Q2 2022 MacroGenics Inc Earnings Call

In terms of our pipeline, since our last quarterly update, we completed enrollment of the Phase, 1-2 Dose Expansion Study of lorigerulamab, a bi-specific DART molecule targeting PD-1 and CTLA-4 in advanced cell and tumors.

Good after noon, we will begin the Macrogenics 2022 second quarter corporate progress and financial results conference call in just a moment.

All participants in the listen only mode at the moment and.

Following completion of the Phase 2 portion of the study, an interim analysis of the data will be performed to further inform the Phase 3 portion, in which we plan to randomize additional patients one-to-one to receive either MgCO18 at the recommended dose or the ARAT agent for the control group.

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 Gaines, Vice President of Investor Relations and corporate communications of Macrogenics.

Thank you operator, good afternoon, and welcome to Macrogenics conference call to discuss our second 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 todays announcements, which is available under the investors tab on our website at Macrogenics Dot com.

We continue to expect to start the Tamarix study by year-end and anticipate delivery of interim data from the study by the end of 2024.

Next, let me update you on loroduralimab. We continue to dose patients in the Phase 1 dose escalation combination study of MgCO18 with loroduralimab in patients with advanced solid tumors, including renal cell carcinoma, pancreatic cancer, ovarian cancer, hepatocellular carcinoma, metastatic castration resistant prostate cancer, and melanoma. Based on data from our preclinical studies, anti-tumor activity with MGCO-18 may be enhanced, by combination therapy with an anti-PD-1 agent without significant incremental toxicities.

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

I would 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 set.

<unk> of our annual quarterly and current reports filed with the SEC.

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.

During the second quarter, we completed enrollment in a Phase I-II dose expansion study with, Laura Jeromeb as monotherapy in cohorts of patients with microsatellite-stable colorectal cancer, MCRPC, melanoma, and checkpoint IE non-small cell lung cancer.

President and Chief Executive Officer of Macrogenics.

We expect to provide a data update from this study by early 2023.

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

Next up, I'll discuss our efforts to advance treatment of patients with CD123-positive, hematological malignancies.

Also in July, we dosed the first patient in the Phase 1 study of MgDL24, our next-generation CD123xCD3 DART molecule in patients with CD123, positive hematologic malignancies.

In addition, we continue to dose patients in the Dose Escalation Combination Study of MgCO18, our B7H3-directed antibody drug conjugate with lorigerulamab, in patients with advanced cell and tumors.

Afternoon, I will provide key updates on our clinical programs as well as the restructuring plan intended to extend our cash runway, but before I do so let me first turn the call to Jim Carroll, Our Chief Financial Officer will review our financial results. Thank you Scott. This afternoon Macrogenics reported financial results for the quarter ended.

MGDL24 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. We recently dosed the first patient in a Phase I study of MGDL24 in CD123-positive relapsed, or refractory hematologic malignancies, including patients with acute myeloid leukemia and myelodysplastic syndromes.

June 32022, which highlight our financial position as well as our recent progress.

As described in our release this afternoon Macrogenics total revenue consisting primarily of revenue from collaborative agreements was $26 million for the quarter ended June 32022, compared to total revenue of $30 8 million for the quarter ended June 32021 revenue for the quarter ended June 32022 included <unk>.

Inovituzumab is an investigational FC-engineered B7H3-directed monoclonal antibody created, using our FC optimization platform being evaluated in solid tumors.

Net sales of $4 $7 million.

Compared to $3 2 million for the quarter ended June 32021.

In July, we issued a press release announcing the closure of the Phase II study, evaluating, the investigational regimen of Inovituzumab in combination with either retifanilumab, an anti-PD-1 monoclonal antibody, or tibotelumab, a PD-1-by-LAG-3 bispecific DART molecule, in the first-line treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck. The decision to discontinue the study was based on an internal review of safety data, and a risk-benefit analysis in front-line patients of squamous cell carcinoma of the head and neck.

As a reminder, mark gender was launched in the U S. In March 2021 in coordination with our commercial partner <unk> or.

Our research and development expenses were $51 7 million for the quarter ended June 30.

2022, compared to $55 8 million for the quarter ended June 32021. The decrease was primarily related to decreased <unk> manufacturing costs for insight and decreased costs related to discontinued studies. These decreases were partially offset by increased development cost of discovery.

We don't believe this decision has any impact on our other B7H3-directed programs or our, ability to develop Inovituzumab in other indications.

Projects.

And preclinical model molecule increased clinical expenses related to Laura <unk> and increased cost related to <unk> or selling general and administrative expenses were $13 7 million for the quarter ended June 32022, compared to $15 2 million for the quarter ended June 30.

At ASCO in June, investigators from Johns Hopkins presented a poster with encouraging, clinical activity from an ongoing Phase II study of Inovituzumab in patients with localized prostate cancer in a neoadjuvant setting. Inovituzumab showed encouraging clinical activity with 66% of patients having PSA0 at one-year, post-op, which correlated with peripheral expansion of tumor-associated T-cell clones. The published data from the ongoing investigative-sponsored trial to date provide rationale for further, evaluation of Inovituzumab in prostate cancer.

2021.

The decrease was primarily related to decreased margins and selling costs as well as decreased consulting expenses. Our net loss was $41 $3 million for the quarter ended June 32022, compared to a net loss of $39 9 million for the quarter ended June 32021.

Our cash cash equivalents in marketable securities balance as of June 32022 was $133 7 million.

Next, I will provide an update of our product candidates being developed by our collaboration, partners for which we retain certain economic rights. 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. Under our 50-50 collaboration, Imidigen is leading clinical development and has indicated, our plan to complete dose escalation in the Phase 1 study evaluating IMGC936 in multiple cell and tumors with initial data anticipated before year end.

Compared to $243 6 million as of December 31, 2021. The June 32022 balance did not include $34 5 million subsequently received from collaboration partners in July 2022.

Finally.

In terms of our cash runway, we anticipate that our cash cash equivalents in marketable securities balance as of June 32022 to $34 5 million in payments subsequently received from collaboration partners <unk>.

<unk> and anticipated payments from partners.

Teplizumab is an anti-CD3 monoclonal antibody that Prevention Bio acquired from us under, an asset purchase agreement in 2018. Prevention is developing teplizumab for the treatment of type 1 diabetes.

Product revenues plus anticipated savings from our corporate restructuring plan announced today, which Scott will walk through momentarily should extend our cash runway into 2024.

This updated cash runway guidance now reflects anticipated expenditures related to the planned phase III portion of the <unk> phase III study in metastatic castration resistant prostate cancer as well as Macrogenics other ongoing studies and now I will turn the call back to Scott.

On June 30th, Prevention announced the FDA had extended its review period by three months for the VLA-4 teplizumab. The extended PADUFA target action date is November 17, 2022. MacroGenics is eligible to receive royalties on net sales of teplizumab, if approved in addition to milestone payments, including $60 million upon VLA approval in the United States.

Thank you Jim we made important progress in the second quarter with regard to multiple investigational molecule.

Retifalumab is an investigational anti-PD-1 mab that we exclusively licensed to Insight Corporation. MacroGenics is eligible to receive royalties on net sales of retifalumab if approved in addition to milestone payments. In July 2022, MacroGenics received $30 million in milestone payments from Insight as part of its collaboration agreement.

Before I walk through progress we've made on our pipeline, let me update you on our Macrogenics restructuring plan that we are announcing today.

Listeners will recall that over the past several quarters, we have prioritized our pipeline of product candidates and discontinue certain studies to reduce our spending.

We have initiated additional cost saving measures to extend our cash runway with the goal of delivering value, creating data with our existing and anticipated financial resources.

Retifalumab is currently being studied as monotherapy or in combination with other agents across multiple studies.

The additional decisive actions, we announced today with Macrogenics in a stronger position to execute on our prioritized programs.

The cost saving measures include an approximate 15% workforce reduction in full time employees and closure of two of our satellite facilities, including our Brisbane, California based research site in a smaller scale noncommercial GMP manufacturing site in Rockville, Maryland.

In conclusion, we continue to believe 2022 will be another important year for MacroGenics. During the first half of the year, we initiated two clinical studies and we expect to start TAMARAC, a registration-directed study of MGC-OAT in MCRPC by year end.

Also, I am happy to announce that our planned Phase 2-3 study of MgCO18 in patients with metastatic castration-resistant prostate cancer, has a name, which is TAMARIC. We continue to expect to start the TAMARIC study by year-end.

In addition to these programs, we and our partners continue to progress our other clinical, and preclinical candidates and expect to provide further updates as the data matures. With that backdrop, let me use our remaining time to walk through our updates on our portfolio, of investigational clinical molecules, starting with MgCO18, our ADC designed to deliver a DNA-alkylating durocomyosin cytotoxic payload to tumors expressing B7H3. B7H3 is a member, of the B7 family of molecules involved in immune regulation. MgCO18 was designed to take advantage of this antigen's broad expression across multiple cell and tumor types.

We remain committed to developing and delivering life-changing medicines to cancer patients.

We continue to make progress as we operationalize the TAMARIC study. After constructive interactions with the FDA and EMA, we provided key details about the design of the TAMARIC study during the first quarter conference call. As a reminder, during the Phase 2 portion of the study, approximately 150 patients will be randomized one-to-one-to-one to receive either 2 mgs per kg or 2.7 mgs per, kg of MgCO18 every four weeks in the experimental groups, or physicians' choice of an antigen receptor access target or ARAT agent, such as abiraterone, enzalutamide, and apalutamide, not previously received in the control group.

Following completion of the Phase 2 portion of the study, an interim analysis of the data will be performed to further inform the Phase 3 portion, in which we plan to randomize additional patients one-to-one to receive, either MgCO18 at the recommended dose or the ARAT agent for the control group.

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

We continue to expect to start the TAMARIC study by year-end and anticipate delivery of interim data from the study by the end of 2024.

We believe these measures will provide resources to advance our pipeline of innovative product candidates.

The reduction in workforce announced today and will be implemented immediately in some areas and complete overtime as certain projects have wound down and sites are closed.

Operator?

Next, let me update you on loriduralmab.

The decision to reduce our workforce and closed two site was not taken lightly and we are grateful to every macrogenics employee who has helped advance our company.

