Q1 2025 Vir Biotechnology Inc Earnings Call & Business Update
We recorded it.
At this time all participants are in a listen only mode.
After the speaker's presentation, there will be a question and answer session.
Speaker Change: I will now turn the call over to Rich Lucky Senior Director Investor Relations you.
Speaker Change: You may begin Mr. Lucky.
Yeah.
Yeah.
Speaker Change: Yeah.
Speaker Change: Thank you and good afternoon with me today are Dr. Mary <unk>, our Chief Executive Officer, Dr. Marc <unk>, our Chief Medical Officer, Jason Osborn, our Chief Financial Officer, and Dr. <unk> <unk>, our executive Vice President of oncology, who will be available during the Q&A session.
Speaker Change: Before we begin I would like to remind everyone that some of the statements. We're making today are forward looking statements under the securities laws.
Speaker Change: 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.
Speaker Change: These risks and uncertainties and risks associated with our business are described in the company's reports filed with the Securities and Exchange Commission, including forms 10-K, 10-Q and 8-K.
Dr. Mary: I will now turn the call over to our CEO Dr. Mary <unk>. Please go ahead.
Dr. Mary: Thank you rich and good afternoon, everyone.
Dr. Mary: Thank you for joining us for <unk> technologies first quarter 2025 earnings call.
Dr. Mary: I'm pleased to share our progress and achievements with you today as we continue to execute on our strategic priority.
Dr. Mary: Before we dive in I want to express my gratitude for your continued support and interest in our mission of R&D immune system to transform patients lives.
Dr. Mary: It had a strong start to 2025 with meaningful progress across our pipeline.
Dr. Mary: Our strategic focus on advancing both our infectious disease and oncology program continues to position us well for future growth and value creation.
Dr. Mary: I'm pleased to share that we successfully initiated our eclipse phase III Registrational program with the first patient enrolled in eclipse one during the first quarter.
Dr. Mary: This is a significant milestone in our commitment to develop a potential new standard of care for patients with hepatitis Delta virus infection.
Dr. Mary: The Eclipse program builds on our solstice phase two data, which demonstrated impressive biological responses in a combination therapy.
Dr. Mary: Today I'd also like to provide a refined assessment of the hepatitis Delta market opportunity, which reflects the prelaunch work you have initiated in parallel with our phase III trials tabetic characterized the addressable patient population.
Dr. Mary: Based on our comprehensive market analysis, we estimate that there are approximately 7 million active or remake HCV RNA positive patients globally.
Dr. Mary: In the United States, we estimate that approximately 61000 RNA positive patients.
Dr. Mary: In EU member countries, plus the U K, we estimate approximately 113000 RNA positive patient.
Dr. Mary: And additional geographies beyond these quicker presents long term opportunity.
Dr. Mary: I want to emphasize that these figures are specifically focused on RNA positive patients with active a remic disease, who would be candidates for treatment.
Dr. Mary: This distinction is important because we focus specifically on patients with detectable viral replication, who face the highest risk of disease progression.
Dr. Mary: We've conducted an extensive evaluation of multiple epidemiological sources and consultants with leading experts in the field to arrive at this estimate.
It's important to note that our updated understanding of the market size underscores that hepatitis Delta has the characteristics of a rare disease market with significant commercial potential.
Dr. Mary: Let me highlight a few key points.
Dr. Mary: First.
Dr. Mary: This is a disease is severe outcomes more than 50% of hepatitis delta patients succumb to liver related death within 10 years of diagnosis.
Dr. Mary: And there are no FDA approved treatments in the United States.
Dr. Mary: Second treatment is managed by a concentrated group of Herpetologist of liver specialists, allowing for a focused commercial engagement.
Dr. Mary: Third the severe clinical outcomes and EMA orphan disease designation support our value based pricing model similar to other rare disease therapies.
Dr. Mary: Fourth the high cost burden of untreated disease progression, including liver transplantation and end stage liver disease management provides a compelling economic case for effective treatments.
Dr. Mary: And finally, our market research indicates high physician intent to treat these patients given the lack of effective option.
Dr. Mary: The regulatory designations, we've received breakthrough therapy, and fast track in United States and Prime an orphan drug in the EU underscore the potential impact of our approach and May help accelerate our development timeline.
Dr. Mary: We are focused on driving enrollment in our eclipse one trial and preparing for the eclipse two and three study initiation.
Dr. Mary: As we advance our hepatitis Delta program I'm also pleased to report during the quarter. We reached an agreement with one item whereby they elected not to opt into the profit sharing arrangement for elektron.
Belting and a continued milestone and royalty based structure.
Dr. Mary: This decision provides clarity for our approach to advance our hepatitis Delta program and gives us the flexibility to partner the program in Europe and other international markets.
Dr. Mary: The outcome of disagreement was anticipated and factored into our long term financial planning and work already included in our projected cash runway extending into mid 2027.
Dr. Mary: Jason will provide additional details on the financial aspects of disagreements later in the call.
Dr. Mary: Turning briefly to our hepatitis B program, we're presenting 24 week post treatment follow up data from our March phase II study at the upcoming Easel Congress on May 9th spin.
Dr. Mary: Specifically, we will be sharing functional cure data from participants who have completed 24 weeks of follow up after treatment discontinuation.
Dr. Mary: Shifting gears to our oncology portfolio.
Dr. Mary: Continue to make steady progress with the pro X sand duel Masters sell engage a program.
Dr. Mary: As a reminder, we have worldwide rights to the pro X 10 platform in infectious disease and oncology.
Foreign fear 50, 80 team our dual masked her to targeted T cell engagement, we're continuing to dose escalate as monotherapy and in combination with temporary leaves them at all.
Operator: A reminder, this conference call is being recorded. At this time, all participants are in a listen-only mode.
Operator: After the speaker's presentation, there will be a question and answer session.
Dr. Mary: Our data presented in January showed a 33% confirmed partial response rate in her two positive colorectal cancer patients at doses of 400 microgram per kilogram and Abbas with one response lasting over 18 months.
Rich Lepke: I will now turn the call over to Rich Lepke, Senior Director, Investor Relations. You may begin, Mr. Lepke. Thank you and good afternoon.
Rich Lepke: With me today are Dr. Marianne DeBacker, our Chief Executive Officer, Dr. Mark Eisner, our Chief Medical Officer, Jason OByrne, our Chief Financial Officer, and Dr. Mika Derynck, our Executive Vice President of Oncology, who will be available during the Q&A session.
Dr. Mary: We're particularly encouraged by these results in colorectal cancer, where there remains a significant unmet need for effective therapy.
Dr. Mary: These responses were observed in microsatellite stable tumors, which are typically resistant to immunotherapy, suggesting for a 50 818 could potentially address an important treatment gap for these patients.
Rich Lepke: Before we begin, I would like to remind everyone that some of the statements we are making today are forward-looking statements under the securities laws. These four 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 four looking statements.
Dr. Mary: Four of your 5500 audio masked P SMA targeted T cell engagement <unk>.
Dr. Mary: Continue to dose escalate, given our favorable safety profile and the learnings from <unk> 58, a cheap.
Rich Lepke: These risks and uncertainties and risks associated with our business are described in the company's reports filed with the Securities and Exchange Commission, including Forms 10-K, 10-Q, and 8-K.
Dr. Mary: We've evaluated multiple additional dose level since our last update our January data showed that 100% of patients at doses above 120 micrograms per kilogram.
Marianne DeBacker: I will now turn the call over to our CEO, Dr. Marianne DeBacker, please go ahead. Thank you, Rich, and good afternoon, everyone. Thank you for joining us for Vir Biotechnology's first quarter 2025 earnings I'm pleased to share our progress and achievements with you today as we continue to execute on our strategic priorities.
Dr. Mary: Appearances, PSA decline with 58% achieving a PSA 50, with Paul all without prophylactic steroids and with minimal cytokine release syndrome.
Dr. Mary: We continue to see strong investigator enthusiasm for this program based on the early signals you've observed.
Marianne DeBacker: Before we dive in, I want to express my gratitude for your continued support and interest in our mission of powering the immune system to transform patients' lives. We've had a strong start to 2025 with meaningful progress across our pipeline. Our strategic focus on advancing both our infectious disease and oncology programs continues the position as well for future growth and value creation. I'm pleased to share that we successfully initiated our ECLIPSE Phase 3 Registrational Program with the first patient enrolled in ECLIPSE 1 during the first quarter. This is a significant milestone in our commitment to develop a potential new standard of care for patients with hepatitis delta virus infection.
Dr. Mary: We're also on track to initiate a phase one study for fear of $55 25 are dual masked egfr targeted T cell engagement this quarter.
Dr. Mary: This program has the potential to address multiple high value indications.
Dr. Mary: Including non small cell lung cancer, colorectal cancer head and neck squamous cell carcinoma, and other egfr expressing tumors.
Dr. Mary: The pro extend universal dual marketing approach continues to demonstrate potential advantages in terms of safety profile and dosing flexibility.
Dr. Mary: Beyond our clinical stage programs, we are rapidly advancing several next generation targets in areas of high unmet medical need.
Dr. Mary: Our antibody discovery and protein engineering capabilities are key to the discovery of new tumor associated antigen binders to quickly advance new TCE program.
