Q2 2024 Vir Biotechnology Inc Business Update & Earnings Call
Speaker Change: Hello, welcome to Vir Biotechnology second quarter 2024 financial results and business update call.
Operator: As a reminder, this conference call is being recorded. At this time, all participants are in a listen-only mode.
Speaker Change: As a reminder, this conference call is being recorded.
Operator: After the speaker's presentation, there will be a question-and-answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad to raise your hand. I would now like to turn the call over to Richard Lepke, Senior Director of Investor Relations. You may begin, Mr. Lepke.
Speaker Change: At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad to raise your hand.
Richard Lepke: I would now like to turn the call over to Richard Lepke, Senior Director of Investor Relations. You may begin, Mr. Lepke.
Richard Lepke: Thank you, operator. And hello, everyone. I'm Richard Lepke, Senior Director of Investor Relations at Vir Biotechnology. Joining me on the call are Dr. Marianne DeBacker, our Chief Executive Officer; Dr. Jennifer Town, our Chief Scientific Officer; Dr. Mark Eisner, our Chief Medical Officer; and Brent Sabatini, our Chief Accounting Officer. Before we begin, I'd like to remind everyone that some of the statements we are making today are forward-looking statements under applicable securities laws.
Richard Lepke: Thank you, Operator, and hello, everyone. I am Richard Lepke, Senior Director of Investor Relations at Vir Biotechnology.
Speaker Change: Joining me on the call are Dr. Marianne DeBacker, our Chief Executive Officer, Dr. Jennifer Town, our Chief Scientific Officer, Dr. Mark Eisner, our Chief Medical Officer, and Brent Sabatini, our Chief Accounting Officer.
Richard Lepke: These forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance, or achievements to differ significantly from those expressed or implied by such forward-looking statements. These risks and uncertainties and risks associated with our business are described in today's press releases and the company's reports on the Securities and Exchange, including Forms 10-K, 10-Q, and 8-K. With that, I'll turn the call over to Marianne. Please go
Richard Lepke: Before we begin, I'd like to remind everyone that some of the statements we are making today are forward-looking statements under applicable securities laws.
Richard Lepke: These forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance, or achievements to differ significantly from those expressed or implied by such forward-looking statements.
Richard Lepke: These risks and uncertainties, and risks associated with our business, are described in today's press releases and the company's reports, files of the Securities and Exchange Commission, including Forms 10-K, 10-Q, and 8-K.
Marianne DeBacker: Good afternoon, everyone, and thank you for joining us today. At VeeR, our mission is powering the immune system to transform lives. During today's earnings call, we will discuss two significant announcements that mark critical milestones on our journey to realize this mission. Before we dive into these announcements, let me quickly highlight some key achievements from the second quarter.
Richard Lepke: With that, I'll turn the call over to Marianne. Please go ahead.
Marianne DeBacker: Good afternoon, everyone, and thank you for joining us today. At VeeR, our mission is powering the immune system to transform lives.
Marianne DeBacker: During today's earnings call, we will discuss two significant announcements that mark critical milestones on our journey to realize this mission.
Speaker Change: Before we dive into these announcements, let me quickly highlight some key achievements from the second quarter. Thank you very much. Thank you. Thank you.
Marianne DeBacker: We presented promising Phase II solstice data in chronic hepatitis delta at the Evo Congress, which generated significant interest from both the scientific as well as the medical community. These preliminary data underscore the potential of our combination therapy with Bevipart and Elapserone to revolutionize the treatment landscape for people living with hepatitis delta. We are now preparing to engage with regulatory authorities to discuss the regulatory path forward.
Speaker Change: We presented promising Phase II solstice data in chronic hepatitis delta at the Evo Congress, which generated significant interest from both the scientific as well as the medical community.
Speaker Change: These preliminary data underscore the potential of our combination therapy to BepiPart and Elapserone to revolutionize the treatment landscape for people living with Hepatitis Delta. We are now preparing to engage with regulatory authorities to discuss the registrational path forward.
Marianne DeBacker: We also recently received FDA IND clearance and fast track designation for this combination therapy. In parallel, we remain focused on advancing our functional cure program for chronic hepatitis B, and we eagerly anticipate reporting 48-week end-of-treatment data from the Phase 2 March Part B study at a major medical congress in the fourth quarter. Now let me turn to the two significant announcements that will be the main focus of today's call. First, I'm excited to announce that F.E.A.R.
Speaker Change: We also recently received FDA IND clearance and fast-track designation for this combination therapy.
Speaker Change: In parallel, we remain focused on advancing our Functional Cure Program for Chronic Hepatitis B, and we eagerly anticipate reporting 48-week end-of-treatment data from the Phase II March Part B study at the major medical congress in the fourth quarter.
Marianne DeBacker: has entered into an exclusive worldwide license agreement with Sanofi for three clinical stage mask T-cell engagers and the exclusive use of the ProX10 protease-treatable masking platform for oncology and infectious diseases. This license agreement is subject to HSR review and clearance, which we expect will take about 30 days from signing.
Speaker Change: Now let me turn to the two significant announcements that will be the main focus of today's call.
Speaker Change: First, I'm excited to announce that F.E.A.R. has entered into an exclusive worldwide license agreement with Sanofi for three clinical stage moth T-cell engagers.
Speaker Change: and the exclusive use of the PRO-X10 Proteus Cleavable Masking Platform for Oncology and Infectious Diseases.
Speaker Change: This type of agreement is subject to HSR review and clearance, which we expect will take about 30 days from signing.
Marianne DeBacker: Second, we will be providing a corporate update on our strategic restructuring. To provide you with a comprehensive overview of these announcements and their impact on our company, we have structured today's call as follows. First, I will summarize the strategic questionnaire behind the Sanofi License Agreement and the corporate restructuring. Then Jen will provide details on the masking platform and its potential applications. Mark will discuss the Clinical Stage Asset Swing-Up License, and Brands will provide a financial overview, including the terms of the agreement and our capital allocation priorities in light of the restructuring.
Speaker Change: Second, we will be providing a corporate update on our strategic restructuring.
Speaker Change: To provide you with a comprehensive overview of these announcements and their impact on our company, we have structured today's call as follows.
Speaker Change: First, I will summarize the strategic rationality behind the Sanofi License Agreement and the corporate restructuring. Thank you.
Speaker Change: Then, Jen will provide details on the masking platform and its potential applications.
Speaker Change: Mark will discuss the clinical stage assets being unlicensed. Brent will provide a financial overview, including the terms of the agreement and our capital allocation priorities in light of the restructuring. And finally, I will offer some closing remarks before we open the call for questions.
Marianne DeBacker: And finally, I will offer some closing remarks before we open the call for questions. Let me now provide more details on our exclusive Worldwide License Agreement with Salafi and the strategic measures we have announced today. First, the agreement as three potentially best-in-class clinical stage efforts: SAR-446309 or AMX-818, a dual-MOSC HER2-targeted T-cell engager in Phase I development. SAR446329, or EMX500, a dual-mask PSMA-targeted T-cell engager in Phase I clinical development; and SAR446368, or AMX525, a dual-masked EGFR-targeted T-cell engager with a cleared IND, scheduled to begin phase 1 in early 2025.
Speaker Change: Let me now provide more details on our Exclusive Worldwide License Agreement with Salafi and the strategic measures we have announced today.
Mark Eisner: First, the agreement of three potentially best-in-class clinical stage efforts.
Speaker Change: SAR446309 for AMX818, a dual-MOSC HER2-targeted T-cell engager in Phase I development.
Speaker Change: SAR446329 or EMX500, a dual-mask PSMA-targeted T-cell engager in Phase I clinical development.
Speaker Change: And SAR-446368 or AMX-525, a dual-masked EGFR-targeted T-cell engager with a cleared IND, scheduled to begin Phase 1 in early 2025.
Marianne DeBacker: For the duration of the call, we will refer to these assets by the last four digits of their drug candidate code 6309, 6329, and 6368, respectively. Looking ahead, these assets have multiple near-term key catalysts expected in the next 9 to 18 months.
Speaker Change: For the duration of the call, we will refer to these assets by the last four digits of their drug candidate code 6309, 6329, and 6368, respectively.
Speaker Change: Looking ahead, these assets have multiple near-term key catalysts expected in the next 9-18 months.
Marianne DeBacker: Second, we obtained the exclusive license to Sanofi's ProX10 Protease Cleavable Masking Platform for Oncology and Infectious Diseases. T cell engagers are, in essence, engineered by specific monoclonal antibodies, and given our deep antibody protein engineering and T cell biology expertise, we believe that we can unlock meaningful synergies and create new best-in-class therapies. Upon closing, we are also excited to strengthen viewers' capabilities by welcoming a team of key Sanofi employees with extensive scientific and oncology development expertise. Finally, we are strategically reprioritizing our pipeline, which has led to a restructuring of our organization.
Speaker Change: Second, we obtained the exclusive license to Sanofi's ProX10 Protease Cleavable Masking Platform for Oncology and Infectious Diseases.
Speaker Change: T cell engagers are, in essence, engineered by specific monoclonal antibodies, and given our deep antibody protein engineering and T cell biology expertise, we believe that we can unlock meaningful synergies and create new best-in-class therapies.
Speaker Change: Upon closing, we are also excited to strengthen viewers' capabilities by welcoming a team of key Sanofi employees with extensive scientific and oncology development expertise.
Speaker Change: Finally, we are strategically reprioritizing our pipeline, which has led to a restructuring of our organization.
Speaker Change: To better understand the potential impact of the licensed assets, let's first discuss the current landscape of cancer therapeutics and the unmet needs that still exist.
