive neoplasm, including acute myeloid leukemia in mid year.

Next I will provide an update of our product candidates being developed by our collaboration partners for which we retained certain economic right.

So <unk> is an anti CD three monoclonal antibody that was acquired from us by prevention bio under an asset purchase agreement in 2018 for which we are entitled to receive future milestone payments and royalties on net sales.

Prevention is developing to prison that for the treatment of type one diabetes.

Scott Koenig: In July 2021, the FDA issued a complete response letter for teplizumab's BLA for the delay of clinical type 1 diabetes in at-risk individuals. In March, Prevention announced that the FDA had accepted the Biologics License Application for teplizumab for the delay of clinical type 1 diabetes in at-risk individuals. The FDA has signed a PDUFA date of August 17, 2022. Our second investigational ADC, IMGC 936, which targets ADAM9, a cell surface protein overexpressed in several solid tumor types, is being advanced under a co-development agreement with Immunogen.

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.

In March prevention announced that the FDA accepted the biologics license application for the prison that so the delay of clinical type one diabetes in at risk individuals.

The FDA assigned a <unk> date of August 17, 2022.

Our second investigational ADC I M D C 936, which targets Adam nine a cell surface protein over expressed in several solid tumor types is being advanced under co development agreement with immunogen.

Scott Koenig: Under our 50-50 collaboration, Immunogen is leading clinical development and has indicated that they will anticipate disclosing initial data from the Phase I study in multiple solid tumors in 2022. I am pleased to announce that a manuscript describing the preclinical evaluation of IMGC-936 was recently accepted for publication in Molecular Cancer Therapeutics. A copy of the manuscript will soon be available online. Finally, I will provide an update on Marjah Tuck's map. As a reminder, margituximab was launched as Margenza in the U.S. in March 2021 in coordination with our commercial partner, Episano.

Under a 50 50 collaboration Immunogen is leading clinical development and has indicated that they will anticipate disclosing initial data from the phase one study in multiple solid tumors in 2022.

I'm pleased to announce that a manuscript describing the preclinical evaluation of I M. G. C. 936 was recently accepted for publication in molecular cancer Therapeutics.

A copy of the manuscript will soon be available online.

Lastly, I will provide an update our margin talks a map.

As a reminder margin toxin that was law launched as more gender and the U S. In March 'twenty, 'twenty, one and coordination with our commercial partner episodic.

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 her two regimens at least one of which was for metastatic disease.

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 Margenza as another option to treat metastatic breast cancer. As reported, net sales were $3.6 million from Argenza in the first quarter.

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

As reported net sales were $3 $6 million for my agenda in the first quarter.

Operator: Given the high level of competition in the HER2-positive breast cancer market, including multiple new approvals, we continue to have modest expectations for Margenza sales. In conclusion, we anticipate that 2022 will be an important year for macrogenics. We remain steadfast in our commitment to becoming a leader in the field of immuno-oncology and are excited about the potential to deliver novel therapies to cancer patients. We would now be happy to open the call to questions. Operator. Thank you. To ask a question, you'll need to press star 1 on your telephone.

Given the high level of competition that her two positive breast cancer market, including multiple new approvals, we continue to have modest expectations for margins itself.

In conclusion, we anticipate that 2022 will be an important year for macrogenics.

We remain steadfast in our commitment to becoming a leader in the field of immuno oncology and are excited about the potential to deliver novel therapies to cancer patients.

We would now be happy to open the call for questions.

Writer.

Thank you to ask a question you need to press star one on your telephone to withdraw your question. Please press the pound key please standby, while we compile the Q&A roster.

Operator: To withdraw your question, please press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from Jonathan Chang with SVB Securities. Your line is now open.

Our first question comes from Jonathan Chang with S. V. B Securities. Your line is now open.

Hi, guys. Thanks for taking my questions first question on the M. G C zero in a phase two three prostate cancer study.

Jonathan Chang: Hi guys, thanks for taking my questions. First question on the MGC-018 Phase 2-3 Prostate Cancer Study. You've guided us to start the study by year-end. How should we be thinking about timelines for the study beyond study initiation? And how do those timelines fit with your cash runway?

You've guided to starting the study by year end, how should we be thinking about timelines for the study beyond study initiation and how do those timelines fit with your cash runway guidance.

Jonathan Thanks, very much for the question.

Scott Koenig: Jonathan, thanks very much for the question. Obviously, we're still in the operational start-up phase of this, working with the identification of sites and finding the organizations that will help us with that study. So it's really too early to project how quickly the 150 patients in the Phase II portion of the study will be enrolled. Obviously, once that study starts, we're willing to provide further guidance. But again, right now, our target is to get the study started by the end of the year.

Obviously, we're still in the operational startup phase of this.

Working with the identification of sites and the and.

And finding the.

Organizations that will help us work with that study. So it's really too early to project how quickly the 150 patients.

In the phase two portion of this study will be enrolled obviously once that study starts were willing to provide further guidance, but again right now our target is to get this study started by the end of the year with regard to the cash.

Scott Koenig: With regard to the cash situation, as Jim commented earlier, we believe with the cash available and anticipated other cash that may be coming in, potentially, we should be able to have enough cash taking us through 2023 and to be able to support the Phase II study of that program.

Situation as Jim commented on earlier, we believe with the cash available and I anticipate.

<unk> other cash that may be coming in.

Potentially.

We should be able to have enough cash taking us through.

2023.

And to be able to support.

The phase two study of that program.

Got it thank you and just a second question on the phase three portion of the study.