Marianne DeBacker: The ECLIPSE program builds on our SOLSTICE Phase II data, which demonstrated impressive biological responses with our combination therapy. Today, I'd also like to provide a refined assessment of the hepatitis delta market. which reflects the pre-launch work we have initiated in parallel with our phase three trials to better characterize the addressable patient. Based on our comprehensive market analysis, we estimate that there are approximately 7 million active viremic HDV RNA-positive patients globally. In the United States, we estimate approximately 61,000 RNA-positive patients. In EU member countries plus the UK, we estimate approximately 113,000 RNA-positive patients. and additional geographies beyond these could represent long-term opportunities.
And the universal nature of the products and platform allows us to efficiently apply our dual masking approach.
Dr. Mary: The synergies between antibody discovery capabilities and the product and platform have begun to translate into meaningful program with seven targets progressing in preclinical development across a number of solid tumor indications with high unmet need.
Dr. Mary: These research efforts represent important long term value drivers for our oncology portfolio.
Dr. Mary: We're also exploring potential collaborations that could further unlock and maximize value from the products and platform.
Dr. Mary: Additionally, leveraging our expertise in infectious disease immunology, we have advanced the broadly neutralizing antibody two development candidates that are in our HIV cure program.
Marianne DeBacker: I want to emphasize that these figures specifically focus on RNA-positive patients with active viremic disease who would be candidates for treatment. This distinction is important because we focus specifically on patients with detectable viral replication who face the highest risk of disease progression. We've conducted an extensive evaluation of multiple epidemiological sources and consulted with leading experts in the field to arrive at these estimates. It's important to note that our updated understanding of the market size underscores that Hepatitis Delta has the characteristics of a rare disease market with significant commercial potential. Let me highlight a few key points.
Dr. Mary: Looking ahead, our financial position remains strong with approximately $1 billion in cash cash equivalents and investments at the end of the first quarter.
Dr. Mary: This provides us with cash runway extending into mid 2027, giving us the resources to advance our key programs so critical Saudi infection point.
Dr. Mary: We are maintaining a disciplined approach to capital allocation focusing our resources on our most promising programs.
Dr. Mary: As he continues to execute on our strategic priorities, we recognize the challenging market environment facing the biotechnology sector as a whole.
Looking ahead, our financial position remains strong with approximately $1 billion in cash cash equivalents and investments at the end of the first quarter.
Dr. Mary: In times like these we believe the most important thing we can do for our shareholders is to remain focused on operational excellence and advancing our pipeline with discipline and purpose.
Marianne DeBacker: First, this is a disease with severe outcomes. More than 50% of hepatitis delta patients succumb to liver-related deaths within 10 years of diagnosis. and there are no FDA approved treatments in the United States. Second, treatment is managed by a concentrated group of hepatologists and liver specialists. allowing for focused commercial engagement. Third, the Severe Clinical Outcomes and EMA Orphan Disease Designation support a value-based pricing model, similar to other rare disease therapies. Fourth, the high cost burden of untreated disease progression, including liver transplantation and end-stage liver disease management, provides a compelling economic case for effective treatment. And finally, our market research indicates high physician intent to treat these patients, given the lack of effective options.
This provides us with cash runway extending into mid 2027, giving us the resources to advance our key programs so critical Saudi infection point.
Dr. Mary: <unk> cash position allows us to weather market volatility.
We are maintaining a disciplined approach to capital allocation focusing our resources on our most promising programs.
Dr. Mary: I am confident that our focused approach to developing potentially transformative medicine for patients with significant unmet needs will make a difference in the lives of patients while driving value creation for our shareholders.
As we continue to execute on our strategic priorities, we recognize the challenging market environment facing the biotechnology sector as a whole.
Dr. Mary: With that I'll now turn the call over to Mark to provide a more detailed update on our clinical development programs.
In times like these we believe the most important thing we can do for our shareholders is to remain focused on operational excellence and advancing our pipeline with discipline and purpose.
Mark: Thank you Mary Anne I'm pleased to provide an update on our clinical development programs. We've made significant progress across both our infectious disease and oncology portfolios during the first quarter and I'll walk you through the key developments.
Strong cash position allows us to weather market volatility.
I am confident that our focused approach to developing potentially transformative medicine for patients with significant unmet needs will make a difference in the lives of patients.
Mark: Let me start with our hepatitis Delta program, where we've achieved an important milestone with the initiation of our Registrational Corpus Phase III program.
Driving value creation for our shareholders.
Marianne DeBacker: The regulatory designations we've received, Breakthrough Therapy, Fast Track in the United States, and Prime and Orphan Drug in the EU, underscore the potential impact of our approach and may help accelerate our development timeline. We are focused on driving enrollment in our ECLIPSE I trial and preparing for the ECLIPSE II and III study initiation. As we advance our Hepatitis Delta program, I'm also pleased to report that during the quarter, we reached an agreement with Alnylam, whereby they elected not to opt-in to the profit-sharing arrangement for Elapsaran, resulting in a continued milestone and royalty-based structure. This decision provides clarity for our approach to advance our hepatitis delta program and gives us the flexibility to partner the program in Europe and other international markets.
Mark: I'm pleased to report that we enrolled the first patient in Corp's won during the first quarter keeping us on track with our development timeline.
With that I'll now turn the call over to Mark to provide a more detailed update on our clinical development programs.
Mark: Thank you Maria I'm pleased to provide an update on our clinical development programs. We've made significant progress across both our infectious disease and oncology portfolios during the first quarter and I'll walk you through the key developments.
Mark: The clips one is designed to evaluate our combination therapy in regions, where our board retired is not available or has limited use including the United States.
Mark: The study will enroll 120 participants randomized two to one to receive either <unk> or combination therapy or for treatment with.
Mark: Let me start with our hepatitis Delta program, where we've achieved an important milestone with the initiation of our Registrational Corpus Phase III program.
Mark: The primary endpoint is a composite endpoint of H D. D. RNA targeted not detected meaning that there was no measurable presence of the virus in the blood and L. P normalization at week 48.
Mark: I'm pleased to report that we enrolled the first patient in Corp's won during the first quarter keeping us on track with our development timeline.
Mark: Key secondary endpoint is H D D RNA target not detected.
Mark: The clips one is designed to evaluate our combination therapy in regions, where board retired is not available or has limited use including the United States.
Mark: We're also preparing for the initiation of a coach two which will evaluate switching to a combination therapy in patients who have not adequately responded to whoever card.
Speaker Change: The study will enroll 120 participants randomized two to one to receive either <unk> or combination therapy org for treatment with <unk>.
Marianne DeBacker: The outcome of this agreement was anticipated and factored into our long-term financial planning and was already included in our projected cash runway extending into mid-2027.
Mark: <unk> two will have a 24 week primary endpoint of HPV target not detected.
Speaker Change: Primary endpoint is a composite endpoint of H D. D. RNA targeted not detected meaning that there was no measurable presence of the virus in the blood and L. P normalization and week 48.
Mark: Together Eclipse, one and two are designed to form the backbone of our regulatory submissions in the United States and Europe.
Jason OByrne: Jason will provide additional details on the financial aspects of this agreement later in the call.
Mark: This comprehensive approach addresses different patient populations and treatment scenarios, providing a robust evidence package for regulatory review.
Marianne DeBacker: Turning briefly to our Hepatitis B program, we are presenting 24-week post-treatment follow-up data from our March Phase 2 study at the upcoming ESL Congress on May 9. Specifically, we will be sharing functional cure data from participants who have completed 24 weeks of follow-up after treatment discontinuation.
Speaker Change: The key secondary endpoint is H D V RNA target not detected.
Speaker Change: We're also preparing for the initiation of a coach two which will evaluate switching to a combination therapy in patients who have not adequately responded to whoever Todd.
Mark: These studies will include both non cirrhotic participants Ambrose with compensated cirrhosis. This broad eligibility is important as it reflects the real world patient population and will provide valuable insight into the treatment effects across different stages of disease.
Speaker Change: Clips two will have a 24 week primary end point of HPV target not detected.
Marianne DeBacker: Shifting gears to our oncology portfolio. We continue to make steady progress with the ProXtend Dual MOS T-cell engagement. As a reminder, we have worldwide rights to the ProXtend platform in infectious disease and oncology. For Vir 5818, our dual mask to her two-targeted T-cell engager, we're continuing to dose escalate as monotherapy and in combination with tembrolizumab. Our data presented in January showed a 33% confirmed partial response rate in her two positive colorectal cancer patients. at doses of 400 micrograms per kilogram and above, with one response lasting over 18 months. We're particularly encouraged by these results in colorectal cancer, where there remains a significant unmet need for effective therapy.
Speaker Change: Together Eclipse, one and two are designed to form the backbone of our regulatory submissions in the United States and Europe.
Mark: The regulatory designations, we received breakthrough therapy and fast track in the United States and Prime an orphan drug in the EU reflects a significant unmet need and the potential of our approach to address it.
Speaker Change: This comprehensive approach addresses different patient populations and treatment scenarios, providing a robust evidence package for regulatory review.
Mark: Patrick Nations May help accelerate our development and review time lines potentially bringing this important therapy to patients sooner.
Speaker Change: These studies will include both non cirrhotic participants Ambrose with compensated cirrhosis. This broad eligibility is important as it reflects the real world patient population and will provide valuable insight into the treatment effects across different stages of disease.