Marianne DeBacker: To better understand the potential impact of the licensed answers, let's first discuss the current landscape of cancer therapeutics and the unmet needs that still exist. Despite advances in cancer research, the global burden of cancer remains high, with 10 million deaths annually and a five-year survival rate of just 5% for some cancers. T-cell engagers have shown promise as a potent therapeutic modality, but they often have low tolerability because of off-tumor and on-target toxicity in healthy tissue, systemic toxicity such as cytokine release syndrome, and the inability to achieve therapeutically active doses in the tumor microenvironment. These limitations have hindered the widespread adoption of T cell engagers today.
Speaker Change: Despite advances in cancer research, the global burden of cancer remains high, with 10 million deaths annually and a five-year survival rate of just 5% for some cancers.
Speaker Change: T-cell engagers have shown promise as a potent therapeutic modality, but they often have low tolerability because of off-tumor, on-target toxicity in healthy tissue, systemic toxicity such as cytokine release syndrome.
Speaker Change: and the inability to achieve therapeutically active doses in the tumor microenvironment.
Speaker Change: These limitations have hindered the widespread adoption of T-cell engagers to date.
Marianne DeBacker: Our solution to addressing these challenges is the potential best-in-class ProXtend Protease Activating Masking Technique. This proprietary platform allows T cell engagers, cytokines, and other molecules to be selectively activated in the tumor microenvironment. By masking the T cell engagers, this technology aims to minimize off tumor toxicities and systemic side effects while enabling the achievement of therapeutically active doses directly in the tumor tissue. This technology has the potential to significantly improve the safety and efficacy profile of future treatment.
Speaker Change: Our solution to addressing these challenges is the potential best-in-class ProXtend Protease Activating Masking Technology.
Speaker Change: This proprietary platform allows T cell engagers, cytokines, and other molecules to be selectively activated in the tumor microenvironment.
Speaker Change: By masking the T cell engagers, this technology aims to minimize off-tumor toxicities and systemic side effects while enabling the achievement of therapeutically active doses directly in the tumor tissue.
Speaker Change: This technology has the potential to significantly improve the safety and efficacy profile of future treatments.
Marianne DeBacker: Now, this strategic transaction not only enhances our clinical pipeline but also augments our core R&D capabilities and, upon closing, will bring a complementary platform to the company. At VIR, we have always prided ourselves on our world-class immunology and virology expertise, which has enabled us to uniquely discover and engineer monoclonal antibodies to address serious infectious diseases.
Speaker Change: Now, this strategic transaction not only enhances our clinical pipeline, but also augments our core R&D capabilities and, upon closing, will bring a complementary platform to the company.
Speaker Change: At VIIR we have always prided ourselves on our world-class immunology and virology expertise, which has enabled us to uniquely discover and engineer monoclonal antibodies to address serious infectious diseases.
Marianne DeBacker: With the anticipated addition of the ProXtend masking platform, we will be even better positioned to develop innovative therapies that selectively target disease-causing cells while sparing healthy cells. Our leading data science capabilities, including machine learning and AI, will further support our efforts to bring transformative therapies to patients fast. An important component of the agreement is that we are adding a team of key employees who offer extensive expertise in oncology clinical development, in-depth knowledge of the proprietary masking platform, and valuable expertise in manufacturing dual-masked molecules.
Speaker Change: With the anticipated addition of the ProXtend masking platform, we will be even better positioned to develop innovative therapies that selectively target disease-causing cells while sparing healthy tissue.
Speaker Change: Our leading data science capabilities, including machine learning and AI, will further support our efforts to bring transformative therapies to patients faster.
Speaker Change: An important component of the agreement is that we are adding a team of key employees who offer extensive expertise in oncology clinical development, in-depth knowledge of the proprietary masking platform, and valuable expertise in manufacturing dual-masked molecules.
Marianne DeBacker: By combining our existing strengths with this new expertise, we will create a powerful synergy to drive innovation, and we look forward to working together to advance our mission following closing the transaction. As we anticipate integrating the licensed assets into our pipeline, we are taking decisive steps to focus on the highest value in the near term.
Speaker Change: By combining our existing strengths with this new expertise, we will create a powerful synergy to drive innovation. And we look forward to working together to advance our mission following closing of the transaction.
Speaker Change: As we anticipate integrating the licensed assets into our pipeline, we are taking decisive steps to focus on the highest value near-term opportunities.
Marianne DeBacker: First, we are focusing our resources on our core programs in Hepatitis Delta, Hepatitis B, and, upon closing, the newly licensed MAS C-cell Engager clinical portfolio. Second, we are phasing out programs in influenza and COVID-19 as well as our T-cell-based viral factor platform and program. Where appropriate, these programs will be made available for partnership. Additionally, we are implementing a workforce restructuring that will result in a reduction of approximately 25% of our employees. These actions are expected to yield significant cost savings while allowing us to effectively utilize our strong balance sheet to advance our strategic priorities. By streamlining our operations and allocating our capital efficiently, we are positioning Veer for long-term success and sustainable growth. In addition, we are revising our 2024 expense guidance lower.
Speaker Change: First, we are focusing our resources on our core programs in Hepatitis Delta, Hepatitis B, and upon closing, the newly licensed MOS T-cell Engager clinical portfolio.
Speaker Change: Second, we are phasing out programs in influenza and COVID-19, as well as our T-cell-based viral vector platform and programs.
Speaker Change: Where appropriate, these programs will be made available for partnering.
Speaker Change: Third, we are implementing a workforce restructuring that will result in a reduction of approximately 25% of our employees.
Speaker Change: These actions are expected to yield significant cost savings while allowing us to effectively utilize our strong balance sheet to advance our strategic priorities.
Speaker Change: By streamlining our operations and allocating our capital efficiently, we are positioning Veer for long-term success and sustainable growth.
Speaker Change: In addition, we are revising our 2024 expense guidance lower. Brent will summarize the details later on the call.
Marianne DeBacker: Brandon will summarize the details later in the call. I do want to take a moment to express my deepest gratitude to all our employees, including those who will be leaving the conference, for their dedication and their significant contributions to our mission. These decisions, while difficult, are necessary to ensure that we are allocating our capital and our talent in the most effective way possible to bring transformative therapies to patients. We believe that this strategic restructuring will enable us to deliver on that promise more effectively than ever before.
Brent Sabatini: I do want to take a moment to express my deepest gratitude to all our employees, including those who will be leaving the company, for their dedication and their significant contributions to our mission.
Brent Sabatini: These decisions, while difficult, are necessary to ensure that we are allocating our capital and our talent in the most effective way possible to bring transformative therapies to patients.
Speaker Change: We believe that this strategic restructuring will enable us to deliver on that promise more effectively than ever before.
Marianne DeBacker: With that, I would now like to turn the call over to Jen, who will provide more details on the masking platform and its potential applications in oncology and in infectious disease. Thank you, Marianne. And hello, everyone.
Speaker Change: With that, I would now like to turn the call over to Jen, who will provide more details on the masking platform and its potential applications in oncology and in infectious diseases.
Jen: As you can see on the slide, the PRO-X10 technology consists of a protease-releasable X10 mask that can be universally applied to various protein therapeutic modalities. First, it employs a universal mask, which in the case of a T-cell engager, is applied to both arms, masking both the parts of the molecule that targets the tumor-associated antigen and the part that activates the T-cell, the CD3 arm.
Jen: Thank you, Marianne. And hello, everyone. As you can see on the slide, the PRO-X10 technology consists of a protease releasable X10 mask that can be universally applied to various protein therapeutic modalities.
Jen: Second, the technology utilizes a protease cleavable linker, which enables preferential unmasking and drug activation specifically in the tumor microenvironment. This is possible because the tumor microenvironment is known to have high levels of specific proteases that can cleave the linker, releasing the active drug from the X10 map.
Jen: The PROx10 technology has two key features.
Jen: First, it employs a universal mask.
Jen: which, in the case of a T-cell engager, is applied to both arms, masking both the parts of the molecule that targets the tumor-associated antigen and the part that activates the T-cell, the CD3 arm.
Jen: Second, the technology utilizes a protease-cleavable linker, which enables preferential unmasking and drug activation specifically in the tumor microenvironment.
Speaker Change: This is possible because the tumor microenvironment is known to have high levels of specific proteases that can cleave the linker, releasing the active drug from the X10 mask.
Jen: The PRO-X10 technology can be applied to T cell engagers, cytokines, and likely other modalities. This masking technology allows for the selective activation of potent immune modulators at the site of the tumor while minimizing their activity in healthy tissue. The X10 mask has been clinically proven with Altuvio, an approved drug, to provide half-life extension to the mask.
Speaker Change: The PRO-X10 technology can be applied to T cell engagers, cytokines, and likely other modalities.
Speaker Change: This masking technology allows for the selective activation of potent immune modulators at the site of the tumor while minimizing their activity in healthy tissues.
Speaker Change: The X10 mask has been clinically proven with Altuvio, an approved drug, to provide half-life extension to the masked molecules.
Jen: Now, let's take a closer look at how this technology can overcome the historical limitation of T cell engagers and unlock new opportunities in cancer treatment. In blood circulation, the molecule remains fully masked, with all of its components, including the X10 mask, the linker, and the tumor targeting and T cell engaging components, all intact and connected. This mask configuration allows for a long half-life in the blood, which is essential for effective drug delivery to the tumor site.
Speaker Change: Now let's take a closer look at how this technology can overcome the historical limitation of T cell engagers and unlock new opportunities in cancer treatment.
