Q2 2024 Mersana Therapeutics Inc Earnings Call

Speaker Change: [music].

Good morning, and welcome to Mcdonalds Therapeutics second quarter, 2024 conference call and webcast.

Operator: Good morning, and welcome to Mersana Therapeutics' second quarter 2024 conference call and webcast. Currently, all participants are in a listen-only mode. There will be a question and answer session at the end of this call. Please note, this call is being recorded. I would now like to turn the call over to Jason Fredette, Senior Vice President, Investor Relations, and Corporate Communications.

Operator: Good morning and welcome to Mersana Therapeutics, 2nd quarter, 2024 Conference Call and Webcast. Currently, all participants are in a listen-only mode. There will be a question and answer session at the end of this call. Please note, this call is being recorded. I would now like to turn the call over to Jason Fredette, Senior Vice President, Investor Relations and Corporate Communications. Thank you, operator, and good morning, everyone. Before we begin, please note that this call will contain forward-looking statements within the meaning of federal securities laws. These statements may include but are not limited to those related to our platforms, product candidates, business strategy, clinical trial execution and data, business development efforts, and cash runway. Each of these forward-looking statements is subject to risks and uncertainties that could cause actual results to differ materially from those projected in such statements. These risks and uncertainties are discussed in our quarterly report on Form 10-Q, filed with the Securities and Exchange Commission on May 9, 2024, and in subsequent SEC filings. Our filings are available at SEC.gov and on our website, mersana.com. Except as required by law, we assume no obligation to update forward-looking statements publicly even if new information becomes available in the future. On today's call, we have Mersana's President and Chief Executive Officer, Dr. Marty Hubert, and our Chief Operating Officer and Chief Financial Officer, Brian DeShightner. With that, let me turn the call over to Marty to begin our discussion. Thank you, Jason, and good morning, everyone. The second quarter of 2024 was a time of continued progress at Mersana as we advanced dose escalation in phase one clinical trials of XMT-1660, our LEED-DOLICENTANT ADC candidate, and XMT-2056, our LEED-immunicENTANT ADC candidate. At the same time, we made further progress in our collaborations while also benefiting from our efforts to reduce our operating expenses last year. We believe these collective accomplishments have put us in a strong position as we approach our initial clinical data readout for XMT-1660, which is planned for the second half of this year. Let's begin with that program. XMT-1660 is an ADC we developed using DOLICENTANT, our next-generation cytotoxic ADC platform. This candidate targets B7H4, a cell surface protein within the B7 family that can suppress anti-tumor immunity and can serve as a negative prognostic indicator for multiple tumor types. In the dose escalation portion of our ongoing phase one clinical trial, we are enrolling patients with tumor types that most commonly express high levels of B7H4. These include patients with recurrent triple negative and hormone receptor positive breast cancers, as well as endometrial and ovarian cancers, all areas with high unmet medical need. For instance, as many know, Trudelby and Orrin HER2 are being used to treat the vast majority of recurrent triple negative breast cancer patients in the US today. Emerging clinical data continue to suggest that patients can develop resistance to ADCs with Topo-1 inhibitor payloads. As a result, we are hearing an increasing call among treating physicians for new ADCs with alternative payloads that aren't subject to Topo 1 or PGP E-Flux resistance mechanisms. XMT-1660 fits this profile, and we are enrolling many patients who have received a prior Topo 1 ADC in our trial.

Jason Fredette: There will be a question and answer session at the end of this call. Please note that this call is being recorded. I would now like to turn the call over to Jason Fredette, Senior Vice President, Investor Relations and Corporate Communications. Thank you, Operator, and good morning, everyone. Before we begin, please note that this call will contain forward-looking statements within the meaning of federal securities laws. These statements may include, but are not limited to, those related to our platforms, product candidates, business strategy, clinical trial execution and data, business development efforts, and cash runway.

Speaker Change: Currently all participants are in a listen only mode.

Speaker Change: There'll be a question and answer session at the end of this call.

Please note this call is being recorded.

Jason Fredette: I would now like to turn the call over to Jason Fredette, Senior Vice President Investor Relations and corporate communications.

Jason Fredette: Thank you operator, and good morning, everyone. Before we begin. Please note that this call will contain forward looking statements within the meaning of federal Securities laws. These statements may include but are not limited to those related to our platforms product candidates business strategy clinical trial execution and data business development efforts in cash.

Jason Fredette: Thank you, operator, and good morning, everyone. Before we begin, please note that this call will contain forward-looking statements within the meaning of federal securities laws. These statements may include, but are not limited to, those related to our platforms, product candidates, business strategy, clinical trial execution and data, business development efforts, and cash runway. Each of these forward-looking statements is subject to risks and uncertainties that could cause actual results to differ materially from those projected in such statements.

Jason Fredette: Each of these forward-looking statements is subject to risks and uncertainties that could cause actual results to differ materially from those projected in such statements. These risks and uncertainties are discussed in our quarterly report on Form 10-Q, filed with the Securities and Exchange Commission on May 9, 2024, and in subsequent SEC filings. Our filings are available at sec.gov and on our website, mersana.com, except as required by law. We assume no obligation to update forward-looking statements publicly even if new information becomes available in the future. On today's call, we have Mersana's President and Chief Executive Officer, Dr. Marty Huber, and our Chief Operating Officer and Chief Financial Officer, Brian DeSchuytner.

Runway each of these forward looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in such statements.

Jason Fredette: These risks and uncertainties are discussed in our quarterly report on Form 10-Q filed with the Securities and Exchange Commission on May nine 2024, and in subsequent SEC filings our filings are available at SEC Gov and on our website MRSA in the dotcom.

Except as required by law, we assume no obligation to update forward looking statements publicly even if new information becomes available in the future.

Speaker Change: On today's call, we have <unk>, President and Chief Executive Officer, Dr. Marty Huber, and our Chief operating Officer, and Chief Financial Officer, Brian <unk> with that let me turn the call over to Marty to begin our discussion.

Jason Fredette: These risks and uncertainties are discussed in our quarterly report on Form 10-Q, filed with the Securities and Exchange Commission on May 9, 2024, and in subsequent SEC filings. Our filings are available at sec.gov and on our website, mersana.com, except as required by law. We assume no obligation to update forward-looking statements publicly, even if new information becomes available in the future. On today's call, we have Mersana's President and Chief Executive Officer, Dr. Marty Huber, and our Chief Operating Officer and Chief Financial Officer, Brian DeSchuytner. With that, let me turn the call over to Marty to begin our discussion.

Martin Huber: Thank you, Jason, and good morning, everyone. The second quarter of 2024 was a time of continued progress at Mersana as we advanced dose escalation in phase one clinical trials of XMT 1660, our lead dolacenthin ADC candidate, and XMT 2056, our lead immunosynthin ADC candidate. At the same time, we made further progress in our collaborations, while also benefiting from our efforts to reduce our operating expenses last year. We believe these collective accomplishments have put us in a strong position as we approach our initial clinical data readout for XMT 1660, which is planned for the second half of this year. Let's begin with that program.

Marty Huber: Thank you, Jason and good morning, everyone.

Marty Huber: With that, let me turn the call over to Marty to begin our discussion. Thank you, Jason, and good morning, everyone. The second quarter of 2024 was a time of continued progress at Mersana as we advanced dose escalation in phase one clinical trials of XMT1660, our lead dolosynthin ADC candidate, and XMT2056, our lead immunosynthin ADC candidate. At the same time, we made further progress in our collaborations, while also benefiting from our efforts to reduce our operating expenses last year.

Marty Huber: The second quarter of 2024 was a time of continued progress in Barcelona, as we advanced dose escalation in phase one clinical trials of X M. T. 16, 60, our lead told sent an ADC candidates an extra <unk> 2056, our lead immuno center ADC candidate.

Marty Huber: At the same time, we made further progress in our collaborations while also benefiting from our efforts to reduce our operating expenses last year.

Marty Huber: We believe these collective accomplishments have put us in a strong position as we approach our initial clinical data readout for XMT 1660, which is planned for the second half of this year. So, let's begin with that program. XMT-1660 is an ADC we developed using DolaSynthin, our next generation cytotoxic ADC platform. This candidate targets B7H4, a cell surface protein within the B7 family that can suppress antitumor immunity and can serve as a negative prognostic indicator for multiple tumor types.

Marty Huber: We believe these collective accomplishments have put us in a strong position as we approach our initial clinical data readout for <unk> 16, 60, which is planned for the second half of this year.

Speaker Change: Let's begin with that program.

Martin Huber: XMT-1660 is an ADC we developed using DolaSynthin, our next generation cytotoxic ADC platform. This candidate targets B7H4, a cell surface protein within the B7 family that can suppress antitumor immunity and can serve as a negative prognostic indicator for multiple tumor types. In the dose escalation portion of our ongoing Phase I clinical trial, we are enrolling patients with tumor types that most commonly express high levels of B7H4. These include patients with recurrent triple negative and hormone receptor positive breast cancers, as well as endometrial and ovarian cancers, all areas with high unmet medical need.

Speaker Change: <unk> 16, 60 is an ADC, we developed using Dolor Simpson, our next generation cytotoxic ADC platform.

Speaker Change: This candidate targets B seven age for a cell surface protein within the B seven family. They can suppress anti tumor immunity and can serve as a negative prognostic indicator for multiple tumor types.

In the dose escalation portion of our ongoing phase one clinical trial, we are enrolling patients with tumor types that most commonly expressed high levels of B seven H for these.

Marty Huber: In the dose escalation portion of our ongoing Phase I clinical trial, we are enrolling patients with tumor types that most commonly express high levels of B7H4. These include patients with recurrent triple negative and hormone receptor positive breast cancers, as well as endometrial and ovarian cancers, all areas with high unmet medical needs. For instance, as many know, Tredelby and or in HER2 are being used to treat the vast majority of recurrent triple negative breast cancer patients in the U.S. today. However, emerging clinical data continue to suggest that patients can develop resistance to ADCs with TOPO1 inhibitor payloads.

Speaker Change: These include patients with recurrent triple negative and hormone receptor positive breast cancers, as well as endometrial and ovarian cancers.

All areas with high unmet medical need.

Martin Huber: For instance, as many know, Tredelby and or in HER2 are being used to treat the vast majority of recurrent triple negative breast cancer patients in the U.S. today. However, emerging clinical data continue to suggest that patients can develop resistance to ADCs with TOPO1 inhibitor payloads. As a result, we are hearing an increasing call among treating physicians for new ADCs with alternative payloads that aren't subject to TOPO1 or PGP efflux resistance mechanisms. XMT 1660 fits this profile, and we are enrolling many patients who have received a prior TOPA1 ADC in our trial.

Speaker Change: For instance, as many know treat lb and or in her two are being used to treat the vast majority of recurrent triple negative breast cancer patients in the U S. Today.

Speaker Change: Emerging clinical data continue to suggest that patients can develop resistance to 86 with topo one inhibitor payloads.

Marty Huber: As a result, we are hearing an increasing call among treating physicians for new ADCs with alternative payloads that aren't subject to TOPO1 or PGP efflux resistance mechanisms. XMT1660 fits this profile, and we are enrolling many patients who have received a prior TOPA1-ADC in our trial. Dose escalation remains ongoing, and we still have not established a maximum tolerated dose. In fact, we are currently at a dose of 80 milligrams per meter squared in escalation.

Speaker Change: As a result, we are hearing and increasing call among treating physicians for new adcs with alternative payloads that aren't subject to total one or PGP eplex resistant mechanisms.

Speaker Change: X M. T 16, 60 fits this profile and we aren't rolling many patients who have received a prior totaled one ADC in our trial.

Speaker Change: Dose escalation remains ongoing and we still have not established a maximum tolerated dose. In fact, we are currently at a dose of 80 milligrams per meter squared in escalation. This.

Martin Huber: Dose escalation remains ongoing, and we still have not established a maximum tolerated dose. In fact, we are currently at a dose of 80 milligrams per meter squared in escalation.

Martin Huber: Dose escalation remains ongoing, and we still have not established a maximum tolerated dose. In fact, we are currently at a dose of 80 milligrams per meter squared in escalation. This is well beyond the dose levels we were able to reach clinically with any of our prior ADCs. We believe our ability to continue to dose escalate can be attributed to two factors. The first is DolaSympton's ability to reduce toxicities commonly associated with other ADC platforms like neutropenia, neuropathy, and ocular toxicity, as well as those that were seen with our first-generation platform, DolaFlex. And the second factor is that, based on data that has been reported to date, there does not appear to be an obvious on-target liability with B7H4.

Martin Huber: This is well beyond the dose levels we were able to reach clinically with any of our prior ADCs. We believe our ability to continue to dose escalate can be attributed to two factors. The first is Dolosynthens' ability to reduce toxicity commonly associated with other ADC platforms like neutropenia, neuropathy, and ocular toxicity, as well as those that were seen with our first-generation platform, Doloflexin. And the second factor is that, based on data that has been reported to date, there does not appear to be an obvious on-target liability with B7H4.

Marty Huber: This is well beyond the dose levels we were able to reach clinically with any of our prior ADCs. We believe our ability to continue to dose escalate can be attributed to two factors. The first is DolaSympton's ability to reduce toxicities commonly associated with other ADC platforms like neutropenia, neuropathy, and ocular toxicity, as well as those that were seen with our first-generation platform, DolaFlex.

Speaker Change: This is well beyond the dose levels, we were able to reach clinically with any of our prior a D. CS.

Speaker Change: We believe our ability to continue to dose escalate can be attributed to two factors.

Speaker Change: The first is dolus symptoms ability to reduce toxicities, commonly associated with other ADC platforms like neutropenia neuropathy, and ocular toxicity as well as those that were seeing with our first generation platform Domo flex it.

Speaker Change: And the second factor is that based on data that has been reported to date. There does not appear to be an obvious on target liability would be 784.

Marty Huber: The second factor is that, based on data that has been reported to date, there does not appear to be an obvious on-target liability with B7H4. In parallel with our dose escalation work, which includes the enrollment of backfill cohorts, we are also proactively exploring different dosing schedules with XNT1660 with the aim of optimizing efficacy and safety. This is included every four weeks, as well as more frequent dosing regimens.

Speaker Change: In parallel with our dose escalation work, which includes the enrollment of backfill cohorts. We are also proactively exploring different dosing schedules with X M. T 16, 60, with the aim to optimize efficacy and safety.

Martin Huber: In parallel with our dose escalation work, which includes the enrollment of BACSO cohorts, we are also proactively exploring different dosing schedules with XMT-1660 with the aim to optimize efficacy and safety. This has included every four weeks, as well as more frequent dosing regimens.

Martin Huber: In parallel, with our dose escalation work, which includes the enrollment of backfill cohorts, we are also proactively exploring different dosing schedules with XMT1660 with the aim to optimize efficacy and safety. This includes every four weeks, as well as more frequent dosing regimens. At the same time, we are progressing our biomarker strategy in preparation for expansion and potential later stages of development. All this work is aimed at building a robust data set that can inform important strategic decisions as we seek to position XMT 1660 as a potential best-in-class asset.

Speaker Change: This has included every four weeks as well as more frequent dosing regiments.