Mark: At the upcoming usual Congress will be presenting a poster showcasing data from a 24 week subgroup analysis of our solstice trial examining the impact of baseline viral parameters and cirrhosis status on responses to our combination therapy.
Speaker Change: The regulatory designations, we received breakthrough therapy and fast track in the United States and Prime an orphan drug in the EU reflects a significant unmet need and the potential of our approach to address it.
Mark: For a hepatitis B program will be presenting 24 week post treatment follow up data from our March phase two study are equal or maybe not.
Speaker Change: These designations may help accelerate our development and review time lines potentially bringing this important therapies to patients sooner.
Mark: Presentation will provide insights into functional cure after treatment discontinuation.
Marianne DeBacker: These responses were observed in micro-satellite stable tumors, which are typically resistant to immunotherapy, suggesting VO5818 could potentially address an important treatment gap for these patients.
Mark: As a reminder, the advancement of this program and to further clinical development is contingent on securing a partner.
Speaker Change: The upcoming usual Congress will be presenting a poster showcasing data from a 24 week subgroup analysis of our solstice trial examining the impact of baseline viral parameters and cirrhosis status on responses to our combination therapy.
Mark: Now I would like to turn to our oncology portfolio, where we continue to make progress with the perks them no T cell engaging programs.
Marianne DeBacker: For VIR 5500, our dual-masked PSMA-targeted T-cell engager, we continue to dose escalate, given our favorable safety profile and the learnings from VIR 5880. We've evaluated multiple additional dose levels since our last update. Our January data showed that 100% of patients at doses above 120 micrograms per kilogram experienced PSA decline, with 58% achieving a PSA-50 response, all without prophylactic steroids and with minimal cytokine releasing. We continue to see strong investigator enthusiasm for this program based on the early signals we've observed.
Speaker Change: For a hepatitis B program will be presenting 24 week post treatment follow up data from our March phase two study an easel on may nine.
Our drug Master approach is designed to selectively activate T cell engages in the tumor microenvironment potentially providing a wider therapeutic window than traditional a master purchase.
Speaker Change: Presentation will provide insights into functional cure after treatment discontinuation.
Mark: Our pro extend enough TCE is achieved this through the addition of long hydrophilic polypeptide to extend masks the chill with both the <unk> three and tumor associated antigen binding domains by a.
Speaker Change: As a reminder, the advancement of this program into further clinical development is contingent on securing a partner.
Speaker Change: Now I'd like to turn to our oncology portfolio, where we continue to make progress with the perks than NAFTA T cell engagement programs.
Mark: Steric hindrance.
Mark: Importantly, these universal masks, a cleaver burkhart is found within the tumor microenvironment, enabling selective activation, where it's needed most.
Speaker Change: Our dual masked approach is designed to selectively activate T cell engages in the tumor microenvironment potentially providing a wider therapeutic window than traditional a master purchase are.
Mark: This technology allows for hard dosing with reduced systemic toxicity, which we believe could translate to improved efficacy and safety profile.
Marianne DeBacker: We're also on track to initiate our phase one study for VIIR 5525, our dual-masked EGSR-targeted T cell engager this quarter. This program has the potential to address multiple high value indications. including non-small cell lung cancer, colorectal cancer, head and neck squamous cell carcinoma, and other EGFR-expressing tumors. The ProX10 universal dual masking approach continues to demonstrate potential advantages in terms of safety profile and dosing flexibility.
Speaker Change: Our pro extent masked TCE is achieved this through the addition of long hydrophilic polypeptide to extend masks the chill with both the <unk> three and tumor associated antigen binding domains by a.
Mark: It's sort of activation in the tumor microenvironment is key to minimizing off target effects, while maximizing anti tumor activity.
Mark: Premier for theater teams or her two targeted T cell engagement, we're continuing dose escalation in both monotherapy and in combination with <unk>.
Speaker Change: Steric hindrance.
Speaker Change: Importantly, these universal masks are cleaved by Proteus is found within the tumor microenvironment, enabling selective activation, where it's needed most.
Mark: As a reminder, our data presented in January showed a 33% confirmed partial response routes in her two positive colorectal cancer at doses of 400 micrograms per kilogram and a ball with one response lasting over 18 months Mr.
Speaker Change: This technology allows for higher dosing with reduced systemic toxicity, which we believe could translate to improved efficacy and safety profiles.
Marianne DeBacker: Beyond our clinical stage programs, we are rapidly advancing several next generation targets in areas of high unmet medical need. Our antibody discovery and protein engineering capabilities are key to the discovery of new tumor-associated antigen binders to quickly advance new TCE programs. And the universal nature of the ProXtend platform allows us to efficiently apply our dual masking approach. The synergies between antibody discovery capabilities and the ProXpand platform have begun to translate into meaningful progress with seven targets progressing in preclinical development across a number of solid tumor indications with high unmet needs.
Speaker Change: The sort of activation in the tumor microenvironment is key to minimizing off target effects, while maximizing anti tumor activity.
Mark: Mr ability is particularly encouraging in this heavily pretreated population.
Mark: Importantly, as Maryann mentioned the responses were observed in microsatellite stable colorectal cancer are noteworthy from a mechanistic perspective.
Speaker Change: For fear of 50, 818 or her two targeted T cell engagement, we're continuing dose escalation in both monotherapy and in combination with <unk>.
Mark: These tumors typically have low tumor mutational burden unlimited T cell infiltration, creating significant challenges for immunotherapy approaches.
Speaker Change: As a reminder, our data presented in January showed a 33% confirmed partial response rates in her two positive colorectal cancer at doses of 400 micrograms per kilogram and above with one response lasting over 18 months.
Mark: Our data suggests the bureau, 50 teams ability to redirect T cells to her two expressing tumor cells may provide a way overcome immunological barriers.
Speaker Change: This durability is particularly encouraging in this heavily pretreated population.
The durability of response, we've seen further supports the potential of this approach in a setting where patients typically experience rapid progression after exhausting standard treatment options.
Speaker Change: Importantly, as Maryann mentioned the responses were observed in microsatellite stable colorectal cancer are noteworthy from a mechanistic perspective.
Marianne DeBacker: These research efforts represent important long-term value drivers for our oncology portfolio. We're also exploring potential collaborations that could further unlock and maximize value from the ProXtend platform.
Mark: We remain focused on evaluating the potential of this program across multiple her two expressing tumor types.
Speaker Change: These tumors typically have low tumor mutational burden unlimited T cell infiltration, creating significant challenges for immunotherapy approaches.
Mark: We believe our approach could address significant unmet needs in various solid tumors, where her true expression plays a role.
Marianne DeBacker: Additionally, leveraging our expertise in infectious disease immunology, we have advanced a broadly neutralizing antibody to development candidate status in our HIV cure program. Looking ahead, our financial position remains strong, with approximately $1 billion in cash, cash equivalents and investments at the end of the first quarter. This provides us with a cash runway extending into mid-2027, giving us the resources to advance our key programs to critical value inflection.
Speaker Change: Our data suggest the bureau of 58, a team's ability to redirect T cells to her two expressing tumor cells may provide a way overcome these immunological barriers.
Mark: For beer 5500 appear from a targeted T cell engaging <unk>, we're advancing our dose escalation strategy, both weekly and Q3 week dosing regimens.
Speaker Change: The durability of response, we've seen further supports the potential of this approach in a setting where patients typically experience rapid progression after exhausting standard treatment options.
Mark: Our January data showed that 100% of patients at doses above 120 micrograms per kilogram experienced PSA declines with 58% achieving a PSA 50 response, all without prophylactic steroids and with minimal cytokine release syndrome.
Speaker Change: We remain focused on evaluating the potential of this program across multiple her two expressing tumor types.
Speaker Change: We believe our approach could address significant unmet needs in various solid tumors, where her true expression plays a role.
Marianne DeBacker: We're maintaining a disciplined approach to capital allocation, focusing our resources on our most promising programs. As we continue to execute on our strategic priorities, we recognize the challenging market environment facing the biotechnology sector as a whole. In times like these, we believe the most important thing we can do for our shareholders is to remain focused on operational excellence and advancing our pipeline with discipline and purpose. A strong cash position allows us to weather market volatility.
Mark: This favorable safety profile differentiates our approach from other P. SMA targeted therapies in development the.
Speaker Change: For beer 5500, a P SMA targeted T cell engaged or we're advancing our dose escalation strategy, both weekly and Q3 week dosing regimens.
Mark: The program continues to evaluate the potential of our approach and dual master perks in metastatic castration resistant prostate cancer setting with significant unmet need despite recent therapeutic advances.
Speaker Change: Our January data showed that 100% of patients at doses above 120 micrograms per kilogram experienced PSA declines with 58% achieving a PSA 50 response, all without prophylactic steroids and with minimal cytokine release syndrome.
Mark: We are particularly encouraged by the potential for Q3 week dosing with a half life of eight to 10 days for beer 5500, and we believe we can offer a much more convenient dosing schedule. This.
Marianne DeBacker: I'm confident that our focused approach to developing potentially transformative medicine for patients with significant unmet needs will make a difference in the lives of patients while driving value creation for our shareholders.
Speaker Change: This favorable safety profile differentiates our approach from other P. SMA targeted therapies in development the.
Mark: This will be especially important for patients and earlier lines of treatment, where quality of life considerations become increasingly significant.
Speaker Change: The program continues to evaluate the potential of our approach and dual masked approach in metastatic castration resistant prostate cancer setting with significant unmet need despite recent therapeutic advances.