Scott Koenig: Thank you. And just a second question on the Phase 3 portion of the study. How should we be thinking about the size of the Phase 3 portion? And could patients treated in the Phase 2 portion of the study count towards the Phase 3? I'll answer the second part first. Yes, there's a potential for patients that are participating in phase two to be treated in phase three. This was designed as a seamless design.

How should we be thinking about the size of the phase III portion and could patients treated in the phase two portion of the study count towards the phase III.

I'll answer the second part first yes, there's a potential oven.

That patients that are participating in the phase two this was designed as a seamless design, but at this point.

Scott Koenig: But at this point, we prefer not to identify the exact number of patients in phase three. We've obviously modeled this out. But again, I like to take this through phase two before we give a little bit more specificity on how many patients we would anticipate in the phase three portion. Got it. And just one last question from me, what do you guys see as the radiographic PFS benchmark for an androgen receptor access targeted therapy in the phase 3 patient population?

We prefer not to.

Identify the exact number of patients in the phase III.

We've obviously modeled this out.

But again I like to take this through the phase two before we give a little bit more specificity on how many patients we would anticipate in that phase in the phase III portion.

Got it and just one last question for me.

What do you guys see as the radiographic PFS benchmark.

For an androgen receptor axis targeted therapy and in the phase III patient population.

Well again, given that right now the.

Scott Koenig: Well, again, given that right now the treatment paradigms are continuing to evolve, we have obviously a new agent on the market. There are obviously switches in frontline therapy, and depending on where the study is being conducted in the US and Europe in terms of the initial agent being given in the castration-resistant population, it's hard for us to give the specifics with regard to the control population.

Treatment paradigms are continuing to evolve we have obviously, a new agent on the market. There is obviously.

Switches in a frontline therapy and depending on where this where the study is being conducted in U S and Europe in terms of the.

Initial agent being given in the castration resistant population.

Hard for us to give the specifics with regard to the control population.

Scott Koenig: We obviously have modeled this with data to date and the various studies out there, but right now, we're not giving specific guidance in terms of the control population responsiveness versus the experimental. Obviously, we're looking certainly for several months of improvement over control.

We obviously have modeled as well.

With the data to date and the various studies out there, but right now we're not giving specific guidance in terms of the control population responsiveness.

Versus the experimental obviously, we're looking certainly for several months of improvements over control.

Got it thank you for taking the questions.

Operator: Thank you for taking the question. Thank you. Our next question comes from Kaveri Pohlman with BTIG. Your line is now open. Good afternoon.

Thank you. Our next question comes from Caveri Polman with B T. I G. Your line is now open.

Good afternoon.

Kaveri Pohlman: Thanks for the updates and thanks for taking my questions. My first question is for MGD-024. How much of the floated-to-isomap data derisks the 024 program?

Jason Thanks for taking my question.

My first question is for M D D.

Hum.

Yes.

Bob.

Four programs.

Okay.

That doesn't mean, it's going to have a very different.

T D D.

Do you think you have to.

Alright.

Quickly.

Uh huh.

Oh, thanks for.

Scott Koenig: Because 024 has an FC domain, it's going to have a very different PK PD profile. Do you think you have to start over or get to a dose that's active and safe enough quickly? Thanks, Kaveri, for the question. We are starting this out as a new study. Obviously, we have a lot of experience with flotatuzumab, but as you point out, with the intermittent dosing here, which was obviously incorporated, we think, as a major attribute for the design of the MgDO24 molecule, we will be starting at low doses.

For the for the question.

We are starting this out as a new study obviously, we have that experience.

On Florida, Tucson, there, but as you point out with the intermittent dosing here, which was obviously.

Cooperated we think is a major attribute for the designer of the M. G. D. O 24 molecule, we will be starting at a low doses.

Scott Koenig: Our hope is that these cohorts will be small and can move up quickly, but again, until we start this study, we won't know how long it will take to move through the various dose levels in the dose escalation study. So, it's too early to say.

Our hope is is that these cohorts will be small and can.

Move up quickly, but again until we start the study we won't know how long it will take to move through the various dose.

Dose levels.

In the dose escalation study so too early to say.

That's fine and well.

Scott Koenig: For Inobutizumab and Pibotelumab, do you plan to screen or test patients for LAG-3 expression? I believe the BMS data shows superior survival in LAG-3 expressors, although it is approved for both types of populations. Good question.

And Cuba.

Do you.

Yes.

Expression I believe.

Sure.

Okay.

Yeah.

Oh no.

Tiger.

<unk>.

The good question and the way. The study was initially designed we did not requires screening for lag three expression.

Scott Koenig: And the way the study was initially designed, we did not require screening for lag-3 expression. Obviously, what we were trying to address here, particularly in the combination using Thiebaud, is in the PD-L1 negative population, we believe that the FC incorporation in nobletuzumab by binding through NK cells and other cells can drive upregulation of gamma interferon and upregulation of multiple checkpoints, including lag-3 We will be looking retrospectively at the patients in that study to understand the baseline and post-treatment levels of PD-L1 and lag-3 in those patients and, obviously, look at how it correlates with response rates. So not required prospectively, but more as a guide in terms of the populations that most benefit from treatment. Thank you. The next question comes from Etzler Darout with BMO Capital Markets. Your line is open.

Obviously, what we were.

Trying to.

Address here, particularly in the combination using T. Bo is in the PD Lone negative population, we believe that the F C.

Incorporation in the notebook Susan that.

By binding to NK cells, and other cells can drive upregulation of gamma interferon and Upregulation.

Regulation of multiple checkpoints, including lag three we will be looking retrospectively.

The patients in that study to understand the baseline.

Post treatment.