Martin Huber: At the same time, we also are progressing our biomarker strategy in preparation for expansion and potential later stages of development. All this work is aimed at building a robust data set that can inform important strategic decisions as we seek to position XMT-1660 as a potential best-in-class asset. One that we believe may have the opportunity to serve both as a monotherapy and in combination with standards of care that may be inaccessible for the other B7H4 ADCs in development. We continue to expect that we will be in a position to announce our initial clinical data and initiate expansion in the second half of this year.

Speaker Change: At the same time, we also are progressing our biomarker strategy in preparation for expansion and potential later stages of development.

Marty Huber: At the same time, we are progressing our biomarker strategy in preparation for expansion and potential later stages of development. All this work is aimed at building a robust data set that can inform important strategic decisions as we seek to position XMT1660 as a potential best-in-class asset, one that we believe may have the opportunity to serve both as monotherapy and in combination with standards of care that may be inaccessible for the other B7H4 ADCs in development.

Speaker Change: All of this work is aimed at building a robust dataset that can inform important strategic decisions as we seek to position except T 16, 60, as a potential best in class asset.

Martin Huber: One that we believe may have the opportunity to serve both as a monotherapy and in combination with standards of care that may be inaccessible for the other B7H4 ADCs in development. We continue to expect that we will be in a position to announce our initial clinical data and initiate expansion in the second half of this year. This readout will include safety, tolerability, efficacy, and biomarker data. Now, let's turn to Immunosynthin and XMT-2056.

Speaker Change: One that we believe they have the opportunity to serve both as a monotherapy and in combination with standards of care that may be inaccessible for the other b seven H for Adcs in development. We continue to expect that we will be in a position to announce our initial clinical data and initiate expansion in the second half of this year.

Marty Huber: We continue to expect that we will be in a position to announce our initial clinical data and initiate expansion in the second half of this year. This readout will include safety, tolerability, efficacy, and biomarker data. Now, let's turn to Immunosynthin and XMT-2056. Immunosynthin is an immune-stimulating ADC platform. Last month, we were pleased to publish preclinical data in Nature Communications regarding some of the key mechanistic underpinnings of our approach to activate sting in a targeted manner using an ADC. This included in vitro and in vivo data demonstrating a 1, 2 punch consisting of target-dependent sting activation in both tumor cells and tumor-response immune cells.

Martin Huber: This read-out will include safety, tolerability, efficacy, and biomarker data.

Speaker Change: This readout will include safety tolerability efficacy and biomarker data.

Martin Huber: Now, let's turn to immunosynthin and XMT-2056. Immunosynthin is an immune-stimulating ADC platform. Last month, we were pleased to publish preclinical data in Nature Communications regarding some of the key mechanistic underpinnings of our approach to activate STING in a targeted manner using an ADC. This included in vitro and in vivo data, demonstrating a one-two punch consisting of target-dependent STING activation in both tumor cells and tumor-resident immune cells. The data also showed increased anti-tumor efficacy and reduced serum cytokine elevations in comparison to a free-sting agonist.

Marty Huber: The data also showed increased anti-tumor efficacy and reduced serum cytokine elevations in comparison to a free sting agonizing. XMT2056 is our lead sting agonist ADC candidate that we developed using immunosynthin. It targets a novel HER2 epitope that we believe could enable it to not only be an effective monotherapy but also could allow for eventual combinations with a range of other agents, including other HER2-targeted therapies. The dose escalation portion of our phase one trial is advancing and is enrolling patients with HER2-positive tumors, including breast, gastric, colorectal, and non-small-cell lung cancer.

Speaker Change: Now, let's turn to immuno Simpson and X M. T 2056, immuno Simpson has an innate immune stimulating ADC platform.

Martin Huber: Immunosynthin is an immune-stimulating ADC platform. Last month, we were pleased to publish preclinical data in Nature Communications regarding some of the key mechanistic underpinnings of our approach to activate sting in a targeted manner using an ADC. This included in vitro and in vivo data demonstrating a 1, 2 punch consisting of target-dependent sting activation in both tumor cells and tumor-response immune cells. The data also showed increased antitumor efficacy and reduced serum cytokine elevations in comparison to free sting activation.

Speaker Change: Last month, we were pleased to published preclinical data in nature communications regarding some of the key mechanistic underpinnings of our approach to activate staying in a targeted manner using an ADC. This included in vitro and in vivo data demonstrating a one two punch consisting of target dependent sting activation in both tumor cells.

Speaker Change: And tumor resident immune cells. The data also showed increased anti tumor efficacy and reduced serum cytokine elevations in comparison to a free Sting agonist <unk> 2056 is our lead Sting agonist ADC candidates that we developed using immuno center.

Martin Huber: XMT 2056 is our lead sting agonist ADC candidate that we developed using immunosynthins. It targets a novel HER2 epitope that we believe could enable it to not only be an effective monotherapy but also could allow for eventual combinations with a range of other agents, including other HER2-targeted therapies. The dose escalation portion of our Phase 1 trial is progressing and is enrolling patients with HER2-positive tumors, including breast, gastric, colorectal, and non-small cell lung cancer.

Martin Huber: XMT-2056 is our lead sting agonist ADC candidate that we developed using immunosynthin. It targets a novel HER2 epitope that we believe could enable it to not only be an effective monotherapy, but also could allow for eventual combinations with a range of other agents, including other HER2-targeted therapies. The dose-escalation portion of our phase-1 trial is advancing and is enrolling patients with HER2-positive tumors, including breast, gastric, colorectal, and non-small cell lung cancer. We expect to make good progress in escalation this year.

Speaker Change: It targets a novel her two epitope that we believe could enable it to not only be an effective monotherapy, but also could allow for eventual combinations with a range of other agents, including other her two targeted therapies. The dose escalation portion of our phase one trial is advancing and is enrolling patients with her two positive tumors, including breast.

Speaker Change: [noise] gastric colorectal and non small cell lung cancer, we expect to make good progress in escalation. This year and finally I'm pleased to report that we continue to advance our discovery collaborations with Johnson <unk> Johnson and Merck <unk>. In fact, we have been performing CMC activities to support J&J and earlier. This month, we earned another milestone.

Marty Huber: We expect to make good progress on escalation this year. And finally, I'm pleased to report that we continue to advance our discovery collaborations with Johnson & Johnson and Merck KGA. In fact, we have been performing CMC activities to support J&J, and earlier this month, we earned another milestone, this one for $8 million, related to that dolacenthin collaboration.

Martin Huber: We expect to make good progress in escalation this year. And finally, I'm pleased to report that we continue to advance our discovery collaborations with Johnson & Johnson and Merck KGA. In fact, we have been performing CMC activities to support J&J, and earlier this month, we earned another milestone, this one for $8 million, related to that dolacenthin collaboration. Payment of this milestone is due in the third quarter of 2024. Now, I'll turn things over to Brian for our Q2 financial update. Thank you, Marty.

Martin Huber: And finally, I'm pleased to report that we continued to advance our discovery collaborations with Johnson & Johnson and Mark KGA. In fact, we have been performing CMC activities to support J&J, and earlier this month, we earned another milestone. This one for $8 million related to that Dolosynthin collaboration. Payment of this milestone is due in the third quarter of 2024.

Speaker Change: This one for $8 million related to that does something collaboration payment of this milestone is due in the third quarter of 2020 for now, let's turn things over to Brian for our Q2 financial update.

Brian DeSchuytner: Payment of this milestone is due in the third quarter of 2024. Now, let's turn things over to Brian for our Q2 financial update. Thank you, Marty. Let's get into the financial highlights for the second quarter of 2024, starting with our balance sheet. We ended the second quarter with $162.7 million in cash, cash equivalents, and marketable securities.

Brian DeSchuytner: Now, let's turn things over to Brian for our Q2 financial update. Thank you, Marty. Let's get into the financial highlights for the second quarter of 2024, starting with our balance sheet. We ended the second quarter with $162.7 million in cash, cash equivalents, and marketable securities. We continue to expect our available funds will support our operating plan commitments into 2026. Please note that our cash runway guidance does not assume any future milestone payments that we may earn from our current collaborations or proceeds that we may realize from future collaborations. Net cash used in operating activities for the second quarter of 2024 was $21.8 million, down significantly from the $61.8 million in net cash used during the year-or-go quarter.

Brian DeSchuytner: Thank you, Marty. Let's get into the financial highlights for the second quarter of 2024, starting with our balance sheet. We ended the second quarter with $162.7 million in cash, cash equivalents, and marketable securities. We continue to expect our available funds will support our operating plan commitments into 2026.

Brian DeSchuytner: We continue to expect our available funds will support our operating plan commitments into 2026. Please note that our cash runway guidance does not assume any future milestone payments that we may earn from our current collaborations or proceeds that we may realize from future collaborations. Net cash used in operating activities for the second quarter of 2024 was $21.8 million, down significantly from the $61.8 million in net cash used during the year-ago quarter.

Brian: Thank you Marty let's get into the financial highlights for the second quarter of 2024, starting with our balance sheet. We ended the second quarter with $162 $7 million in cash cash equivalents in marketable securities. We continue to expect our available funds will support our operating plan commitments into 2026. Please note that our cash runway guidance does not assume any future.

Brian DeSchuytner: Please note that our cash runway guidance does not assume any future milestone payments that we may earn from our current collaborations or proceeds that we may realize from future collaborations. Net cash used in operating activities for the second quarter of 2024 was $21.8 million, down significantly from the $61.8 million in net cash used during the year-ago quarter. This decrease primarily reflects the portfolio reprioritization efforts and OPEX reductions we implemented in the second half of 2023.

Brian: Milestone payments that we may earn from our current collaborations are proceeds that we may realize from future collaborations net cash used in operating activities for the second quarter of 2024 was $21 $8 million down significantly from the $61 $8 million and net cash used during the year ago quarter. This decrease primarily reflects the portfolio re prioritization.

Brian DeSchuytner: This decrease primarily reflects the portfolio reprioritization efforts and OPEX reductions we implemented in the second half of 2023. Turning to our income statement, collaboration revenue for the second quarter of 2024 was $2.3 million, compared to $10.7 million for the same period of 2023. The year-over-year change was primarily related to reduced collaboration revenue recognized under our Johnson & Johnson and Merck KJA collaboration agreements. Research and development expenses for the second quarter of 2024 declined significantly to $17.2 million, compared to $49 million for the same period in 2023.

Brian DeSchuytner: List decrease primarily reflects the portfolio repairization efforts and op-x reductions we implemented in the second half of 2023. Turning to our income statement, collaboration revenue for the second quarter of 2024 was $2.3 million compared to $10.7 million for the same period of 2023. The year-over-year change was primarily related to reduced collaboration revenue recognized under our Johnson & Johnson and Mark KJA collaboration agreements. Research and development expenses for the second quarter of 2024 declined significantly to $17.2 million compared to $49 million for the same period in 2023. For the most recent quarter, approximately $2.4 million of this spending was related to non-cash stock-based compensation.

Brian: And Opex reductions we implemented in the second half of 2023, turning to our income statement collaboration revenue for the second quarter of 2024 was $2 $3 million compared to $10 $7 million for the same period of 2023 the year over year change was primarily related to reduced collaboration revenue recognized under our Johnson <unk> Johnson and Merck.

Brian DeSchuytner: Turning to our income statement, collaboration revenue for the second quarter of 2024 was $2.3 million, compared to $10.7 million for the same period of 2023. The year-over-year change was primarily related to reduced collaboration revenue recognized under our Johnson & Johnson and Merck KJA collaboration agreements. Research and development expenses for the second quarter of 2024 declined significantly to $17.2 million, compared to $49 million for the same period in 2023. For the most recent quarter, approximately $2.4 million of this spending was related to non-cash, stock-based compensation.

Brian DeSchuytner: For the most recent quarter, approximately $2.4 million of this spending was related to non-cash, stock-based compensation. The year-over-year decline in R&D expenses was primarily related to reduced costs associated with manufacturing and clinical activities for our discontinued ADC UPRE and reduced employee compensation expense following the restructuring we completed in 2023. General and administrative expenses for the second quarter of 2024 declined significantly to $10.5 million, compared to $18.2 million during the same period in 2023. Additionally, approximately $2 million in non-cash, stock-based compensation expenses were included in G&A for the most recent quarter.

J a collaboration agreements research and development expenses for the second quarter of 2024 declined significantly to $17 $2 million compared to $49 million for the same period in 2023 for the most recent quarter approximately $2 $4 million of this spending was related to noncash stock based compensation the year over year decline in R&D.

Brian DeSchuytner: The year-over-year decline in R&D expenses was primarily related to reduced costs associated with manufacturing and clinical activities for our discontinued ADC UPRE and reduced employee compensation expense following the restructuring we completed in 2023. General and administrative expenses for the second quarter of 2024 declined significantly to $10.5 million, compared to $18.2 million during the same period in 2023. Approximately $2 million in non-cash, stock-based compensation expenses were included in G&A for the most recent year.

Brian DeSchuytner: The year-over-year decline in R&D expenses was primarily related to reduced costs associated with manufacturing and clinical activities for our discontinued ADC uppery and reduced employee compensation expense following the restructuring we completed in 2023. General and administrative expenses for the second quarter of 2024 declined significantly to $10.5 million compared to $18.2 million during the same period in 2023. Approximately $2 million in non-cash stock-based compensation expenses were included in G&A for the most recent. Corp. The year-over-year decline in GNA was primarily related to reduced consulting and professional services fees and reduced employee compensation expenses following our restructuring.

Brian: Expenses was primarily related to reduced costs associated with manufacturing and clinical activities for our discontinued ADC Opry and reduced employee compensation expense. Following the restructuring we completed in 2023.

Brian: General and administrative expenses for the second quarter of 2024 declined significantly to $10 $5 million compared to $18 $2 million. During the same period in 2023, approximately $2 million in noncash stock based compensation expenses were included in G&A for the most recent quarter the year over year decline in G&A was primarily related to reduced consulting and professional <unk>.

Brian DeSchuytner: The year-over-year decline in G&A was primarily related to reduced consulting and professional services fees and reduced employee compensation expenses following our restructuring. And finally, Mersana's net loss for the second quarter of 2024 was $24.3 million, compared to a net loss of $54.3 million for the same period in 2023.

Speaker Change: Services fees and reduced employee compensation expenses, following our restructuring and finally, where sun is net loss for the second quarter of 2024 was $24 $3 million compared to a net loss of $54 $3 million for the same period 2023 that concludes our business update operator would you. Please open the call for questions from the audience.

Brian DeSchuytner: And finally, Mersana's net loss for the second quarter of 2024 was $24.3 million compared to a net loss of $54.3 million for the same period in 2023.

Operator: The year-over-year decline in G&A was primarily related to reduced consulting and professional services fees and reduced employee compensation expenses following our restructuring. And finally, Mersana's net loss for the second quarter of 2024 was $24.3 million, compared to a net loss of $54.3 million for the same period in 2023. That concludes our business update. Operator, would you please open the call to questions from the audience? We will now begin the question and answer session. To ask a question, you may press star, then one on your touchtone phone.

Unknown Executive: That concludes our business update.

Operator: That concludes our business update. Operator, would you please open the call for questions from the audience? We will now begin the question period.

Operator: Operator, would you please open the call for questions from the audience? We want to begin the question and answer session. To ask a question, you may press star, then one, on your touchtone phone. To withdraw your question, please press star, then two. At this time, we will pause momentarily to assemble our roster.