Mark: We've successfully evaluated multiple dose levels since the data we shared in our January is about and are continuing with those escalation.
Mark Eisner: With that, I'll now turn the call over to Mark to provide a more detailed update on our clinical development program. Thank you, Marianne. I'm pleased to provide an update on our clinical development programs. We've made significant progress across both our infectious disease and oncology portfolios during the first quarter, and I'll walk you through the key development.
Mark: This ongoing dose optimization is critical to identifying a regimen that provides the optimal balance of efficacy and safety.
Speaker Change: We are particularly encouraged by the potential for Q3 week dosing with a half life of eight to 10 days for beer 5500, and we believe we can offer a much more convenient dosing schedule. This.
Mark: We believe you're 5500 and the potential to be a best in class treatment option in this area of significant unmet medical need offering a combination efficacy safety and convenience that could meaningfully improve outcomes for patients with prostate cancer.
Speaker Change: This will be especially important for patients and earlier lines of treatment, where quality of life considerations become increasingly significant.
Mark Eisner: Let me start with our Hepatitis Delta program, where we've achieved an important milestone with the initiation of our Registrational ECLIPSE Phase 3 program. I'm pleased to report that we enrolled the first patient in ECLIPSE 1 during the first quarter, keeping us on track with our development timeline. ECLIPSE1 is designed to evaluate our combination therapy in regions where bilivertide is not available or has limited use, including the United States. The study will enroll 120 participants, randomized 2 to 1, to receive either a combination therapy or a deferred treatment. The primary endpoint is a composite endpoint of HDV RNA target not detected, meaning that there was no measurable presence of the virus in the blood and ALT normalization at week 48.
Speaker Change: We've successfully evaluated multiple dose levels since the data we shared in our January he said that and are continuing with those escalation.
Mark: Building on our progress with her first two TCE programs, we're now expanding our portfolio with her third clinical candidate we are on track to initiate our phase one study Revere 50, 525, our egfr targeted T cell and user during this quarter.
Speaker Change: This ongoing dose optimization is critical to identifying a regimen that provides the optimal balance of efficacy and safety.
Speaker Change: We believe you're 5500 at the potential to be a best in class treatment option in this area of significant unmet medical need offering a combination efficacy safety and convenience that could meaningfully improve outcomes for patients with prostate cancer.
Mark: This program has the potential to address multiple high unmet need and high value indications with egfr expression, including non small cell lung cancer, colorectal cancer head and neck squamous cell carcinoma, and other egfr expressing tumors.
Speaker Change: Building on our progress with her first two TCE programs, we're now expanding our portfolio with our third clinical candidate we are on track to initiate our phase one study Revere 50, 525, our egfr targeted T cell and user during this quarter.
Mark: Government need in these indications remain substantial despite recent advances with hundreds of thousands of patients diagnosed annually with egfr expressing tumors across these indications.
Mark Eisner: key secondary endpoint is HDV RNA target not detected.
Mark Eisner: We're also preparing for the initiation of ECLIPSE-2, which will evaluate switching to our combination therapy in patients who have not adequately responded to Blubr tag. Clips two will have a 24-week primary endpoint of HDV target not detected. Together, Eclipse I and II are designed to form the backbone of our regulatory submissions in the United States and Europe. This comprehensive approach addresses different patient populations and treatment scenarios, providing a robust evidence package for regulatory review. These studies will include both non-cirrhotic participants and those with compensated cirrhosis. This broad eligibility is important as it reflects the real world patient population and will provide valuable insight into the treatment effects across different stages of disease.
Mark: There are 50 525 has the potential to address the substantial unmet need for a novel modality that harnesses the patient's T cells to kill Egfr expressing cancer cells.
Speaker Change: This program has the potential to address multiple high unmet need and high value indications with egfr expression, including non small cell lung cancer, colorectal cancer head and neck squamous cell carcinoma, and other egfr expressing tumors.
Our first then duel masters approach could offer a differentiated safety profile potentially allowing for more aggressive targeting of egfr expressing tumors compared to traditional approaches.
Speaker Change: The unmet need in these indications remain substantial despite recent advances with hundreds of thousands of patients diagnosed annually with egfr expressing tumors across these indications.
Mark: The universal nature of the products then platform enables us to leverage our learnings from our earlier T cell and get your programs. The optimized study design and dose escalation Revere 50 525.
Speaker Change: There are 50 525 has the potential to address a substantial unmet need through.
Mark: In conclusion, I'm very pleased with the progress, we're making across our entire portfolio. The initiation of our eclipse phase III program and continued advancement of our T cell engaging programs demonstrates our commitment to addressing significant unmet medical needs.
Speaker Change: Through a novel modality that harnesses, the patient's T cells to kill Egfr expressing cancer cells.
Speaker Change: Our first end duel Masters approach could offer a differentiated safety profile potentially allowing for more aggressive targeting of egfr expressing tumors compared to traditional approaches.
Mark Eisner: The regulatory designations we've received, Breakthrough Therapy and Fast Track in the United States, and Prime and Orphan Drug in the EU, reflect the significant unmet need and the potential of our approach to address. These designations may help accelerate our development and review timelines, potentially bringing this important therapy to patients sooner.
Jason: We remain focused on executing our clinical development plans with scientific rigor and operational excellence always keeping in mind, the patients who could benefit from these potential therapies with that I'll now hand over the call to Jason.
Speaker Change: The universal nature of the products then platform enables us to leverage our learnings from our earlier T cell and get your programs. The optimized study design and dose escalation Revere 50 525.
Jason: Thank you Mark I'm pleased to share our first quarter financial performance and overall financial position.
Mark Eisner: At the upcoming ESL Congress, we'll be presenting a poster showcasing data from a 24-week subgroup analysis of our SOLSTICE trial, examining the impact of baseline viral parameters and cirrhosis status on responses to our combination therapy.
Speaker Change: In conclusion, I'm very pleased with the progress, we're making across our entire portfolio. The initiation of our eclipse phase III program and continued advancement of our T cell engaging programs demonstrates our commitment to addressing significant unmet medical needs.
Jason: We continue to maintain a strong financial foundation, while advancing our key programs and I'll start with several key financial metrics for this past quarter.
Jason: R&D expenses for the first quarter of 2025 were $118 6 million, which included $7 million of non cash stock based compensation expense.
Mark Eisner: For our Hepatitis B program, we'll be presenting 24-week post-treatment follow-up data from our March Phase 2 study at ESL on May 9. This presentation will provide insights into functional cure after treatment discontinuation.
Jason: We remain focused on executing our clinical development plans, the scientific rigor and operational excellence always keeping in mind, the patients who could benefit from these potential therapies with that I'll now hand over the call to Jason.
Jason: Compared to $100 $1 million for the same period in 2024, which included $13 6 million of stock based compensation expense.
Jason: Thank you Mark I am pleased to share our first quarter financial performance and overall financial position.
Mark Eisner: As a reminder, advancement of this program into further clinical development is contingent on securing a partner.
Jason: The increase in R&D expenses was primarily driven by a $30 million payment to all Mylan and.
Jason: We continue to maintain a strong financial foundation, while advancing our key programs and I'll start with several key financial metrics for this past quarter.
Mark Eisner: Now I'd like to turn to our oncology portfolio, where we continue to make progress with the ProXtend Mast T-cell Engager Program. Our dual masked approach is designed to selectively activate T cell engagers in the tumor microenvironment, potentially providing a wider therapeutic window than traditional unmasked approach. Our ProXtend masked TCEs achieve this through the addition of long hydrophilic polypeptide Xtend masks that shield both the CD3 and tumor-associated antigen binding domains via steric hindrance. Importantly, these universal masks are cleaved by proteases found within the tumor microenvironment, enabling selective activation where it's needed most. This technology allows for higher dosing with reduced systemic toxicity, which we believe could translate to improved efficacy and safety profiles.
Jason: And expenses related to the initiation of the Eclipse Registrational program.
Jason: These increases were partially offset by lower R&D expenses associated with past head count reductions do.
Jason: R&D expenses for the first quarter of 2025 or $118 6 million.
Jason: <unk> prioritized programs and the closing of our St. Louis, Missouri in Portland, Oregon sites.
Jason: Which included $7 million of non cash stock based compensation expense.
Jason: SG&A expenses for the first quarter of 2025 were $23 $9 million, which included $7 1 million of stock based compensation expense.
Jason: Compared to $100 1 million for the same period in 2024, which included $13 6 million of stock based compensation expense.
Jason: The increase in R&D expenses was primarily driven by a $30 million payment to all Mylan and.
Jason: Compared to $36 3 million for the same period in 2024, which included $10 2 million of stock based compensation expense.
Jason: And expenses related to the initiation of the Eclipse Registrational program.
Jason: The decrease was largely due to ongoing cost savings realized through head count reductions and other initiatives.
Jason: These increases were partially offset by lower R&D expenses associated with past head count reductions few.
Jason: Combined our first quarter operating expense of $142 $6 million increased modestly by approximately $6 million year over year.
Jason: <unk> prioritized programs and the closing of our St. Louis, Missouri in Portland, Oregon sites.
Jason: SG&A expenses for the first quarter of 2025 were $23 $9 million, which included $7 1 million of stock based compensation expense.
Jason: Net loss for the first quarter of 2025 was $121 million compared to a net loss of $65 3 million for the same period in 2024.