Expressions levels of PDL, one and lag three in those patients and obviously look how it correlates with response rates. So.

Not required prospectively, but more as a guide in terms of the populations that most benefit by treatment.

Thank you.

Next question comes from Etzler, Dara with BMO capital markets. Your line is open.

Great. Thanks for taking the questions I have a couple on N. G. C O N eight updates in the second half of this year I guess first could we see updated prostate cancer data that includes a PFS in the second half and.

Etzer Darout: Thanks for taking the questions. I have a couple on MGC-018 updates in the second half of this year. I guess first, could we see updated prostate cancer data that includes PFS in the second half, and I guess, you know, as far as sort of the dose and interval modifications noted in the Phase 2-3 studies, could we see some clinical data on that particular or those dose modifications in prostate or in melanoma cohorts being sort of reported in the second half of this year?

I guess, you know as far as sort of the dose in integral modifications noted in the phase two three.

Could we see some clinical data.

On that particular or sort of those those modifications and prostate or in melanoma cohorts being sort of reported in the second half of this year. Thank you.

So answer with regard to the modifications a dose that has not been initiated in the.

Etzer Darout: Thank you. So, Etzer, with regard to the modifications of dose, that has not been initiated in the expansion cohorts that we have treated to date. And that was obviously part of the objective of this phase two design. As you know, and as we stated earlier today, we have modeled this out looking at the pharmacokinetics, looking at the side effect profile, and the responses. And we think we've come up with two potential doses with the modified intervals that would end up giving higher efficacy and, potentially, as well as a much reduced mitigated side effect profile. But until we test that prospectively, we'll not know the answer.

Expansion cohorts that we have treated to date and that was obviously part of the objective of this phase.

As to design.

Scott Koenig: And that's part of the reason to understand looking at those two doses, which one will perform best and then ultimately take that forward into the phase three portion of the study. With regard to the specific updates on prostate cancer and O18, we have not made any specific decisions with regard to this program either on prostate cancer or on the specific expansion cohorts. We will provide some updates, but right now, we have not submitted an abstract specifically for the updated prostate. Given that patients are still being dosed, we obviously would like to see that study completed before reporting out the final result. Thank you all.

As you know and as we stated earlier today.

We have modeled this out.

Looking at the pharmacokinetics looking at the side effect profile and the responses and we think we've come up with a two.

Two potential doses.

With the modified integrals that would end up giving a higher efficacy and potentially.

As well as a much reduced mitigated side effect profile, but until we test that prospectively, we will not know the answer and that's a part of the reason to understand looking at those two doses, which one will perform the test and then ultimately take that forward into the phase III portion.

The study with regard to those specific updates on the prostate no 18.

We have not made any specific decisions with regard to this program either on prostate.

Sure on the specific expansion cohorts, we will provide some updates but right now.

We have not.

Submitted an abstract specifically for the updated prostate given that patients are still being dose. We obviously, we'd like to see that study completed.

Before reporting out the final results.

Got it. Thank you I will look forward to the disclosures in the second half. Thank you.

Peter Lawson: We'll look forward to the disclosures in the second half. Thank you. Our next question comes from Peter Lawson with Barclays. Your line is now open.

Okay.

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

Great. Thank you so much.

Scott Koenig: Great, thank you so much. The Phase II Interim for B7H3, when could we potentially start? Are we talking about the study that we just described for the phase 2, 3, 2 portion? As I said in an earlier question, we want to get the study started. Again, we're targeting the start at the end of the year.

Ali.

The phase two interim piece of an H three when could we potentially see that.

Are we talking about the study that we just described with phase two three to two portion.

As I said earlier to an earlier question, we want to get the study started again, we're targeting for the start at the end of the year so until.

Scott Koenig: So until, you know, things are operational, it would be just too early to project when we'd see that data. Clearly, we'll be working very diligently to enroll the 150 patients to get that answer, but at this point, it's just too early to estimate.

Things are operational will be just too early to project when we'd see that data clearly we'll be working very diligently.

To enroll the 150 patients to get that answer but.

But at this point, it's just too early to.

Estimate.

Scott Koenig: And then, why the two potentials, why the two doses for... (inaudible) Well, I think that's a very good question. As I said, we selected these doses based on the actual data we had on hand from the patients. Why test two doses? Well, you know, obviously, the FDA is providing guidance all the time, and it's really good development practice to really define a dose to assure the maximum therapeutic index rather than just proceeding with a maximum tolerated dose. They were very, our interactions with them were very positive.

Got you. Thank you and then why the.

Two potential whether two doses.

M G C.

Eight.

Well I think.

That's a very good question as I said, we selected these doses based on the actual data we had on hand from the the patients Y test two doses well you know obviously the SBA is providing guidance all the time and it's really good development practice to really define a dose.

To ensure the maximum therapeutic index, rather than just proceeding with a maximum tolerated dose.

They were very.

Our interactions with them, we're very positive.

And in our discussion.

We certainly are encouraged us to look at the.

The two doses going forward. So at this point I think this is the most prudent thing to do to ultimately get the.

The most appropriate dose for treating these patients.

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

Stephen Willey: And in our discussion, they certainly encouraged us to look at the two doses going forward. So at this point, I think this is the most prudent thing to do to ultimately get the most appropriate dose for treating these patients. Thank you. The next question comes from Stephen Willey with Stifel. Your line is now open. Yeah, good afternoon.

Yeah. Good afternoon, thanks for taking the questions.

Scott Koenig: Thanks for taking the questions. Maybe just to follow up on the phase two, three study design. Does the eligibility criteria allow for taxing use in the castration-sensitive setting, and is there a limit to the number of taxing regimens that are allowed? There is a limit on the second to the number of taxing agents, so it's one taxing agent and most likely will be doci-taxal.