Speaker Change: In blood circulation, the molecule remains fully masked with all of its components, including the X10 masks, the linker, and the tumor targeting and T cell engaging components, all intact and connected.
Speaker Change: This mask configuration allows for a long half-life in the blood, which is essential for effective drug delivery to the tumor site.
Jen: As the masked T cell engager reaches healthy tissue, the dual masking of both the tumor-associated antigen and the CD3 arms limits binding to healthy cells and T cells. This unique feature reduces T cell-mediated cytotoxicity, thereby improving the tolerability of the treatment. However, when the mass T cell engager enters the tumor microenvironment, a critical transformation occurs. The tumor microenvironment is characterized by high levels of tumor-associated protein.
Speaker Change: As the masked T-cell engager reaches healthy tissue, the dual masking of both the tumor-associated antigen and the CD3 arms limit binding to healthy cells and T-cells.
Speaker Change: This unique feature reduces T cell mediated cytotoxicity, thereby improving the tolerability of the treatment.
Speaker Change: However, when the mass T-cell engager enters the tumor microenvironment, a critical transformation occurs. The tumor microenvironment is characterized by high levels of tumor-associated proteases.
Jen: These proteases recognize and cleave the protease-cleavable linkers on the Pro-X10-masked T-cell engager and therefore unmask and activate the molecule specifically in the tumor. The selective unmasking and activation in the tumor microenvironment allows for higher concentrations of the active drug where it's needed most, while minimizing exposure and toxicity in the healthy tissue. Once unmasked, the active T-cell engager can engage T-cells and tumor cells, promoting potent anti-tumor activity, resulting in the killing of the tumor cell.
Speaker Change: These proteases recognize and cleave the protease-cleavable linkers on the ProX10-masked T-cell engager and therefore unmask and activate the molecules specifically in the tumor tissue.
Speaker Change: The selective unmasking and activation in the tumor microenvironment allows for higher concentration of active drug where it's needed most, while minimizing exposure and toxicity in the healthy tissues.
Speaker Change: Once unmasked, the active T cell engager can engage T cells and tumor cells, promoting potent anti-tumor activity, resulting in killing of the tumor cells.
Jen: Importantly, any unmasked molecules that exit the tumor microenvironment are rapidly eliminated from the body due to a short half-life once unmasked, further reducing the risk of off-tumor toxicity. We believe that this approach has the potential to revolutionize the field of T cell engagers and other immunotherapies. Now, I'd like to share some compelling preclinical proof of concept data to demonstrate the ability of the Pro-X10 masked HER2 T cell engager to be conditionally activated in the tumor microenvironment.
Speaker Change: Importantly, any unmasked molecules that exit the tumor microenvironment are rapidly eliminated from the body due to a short half-life once unmasked, further reducing the risk of off-tumor toxicity.
Speaker Change: We believe that this approach has the potential to revolutionize the field of T cell engagers and other immunotherapies.
Jen: Let's start with the graph on the left, which shows the in vitro T cell dependent killing of her two positive tumor cells and the presence of pro-X10 masked and unmasked T cell engagement. As you can see, the masked HER2 T cell engager leads to a 10,000 volt shift in cytotoxicity compared to the unmasked HER2 T cell engager in BC. In other words, the MAP T-cell engager is essentially hidden in the absence of the proteases found in the tumor microenvironment, which is exactly what we want to minimize off-target traction.
Speaker Change: Now I'd like to share some compelling preclinical proof-of-concept data to demonstrate the ability of the PRO-X10 masked HER2 T cell engager to be conditionally activated in the tumor microenvironment.
Speaker Change: Let's start with the graph on the left, which shows the in-vitro T-cell-dependent killing of HER2-positive tumor cells in the presence of pro-X10 masked and unmasked T-cell engagers.
Speaker Change: As you can see, the masked HER2 T cell engager leads to a 10,000 fold shift in cytotoxicity compared to the unmasked HER2 T cell engager in vitro.
Speaker Change: In other words, the MAP T cell engager is essentially hidden in the absence of the proteases found in the tumor microenvironment, which is exactly what we want to minimize off-target toxicity.
Jen: Moving to the middle graph, we see the in vivo antitumor efficacy in a HER2 positive tumor model following treatment with masked or unmasked HER2 T cell engagement. The masked HER2 T cell engager induces robust tumor regression, demonstrating equivalent efficacy to the unmasked moly. This provides strong evidence that the unmasking process is occurring as intended in the tumor. Finally, the graph on the right shows the relative levels of masked and unmasked T-cell engager present in tumors versus healthy tissues 48 hours after treatment with the masked HER2 T-cell engager. As predicted, the only site where we see an accumulation of unmasked active T-cell engagers is in the tumor.
Speaker Change: Moving to the middle graph, we see the in vivo anti-tumor efficacy in a HER2 positive tumor model following treatment with masked or unmasked HER2 T cell engagers.
Speaker Change: The masked HER2 T cell engager induces robust tumor regression, demonstrating equivalent efficacy to the unmasked molecule. This provides strong evidence that the unmasking process is occurring as intended in the tumor tissue.
Speaker Change: Finally, the graph on the right shows the relative levels of masked and unmasked T-cell engager present in tumors versus healthy tissues 48 hours after treatment with the masked HER2 T-cell engager.
Speaker Change: As predicted, the only site where we see an accumulation of unmasked active T-cell engagers is in the tumor. In contrast, the masked inactive molecule is present across many tissue types.
Jen: In contrast, the mass inactive molecule is present across many tissues. This preferential unmasking in the disease sites with minimal to no exposure of active molecule in normal tissue is critical to reduce tumor toxicity. Now let's explore how this technology can also maximize therapeutic impact. Starting with the graph on the left, we see that the masked HER2 T cell engager demonstrates extended pharmacokinetics as compared to the unmasked molecule. The prolonged circulation time of the masked molecule allows the drug to reach the tumor tissue, while the rapid clearance of any unmasked molecule in the periphery helps to minimize off-target toxin.
Speaker Change: This preferential unmasking in the disease site with minimal to no exposure of active molecules in normal tissue is critical to reduce tumor toxicity.
Speaker Change: Now let's explore how this technology can also maximize the therapeutic index.
Jen: Moving to the middle graph, we observe minimal cytokine release with the mass T cell engager as indicated by the low levels of IL-6. Cytokine release syndrome has been a major limitation for the current T cell engagers, and this evidence is highly encouraging for the. Finally, the box on the right showcases the Improvement in Therapeutics Index achieved. In non-human primate studies, the maximum tolerated dose of the matched FIR2 T cell engager was 43 milligrams per kilogram, compared to just 0.2 milligrams per kilogram for the unmatched FIR2 molecule.
Speaker Change: Starting with the graph on the left, we see that the masked HER2 T cell engager demonstrates extended pharmacokinetics as compared to the unmasked molecule.
Speaker Change: The prolonged circulation time of the masked molecule allows the drug to reach the tumor tissue, while the rapid clearance of any unmasked molecule in the periphery helps to minimize off-target toxicity.
Speaker Change: Moving to the middle graph, we observe minimal cytokine release with the mass T cell engager as indicated by the low levels of IL-6.
Speaker Change: Cytosine release syndrome has been a major limitation for the current T cell engagers and this is evidence is highly encouraging for the platform.
Speaker Change: Finally, the box on the right showcases the Improvement in Therapeutics Index achieved.
Speaker Change: In non-human primate studies, the maximum tolerated dose of the Master 2 T-Cell Engager was 43 mg per kg.
Speaker Change: Compared to just 0.2 mg per kg for the unmatched FIR2 molecule, this represents a greater than 100-fold improvement in therapeutic index.
Jen: This represents a greater than 100 fold improvement in Therapeutic Index. However, notably, the unmasked HER2 T cell engager was lethal due to cytokine release syndrome at a dose of 0.3 milligrams per kilogram, highlighting the significant safety challenges associated with conventional T cell engagers. As we anticipate integrating the Pro X10 masking platform and the talented team from Sanofi and Devere, I'd like to highlight the synergistic capabilities and expertise that this deal brings together. First, at FEAR, we have a deep understanding of T cell biology and how to optimize their activity to kill cells in infectious diseases.
Speaker Change: Notably, the unmasked HER2 T cell engager was lethal due to cytokine release syndrome at a dose of 0.3 mg per kg, highlighting the significant safety challenges associated with conventional T cell engagers.
Speaker Change: As we anticipate integrating the PRO-X10 masking platform and the talented team from Sanofi and Devere, I'd like to highlight the synergistic capabilities and expertise that this deal brings together.
Speaker Change: First, at FEAR, we have a deep understanding of T cell biology and how to optimize their activity to kill cells in infectious diseases.
Jen: This expertise can be directly applied to maximizing the ability of the mass T cell engagers to eliminate tumors. Additionally, our monoclonal antibody platform enables the rapid generation of novel antibodies for identified tumor targets. By combining our antibody discovery capabilities with the ProX10 masking technology, we can rapidly create a new generation of masked T-cell engagers that can address a broad range of tumor antibodies, expanding the potential impact of this modality. Third, our next-generation protein engineering capabilities, which leverage proprietary AI and machine learning tools and high-throughput wet lab selection, enable us to optimize the properties of any protein.
Speaker Change: This expertise can be directly applied to maximizing the ability of the mass T cell engagers to eliminate tumor cells.
Speaker Change: Second, our monoclonal antibody platform enables the rapid generation of novel antibodies for identified tumor targets.
Speaker Change: By combining our antibody discovery capabilities with the PRO-X10 masking technology, we can rapidly create a new generation of masked T-cell engagers that can address a broad range of tumor antigens, expanding the potential impact of this modality.