Mark Eisner: The selective activation in the tumor microenvironment is key to minimizing off-target effects while maximizing anti-tumor activity.
Jason: Compared to $36 3 million for the same period in 2024, which included $10 2 million of stock based compensation expense.
Jason: The higher net loss was largely driven by $52 million of revenue in the first quarter of 2024 <unk>.
Mark Eisner: For VIR5818, our HER2-targeted T cell engager, we're continuing dose escalation in both monotherapy and in combination with cumberlizumab. As a reminder, our data presented in January showed a 33% confirmed partial response rate in HER2-positive colorectal cancer at doses of 400 micrograms per kilogram and above, with one response lasting over 18 months. This durability is particularly encouraging in this heavily pretreated population. Importantly, as Marianne mentioned, the responses we observed in microsatellite-stable colorectal cancer are noteworthy from a mechanistic perspective. These tumors typically have low tumor mutational burden and limited T cell infiltration, creating significant challenges for immunotherapy approaches.
Speaker Change: The decrease was largely due to ongoing cost savings realized through head count reductions and other initiatives.
Jason: Compared to approximately $3 million of revenue in the first quarter of 2025.
Jason: Turning to cash our net cash consumed in the first quarter was $75 6 million, which is in line with our expectations.
Speaker Change: Combined our first quarter operating expense of $142 $6 million increased modestly by approximately $6 million year over year.
We ended the quarter with approximately $1 billion in cash cash equivalents and investments based on our current operating plan. We continue to project our cash runway extending into mid 2027.
Speaker Change: Net loss for the first quarter of 2025 was $121 million compared to a net loss of $65 3 million for the same period in 2024.
Jason: This provides us with the resources to advance key programs through planned value inflection points.
Speaker Change: The higher net loss was largely driven by $52 million of revenue in the first quarter of 2024.
Speaker Change: As Mary Lynne mentioned earlier I'll now Luna has elected not to opt into the profit sharing arrangement for our lips right.
Speaker Change: Compared to approximately $3 million of revenue in the first quarter of 2025.
Speaker Change: As a result, we recognized $6 million as R&D expense in the first quarter, which was paid in cash flow on the island in April of this year.
Speaker Change: Turning to cash our net cash consumed in the first quarter was $75 6 million.
Mark Eisner: Our data suggests that VIR5818's ability to redirect T-cells to HER2-expressing tumor cells may provide a way to overcome these immunological barriers. The durability of response we've seen further supports the potential of this approach in a setting where patients typically experience rapid progression after exhausting standard treatment options. We remain focused on evaluating the potential of this program across multiple HER2-expressing tumor types, as we believe our approach could address significant unmet needs in various solid tumors where HER2 expression plays a role.
Speaker Change: Which is in line with our expectations.
Speaker Change: This payment reduced potential future development and regulatory milestones that were described in our most recent 10-K from $175 million to $145 million.
Speaker Change: We ended the quarter with approximately $1 billion in cash cash equivalents and investments based on our current operating plan. We continue to project our cash runway extending into mid 2027. This.
Speaker Change: This provides us with the resources to advance key programs through planned value inflection points.
Speaker Change: The amended terms are further described in our first quarter 10-Q.
Speaker Change: The agreement with them the island remains in milestone and royalty based arrangements. This was our base case outcome and was assumed in our current runway guidance.
Speaker Change: As Mary Lynne mentioned earlier I'll now Luna has elected not to opt into the profit sharing arrangement for <unk>.
Speaker Change: As a result, we recognized $6 million as R&D expense in the first quarter, which was paid in cash flow on the island in April of this year.
Speaker Change: Our capital deployment strategy remains focused on our most promising programs.
Speaker Change: Dancing, our hepatitis Delta Eclipse Registrational studies with eclipse, one continuing to enroll and preparations underway for eclipse two and eclipsed three.
Speaker Change: This payment reduced potential future development and regulatory milestones that were described in our most recent 10-K from $175 million to $145 million.
Mark Eisner: For VR5500, our PSMA-targeted T cell engager, we're advancing our dose escalation strategy in both weekly and Q3 week dosing regimen. Our January data showed that 100% of patients at doses above 120 micrograms per kilogram experienced PSA declines, with 58% achieving a PSA-50 response, all without prophylactic steroids and with minimal cytokine release syndrome. This favorable safety profile differentiates our approach from other PSMA-targeted therapies in development. The program continues to evaluate the potential of our ProXtend dual mast approach in metastatic castration-resistant prostate cancer, a setting of significant unmet need despite recent therapeutic advances. We are particularly encouraged by the potential for Q3 week dosing.
Speaker Change: Continuing dose escalation for our Tucson engage a program Spirit 50, 818 and Bureau 5500.
Speaker Change: The amended terms are further described in our first quarter 10-Q.
Speaker Change: And finally initiating in advancing the phase one study for 50 525.
Speaker Change: The agreement with on the island remains in milestone and royalty based arrangements. This was our base case outcome and was assumed in our current runway guidance.
Speaker Change: For hepatitis B program any further development will be contingent upon securing development and commercialization partner.
Speaker Change: Our capital deployment strategy remains focused on our most promising programs.
Speaker Change: We continue to apply financial discipline as we deploy resources toward advancing these key programs to create value and benefit for patients with that I'll hand, it back to rich to initiate the Q&A session.
Speaker Change: <unk>, our hepatitis Delta Eclipse Registrational studies with eclipse, one continuing to enroll and preparations underway for eclipse two and eclipsed three.
Speaker Change: Thank you Jason This concludes our prepared remarks, and we'll now start the Q&A session.
Speaker Change: Continuing dose escalation for our T cell engaging programs spirit, 50, 818 and beer 5500.
Speaker Change: Limit your questions to two per person so that we can get to all of our covering analysts I'll turn it over to you operator.
Speaker Change: And finally initiating in advancing the phase one study for 50 525.
Speaker Change: Yes.
Speaker Change: At this time, we will begin conducting our analyst Q&A session.
Speaker Change: For a hepatitis B program any further development will be contingent upon securing a development and commercialization partner.
Mark Eisner: With a half-life of eight to 10 days for VIR 5500, we believe we can offer a much more convenient dosing schedule. This would be especially important for patients in earlier lines of treatment where quality of life considerations become increasingly significant. We've successfully evaluated multiple dose levels since the data we shared in our January 8 event and are continuing with those escalations. This ongoing dose optimization is critical to identifying a regimen that provides the optimal balance of efficacy and safety. We believe VEER 5500 has the potential to be a best-in-class treatment option in this area of significant unmet medical need, offering a combination of efficacy, safety, and convenience that could meaningfully improve outcomes for patients with prostate cancer.
Speaker Change: Your first question comes from the line of Gena Wang with Barclays.
Speaker Change: We continue to apply a financial discipline as we deploy resources towards advancing these key programs to create value and benefit for patients.
Speaker Change: Please go ahead.
Speaker Change: Thank you I have a two questions. So the first one regarding to all Mylan decision did they see most up to date data for both HBV and H.
Speaker Change: With that I'll hand, it back to rich to initiate the Q&A session.
Rich: Thank you Jason This concludes our prepared remarks, and we'll now start the Q&A session.
Speaker Change: Limit your questions to two per person so that we can get to all of our covering analysts I'll turn it over to you operator.
Speaker Change: And what was the reason they provided footnotes update.
Speaker Change: And the second question is kind of thinking about you have so many probes are progressing so rapidly.
Rich: Yes.
Speaker Change: At this time, we will begin conducting our analyst Q&A session.
Speaker Change: College space, So what should we see the next update from the programs.
Speaker Change: Your first question comes from the line of Gena Wang with Barclays.
Speaker Change: It would be likely to vacuum.
Speaker Change: Data update.
Speaker Change: Please go ahead.
Speaker Change: Yes. Thank you gena for those questions, maybe I'll start with the last one first.
Speaker Change: Thank you I have a two questions. So the first one regarding to all Mylan decision.
Speaker Change: One our next oncology data update will be coming so the way we think about it for any next data update once we would be anticipating to share and.
Speaker Change: D C. Most up to date data for both HBV and H.
Mark Eisner: Building on our progress with our first two TCE programs, we're now expanding our portfolio with our third clinical candidate. We're on track to initiate our phase one study, Revere 5525, our EGFR-targeted T-cell engager during this quarter. This program has the potential to address multiple high-unmet need and high-value indications with EGFR expression, including non-small-cell lung cancer, colorectal cancer, head-to-neck squamous cell carcinoma, and other EGFR-expressing tumors. The unmet need in these indications remain substantial, despite recent advances, with hundreds of thousands of patients diagnosed annually with EGFR-expressing tumors across these indications. Vera 5525 has the potential to address the substantial unmet need through a novel modality that harnesses the patient's T-cells to kill EGFR-expressing cancer cells.
Speaker Change: And what was the reason they provided footnotes.
Speaker Change: And the second question is kind of thinking about you have so many programs are progressing rapidly.
Speaker Change: First of all let's say more mature data at a higher dose level you all what he presented just a couple of months ago in January.
Speaker Change: College space, So what should we see the next update.
Speaker Change: It would also want to share comparison data between weekend, and Oh, Hey, Sammy dosing.
Speaker Change: From the programs.
Speaker Change: Which would be likely to vacuum.