Maybe just a follow up on the phase two three study design.

Does does does the eligibility criteria allow for taxane use in the castration sensitive setting.

And is there a limit to the number of Taxane regimens that are allowed.

And there is a limit on the second on the.

Number of taxpaying. So it's it's one taxane and most likely will be docetaxel.

Scott Koenig: With regard to its use in castration sensitive, I actually don't know the answer, Stephen. I'll have to follow up with you on that question. Okay, and I guess in the discussion with FDA was, Was there any... In terms of trial design, was there any discussion just around, I guess, the card results? and...

With regard to its use in their castration sensitive I actually don't know the answer to Steven will have to follow up with you on that on that question.

Yeah.

Okay, and I guess in the discussion with FDA was.

Was there any.

In terms of trial design was there any discussion just around I guess the card results.

And.

Scott Koenig: I guess some of the clinical awareness now that sequencing these novel hormonals behind each other doesn't necessarily achieve a maximal amount of clinical benefit, and I know from just having some physician conversations with regard to other development programs. There's been a little bit of a pushback on this notion of sequencing these agents in patients in later lines of therapy. So just wondering if, I guess even outside of your FDA discussions you've had. Any kind of clinical or KOL conversations to inform the selection of a..., of a control arm.

I guess some of the.

Sure.

Of the clinical awareness now that that sequencing. These these novel hormonal is behind each other don't necessarily achieve a maximum amount of clinical benefit and I know and just having some physician conversations with regards to other development programs.

Theres been a little bit.

Of a pushback on this on this notion of sequencing these agents and in patients.

In later lines of therapy. So just wondering if I guess, even outside of your FDA discussions you've had.

Any kind of.

Ah clinical or Kols conversations too.

Inform the selection.

Of a control arm here.

Yes, Steve we had.

Scott Koenig: Steve, we had both extensive discussions with investigators, and we've also had a very good discussion with the FDA. And what I would say is there is no easy solution given where the state of treatment is right now. As you know, there are different things one could select from, and there was no perfect answer to that question.

Both extensive discussions.

With investigators and we've also had a very good discussion with the FDA and what I would say.

Is there is no one easy solution, given where the state of treatment is right now.

As you know there are different things one could select and there was no perfect answer to that question and actually the F. D. A.

Scott Koenig: And actually, the FDA, in fact, commented on that point. And so they, again, discussed with us, obviously, in any of these studies, it's always up to the investigator unless it's a huge safety concern, and that was not raised. And obviously, we've incorporated the design to deal with safety issues in the future.

In fact commented.

To that point and so.

They.

Again.

Discussed with us.

Obviously in any of these studies, it's always up to the investigators it unless it's a huge safety concern and that was not raised and obviously we've incorporated the design.

To deal with safety issues in the future but.

Jonathan Miller: But the fact of the matter is, there is something we will obviously continue to examine as we go through the phase two portion of the study and see where the state of treatment is at that time. The FDA definitely agreed that this selection for the control population was one that was certainly adequate to move forward. Thank you. Our next question comes from Jonathan Miller with Evacor ISI. Your line is now open.

The fact that in a manner. There is something we will obviously continue to examine.

Examine as we go through the phase two portion of the study.

And see where the state of the treatment is at that time, but the F. D. A definitely agreed.

At this.

Selection for the control population was one that.

Was certainly adequate to move forward.

Thank you. Our next question comes from Jonathan Miller with Evercore ISI. Your line is now open.

Scott Koenig: Hey guys, thanks for taking my question. One more maybe on the 018 dosing. Obviously, it's less intense, so I understand the better expected tax profile, but the PR in your prepared remarks seems to suggest that it's getting close to the practical realized dose in phase 1 after you account for dose reductions and delays that those patients were getting. So I guess how would you characterize or how much lower is the exposure at the new dose versus where patients ended up at later cycles in phase 1 at the 3 megakig Q3 dose?

Hey, guys. Thanks for taking my question.

One more maybe on the zero when a dosing obviously less intense I understand the better expected tax profile, but the P or in your prepared remarks seemed to suggest that it's.

Getting close to the practical realized dose in the phase in phase one after you account for dose reductions and delays of those patients were getting so I guess, how would you characterize or how much lower the exposure at the new dose versus where patients ended up at leader cycles in the phase one at the three Mega keg.

Q3 dose.

Scott Koenig: And then secondly, maybe switching gears a little bit on the runway guidance, presumably that includes the admirable job that you've done so far streamlining the pipeline, but you also suggest that there might be additional prioritization or optimization to come. So beyond 018, which assets remain a focus for accelerating development versus maybe sitting on the back burner a little while while you try and get through the lead program phase 2?

And then secondly, maybe switching gears a little bit on the runway guidance, presumably that includes that admirable job that you've done so far streamlining the pipeline, but you're also suggests that there might be additional prioritization or optimization to come.

1018, which assets remain a focus for accelerating development versus maybe sitting on the backburner, a little while while you try and get through the the lead program phase two.

Scott Koenig: A lot of questions there, so let me sort of start with the address, the first part, which was the dose. As you saw, we made modifications that are bounded both by between 2 and 2.7 with obviously a slightly increased dosing interval. What I would say is that, given the size of the number of patients we had to evaluate, the dose that we approximated was sort of right in the middle there, so the question is, is it a little bit more or a little bit less?

Well the question there so let me sort of start with the address the first part which was the dose.

As you saw that we made modifications.

That is.

Is bounded both by between two and 2.7 with obviously a slightly increased dosing interval.