Speaker Change: Third, our next-generation protein engineering capabilities, which leverage proprietary AI and machine learning tools and high-throughput wet lab selection, enable us to optimize the properties of any protein. This expertise allows us to fine-tune and enhance multiple protein characteristics simultaneously.
Jen: This expertise allows us to fine-tune and enhance multiple protein characteristics simultaneously. For example, we can potentially create masked molecules with optimized stability, pharmacokinetics, and tumor specific activation, further improving their therapeutic potential. Now let's discuss how the unique combination of properties offered by this proprietary platform sets it apart from other masking technologies. First, the ProX10 platform employs a dual masking approach where both the tumor-associated antigen and CD3 binding domains are masked. This feature maximizes the therapeutic index by decreasing both the optimal activity and systemic immune activation.
Speaker Change: We can potentially create masked molecules with optimized stability, pharmacokinetics, and tumor-specific activation, further improving their therapeutic potential.
Speaker Change: Now let's discuss how the unique combination of properties offered by this proprietary platform sets it apart from other masking technologies.
Speaker Change: First, the ProX10 platform employs a dual masking approach, where both the tumor-associated antigen and CD3 binding domains are masked. This feature maximizes the therapeutic index by decreasing both the off-tumor activity and the systemic immune activation.
Jen: Second, the platform is designed to provide a short half-life of the active drug while maintaining a long half-life of the mass drug. This allows the mass drug to reach the site of action before being removed, enhancing its therapeutic potential. Additionally, once activated, the short half-life of the active drug provides a safety advantage by limiting systemic exposure.
Speaker Change: Second, the platform is designed to provide a short half-life of the active drug while maintaining a long half-life of the mass drug.
Speaker Change: This allows the mass drug to reach the site of action before being removed, enhancing its therapeutic potential. Once activated, the short half-life of the active drug provides a safety advantage by limiting systemic exposure.
Jen: Third, the platform features universal tunable masks that can be applied to any T cell engagement. This innovative plug-and-play format allows us to use the same mass across multiple therapeutic candidates, saving time and resources compared to developing new masses for each antibody and expediting the development process. Fourth, the platform has broad applicability, as it can be used to map not only T-Song gaugers but also cytokines and other therapeutic modalities. This versatility expands the potential impact of the technology and allows us to explore a wide range of ambient targeting approaches.
Speaker Change: Third, the platform features universal tunable masks that can be applied to any T cell engager.
Speaker Change: This innovative plug-and-play format allows us to use the same maps across multiple therapeutic candidates, saving time and resources compared to developing new maps for each antibody and expediting the development process.
Speaker Change: Fourth, the platform has broad applicability, as it can be used to map not only TSON gaugers, but also cytokines and other therapeutic modalities.
Speaker Change: This versatility expands the potential impact of the technology and allows us to explore a wide range of ambient targeting approaches.
Jen: Finally, the masking technology has been validated in human clinical studies, providing a strong foundation for its use in our pipeline. We believe that with the unique properties of the platform and our combined expertise, we are uniquely positioned to develop the next generation of mass T cell engagers and cytokines. This powerful combination will set Beer apart and strengthen our position as a leader in the development of transformative immunotherapy. With that, I'd like to hand the presentation over to Mark. Thank you, Jen, and hello, everyone.
Speaker Change: Finally, the masking technology has been validated in human clinical studies, providing a strong foundation for its use in our pipeline.
Speaker Change: We believe that with the unique properties of the platform and our combined expertise, we are uniquely positioned to develop a next generation of mass T cell engagers and cytokines. This powerful combination will set beer apart and strengthen our position as a leader in the development of transformative immunotherapies.
Mark: I'll now provide an overview of these programs and our plans for clinical development. Following closing, the licensing agreement would provide us with a robust portfolio of assets targeting clinically validated antigens in oncology. These assets include three dual-masked T cell engagers, each targeting a different antigen, HER2, PSMA, and UGFR. 6309 is a dual-masked HER2 CD3 T-cell engager. This approach has the potential to address significant unmet needs in HER2-expressing cancers, with initial indications including third-line or later HER2-positive metastatic colorectal cancer and second- to third-line HER2-positive metastatic breast cancer.
Speaker Change: With that, I'd like to hand the presentation over to Mark.
Mark Eisner: Thank you, Jen, and hello, everyone. I'll now provide an overview of these programs and our plans for clinical development.
Mark Eisner: Following closing, the licensing agreement would provide us with a robust portfolio of assets targeting clinically validated antigens and oncology.
Mark Eisner: These assets include three dual masked T cell engagers, each targeting a different antigen, HER2, PSMA, and EGFR.
Speaker Change: 6309 is a dual-masked HER2 CD3 T-cell engager.
Speaker Change: This outset has the potential to address significant unmet needs in HER2-expressing cancers.
Speaker Change: with initial indications including third-line or later HER2-positive metastatic colorectal cancer and second- to third-line HER2-positive metastatic breast cancer.
Mark: 6329 is a dual masked PSMA CD3 T cell engager. This outset is initially being developed for the treatment of third line or later metastatic castration resistant prostate cancer, for Disease with Limited Treatment Options and Poor Outcomes. 6368 is a dual masked EGFR CD3 T cell engager.
Speaker Change: 6329 is a dual masked PSMA CD3 T cell engager. This outset is initially being developed for the treatment of third line or later metastatic castration resistant prostate cancer, a disease with limited treatment options and poor outcomes.
Speaker Change: 6368 is a dual mouse EGFR CD3 T-cell engager.
Mark: This asset has the potential to address multiple EGFR-expressing tumors with initial indications including third-line or later metastatic colorectal cancer, second-to-third-line metastatic non-small cell lung cancer, and second-to-third-line metastatic head and neck carcinoma. While we refer to specific lines of therapy and initial indications for these episodes, it's important to note that our goal is ultimately to move up to earlier lines over time as PIR2, PSMA, and UGFR are all known to be important targets in a variety of solid tumors.
Speaker Change: This outset has the potential to address multiple EGFR-expressing tumors.
Speaker Change: with initial indications including third-line or later metastatic colorectal cancer, second- to third-line metastatic non-small cell lung cancer, and second- to third-line metastatic head and neck carcinoma.
Speaker Change: While we refer to specific lines of therapy and initial indications for these upsets, it's important to note that our goal is ultimately to move up to earlier lines over time as the data supports.
Speaker Change: Per 2, PSMA and UGFR are all known to be important targets in a variety of solid tumors.
Speaker Change: And existing therapies against these targets have demonstrated clinical benefit. However, existing therapies often come with significant toxicities, which can limit their ability to be dosed high enough to achieve optimal efficacy.
Speaker Change: In the following slides, I will provide more details on each of these assets, including their current clinical development plans.
Speaker Change: Now, let's dive deeper into 6309, the dual-masked HER2 CD3 T cell engager.
Mark: And existing therapies against these targets have demonstrated clinical benefit. However, existing therapies often come with significant toxicities, which can limit their ability to be dosed high enough to achieve optimal efficacy. In the following slides, I will provide more details on each of these assets, including their current clinical development plan. Now, let's dive deeper into 6309, the dual-masked HER2 CD3 T cell engager. As you can see on the left side of this slide, there is a significant disease burden associated with HER2-positive cancers, particularly metastatic colorectal cancer, breast cancer, and gastroesophageal junction cancer.
Speaker Change: As you can see on the left side of the slide.
Speaker Change: There's a significant disease burden associated with HER2-positive cancers.
Speaker Change: Particularly in metastatic colorectal cancer, breast cancer, and gastroesophageal junction cancer, we estimate that annually there are tens of thousands of newly diagnosed patients with metastatic HER2-positive cancers in key regions.
Mark: We estimate that annually there are tens of thousands of newly diagnosed patients with metastatic HER2-positive cancers in key regions. Despite the availability of HER2 targeting agents, there remains a significant unmet need in the treatment of HER2-positive tumors.
Speaker Change: Despite the availability of HER2 targeting agents, there remains a significant unmet need in the treatment of HER2-positive tumors.
Mark: While these therapies have improved outcomes for patients, mortality rates remain high due to disease progression. Additionally, there are major safety concerns associated with current HER2-targeted therapies, particularly cardiac dysfunction, interstitial lung disease, and pneumonitis, and the HER2 low seven, which represents the majority of breast cancer. Therefore, treatment options are even more limited.
Speaker Change: While these therapies have improved outcomes for patients, mortality rates remain high due to disease progression. Additionally, there are major safety concerns associated with current HER2-targeted therapies, particularly cardiac dysfunction, interstitial lung disease, and pneumonitis.
Speaker Change: And the HER2 low seven, which represents the majority of breast cancers.
Mark: There is only one approved HER-TU targeted therapy for this population, and HER-TU highlights the need for additional effective and well-tolerated treatment options. The current phase one study design for 6309 is carefully crafted to optimize the dose, demonstrate proof of concept for the dual masking platform, and evaluate its potential across multiple HER2-expressing solid tumors. Now, let's shift our focus to 6329, a dual NAFT PSMA directed T cell engager. We believe that 6329 is a highly differentiated candidate.
Speaker Change: The treatment options are even more limited. There's only one approved HER-TU targeted therapy for this population, and HER-TU highlighting the need for additional effective and well-tolerated treatment options.
Speaker Change: The current Phase I study design for 6309 is carefully crafted to optimize the dose, demonstrate proof of concept for the dual masking platform, and evaluate its potential across multiple HER2-expressing solid tumors.