We will now begin the question and answer session.

We will now begin the question and answer session. To ask a question, you may press star, then one on your touchtone phone. To withdraw your question, please press star then 2. At this time, we will pause momentarily to assemble our roster. The first question today comes from Tara Bancroft with TD Cowan. Please go ahead. Hi, good morning, everyone.

Speaker Change: To ask a question you May Press Star then one on your Touchtone phone.

To withdraw your question. Please press Star then two.

Speaker Change: At this time, we will pause momentarily to assemble our roster.

Operator: To withdraw your question, please press star then 2. At this time, we will pause momentarily to assemble our roster. The first question today comes from Tara Bancroft with TD Cowan. Please go ahead. Hi, good morning, everyone.

Tara Bancroft: The first question today comes from Tara Bancroft with TD Cowan. Please go ahead. Hi, good morning, everyone. So I'm hoping you could give us maybe a qualitative measure of how patients are doing in the trial. I mean, you previously noted that responses are being observed, but have you observed more or deepening since then and for safety, you know, other than no MTD being reached. Are you happy with the level of grade three events that you're seeing? Thanks.

Speaker Change: The first question today comes from Tara Bancroft with TD Cowen. Please go ahead.

Tara Bancroft: Hi, good morning, everyone.

Marty Huber: So I was hoping you could give us maybe a qualitative measure of how patients are doing in the trial. I mean, you previously noted that responses are being observed, but have you observed more or deepening since then? And for safety, other than no MTD being reached, are you happy with the level of grade 3 events that you're seeing? Thanks. Thank you, Tim.

Tara Bancroft: If you could give us maybe a qualitative measure of how patients are doing and the trial. I mean, you. You previously noted that responses are being observed but have you observed more or deepening since then and for.

Speaker Change: For safety you know other than no M. T. D. Being reached are you happy with the level of grade three events that you're seeing thanks.

Marty Huber: While we're not giving any details on the 1660 clinical data, I think there are a couple points. One, we are at 80 milligrams per meter squared, and this is a dose that equates to roughly 2.2 milligrams per kilogram, which is much higher than we've previously gone on the platform. So while we're not talking about details of grade 3, et cetera, events, we are comfortable that we're able to escalate to this dose range.

Unknown Executive: Thank you, too.

Chad: Thank you Chad.

Martin Huber: Well, we're not giving any details on the 1660 clinical data. I think there are a couple points. Is one. We are at 80 milligrams per meter squared. And this is a dose that it would show roughly 2.2 milligrams per kilogram, which is much higher than we previously gone on the platform. So while we're not talking about details of grade three, et cetera, events, we are comfortable that we're able to escalate to this dose range. We're not getting into any details on the responses at this point in time.

Speaker Change: Well, we're not giving any details on the 16 60 clinical data I think there are.

Speaker Change: A couple of points is one we are at 80 milligrams per meter square and this is a dose that equity.

Speaker Change: Roughly 2.2 milligrams per kilogram, which is much higher than we previously go onto the platform.

Marty Huber: We're not getting into any details on the responses at this point in time. That information will be included in our second half data disclosure. Okay, thanks so much. The next question comes from Jonathan Chang with Lee Rink Partners. Please go ahead. Good morning. Thanks for taking my questions. First question at 1660.

Speaker Change: So while we're not talking about details of grade III et cetera events.

Speaker Change: We are comfortable that we're able to escalate to this to this dose range.

Speaker Change: Not getting into any details all the responses at this point in time all of that information will be included in our second half data disclosure.

Martin Huber: That information will be included in our second half data disclosure.

Tara Bancroft: Okay, thanks a bunch.

Speaker Change: Okay. Thanks, so much.

Jonathan Chang: The next question comes from Jonathan Chang with Lee Rink Partners. Please go ahead.

Speaker Change: The next question comes from Jonathan Chang with Leerink Partners. Please go ahead.

Jonathan Chang: Good morning. Thanks for taking my questions. First question on 1660. Can you discuss the progress you're making on the biomarker front and how much and what biomarker data we could see in the second half disclosure? And second question, can you provide any more granularity on when and how you plan to disclose the initial 1660 clinical data. Thank you.

Jonathan Chang: Good morning, Thanks for taking my questions.

Marty Huber: Can you discuss the progress you're making on the biomarker front and how much and what biomarker data we could see in the second half disclosure? And second question, can you provide more granularity on when and how you plan to disclose the initial 1660 clinical data? Thank you. I'm going to cover the biomarker answer, and then I'm going to turn it over to Jason regarding future disclosure. With regard to biomarkers, just to remind everybody, we selected patient populations that, with the tumor types, triple negative breast cancer, hormone receptor positive breast cancer, endometrial, and ovarian, that all have higher levels of expression of B7H4. However, within those populations, we are not requiring a patient to be biomarker positive to be enrolled. In other words, we're enrolling all comers across the country.

First question on 16 60.

Jonathan Chang: Can you discuss the progress you're making on the biomarker front and how much and what biomarker data we could see in the second half disclosure.

Speaker Change: And second question.

You can provide any more granularity on when and how you plan to disclose the initial 16 60 clinical data. Thank you.

Martin Huber: I'm going to cover the biomarker answer, and then I'm going to turn it over to Jason regarding the future disclosure. With regards to biomarker, just to remind everybody, we selected patient populations that with the tumor types, triple negative risk cancer, hormone receptor positive risk cancer, endometronovarium that all have higher levels of expression of the seven age for. However, within those populations, we are not requiring inpatient to be biomarker positive to be enrolled. In other words, we're enrolling all comers across that.

Speaker Change: Well I'm going to cover the biomarker answer and then I'm going to turn it over to Jay said regarding the future disclosure.

Jay: With regards to the biomarker just to remind everybody we selected patient populations that with the tumor types triple negative breast cancer hormone receptor positive breast cancer endometrial and ovarian that all have higher levels of expression of <unk> seven age four however, within those populations we are not.

Jay: Requiring the patient to be biomarker positive to be enrolled in other words, we're enrolling all comers across that we are capturing tissue, which we are analyzing retrospectively for the expression of <unk> seven age four so what our plan would be and the initial data disclosure is to provide some information.

Marty Huber: We are capturing tissue, which we are analyzing retrospectively for the expression of B7H4. So what our plan would be in the initial data disclosure is to provide some information that would allow us to, we'll share with you kind of our thinking on, do we believe a biomarker will be necessary for patient selection going forward or not? As of today, we have not made that decision, but we'll continue to gather data on biomarkers negative and positive to inform that decision. And on Jonathan, additional color, we really don't have any additional color to share at this stage.

Martin Huber: We are capturing tissue, which we are analyzing retrospectively for the expression of the seven age for so. What our plan would be in the initial data and disclosure is to provide some information that would allow us. We'll share with you kind of our thinking on do we believe a biomarker will be necessary for patients watching going forward or not as of today. We have not made that decision, but will continue to gather data on biomarker negative and positive to inform that.

Jay: That would allow us well share with you kind of our thinking on do we believe a biomarker will be necessary for patient selection going forward or not as of today. We have not made that decision, but we will continue to gather data on biomarker negative and positive to inform that decision.

Martin Huber: And Jonathan, on additional color, we really don't have additional color to share at this stage. We're keeping the guidance at second half.

Jay: And John it's been an additional color, we really don't have additional color to share at this stage, we're keeping the guidance at the second half.

Jason Fredette: We're keeping the guidance at second half. If that could be a company event, or it could be a medical congress at this stage, we haven't defined that yet.

Martin Huber: If that could be a company event or it could be a medical congress, at this stage, we haven't defined that. Got it.

John: If that could be a company event or it could be a medical Congress.

John: At this stage, we haven't defined that.

John: Okay.

Unknown Executive: Good morning and welcome to Mersana Therapeutics, 2nd quarter, 2024 Conference Call and Webcast Currently, all participants are in a listen only mode There will be a question and answer session at the end of this call Please note, this call is being recorded I would now like to turn the call over to Jason Fredette, Senior Vice President, Investor Relations and Corporate Communications Thank you operator and good morning everyone Before we begin, please note that this call will contain forward-looking statements within the meaning of federal securities laws These statements may include but are not limited to those related to our platforms, product candidates, business strategy, clinical trial, execution and data, business development efforts and cash runway Each of these forward-looking statements is subject to risks and uncertainties that could cause actual results to differ materially from those projected in such statements These risks and uncertainties are discussed in our quarterly report on form 10 Q, filed with the Securities and Exchange Commission on May 9, 2024 and in subsequent SEC filings Our filings are available at SEC.gov and on our website, mersana.com Except is required by law, we assume no obligation to update forward-looking statements publicly even if new information becomes available in the future On today's call, we have mersana's president and chief executive officer Dr. Marty Hubert and our chief operating officer and chief financial officer Brian DeShightner With that, let me turn the call over to Marty to begin our discussion Thank you Jason and good morning everyone The second quarter of 2024 was the time of continued progress and mersana as we advanced dose escalation in phase one clinical trials of XMT-1660, our LEED-DOLICENTANT ADC Candidate, and XMT-2056, our LEED-immunicENTANT ADC Candid At the same time, we made further progress in our collaborations while also benefiting from our efforts to reduce our operating expenses last year We believe these collective accomplishments have put us in a strong position as we approach our initial clinical data readout for XMT-1660, which is planned for the second half of this year Let's begin with that program XMT-1660 is an ADC we developed using DOLICENTANT, our next-generation cytotoxic ADC platform This candidate targets B7H4, a cell surface protein within the B7 family that can suppress anti-tumor immunity and can serve as a negative, prognostic indicator for multiple tumor types In the dose escalation portion of our ongoing phase one clinical trial, we are enrolling patients with tumor types that most commonly express high levels of B7H4 These include patients with recurrent triple negative and hormone receptor positive breast cancers, as well as endometrial and ovarian cancers, all areas with high unmet medical need For instance, as many know, Trudelby and Orrin HER2 are being used to treat the vast majority of recurrent triple negative breast cancer patients in the US today Emerging clinical data continue to suggest that patients can develop resistance to ADCs with Topo-1 inhibitor payloads As a result, we are hearing an increasing call among treating physicians for new ADCs with alternative payloads that aren't subject to Topo 1 or PGP E-Flux resistance mechanisms. XMT 1660 fits this profile, and we are enrolling many patients who have received a prior Topo 1 ADC in our trial. Dose escalation remains ongoing, and we still have not established a maximum tolerated dose. In fact, we are currently at a dose of 80 milligrams per meter squared in escalation.

Speaker Change: Got it if I could just maybe throw in one more a.

Marty Huber: If I could just maybe fill in one more follow-up question here, also on 1660. Just to clarify, have you already committed to this expansion portion of the study? I guess, what do you need to see and address before initiating the expansion portion of the study? We have built the expansion cohorts into the existing protocol, so that work has already been done.

Jonathan Chang: If I could just maybe fill in one more follow-up question here.

Speaker Change: Follow up question here.

Martin Huber: Also, in 1660, just to clarify, have you already committed to this expansion portion of the study? I guess what do you need to see in a dress before initiating the expansion portion of the study?

Speaker Change: Also on $6 60.

Speaker Change: Just to clarify have you already committed to the expansion portion of the study.

Speaker Change: I guess, what do you need to see in a dress before initiating the expansion portion of the study.

Martin Huber: Thank you. We have built the expansion cohorts into the existing protocol. So that work has all been done. The step we're left is the identification of a recommended phase to at least one recommended phase two dose to take forward into the expansion. And as we have not yet defined an entity, we are not ready to declare a recommended phase two days to do phase two dose at this point in time.

Speaker Change: We have built the expansion cohorts into the existing protocol. So that work has all been done.

Marty Huber: The step we're left with is the identification of a recommended Phase 2, at least one recommended Phase 2 dose to take forward into the expansion. And as we have not yet defined an MTD, we are not ready to declare a recommended Phase 2 dose at this point in time.

Speaker Change: He stepped on the left is the identification of a recommended phase II at least one recommended phase two dose to take forward into the expansion.

And as we have not yet defined and M. T. D. We are not ready to declare a recommended phase two days. She does phase two dose at this point in time.

Speaker Change: Okay.

Jonathan Chang: Understood. Thank you.

Speaker Change: Understood. Thank you.

Speaker Change: Yeah.

Ashiq Mubarak: The next question comes from Ashik Mubarak with City. Please go ahead. Hi, guys. Thanks for taking my question. In the press release, you called out the 80 make dose every four weeks, which seems to be less frequent dose sync compared with some of the data we've seen from your peers in the B7H4 space. I'm just curious how important you think dosing frequency could be as a potential differentiator. And on a similar point, I think in the past, you've talked about the need to sort of work through the exposure optimization. I'm wondering if you can share any color on where you are in that process and how close you are to figuring out optimal exposure.

Speaker Change: The next question comes from Sheikh Mubarak with Citi. Please go ahead.

Operator: Thank you. The next question comes from Ashiq Mubarack with Citi. Please go ahead. Hi guys.

Sheikh Mubarak: Hi, guys. Thanks for taking my question in the press release, you called out.

Ashiq Mubarack: Thanks for taking my question. In the press release, you called out the 80 make-dose every four weeks, which seems to be less frequent dosing compared with some of the data we've seen from your peers in the BCMH force base. I'm just curious how important you think dosing frequency could be as a potential differentiator. And on a similar point, I think in the past, you've talked about the need to sort of work through exposure optimization. I'm wondering if you can share any color on where you are in that process and how close you are to figuring out optimal exposure.

Sheikh Mubarak: Dose every four weeks, which seems to be.

Sheikh Mubarak: Less frequent dosing compared with some of the data we've seen from your peers seem to be some need for space.

Speaker Change: Central differentiator.

Speaker Change: And.

Speaker Change: On a similar point I think in the past you've talked about the need to sort of walk through that.

Speaker Change: Exposure optimization I'm wondering if you could share any color on where you are in that process and how close you are to us.

Speaker Change: So figuring out afterwards.

I'll talk about her thank you.

Martin Huber: Thank you. Thank you for the question.

Speaker Change:

Marty Huber: First of all, we have spoken about every four weeks, and one of the reasons we're able to explore the every four week schedule is because our molecule, and we have shared preclinical data that shows an extended half-life compared to other molecules. We have antibody-like half-life or adolescence in ADCs.

Speaker Change: Thank you for the question first of all we we have spoken about the every four weeks in one of the reasons, we're able to explore the every four week schedule is because our molecule and we have shared preclinical data shows an extended half life compared to other molecules, we have antibody like half life or.

Martin Huber: First of all, we have spoken about the every four weeks. And one of the reasons we're able to explore the every four week schedule is because our molecule and we have shared preclinical data shows an extended half-life compared to other molecules. We have antibody-like half-life or adolescence in ADCs. So when you have that long a half-life that allows you to explore these longer schedules, which we do think could be a potential advantage in the clinic. But at the same time, it may be more effective to have more frequent dosing to decrease CMax relative to AUC and maintain more exposure over time.

Speaker Change: <unk> 86, so when you have that long half life that allows you to explore these longer schedules, which we do think could be a potential advantage in the clinic.