What I would say is dead.

You know given the size of the number of patients we had to evaluate the.

The dose that we approximated was sort of right in the middle there. So the question is is a little bit more a little bit less the ideal one that's why we ultimately selected these two doses to go forward. So I think.

Scott Koenig: The ideal one, that's why we ultimately selected these two doses to go forward. So I think, hopefully, with the appropriate guidance to the Data Safety and Monitoring Committee, we will be able to select the best dose to move forward in the Phase 3 arm of the study. With regard to the runway guidance, we obviously are continually looking at the portfolio and pruning things which we don't think will have the highest prospects for the greatest success.

Hopefully.

With the appropriate guidance to the data safety monitoring committee, and we will be able to select the.

Best dose to move forward in the phase III arm of the study with regard to the runway guidance. We obviously are continually looking at the portfolio and tuning things, which we don't think will have.

The highest project prospects for the greatest success.

Scott Koenig: You know, it's very clear that we have held off on accelerating the PBO program beyond the combination study in the head and neck at this point, but we certainly are spending a lot of effort in the background determining what the best trial design is for both solid tumors and potentially for lymphoma. But again, we will not engage in the development of that until we have certainly enough capital to support the MGCO-18 study and some other programs that you'll hear about later in this year that we have high hopes for. So you'll continue to hear more, Jonathan, on how we will prioritize our programs going forward and where we think we will have the greatest chance to succeed.

It's very clear that we have held off on accelerating the tebow program beyond the combination study in the <unk>.

Head and neck.

At this point, but.

But we certainly are spending a lot of effort in the background.

Determining.

What the best.

This trial design is for both solid tumor and potentially for lymphoma, but again, we will not.

Engage in the development of those of that.

Until we have certainly enough capital.

To support the M D C O 18th study and.

Some other other programs that Youll hear about later in this year that we have high hopes for so you'll continue to hear more Jonathan.

On how we will prioritize our programs going forward, where we think we will have the greatest chance for success.

Thank you.

Scott Koenig: Our next question comes from Yigal Novovodzic with Citigroup. Your line is now open. Hi, thanks, Scott. I'm Jim.

Next question comes from Yigal <unk> with Citigroup. Your line is now open.

Hi, Thanks.

Yigal Novovodzic: On the interim analysis for the Phase II for MGC-018, what have you said about what will trigger that interim analysis? Is this a typical situation, just a certain number of radiographic CFS events? Could you share what that is? We haven't given the specifics with regard to what moves things forward. There is a futility component to this analysis, which will be guarded via the Data Safety Monitoring Committee, but at this time, we're not in a position to specify the go-no-go decisions with regard to that.

Yes.

On the interim analysis for the phase two.

Sure.

Oh <unk>.

What you said about what will trigger that interim.

Nickel situations, just a certain number of radiographic PFS event.

And if you could share.

Yes.

We haven't given the specifics with regard what.

Whose things forward there is a futility component to this analysis.

Which will be guarded.

The data safety monitoring committee, but at this time, we're not.

You too.

Specify the go no go decisions with regard to that.

Okay.

Yigal Novovodzic: And then on MgD-024, I'm just curious if you could help put this molecule in perspective with some of the other competitors out there that have the same construct. For example, just as one example, there's another one from Pevo.

Hum.

Or I'm just curious if you could help put.

This molecule perspective.

Editors out there that have the same.

<unk> construct.

One example.

Either one.

Hello.

Scott Koenig: B.O. 436, Off the target. 21-23, wondering if you could help www.microsoft.com.au, Well, you know, we have actually constructed a PIVO-mimic version. It has some nice properties about it, but we've certainly, from our preclinical analysis of our molecule of MgDL24, we certainly think that this can be a superior molecule. I should point out, as I stated earlier, not only do we see this being developed in late-line refractory populations, but given very robust activity we've seen in preclinical models, combining these with other approved active agents that are used for AML number one, and then our plans, which are much broader beyond AML to using this in other hematologic malignancies, once we have established the dose, I think this could be really a standalone TD123 in its class, especially given the way it's designed.

T O.

Thanks Austin.

PD 123.

Wondering if you could help.

No.

How your molecule.

Yeah.

Well.

We have actually constructed.

So mimic version.

Has.

Some nice properties about it but.

We've certainly from our preclinical analysis of our molecule.

M. G. D. O 24, we we certainly think that this can be a superior molecule I should point out as I stated earlier not only do we see this being developed in late line refractory population, but.

Given very robust activity, we've seen in preclinical models.

Combining these with other approved active agents.

That are used for AML number one and then our plans.

Which are much broader beyond AML to using this in other hematologic malignancies. Once we have established the dose I think this could be a really are a stand alone.

<unk> 22 in its class.

Especially.

Given the way it's designed it.

Scott Koenig: If we see the remarkably reduced cytokine release profile, that will certainly add greater value to this molecule compared to what has been at least discussed publicly about the Aptiva molecule in terms of cytokine release. Thank you. And the next question comes from David Day with SMBC. Your line is now open.

We see the re markedly reduced.

Cytokine release profile.

That will certainly add greater value to this molecule compared to what has been at least.

Discuss publicly on the <unk> molecule in terms of cytokine release.

Thank you. Our next question comes from David Day with S. M. D. C. Your line is now open.

I think it's a game of questions. So one question on the TCR T program. The phase III design could you just comment on the receptor occupancy at the lower doses.

David Day: Hi, thank you for taking my questions. So, one question on the MGC-018 program, the Phase 2-3 design, could you comment on the receptor occupancy at the lower dose? Particularly based on the PK-PD modeling, could you share whether you will be able to occupy a similar amount of receptors at lower doses? I know this might be a little bit tough to do because the molecules are internalized, but any color would be helpful.