Speaker Change: Later, especially relevant for our ambition to go into earlier lines also appear a picture of a scale of a dose response.
Speaker Change: Data update.
Speaker Change: Yes. Thank you gena for those questions, maybe I'll start with the last one first so when our next oncology data update will be coming so the way we think about it for any next data update was we would be anticipating to share it.
Speaker Change: Relationships.
Speaker Change: Additional insights into the safety profile at higher doses.
Speaker Change: Of course also PSA responses. So once we have all of that four.
Four five to 504 or five days, one eight I mean there'll be sharing it of course it is to a medical Congress or still a more focused and best treat them. So soon US you know you already they build it out yourself.
Speaker Change: First of all let's say more mature data at higher dose levels beyond what we presented just a couple of months ago in January.
Speaker Change: I'd also want to share comparison data between weekend, and Oh, Hey, Sammy dosing.
Speaker Change: Yes second question Gena related to item.
Speaker Change: Especially relevant for our ambition to go into earlier line.
Speaker Change: So a lot of made their decision to upsize the profit sharing arrangement before our most recent H E. B functional cure data was available as you know that data is only going to be precise.
Speaker Change: Also a clear picture of the scale of the dose response.
Mark Eisner: Our ProExtend dual mast approach could offer a differentiated safety profile, potentially allowing for more aggressive targeting of EGFR-expressing tumors compared to traditional approach . The universal nature of the ProXtend platform enables us to leverage our learnings from our earlier T cell engager programs to optimize study design and dose escalation for VIRA5525.
Speaker Change: Relationships.
Speaker Change: Additional insights into the safety profile at higher doses.
Speaker Change: Of course also PSA responses. So once we have all of that.
Speaker Change: For the first time on Friday of diesel on May nine.
Speaker Change: Four five to 504 is 5818, I mean there'll be sharing it of course needed to a medical Congress or still more focused investor event. So soon.
Speaker Change: Here's the thing unless we get based on their own strategic portfolio prioritization.
Speaker Change: Thank you.
Speaker Change: Sure.
Speaker Change: He already beeville that gave up yourself.
Mark Eisner: In conclusion, I'm very pleased with the progress we're making across our entire portfolio. The initiation of our Eclipse Phase 3 program and continued advancement of our T cell engager programs demonstrates our commitment to addressing significant unmet medical needs. We remain focused on executing our clinical development plans with scientific rigor and operational excellence, always keeping in mind the patients who could benefit from these potential therapies.
The next question comes from the line of Paul Choi.
Speaker Change: Yes second question Gena related to an item.
Speaker Change: With Goldman Sachs.
Speaker Change: So a lot of made their decision to upsize the profit sharing arrangements before our most recent HBV.
Speaker Change: Please go ahead.
Speaker Change: Hi, everyone. Thanks for taking our questions.
Speaker Change: I want to ask about first about <unk> and it looks like you have a late breaker.
Speaker Change: Functional cure data wasn't available as you know that data is only going to be Chris added that's for the first time on Friday of diesel on May nine.
Speaker Change: The doublet in combination with the buyer on 200 asset just curious I think thats. The first look what will get us.
Speaker Change: So this decision was really based on their own strategic portfolio prioritization.
Jason OByrne: With that, I'll now hand over the call to Jason. Thank you, Mark. I'm pleased to share our first quarter financial performance and overall financial position. We continue to maintain a strong financial foundation while advancing our key programs, and I'll start with several key financial metrics for this past quarter. R&D expenses for the first quarter of 2025 were $118.6 million, which included $7 million of non-cash stock based compensation compared to $100.1 million for the same period in 2024, which included $13.6 million of stock based compensation The increase in R&D expenses was primarily driven by a $30 million payment to Alnylam and expenses related to the initiation of the Eclipse Registrational Program.
Speaker Change: Get a at that program and so just curious sort of what the rationale is behind that trip that newer triplet combination strategy, there and just sort of how you think about the development plans for that versus other.
Speaker Change: Thank you.
Speaker Change: Sure.
Speaker Change: Yeah.
Speaker Change: Your next question comes from the line of Paul.
Paul Choi: Paul Choi.
Speaker Change: With Goldman Sachs.
Paul Choi: Please go ahead.
Speaker Change: Other combinations.
Speaker Change: And my second question is.
Paul Choi: Hi, everyone. Thanks for taking our questions.
Speaker Change: Can you comment maybe in broad strokes on how youre thinking about completing enrollment or completing either they are except Warner eclipse two studies.
Paul Choi: I want to ask about first about <unk> and it looks like you have a late breaker.
Paul Choi: The doublet in combination with the V. Two.
Speaker Change: It would be helpful to understand in the context of your your cash guidance runway to 2027 and since you're just putting our first patient in the first quarter here just some context on that timing would be helpful. Thank you very much.
Paul Choi: 200 assets.
Paul Choi: Curious I think thats, the first look what will get us.
Paul Choi: Get a at that program and so just curious sort of what the rationale is behind that trip that new triple combination strategy, there and just sort of how you think about the development plans for that versus other.
Speaker Change: Okay. Thank you Paul So maybe the first question on the theory of combination Mark do you want to answer.
Speaker Change: All set up.
Paul Choi: Other combinations.
Speaker Change: Yeah. So thanks, Paul for the question I mean first of all that that's a study conducted by Varian and yeah. We did provide access to different Barton a lobster around for that.
Paul Choi: And my second question is.
Jason OByrne: These increases were partially offset by lower RMD expenses associated with past headcount reductions, deprioritized programs, and the closing of our St. Louis, Missouri and Portland, Oregon site. SG&A expenses for the first quarter of 2025 were $23.9 million, which included $7.1 million of stock based compensation expense. compared to $36.3 million for the same period in 2024, which included $10.2 million of stock based compensation. The decrease was largely due to ongoing cost savings realized through headcount reductions and other initiatives. Combined, our first quarter operating expense of $142.6 million increased modestly by approximately $6 million year over year.
Paul Choi: Can you comment maybe in broad strokes on how youre thinking about completing enrollment or completing either they are except Warner eclipse two studies.
Speaker Change: That study, but we're we're not you know it's being run by very on and it's in their portfolio and not ours. So I think the data are interesting in terms of you know.
Paul Choi: It'd be helpful to understand in the context of your your cash guidance runway to 2027 since you're just.
Paul Choi: The first patient in in the first quarter here, just some context on that timing would be helpful. Thank you very much.
Speaker Change: Some of the our early responses in terms of surface antigen decline, but that's really a in their portfolio rather rather than ours.
Speaker Change: Okay. Thank you Paul So maybe the first question on the Helios combination Mark do you want to answer.
Speaker Change: You're asking a really good question about H D V and our timelines you know we did announce first patient dosed for eclipse one.
Paul Choi: All set up.
Paul Choi: Yeah. So thanks, Paul for the question I mean first of all that that's a study conducted by Varian and.
Speaker Change: And we have a study estimated completion date of the end of 2026. So that means we would be aiming to complete enrollment in that study by the end of this year I mean, that's an aggressive target, but we are putting all of our resources behind getting these trials up and running for eclipse two we have.
Paul Choi: We did provide access to different Barton a lobster around four.
Paul Choi: That study, but we're not it's being run by very on and it's in their portfolio and not ours. So I think the the data are interesting in terms of.
Jason OByrne: Net loss for the first quarter of 2025 was $121 million, compared to a net loss of $65.3 million for the same period in 2024. The higher net loss was largely driven by $52 million of revenue in the first quarter of 2024, compared to approximately $3 million of revenue in the first quarter of 2025. Turning to cash, our net cash consumed in the first quarter was $75.6 million, which is in line with our expectation. We ended the quarter with approximately $1 billion in cash, cash equivalents and investment. Based on our current operating plan, we continue to project our cash runway extending into mid 2027.
Paul Choi: Some of the early responses in terms of surface antigen decline, but that's really a and in their portfolio, rather rather than hours, you're asking a really good question about H D V and our timelines you know we did announce first patient dosed for eclipse one.
Speaker Change: <unk> provided guidance, yet, but I can assure you that we are laser focused on getting that study up and running it's important to note that the eclipse two actually has a 24 week end point, so even though it's starting dosing.
Speaker Change: Dosing a little bit later, we will have a 24 versus <unk> 48 week readout. So the timing, we'll provide some more guidance when we're when we're able to do that but that's an important point to consider.
Paul Choi: And we have a study estimated completion date of the end of 2026. So that means we would be aiming to complete enrollment in that study by the end of this year I mean, that's an aggressive target, but we are putting all of our resources behind getting these trials up and running for eclipse two we have.
Speaker Change: Got it that's helpful color Mark Thank you very much.
Speaker Change: Your next question comes from the line of Mike Olson with.
Paul Choi: <unk> provided guidance, yet, but I can assure you that.
Paul Choi: We are laser focused on getting that study up and running it's important to note that the clips to actually has a 24 week end point, so even though it's starting dosing a little bit later, we will have a 24 versus <unk> 48 week readout. So the timing, we'll provide some more guidance when we.
Jason OByrne: This provides us with the resources to advance key programs through planned value inflection points. As Marianne mentioned earlier, Al-Nadlam has elected not to opt in to the profit sharing arrangement for Elepserat. As a result, we recognized $3 million as RMD expense in the first quarter, which was paid in cash to Alnylam in April of this year. This payment reduced potential future development and regulatory milestones that were described in our most recent 10-K from $175 million to $145 million. The amended terms are further described in our first quarter, 10-2. The agreement with Long Island remains a milestone and royalty based arrangement.