Marty Huber: So when you have that long and half-life, that allows you to explore these longer schedules, which we do think could be a potential advantage in the clinic. But at the same time, it may be more effective to have more frequent dosing to decrease CMACs relative to AUC and maintain more exposure over time. That is an unknown; we have the question we don't have an answer for.

Speaker Change: But at the same time.

Speaker Change: It may be more effective to have more frequent dosing two.

Speaker Change: Decreased feedbacks relative to AUC and maintain more exposure over time.

Martin Huber: That is an unknown; we have the question, we don't have an answer for. And that's one of the reasons we made the decision to proactively explore the every four-week schedule dose escalation in parallel to more frequent dose of more frequent schedules. So we are generating data on both, I mean, every four weeks as well as shorter intervals, and we should have that data as part of the second half presentation, which will allow us as part of the recommended phase two dose to define not only what that dose is, but also the appropriate.

Speaker Change: That is the <unk>.

Speaker Change: No. We ask the question, we don't have an answer for and that's one of the reasons. We made the decision to proactively explore the every four week schedule dose escalation in parallel to more frequent dose.

Marty Huber: And that's one of the reasons we made the decision to proactively explore the every four week schedule dose escalation in parallel to more frequent doses. And that's one of the reasons we made the decision to proactively explore the every four week schedule because we have the question we don't have an answer for about the more frequent schedules. So, we are generating data on both every four weeks, as well as shorter intervals, and we should have that data as part of the second half presentation, which will allow us, you know, as part of the recommended phase two dose, to define not only what that dose is, but also the appropriate. Okay. Okay. I got it.

Speaker Change: More frequent schedules. So we are generating data on both.

Speaker Change: On every four week as well as shorter intervals and we should have that data as part of the second half presentation, which would then allow US you know as part of the recommended phase two dose to define not only what that doses, but also that's got the appropriate scale.

Speaker Change: Okay, Okay got it and I would ask one follow up.

Ashiq Mubarak: Okay, got it. I could ask one follow-up. I think you would, in the past, to maybe needing to establish a phase two dose before sharing the data with us.

Ashiq Mubarack: I can ask one follow-up question. I think you alluded in the past to maybe needing to establish a Phase II dose before sharing the data with us. Is it also necessary to establish an MTD as per the primary endpoint of the study before you show the data, or is that not necessary? Thank you.

Speaker Change: I think you alluded in the past.

Speaker Change: Needing to establish a phase two dose before.

Speaker Change: Sharing the data with US is it does it also necessary to establish an M. T D for the primary endpoint of the study.

Martin Huber: Is it also necessary to establish an MTD as for the primary endpoint of the study before you show the data, or is that not necessary? Thank you. But an MTD is not critical. We don't necessarily have to get to an MTD. I think we want to, before we declare a recommended phase two dose, though, have some understanding of kind of where is the upper bound that you can get to, whether that's a formal protocol specified MTD or just a general observation of your starting to see, you know, payload effects. So I think we want to be a little careful saying we have to see an MTD.

Speaker Change: Before ensure the data or is that that's not necessary. Thank you.

Speaker Change: A N G. D is not critical we don't necessarily have to get to an M. T D.

Marty Huber: I think we wanted, before we declared a recommended phase two dose, though, to have some understanding of kind of where the upper bound that you can get to, whether that's a formal protocol specified in T.D. or just a general observation of you starting to see, you know, payload effects. So I think we want to be a little careful, say we have to see an MTV, but I think we've given the fact that ADCs historically have had relatively narrow therapeutic indices. I think we do want to see kind of where that upper bound is before we make a call on what shows we're taking away. Thank you very much.

Speaker Change: I think we wanted before we declare a recommended phase two dose though is have some understanding of kind of where is the upper bound that you could get to whether that's a formal protocol specified MTV or just a general observation of you're starting to see.

Martin Huber: This is well beyond the dose levels we were able to reach clinically with any of our prior ADCs. We believe our ability to continue to dose escalate can be attributed to two factors. The first is Dolosynthens ability to reduce toxicity commonly associated with other ADC platforms like neutropenia, neuropathy, and ocular toxicity, as well as those that were seen with our first-generation platform, Doloflexin. And the second factor is that based on data that has been reported to date, there does not appear to be an obvious on-target liability with B7H4.

Speaker Change: Payload effects, so I think.

Speaker Change: What we want to be a little careful saying, we have to see an empty D. But I think given the fact that ADC historically I've had relatively narrow therapeutic indices I think we do want to see kind of where is that upper bound before we make a call on what steps, we're taking to expansion.

Martin Huber: But I think we've given the fact that ADCs historically, I've had relatively narrow therapeutic indices.

Martin Huber: I think we do want to see kind of where is that upper bound before we make a call on which dose we're taking to expansion.

Ashiq Mubarak: Thank you very much.

Speaker Change: Got it thank you very much.

Michael Schmidt: The next question comes from Michael Schmidt with Guggenheim. Please go ahead. Hey, good morning. Thanks for taking my questions. I was wondering if you could comment a bit more on whether you have observed a dose response in the. Every four weeks, there's a cohort so far. Now you've commented on seeing responses earlier than the 80 milligrams dose. It's just curious. And then also what magnitude of increase in those exposures one would expect perhaps with a more frequent dosing schedule.

Speaker Change: The next question comes from Michael Schmidt with Guggenheim. Please go ahead.

Michael Schmidt: The next question comes from Michael Schmidt with Guggenheim. Please go ahead. Good morning.

Michael Schmidt: Hey, good morning, Thanks for taking my questions I was wondering if you could comment a bit more on.

Marty Huber: Thanks for taking my questions. I was wondering if you could comment a bit more on whether you have observed a dose response in the Every Four Weeks Dosing cohort so far. I know you've commented on seeing responses earlier than the 80 mg dose. I'm just curious.

Martin Huber: In parallel with our dose escalation work, which includes the enrollment of BACSO cohorts, we are also proactively exploring different dosing schedules with XMT-1660 with the aim to optimize efficacy and safety. This has included every four weeks as well as more frequent dosing regimens. At the same time, we also are progressing our biomarker strategy in preparation for expansion and potential later stages of development. All this work is aimed at building a robust data set that can inform important strategic decisions as we seek to position XMT-1660 as a potential best-in-class asset.

Michael Schmidt: Whether you have observed a dose response in the.

Speaker Change: Every four week dosing cohort so far I know you've commented on seeing responses.

Speaker Change: And then the 80 milligrams a day.

Speaker Change: But just curious and then also.

Marty Huber: And also, what magnitude of increase in dose exposure one would expect, perhaps, with a more frequent dosing schedule? Thank you, Michael. We're not sharing any further color on exposure-response relationships. I think we did disclose that we had responses at doses previously before we got to 80, so I think what we can be explicit about is that we have seen responses at lower doses lower than 80, and that was in our previous disclosure.

Speaker Change: What what magnitude of increase didn't go with each well we show one would.

Speaker Change: Expect perhaps with a more frequent dosing schedule.

Martin Huber: Thank you, Michael. We're not sharing any further color on exposure-response relationships. I think we did disclose that we have responses at doses previously before we got to 80. So I think what we, we can be explicit that we have seen responses at the lower doses lower than 80. And that was in our previous disclosure. And with regards to exposure response relationships, that would be premature at this point in time, and that will be part of the second half data disclosure. The second part of your question was, I think there was it on that topic.

Speaker Change: Thank you Michael.

Speaker Change: We're not sharing any further color on exposure response relationships.

Martin Huber: One that we believe may have the opportunity to serve both as a monotherapy and in combination with standards of care that may be inaccessible for the other B7H4 ADCs in development. We continue to expect that we will be in a position to announce our initial clinical data and initiate expansion in the second half of this year. This read-out will include safety, tolerability, efficacy, and biomarker data.

Speaker Change: I think we did disclose that we have responses at doses.

Speaker Change: Before we got to eight so I think what we.

Speaker Change: We could be exposed to that we have seen it.

Speaker Change: Responses at the lower doses lower than 80.

Speaker Change: That within our previous disclosure.

Speaker Change: And with regards to exposure response relationship that would be premature at this point in time and that will be part of the second half data disclosure.

Marty Huber: And with regard to exposure response relationships, that would be premature at this point in time, and that will be part of the second half of the data disclosure. The second part of your question was... I think that was it on that topic. Yeah, the other question I had is as we monitor forthcoming data from other companies pursuing B7H4, for example, AstraZeneca, who will have some data as well. Yeah, I'm just curious. Ashiq Mubarak, Brian DeSchuytner, Colleen Kusy, Ashiq Mubarak, Darren Benjamin, Ashiq Mubarak, Yeah, Michael, you're you're coming in and out.

Martin Huber: Now, let's turn to immunosynthin and XMT-2056. Immunosynthin is an immune-stimulating ADC platform. Last month, we were pleased to publish preclinical data and nature communications regarding some of the key mechanistic underpinnings of our approach to activate sting in a targeted manner using an ADC. This included in vitro and in vivo data, demonstrating a one-to-punch consisting of target-dependent sting activation in both tumor cells and tumor-resident immune cells. The data also showed increased anti-tumor efficacy and reduced serum cytokine elevations in comparison to a free-sting agonist.

The second part of your question was.

Speaker Change: Okay.

Speaker Change: I think that was it on.

Speaker Change: On that topic.

Speaker Change: <unk>.

Michael Schmidt: And the other question I had is, as we monitor, you know, forthcoming data from other companies pursuing seven age four. For example, AstraZeneca, who will have data as well. Yeah, I'm just curious.

Speaker Change: Yes. The other question I had is as we as we monitor.

Speaker Change: Forthcoming data from other companies pursuing an edge for for example, Astrazeneca who will have.

Speaker Change: Small, yes, I'm just curious.

Speaker Change: Yes.

Speaker Change: <unk>.

Speaker Change: Yeah.

Martin Huber: XMT-2056 is our lead sting agonist ADC candidate that we developed using immunosynthin. It targets a novel HER2 epitope that we believe could enable it to not only be an effective monotherapy, but also could allow for eventual combinations with a range of other agents, including other HER2 targeted therapies. The dose-escalation portion of our phase-1 trial is advancing and is enrolling patients with HER2 positive tumors, including breast, gastric, colorectal, and non-small cell lung cancer. We expect to make good progress in escalation this year.

Martin Huber: Yeah, Michael, you're coming in and out. Are you asking for some speculation about easy? Yeah, I'm just curious as we kind of look forward to more where they have an update on their data. How would you message it? Interpret, Sarah Derrassada, and how it may regroup to a key of program.

Speaker Change: Yeah, Michael Youre coming in and out Hum.

Brian DeSchuytner: Are you asking for some speculation about AZ? Yeah, I'm just curious as we kind of look forward to this moment that I have an update on that data, how it must be shit, their results, and how it may return to your program. Sure, Michael, maybe I can handle that.

Speaker Change: Are you asking for some speculation about AZ.

Yeah, I'm just curious as you kind of look forward small where they have an update on that data how investors should.

Speaker Change: Yes.

Dara: Yeah, Dara side through it and how it may read through to your program.

Dara: Yeah.

Martin Huber: Sure, Michael, maybe I can handle that. You know, from a safety and tolerability perspective, we would expect to see the typical Topo-1 platform toxicity. Those include things like myelosuppression. You know, I think that's relevant because it speaks to which combination opportunities may be more or less challenging for an asset like that. From an efficacy standpoint, to the extent that A.V. shows responses and breast cancer. We frankly believe the question in this space will be how many of those responses were generated in patients who have been previously treated with a prior Topo-1 ADCs? A.V. has been involved in a trial globally, including in potentially locations where patients are more likely to be naive to Topo-1 ADCs.

Dara: Sure, Mike maybe I can handle that.

Brian DeSchuytner: You know, from a safety and tolerability perspective, we would expect to see the typical Topo 1 platform toxicity, which includes things like myelose suppression. I think that that's relevant because it speaks to which combination opportunities may be more or less challenging for an asset like that. From an efficacy standpoint, to the extent that A.V. shows responses in breast cancer, we frankly believe the question in this space will be how many of those responses were generated in patients who have been previously treated with a prior Topo 1 ADC. A.D.C.

Speaker Change: Safety and Tolerability perspective, we would expect to see the typical chapel one platform toxicity.

Martin Huber: And finally, I'm pleased report that we continued to advance our discovery collaborations with Johnson & Johnson and Mark KGA. In fact, we have been performing CMC activities to support J&J and earlier this month, we earned another milestone. This one for $8 million related to that Dolosynthin collaboration. Payment of this milestone is due in the third quarter of 2024.

Speaker Change: Include things like mile of suppression.

Speaker Change: I think that's relevant because it.

Speaker Change: Speaks to which combination opportunities may be more or less challenging.

Speaker Change: Or for an asset like that.

Speaker Change: From an efficacy standpoint to the extent that AZ shows responses in breast cancer. We frankly believe the question in this space will be how many of those responses regenerated in patients who had been previously treated with a prior to April one.

Brian DeSchuytner: Now, let's turn things over to Brian for our Q2 financial update. Thank you, Marty. Let's get into the financial highlights for the second quarter of 2024, starting with our balance sheet. We ended the second quarter with $162.7 million in cash, cash equivalents, and marketable securities. We continue to expect our available funds will support our operating plan commitments into 2026. Please note that our cash runway guidance does not assume any future milestone payments that we may earn from our current collaborations or proceed that we may realize from future collaborations. Net cash used in operating activities for the second quarter of 2024 was $21.8 million, down significantly from the $61.8 million in net cash used during the year-or-go quarter.

Brian DeSchuytner: 's been enrolling its trial globally, including in potentially locations where patients are more likely to be naive to TOPO1 A.D.C.'s. You know, here in the U.S., the vast majority of recurrent triple negative breast cancer patients are being treated with Trevelvy and or in HER2. Emerging data, and we've spoken about this before, continue to suggest that patients can develop resistance to ADCs with those Topo-1 payloads. As a result, as Marty noted in the opening remarks, there's an increase in calls from physicians to find ADCs with new, sort of, vaginal payloads that aren't subject to the Topo-1 resistance mechanisms or PGP pumps. So, I guess the key question that people should be looking for is, what are those prior treatments in the time-crap? Great, thank you so much.

Speaker Change: He's been enrolling these trials globally, including in potentially locations, where patients are more likely to be naive to tumble one ADC here.

Operator: As a reminder, if you would like to ask a question, please press star then 1 to join the question queue. The next question comes from Charles Hsu on Lifesci. Please go ahead.

Martin Huber: You know, here in the U.S., the vast majority of recurrent triple-legged breast cancer patients are being treated with Travelvy and/or in HER2. Emerging data, and we've spoken about this before, continue to suggest that patients can develop resistance to ADCs with those Topo-1 payloads. As a result, as Marty noted in the opening remarks, there's an increase in call from physicians to find ADCs with new sort of vaginal payloads that aren't subject to the Topo-1 resistance mechanisms or PGP funds. So, I guess the key question that people should be looking for is, what are those prior treatments and the darn graphics of those patients?

Speaker Change: Here in the U S. But the vast majority are recurrent triple negative breast cancer patients.

Speaker Change: Being treated with <unk> and ore and hurt you.

Speaker Change: Emerging data and we've spoken about this before continue to suggest that patients can develop resistance to adcs with those triple one payloads.