Based on the PK PD modeling could you share whether you will be able to occupy the similar amount of receptors at lower doses I know this might be a little bit tough to perform because.

Molecules are internalized, but any color would be helpful.

David I don't I can't really answer that question. There I think you alluded to the problem here is that.

Scott Koenig: David, I don't, and I can't really answer that question. I think you've alluded to the problem here is that because this is an ADC molecule, you actually don't need full receptor occupancy to get biological activity. What you need is an antibody directed to an epitope on the receptor that will incorporate that molecule.

Because this is an ADC molecule you actually don't need all fully set their occupancy.

To get the biological activity, what you need is a.

An antibody directed to an epitope on the reset there that will incorporate that molecule. In this case will go through the lysosomal pathway and get the cleavage of the toxin, which then travels to the nucleus.

Scott Koenig: In this case, we'll go through the lysosomal pathway and get the cleavage of the toxin, which then travels to the nucleus and promotes alkylation of DNA. And so really, you don't need full saturation of this, the subsaturating levels, given that the doses we have intended to move forward in phase two and three are not that different from what we have already described in phase one. And given the broad activity we've seen, and furthermore, in our dose escalation study, even seeing activity at lower doses, I think we have a sufficient drug in the circulation to do what we want to do, and again, hopefully mitigate some of the side effects by this dose reduction. That's really helpful, Scott. So just another question on O18.

And promotes alkylation of DNA and so really you don't need full saturation of this.

Sub saturating levels given that.

The.

Doses, we have Intel.

Intending to move forward in the phase two three are not that different.

And what we have already described in phase one and given the broad activity, we've seen and Furthermore, in our dose escalation study, even seeing activity at lower doses.

I think we have a sufficient drug in the circulation.

To do what we want it to do.

And again, hopefully mitigate some of the side effects of Baidu.

This dose reduction.

That's really helpful. Scott So just another question on <unk>.

From your phase one study the safety profile looks pretty clean.

Scott Koenig: From your phase one study, the safety profile looked pretty clean, where we didn't see any colitis, and we saw some lower levels of grade 3 diarrhea and rash. So to reduce the levels to 2 and 2.7 mgs per kg, just show us what kind of adverse event you're trying to mitigate at the lower dose. Excellent question.

We didn't see any colitis, and we saw some lower levels of grade three diarrhea, and rash so to reduce the levels two two and two parts of a metric you can just show us what kind of adverse event youre trying to mitigate the lower dose.

Scott Koenig: We modeled this on the major side effect profiles, and the one that we saw that was not as big an issue with the investigators themselves but more with the patients, was hand-foot syndrome, where we saw a very low grade three side effect profile. But the fact is, we had higher levels of grade two, which causes pain in patients. And so our goal here is both to decrease, in this instance, the incidence of hand-foot syndrome, but also the grade, hopefully driving them to more grade one-type side effects for hand-foot, and hopefully, obviously, for other side effects that are most prominent, most notably some of the hemologic side effects, which include neutropenia.

Excellent question, we modeled this on the major side effect profiles and the one that we saw that was.

It was not as big an issue with the investigators themselves, but more with the patients with hand foot syndrome, where we saw a very low grade three.

A side effect profile, but the fact is we had higher levels of a grade two which causes pain in patients and so our goal here is both to a decrease in this instance.

The hand foot syndrome incidents, but also the grade.

Hopefully driving them to more of a grade one tie.

<unk> side effects poor hand foot hopefully obviously for other.

Side effects that are most prominent most notably some of the hematologic.

Hum.

Good effects, which include neutropenia.

Scott Koenig: In that case, we can treat the neutropenia by giving GCSF. And the fact is, to date, we're not seeing a major clinical problem with neutropenia, meaning we are not seeing any febrile neutropenia or any notable increased infectious infection rates as a result. So oncologists have good ways to treat neutropenia and also thrombocytopenia both by holding doses and giving stimulating agents. So that is the intent of these dose modifications. Thank you. The next question comes from Charles Hu with Guggenheim Securities. Your line is open.

In that case.

Uh huh.

We can treat the neutropenia by giving G. CSF and the fact is today, we're not seeing a major clinical problem with the neutropenia, meaning we are not seeing any febrile neutropenia or any notable.

Increased infectious.

Infectious action rates as a result so.

Oncologists have a good ways to.

Treat the neutropenia and also thrombocytopenia, both by holding doses and giving a stimulating agents. So that is the intent of these dose modification.

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

Charles Hu: Good afternoon, everyone, and thanks for taking my question. Just one quick one on inoplatuzumab. So it sounds like you'll have that combination update in PD-L1 positive head and neck cancer later this year. And we have a pretty good idea of what the single agent PD-1 benchmarks look like. But, you know, just given your data coming up, as well as given some of the language and guidance around cash runway, I guess, what are you looking for out of this program in terms of go, no-go decisions? And, you know, what would give you confidence in really pursuing this on some sort of a more potentially registrational development path? Thanks. Yeah, an excellent question, Charles.

Good afternoon, everyone and thanks for taking my question just one quick one on a notebook two's enough. So it sounds like you'll have that.

Combination updates in PD lone positive head and neck cancer. Later this year. So we have a pretty good idea of what the single agent PD, one benchmarks look like but you know just given your data coming up as well as given some of the language in guidance around cash one way I guess what are you looking for out of this programs in terms of go no go decision.

And no we wont give you confidence in really pursuing this in some sort of a more potentially registrational development path.