Speaker Change: Morgan Stanley.
Speaker Change: Please go ahead.
Hi, Good afternoon. This is avi now that kind of line for Mike. Thank you for taking our question. So a competitor of yours recently shared updated data from the T. C. A T C. P. SMA targeting program in metastatic CRP C. So I was wondering if you had any updated thoughts on your competitive positioning.
Speaker Change: When we're able to do that but that's an important point to consider.
Speaker Change: Got it that's helpful color Marc Thank you very much.
Speaker Change: <unk> zero and do you see a median PFS of around seven five months.
Speaker Change: Your next question comes from the line of Mike <unk> with.
Speaker Change: That's a fair and achievable benchmark before he got a program. Thanks.
Speaker Change: Morgan Stanley.
Speaker Change: Please go ahead.
Speaker Change: So yeah I can take that question.
Avi: Hi, Good afternoon. This is avi now that kind of line for Mike. Thank you for taking our question. So a competitor of yours recently shared updated data from the TCA TCE P. SMA targeting program in metastatic CRP C. So I was wondering if you had any.
Speaker Change: First of all where are actually very encouraged them.
Jason OByrne: This was our base case outcome and was assumed in our current runway guide.
That they that their continued progress.
Speaker Change: For T cell engagement in general, including the fact that <unk> continues to prove.
Jason OByrne: Our Capital Deployment Strategy remains focused on our most promising programs. Advancing our Hepatitis Delta Eclipse Registrational Studies with Eclipse 1 continuing to enroll and preparations underway for Eclipse 2 and Eclipse 3. Continuing dose escalation for our T cell engager programs, VIR 5818 and VIR 5500. And finally, Initiating and Advancing the Phase I Study for 5525. For our Hepatitis B program, any further development will be contingent upon securing a development and commercialization partner.
Speaker Change: Tough a concept that masking technology actually extend the therapeutic index and while I can't comment directly on how we would be compared because we are relatively earlier in our dose escalation comparison, where they are we do think that we are quite differentiated in that.
Avi: David thoughts on your competitive positioning.
Avi: <unk> zero and do you see a median PFS of around seven five months.
Avi: I guess, a fair and achievable benchmark before you got program. Thanks.
Avi: So yeah I can take that question.
Speaker Change: Our product <unk> is a dual mask technology.
Avi: First of all and we're actually very encouraged about.
Speaker Change: Technology, it's quite a different masking technology than the other masks that are out there. It's a universal masking T. Only clinically validated last in terms of having clinical validation and other platforms such as the drug out to be a hemophilia drug.
Avi: About the continued progress and for T cell engagement in general.
Rich Lepke: We continue to apply financial discipline as we deploy resources toward advancing these key programs to create value and benefit for With that, I'll hand it back to Rich to initiate the Q&A session. Thank you, Jason.
Avi: Including the fact that <unk> continues to add too tough a concept that masking technology actually extend the therapeutic index and while I can't comment directly on how we would be compared because we are relatively earlier in our dose escalation comparison right.
Speaker Change: And we do think that we have a really very favorable safety profile I wish we demonstrated in our January update that we have a very low rate of Crs, we do not use any prophylactic steroids are we we know that every other T cell engage your program in <unk>.
Operator: This concludes our prepared remarks.
Operator: And we will now start the Q&A session. Please submit your questions to two per person so that we can get to all of our covering analysts.
Avi: Uh huh.
Operator: I'll turn it over to you, operator.
Avi: We do think that we are quite differentiated in that or Kazakhstan is a dual role of ask.
Gina Wang: At this time, we will begin conducting our analyst Q&A session. Your first question comes from the line of Gina Wang with Barclays. Please go ahead. Thank you. I have two questions. So maybe the first one regarding the Al-Nahlan decision.
Avi: Technology, it's quite a different masking technology than the other masks that are out there. It's a universal masking T. Only clinically validated last in terms of having clinical validation and other platforms such as the drug out to be a hemophilia drug.
Speaker Change: Some form of prophylaxis and despite the lack of abuse of Scott corticosteroids. We have this very low grade Trs and also no evidence of significant IL six elevation.
Speaker Change: And despite that we are seeing some nice really early activity.
Avi: And we do think that we have a really very favorable safety profile I wish we demonstrated in our January update that we have a very low rate of Crs, we do not use any prophylactic steroids are we we know that every other T cell engage your program in <unk>.
Gina Wang: Did they see most up-to-date data for both HPV and And the second question is, you know, thinking about your... Progress. So I hope Technology Space. So, thank you.
Speaker Change: The other big differentiator, which I think is important.
Speaker Change: Both for safety and is and isn't a frontline is is that we have.
Speaker Change: As longer half life of eight to 10 days, which enables a Q3 week dosing schedule, we know that for convenience and quality of life that frontline setting for prostate cancer in particular.
Avi: Some form of couple axis and despite the lack of abuse of Scott corticosteroids. We have this very low grade Prs and also no evidence of significant IL six elevation.
Mark Eisner: The next update from the programs and which will be like Yes, thank you, Gina, for those questions. Maybe I'll start with the last one first. So when a next oncology data update will be coming. So the way we think about it for any next data update, what we would be anticipating to share is, first of all, obviously, more mature data at higher dose levels beyond what we presented just a couple of months ago in January. We would also want to share comparative data between weekly and every three-week dosing. We think the latter is especially relevant for our ambition to go into earlier lines.
These types of differentiation, that's going to be critically important.
Speaker Change: For overall Tolerability, a huge unmet need where we think these drugs cause could potentially offer significant convenience for that.
Avi: And despite that we are seeing some nice really early activity.
Avi: The other big differentiator, which I think is important.
Speaker Change: Okay, great. Thank you.
Avi: Both for safety and is and is in the frontline is is that we have.
Speaker Change: The next question comes from the line of.
Eric Joseph: Eric Joseph with JP Morgan.
Avi: As longer half life of eight to 10 days, which enables a Q3 week dosing schedule, we know that for convenience and quality of life that frontline setting for prostate cancer in particular.
Speaker Change: Please go ahead.
Speaker Change: Okay.
Speaker Change: Hey, guys. This is Ryan on for Eric I wanted to ask how does the recent umbrella very tied to update and thought your second or about potential finite versus long term chronic treatment.
Avi: These types of differentiation, that's going to be critically important.
Speaker Change: It's a combination for H D D.
Avi: For overall Tolerability, a huge unmet need where we think these drugs could could potentially offer significant convenience for that.
Speaker Change: Yeah.
Mark Eisner: Also, a clearer picture, obviously, on those response relationships, additional insights into the safety profile at higher doses, and of course, also PSA responses.
Speaker Change: Sure Mark Thanks for that.
Speaker Change: Question.
Mark: Yeah sure. So I think your question is about <unk>.
Mark: <unk> tied in and their long term outcome data in their ability to achieve finite.
Avi: Okay, great. Thank you.
Speaker Change: The next question comes from the line of.
Mark Eisner: So once we have all that for 5500 and for 5818, we will be sharing it, of course, either through a medical congress or through a more focused investor event. So as soon as we are ready, we will do that.
Mark: Treatment, how does that affect our program. So we just to remind everybody I mean, we achieve and are supposed to study.
Eric Joseph: Eric Joseph with JP Morgan.
Speaker Change: Please go ahead.
Eric Joseph: Hi, guys. This is Ryan on for Eric.
Mark: Very high rates of target not detected or complete viral suppression.
Speaker Change: I would ask how does the recent <unk> put a very tight update in terms of your second or potential finite versus long term chronic treatment.
Mark: We were achieving it in the majority of patients by week 24, and week 36 and.
Mark Eisner: Your second question, Gina, related to Al-Naylem. So, Al-Naylem made their decision to opt out of the profit-sharing arrangement before our most recent HCV functional cure data was available. As you know, that data is only going to be presented for the first time on Friday at ESL on May 9th. So, this decision was really based on their own strategic portfolio prioritization. Thank you. Sure.
Speaker Change: It's a combination for H D D.
Eric Joseph: Thanks.
Mark: We're getting to a 64% at week 36, so that compares to blubber tide and week 48 of only 12%. So we think we can achieve very high rates of viral suppression.
Eric Joseph: Sure Mark Thanks for that.
Eric Joseph: Question.
Eric Joseph: Yeah sure. So I think your question is about <unk>.
Eric Joseph: <unk> tied in and their long term outcome data and our ability to achieve finite.
Eric Joseph: Treatment, how does that affect our program. So we just to remind everybody I mean, we achieve and are supposed to study.
In terms of long term suppression.
Mark:
Mark: Yeah.
Mark: Bill ever tried data that are.
Mark: Are related to.
Eric Joseph: Very high rates of target not detected or complete viral suppression.
Mark: You know finite treat star with or a higher dose. So that's one thing to consider and you know it's not really a something that's in their off label right. Now. So we are aiming for chronic oral suppressive regimen. We think we can suppress the virus and the vast majority of patients. We're also achieving a.
Eric Joseph: We are achieving it in the majority of patients by week, 24, and week 36 and <unk>.