Speaker Change: The study began with a single-agent dose escalation phase to optimize the dose of 6309. Patients are enrolling at increasing dose levels until an optimized dose is determined.
Speaker Change: The study also includes a combination dose-escalation PHIS with pembrolizumab.
Speaker Change: In addition, there are potential expansion cohorts to evaluate the efficacy and safety of 6309 in specific tumor types, such as HER2-positive metastatic colorectal cancer, HER2-positive breast cancer, and HER2-low breast cancer.
Speaker Change: The data from these expansion cohorts will inform further development in these indications.
Speaker Change: We are excited about the potential of 6309 to transform the treatment landscape for patients with HER2-expressing cancers.
Speaker Change: As the only mass HER2 T cell engager currently in clinical development, 6309 is designed to offer lower off-tumor and systemic toxicity, allowing for higher doses and potentially improved efficacy and benefit-risk profile compared to existing HER2-targeted therapies.
Speaker Change: The Phase 1 study is currently being conducted at 10 active sites in Europe and Australia. Monotherapy and combination therapy data is anticipated to be available in the second half of 2025, which will be a key catalyst for the program.
Speaker Change: Now, let's shift our focus to 6329, a dual-mask PSMA-directed T cell engager.
Speaker Change: Metastatic castration-resistant prostate cancer represents a significant disease burden with a large number of patients across lines of therapy.
Speaker Change: Despite currently available treatments, approximately 50% of patients with non-metastatic castration-resistant prostate cancer experience metastatic recurrence within three years.
Speaker Change: Furthermore, only 34% of patients with metastatic prostate cancer are alive five years after diagnosis, highlighting the need for more effective therapies.
Speaker Change: We believe that 6329 is a highly differentiated outset.
Speaker Change: By leveraging the ProXtend masking technology, 6329 targets PSMA, a highly expressed antigen on prostate cancer cells, to drive T-cell mediated intratumor responses in the TME.
Speaker Change: As the only dual-mass PSMA-directed T-cell engager currently in clinical development, 6329 is designed to offer lower off-tumor toxicity, allowing for higher doses and potentially improved efficacy compared to existing PSMA-targeted therapies.
Mark: Consequently, we believe that 6329 can offer patient benefit in third-line metastatic castration-resistant prostate cancer with the potential to move into earlier lines of therapy in combination with antiandrogen therapies, which are the standard of care for these patients. The key advantage of the ProXtend technology is universal mass. EGFR is broadly expressed across a wide range of tumor types, making it an attractive target for cancer therapy. Leveraging the ProXtend masking technology, we believe that 6368 has the potential to provide a safe and tolerable treatment option for patients in the second line and beyond settings for these difficult-to-treat cancers. In vitro, the masking of 6368 leads to a 10,000 fold shift in cytotoxicity compared to the unmasked EGFR T cell engager, highlighting the ability of the ProXtend technology to prevent off-target immune synapse formation.
Speaker Change: Consequently, we believe that 6329 can offer patient benefit in third-line metastatic castration-resistant prostate cancer with the potential to move into earlier lines of therapy in combination with antiandrogen therapies, which are the standard of care for these patients.
Speaker Change: The Phase I study is ongoing, evaluating 6329 as monotherapy in a dose-escalation design with the potential to advance into monotherapy and combination therapy expansion cohorts. A key advantage of the ProXtend technology is universal masking.
Speaker Change: This allows the use of the safety experience, especially about the risk of cytokine release syndrome from the 6309 Phase 1 study. This knowledge enabled 6329 to start at higher dose and potentially dose titrate faster, accelerating the development timeline.
Speaker Change: The Phase I study is currently being conducted at six active sites in Europe and Australia. Monotherapy data is expected to be available in the second half of 2025. This data readout will be a key catalyst for the program.
Speaker Change: Now, let's turn our attention to 6368, a dual-mass EGFR-CD3 T-cell engager with IND clearance. The EGFR-CD3 T-cell engager is a dual-mass EGFR-CD3 T-cell engager with IND clearance.
Speaker Change: These preclinical findings support the clinical development of $63 68, and was RMB clearance. This asset is well positioned to rapidly advance into a phase one clinical study in patients with metastatic head and neck squamous cell carcinoma, non small cell lung cancer and colorectal cancer.
Speaker Change: The phase one clinical study for 63 to 68 is targeted to begin in the first quarter of 2025.
Speaker Change: Importantly, egfr expression in healthy tissues poses a significant challenge with potential therapeutics minimized off tumor toxicity could be clinically viable to do.
Speaker Change: <unk> masking technology more than 63 to 68.
Speaker Change: Temporary offer a critical advantage for conventional egfr targeted approaches the rapid clearance of 63 to 68 achieved or shorten California outside of the tumor microenvironment enhances the safety profile and suggest that it could be a transformative treatment option for these patients to.
Speaker Change: To conclude the pro extend masking platform and the clinical aspects license from Cherokee will follow on closings represent a significant step forward in our mission to develop innovative therapies that address unmet needs of people living with cancer with that I would like to hand, the presentation over to Bryan.
Mark: Thank you, Mark. I would now like to discuss the financial aspects of this transaction and how it aligns with our strategic priorities. As part of the agreement, at closing, we will make an upfront payment of $100 million, as well as a near-term escrow milestone payment of $75 million, which is subject to 6368 achieving first-in-human dosing, totaling $175 million in near-term payments and lower personnel costs related to cost savings initiatives implemented in 2020. Restructuring, long-lived asset impairment, and related charges for the second quarter of 2024 were $26.3 million, compared to $5.4 million for the same period in 2022.
Bryan: Thank you Marc I would now like to discuss the financial aspects of this transaction and how it aligns with our strategic priorities.
Bryan: Following closing.
Bryan: Our license agreement with Sanofi will provide us with exclusive rights to three clinical stage dual map to filling cruisers and.
Bryan: In addition to these clinical stage assets. The agreement will also provide us with exclusive use of Sanofi as protease cleavable masking platform for oncology and infectious diseases.
Speaker Change: After HSR clearance, which we expect will take about 30 days from Dupont Bayer will be responsible for and have sold decision, making authority over all development and commercialization activities related to these assets in exchange for these rights Sanofi will be eligible for future development regulatory and commercial net sales based.
Bryan: Stone payments as well as tiered royalties on worldwide net sales. These payments are structured to allow sanofi to benefit from <unk> successful advancement and commercialization of these assets.
Speaker Change: Part of the agreement are closing, we will make an upfront payment of $100 million as well as a near term extra milestone payment of $75 million, which.
Speaker Change: <unk> subject to $63 63, achieving first in human dosing totaling $175 million in near term payments.
Speaker Change: As we anticipate integrating the newly licensed assets into our pipeline. We're also taking steps to prioritize our R&D portfolio and restructure our workforce to ensure that we are allocating our resources to the opportunities with the highest potential for patients.
Speaker Change: By concentrating our efforts on our key programs. We believe we can maximize value creation as part of this prioritization. We have made the decision to stop our R&D programs and influenza COVID-19, and the furlough based viral vector platform, where appropriate we will seek strategic partners to continue.
Speaker Change: The development of these assets.
Speaker Change: We are also implementing a workforce restructuring that will result in a reduction of approximately 25% or approximately 140 employees.
Speaker Change: Reduction excludes the Onboarding post closing of approximately 52 employees from Sanofi, We expect to end 2024 with around 435 employees a reduction of close to 200 employees versus our peak in 2023.
Speaker Change: We estimate this workforce restructuring will result in a reduction of our cost structure by approximately $50 million annually with savings expected to begin to be fully realized in the first quarter of 2025.
Speaker Change: In addition, we anticipate cost savings of approximately $50 million through the end of 2025 from a phase out programs. These cost reductions will allow us to allocate more resources to our core programs, while maintaining strong financial position.
Speaker Change: Combined with our strategic restructuring efforts announced in late 2023, we have successfully streamlined our operations and reduced our annual cost structure by an estimated $90 million and told from our peak.
Speaker Change: And therefore enhanced financial resilience, we remain committed to identifying additional cost saving measures as we move forward.
Speaker Change: I'll now briefly touch on some key financial highlights for the second quarter of 2024.
Speaker Change: R&D expenses for the second quarter of 2024 or $105 1 million.
Speaker Change: Compared to $169 1 million.
Speaker Change: For the same period in 2023.
Speaker Change: The decrease was primarily driven by lower clinical development costs and manufacturing costs associated with beyond 2014, due to lower manufacturing costs associated with our hepatitis programs and lower personnel costs related to cost savings initiatives implemented in 2023.
Speaker Change: SG&A expenses for the second quarter of 2024 or $30 3 million.
Speaker Change: Compared to $45 5 million for the same periods in 2023.
Speaker Change: The decrease was primarily related to cost savings initiatives implemented during the second half of 2023 <unk>.
Speaker Change: Restructuring long lived asset impairment and related charges for the second quarter of 2004 were $26 3 million compared to $5 4 million for the same periods. In 2023. The increase was primarily related to impairment charges related to closing our St. Louis Missouri facility previously announced on December 13 2000.
Speaker Change: One three.
Speaker Change: We ended the second quarter of 2024 with cash cash equivalents and investments of $143 billion compared to 151 billion at the end of the first quarter of 2024, representing a $78 million declined quarter over quarter.
Speaker Change: I will now summarize our revised financial guidance for 2024.