Yeah excellent question Joel.

Scott Koenig: The fact is, as we pointed out today, the historical data in later line, even though the cohort was small, we were seeing overall response rates of 30%. And, as we reported today, very much more prolonged overall survival in the population, certainly about doubling from the historical data. So again, in a chemo-free regimen, in this frontline head and neck study, if we're achieving a 25 to 30% response rate, and we're in that range, in a chemo-free regimen, I think we have both the ability to develop this further as a potential chemo-free regimen or, in fact, pursue other possibilities of combining with chemo going forward. So, well, we look forward to having some maturation of the data later this year to be able to update that. Great

The fact is as we pointed out today.

Historical data in later line, even though the Oh, where it was small we were seeing them.

Overall response rates in that 30% and as we reported on today.

I'm very much more prolonged overall survival in the population certainly about doubling from the historical data. So it's again in a chemo free regimen as frontline head and neck study, if we're achieving a 25% to 30%.

Response rate where in that range in a chemo free regimen I think we have both the ability to develop this further as the potential chemo free regimen or in fact pursue.

Other possibilities of combining with chemo going forward, so well, we look forward to having some maturation of the data later this year to be able to update.

Great. Thanks for taking my questions. Thanks. Thank.

Operator: Thanks for taking my question. Thanks. Thank you. As a reminder, ladies and gentlemen, that's star number one to ask your question. Our next question comes from Silvan Tuerkcan with JMP Securities. Your line is open.

Thank you.

As a reminder, ladies and gentlemen that star one to ask a question. Our next question comes from Silvan <unk> with JMP Securities. Your line is open.

Thank you and good afternoon, and congrats on the quarter and thanks for taking my question.

Silvan Tuerkcan: Thank you. Good afternoon, and congratulations on the quarter and thanks for taking my question. My first question is a little bit more on the O18.

First question, a little bit more on the OE team.

I guess spacing out of going from three weeks to four weeks dosing.

Scott Koenig: Spacing out of going from three weeks to four weeks of dosing. What evidence do you have from the PKPD profile that you'll have a shot at maintaining the efficacy? In part from the AUC.

What evidence we have from the PK PD profile.

Youll have a shot at maintaining the efficacy you've seen before apart from the AUC and have there been any patients in the ongoing I guess dose expansion arms.

Scott Koenig: And have there been any patients in the ongoing, I guess, those expansion arms? That Harvard's Unknown Executive, Scott Koenig, Mayank Mamtani, James Karrels, Peter Lawson, Peter Lawson, Silvan, yes, exactly. That's what we did in our retrospective analysis of the patients on the 3MIG Q3 weekly. All the patients started out at the dose, but a large percent of those patients were either having dose reductions or doses were held mostly for side effects before they were resuming, so there were a number of patients that actually were held for four weeks or even longer, up to six weeks in some of these patients.

That have received.

Spaced out further maybe due to the dose reductions or it by giving freedom to be investigators to space them out and then I'll have a follow up thank you.

And so then yes exactly that's what we did in our.

Retrospective analysis of the patients on it.

Three three make Q3 weekly.

All of the patient started out at that dose.

A large percentage of those patients were either having dose reductions or.

Doses were hell be the precise mostly decided that.

Side effects and before they were resuming so there were a number of patients that actually were held.

Or four weeks or even longer up to six weeks and in some of these patients and so we were able to model that and compare the responsiveness of those patients with these are longer intervals.

Scott Koenig: And so we were able to model that and compare the responsiveness of those patients with these longer intervals and side effects and their response rates. And that's how we were able to simulate and come to the doses and the dosing intervals that we've ultimately decided on.

And side effects and there.

Response rates.

And that's how we were able to simulate and come to the doses and the dosing intervals that we ultimately decided on so yes, we did have patients.

Scott Koenig: So, yes, we did have patients that, in fact, were not treated on a Q3 weekly basis but less frequently. Great, thank you. And just a quick question on Lori Gelleymouth. Here, I think your partner in China, Xilab. Confinite Rallup.

That in fact were not treated on a Q3 weekly basis, but.

Less frequently.

Great. Thank you.

A quick question on.

Laurie Kelly map.

Here.

Actually sorry, if we're talking about.

Here I think your partner in China by lap.

Development.

I think you just closed on a.

For Q call, but.

And then you said that they may have future plans.

Scott Koenig: Thank you, Paul said that they may have future plans. What are those? Did you have any update on their future plans and how they may align with your future plans? Following the update. Yeah, I think that, again, I think they are looking towards us in terms of next opportunities.

Do you have any update on their future plans and how they may align with your future plans.

Following the update that we'll get in the second half.

Yeah, I think that again.

They are looking towards us in terms of next opportunities.

As I alluded to before we're looking at the potential a solid tumor indication and potentially in a lymphoma setting them too.

Scott Koenig: As I've alluded to before, we're looking at the potential of a solid tumor indication and potentially in a lymphoma setting to explore the use of Pebotelumab. And depending on what we decide, patients will potentially have an opportunity to participate in those studies, but nothing has been formalized as yet. Thank you. I have a follow-up with Stephen Willey of the Four Year Linus Network. Yeah, thanks for the follow-up. So Lord Gerlimad is currently being evaluated on a Q3W schedule, and I was just wondering if there's going to be any attempt to harmonize dosing when you start combining this with MGC018 on a Q4. Yes, in fact, there will be an amendment to provide Laura Gerlameb on a Q4 weekly regimen to coincide with the dosing of MGCO-18.

To explore the use of our T botelho, Matt and depending on what we decide they will they will potentially have an opportunity to participate in those studies, but nothing has been formalized.