We continue to dose patients in the Phase 1 dose escalation combination study of MgCO18 with loriduralmab in patients with advanced solid tumors, including renal cell carcinoma, pancreatic cancer, ovarian cancer, hepatocellular carcinoma, metastatic castration-resistant prostate cancer, and melanoma. Based on data from our preclinical studies, anti-tumor activity with MGCO-18 may be enhanced, by combination therapy with an anti-PD-1 agent without significant incremental toxicities.

During the second quarter, we completed enrollment in a Phase I-II dose expansion study with, Laura Jeromeb as monotherapy in cohorts of patients with microsatellite-stable colorectal cancer, MCRPC, melanoma, and checkpoint IE non-small cell lung cancer.

With these actions we believe our updated cash runway should enable the delivery of interim data from the phase II portion of the <unk> prostate cancer study by the end of 2024 data from the phase one dose expansion of larger met by early 2023 and data from the dose escalation.

Okay.

We expect to provide a data update from this study by early 2023.

Next up, I'll discuss our efforts to advance treatment of patients with CD123-positive, hematological malignancies. MGDL24 is our next-generation bi-specific 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. We recently dosed the first patient in a Phase I study of MGDL24 in CD123-positive relapsed, or refractory hematologic malignancies, including patients with acute myeloid leukemia and myelodysplastic syndromes.

Inovituzumab is an investigational FC-engineered B7H3-directed monoclonal antibody created, using our FC optimization platform being evaluated in solid tumors.

In July, we issued a press release announcing the closure of the Phase II study, evaluating, the investigational regimen of Inovituzumab in combination with either retifanilumab, an anti-PD-1 monoclonal antibody, or tibotelumab, a PD-1-by-LAG-3 bi-specific DART molecule, in the first-line treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck. The decision to discontinue the study was based on an internal review of safety data, and a risk-benefit analysis in front-line patients of squamous cell carcinoma of the head and neck.

We don't believe this decision has any impact on our other B7H3-directed programs or our, ability to develop Inovituzumab in other indications.

At ASCO in June, investigators from Johns Hopkins presented a poster with encouraging, clinical activity from an ongoing Phase II study of Inovituzumab in patients with localized prostate cancer in a neoadjuvant setting. Inovituzumab showed encouraging clinical activity with 66% of patients having PSA0 at one-year, post-op, which correlated with peripheral expansion of tumor-associated T-cell clones. The published data from the ongoing investigative-sponsored trial to date provide rationale for further, evaluation of Inovituzumab in prostate cancer.

Next, I will provide an update of our product candidates being developed by our collaboration, partners for which we've retained certain economic rights. 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. Under our 50-50 collaboration, Imidigen is leading clinical development and has indicated, our plan to complete dose escalation in the Phase I study evaluating INGC 936 in multiple cell tumors with initial data anticipated before year-end.

<unk> of <unk> 24 in AML patients as well as the execution of our other ongoing clinical and preclinical settings.

The floor is now open for your questions.

Teplizumab is an anti-CD3 monoclonal antibody that Prevention Bio acquired from us under, an asset purchase agreement in 2018. Prevention is developing teplizumab for the treatment of type 1 diabetes. On June 30th, Prevention announced the FDA had extended its review period by three months for the BLA for teplizumab. The extended to target action date is November 17, 2022. MacroGenics is eligible to receive royalties on net sales of teplizumab if approved, in addition to milestone payments, including $60 million upon BLA approval in the United States.

Retifalumab is an investigational anti-PD-1 mab that we exclusively licensed to Insight Corporation. MacroGenics is eligible to receive royalties on net sales of retifalumab if approved in addition, to milestone payments. In July 2022, MacroGenics received $30 million in milestone payments from Insight as part of its collaboration agreement. Retifalumab is currently being studied as, monotherapy or in combination with other agents across multiple studies.

In terms of our pipeline since our last quarterly update we completed enrollment of the phase <unk> dose expansion study of Laura <unk>, a bispecific dart molecule targeting PD, one and <unk> four in advanced solid tumors.

In conclusion, we continue to believe 2022 will be another important year for MacroGenics. During the first half of the year, we initiated two clinical studies and we expect to start, Tamarack, a registration-directed study of MGC-OAT in MCRPC by year end.

We remain committed to developing and delivering life-changing medicines to cancer patients.

To ask a question at this time, please press star 1 on your telephone keypad. At any point, you would like to withdraw from the queue, please press star 1 again.

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

Also in July we dosed the first patient in the phase one study of <unk> for our next generation CD 123 by <unk> Dart molecule in patients with CD 120, <unk> positive hematologic.

You will be provided with the opportunity to ask one question and one further follow-up question.

Operator?

If you have any further questions, you may raise your hand and queue up again.

We'll take a moment to render our roster.

Okay.

Dave Milligan malignancies.

In addition, we continue to dose patients in the dose escalation combination study of <unk> 300.

Our first question comes from, John Miller from Evercore.

Please go ahead.

73, directed antibody drug conjugate with Laura <unk> in patients with advanced solid tumors.

Hi, guys.

Also I am happy to announce that our planned phase III study of <unk> in patients with metastatic castration resistant prostate cancer has the name which is turmeric.

Thanks so much for taking the question.

And congrats on restructuring it by a little bit and extending the runway a little further.

We continue to expect to start with turmeric study by year end.

In addition to these programs with our partners continue to progress our other clinical and preclinical candidates and expect to provide further updates as the data matures.

I'd, love to get a sense of exactly what the new guidance is, though, precisely, because it seems like there were two different languages being used.

With that backdrop, let me use our remaining time to walk through our update on our portfolio of investigational clinical molecules, starting with <unk>, our ABC designed to deliver DNA alkylating do are combined.

Cytotoxic payloads in tumors expressing <unk> <unk> three.

<unk> three is a member of the <unk> family of molecules involved in immune regulation.

<unk> was designed to take advantage of this antigen broad expression across multiple solid tumor types.

We continue to make progress as we operationalize the tamarac study.

After constructive interactions with the FDA and EMA, we provided key details about the design of the tamarac steady during the first quarter conference call.

As a reminder, during the phase two portion of the study approximately 150 patients will be randomized one to one to one to receive either <unk> or $2 76 per kg of <unk> every four weeks.

Okay, the floor is now open for your questions.

To ask a question at this time, please press star 1 on your telephone keypad.

At any point you would like to withdraw from the queue, please press star 1 again.

Fair mental groups.

<unk> choice of an engine reset their access target, Hey, Brad agents, such as abiraterone and <unk> minimized.

<unk> not previously received in the control group.

Following completion of the phase <unk> portion of the study and interim analysis, the data will be Brooklyn to further inform the phase III portion.

Which we plan to randomize additional patients one to one to receive either energy.

INTO24, I think, was mentioned in the press release.

But then also, Scott, you mentioned having runway through URN24, where the Tamarack data was expected.

<unk> at the recommended dose.

Hey, Rod agent for the control group.

We continue to expect to start the <unk> study by year end and anticipate delivery of interim data from this study by the end of 2024.

So just remind me what the exact guidance is with the languages, you're going with.

You will be provided with the opportunity to ask one question and one further follow-up question.

Yeah, thanks, John.

If you have any further questions, you may raise your hand and queue up again.

We'll take a moment to render our roster.

Next let me update you on larger one that we continue to dose patients in the phase one dose escalation combination study of <unk> with Laurent Gerald <unk> in patients with advanced solid tumors included including renal cell carcinoma, pancreatic cancer ovarian cancer and <unk>.

Carcinoma, metastatic castration resistant prostate cancer and melanoma.

Based on data from our preclinical studies anti tumor activity with MTT team may be enhanced by combination therapy with an anti PD, one agent without significant incremental toxicities.

During the second quarter, we completed enrollment in the phase <unk> dose expansion study with larger <unk> as monotherapy in cohorts of patients with microsatellite satellite stable colorectal cancer and CRP C.

Sure and checkpoint naive non small cell lung cancer.

I'll start, and I think Scott will probably finish. So the exact guidance is that our cash runway, which reflects not only the $134 million that, we had at June 30, but the additional $34.5 million that we received subsequently in the month of July, plus product revenues and other anticipated payments from partners, pushes our cash runway into 2024.

We expect to provide a data update from this study by early 2023.

Next I'll discuss our efforts to advance treatment of patients with CD 123 positive Hematological malignancies.

Yeah, and just further on, John, obviously, we can get more precision on this when the study starts and how quickly the patients get enrolled.

<unk> 24 is our next generation bi specific CD 123 by CD three dart molecule that incorporates a CD three components designed to minimize satisfied with <unk> syndrome.

But given where we are right now in that process, we are confident that we'll be able to start the, study before the end of the year, get enrolled during 23, and have the readout by the end of the year.

So we think that without exact precision right now, because in addition to the milestone payments, which obviously we can never guarantee, we have a considerable amount of BD activity ongoing, which could obviously extend runway further.

Maintaining antitumor side Olympic activity, and permitting intermittent dosing to a longer half life.

We recently dosed the first patient in a phase one study of <unk> 24, and CD 123 positive relapsed or refractory hematologic malignancies, including patients with acute myeloid leukemia and Myelodysplastic syndromes.

We should be able to provide further precision in the future with regard to how far into 2024 that goes.

All right, thanks very much.

And one, maybe one or two more, if I may.

I'm curious now at this, point about Inoble versus 018 overlap.

<unk> is an investigational FC engineered <unk> directed monoclonal antibody created using our FC optimization platform being evaluated in solid tumors.

In July we issued a press release announcing the closure of the phase II study evaluating the investigational regiment of <unk> in combination with <unk>, an anti PD, one monoclonal antibody or <unk>.

<unk>, our PD one by lag three Bispecific dart molecule in the first line treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

The decision to discontinue the study was based on an internal review of safety data and the risk benefit analysis and frontline patients with squamous cell carcinoma of the head and neck.

We don't believe that decision has any impact on our other <unk> directed programs or our ability to develop a novel to the mab and other indications.

And also in June investigators from Johns Hopkins presented a poster with encouraging clinical activity from an ongoing phase II study of <unk> in patients with localized prostate cancer in the neo adjuvant setting.

<unk> that showed encouraging clinical activity with 66% of the patients have a PSA zero at one year post up which correlated with peripheral expansion of tumor associated T cell phone.

The published data from the ongoing investigator sponsored trial to date provide rationale for further evaluation of the novel <unk> in prostate cancer.

Next I will provide an update of our product candidates being developed by our collaboration partners Fortunately retain certain economic rights.

Our second investigational ADT, IMTT, 96, which targets Adam nine.