Brandon: I'll now summarize our revised financial guidance for 2024, which takes into account the anticipated impact of the licensing agreement and the workforce restructure. From a cash perspective, our cash utilization in the second half of 2024 is expected to be similar to the first half of 2024. We have committed to leverage our scientific expertise, our proprietary antibody platform, and our capabilities to broaden our aperture beyond infection. And with that, I'll turn the call back to Rich to begin the Q&A. Thank you, Marianne. We will now start the Q&A session. Please limit questions to two per person so we can get to all of our covering analysts. I'll turn it over to you, Operator. Thank you, Phil.
Speaker Change: Mix into account the anticipated impact of a licensing agreement and the workforce restructuring.
Speaker Change: We now expect our 2020 for full year GAAP operating expenses to be in the range of $580 million to $610 million. Our revised expense guidance reflects a $70 million reduction compared to our prior guidance and demonstrates our commitment to financial discipline.
Speaker Change: When excluding noncash stock based compensation and restructuring expenses from the GAAP operating expense range.
Speaker Change: The resulting range of $450 million to $500 million, which represents a 26% year over year decline at <unk>.
Speaker Change: <unk> from.
Speaker Change: From a cash perspective, our cash utilization in the second half of 'twenty 'twenty four is expected to be similar to the first half of 2024.
Speaker Change: And cash guidance include anticipated operating expenses associated with the license agreement. However, exclude the impact of the previously mentioned $100 million upfront payment due to Sanofi are closing and the $75 million of escrow payment, we will incorporate any associated impact on our guidance.
Speaker Change: During our third quarter 2024 earnings press release.
Speaker Change: As we move forward, we remain confident in our ability to execute on our strategic priorities and create long term value for our shareholders with that I will now turn the call back over to Mary Anne for closing remarks.
Mary Anne: Thank you Brad.
Mary Anne: As we have shared previously our goal is to become a sustainable fully integrated commercial company and we have committed to utilize our strong cash position to invest in complementary attractive clinical stage assets.
Speaker Change: We have committed to leverage our scientific expertise, our proprietary antibody platform and our capabilities to broaden our aperture beyond infectious disease.
Mary Anne: We have committed to increase our financial discipline and build a more fit for purpose organization and we have committed to sharpen our investment focus on areas, where we can make the greatest impact on patients.
Mary Anne: Creation.
Speaker Change: Turning to close at the license agreement with Sanofi and coupled with our strategic restructuring we will have successfully delivered on all of these commitments.
Speaker Change: Looking ahead, well be positioned well with a focused set of development priority to accelerate near term value creation.
Speaker Change: Our development priorities include promising program in hepatitis Delta hepatitis B and a newly licensed T cell engagements.
Speaker Change: We are looking forward to sharing more with you on these programs as well as our earlier stage programs during our R&D day in late November.
Speaker Change: As we look to the future. We are excited about the multiple value driving catalysts anticipated across our pipeline in the next four to 18 months <unk>.
Speaker Change: We expect to report additional clinical data from our hepatitis Delta and our hepatitis B program later this year as well as share update subject to closing on the progress of our newly licensed T cell engages during the course of 2025 and 2026.
Speaker Change: These milestones highlight the potential of our pipeline to deliver meaningful near term value.
Speaker Change: In conclusion today marks a pivotal moment for the year as we embark on a new chapter in our journey of powering the immune system to transform lives with it.
Speaker Change: Strength in pipeline, our talented team and a clear vision for the future we are well positioned to deliver on our mission and create long term value for all our stakeholders.
Speaker Change: Thank you for your continued support and your interest in beer, we look forward to keeping you updated on our progress.
Speaker Change: And with that I'll turn the call back to rich to begin the Q&A session.
Rich: Thank you Mary Anne we will now start the Q&A session. Please limit questions to two per person. So we get to all of our covering analysts I'll turn it over to you operator.
Speaker Change: Thank you rich at this time, we will begin conducting our analyst Q&A session for analysts. Please raise your hand to indicate you would like to join the queue. If you have not done so already to raise your hand, you must press Star then the number one on your telephone keypad, if you would like.
Speaker Change: To withdraw your question Press Star one again once you hear your name you can on mute your line and ask your question.
Speaker Change: Our first question comes from Phil Nadeau with TD Cowen. Please go ahead.
Phil Nadeau: Good afternoon, Thanks for taking my questions and congratulations on the deal.
Speaker Change: Two frozen on the new molecules I guess first.
Speaker Change: 6300, 963, 29 dose escalation phases that are ongoing now from which we'll get data next year are those in.
Speaker Change: On selected patient population is kind of all comer refractory patients.
Speaker Change: Or are they being.
Speaker Change: Her compare SMA specific.
Speaker Change: Patients being enrolled in those trials.
Speaker Change: That's the first question and then second.
Speaker Change: More broadly can you give us some idea of the framework by which you're evaluating all three the TCE is to continue investment and move forward.
Speaker Change: Mr I'm very very interesting.
Speaker Change: Nonetheless, there are other agents, obviously already on the market or in development targeting <unk>.
Speaker Change: In Egfr, so what broadly what do you hope to see you do you want to see best of class simply competitive enough or do.
Speaker Change: Do you expect there to be populations in which these work that some of the other edge and stuff.
Speaker Change: Thank you.
Clark: Thank you Phil I appreciate the question so maybe I'll ask Clark our CMO to address your first question sure and I. Appreciate the question I think it's a really good one.
Richard Lepke: I appreciate the question. So maybe I'll ask Mark, our CMO, to address your first question. Sure. And I appreciate the question. I think it's a really good one.
Mark: For both 6309 and 6329, we are, as you said, enrolling tumor types that are, you know, heavily pretreated. In the case of 6309, both HER2 positive and HER2 high, and HER2 low patients are being enrolled. For the PSMA program, you know, there's not a specific requirement for PSMA positivity, but that certainly will be something that's looked at. In terms of your question about the framework for how the assets will be evaluated, you know, the phase one studies allow dose escalation to test the hypothesis that we can achieve a superior therapeutic index with better safety and efficacy than unmasked TCEs can achieve.
Clark: For both 63 or 9% and $63 29.
Clark: And as you said.
Clark: Enrolling with tumor types that are heavily pretreated in the case of <unk>.
Clark: Her two positive add virtue personal high virtue Lowe patients are being enrolled.
Speaker Change: For the PSA program.
Speaker Change: As noted specific requirement for TSMC positivity, but that certainly will be something thats worked out well in terms of your question about the framework for how the assets will be evaluated the phase one studies allow both dose escalation.
Speaker Change: Test the hypothesis that we can achieve a superior therapeutic index with better safety and efficacy than <unk>.
Speaker Change: <unk> tissue use can achieve so that's one point the second point is that it allows for potential.
Speaker Change: Expansion cohorts and the different diseases.
Speaker Change: Mono therapy and in combination therapy, so as the data evolve we'll be able to determine what are the most promising.
Speaker Change: And tumor types combinations versus monotherapy now in terms of very specific hurdles or borrowers I think that's something we'll have to get back to you on a subsequent call but.
Mark: So, you know, in terms of very specific hurdles or bars, you know, I think that's something we'll have to, you know, get back to on a subsequent call. But, you know, what I would end with saying is that the way the program is currently designed will allow, you know, a very intensive investigation of monotherapy and combination therapy in a variety of tumor types and, in the case of PSMA and prostate cancer, That's very helpful. Congratulations again on the deal and thanks for taking our questions.
Speaker Change: And we are saying is that the way. The program is currently designed will allow.
Speaker Change: <unk>.
Speaker Change: Intensive interrogation of monotherapy and combination therapy in a variety of tumor types and in the case of P. SMA in prostate cancer.
Speaker Change: Yes, that's very helpful.
Speaker Change: Yeah, Yeah, the only thing I would add there as we discussed I mean, the unmet medical need is still incredibly high.
Ken: Each of these areas start to account for some of <unk> Ken.
Ken: Cancers, and there was no <unk> is approved in either of the areas that we are discussing today.
Speaker Change: That's very helpful. Congrats again on the deal and thanks for taking our questions.
Speaker Change: Thank you.
Mariarosa Ruiz: Our next question comes from marijuana Ruiz with Leerink. Please go ahead.
Marijuana Ruiz: Hey, good afternoon. This is <unk>. Thanks for taking our questions maybe first for most of the new deal with incentive fee.
Marijuana Ruiz: I guess, what should the free T cell engaging programs are you most excited about I'm curious.
Speaker Change: You know what your thoughts are on the competitive positioning across the three.
Speaker Change: I have a follow up on an H D D.
Speaker Change: Yes. Thank you for that question I'll start and then also ask Mark to chime in.
Speaker Change: Just again to reiterate for her to PMA in Egfr, even though those are obviously biologically balls holiday to target centers.
Speaker Change: A lot of activity that has been.
Speaker Change: All of these targets I think that if you look at the landscape today again, theres still a very high unmet medical need higher mortality for people diagnosed with her two cancers again, you talked about you know only 34 beside the patients being alive after five years.
Speaker Change: You know are diagnosed with P. S M a.
Speaker Change: Prostate cancer, and then only a five year survival of five year survival rate of.
Marijuana Ruiz: Really being very low between three and 38% for Egfr related cancers. So the unmet need despite everything that's might be approved.
Marijuana Ruiz: Approved or in development is incredibly high.
Marijuana Ruiz: No T cell engagement for each each any of these targets that are currently being approved again, despite other modalities being approved especially for her.
Speaker Change: Two P S M a.
Marijuana Ruiz: You are still faced with this high mortality on a hold of.
Speaker Change: Challenging side effects for patients so yeah unmet need remains 70 sector Sweeney.
Marijuana Ruiz: Each for each of these therapeutic agents and opportunity to potentially really drive a differentiated impact for patients.