Brian DeSchuytner: List decrease primarily reflects the portfolio repairization efforts and op-x reductions we implemented in the second half of 2023. Turning to our income statement, collaboration revenue for the second quarter of 2024 was $2.3 million compared to $10.7 million for the same period of 2023. The year-over-year change was primarily related to reduced collaboration revenue recognized under our Johnson & Johnson and Mark KJA collaboration agreements. Research and development expenses for the second quarter of 2024 declined significantly to $17.2 million compared to $49 million for the same period in 2023.

Speaker Change: As a result as Marty noted in.

Speaker Change: In your opening remarks.

Speaker Change: An increase in call from physicians to find Adcs with new.

Marty Huber: <unk> payloads that arent subject to that.

Speaker Change: One resistance mechanisms or P. GP pump, so I guess the key question.

Speaker Change: We're looking for is what are those prior treatments in the midterm.

Speaker Change: Grabbing some of those patients.

Speaker Change: Alright, thank you so much.

Michael Schmidt: Great.

Unknown Executive: Thank you so much.

Brian DeSchuytner: For the most recent quarter, approximately $2.4 million of this spending was related to non-cash stock-based compensation. The year-over-year decline in R&D expenses was primarily related to reduced costs associated with manufacturing and clinical activities for our discontinued ADC uppery and reduced employee compensation expense following the restructuring we completed in 2023. General and administrative expenses for the second quarter of 2024 declined significantly to $10.5 million compared to $18.2 million during the same period in 2023.

Operator: As a reminder, if you would like to ask a question, please press star, then one, to join the question, Q.

Speaker Change: As a reminder, if you would like to ask a question. Please press Star then one to join the question queue.

Charles Shoe: The next question comes from Charles Shoe with Lifesaie. Please go ahead. Good morning, everyone, and thanks for taking the questions. Given that your XMT-1660 protocol allows for pretty sizable backfilling, how are you thinking or have been thinking about prioritizing enrollment towards further advancing dose escalation slash exploration versus collecting more data at any given backfill cohort? And has this thinking evolved as you've continued to advance further into clinically relevant doses and schedules? Thank you. Well, first of all, yeah, the protocol just to remind you for everybody allows up to 12 patients at a given dose, as well as at a given indication.

Speaker Change: The next question comes from Charles Chu with lifestyle. Please go ahead.

Charles Chu: Good morning, everyone and thanks for taking the questions.

Charles Hsu: Good morning everyone, and thanks for taking the questions. Given that your XMT 1660 protocol allows for pretty sizable backfilling, how are you thinking or have been thinking about prioritizing enrollment towards further advancing dose escalation slash exploration versus collecting more data at any given backfill cohort? And has this thinking evolved as you've continued to advance further into clinically relevant doses and schedules? Thank you. Thank you. Thank you.

Charles Chu: Given that your ex <unk> 16, 60 protocol allows for pretty sizable back feeling how are you thinking or had been thinking about prioritizing enrollment towards further advancing dose escalation.

Brian DeSchuytner: Approximately $2 million in non-cash stock-based compensation expenses were included in G&A for the most recent. Corp. The year over year decline in GNA was primarily related to reduced consulting and professional services fees and reduced employee compensation expenses following our restructuring. And finally, Mersana's net loss for the second quarter of 2024 was $24.3 million compared to a net loss of $54.3 million for the same period in 2023.

Speaker Change: Escalations slash exploration versus collecting more data at any given backfill cohort and has us thinking evolved as you've continued to advance further into clinically relevant doses and schedules. Thank you.

Speaker Change: Well.

Speaker Change: First of all yes. The protocol just to provide you for everybody allows up to 12 patients at a given dose as well as at a given indication. So it does give us a lot of flexibility to get significant patient numbers at a given dose in tumor type.

Marty Huber: First of all, yeah, the protocol, just to remind you all, allows up to 12 patients at a given dose as well as at a given indication. So it does give us a lot of flexibility to get significant numbers of patients at a given dose and tumor type. What do we think about that?

Martin Huber: So it does give us a lot of flexibility to get significant patient numbers at a given dose and tumor type. How do we think about that? I think we've probably been fairly explicit that TNBC is probably the one we spend the most time talking about as it's the area of highest unmet medical need. So I do think what we would look toward in this data set is, if one, we're getting TNBC patients, high unmet medical needs, the 7H4 is currently frequent there. It's a second scenario, as Brian alluded to in the differentiation from the others, looking at a U.S.-based population where most TNBC patients will have seen Trudelvy and/or in her two is a great place to explore the hypothesis that our ADC, with its novel Scapple Linker payload, will have an opportunity to show activity in settings where topo payloads are unmet medical.

Unknown Executive: That concludes our business update.

Unknown Executive: Operator, would you please open the call for questions from the audience? We want to begin the question and answer session. To ask a question, you may press star, then one, on your touchtone phone. To withdraw your question, please press star, then two. At this time, we will pause momentarily to assemble our roster.

Marty Huber: I think we've probably been fairly explicit that, you know, TNBC is probably the one we spend the most time talking about as it's the area of highest unmet medical need. So I do think what we would look toward in this data set is, One, we're getting TNBC patients with high medical need, and B7H4 is fairly frequent there. Second, as Brian alluded to in the differentiation from the others, looking at a U.S.-based population where most TNBC patients will have seen Tredelvi and or HER2 is a great place to explore the hypothesis that our ADC, with its novel scapholinker payload, will have an opportunity to show activity in settings where topo payloads are unlikely to be effective. So I think for us, the...

Speaker Change: How do we think about that I think we've probably been fairly.

Speaker Change: Blitzer debt.

Speaker Change: CNBC is probably the one we spend the most time talking about as it's the area of highest unmet medical need. So I do think what we would look toward in this data set is.

Speaker Change: How did it one.

Speaker Change: One we're getting T N B C patients high unmet medical need seven age for us fairly frequent there.

Tara Bancroft: The first question today comes from Tara Bancroft with TD Cowan. Please go ahead.

Brian: Second its an area as Brian alluded to in the differentiation from the others looking at a U S. Based population, where most CNBC patients will have featured Lv Android her two is a great place to explore the hypothesis that our ADC with it.

Martin Huber: Hi, good morning, everyone. So I'm hoping you could give us maybe a qualitative measure of how patients are doing in the trial. I mean, you previously noted that responses are being observed, but have you observed more or deepening since then and for safety, you know, other than no MTD being reached. Are you happy with the level of grade three events that you're seeing? Thanks. Thank you, too.

Brian: Novel Scaffold linker payload will have an opportunity to show activity in settings, where towboat payloads are unlikely to be effective. So so I think for us the.

Martin Huber: Well, we're not giving any details on the 1660 clinical data. I think there are a couple points is one. We are at 80 milligrams per meter squared. And this is a dose that it would show roughly 2.2 milligrams per kilogram, which is much higher than we previously gone on the platform. So while we're not talking about details of grade three, et cetera, events, we are comfortable that we're able to escalate to this to this dose range. We're not getting into any details on the responses at this point in time.

Martin Huber: It's unlikely to be effective. So I think for us the Well, we're not giving details of exactly what patient types, the way the protocols design, we can enroll, expand back cells that it would TNBC or other timber types, and really try to answer that question of, what's the activity in this kind of post-toko environment? So that would be one of the data sets that we should, well, one of the data points we should be able to include in our second half disclosure. And maybe if I could just ask one follow-up on that, you know, just given the FDA Project Optimist environment and what sounds like your intention to take one go-forward dose as opposed to more than one.

Speaker Change: Well, we're not giving details of exactly what patient types. The way the protocol design, we can enroll expand backfill that with.

Marty Huber: While we're not giving details of exactly what patient types, the way the protocol is designed, we can enroll, expand back cells that it would TNBC or other different types, and really try to answer that question of what activity there is in this kind of post-transplant environment. So that would be one of the data sets that we should, one of the data points we should be able to include in our second half, just close.

Speaker Change: T NBC or other tumor types and really try to answer that question, what's the activity and it's kind of a post hobo environment. So that would be one of the datasets that we should or what are the data points, we should be able to include in our second half disclosure.

Speaker Change: Okay.

Unknown Executive: That information will be included in our second half data disclosure. Okay, thanks a bunch.

Marty Huber: And maybe if I could just ask one follow-up question on that, you know, just given the FDA project optimist environment and what sounds like your intention to take one go forward dose as opposed to more than one. I guess then, you know, it is fair to assume then that you would have backfilled across or backfilled enough patients at each given dose level to have made that determination by the end of this year. Thank you. I think one of the things we're careful about is that we need at least one recommended phase two dose, so I want to be careful. It could be two or three.

Speaker Change: Got it and maybe if I could just ask one follow up on that just given the FTA project Optimus environment and what sounds like your intention to take one go forward dose as opposed to more more than one.

Jonathan Chang: The next question comes from Jonathan Chang with Lee Rink Partners. Please go ahead.

Martin Huber: I guess then, you know, is it fair to assume then that you would have backfilled a cross or backfilled enough patients at each given dose level to have made that determination by end of this year? Thank you. I think one of the things we're careful, we need at least one recommended phase to dose, so I want to be careful; it could be two. The way expansion is written in the protocol, it gives us the flexibility to take one or two. We do recognize that with the way Project Optimists is rolling out, at some point in time we will formally, we will likely formally have to study two doses.

Speaker Change: Then is it fair to assume then that you would have backfill to cross over backfill enough patients at each given dose level to have made that determination by end of this year. Thank you.

Martin Huber: Good morning. Thanks for taking my questions. First question on 1660. Can you discuss the progress you're making on the biomarker front and how much and what biomarker data we could see in the second half disclosure? And second question can provide any more granularity on when and how you plan to disclose the initial 1660 clinical data.

Speaker Change: I think one of the things we're careful we need at least one.

Speaker Change: Recommended phase two dose.

Marty Huber: The way expansion is written in the protocol, it gives us the flexibility to take one or two. We do recognize that with the way Project Optimus is rolling out, at some point in time, we will formally, we will likely formally have to study two doses. [inaudible] But if you look at the precedent here, some of the guidance from the agency, having... Meaningful backfill patients at multiple doses does go in the direction of helping answer questions for Project Optimist, so hopefully, it'll minimize the number of doses we would have to take into the actual pivotal programs.

Speaker Change: Be careful it could be to the the way expansion is written in the protocol. It gives us the flexibility to take one or two.

Speaker Change: We do recognize that with the way project Optimus is rolling out at some point in time, we will formally we will likely formerly have to study two doses, but if you. If you look at the precedence here in some of the guidance from the agency having.

Martin Huber: Thank you. I'm going to cover the biomarker answer and then I'm going to turn it over to Jason regarding the future disclosure. With regards to biomarker, just to remind everybody, we selected patient populations that with the tumor types, triple negative risk cancer, hormone receptor positive risk cancer, endometronovarium that all have higher levels of expression of the seven age for. However, within those populations, we are not requiring inpatient to be biomarker positive to be enrolled.

Martin Huber: But if you look at the precedence here and some of the guidance from the agency, having meaningful backfill patients at multiple doses does go in the direction of help answering questions for Project Optimists. So hopefully it will minimize the number of doses we would have to take into the actual pivotal programs. I mean, there are folks out there today who are taking three or four doses and schedules into large registration enabling or registration targeted programs. And I think there is an opportunity, based on precedent, to narrow again. We're going to have to study two doses in the pivotal, potentially.

Speaker Change: Meaningful backfill patients at multiple doses does go in the direction of help answering questions for project Optimists. So hopefully it'll minimize the number of doses, we would have to take into the actual pivotal programs.

Marty Huber: I mean, there are folks out there today who are taking three or four doses and schedules into large registration-enabling or registration-targeted programs, and we think there is an opportunity, based on precedent, to narrow it down. Are we going to have to study two doses in the pivotal? Potentially, but the more information we get out of these backfills at multiple doses, the better we'll inform that discussion with the agency.

Martin Huber: In other words, we're enrolling all comers across that. We are capturing tissue, which we are analyzing retrospectively for the expression of the seven age for so what our plan would be in the initial data and disclosure is to provide some information that would allow us. We'll share with you kind of our thinking on do we believe a biomarker will be necessary for patients watching going forward or not as of today. We have not made that decision, but will continue to gather data on biomarker negative and positive to inform that.

Speaker Change: There are folks out there today, who are taking three or four doses and schedules into large registration, enabling or registration targeted programs.

Speaker Change: And we think there is an opportunity based on precedent to narrow it down or we can have to study two doses in the pivotal potentially.

Martin Huber: But the more information we get out of these backfills at multiple doses, the better will inform that discussion with the agency.

Speaker Change: But the more information we get out of these backfill that multiple doses the better will inform that.

Speaker Change: Discussion with the agency.

Speaker Change: Understood. Thanks for taking the questions.

Charles Shoe: Understood.

Colleen Kusy: Okay. Thanks for taking the questions. The next question comes from Colleen Kusy with Baird. Please go ahead.

Charles Shoe: Thanks for taking the questions.

Speaker Change: Charles.

Martin Huber: And Jonathan, on additional color, we really don't have additional color to share at this stage. We're keeping the guidance at second half. If that could be a company event or it could be a medical Congress at this stage, we haven't defined that.

Colleen Kusy: The next question comes from Colleen Kussi with Beard. Please go ahead. Thanks. Good morning, and thanks for taking our questions on the upcoming 1660 readout.

Speaker Change: The next question comes from Colin <unk> with Baird. Please go ahead.

Colin: Thanks, Good morning, and thanks for taking our questions.

Marty Huber: Thanks, good morning, and thanks for taking our questions. On the upcoming 1660 readout, can we expect biomarker data from all patients enrolled in escalation backfill? And will that be a meaningful enough data set to determine an ORR and that biomarker positive subgroup? And then for the expansion cohorts that you plan to open in the second half of this year, would you be looking to open one or multiple tumors? With regard to biomarkers, I mean, one of the challenges of a retrospective analysis is...

Colin: On the upcoming 16 60 read out can we expect biomarker data from all patients enrolled in escalation backfill and will that be a meaningful enough dataset to determining or are in that biomarker positive subgroups and then for the expansion cohorts that you plan to open a second half of this year would you be looking to open one or multiple tumors.

Colleen Kusy: Can we expect biomarker data from all patients enrolled in escalation backfill, and will that be a meaningful enough data set to determine an ORR in that biomarker positive subgroup? And then for the expansion cohorts that you plan to open a second half of this year, would you be looking to open one or multiple to specific expansion cohorts?

Martin Huber: Got it. If I could just maybe fill in one more follow-up question here. Also in 1660, just to clarify, have you already committed to this expansion portion of the study? I guess what do you need to see in a dress before initiating the expansion portion of the study?

Speaker Change: Like expansion cohorts.

Martin Huber: With regards to biomarker, I mean, one of the challenges of a retrospective analysis is that you don't require the patient to have a documented positive before they roll. You will have samples that will be valuable for the biomarker. So it would be presumptuous for you to sit here and say, we're going to have 100% of the data on that topic. But what we, and the second thing remember, these are backfills. This is not a full expansion. So your confidence intervals around any point estimate. And by the way, this applies to the FIJN data set as well as the HESA data sets that they presented last year as well are going to be relatively wide.

Speaker Change: With regards to the biomarker I mean, one of the challenges of a retrospective analysis is.