Surface protein over expressed in several solid tumor types is being advanced under our co development agreement with Immunogen.

Under a 50 50 collaboration Immunogen is leading clinical development and indicated our plan to complete dose escalation in the phase one study evaluating <unk> 936 in multiple solid tumors with initial data anticipated before year end.

Okay, our first question comes from John Miller from Evercore.

And I think maybe it made sense to have them separate before, but I'd love, in light of the prioritization, for you to tell me a little bit about how you're feeling about having both of these, having studies ongoing for both these programs.

Please go ahead.

To put the mat is an anti <unk> monoclonal antibody as a prevention bio required from us under an asset purchase agreement in 2018.

Are they differentiated enough to justify keeping both active, especially as 018 sort of advances to later stage trials?

Hi, guys.

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

On June 30th Prevention announced the FDA has extended its review period by three months for the BLA for daclizumab.

<unk> tended to do put target action date is November 17 2022.

Macrogenics is eligible to receive royalties on net sales of the person that is approved in addition to milestone payments, including $60 million upon BLA approval in the United States.

And then, you know, not exactly the same, obviously, but a little bit related.

Thanks so much for taking the question.

And congrats on restructuring and biting the bullet, a little bit and extending the runway a little bit further.

I'd love to get a sense of exactly what the new guidance is, though, precisely because it seems like there were two different languages being used into 24, I think, was mentioned in the press release.

<unk> is an investigational anti PD, one that that we exclusively licensed to <unk> Corporation.

But then also, Scott, you mentioned having runway through year-end 24 where the Tamarack data was expected.

Macrogenics is eligible to receive royalties on net sales of <unk>. If approved in addition to milestone payments.

In July 2020 to Macrogenics received $30 million in milestone payments from insight as part of the collaboration agreement.

So just remind me what the exact guidance is with the languages you're going with.

<unk> is currently being studied as monotherapy or in combination with other agents across multiple studies.

In conclusion, we continue to believe 2022 will be another important year for macrogenics.

During the first half of the year, we initiated two clinical studies and we expect to start Tamarac, a registration directed study of <unk>.

MCR PC by year end, we remain committed to developing and delivering life changing medicines to cancer patients.

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

Operator.

Yeah.

Okay. The floor is now open for your questions to ask a question at this time. Please press star one on your telephone keypad any point, we'd like to withdraw from the queue.

Please press star one again.

We will be provided with the opportunity to ask one question and one further follow up question. If you have any further questions you may raise your hand and queue up again.

We'll take a moment to render our roster.

Okay. Our first question.

John Miller from Evercore. Please go ahead.

Hi, guys. Thanks for taking the question.

And congrats on restructuring and payable at a little bit and extending the runway a little bit further I'd love to get a sense of exactly what the new guideline guidance is though precisely because it seemed like there were two different languages being used.

Into 'twenty four I think we've mentioned in the press release, but then also Scott you mentioned, having runway through year end 24, where the tamarack data was.

As expected.

Remind me what the exact guidance.

The languages are going global.

Yes, Thanks, John I'll start and I think Scott will probably finished so the exact guidance is that our cash runway, which reflects not only be $134 million that we had at June 30, but the additional $34 5 million that we received subsequently in the month of July plus product revenues and other anticipated payments from partners push.

Should we expect similar dynamics for 024 as we had from flotacuzumab?

As our cash runway into 2024.

Yes, and just first of all John obviously, we can get more precision on this when the study starts and how quickly these patients get enrolled but.

Given.

Where we are right now in that process. We are confident that we'll be able to start the study before the end of the year again or no.

So should we be looking, for the same sorts of signals in terms of patients and populations, refractory versus relapsed patients, that sort of thing, as we approach it early day to day?

Yeah, thanks, John.

During 'twenty three and have the readout by the end of the year.

Thanks.

So we think that.

Without exact precision right now because in addition to milestone payments, which obviously, we can never guarantee we have considerable amount of BD activity ongoing.

Great questions.

Which could obviously extend runway further.

We should be able to provide further precision.

In the future with regard to how far into 2004 that goes.

Alright, thanks, very much and one maybe one or two more.

If I may.

I'm curious now at this point about.

<unk> versus one eight overlap and I think maybe it made sense to have them separate before but I'd love in light of the prioritization for you to tell me a little bit about how you're feeling about having both of these studies ongoing for both of these programs are they differentiated enough to justify keeping both active.

So we were very excited about the update that the Johns Hopkins group was able, to provide at ASCO.

I'll start, and I think Scott will probably finish. So the exact guidance is, that our cash runway, which reflects not only the $134 million that we had at June 30, but the additional $34.5 million that we received subsequently in the month of July, plus product revenues and other anticipated payments from partners, pushes our cash runway into 2024.

Especially as <unk> sort of advances to later stage trials and then.

Not exactly the same obviously, but a little bit related should we expect similar dynamics for Q4 as we had from <unk>. So should we be looking for the same sorts of signals in terms of patient sub populations refractory versus relapsed patients that sort of thing as we look forward to early data that thanks, Greg.

Yeah, and just further on, John, obviously, we can get more precision on this when the study starts and how quickly the patients get enrolled.

But given where we are right now in that process, we are confident that we'll be able to start the, study before the end of the year, get enrolled during 23, and have the readout by the end of the year.

Great questions.

So we were very excited about the update is that the Johns Hopkins Group Board of tables are provided us. So as you know that's received a lot of positive feedback.

So we think that without exact precision right now, because in addition to the milestone payments, which obviously we can never guarantee, we have a considerable amount of BD activity ongoing, which could obviously extend runway further.

Neo adjuvant setting, which as you know is.

Either that or are you a little efforts are being conducted there in that early early setting.

Despite the fact of the head and neck setback with regard to the.

Stopping the study for another two than that.

The safety profile for novel <unk> early Ashland prostate setting.

It was excellent and based on both the encouraging data.

Biomarker data.

And the patients' responses.

The group that conducting that study.

An expanded group is a very enthusiastic so look at it very early setting.

Sure.

Prostate cancer in a notebook Susan that as you know.

Current efforts right now with regard to <unk> is in the later line metastatic setting and so we're again focused on.

Both.

Patients that had been experienced with.

Hey, Rod agents as well as tax paying agents.

Still opportunity to move up the line, but given.

We need to have.

Very clean.

<unk>.

Drug for treating patients with localized disease.

Another <unk> of that is better set up.

For pursuing that indication.

Also indicate that we are looking at other possibilities in the novel.

Susan.

Beyond that.

Early stage prostate cancer and of course as you know we have the ongoing combination studies of <unk> or Joe Matt in seven different tumor types and based on the results of those studies.

<unk>.

Other.

Solid tumor indications going forward with <unk>.

Now with regards to the question you had about.

The <unk> 24 with respect to quality to the Nab and its used in refractory disease as we've outlined at the last Ash meeting we are very encouraged that the use of <unk> 24 based on the better.

Profile, and reducing cytokine release as well as intermittent dosing will allow a much broader application of NGL 24 beyond what we were able to do with potent Susan that both in late line refractory patients as well as patients with early disease in particular.

We're extremely encouraged by the combination studies, we had with <unk> 24, and understand the therapies and look to using this quite broadly after we initially do the dose escalation studies in patients with relapsed refractory disease. We're also looking at the opportunity in <unk>.

24 beyond AML.

Using is in.

Tumor settings.

We're a CD 123 is over expressed including a myelodysplastic syndrome and other indications. So there is certainly a differentiation and expansion of our intended use for <unk> 24, which provided some of the rationale of why we stopped.

Tried to pursuing floated to the mass development.

Our next question comes from David Dye from AST and BC.

Okay, great. Thanks for taking my questions.

I have a couple of questions as well. So first question is just around <unk>. So we will look at the phase one dose expansion study that was presented at ESMO last year, we saw that about 30% of patients dose reduced and 55% of the CRP C patients where it dose interrupted.

So could you provide some color on what.

What's the lowest dose level that was dose reduced and how long were the duration of those interruptions for these patients and then how should we think about the potential read through to the reduce the dose regimen for them for the <unk> trial, the phase III <unk> trial.

David Thank you very much for that question, obviously, we've been spending a lot of time.

Analyzing the data that we extracted from this study not only in patients with prostate cancer, but those.

That we tested in other solid tumor indications.

Again, just to refresh everyone's memory.

The expansion cohorts for these studies started out with a three Meg per kg dosing Q3 week level it turn.

Turns out the majority of patients.

Either dose reductions or holding doses with <unk>.

Longer.

Periods before the patients will restart in dosing.

Largely due to side effect profile.

We took this into account we looked at the full dataset from all patients treated with <unk>.

<unk> and identified the ultimate dose that every patient.

Ultimately treated with during the course of therapy.

Came out with a average amount of drug that was delivered to those patients.

We sized up that result with their <unk>.

Clinical responses, both in terms of side effect profile as well as responsiveness.

By doing this we were highlighting in particular side effects seen most problematic to the continued treatment of patients.

Ones that we highlighted before was hand foot syndrome, where well the majority of patients had only grade one grade two side effects profile is very few grade three.

It turned out a significant number of patients who are likely twos, which was.

Manifested by the appearance of pain in those patients.

Cause many of those patients who stopped continuing treatment and so when we did an analysis of the actual dose.

Both.

<unk> inducing responsiveness as well as reducing the incidence and severity of side effects, we saw a.

Difference that fell in that range that we ultimately decided on treating these patients.

Two mix per kg on a Q4 weekly basis up to $2 700 expert kick on a Q4 weekly basis, so boxes that dosing range to ultimately move forward in this now phase II component of the phase three study.

Yes.

Our next question comes from Steven wildly from Stifel.

Okay.

Yes, good afternoon, thanks for taking the questions.

Maybe just with respect to OTT four is there anything that you can say about <unk>.

Yes, how you're dosing this drug during cycle. One is it just is it just a flat dose that you're administering is there going to be sort of attempt to migrate over to some kind of a titration regimen.

Could speak to the pre medication that you're using as well that'd be helpful.

And then just a quick follow up on Tamar.

Yeah.

It's Steve.

Based on interactions with the FDA, we started out with enable dosing.

This drug was.

The requirement.

And as you know we spend a lot of time with cloud to demand ultimately getting.

Dose escalation and.

Increased particularly on the plug in to the first week, we ultimately believe.

On the dosing that this can be.

<unk>.

Either wait or body weight or on a flat dosing.