Marijuana Ruiz: You want to sure Thanks, Mary Anne So.
Speaker Change: I would note is that these are all clinically validated targets. So we're very excited about all three of them.
Speaker Change: There are different phases of development. The her two programs farthest along in the clinic.
Speaker Change: So we're getting.
Speaker Change: Efficacy preliminary efficacy and safety data in.
Speaker Change: In these patients with multiple tumor types and I think there is an opportunity to be first achieve clinical proof of concept with announced TCE for PSM may word phase one as well.
Speaker Change: <unk> offers a powerful proof point for the approach, which is another outfit also in phase one and the other thing I would add is that.
Speaker Change: Because of the universe Universal masking, we're able to leverage to $63 nine her two program to dose escalate more quickly in the P. SMA program and then Egfr.
Speaker Change: Which as we've said before it is looking to go to phase one early next year in Q1, as a potential high risk high reward opportunities there's multiple competitors in the clinic three but theres multiple tumor types that are Jeff are positive yes.
Speaker Change: Here are the potential of the masking is really impactful because this is such a widely.
Speaker Change: Forest marker molecule that in order to achieve a therapeutic index that can actually treat the cancers without with acceptable safety. This is where I think the exciting aspect of the Egfr program.
Speaker Change: Well. Thanks, Thanks for that color maybe second question just on HDD curious how your interactions with the FDA is in going after the breach and H D V data diesel and I'd be curious what your latest outlook is on a potential accelerated approval pathway here.
Speaker Change: Yes. So good question. So we already announced that we have fast track designation from the FDA, which I think speaks to.
Speaker Change: The high unmet medical need in the very compelling clinical data we are pursuing other accelerated clinical development pathways, such as breakthrough therapy designation and we are pursuing.
Speaker Change: And engagement with FDA starting <unk>.
Speaker Change: This quarter Q3 to talk about the Registrational program. So we're very excited about the Delta program, we're moving quickly to <unk>.
Speaker Change: <unk> into Registrational studies.
Speaker Change: Thanks.
Speaker Change: Thank you.
Speaker Change: Our next question comes from Paul Choi with Goldman Sachs. Please go ahead.
Paul Choi: Hi, Thank you good afternoon, and let me also offer my congratulations on the deal.
Paul Choi: My first question either for for Jennifer or for Mark.
Paul Choi: Can you maybe share any additional insights with regard to the <unk>.
Paul Choi: Safety profile of your of the T cell engagements that you're just in license with from Sanofi, particularly with regard to any anything in healthy volunteers that would suggest.
Speaker Change: That you can avoid some of the issues with cytokine release syndrome, but have been a hallmark of the class and just any other evidence you can share with regard to the safety profile.
Speaker Change: And then my second question more for Mark probably as.
Mark Eisner: As you think about prosecuting next stage clinical trials after that dose escalation studies.
Mark Eisner: Can you comment on your ability and the company's ability to pursue multiple drugs here I guess in the clinic at the same time or will you prioritize one over the other depending on the dose escalation data.
Mark Eisner: Sure.
Mark Eisner: Go ahead, Mark sure Thanks, Paul for the questions.
Mark Eisner: In terms of the safety data in the first thing I would.
Mark Eisner: Mentioned is the preclinical data that Jim described in detail that shows the fact that there is a 10000 fold.
Mark Eisner: <unk>.
Steve: Reduction in potency and the math, Steve as opposed to in the tumor microenvironment, where the molecules are activated and form synopsys with the tumor cells. We have had the opportunity during the diligence to look out preliminary clinical data, including safety data thats been very valuable to be able to see that.
Mark Eisner: We are not on the.
Speaker Change: Able to comment on that today, but I can say that we gained some valuable insights that gave us confidence to move move into.
Steve: Prosecuting the deal in terms of the next phase clinical trials, great great questions about that.
Speaker Change: In terms of our development capabilities I think there has demonstrated that we can run large trials at scale, including the peninsula trial of influenza prevention 3000, or so patients multiple phase.
Steve: One and two studies simultaneously.
Mark Eisner: Delta.
Mark Eisner: We are bringing on.
Speaker Change: The churn of the employees I think we will see a lot of synergies between what we can provide in terms of clinical operations regulatory and other infrastructure and their knowledge and in depth experience with these assets and their deep.
Speaker Change: Our relationships with the Kols and the sites are feel confident that we'll be able to prosecute multiple.
Speaker Change: Trials simultaneously.
Speaker Change: We'll follow the data.
Speaker Change: We will prioritize programs that have the most compelling clinical data as those data evolve.
Speaker Change: Okay, great. Thank you for taking my questions.
Speaker Change: Okay.
Speaker Change: Our next question comes from Eric Joseph with Jpmorgan. Please go ahead.
Eric Joseph: Hi, Thanks for taking the questions.
Eric Joseph: Maybe just one or two 160 309.
Speaker Change: As the trial is designed to contemplate a combination with <unk>.
Speaker Change: One federalism.
Speaker Change: If you can shed.
Unknown Speaker: Thank you. shed some light on the biological rationale behind that combination. This requires that you have T cells there that can be activated. And so this is where I think you have real synergy with something like PD-1, which really removes a break in a T cell and allows them to be active. So that's really the fundamental concept behind the use of a checkpoint inhibitor with a T cell engager. Yeah, in terms of the safety of dose escalation in combination with Pembroke, I'll just refer to my prior statement, which is, you know, we have had the opportunity to see preliminary clinical data, including safety data, and preliminary efficacy data.
Speaker Change: <unk> had some light on the biological rationale behind that combination.
Speaker Change: Or any PD, one thought to be potentially hitters.
Speaker Change: T cell engages in.
Speaker Change: Any visibility that you might have at this stage on the.
Speaker Change: The safety of the combination so far.
Speaker Change: Hi, This is Dan I can start with that and so maybe I'll start and then hand, it over to Mark furlong the ideas of the safety.
Mark Furlong: I think fundamentally what a T cell engagement requires is both the targeting the tumor with a tumor associated antigen and an activation of the T cells for the city three arm. This sudden farms the immune synapse and allows the T cells to directly kill the tumor itself.
Mark Furlong: This requires that you have T cells, there that can be activated and so there is where I think you have real synergy it was something like a PD, one which really removes a break on a T cell and allows them to be active so that's that's really the fundamental.
Mark Furlong: The concept behind you so that checkpoint inhibitor with a T cell <unk>.
Unknown Speaker: And, you know, we found this information really valuable. We're not really able to comment in detail on that at this point, but this is information we'll be providing as a subsequent interaction. Maybe just give us a sense of where you initially think you might go with your next generation antibodies that could be mass now or, Jen, do you want to take that? Yeah, no, thank you for the question.
Speaker Change: Now in terms of the safety of dose escalation in combination with <unk> I'll just refer to my prior statement, which is we have had the opportunity to see a preliminary clinical data, including safety data and preliminary efficacy data.
Mark Furlong: We found this information really valuable we are now.
Speaker Change: We're really able to comment in detail on that at this point, but this is information we'll be providing subsequent interaction.
Speaker Change: Okay, great well, thanks for the color and congrats on the deal.
Eric: Thanks, Eric.
Mike <unk>: Our next question comes from Mike <unk> with Morgan Stanley. Please go ahead.
Mike <unk>: Yeah, Hey, guys. Thanks for taking the question.
Mike: Maybe just now that you have this approach.
Mike: Pro X 10, masking platform, you mentioned the potential to leverage it with your own monoclonal antibody platform.
Speaker Change: Can you maybe just give us a sense where you. Initially think you might go with your next generation antibodies that are that could be mass now or any particular targets you might be interested in.
Mike: John do you want to take that yes, no. Thank you for the question. So yes, I do think there are real synergies I mean fundamentally what the T cell engaging <unk> or is that they are built off of the antibodies and so did you had single chain at me, which are the binding portion of the antibody so our antibody to <unk>.
Jen: So, you know, I do think there are real synergies. Fundamentally, what the T cell engagers are is they are built off of antibodies. And so these use single-chain FBs, which are the binding portion of the antibody.
Jen: So our antibody discovery engine really does provide quite complementary and synergistic power to developing the next stage of T cell engagers. I think, as you can see by the first three molecules, they really have focused in on ones for which there is biological proof of concept for these being bona fide tumor associated antigens. And, you know, Frankly, there's a number of others that one could consider developing. I think that's where it will start. I do think the platform has really broad, broad potential and broad ability. The first time an X10 was used was with this molecule L-Tubio, which was really just used to extend its half life.
Speaker Change: Every engine really does provide quite complementary and synergistic power to developing the next stage of <unk> I think as you can see by the first three molecules and they really have focused in on one that for which there is biological proof of concept for these being bona fide tumor associated antigen and <unk>.
Speaker Change: Frankly, there's a number of others. So that that one could consider developing I think that's where it will start I do think the platform has really broad broad potential and brought up the ability. The first time, an X 10 was used with this molecule <unk>, which was really just used to extend its half life I think from that it's been shown that it can be applied.
Jen: I think from that, it's been shown that it can be applied to not only T cell engagers but also to other biologics, including cytokines and probably antibodies as well. So I think there really is a broad potential for this. But I think focusing in first on those that have, you know, a biological proof of concept, and the next step may come from there. Yeah, the only thing I would add is if you think about, you know, these mask T-cell engagements and the components of them, as Jen was saying, I mean, on the T-cell engagement side itself, the therapeutic modality, I think we can contribute tremendously with our antibody engineering expertise.
Speaker Change: To not only.