Marty Huber: Since you don't require the patient to have a documented positive before they roll, you will have samples that will be invaluable for the biomarker. So it would be the heads of the data set that they presented last year but is going to be relatively wide.

Speaker Change: Since you don't requires the patient to have a documented positive before they enroll you will have samples that will be invaluable for the biomarker. So it would be.

Martin Huber: Thank you. We have built the expansion cohorts into the existing protocol. So that work has all been done. The step we're left is the identification of a recommended phase to at least one recommended phase two dose to take forward into the expansion. And as we have not yet defined an entity, we are not ready to declare a recommended phase two days to do phase two dose at this point in time.

Unknown Executive: Understood.

Unknown Executive: Thank you.

Speaker Change: Presumptuous of me to sit here and say, we're going to have 100% of the data on that topic.

Speaker Change: But what we and the second thing remember these are backfill. This is not a full expansion. So your confidence intervals around any point estimate.

Speaker Change: By the way this applies to the <unk> data set as well as the heads of the data that they presented last year that are going to be relatively wide. So trying to say we have a definitive response rate determination out of a phase one dose escalation.

Martin Huber: So trying to say we have a definitive response rate determination out of a phase one dose escalation would be overreaching. However, I do think we should have sufficient patients to get a directional answer. How do these data look in the greater universe of data out there? And two, is there some differentiation in biomarker positive versus negative?

Marty Huber: So trying to say we have a definitive response rate determination out of a phase one dose escalation would be overreaching. However, I do think we should have sufficient patients to get a directional answer: how do these data look in the greater universe of data out there? And two, is there some differentiation between biomarker positive versus negative? We may still need to carry out an expansion and, or, for that matter, a pivotal study. All comers, based on the evolving data.

Ashiq Mubarak: The next question comes from Ashik Mubarak with city. Please go ahead. Hi, guys. Thanks for taking my question. In the press release, you called out the 80 make dose every four weeks, which seems to be less frequent dose sync compared with some of the data we've seen from your peers in the B7H4 space. I'm just curious how important you think dosing frequency could be as a potential differentiator. And on a similar point, I think in the past, you've talked about the need to sort of work through the exposure optimization.

Speaker Change: Would be overreaching. However, I do think we should have sufficient patients to get a directional answer is how do these data look into a greater universe of data out there and two is there some differentiation in biomarker positive versus negative.

Martin Huber: We may still need to carry into expansion and or for that matter of pivotal studies, all comers based on the evolving data.

Speaker Change: We may still need to carry into expansion and or for that matter pivotal studies.

Marty Huber: One of the things I learned, you know, back in the Keytruda experience, if you don't have a clear signal, you want to be really careful there. After, you know, less than 100 lung cancer patients, we had quite a clear signal that we were able to select out a subset. I think when we go back to our UPRI experience, the biomarker there didn't perform so well. And that, ultimately, the pivotal study had a negative consequence on our ability to interpret the data.

Speaker Change: All comers based on the evolving data.

Martin Huber: One of the things I learned, you know, back on the key true experience, if you don't have a clear signal, you want to be really careful there. After, you know, less than 100 lung cancer patients, we had quite a clear signal that we were able to select down a subset. I think when we go back to our up re-experience, the biomarker there didn't perform so well. And that ultimately the pivotal study had a negative consequence on our ability to on the data. So I think it's really is a data driven decision based on not only the performance, I mean the biology of a specific biomarker.

Speaker Change: One thing I learned you know.

Speaker Change: Back on the Keytruda experience.

Speaker Change: If you don't have a clear signal you want to be really careful there.

Ashiq Mubarak: I'm wondering if you can share any color on where you are in that process and how close you are to figuring out optimal exposure. Thank you. Thank you for the question. First of all, we have spoken about the every four weeks. And one of the reasons we're able to explore the every four week schedule is because our molecule and we have shared pre clinical data shows an extended half life compared to other molecules.

Speaker Change: After.

Speaker Change: Less than 100 lung cancer patients, we had quite a clear signal that we were able to select out a subset.

Speaker Change: When we go back to our up re experience the biomarker there didn't perform so well.

Speaker Change: And that ultimately the pivotal study had a negative consequence on our ability to on the data. So I think it's really is a data driven decision based on not only.

Marty Huber: So I think it really is a data-driven decision based on not only the performance, I mean, the biology of a specific biomarker, how the drug performs, but also the performance of the biomarker itself. So there are a lot of questions that we want to answer based on data. Great, that's helpful. Thank you. And then just on the expansion cards, if you would open one or multiple in a second.

Speaker Change: The performance of the biology of a specific biomarker how the drug performs but also then the performance of the biomarker itself.

Ashiq Mubarak: We have antibody-like half life or adolescence in ADCs. So when you have that long a half life that allows you to explore these longer schedules, which we do think could be a potential advantage in the clinic. But at the same time, it may be more effective to have more frequent dosing to decrease CMax relative to AUC and maintain more exposure over time. That is an unknown, we have the question we don't have an answer for.

Martin Huber: Or how the drug performs, but also the performance of the biomarker itself. So there are a lot of questions that we want to, you know, answer based on data.

Speaker Change: So there are a lot of questions that we want to answer based on data.

Speaker Change: Okay. Great. That's helpful. Thank you and then just on that expansion.

Colleen Kusy: Great, the tough one.

Colleen Kusy: Thank you.

Unknown Executive: And then some expansion courts, if you would open one or multiple in the second half. We have all four written, at least four written into the protocol. However, based, you know, we'll probably make some decisions on which ones we prioritize based on the data from the phase one. We can flexibly either do a more stage of more; however, and that that'll be a data driven decision at that point in time.

Speaker Change: Expansion cards, if you would open one or multiple in the second half.

Marty Huber: We have all four written in, at least four written into the protocol. However, based on, you know, we'll probably make some decisions on which ones we prioritize based on the data from phase one. We can flexibly either do them or stage them, or however, and that'll be a data-driven decision at that point in time. Great, that makes sense. Thanks for taking your... The next question comes from Brian Chang with JP Morgan. Please go ahead. Hey, guys. Hey, Marty.

We have all four written and at least for written into the protocol.

Speaker Change: However.

Speaker Change: Base.

Speaker Change: We will probably make some decisions on which ones we prioritize based on the data from the phase one.

Ashiq Mubarak: And that's one of the reasons we made the decision to proactively explore the every four week schedule dose escalation in parallel to more frequent dose of more frequent schedules. So we are generating data on both, I mean, every four week as well as shorter intervals, and we should have that data as part of the second half presentation, which within allow us as part of the recommended phase two dose to define not only what that dose is, but also the appropriate.

Speaker Change: We we can flexibly either duo more stage or more however.

Speaker Change: That'll be a data driven decision at that point in time.

Unknown Executive: Great. That makes sense.

Speaker Change: Okay that makes sense, thanks for taking our questions.

Brian Chang: Thanks for taking our questions. The next question comes from Brian Chang with JP Morgan. Please go ahead. Hey guys. Hey, Marty. Thanks for taking our question this morning. Just want to follow up on your comments earlier.

Speaker Change: The next question comes from Brian Cheng with J P. Morgan. Please go ahead.

Brian Cheng: Hey, guys, Hey, Marty Thanks for taking my question. This morning, just wanted to follow up on your comments earlier.

Brian Chang: Thanks for taking our question this morning. I just want to follow up on your comment earlier. Do you need to reach MTD to declare the recommended phase 2 dose and then move into expansion? And then secondly, is, you know, related to your ongoing work around more frequent dosing, is that just a typical part of any development plan to satisfy perhaps some of the requirements of Project Optimist, or is that actively driven by your observations to date in the clinic?

Brian Chang: Do you need to reach MTB to declare the recommended face to dose and then move into expansion? And then secondly is you know related to your ongoing work around more frequent dosing. Is that just a typical part of any development plan to satisfy perhaps some of the requirements by project optimists, or is that actively driven by observation to date in the clinics? Thanks. With regards to the first question on MTB, I think we want to say, in a perfect world, we would actually define a formal MTB and know what that is before we pick a recommended face to dose.

Do you need to reach emptied D declared a recommended recommended phase two dose and then move into expansion.

Ashiq Mubarak: Okay, got it. I could ask one follow-up. I think you would in the past to maybe needing to establish a phase two dose before sharing the data with us. Is it also necessary to establish an MTD as for the primary endpoint of the study before you show the data or is that not necessary? Thank you. But an MTD is not critical. We don't necessarily have to get to an MTD. I think we want to, before we declare a recommended phase two dose, though, it's have some understanding of kind of where is the upper bound that you can get to, whether that's a formal protocol specified MTD or just a general observation of your starting to see, you know, payload effects.

Speaker Change: And then secondly, as you know we laid out to you our ongoing work around more frequent dosing.

Speaker Change #100: Is that just a typical part of any development plan to satisfy perhaps somewhat the requirement by project optimists or is that actively and driven by our observations to date in the clinics.

Speaker Change #101: With regards to the first question on M T D.

Brian Chang: With regard to the first question on MTD, I think we want to say, in a perfect world, we would actually define a formal MTD and know what that is before we pick a recommended phase 2 death. The one thing we'd like to highlight, especially when we see these ADCs, is sometimes you can have toxicities that don't achieve the level of a formal protocol-specified MTD, but patients aren't able to stay on that dose for more than a couple cycles.

Speaker Change #102: I think we want to say in a perfect world, we would actually define a formal M. T D and know what that is before we'd pick a recommended phase two dose.

Martin Huber: The one thing we'd like to highlight on, especially when we see these ADCs, is sometimes you can have toxicities that don't achieve the level of a formal protocol specified MTB, but patients aren't able to stay on that dose for more than a couple of cycles. And then you end up in this project optimist situation where laid in your program, you get taken to a lower dose. So part of it is we understand, we say, we want to make sure our recommended face-to-dose has an opportunity to be truly tolerable, which means the vast majority of patients can stay on that dose throughout their treatment cycle.

Speaker Change #103: The one thing we'd like to highlight on especially when we see these adcs.

Ashiq Mubarak: So I think we want to be a little careful saying we have to see an MTD. But I think we've given the fact that ADCs historically, I've had relatively narrow therapeutic indices. I think we do want to see kind of where is that upper bound before we make a call on which dose we're taking to expansion.

Speaker Change #103: Sometimes you can have toxicities that don't achieve the level of a formal protocol specified MTBE, but patients aren't able to stay on that dose for more than a couple of cycles.

Martin Huber: Thank you very much.

Brian Chang: And then you end up in this Project Optimist situation where, late in your program, you get taken to a lower dose. So part of it is we want to understand, we want to make sure our recommended Phase 2 dose has an opportunity to be truly tolerable, which means the vast majority of patients can stay on that dose throughout their treatment cycle. But it may not be a formal NTD protocol.

Speaker Change #103: And then do you end up.

Speaker Change #103: And this project after the situation were laid in your program you get taken to a lower dose. So so part of it is we understand we say we want to make sure. Our recommended phase II dose has an opportunity to be truly tolerable, which means the vast majority of patients can stay on that goes throughout their treatment cycle.

Michael Schmidt: The next question comes from Michael Schmidt with Guggenheim. Please go ahead. Hey, good morning. Thanks for taking my questions. I was wondering if you could comment a bit more on whether you have observed a dose response in the. Every four weeks, there's a cohort so far. Now you've commented on seeing responses earlier than the 80 milligrams dose. It's just curious. And then also what magnitude of increase in those exposure, one would expect perhaps with a more frequent dosing schedule.

Marty Huber: That's where I want to clarify. We do want to see where toxicity becomes, does it? This with regard to your second question was the more frequent, oh, yes. We...

Martin Huber: But it may not be a formal MTB protocol. That's where I want to clarify. We do want to see where does toxicity become dose limiting.

Speaker Change #103: But it may not be a formal MTV per protocol, that's where I want to clarify we do want to see where does toxicity become dose limiting.

Martin Huber: With regards to your second question, was the more frequent? Yes. If you look at data on ADCs and we looked at data from the CGM platform with the BCMMAE, there's this observation that certain toxicities tend to be CMACs related. We made the decision with the initial delay that we announced in Q2, that instead of doing a sequential see how high we can go with an every three or four weeks schedule, and then at that point going back and seeing could we increase exposure by doing a more frequent dosing, we made the decision to explore in Kerala.

Speaker Change #103: With regards to your second question.

Speaker Change #103: We'll see.

Speaker Change #104: What was the more frequent.

Speaker Change #103: Yes.

Speaker Change #103: We.

Speaker Change #103: If you look at data on Adcs, and we looked at data from the Ctrip platform with the V C N N E.

Marty Huber: If you look at data on ADCs, and we looked at data from the cGen platform with the VCMMAE, there's this observation that certain toxicities tend to be CMAX related. We made the decision with the initial delay that we announced in Q2, instead of doing a sequential, see how high we can go within every three or four weeks, and then at that point, go back and see if we can increase exposure.

Speaker Change #103: This observation that certain toxicities tend to be C. Max related.

Speaker Change #103: We made the decision with the initial delay that we announced in Q2.

Michael Schmidt: Thank you, Michael. We're not sharing any further color on exposure response relationships. I think we did disclose that we have responses at doses previously before we got to 80. So I think what we, we can be explicit that we have seen responses at the lower doses lower than 80. And that was in our previous disclosure.

Speaker Change #103: That instead of doing a sequential see how high we can go with it every three or four week schedule at <unk>.

Speaker Change #103: Then at that point going back and saying could we increase exposure.

Marty Huber: By doing more frequent dosing, we made the decision to explore in parallel. So today, we don't know if dose-limiting toxicity is going to be CMAX or AUC-related for this platform. One of the things we like to remind people is this is the first molecule on this platform that we've been able to get into this dose range. So we are still learning how the platform behaves. As you recall, for our initial molecules, the 1592, and the NAPI-2V, the dose-limiting toxicity was driven by on-target, And that's where we saw the NAPI-2B mediated ILD in the...

Speaker Change #103: By doing a more frequent dosing we made the decision to explore in parallel so today, we don't know.

Martin Huber: So today we don't know if dosing in toxicity is going to be CMACS or AUC related for this platform. One of the things we like to remind people: this is the first molecule on this platform that we've been able to get into this dose range. So we are still learning how the platform behaves. As you recall, for our initial molecules, the 1592, the NAPI2V, the dose limiting toxicity was driven by on target toxicity, and that's when we saw the NAPI2V mediated ILD in the so far B7H4, not just when we look at the competitors, has not really shown target mediated dose limiting toxicity.

Speaker Change #103: If dose limiting toxicity is going to be C Max or AUC related for this platform.

Michael Schmidt: And with regards to exposure response relationships that would be premature at this point in time, and that will be part of the second half data disclosure. The second part of your question was, I think there was it on that topic. And the other question I had is as we, as we monitor, you know, forthcoming data from other companies pursuing seven age four. For example, AstraZeneca, who will have data as well. Yeah, I'm just curious.

Speaker Change #103: One of the things we like to remind people. This is the first.

Speaker Change #103: Molecule on this platform that we've been able to get into this dose range. So we are still learning.

Speaker Change #103: How the platform behaves.