Regimen going forward.

So we'll have to see how that goes.

Particularly at the lower doses, we expect those to move up quite.

Quickly.

But we'll have to see as we move up the line.

Okay and then.

With respect to tumor can you.

I guess speak to the number of sites that you are hoping to enroll these 150 patients across.

Should we just expect that.

In term analysis.

<unk>.

I guess, if the efficacy data what is the trigger for the presentation of that from that interim data on the efficacy side is it going to be based upon some threshold number of <unk>.

Radiographic progression events. If there is I guess anything that you can say that it would be.

Would be helpful.

So with regards to number of sites that we haven't come up with a final number we're obviously starting.

Given.

On the regulatory timing of things in U S sites are.

<unk> this is though.

A worldwide study.

U S Europe and Asia.

So.

I cant come up with a specific number that we will ultimately end up with obviously will be.

A large number of double digit initially.

As we do the phase III studies and will be expand the intent would be to expand as.

As we moved over from Phase II Phase III and we hope by the time, we start the enrollment at the end of the year, we'll be able to be a little bit more precision.

As you know, that received a lot of positive feedback in a neoadjuvant setting, which, as you know, is either not or very little efforts are being conducted there in that early setting.

We should be able to provide further precision in the future with regard to how far into 2024 that goes.

On.

Site engagement.

As plans for expansion, especially when we get feedback from the European sites.

Yes.

With regard to the analysis of this data we have.

Predefined.

Analysis defined in our protocol.

That is being given to the DSM.

Again, we're not at Liberty right now to disclose what those specific patrolled include obviously response rate.

Going forward. We obviously also have the ability to amend that at any particular time.

During that course of that phase II study there will be a futility analysis that has been incorporated in this.

During the course of enrollment again the plan is to enroll 150 patients in those three.

The two experimental groups more controllable.

Okay. Thanks for taking the questions.

Steve.

Our next question comes from Exar drought.

Great. Thanks for taking the question just again on <unk>, just wondering if you could speak to a little bit about <unk>.

Thats the population of patients that Youll look at the metastatic castrate resistant.

Prostate cancer cohort should we think about it similar to what.

You looked at in the Phase one two and then maybe if you can again speak to any appropriate benchmarks. We should think about now prefer that study in terms of how to kind of compare.

Responses that we'll see.

Interim analysis thank.

Thank you.

And so thanks, so much for that.

Question or set of questions with regards to tamarac, So again.

Similar to what we had enrolled.

In the expansion cohort.

Of the 40 40 patients.

These will be metastatic castration resistant prostate patients that had one prior.

<unk> receptor.

<unk> targeting agents.

They can have they will have one prior docetaxel regimen.

And we will also allow up to one prior capozzi taxon regimen, obviously an optional.

But no other prior chemotherapy.

Patients will be stratified based on that.

Visceral disease.

Whether they've had about the taxable and also regional analysis.

Of the drug.

Again, I think the benchmarks differ.

Depending on lines of therapy.

And you're very well aware that that has a wide range of baseline responses.

Overall response rates.

Two to three months.

Two to four months.

Based on depending on the.

Previous lines of therapy so.

For that reason and obviously the changing landscape of what keep patients are now receiving an obviously introduction of <unk>.

New agents into the Administaff market.

It included a control group.

So we'd be able to.

Do a very good job.

<unk> marketing to the current <unk>.

That is for patients.

Our next question comes from Jim Macdonald from Factset.

Your line is open. Please go ahead.

We can skip to the next one.

<unk>.

Our next question comes from Jonathan Chang from <unk> Securities.

Hi, guys. Thanks for taking the question. This is central associated on for Jonathan I wanted to ask for the <unk> eight plus Larry Cherilyn that combination can you remind us. The study designed here in particular, what dose of <unk> is being used and then also when we might be able to.

See data for that combination. Thank you.

Yes, thanks very much.

So the starting dose for <unk> is one thing.

On our Q.

I think it's Q4 weekly basis now.

And more general math is that <unk> mix per kg on the same dosing regimen.

The plan would be to dose escalate the <unk>, we're going to be expected next dose would be.

Two megs per keg.

And we have other.

<unk> dosing that can be modifications based on side effect profiles et cetera.

But right now we are.

Targeting the.

The larger one that those who like to take forward, both as monotherapy and combination.

Slowly titrated up.

The <unk> dosing.

Our next question comes from Charles Zhou from Guggenheim.

Hi, This is Edward on for Chuck.

Charles Thanks for taking our question maybe regarding <unk> I apologize if I missed this but are you planning to present, but the extension data that you had on the old dosing regimen. I think you talked about last time about maybe later this year, having some prostate melanoma data.

Yes, so thanks very much of a question.

At this time.

Discusses we were intending to add an expansion cohort four melanoma.

And as you've heard today with regard to the prioritization of programs.

One of the things, we said, we're going to hold off on was.

Any additional patients to the melanoma cohort.

Time, despite the encouraging data that we had seen so our plans right now on updates on this program.

It will depend on when we are going to initiate.

Additional.

Studies.

With other indications and at that time with the update.

Everyone regarding our experience with these other indications as well.

The prostate.

We have.

<unk>.

Our feedback.

From the key experts from the regulators and the plan going forward with regard to.

Two the Tamarac studies right now.

Further updates on this to come in some sort of a scientific publication at a future date.

Great. Thank you.

Our final question comes from Peter Lawson from Barclays.

Okay.

Hi, This is Jay on for Peter Lawson, Thanks for taking the question.

The restructuring could you help us.

How we should be thinking about the opex for the remainder of 2022 and through 2023. Thank you.

Yes, we're not providing specific guidance today is shared with regard to the expenses, what we are providing as you've heard us say if the cash runway.

Note that the.

The anticipated savings from head count on a steady state basis should be approximately $10 million annually. That's not this year, obviously, because we're more than halfway through the year, but.

And for the full amount of the savings from the approximately 15% of reduction in force.

Great. Thank you.

Okay.

Alright, we do have a final question from Jim Massawa from Factset.

Okay.

Your line is open. Please go ahead.

At this time I would now like to turn the call over to Doctor Scott <unk> for closing remarks.

Thank you everyone for joining our call today, we look forward to updating you on the progress of our various programs in the near future and hope you have a good evening.

Thank you ladies and gentlemen. This concludes today's call. Thank you for your participation you may now disconnect.

Please wait the conference will begin shortly.

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Despite the fact of the head and neck setback with regard to the stopping the study for novotuzumab, the safety profile for novotuzumab in the early neoadjuvant prostate setting was excellent. And based on both the encouraging data, the biomarker data, and the patient's responses, the group that conducted that study and an expanded group are very enthusiastic to look at a very early setting for prostate cancer and novotuzumab.

All right, thanks very much.

Sure.

Okay.

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As you know, our current efforts right now with regard to MGCO18 is in the later line metastatic setting.

And one, maybe one or two more, if I may.

And so we're again focused on both patients that have been experienced with ARAT agents as well as Taxane agents.

Okay.

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Still opportunities to move up the line, but given that you need to have a very clean, drug for treating patients with localized disease, we think novotuzumab is better set up for pursuing that indication.

I'm curious now at this, point about Inoble versus 018 overlap.

Now, I should also indicate that we are looking at other possibilities of novotuzumab beyond that of early stage prostate cancer.

And I think maybe it made sense to have them separate before, but I'd love, in light of the prioritization, for you to tell me a little bit about how you're feeling about having both of these, having studies ongoing for both these programs.

And of course, as you know, we have the ongoing combination studies of MGCO18 and lorodromab in seven different tumor types.

Are they differentiated enough to justify keeping both active, especially as 018 sort of advances to later stage trials?

And then, you know, not exactly the same, obviously, but a little bit related.

And based on the results of those studies can guide us in other solid tumor indications, going forward with MGCO18.

Should we expect similar dynamics for 024 as we had from flotacuzumab?

Now, with regard to the question you had about the MgD-024 with respect to Clotetuzumab and, its use in refractory disease, as we've outlined at the last ASH meeting, we are very encouraged that the use of MgD-024, both based on the better profile in reducing cytokine release as well as intermittent dosing will allow a much broader application of MgD-024 beyond what we were able to do with Clotetuzumab, both in late-line refractory patients as well as patients with early disease.

In particular, we are extremely encouraged by the combination studies we had with MgD-024 and other standard therapies and look to using this quite broadly after we initially do the dose escalation studies in patients with relapsed refractory disease.

Okay.

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So should we be looking, for the same sorts of signals in terms of patient subpopulations, refractory versus relapsed patients, that sort of thing, as we look forward to early data there?

Thanks.

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We're also looking at the opportunity of MgD-024 beyond AML, using it in tumor settings where CD123 is overexpressed, including monodysplastic syndrome and other indications.

So there is certainly a differentiation and expansion of our intended use for MgD-024, which provided some of the rationale of why we stopped further pursuing Clotetuzumab development.

Our next question comes from David Dai from SMBC.

Hey, great.

Thanks for taking my questions.

So I have a couple of questions as well.

Okay.

Great.

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So, first question is just around MgC018.

So when we look at the phase one dose expansion study that was presented at ESMO last year, we saw that about 30% of patients were dose reduced and 55% of the MCRPC patients were dose interrupted.

So could you provide some color on what was the lowest dose level that was dose reduced and how long were the duration of the dose interruption for these patients?

Yes.

Yeah.

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And then how should we think about the potential read-through to the reduced dose regimen for the TEMRAC trial, the phase two, three TEMRAC trial?

Yes.

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David, thank you very much for that question.

Okay.

Yeah.

Okay.

Okay.

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Thanks.

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Okay.

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And obviously we've been spending a lot of time, of analyzing the data that we extracted from the study, not only in patients with prostate cancer, but those that we tested in other solid tumor indications.

Okay.

Okay.

Yes.

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Again, just to refresh everyone's memory, the expansion cohorts for these studies started out with a three mc per kg dosing on a two, three week level. It turns out the majority of patients had either dose reductions or holding doses with a longer period before the patients were restarted in dosing, largely due to side effect profiles.

We took this into account.

We looked at the full data set from all patients treated with MGCO18 and identified the ultimate dose that every patient was ultimately treated with during their course of therapy and came out with an average amount of drug that was delivered to those patients. We sized up that result with their clinical responses, both in terms of side effect profiles, as well as responsiveness.

And by doing this, we were highlighting particular side effects that seemed most problematic to the continued treatment of patients.