Speaker Change: T cell engagement, but also also two other biologics, including cytokines and probably antibodies as well. So I think that really is a broad potential of this but I think focusing first on those that have a biological proof of concept and an extra benefit from there.
Speaker Change: Got it yes, it might be only.
John: Yeah. The only thing I would add is if you think about the small screen still engage with some of the components of it as John was saying I mean on the T cell engagement side itself.
Jen: Critic modality I think you can come to the tremendous thing that our antibody engineering.
Jen: And then what is also, I think, very encouraging is that both on the mask side, as Jen said, there's a considerable amount of risk that has happened given that there is a drug on the market that has been using this mask. And also on the pleavable linker side, I think you have seen what Jen presented with the preclinical data, which is very convincingly showing, of course, preclinically in vitro and in vivo, that this actually works.
Jen: Expertise.
Speaker Change: And then what is also I think very encouraging is that both on the mob side is just that there's a considerable amount of de risking death has happened given that does the job on the markets that have been using this model and also on the capable linker side I think you have seen what Jan presented on the preclinical data, which is very convincingly.
Speaker Change: Showing of course preclinical in vitro and in vivo that this actually works. So I think theres a lot of Derisking Douglas has been on the platform and as it relates to then really going for new targets I think we can add a really unique capability.
Unknown Speaker: So I think there's a lot of de-risking that has happened on the platform. And as it relates to then really going for new targets, I think we can add a really unique capability. You mentioned the broad potential of the platform and the in-license statuses. Just curious if you could provide some additional color behind that.
Speaker Change: Thanks.
Speaker Change: Our next question comes from Joseph Stringer with Needham <unk> Company. Please go ahead.
Joseph Stringer: Hi, Thanks for taking our questions.
Speaker Change: You mentioned the broad potential of the.
Speaker Change: <unk> platform and the in licensed assets just curious if you could.
Speaker Change: Provide some additional color behind.
Speaker Change: The decision for the in licensing and was to move into oncology potential or are there other assets in other therapeutic areas that were considered and then lastly.
Unknown Speaker: Does the updated corporate update here.
Unknown Speaker: Does that affect any of us.
Speaker Change: The timelines are any of the resources that you can devote to the <unk>.
Speaker Change: HBV or HBV programs. Thank you.
Unknown Speaker: Yes. Thank you for that question Joey so.
Speaker Change: The corporate update absolutely no impact on our timelines for the hepatitis Delta and hepatitis B studies I mean, our focus will be on clinical execution that is really a strategic priority for our hepatitis programs and then after closing of this transaction also the annuity licensed.
Speaker Change: T cell engagements.
Unknown Speaker: Now, coming to your earlier question about how we came to the decision, so, you know, during the course of, I think, the last year, we have said that we wanted to be really strategic and thoughtful about how we would be using our cash balance, which, as Brent mentioned, was $1.43 billion at the end of the second quarter, and that we would be looking to potentially bring in a clinical stage asset or assets. And really look for opportunities that would build strongly on our existing expertise.
Speaker Change: Now coming to your earlier question about how we came about the decision. So during the course of the last year behalf.
Unknown Speaker: Not that we wanted to be really strategic and thoughtful about how we would be using our cash.
Speaker Change: Cash balance which us.
Unknown Speaker: I mentioned plus $1.43 billion at the end of the second quarter and that we would be looking for potentially bringing in a clinical stage asset or assets.
Unknown Speaker: So, really, opportunities where there would be strong synergy. So, obviously, we have looked at a lot of opportunities that would fit that mold, but I would say that, you know, we really believe this is a very, very unique fit for a lot of different reasons. Obviously, to start, the opportunity addresses a very high net need. We talked about it, and we did very rigorous due diligence and became, in a way, very convinced about the value of, you know, the clinical assets, but also the value of the platform and the science behind it.
Unknown Speaker: And really look for opportunities that would build strongly.
Unknown Speaker: Existing expertise, so really opportunities whether it would be strong synergy. So obviously, we have looked at a lot of opportunities that would fit that mold but.
Unknown Speaker: But I would say that we really believe this is a very very unique fit for a lot of different reasons, obviously to start to opportunity addresses a very high unmet need we talked about it.
Unknown Speaker: Immediate very rigorous due diligence and we came away very convinced about the value of clinical assets, but also we need to file with the platform.
Unknown Speaker: And the science behind it as we set the targets the biological targets on the ski clinical assets are de risked the.
Unknown Speaker: As we said, the targets, the biological targets on the three clinical assets are de-risked. The masking is, you know, to some extent, de-risked, and the cleavable linkers, again, we have very strong preclinical data in vitro and in vivo to show that this actually all works.
Unknown Speaker: The masking is you know to some extent the risks and the cleavable linker again, we have very strong preclinical data in vitro and in vivo to show that this actually all.
Unknown Speaker: So.
Unknown Speaker: And again in addition, highly synergistic we discussed them with every capability that we have here in house, our antibody expertise a clinical development organization that has proven to be very very strong in and operating our clinical trials and also our deep immunology.
Speaker Change: <unk> expertise in Pn T cell expertise, which we haven't talked about that much and then finally this deal brings a number of near term catalysts and value inflection points for the company.
Unknown Speaker: We did the next slide to 18 months.
Speaker Change: <unk> be able to see data on these clinical stage T cell engagement. So that's all taken together so you're right.
Unknown Speaker: Very excited.
Speaker Change: Great moment for us here at <unk>.
Speaker Change: Our next call our final call for today comes from Alec Stranahan with Bank of America. Please go ahead.
Operator: Our next call, our final call for today, comes from Alec Stranahan with Bank of America. Please go ahead. Thank you for the question. Thank you.
Operator: Thanks.
Alec Stranahan: Appreciate you taking my questions.
Alec Stranahan: Two from US first just on the new TC assets, just trying to understand the competitive positioning a bit more anything unique that you could point us to in terms of the design of the mass versus say <unk> Sir.
Speaker Change: Well mix or is it more due to the fact that you're using a mask on both the anti tumor and the anti CD three arms.
Alec Stranahan: The actual structure of them ask itself and then I've got a follow up.
Ken: Hey, Ken do you want to take that yeah sure happy to so you know it really I think that the that the uniqueness is actually and that the combination of attributes for that platform and so I spoke about this but it was at a fairly high level. So let me elaborate a little bit more so I think there is some major components when you hit upon one of the the dual.
Speaker Change: I'm asking so anything there provides a real advantage to them asking both the tumor associated antigen as well as the CD three arm and then both arms can be cause of safety issues and so im asking both of them really have.
Speaker Change: Has the best potential to eliminate those issues.
Speaker Change: Importantly, this is also.
Speaker Change: A different design and that it's a universal mask, so that's where it comes but that's like plug and play concept and at the same math can be used across multiple different therapeutic. So essentially the same math is on all three of the T cell engaging that are in or close to the clinic and this allows for rapid execution, both pre clinically but also rapid execution.
Speaker Change: In the clinic as Mark highlighted this does make it a quicker path towards dose escalation for IP SMA because the market itself has been derisked and automobile itself does also derisk a mask I mean, so there has been an unapproved product for which the small ticket is providing additional concept around it and safety.
Speaker Change: Lack of Immunogenicity.
Operator: And then finally I think the other component that we've hit on but I think is also quite exciting is that this broader applicability of the masks are not only for T cell engagement, but also potentially for other molecules.
Speaker Change: <unk> cytokines or potentially other protein therapeutics like antibodies.
Operator: Okay.
Speaker Change: I would just add that from a from a competitive landscape perspective for her too.
Speaker Change: No other marks a T cell engagement and development for PSM majors one.
Speaker Change: <unk> TCE in development and for Egfr. There are three so I mean in the broader context of things here, where TCE says we discussed have a lot of shortcomings.
Speaker Change: You know toxicity and really challenging profiles for patients.
Speaker Change: We have an opportunity here for these mark TCE to really drive the difference.
Speaker Change: Competitive landscape its really not studying tons.
Alec Stranahan: Okay. Thanks.
Speaker Change: Clear and then maybe one quick one just putting a finer point on the applications in immunology with us mostly being through half life extension.
Speaker Change: For <unk> cytokines or are there any <unk>.
Speaker Change: <unk> indication do you think could be most apt initial avenues for development.
Speaker Change: Yeah, So and so you know we can extend the half life, but I think actually there are.
Speaker Change: Two attributes so the way that the math because she is Danielle Tokyo is purely fixed on the half life. The way. The math is used for the T cell engaging <unk> is that it does extend the half life and allows them to get to the site of action. However, once they are cleaved. They didn't have a very short half life, which then allows them to act in that tumor mic.
Operator: Our environment because they are right there with their target antigen activates the T cells, which are then have a longer lived activation profile, but that active molecule. Once it circulates then has a very short half life and that provides an added safety benefit you can envision the same type of thing being applied to our cytokines, having it be activated only at the site where you want it.
Speaker Change: To be activated and then having that short half life be an attribute because we all know that these cytokines, while incredibly potent and beneficial for activating immune cells. They are often have very high associated toxicity of sub salt. So while they have a short half life you don't want them to have too long of half life or youre going to have greater toxicity. So I think.
Speaker Change: Both are chip.
Speaker Change: Thank you for the question.
Speaker Change: Thank you.
Speaker Change: Alright. This concludes the Q&A session of the call. Thank you for participating and I will turn the call back over to Mary Anne.
Speaker Change: Well, thank you everyone.
Speaker Change: Yes, apologies thanks, everyone for their interest in listening to our earnings call today.
Speaker Change: People, which that's a close call. Thank you.
Operator: Yeah.
Operator: [music].
Operator: Sure.