Speaker Change #103: You recall for initial molecules. The 15, 90, twos and happy to be the dose limiting toxicity was driven by on target toxicity and that's what we saw the mapping to be mediated IL.

Speaker Change #103: L D.

Speaker Change #103: The.

Speaker Change #103: So far be seven H four notches.

Marty Huber: So far, B7H4, not just when we look at the competitors, has not really shown target mediated dose-limiting toxicity. So this is an opportunity for us to really learn about our platform at higher doses and exposures.

Speaker Change #105: We look at the competitors has not really shown hargett mediated.

Michael Schmidt: Yeah, Michael, you're coming in and out. Are you asking for some speculation about easy? Yeah, I'm just curious as we kind of look forward to more where they have an update on their data. How would you message it? Interpret, Sarah Derrassada, and how it may regroup to a key of program.

Speaker Change #105: Dose limiting toxicity. So this is an opportunity for us to really learn about our platform and these higher doses and exposures.

Martin Huber: So this is an opportunity for us to really learn about our platform in these higher doses and exposures. Got it.

Brian Chang: And maybe just one more follow-up, if I may. You know, I think it's interesting that you talk about CMAX, your thoughts about CMAX, and how you're thinking about, you know, evaluating it to make sure that you have the optimal profile. You know, just going back to your comments and your press release, I think you emphasize a lot on your current efforts in understanding how to optimize frequent dosing.

Got it and maybe just one more follow up if I may you know I think it's interesting if you can talk about that the C. Max.

Brian Chang: And maybe just one more follow up if I may. I think it's interesting that you talk about the CMACS, your thoughts around CMACS and how you're thinking about evaluating it to make sure that you have the optimal profile. Just going back to your comments and your press release, I think you emphasize a lot on your current efforts in understanding how to optimize the frequent dosing. So, as you think about your current progress today, are you closely in understanding how high you can go with 1660 or this platform? Thanks. Yeah, I think Ryan, we've probably said as much as we can. You know, we're still in dose escalation, have not hit an MTD, and we'll just have to leave it at that for the time being.

Your thoughts around C Max and how you're thinking about you know are evaluating it to make sure that you have the optimal profile you know just going back to your comment in your press release, I think you emphasize a lot on.

Martin Huber: Sure, Michael, maybe I can handle that. You know, from a safety and tolerability perspective, we would expect to see the typical Topo-1 platform toxicity, those include things like myelose suppression. You know, I think that's relevant because it speaks to which combination opportunities may be more or less challenging for an asset like that. From an efficacy standpoint, to the extent that A.V, shows responses and breast cancer, we frankly believe the question in this space will be how many of those responses were generated in patients who have been previously treated with a prior Topo-1 ADCs?

Speaker Change #106: Our current efforts and understanding.

Speaker Change #107: How to optimize that frequent dosing. So you know as you think about your current progress today are you close an understanding how high you can go.

Brian Chang: So, you know, as you think about your current progress to date, are you close to understanding how high you can go with 1660 or this platform? Yeah, I think Brian, we've probably said as much as we can, you know, we're still in dose escalation, have not hit an MTD, and we'll just have to leave it at that for the time. Great. Thank you, Jay. Once again, if you'd like to ask a question, please press star and then 1 to join the question queue. The next question comes from Asthika Goonewardene with Truist.

Speaker Change #108: With 16, 60, it or that platform. Thanks.

Speaker Change #109: Yeah I think.

And we've probably said as much as we can and you know we're still in dose escalation have not hitting mgd and we'll just have to leave it at that for the time being.

Unknown Executive: Great. Thank you, Jason. Sure.

Jason Fredette: Great. Thank you Jason.

Jason Fredette: Sure.

Martin Huber: A.V, has been involved in a trial globally, including in potentially locations where patients are more likely to be naive to Topo-1 ADCs. You know, here in the U.S., the vast majority of recurrent triple-legged breast cancer patients are being treated with travelvy and or in HER2. Emerging data, and we've spoken about this before, continue to suggest that patients can develop resistance to ADCs with those Topo-1 payloads. As a result, as Marty noted in the opening remarks, there's an increase in call from physicians to find ADCs with new sort of vaginal payloads that aren't subject to the Topo-1 resistance mechanisms or PGP funds. So, I guess the key question that people should be looking for is, what are those prior treatments and the darn graphics of those patients?

Speaker Change #110: Once again, if you'd like to ask a question. Please press Star then one to join the question queue.

Operator: Once again, if you'd like to ask a question, please press star, then one to join the question queue.

Asthika Goonewardene: The next question comes from Estica Guna Wardens with Truis. Please go ahead. Hey, good morning, guys, and thanks for thinking the question. So I appreciate that you might be taking more than one dose level into the expansion cohort and then next sense. But would you be conducting expansion cohorts with multiple frequencies running in parallel? So maybe a Q2W, Q3W running in parallel at the same dose cohort at the same dose level?

Speaker Change #111: The next question comes from S. T get Gounod Barden with choice. Please go ahead.

Unknown Executive: Great. Thank you so much.

Speaker Change #112: Hey, good morning, guys and thanks for taking the question.

Asthika Goonewardene: Please go ahead. Hey, good morning, guys, and thanks for thinking about the question. So I appreciate that you might be taking more than one dose level into the expansion cohort, and that makes sense. But would you be conducting expansion cohorts with multiple frequencies running in parallel? So maybe a Q2WQ3W running in parallel at the same dose cohort at the same dose level? And then Marty, would you not go to my project optimist's requirements?

Speaker Change #113: So I appreciate that you might be taking more than one dose level into the expansion cohort.

Speaker Change #114: And that makes sense, but would you be conducting expansion cohorts.

Speaker Change #115: With multiple frequencies running in parallel so maybe.

Speaker Change #116: Q2, definitely Q3 W are running in parallel at the same dose cohort.

Marty Huber: At the same dose level and then Marty.

Asthika Goonewardene: And then Mari, would you not go to me project optimist's requirements with the expansion cohorts that say if you were to recruit maybe 30 to 40 patients needs cohort at a couple of different dose levels, would that not meet their case requirements or do you think you need to do that in a pivotal phase study and then have a quick follow. With regards to your first question. Yeah, when I say dose or recommend a phase two dose, I probably should be more explicit. It's recommend a phase two dose and schedule. And yes, it is possible that you would take two different dose schedules forward if that's the question. Is you really want to answer.

Speaker Change #117: Would you not be able to meet project optimists requirements with the expansion cohort, let's say if you were to recruit maybe 30 to 40 patients in each cohort at a couple of different dose levels would that not meet the fda's requirements or do you think you need to do that in a pivotal phase <unk> study and then I have a quick follow up.

Asthika Goonewardene: With the expansion cohorts, let's say if you were to recruit maybe 30 to 40 patients in the expansion cohort at a couple of different dose levels, would that not meet their case requirements, or do you think you need to do that in a pivotal phase study? And then have a quick follow-up.

Marty Huber: With regard to your first question, yeah, when I say dose or recommended phase two dose, I probably should be more explicit; it's recommended phase two dose and schedule. And yes, it is possible that you would take two different dose schedules forward if that's the question you really want to answer. But at this point in time, it would be premature to speculate on how we're going to do that. Just the protocol is written so we have the flexibility that if we want to take a more frequent dose versus a less frequent dose forward, we could do that. With regard to your second question, we are now getting purely into speculation as we have not had, you know, we're not coming forward with a specified registration enabling study.

Unknown Executive: As a reminder, if you would like to ask a question, please press star, then one, to join the question, Q.

Speaker Change #118: With regards to your first question, yes, when I say dose or recommended phase two dose I, probably should be more explicit its recommended phase two dose and schedule and yes. It is possible that you would take two different dose schedules forward. If that's the question is you really want to answer.

Charles Shoe: The next question comes from Charles Shoe with Lifesaie. Please go ahead. Good morning, everyone, and thanks for taking the questions. Given that your XMT-1660 protocol allows for pretty sizable backfilling, how are you thinking or have been thinking about prioritizing enrollment towards further advancing dose escalation slash exploration versus collecting more data at any given backfill cohort? And has this thinking evolved as you've continued to advance further into clinically relevant doses and schedules?

Martin Huber: But at this point in time, it would be premature to speculate on how we're going to do that. Just the protocol is written. So we have the flexibility that if we want to take a more frequent dose versus a less frequent dose forward, we could do that.

Speaker Change #119: But at this.

Speaker Change #119: Point in time, it would be premature to speculate on how we're going to do that just the protocol is written so we have the flexibility that if we want to take a more frequent dose versus a less frequent dose forward.

Speaker Change #119: Could do that.

Martin Huber: With regards to your second question, we are now getting purely into speculation as we have not had, you know, we're not coming forward with a specified registration labeling study. So, I mean, clear what I'm giving you is a theoretical. To your point, generally, most people are having to do some form of randomization or dose in the current environment. I think if you look at all the precedents out there today in the ADC space, they're doing randomization somewhere. I don't think there's a strong rule on whether you do that as part of expansion or whether you do that as part of your pivotal.

Speaker Change #119: With regards to your second question, we are now getting purely into speculation as we have not had.

Speaker Change #119: We were not coming forward with a specified registration, enabling studies only clear what I'm, giving you is the theoretical.

Charles Shoe: Thank you. Well, first of all, yeah, the protocol just to remind you for everybody allows up to 12 patients at a given dose, as well as at a given indication. So it does give us a lot of flexibility to get significant patient numbers at a given dose and tumor type. How do we think about that? I think we've probably been fairly explicit that TNBC is probably the one we spend the most time talking about as it's the area of highest unmet medical need.

Marty Huber: So I want to be clear, what I'm giving you is a theoretical example. To your point, generally, most people are having to do some form of randomization for dose in the current environment. I think if you look at all the precedents out there today in the ADC space, they're doing randomization somewhere. [inaudible] I don't think there's a strict rule on whether you do that as part of expansion or whether you do that as part of your pivot. Ultimately, you're going to need some data justifying the therapeutic index, the benefit risk of your dose versus an alternative dose.

Speaker Change #120: To your point generally most people are having to do some form of randomization per dose in the current environment. I think if you look at all the precedence out there today in the ADC space Theyre doing randomization somewhere.

Charles Shoe: So I do think what we would look toward in this data set is, if one, we're getting TNBC patients, high unmet medical needs, the 7H4 is currently frequent there. It's a second scenario as Brian alluded to in the differentiation from the others, looking at a U.S.-based population where most TNBC patients will have seen Trudelvy and or in her two is a great place to explore the hypothesis that our ADC with its novel Scapple Linker payload will have an opportunity to show activity in settings where topo payloads are unmet medical.

Speaker Change #120: I don't think there's a strong.

Speaker Change #120: Rule on whether you do that as part of expansion or whether you do that as part of your pivotal ultimately youre going to need some data justifying the therapeutic index the benefit risk of your dose versus an alternative dose.

Martin Huber: Ultimately, you're going to need some data justifying the therapeutic index, the benefit-risk of your dose versus an alternative dose. And I think what that becomes a matter, to be frank, efficiency of execution, et cetera.

Speaker Change #120: And I think.

Speaker Change #121: What what that becomes a matter ought to be Frank.

Marty Huber: And I think that it becomes a matter to be frank, efficiency of execution, etc. And those are all details that when we start talking about our expansion of registration plans, which we're not doing at this time, we'll go into in our thinking. Got it. And then, If you're in the indivisible situation where you have pushed the dose in the escalation and you're not seeing a big signal that you're approaching dose limiting, that's going to be dose limiting. Would you continue the escalation while also running the expansion at a public cohort?

Speaker Change #121: Efficiency of execution et cetera. Those are all details that when we start talking about our expansion of registration plans, which we're not doing at this time.

Martin Huber: And those are all details that, when we start talking about our expansion to registration plans, which we're not doing at this time, we'll go into our thinking there. Got it.

Speaker Change #121: We'll go into our thinking there.

Speaker Change #121: Got it and then.

Martin Huber: And then if you're in the in vivo situation where you have pushed the dose in the escalation and you're not seeing a big signal that you're approaching dose limiting, that's going to be dose limiting, would you continue the escalation while also running the expansion at a couple of cohorts? I mean, it's possible if we get into that scenario. As we say, we don't have to get to an MDD to declare a recommended phase to dose and move forward. And that can be part of our judgment as the data merges if we're comfortable that we've got enough confidence in the dose.

Speaker Change #122: If you are in the enviable situation, where you have pushed the dosing escalation and you're not seeing big signals that you're approaching dose limiting.

Charles Shoe: It's unlikely to be effective. So I think for us the Well, we're not giving details of exactly what patient types, the way the protocols design, we can enroll, expand back cells that it would TNBC or other timber types, and really try to answer that question of, what's the activity in this kind of post-toko environment? So that would be one of the data sets that we should, well, one of the data points we should be able to include in our second half disclosure.

Speaker Change #122: That's gonna be dose limiting.

Speaker Change #123: Would you continue the escalation while also running the expansion at a couple of cohorts.

Speaker Change #124: I mean, it's possible if we get into that scenario, we do not.

Marty Huber: I mean, it's possible if we get into that scenario; we don't, as we said, we don't have to get to an MTD to declare a recommended phase two dose to move forward. And that can be part of our judgment as the data emerges. If we're comfortable that we've got enough confidence in the dose and we want to continue to escalate and initiate expansion parallel, that is an option for us. However, we have not made that decision today. And that will be based on data.

Speaker Change #124: As we stated that we don't have to get to an M. D. D to declare a recommended phase II dose and forward.

Asthika Goonewardene: Thanks guys. The next question comes from Justin Zelin with BTIG. Please go ahead.

Speaker Change #124: That can be part of our judgment as we as the data emerges if we're comfortable that we've got enough confidence and the dose and we want to continue to escalate and initiate expansion parallel that as an option for us we have not made that decision today.

Charles Shoe: And maybe if I could just ask one follow up on that, you know, just given the FDA project optimist environment and what sounds like your intention to take one go forward dose as opposed to more than one. I guess then, you know, is it fair to assume then that you would have backfilled a cross or backfilled enough patients at each given dose level to have made that determination by end of this year?

Martin Huber: And we want to continue to escalate and initiate expansion parallel. That is an option for us. We have not made that decision today, and that will be based on data.

Speaker Change #124: That will be based on data.

Speaker Change #125: Okay. Thanks, guys.

Asthika Goonewardene: Thanks, guys.

Justin Zelin: Thank you. The next question comes from Justin Zellin with BTIG. Please go ahead. Good morning, and thanks for taking the question. With a discussion of unmet need for typoisomerase experience and resistant patients, can you talk to your confidence of differential activity of 16-16 patients?

Speaker Change #126: Thank you.

Speaker Change #126: The next question comes from Justin Phelan with P. T. I G. Please go ahead.

Charles Shoe: Thank you. I think one of the things we're careful, we need at least one recommended phase to dose, so I want to be careful, it could be two. The way expansion is written in the protocol, it gives us the flexibility to take one or two. We do recognize that with the way project optimists is rolling out, at some point in time we will formally, we will likely formally have to study two doses.

Justin Phelan: Good morning, and thanks for taking the question with a discussion of unmet need for tip isomerase experience in resistant patients can you talk to your confidence of differential activity of 16 60 in these patients.