Good afternoon, we will begin the macro Janet 2022 second quarter corporate progress and financial results conference call in just a moment.

Ones that we highlighted before was hand foot syndrome, where while the majority of patients had only grade one or grade two side effect profiles, very few grade threes, it turned out a significant number of patients who had grade twos, which was manifested by the appearance of pain in those patients, caused many of those patients to stop continuing treatment.

All participants in the listen only mode at the moment.

And so when we did an analysis of the actual dose that was both effective in inducing responsiveness, as well as reducing the incidence and severity of side effects, we saw a difference that fell in that range that we ultimately decided on treating these patients. 2 mg per kg on a Q4 weekly basis, up to 2.7 mg per kg on a Q4 weekly basis.

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 <unk>, Vice President of Investor Relations and corporate communications of Macrogenics.

So we've boxed, in that dosing range to ultimately move forward in this now Phase II component of the Phase, II-III study.

Our next question comes from Stephen Wiley from CFL.

Thank you operator, good afternoon, and welcome to Macrogenics conference call to discuss our second 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 todays announcements, 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 will be archived for 30 days beginning approximately two hours after the call is completed.

I would 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 set.

<unk> of our annual quarterly and current reports filed with the SEC.

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 would like to turn the call over to Dr. Scott.

President and Chief Executive Officer of Macrogenics.

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

This afternoon I will provide key updates on our clinical program as well as our restructuring plan intended to extend our cash runway.

But before I do so let me first turn the call to Jim Carroll, Our Chief Financial Officer, who will review our financial results.

Scott This afternoon Macrogenics reported financial results for quarter ended June 32022, which highlight our financial position as well as our recent progress.

As described in our release this afternoon Macrogenics total revenue consisting primarily of revenue from collaborative agreements was $26 million for the quarter ended June 32022, compared to total revenue of $38 million for the quarter ended June 32021 revenue for the quarter ended June 32022 included Mark Jensen.

Net sales of $4 7 million.

Compared to $3 2 million for the quarter ended June 32021.

As a reminder, mark gender was launched in the U S. In March 2021 in coordination with our commercial partner ever sign up our research and development expenses were $51 7 million for the quarter ended June 30.

2022, compared to $55 8 million for the quarter ended June 32021. The decrease was primarily related to decreased <unk> manufacturing costs for insight and decreased costs related to discontinued studies. These decreases were partially offset by increased development cost of discover.

New projects.

And preclinical model molecules increased clinical expenses related to larger la map and increased costs related to <unk> or selling general and administrative expenses were $13 $7 million for the quarter ended June 32022, compared to $50 2 million for the quarter ended June 30.

So we were very excited about the update that the Johns Hopkins group was able, to provide at ASCO.

As you know, that received a lot of positive feedback in a neoadjuvant setting, which, as you know, is either not or very little efforts are being conducted there in that early setting.

<unk> 2021.

The decrease was primarily related to decreased Mark Jensen selling costs as well as decreased consulting expenses. Our net loss was $41 $3 million for the quarter ended June 32022, compared to a net loss of $39 9 million for the quarter ended June 32021.

Our cash cash equivalents in marketable securities balance as of June 32022 was $133 $7 million.

Compared to $243 6 million as of December 31, 2021. The June 32022 balance did not include $34 5 million subsequently received from collaboration partners in July 2022.

Finally.

In terms of our cash runway, we anticipate that our cash cash equivalents in marketable securities balance as of June 32022 to $34 5 million in payments subsequently received from collaboration partners.

<unk> and anticipated payments from partners.

Product revenues plus anticipated savings from our corporate restructuring plan announced today, which Scott will walk through momentarily should extend our cash runway into 2024.

This updated cash runway guidance now reflects anticipated expenditures related to the planned phase III portion of the <unk> phase III study in metastatic castration resistant prostate cancer as well as Macrogenics other ongoing studies and now I will turn the call back to Scott.

Thank you Jim we made important progress in the second quarter with regard to multiple investigational molecule.

Before I walk through progress we've made on our pipeline, let me update you on our Macrogenics restructuring plan that we are announcing today.

Listeners will recall that over the past several quarters, we have prioritized our pipeline of product candidates and discontinued certain studies to reduce our spending.

We have initiated additional cost saving measures to extend our cash runway with the goal of delivering value, creating data with our existing and anticipated financial resources.

The additional decisive actions, we have announced today she put macrogenics in a stronger position to execute on our prioritized programs.

Yeah, good afternoon.

The cost saving measures include an approximate 15% workforce reduction in full time employees and closure of two of our satellite facilities, including our Brisbane.

California based research site in a smaller scale noncommercial GMP manufacturing site in Rockville, Maryland.

We believe these measures will provide resources to advance our pipeline of innovative product candidates.

The reduction in workforce announced today and will be implemented immediately in some areas and completed overtime as certain projects have wound down in fact are closed.

The decision to reduce our workforce and close two site was not taken lightly and we are grateful to every macrogenics employee who has helped advance our company.

Thanks for taking the questions.

With these actions we believe our updated cash runway should enable the delivery of interim data from the phase II portion of <unk>.

Prostate cancer study by the end of 2024 data from the phase one dose expansion of larger mab by early 2023 and data from the dose escalation of NGL 24 in AML patients as well as the execution of our other ongoing clinical and preclinical studies.

Maybe just with respect to O2-4, is there anything that you can say about, I guess, how you're dosing this drug during Cycle I?

Yes.

In terms of our pipeline since our last quarterly update we completed enrollment of the phase one two dose expansion study of Lora General map, our bi specific dart molecule targeting PD, one and <unk> four in advanced solid tumors.

Is it just a flat dose that you're administering?

Also in July we dosed the first patient in the Phase one study of NGL 24, our next generation CD 123 by CDP Dart molecule in patients with CD 123 positive hematologic malignancy malignancies.

Is there going to be some attempt, to migrate over to some kind of titration regimen?

In addition, we continue to dose patients in the dose escalation combination study of <unk>, our <unk> directed antibody drug conjugate with Laura <unk> in patients with advanced solid tumors.

Also I am happy to announce that our planned phase III study of <unk> in patients with metastatic castration resistant prostate cancer has a name which is turmeric.

And if you could speak to the premeditation that you're using as well, that'd be helpful.

And then just have a quick follow-up on Tamera.

We continue to expect to start the tamarac studies by year end.

To these programs, we and our partners continue to progress our other clinical and preclinical candidates and expect to provide further updates as the data matures.

Yeah, thanks, Steve.

With that backdrop, let me use our remaining time to walk through our update on our portfolio of investigational clinical molecules, starting with <unk>, our ADC designed to deliver DNA alkylating door combined cytotoxic payload in tumors expressing b 783.

You know, based on interactions with the FDA, we started out with Mabel dosing, of this drug. This was a requirement.

<unk> is a member of the <unk> family of molecules involved in immune regulation.

<unk> was designed to take advantage of this antigen broad expression across multiple solid tumor types.

We continue to make progress as we operationalize the tamarac study.

After constructive interactions with the FDA and EMA, we provided key details about the design of the tamarac steady during the first quarter conference call.

As a reminder, during the phase two portion of the study approximately 150 patients will be randomized one to one to one to receive either two makes for kids or $2 seven mix per kg of <unk> every four weeks in the experimental groups or physician's choice of an engine reset their access.

Hey, Brad agent, such as Abiraterone, and <unk> minimized Alapa absolute of mine not previously received in the control group.

Following completion of the phase two portion of the study and interim analysis. The data will be broker one to further inform the phase III portion in which we plan to randomize additional patients one to one to receive either <unk> at the recommended dose for the Rad agent for the control group we.

Continue to expect to start the Tamarac studies by year end and anticipate delivery of interim data from this study by the end of 2024.

Next let me update you on larger one that we continue to dose patients in the phase one dose escalation combination study of MTT, Oh, 18, with Orange <unk> and patients with advanced solid tumors included including renal cell carcinoma pancreatic cancer ovarian cancer. The patents are there.

Carcinoma, metastatic castration resistant prostate cancer and melanoma.

Despite the fact of the head and neck setback with regard to the stopping the study for novotuzumab, the safety profile for novotuzumab in the early neoadjuvant prostate setting was excellent.

Based on data from our preclinical studies anti tumor activity with <unk> may be in hand by combination therapy with an anti PD, one agent without significant incremental toxicities.

During the second quarter, we completed enrollment in a phase <unk> dose expansion study with larger lab as monotherapy in cohorts of patients with microsatellite satellite stable colorectal cancer and CRP C dollar and checkpoint naive non small cell lung cancer.

And based on both the encouraging data, the biomarker data, and the patient's responses, the group that conducted that study and an expanded group are very enthusiastic to look at a very early setting for prostate cancer and enoblatozumab.

We expect to provide a data update from this study by early 2023.

Next I'll discuss our efforts to advance treatment of patients with CD 193 positive Hematological malignancy.

As you know, our current efforts right now with regard to MGCO-18 is in the later-line metastatic setting.

<unk> 24 is our next generation bi specific CD 123 by CD three dart molecule that incorporates a CD three component designed to minimize satisfied released syndrome, while maintaining antitumor side Olympic activity and permitting intermittent dosing to a longer half life.

And so we're, again, focused on both patients that have been experienced with ARAT agents as well as taxidermy agents, still opportunities to move up the line.

We recently dosed the first patient in a phase one study of <unk>, four and CD 123 positive relapsed or refractory hematologic malignancies, including patients with acute myeloid leukemia and Myelodysplastic syndrome.

But given that you need to have a very clean drug for treating patients with localized disease, we think enoblatozumab is better set up for pursuing that indication.

Now, I should also indicate that we are looking at other possibilities of enoblatozumab beyond that of early-stage prostate cancer.

The novel, Susan that the investigational FC engineered <unk> directed monoclonal antibody created using our FC optimization platform being evaluated in solid tumor.

And, of course, as you know, we have the ongoing combination studies of MGCO-18 and lorodromab in seven different tumor types.

In July we issued a press release announcing the closure of the phase II study.

We are waiting the investigational regiment of another two that in combination with either at a battle of map and anti PD, one monoclonal antibody or T. Mo tell them at our PD one by lag three bispecific dart molecule in the first line treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

And based on the results of those studies can guide us in other solid tumor indications going forward with MGCO-18.