Yes.

Thank you I have a follow up for Stephen Willey with Stifel. Your line is now open.

Yeah, Thanks for the follow up.

So Laura drill them out I believe is currently being evaluated on at Q3 W schedule.

And just wondering if theres going to be any attempt to harmonize dosing. When you start combining this with M. G. C 018 on a Q4 W schedule. Thanks.

Uh huh.

Yes.

There will be an amendment to.

Provide lora journal on a Q O Q4 weekly regimen.

Coincide with the dosing of the M D C O a T.

Okay. Thanks, taking the question.

Thank you.

Scott Koenig: Thanks for taking the question. Thank you. And I have a follow-up with Yigal Nochomovitz of Citigroup. Your line is open.

And I have a follow up with.

Notable move its with Citigroup Your line is open.

Yigal Nochomovitz: Thanks. Yeah, Scott, just one more on O18 and the Phase I-II expansion. He noted encouraging activity in melanoma, and given that you're seeking to add patients to non-small cell lung cancer, that also appears to be generating an interesting signal. I'm not sure it's been elaborated at this point in time in terms of any more quantification, but I think our plan is to provide some guidance, again, on some of these expansion cohorts later this year.

Yes, one more.

In the phase two expansion.

What is encouraging activity in melanoma, and given that you're seeking to add patients in non small cell.

That also appears to generate interesting signal I'm.

I'm not sure elaborate at this point in time in terms of any more quantification of those trends.

I think I players to provide some binds again on some of these expansion cohorts later this year, so stay tuned for that but again.

Yigal Nochomovitz: So stay tuned for that. But, again, as I've noted before, first, obviously, on the melanoma. We'd like to see response rates for this 2.7q4 in melanoma in a similar population and how those additional 20 patients will respond, both in terms of safety and efficacy.

As I've noted before first obviously on the melanoma, we'd like to see on this.

2.7, Q4 response rates in melanoma in a similar population and how those additional 20 patients will respond.

Both in terms of safety and efficacy with regard to lung.

Scott Koenig: With regard to the lung, we need to do a little more work in terms of given the heterogeneity of the lung population both in terms of histologies as well as the expression pattern of B7H3 among the different tumor types, which specific lung population we want to further explore. So we're doing a little bit more homework on that before we decide to move forward for expansion in the lung population. Thank you. And our next follow-up comes from Silvan Tuerkcan with JMP Securities. Your line is open.

We need to do a little more work in terms of the.

Given the heterogeneity of the lung population population both in terms of.

Histology as well as the expression pattern of <unk> 783.

The different tumor types.

Which specific lung population, we want to further explore so we're doing a little bit more homework on that before we decide.

The move forward for expansion in the lung population.

Thank you and our next follow up comes from Silvan <unk> with JMP Securities. Your line is open.

Thank you.

Yes.

Now that you're enrolling.

Silvan Tuerkcan: Thank you. Just one last follow-up here, now that you're enrolling.

Scott Koenig: Patients at 2.7 mg in melanoma and potentially also non-small cell lung cancer and your other expansion cohorts. Is there any way that, in that scenario, having those patients already in phase 1-2? to those expansions that you could skip the phase 2, 3 of a pivotal trial and just go into phase 3 following that or change the dose. Faisal Khurshid, So let me be quite clear; we have not started dosing at 2.7 in the melanoma population, nor obviously in the lung population.

At two milligrams in melanoma and potentially also non small cell lung cancer.

Expansion cohorts is there any way that in that scenario, having those patients already in that phase.

Phase one to phase two.

Two dose expansion that you could skip the phase two three of our pivotal trial and just go into phase III following that or converted dose.

Expansion into a pivotal trial by enrolling more patients. Thank you.

So let me be quite clear we have not started dosing at 2.7 in the melanoma nor in obviously in the lung.

Population.

We are likely given the ease of adding additional patients to be able to start that before or approximately at the same time as.

Scott Koenig: We are likely, given the ease of adding additional patients, to be able to start that before or approximately at the same time as the phase 2-3 prostate, but we will not use that data because it will be just too early and too delayed to get sufficient enough data to guide the prostate. The prostate will be independent, and actually, more importantly, it's having it as a controlled study to understand the response rate as well as the safety profile compared to the control population in a sizable number of patients. So no, we will not use the data from those other tumor types to guide us for the prostate study.

As the phase two three prostate but.

We will not use that data because it would be just too early into delayed to get sufficient enough data to guide the prostate approach they will be an independent and actually more importantly, it's the having it as a controlled study.

To understand the response rate as well as the safety profile.

Compared to the control population and a sizable number of patients. So no we will not use the data in those other tumor types to guide us for the prostate study.

Thank you.

Scott Koenig: Thank you. And I'm currently showing no further questions in the queue at this time. I'd like to hand the conference back to Dr. Koenig for any closing comments. Thank you, operator. And thank you all for participating in our earnings call today. We look forward to providing further updates on so many of our programs later this year. We hope you have a great afternoon and evening. Ladies and gentlemen, thank you for your participation in today's conference. You may now disconnect. Everyone have a wonderful day. [music] BF-WATCH TV 2021 BF-WATCH TV 2021 BF-WATCH TV 2021

And I'm currently showing no further questions in the queue at this time I'd like to hand, the conference back to Dr. <unk> for any closing comments.

Thank you operator, and thank you all for participating in our earnings call. Today, we look forward to providing further updates on so many of our programs. Later this year. We hope you have a great afternoon and evening.

Ladies and gentlemen, thank you for your participation in today's conference you May now disconnect everyone have a wonderful day.

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