Justin Zelin: Good morning, and thanks for taking the question. With the discussion of the unmet need for typoisomerase experience in resistant patients, can you talk about your confidence in the differential activity of 1660 in these patients? Yeah, maybe I can take that.

Martin Huber: Yeah, maybe I can take that. I think there are a number of hypotheses that would maybe lend themselves to think that our payload might not be subject to the same resistance mechanism. So, as you're probably well aware, there have been a number of real world data sets, retrospective analyses, single sites, that have shown that typoisomerase, ADCs used after other typoisomerase ADCs, have a substantial degradation in time to event endpoints. And this data really started to come out last ASMO, and it's been reinforced at ASCO, and FAPCS, and other places. There are papers out there that really speak to the mechanisms for how that resistance might occur.

Speaker Change #128: Yeah, maybe I can I can take that I think there are a number of hypotheses that would maybe lend themselves to think that our payload might not be subject to the same resistance mechanism. So as you're probably well aware there have been a number of real world data sets a retrospective analyses single site.

Brian DeSchuytner: I think there are a number of hypotheses that would maybe lend themselves to think that our payload might not be subject to the same resistance mechanism. So, as you're probably well aware, there have been a number of real-world data sets, retrospective analyses of single sites, that have shown that topoisomerase ADCs used after other topoisomerase ADCs have a substantial degradation in time-to-event endpoints. And, you know, this data really started to come out last ESMO, and it's been reinforced at ASCO and SABCS and other places. There are papers out there that really speak to the mechanisms for how that resistance might occur.

Charles Shoe: But if you look at the precedence here and some of the guidance from the agency, having meaningful backfill patients at multiple doses does go in the direction of help answering questions for project optimists. So hopefully it will minimize the number of doses we would have to take into the actual pivotal programs. I mean, there are folks out there today who are taking three or four doses and schedules into large registration enabling or registration targeted programs.

Speaker Change #128: That have shown that.

Speaker Change #129: Oh boy salaries ADC is used after other tomboy in summary, as a disease.

Substantial degradation in time to event endpoints.

Charles Shoe: And I think there is an opportunity based on precedent to narrow again. We're going to have to study two doses in the pivotal potentially. But the more information we get out of these backfills at multiple doses, the better will inform that discussion with the agency. Understood. Thanks for taking the questions.

Speaker Change #129: And you know there's this data really starting to come out last ESMO and its been Green force of ESCO and sbcs.

Speaker Change #129: Other places.

Brian DeSchuytner: It might be related to the switch of topo-1 enzyme complexes to topo-2, which, you know, don't share a sort of chemical similarity. Or it could also be upregulation of PGP pumps. That's a pretty common resistance mechanism in cancer, just reducing drug concentrations in the cancer cells themselves. So, our payload, a novel or a statin with a controlled bystander effect, is not subject to either of those mechanisms. It's not acting on topoisomerase.

Speaker Change #129: There are papers out there that really speak to the mechanisms for how that resistance might occur.

Martin Huber: It might be related to the switch of typo-1, and I'm complex as to typo-2, which, you know, don't share a sort of a chemical similarity, or could also be a regulation of PGP pumps. That's a pretty common resistance mechanism in cancer, just reducing drug concentrations in the cancer cells themselves. You know, our payload, a novel or a statin with controlled bystander effect, is not subject to either of those mechanisms. It's not acting on typoisomerase, not acting on DNA, acting on the microtubules. And once the satellite, that payload is not a PGP pump, so... So, those are, at least theoretically, reasons we would think that you might see some differential activity.

Speaker Change #130: Might be related to the switch of trouble one enzyme complex is to talk about too, which you know don't share a oh, sorry about chemical similarity.

Speaker Change #131: Or could it also be upregulation of PGP pumps, that's a pretty common resistance mechanisms and cancer, just reducing drug concentrations in the cancer cells themselves.

Brian DeSchuytner: It's not acting on DNA. It's acting on the microtubules. And once metabolized, that payload is not a PGP pump substrate. So those are, at least theoretically, reasons we would think that you might see some differential activity.

Speaker Change #130: Our payload.

Unknown Executive: The next question comes from Colleen Kussi with Beard. Please go ahead. Thanks.

Speaker Change #130: <unk> or a statin.

Speaker Change #130: With the controlled bystander effect is not subject to either of those mechanisms. It's.

Speaker Change #130: It's not acting on top of like summer start acting on DNA acting on the microtubules.

Colleen Kusy: Good morning and thanks for taking our questions on the upcoming 1660 readout. Can we expect biomarker data from all patients enrolled in escalation backfill and will that be a meaningful enough data set to determine an ORR in that biomarker positive subgroup. And then for the expansion cohorts that you plan to open a second half of this year, would you be looking to open one or multiple to specific expansion cohorts? With regards to biomarker, I mean, one of the challenges of a retrospective analysis is that you don't require the patient to have a documented positive before they roll.

Speaker Change #130: Once a metabolite that payload is not a PGP pumps substrate.

Speaker Change #130: So those are at.

Speaker Change #130: At least theoretically reasons, we would think that you might see some differential.

Speaker Change #130: Good.

Speaker Change #132: Great. Thanks for taking my question.

Operator: Great, thanks for taking our questions. This concludes our question and answer session. I would like to turn the conference back over to CEO Dr. Marty Huber for any closing remarks. Thank you, operator, and thanks everyone for dialing in. We'll be seeing some of you in New York at the WEDGBUSH Healthcare Conference, and we hope the rest of you enjoy the rest of your summer.

Unknown Executive: This concludes our question and answer session.

Speaker Change #133: This concludes our question and answer session I would like to turn the conference back over to CEO, Dr. Marty Huber for any closing remarks.

Martin Huber: I would like to turn the conference back over to CEO, Dr. Marty Huber, for Friday closing remarks. Thank you, operator. And thanks, everyone, for dialing in. We'll be seeing some of you in New York at the Web Bush Healthcare Conference, and hope the rest of you enjoy the rest of your summer.

Speaker Change #134: Thank you operator, and thanks, everyone for dialing in we'll be seeing some of you in New York at the Wedbush Healthcare Conference and hope the rest of you enjoy the rest of your summer.

Colleen Kusy: You will have samples that will be in a valuable for the biomarker. So it would be presumptuous for you to sit here and say, we're going to have 100% of the data on that topic. But what we, and the second thing remember, these are backfills. This is not a full expansion. So your confidence intervals around any point estimate. And by the way, this applies to the FIJN data set as well as the HESA data sets that they presented last year as well are going to be relatively wide.

Operator: This concludes the call operator. Thank you. The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.

Speaker Change #135: This concludes the call operator.

Speaker Change #134: Okay.

Speaker Change #136: The conference has now concluded. Thank you for attending today's presentation you may now disconnect.

Marty Huber: This concludes the call operator. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect. Copyright 2020 Mooji Media Ltd. All Rights Reserved. The Bulletproof Executive 2013

Speaker Change #134: [music].

Colleen Kusy: So trying to say we have a definitive response rate determination out of a phase one dose escalation would be overreaching. However, I do think we should have sufficient patients to get a directional answer is how do these data look in the greater universe of data out there? And two, is there some differentiation in biomarker positive versus negative? We may still need to carry into expansion and or for that matter of pivotal studies, all comers based on the evolving data.

Colleen Kusy: One of the things I learned, you know, back on the key true experience, if you don't have a clear signal, you want to be really careful there. After, you know, less than 100 lung cancer patients, we had quite a clear signal that we were able to select down a subset. I think when we go back to our up re-experience, the biomarker there didn't perform so well. And that ultimately the pivotal study had a negative consequence on our ability to on the data.

Colleen Kusy: So I think it's really is a data driven decision based on not only the the performance, I mean the biology of a specific biomarker. Or how the drug performs, but also the performance of the biomarker itself. So there are a lot of questions that we want to, you know, answer based on data. Great, the tough one. Thank you. And then some expansion courts, if you would open one or multiple in the second half.

Colleen Kusy: We have all four written, at least four written into the protocol. However, based, you know, we'll probably make some decisions on which ones we prioritize based on the data from the phase one. We can flexibly either do a more stage of more however, and that that'll be a data driven decision at that point in time. Great. That makes sense.

Colleen Kusy: Thanks for taking our questions.

Brian Chang: The next question comes from Brian Chang with JP Morgan. Please go ahead. Hey guys. Hey, Marty. Thanks for taking our question this morning. Just want to follow up on your comments earlier.

Martin Huber: Do you need to reach MTB to declare the recommended face to dose and then move into expansion? And then secondly is you know related to your ongoing work around more frequent dosing. Is that just a typical part of any development plan to satisfy perhaps some of the requirement by project optimists or is that actively driven by observation to date in the clinics? Thanks. With regards to the first question on MTB, I think we want to say, in a perfect world, we would actually define a formal MTB and know what that is before we pick a recommended face to dose.

Martin Huber: The one thing we'd like to highlight on, especially when we see these ADCs, is sometimes you can have toxicities that don't achieve the level of a formal protocol specified MTB, but patients aren't able to stay on that dose for more than a couple of cycles. And then you end up in this project optimist situation where laid in your program, you get taken to a lower dose. So part of it is we understand, we say, we want to make sure our recommended face to dose has an opportunity to be truly tolerable, which means the vast majority of patients can stay on that dose throughout their treatment cycle. But it may not be a formal MTB protocol. That's where I want to clarify. We do want to see where does toxicity become dose limiting.

Martin Huber: With regards to your second question, was the more frequent? Yes. If you look at data on ADCs and we looked at data from the CGM platform with the BCMMAE, there's this observation that certain toxicities tend to be CMACs related. We made the decision with the initial delay that we announced in Q2, that instead of doing a sequential see how high we can go with an every three or four weeks schedule, and then at that point going back and seeing could we increase exposure by doing a more frequent dosing, we made the decision to explore in Kerala.

Martin Huber: So today we don't know if dosing in toxicity is going to be CMACS or AUC related for this platform. One of the things we like to remind people, this is the first molecule on this platform that we've been able to get into this dose range. So we are still learning how the platform behaves. As you recall, for our initial molecules, the 1592, the NAPI2V, the dose limiting toxicity was driven by on target toxicity, and that's when we saw the NAPI2V mediated ILD in the so far B7H4, not just when we look at the competitors, has not really shown target mediated dose limiting toxicity. So this is an opportunity for us to really learn about our platform in these higher doses and exposures. Got it.

Martin Huber: And maybe just one more follow up if I may. I think it's interesting that you talk about the CMACS, your thoughts around CMACS and how you're thinking about evaluating it to make sure that you have the optimal profile. Just going back to your comments and your press release, I think you emphasize a lot on your current efforts in understanding how to optimize the frequent dosing. So as you think about your current progress today, are you closely in understanding how high you can go with 1660 or this platform?

Martin Huber: Thanks. Yeah, I think Ryan, we've probably said as much as we can, you know, we're still in dose escalation, have not hit an MTD and we'll just have to leave it at that for the time being. Great.

Unknown Executive: Thank you, Jason. Sure.

Unknown Executive: Once again, if you'd like to ask a question, please press star, then one, to join the question queue.

Asthika Goonewardene: The next question comes from Estica Guna Wardens with Truis. Please go ahead. Hey, good morning, guys, and thanks for thinking the question. So I appreciate that you might be taking more than one dose level into the expansion cohort and then next sense. But would you be conducting expansion cohorts with multiple frequencies running in parallel? So maybe a Q2W, Q3W running in parallel at the same dose cohort at the same dose level?

Martin Huber: And then Mari, would you not go to me project optimist's requirements with the expansion cohorts that say if you were to recruit maybe 30 to 40 patients needs cohort at a couple of different dose levels, would that not meet their case requirements or do you think you need to do that in a pivotal phase study and then have a quick follow, with regards to your first question. Yeah, when I say dose or recommend a phase two dose, I probably should be more explicit.

Martin Huber: It's recommend a phase two dose and schedule. And yes, it is possible that you would take two different dose schedules forward if that's the question is you really want to answer. But at this point in time it would be premature to speculate on how we're going to do that. Just the protocol is written. So we have the flexibility that if we want to take a more frequent dose versus a less frequent dose forward, we could do that.

Martin Huber: With regards to your second question, we are now getting purely into speculation as we have not had, you know, we're not coming forward with a specified registration labeling study. So I mean, clear what I'm giving you is a theoretical. To your point, generally most people are having to do some form of randomization or dose in the current environment. I think if you look at all the precedents out there today in the ADC space, they're doing randomization somewhere.

Martin Huber: I don't think there's a strong rule on whether you do that as part of expansion or whether you do that as part of your pivotal. Ultimately, you're going to need some data justifying the therapeutic index, the benefit risk of your dose versus an alternative dose. And I think what that becomes a matter to be frank, efficiency of execution, et cetera.

Martin Huber: And those are all details that when we start talking about our expansion to registration plans, which we're not doing at this time, we'll go into our thinking there. Got it.

Martin Huber: And then if you're in the in vivo situation where you have pushed the dose in the escalation and you're not seeing a big signal that you're approaching dose limiting, that's going to be dose limiting, would you continue the escalation while also running the expansion at a couple of cohorts? I mean, it's possible if we get into that scenario. As we say, we don't have to get to an MDD to declare a recommended phase to dose and move forward.

Martin Huber: And that can be part of our judgment as the data merges if we're comfortable that we've got enough confidence in the dose. And we want to continue to escalate and initiate expansion parallel. That is an option for us. We have not made that decision today, and that will be based on data. Thanks, guys. Thank you.

Justin Zelin: The next question comes from Justin Zellin with BTIG. Please go ahead. Good morning, and thanks for taking the question. With a discussion of unmet need for typoisomerase experience and resistant patients, can you talk to your confidence of differential activity of 16-16 patients? Yeah, maybe I can take that. I think there are a number of hypotheses that would maybe lend themselves to think that our payload might not be subject to the same resistance mechanism.

Justin Zelin: So, as you're probably well aware, there have been a number of real world data sets, retrospective analyses, single sites, that have shown that typoisomerase, ADCs used after other typoisomerase ADCs, have a substantial degradation in time to event endpoints. And this data really started to come out last asmo, and it's been reinforced at ASCO, and FAPCS, and other places. There are papers out there that really speak to the mechanisms for how that resistance might occur.

Justin Zelin: It might be related to the switch of typo-1, and I'm complex as to typo-2, which, you know, don't share a sort of a chemical similarity, or could also be a regulation of PGP pumps. That's a pretty common resistance mechanism in cancer, just reducing drug concentrations in the cancer cells themselves. You know, our payload, a novel or a statin with controlled bystander effect, is not subject to either of those mechanisms. It's not acting on typoisomerase, not acting on DNA, acting on the microtubules. And once the satellite, that payload is not a PGP pump, so...

Martin Huber: So, those are, at least theoretically, reasons we would think that you might see some differential activity. Great, thanks for taking our question.

Unknown Executive: This concludes our question and answer session.

Martin Huber: I would like to turn the conference back over to CEO, Dr. Marty Huber, Friday Closing remarks. Thank you, operator. And thanks everyone for dialing in. We'll be seeing some of you in New York at the Web Bush Healthcare Conference and hope the rest of you enjoy the rest of your summer.

Unknown Executive: This concludes the call operator. Thank you. The conference is now concluded. Thank you for attending today's presentation.

Unknown Executive: You may now disconnect.