Now, with regard to the question you had about the MGD-024 with respect to protetuzumab and, its use in refractory disease, as we've outlined at the last ASH meeting, we are very encouraged that the use of MGD-024, both based on the better profile in reducing cytokine release as well as intermittent dosings, will allow a much broader application of MGD-024 beyond what we were able to do with protetuzumab, both in late-line refractory patients as well as patients with early disease.

The decision to discontinue the study was based on an internal review of safety data and a risk benefit analysis and frontline patients with squamous cell carcinoma of the head and neck.

We don't believe this decision has any impact on our other <unk> directed programs or our ability to develop a novel to the NAV and other indications.

At <unk> in June investigators from Johns Hopkins presented a poster with encouraging clinical activity from an ongoing phase two study that I'll go to the mat and patients with localized prostate cancer in the neo adjuvant setting.

In particular, we are extremely encouraged by the combination studies we had with MGD-024 and other standard therapies and look to using this quite broadly after we initially do the dose escalation studies in patients with relapsed refractory disease.

Novelties and that showed encouraging clinical activity with 66% of the patients have a PSA zero at one year post.

Which correlated with peripheral expansion of tumor associated T cell phone.

The published data from the ongoing investigator sponsored trial to date provide rationale for further evaluation of the novel <unk> in prostate cancer.

We're also looking at the opportunity of MGD-024 beyond AML, using it in tumor settings where CD123 is overexpressed, including monodysplastic syndrome and other indications.

Next I will provide an update of our product candidates being developed by our collaboration partners for working to retain certain economic rats.

Our second investigational ADC, <unk>, 96, which targets Adam nine a cell surface protein over expressed in several solid tumor types.

So there is certainly a differentiation and expansion of our intended use for MGD-024, which provided some of the rationale of why we stopped further pursuing protetuzumab development.

The advanced under our co development agreement with Immunogen.

Under a 50 50 collaboration images, leading clinical development as an indicated our plan to complete dose escalation in the phase one study evaluating <unk> 936 in multiple solid tumors with initial data anticipated before year end.

Our next question comes from David Dai from SMBC.

Hey, great.

Suppose the map is an anti <unk> three monoclonal antibodies that prevention bio required from us under an asset purchase agreement in 2018.

Thanks for taking my questions.

Prevention is developing to play the math of the treatment of type one diabetes on.

On June 30th Prevention announced the FDA has extended the review period by three months for the BLA for Daclizumab.

<unk> tended to do put target action date is November 17 2022.

Macrogenics is eligible to receive royalties on net sales of proposing that they put through in addition to milestone payments, including $60 million upon BLA approval in the United States.

So I have a couple of questions as well.

Red <unk> is an investigational anti PD, one that that we exclusively licensed to <unk> Corporation.

Macrogenics is eligible to receive royalties on net sales of <unk>. If approved in addition to milestone payments.

In July 2020 to Macrogenics received $30 million in milestone payments from insight as part of the collaboration agreement.

So, first question is just around MGD-018.

But if that amount is currently being studied as monotherapy or in combination with other agents across multiple studies.

So when we look at the phase one dose expansion study that was presented at ESMO last year, we saw that about 30% of patients were dose reduced and 55% of the MCRPC patients were dose interrupted.

So could you provide some color on what was the lowest dose level that was dose reduced and how long were the duration of the dose interruption for these patients?

In conclusion, we continue to believe 2022 will be another important year for macrogenics during.

During the first half of the year, we initiated two clinical studies and we expect to start Tamarac, a registration directed study of MDC.

And then how should we think about the potential read-through to the reduced dose regimen for the TEMRAC trial, the phase two, three TEMRAC trial?

In N C. RPC by year end, we remain committed to developing and delivering life changing medicines to cancer patients.

We will be now happy to open the call for questions operator.

Okay.

Sure.

Yes.

Okay. The floor is now open.

<unk> for your questions to ask a question at this time. Please press star one on your telephone keypad any point, we'd like to withdraw from the queue.

Please press Star one again, you will be provided with the opportunity to ask one question and one further follow up questions. If you have any further questions you may raise your hand and queue up again.

I'll take a moment to render our roster.

Okay. Our first question comes.

Yes.

<unk>.

John Miller from Evercore. Please go ahead.

Hi, guys. Thanks for taking the question.

And congrats on restructuring and payable at a little bit and extending the runway a little bit further I'd love to get a sense of exactly what the new guideline guidance is though precisely because it seemed like there were two different languages being used.

Into 'twenty four I think we've mentioned in the press release, but then also Scott you mentioned, having runway through yearend 24, where the tamarack data was that I was expecting so can you just.

Remind me what the exact guidance.

Languages are going global.

Yeah. Thanks, John I'll start and I think Scott will probably finished so the exact guidance is that our cash runway, which reflects not only the $134 million that we had at June 30, but the additional $34 5 million that we received subsequently in the month of July plus product revenues and other anticipated payments from partners push.

David, thank you very much for that question.

As our cash runway into 2024.

Yeah, and just first of all John obviously, we can get more precision on this when the study starts and how quickly these patients get enrolled but.

Given where we are right now in that process. We are confident that we'll be able to start the study before the end of the year getting enrolled.

And obviously we've been spending a lot of time, of analyzing the data that we extracted from the study, not only in patients with prostate cancer, but those that we tested in other solid tumor indications.

During 'twenty three and have the readout by the end of the year.

And as you know, we spent a lot of time with Clotatuzumab, ultimately getting a dose escalation and a increase, particularly on the Clotatuzumab in the first week.

Again, just to refresh everyone's memory, the expansion cohorts for these studies started out with a three mcg per kg dosing on a two, three week level. It turns out the majority of patients had either dose reductions or holding doses with a longer period before the patients were restarted in dosing, largely due to side effect profiles.

So we think that without exact precision right now because in addition to milestone payments, which obviously, we can never guarantee we have considerable amount of BD activity ongoing.

We took this into account, we looked at the full data set from all patients treated with MGCO18 and identified the ultimate dose that every patient was ultimately treated with during their course of therapy and came out with an average amount of drug that was delivered to those patients. We sized up that result with their clinical responses, both in terms of side effect profiles, as well as responsiveness.

You could obviously extend runway further.

We ultimately believe on the dosing that this can be based on either weight or body weight or on a flat dosing regimen going forward.

Should be able to provide further precision.

In the future with regard to how far into 2000 and for that goes.

Alright, thanks, very much and one maybe one or two more.

If I may.

There is no at this point about.

So, you know, we'll have to see how that goes.

I believe versus one eight overlap and I think maybe it made sense to have them separate before but I'd love in light of the prioritization for you to tell me a little bit about how you're feeling about having both of these studies ongoing for both of these programs are they differentiated enough to justify keeping both active.

But particularly at the lower doses, we expect those to move up quite quickly.

And by doing this, we were highlighting particular side effects that seemed most problematic to the continued treatment of patients.

Ones that we highlighted before was hand-foot syndrome, where while the majority of patients had only grade one or grade two side effect profiles, very few grade threes, it turned out a significant number of patients who had grade twos, which was manifested by the appearance of pain in those patients, caused many of those patients to stop continuing treatment.

She is a one eight sort of advances to later stage trials and then.

But we'll have to see as we move up the line.

Not exactly the same obviously, but a little bit related should we expect similar dynamics.

For Q4, as we had from <unk>. So should we be looking for the same sorts of signals in terms of patient sub populations refractory versus relapsed patients that sort of thing as we look forward to early data there. Thanks, Greg.

Great questions.

So we were very excited about the update is that the Johns Hopkins Group Board of tables are provided us though is as you know that it received a lot of positive feedback.

A neo adjuvant setting, which as you know is.

And so when we did an analysis of the actual dose that was both effective in inducing responsiveness, as well as reducing the incidence and severity of side effects, we saw a difference that fell in that range that we ultimately decided on treating these patients. 2 mg per kg on a Q4 weekly basis, up to 2.7 mg per kg on a Q4 weekly basis.

Either that or very little efforts are being conducted there in that very early setting.

Despite the fact of the head and neck setback with regard to the.

Stopping the study for Nova Susan that the safety profile for another two that are in the early <unk> and.

Prostate setting was was excellent and based on both the encouraging data.

So we've boxed, in that dosing range to ultimately move forward in this now Phase II, the component of the, Phase II-III study.

Biomarker data.

And the patients' responses.

The group that conducting that study is an expanded group is our very enthusiastic so look at it very early setting for <unk>.

Prostate cancer in a number to that as you know.

Current efforts right now with regard to <unk> is in the later line metastatic setting and so we're again focused on.

Both.

Patients that had been experienced with.

Hey, Rod agents as well as Taxane agents.

Still opportunity to move up the line, but given.

We indeed have a.

Very clean.

<unk>.

Drug between patients with localized disease.

Think another two that is better set up for pursuing that indication now I should also indicate that we are looking at other possibilities in the novel.

Susan.

Beyond that.

Early stage prostate cancer and of course as you know we have the ongoing combination studies of <unk> in a more general mad in seven different tumor types and based on the result of valve studies and guide us in.

Okay.

Our next question comes from Stephen Wiley from CFL.

And then just with respect to Tamera, can you, I guess, speak to the number of sites, that you're hoping to enroll these 150 patients across?

Yeah, good afternoon.

And should we just expect that interim analysis of, I guess, of efficacy data?

Thanks for taking the questions.

Other.

Solid tumor indications going forward with <unk>.

Now with regard to the question you had about.

What is the trigger for the presentation of that interim data on the efficacy side? Is it going to be based upon some threshold number of radiographic progression events?

The <unk> 24 with respect to quantity of that and it's used in refractory disease as we've outlined at the last Ash meeting we are very encouraged that the use of Mvpds 24, both based on the better.

File and reducing cytokine release as well as intimate dosing will allow a much broader application of NGL 24 beyond what we were able to do with quality to them that both in late line refractory patients as well as patients with early disease in particular, we are.

Extremely encouraged by the combination studies, we had with <unk> 24, and other standard therapies and look to using this quite broadly after we initially do the dose escalation study in patients with relapsed refractory disease. We're also looking at the opportunity of NGL.

24 beyond AML.

Using is in.

Tumor settings.

We're a CD 123 is over expressed including a myelodysplastic syndrome and other indications. So there is certainly a differentiation and expansion of our intended use for <unk> 'twenty for providing some of the rationale of why we stopped.

Tried to pursuing the plug to the mass development.

Alright.

Our next question comes from David Dye from AST and BC.

Okay, great. Thanks for taking my questions. So I have a couple of questions as well. So first question is just around <unk>. So we will look at the phase one dose expansion study that was presented at ESMO last year, we saw that about 30% of patients where those reduced by 55% of the CRP.

Patients were at dose interrupted.

So could you provide some color on what was the lowest dose level that was dose reduced and how long were the duration of those interruptions for these patients and then how should we think about the potential read through to the reduce the dose regimen, Phil for the <unk> trial, the phase III trial.

David Thank you very much for that question.

Honestly, we've been spending a lot of time.

If there's, I guess, anything that you can say to that, that'd be helpful.

Analyzing the data that we extracted from that study not only in patients with prostate cancer, but those.

That we tested in other solid tumor indications.

Again, just to refresh everyone's memory.

The expansion cohorts for the study started out with a three Meg per kg dosing Q3 week level. It turns out the majority of patients.

So with regards to the number of sites, we haven't come up with a final number.

At either dose reductions or holding doses with.

We're, obviously starting given the regulatory timing of things in U.S. sites.

Maybe just with respect to O2-4, is there anything that you can say about, I guess, how you're dosing this drug during Cycle I?

Longer.

Period before the patients we're restarting in dosing.

Our plan is to have this as a worldwide study in U.S., Europe, and Asia.

Is it just a flat dose that you're administering?

Largely due to side effect profile.

Is there going to be some attempt, to migrate over to some kind of titration regimen?

We took this into account we looked at the full dataset from all patients treated with <unk>.

And if you could speak to the pre-medication that you're using as well, that'd be helpful.

<unk> and identified the ultimate dose that every patient.

And then just have a quick follow-up on Tamarack.

So I can't come up with a specific number that we will ultimately end up with.

Yeah.

Was.

Similarly treated with during the course of therapy.

Obviously, it will be a large number of double digit initially as we do the Phase 2 studies.

Thanks, Steve.

And we'll be expanding.

It came out with a average amount of drug that was delivered to those patients.

We sized that result with there.

You know, based on interactions with the FDA, we started out with Mabel dosing, of this drug. This was a requirement.

And as you know, we spent a lot of time with Clotatuzumab ultimately getting a dose escalation and a increase, particularly on the Clotatuzumab in the first week.

Clinical responses, both in terms of side effect profile as well as responsiveness.

The intent would be to expand as we move over from Phase 2 to Phase 3.

We ultimately believe on the dosing that this can be based on either weight or body weight or on a flat dosing regimen going forward.

We hope, you know, by the time we start the enrollment at the end of the year, we'll be able to do a little bit more precision on site engagement and planetary expansion, especially when we get feedback from the European sites.

By doing this we were highlighting in particular side effects that team most problematic to the continued treatment of patients.

With regard to the analysis of the data, we have a predefined analysis defined in our protocol that is being given to the DSMV.

So we'll have to see how that goes.

Ones that we highlighted it before was hand foot syndrome, where well the majority of patients had only grade one grade two side effects profile very few grade three.

But particularly at the lower doses, we expect those to move up quite quickly.

It turned out a significant number of patients who agree twos, which was.

But we'll have to see as we move up the line.

Manifested by the appearance of pain in those patients.

Cause many of those patients who stopped continuing treatment and so when we did an analysis of the actual dose that was both.

Okay.

Effective in inducing responsiveness as well as reducing the incidence and severity of side effects, we saw a.

And then just with respect to Tamarack, can you, I guess, speak to the number of sites that you're hoping to enroll these 150 patients across?

And should we just expect that interim analysis of, I guess, of efficacy data?

What is the trigger for the presentation of that interim data on the efficacy side? Is it going to be based upon some threshold number of radiographic progression events?

A difference that fell in that range that we ultimately decided on treating these patients.

Two two <unk> per kit on a Q4 weekly basis up to $2 seven expert CAGR on a Q4 weekly basis. So we've boxes that dosing range to ultimately move forward in this now phase II component of the phase two three study.

If there's, I guess, anything that you can say to that, that'd be helpful.

So with regards to number of sites, we haven't come up with a final number.

We're obviously, starting given the regulatory timing of things in U.S. sites.

Our plan is to have this as a worldwide study in U.S., Europe, and Asia.

Our next question comes from Steven wildly from Stifel.

So I can't come up with a specific number that we will ultimately end up with.

Obviously, it will be a large number of double-digit initially as we do the phase two studies.

Okay.

Yes, good afternoon, thanks for taking the questions.

Maybe just with respect to OTT or is there anything that you can say about.

And the intent would be to expand as we move over from phase two to phase three.

We hope, you know, by the time we start the enrollment at the end of the year, we'll be able to do a little bit more precision on site engagement and plans for expansion, especially when we get feedback from the European sites.

I guess, how youre dosing this drug during cycle. One is it just is it just a flat dose that you're administering if theyre going to be sort of attempt to migrate over to some kind of a titration regimen.

With regard to the analysis of the data, we have a predefined analysis defined in our protocol, that is being given to the DSMB.

Speak to the pre medication that you're using as well that'd be helpful.

And then just have a quick follow up on Tamar.

Yep Thanks, Steve.

Based on.

Interactions with the FDA, we started out with the label dosing.

This drug and this was or.

Or the requirement.

And as you know we spend a lot of time with quality to the Nab ultimately getting.

A dose escalation and.

Increased particularly on the club to ban the personally we ultimately believe.

On the dosing that this can be.

Based on.

Either wait or body weight or on a flat dosing.

Regimen going forward.

So we'll have to see how that goes.

But particularly at the lower doses.

Again, we're not at liberty right now to disclose what those specific, which will include, obviously, response rates going forward.

Again, we're not at liberty right now to disclose what those specific, which will include, obviously, response rates going forward.

We obviously also have the ability to amend that at any particular time during that course of that Phase 2 study.

We obviously have also had the ability to amend that at any particular time during that course of that phase two study.

We expect those to move up quite.

There will be a futility analysis that is incorporated in this during the course of enrollment.

There will be a futility analysis that is incorporated in this during the course of enrollment.

Again, the plan is to enroll 150 patients in those three groups, the two experimental groups and one control group.

Again, the plan is to enroll 150 patients in those three groups, the two experimental groups and one control group.

Quickly.

Thanks for taking the questions.

Okay.

But we'll have to see.

As we move up the line.

Our next question comes from Etzer Darout from BMO Capital Markets.

Thanks for taking the questions.

Okay and then.

Just with respect to tamarac can you.

I guess speak to the number of sites that you are hoping to enroll these 150 patients across.

Great.

Thanks for taking the question.

Just, again, on MGC01A, just wondering if you could speak to a little bit about perhaps the population of patients that you'll look at in the metastatic prostate cancer cohort.

And.

Should we think about it similar to what you looked at in the Phase 1-2?

Then maybe if you can, again, speak to any appropriate benchmarks we should think about now for that study in terms of how to kind of compare responses that we'll see in our interim analysis.

Should we just expect that.

In term analysis.

Yes.

Thank you.

I guess the efficacy data what is the trigger for the presentation of that of that interim data on the efficacy side is it going to be based upon some threshold number.

Etzer, thanks so much for that question or set of questions in regards to TAMRAC.

Again, very similar to what we had enrolled in the expansion cohort of the 40 patients.

Our next question comes from Jim Masaga from FACSET.

These will be metastatic castration-resistant prostate patients that had one prior angioreceptor targeting agent. They will have one prior docetaxel regimen, and we will also allow up to one prior cabozitaxel regimen, obviously optional, but no other prior chemotherapy. The patients will be stratified based on visceral disease, whether they've had cabozitaxel, and also regional analysis of the drug.

Again, I think the benchmarks differ depending on lines of therapy.

You're very well aware that that has a wide range of baseline responses of overall response rates in the two to three months to up to four months of baseline depending on the previous lines of therapy.

For that reason, and obviously the changing landscape of what these patients are now receiving, and obviously introduction of new agents into the metastatic market, we have included a control group so we'd be able to do a very good job of benchmarking to the current status of patients.

Radiographic progression events.

I guess anything that you can say that that'd be that'd be helpful.

Your line is open.

Please go ahead.

Thanks, Peter.

So with regard to number of sites that we haven't come out with a final number we're obviously starting.

Given the.

The regulatory timing of things in U S sites are.

<unk> has just said, though a worldwide study.

We can skip to the next one.

Our next question comes from Etzer Darout from BMO Capital Markets.

Our next question comes from Jonathan Chang from SVB Securities.

Great.

In the U S Europe and Asia.

Hi, guys.

Thanks for taking the question.

So right now, further updates on this would come in some sort of scientific or publication, at a future date.

So right now, further updates on this would come, in some sort of scientific publication at a future date.

Thanks for taking the question.

Just, again, on MGC01A, just wondered if you could, speak to a little bit about perhaps the population of patients that you'll look at in the metastatic prostate cancer cohort.

This is Faisal Khurshid on for Jonathan.

Should we think about it similar to what you looked at in the phase one, two?

So I.

I wanted to ask for the MGC018 plus large erylamab combination.

Then maybe if you can, again, speak to any appropriate benchmarks we should think about now for that study in terms of how to compare responses that we'll see in our interim analysis.

Can you remind us the study design here, in particular, what dose of MGC018 is being used?

Thank you.

I can come up with a specific number that we will ultimately end up with obviously it will be a large number of double digit initially.

And then also when we might be able to see data for that combination.

Etzer, thanks so much for that question or set of questions, with regard to Tamarack.

Thank you.

Again, very similar to what we had enrolled in the expansion cohort of the 40 patients.

Yeah.

These will be metastatic castration resistant prostate patients that had one prior angioreceptor targeting agent. They will have one prior docetaxel regimen, and we will also allow up to one prior cabozitaxel regimen, obviously an optional, but no other prior chemotherapy.

Thanks very much.

The patients will be stratified based on visceral disease, whether they've had cabozitaxel, and also regional analysis of the drug.

So the starting dose for MGC018 is one mix per kick on a, I think it's a Q4 weekly basis, now.

Again, I think the benchmarks differ depending on lines of therapy, and you're very well aware, that that has a wide range of baseline responses of overall response rates in the two to three months to up to four months of baseline, depending on the previous lines of therapy.

And more erylamab is that six mix per kick on the same dosing regimen.

So for that reason, and obviously the changing landscape of what these patients are now, receiving, and obviously introduction of new agents into the metastatic market, we have included a control group so we'd be able to do a very good job of benchmarking to the current status of patients.

The plan would be the dose escalate, the MGC018, we're going to, the expected next, dose would be two mix per kick, and we have other interval dosing that can be modifications based on side effect profiles, et cetera.

Our next question comes from Jim Masaga from FACTSET.

But right now we're targeting the large erylamab dose we'd like to take forward both as monotherapy, and combination and slowly titrate up the MGC018 dosing.

Your line is open, please go ahead.

Great, thank you.

Great, thank you.

Our next question comes from Charles Zhu from Guggenheim.

We can skip to the next one.

Our final question comes from Peter Lawson from Barclays.

Our final question comes from Peter Lawson from Barclays.

Hi, this is Edward for Charles.

Our next question comes from Jonathan Chang from SVB Securities.

Thank you, everyone, for joining our call today.

Thank you, everyone, for joining our call today.

Hi, this is Shayan for Peter Lawson, thanks for taking the question.

Hi, this is Shea Young for Peter Lawson.

Thanks for taking our question.

Hi, guys.

As we do the phase II studies and will be expanding the intent would be to expand as.

We look forward to updating you on the progress of our various programs in the near future.

We look forward to updating you on the progress of our various programs in the near future.

With the restructuring, could you help us, how we should be thinking about the OPEX for, the remainder of 2022 and through 2023, thank you.

Thanks for taking the question.

Maybe regarding MGC018, and apologies if I missed this, but are you planning to present, some of the expansion data that you had on the old dosing regimen?

Thanks for taking the question.

We hope you have a good evening.

We hope you have a good evening.

Yeah, we're not providing specific guidance today, Shayan, with regard to the expenses.

With the restructuring, could you help us how we should be thinking about the OPEX for, the remainder of 2022 and through 2023?

Thank you, ladies and gentlemen.

Thank you, ladies and gentlemen.

I think you talked about last time about maybe later this year having some prostate and melanoma, data.

This is Faisal Khurshid on for Jonathan.

What we are providing, as you've heard us say, is the cash runway. I'll note that the anticipated savings from headcount on a steady-state basis should be, approximately $10 million annually. Now, that's not this year, obviously, because we're more than halfway through the year, but in full, the full amount of the savings from the approximate 15% of reduction in force.

Thank you.

This concludes today's call.

This concludes today's call.

Yeah.

I wanted to ask for the MGC018 plus allergy or LIMAB combination.

You may now disconnect.

You may now disconnect.

Great, thank you.

Yeah, we're not providing specific guidance today, Shea, with regard to the expenses.

Thank you for your participation.

Thank you for your participation.

So thanks very much for the question.

Can you remind us the study design here, in particular, what dose of MGC018 is being used, and then also when we might be able to see data for that combination?

Please wait.

All right, we do have a final question from Jim Misaga from FACSET.

What we are providing, as you've heard us say, is the cash runway. I'll note that the anticipated savings from headcount on a steady-state basis should be, approximately $10 million annually. Now, that's not this year, obviously, because we're more than halfway through the year, but, you know, in full, the full amount of the savings from the approximate 15% of reduction in force.

At the time we discussed this, we were intending to add an expansion cohort for melanoma.

Yeah, thanks very much.

Your line is open, please go ahead.

Great.

As we moved over from Phase II Phase III and we hope by the time, we start the enrollment at the end of the year, we'll be able to be a little bit more precision on that.

And as you've heard today with regard to the prioritization of programs, one of the, things we said we're going to hold off on was adding additional patients to the melanoma cohort at this time, despite encouraging data that we had at scene.

So the starting dose for MGC018 is one mix per kick on a, I think it's a Q4 weekly basis now.

At this time, I would now like to turn the call over to Dr. Scott Koehning for closing remarks.

Thank you.

So our plans right now on updates on this program, it will depend on when we are going, to initiate additional studies with other indications.

And more general MAB is that six mix per kick on the same dosing regimen.

All right.

And at that time, we'd update everyone regarding our experience with these other indications.

The plan would be to dose escalate the MGC018.

We do have a final question from Jim Misaga from FACSET.

As for the prostate, we have our feedback from the key experts, from the regulators, and the plan going forward with regard to the Tamarack study.

We're going to, the expected next dose would be two mix per kick.

Your line is open.

And we have other interval dosing. There can be modifications based on side effect profiles, et cetera.

Please go ahead.

But right now we're targeting the lower general MAD dose.

At this time, I would now like to turn the call over to Dr. Scott Koehning for closing, remarks.

We'd like to take forward both as monotherapy and combination, and slowly titrate up the MGC018 dosing.

Our next question comes from Charles Zhu from Guggenheim.

Hi, this is Edward for Charles.

Thanks for taking our question.

Maybe regarding MGC018, apologies if I missed this, but are you planning to present some of the expansion data that you had on the old dosing regimen I think you talked about last time about maybe later this year having some prostate and melanoma data?

Site engagement.

Yeah, so thanks very much for the question.

At the time we discussed this, we were intending to add an expansion cohort, for melanoma.

As plans for expansion, especially when we get the feedback from the European sites.

And as you've heard today with regard to the prioritization of programs, one of the things we said we're going to hold off on was adding additional patients to the melanoma cohort at this time, despite encouraging data that we had at scene.

So our plans right now on updates on this program, it will depend on when we are going to initiate additional studies with other indications, and at that time we'll update everyone regarding our experience with these other indications.

As for the prostate, we have our feedback from the key experts, from the regulators, and the plan going forward with regard to the Tamarack study.

Yes.

With regard to the analysis of the data we have.

Predefined.

Analysis defined in our protocol.

That is being given to the SMB.

Again, we're not at Liberty right now to disclose what those specific patrol include obviously response rate.

Going forward. We obviously have also had the ability to amend that at any particular time.

During that course of that phase II study there will be a futility analysis that has been incorporated in this.

During the course of enrollment again the plan is to enroll 150 patients in those three.

The two experimental groups more controllable.

Okay. Thanks for taking the questions.

Steve.

Our next question comes from Exar drought.

From BMO capital markets.

Great. Thanks for taking the question just again on <unk>, just wondering if you could speak to a little bit about <unk>.

The population of patients that you'll look at the metastatic castrate resistant.

Prostate cancer cohort should we think about it similar to what you know.

You looked at in the Phase one two and then maybe if you can again speak to any appropriate benchmarks. We should think about now prefer that study in terms of you know how to kind of compare.

Responses that we'll see.

Interim analysis. Thank you.

And so thanks, so much for that.

Question or set of questions with regard to tamarac.

So again very similar to what we had enrolled in the expansion cohort.

Of the 40 40 patients.

These will be metastatic castration resistant prostate patients that had one prior androgen receptor.

Targeting agents.

They can have they will have one prior docetaxel regimen.

And we will also allow up to one prior capozzi taxon regimen, obviously an optional.

But no other prior chemotherapy.

Patients will be stratified based on the grid.

Visceral disease.

Whether they've had about the taxol and also regional analysis.

The drug.

Again, I think the benchmarks differ.

Depending on lines of therapy.

<unk>.

You're very well aware that debt as they are.

A wide range of baseline responses.

Overall response rates.

The two to three months.

Two to four months.

A faithful and depending on the.

Previous lines of therapy so.

For that reason and obviously the changing landscape of what keep patients are now receiving an obviously introduction of.

New agents into the Administaff market.

We've included a control group.

So we'd be able to.

Do a very good job of benchmarking to the current status of patients.

Our next question comes from Jim Macdonald from Factset.

Your line is open. Please go ahead.

We can skip to the next one.

Yes.

Sure.

Our next question comes from Jonathan Chang from <unk> Securities.

Hi, guys. Thanks for taking the question. This is special associated on for Jonathan I wanted to ask for the <unk> eight plus Larry Cherilyn that combination can you remind us the study design here in particular, what dose of Mt's easier. One eight is being used and then also when we might be able to see.

See data for that combination. Thank you.

Yeah, Thanks very much.

So the starting dose for <unk> is what makes her kids on that on our Q.

I think it's a Q4 weekly basis now.

Laurent Gerald Mad is that six mix per kg on the same dosing regimen.

The plan would be to dose escalate the <unk>, we're going to be expected next dose would be.

To make spurt keg.

And we have other.

Dosing that can be modifications based on.

Side effect profiles et cetera.

But right now we're.

Targeting the.

The large aero med, those who like to take forward, both as monotherapy and combination and slowly titrated up.

The <unk> dosing.

Our next question comes from Charles Zhou from Guggenheim.

Hi, This is Edward on for Charles Thanks for taking our question maybe regarding <unk> I apologize if I missed this but are you planning to present, but the extension data that you had on the old dosing regimen I think you'd talked about last time about maybe later this year, having some prostate melanoma.

On the data.

Yes, so thanks very much for the question.

At this time, we discussed this we are.

We're intending to add an expansion cohort four melanoma.

As you've heard today with regard to the prioritization of programs.

One of the things, we said, we're going to hold off on was.

Any additional patients to the melanoma cohort at this this time despite encouraging data that we had as seen so we're our plans right now on updates on this program.

It will depend on when we are going to initiate.

Additional.

Studies.

The other indications and at that time with the update.

Everyone have with regarding our experience with these other indications as to the prostate.

We have.

Sure.

Our feedback from the key experts from the regulators and the plan going forward with regard.

Two the Tamarac studies held right now.

Further updates on this would come and some sort of a scientific publication at a future date.

Great. Thank you.

Okay.

Final question comes from Peter Lawson from Barclays.

Hi, This is Jay on for Ben Thanks for taking the question.

With the restructuring could you help us.

How we should be thinking about the opex for the remainder of 2022 and entering 2023. Thank you.

Yes, we're not providing specific guidance today is Shane with regard to the expenses, what we are providing as you've heard us say if the cash runway.

Note that the.

Anticipated savings from head count on a steady state basis should be approximately $10 million annually now that's not this year, obviously, because there were more than halfway through the year, but.

And for the full amount of the savings from the approximately 15% of reduction in force.

Great. Thank you.

Okay.

Alright, we do have a final question from Jim Massawa from Factset.

Okay.

Your line is open. Please go ahead.

At this time I would now like to turn the call over to Doctor Scott <unk> for closing remarks.

Thank you everyone for joining our call today, we look forward to updating you on the progress of our various programs in the near future and hope you have a good evening.

Thank you ladies and gentlemen. This concludes today's call. Thank you for your participation you may now disconnect.