Paul Choi: The next question comes from the line of Paul Choi with Goldman Sachs. Please go ahead. Hi, everyone. Thanks for taking our questions. I want to ask first about Eazl and it looks like you have a late breaker of the doublet in combination with the Veron 200 asset. Curious, I think that's the first look we'll get at that program. And so just curious sort of what the rationale is behind that new triplic combination strategy there and just sort of how you think about the development plans for that versus your other combination. And my second question is, can you comment maybe in broad strokes on how you're thinking about completing enrollment or completing either the ECLIPSE-1 or ECLIPSE-2 studies?
Eric Joseph: We're getting to a 64% at week 36, so that compares to blubber tide and week 48 of only 12%. So we think we can achieve very high rates of viral suppression.
Mark: Re logged declines in hepatitis B surface antigen again, just pointing to the potency and the depth and breadth of our viral suppression for Delta. So we're really excited to be moving into the phase III program.
Eric Joseph: In terms of long term suppression.
Eric Joseph: Julia.
Eric Joseph: Whoever tide data that.
Eric Joseph: Are related to <unk>.
Ryan Ruiz: Your next question comes from the line of Ryan Ruiz with Leerink Partners. Please go ahead.
Eric Joseph: You know finite treat star with or a higher dose. So that's one thing to consider and you know it's not really a something that's in their off label right. Now. So we are aiming for chronic viral suppressive regimen. We think we can suppress the virus and the vast majority of patients. We're also achieving a three.
Speaker Change: Hey, good afternoon. This is Nick <unk> on for Walter.
Ryan Ruiz: Thanks for taking our questions maybe first on HBV.
Ryan Ruiz: How should we think about your expectations heading into the 24 week off treatment data for March at Eagle.
Eric Joseph: Relog declines in hepatitis B surface antigen again, just pointing to the potency and the depth and breadth of our viral suppression for Delta. So we're really excited to be moving into the phase III program.
Ryan Ruiz: Are you, hoping to see from a functional cure standpoint relative to the end of treatment data, we got at <unk> D and maybe what.
Paul Choi: This would be helpful to understand in the context of your cash guidance runway to 2027, since you're just putting in first patient in the first quarter here. Just some context on that timing would be helpful. Thank you very much. Okay, thank you, Paul.
Ryan Ruiz: Patients could this new data have for potential partnership partnership discussions in HBV.
Speaker Change: Your next question comes from the line of Ryan Ruiz with Leerink Partners. Please go ahead.
Ryan Ruiz: Okay.
Mark Eisner: So maybe the first question on the theory of combination, Mark, do you want to answer that? Yeah, so thanks, Paul, for the questions. I mean, first of all, that that's a study conducted by Virion. And, you know, we did provide access to Biverbard and Elapsaran for that study, but we're not, you know, it's being run by Virion, and it's in their portfolio and not ours. So I think, you know, the data are interesting in terms of, you know, some of the early responses in terms of decline, but, you know, that's really in their portfolio rather than ours.
Ryan Ruiz: That's it.
Speaker Change: Hey, good afternoon. This is Nick <unk> on for Walter.
Ryan Ruiz: Congrats on I'm sure I'll have Marc.
Speaker Change: Yeah. So I was just going to say we are looking forward to presentation of our March.
Speaker Change: For taking our questions maybe first on HBV.
Speaker Change: How should we think about your expectations heading into the 24 week off treatment data for March and easel. What are you hoping to see from a functional cure standpoint relative to the end of treatment data.
Speaker Change: Data 24 week off treatment that are this friday at ease all this.
Speaker Change: This will be the look at our functional cure rates as you might imagine we are going into a quiet period because it is just a very short period between now and then so you don't want to comment extensively except to say that we would have been signaled in the past that we're looking for 20% and the doublet in the 30% from filter.
Speaker Change: Got it.
Speaker Change: And maybe what implications could this new data have for potential partnership partnership discussions in HBV.
Speaker Change: Okay.
Speaker Change: Yeah.
Mark Eisner: You're asking a really good question about HDV and our timelines. You know, we did announce first patient dose for Eclipse 1, and we have a study estimated completion date of the end of 2026. So that means we would be aiming to complete enrollment in that study by the end of this year. I mean, that's an aggressive target, but we are putting all of our resources behind getting these Eclipse trials up and running. For Eclipse 2, we haven't provided guidance yet, but I can assure you that, you know, we are laser focused on getting that study up and running.
Speaker Change: The triplet, but you know I think.
Speaker Change: Oh go ahead, sorry, I'm sure I'll have Marc.
Speaker Change: Yeah. So I was just going to say we are looking forward to presentation of our March.
Speaker Change: Stay tuned and you'll see the full data of diesel in just a couple of days.
Speaker Change: Data 24 week off treatment that are this Friday at Eagle.
Speaker Change: Yes, the only thing I would add is that as we have already mentioned.
Speaker Change: This will be the look at our functional cure rates as you might imagine we are going into a quiet period. Because it is just a very short period between now and then so I don't want to comment extensively except to say that we would have been signaled in the past that we're looking for 20% and the doublet in the 30% from filter.
Speaker Change: And generally any further development on the HBV program is contingent on securing a worldwide development and commercial sterilization partner.
Speaker Change: Your next question comes from the line of Phil Nadeau with T. D. Cowen. Please go ahead.
Speaker Change: Sure and the triplet, but you know I think.
Mark Eisner: It's important to note that the Eclipse 2 actually has a 24-week endpoint. So even though it's starting dosing a little bit later, you know, we'll have a 24 versus 48-week readout. So, you know, the timing will provide some more guidance, you know, when we're able to do that, but that's an important point to consider. Got it. That's helpful color, Mark. Thank you very much.
Phil Nadeau: Good afternoon. Thanks for taking my questions two from US first on 5500, you mentioned that there have been multiple doses tested since the data in January.
Speaker Change: Stay tuned and you'll see the full data of diesel in just a couple of days.
Speaker Change: Yes, the only thing I would add is that as we have already mentioned.
Speaker Change: We're wondering if you would care to comment on whether there is additional basis doses have continued to suggest a dose response and efficacy in terms of PSA response rate and durability.
Speaker Change: And generally any further development on the HBV program is contingent on securing a worldwide development and commercial transportation partner.
Phil Nadeau: That's first question and then second on HDD.
Phil Nadeau: The RNA positive figures that you gave for the prevalence of the condition can you clarify are those.
Mike Ulz: Your next question comes from the line of Mike Ulz with Morgan Stanley.
Speaker Change: Your next question comes from the line of Phil Nadeau with T. D. Cowen. Please go ahead.
Phil Nadeau: Overall prevalent or patients diagnosed.
Avi Novick: Please go ahead. Hi, good afternoon.
Phil Nadeau: Good afternoon. Thanks for taking my questions two from US first on 5500, you mentioned that there have been multiple doses tested since the data in January.
Phil Nadeau: Having positive RNA and if it's not diagnosed do you have a sense of what the diagnosis rate is.
Mike Ulz: This is Avi Novick on the line for Mike. Thank you for taking our question. So, a competitor of yours recently shared updated data from its TCE PSMA targeting program in metastatic CRPC. So I was wondering if you had any updated thoughts on the competitive positioning of VAR5500 and do you see a median PFS of around seven and a half months as, I guess, a fair and achievable benchmark for your program? Thanks.
Phil Nadeau: Yes. Thank you Phil maybe I'll start with your last question on Delta prevalence. So so what we did see a really looks across.
Phil Nadeau: We're wondering if you would care to comment on whether there is additional basis doses have continued to suggest a dose response and efficacy in terms of PSA response rate and durability.
Phil Nadeau: All available studies, all available reports sundial soft Providence.
Phil Nadeau: That's first question and then second on HDD.
Phil Nadeau: It sort of started out with.
Phil Nadeau: The RNA positive figures that you gave for the prevalence of the condition can you clarify are those.
Phil Nadeau: Determining that based on all the numbers, we could get our hands on that of about 2 million patients in U S that are HPV positive.
Phil Nadeau: Overall prevalence or patients diagnosed.
Mark Eisner: So, yeah, I can take that question. First of all, we're actually very encouraged about the continued progress for T cell engagers in general, including the fact that Janux continues to prove proof of concept that masking technology actually extends the therapeutic index. And while I can't comment directly on how we would be compared, because we are relatively earlier in our death escalation compared to where they are, we do think that we are quite differentiated in that. Our product is a dual mask technology. It's a quite a different masking technology than the other masks that are out there.
Phil Nadeau: Having positive RNA and if it's not diagnosed do you have a sense of what the diagnosis rate is.
Phil Nadeau: And again through a very extensive literature search talking to kols different sources.
Speaker Change: Yes. Thank you Phil maybe I'll start with your last question on Delta prevalence. So so what we did see it really looks across.
Phil Nadeau: We found that on average about four 7% of dose.
Phil Nadeau: The patients are delta antibody positive.
Phil Nadeau: And again that further drilling down so that.
Speaker Change: All available studies all available report some doubts on Providence.
Phil Nadeau: So about 90 to 1000 patients actually in United States, but if you had to think about the patients that are actually going to get treated those other patients. That's you know our RNA positive you know that our activity environment and so again based on on a lot of Oh.
Speaker Change: Sort of started out with.
Speaker Change: Determining that based on all the numbers, we could get our hands on that of about 2 million patients in U S that are HPV positive.
Speaker Change: And again through a very extensive literature search talking to kols different sources.
Phil Nadeau: So she came to a conclusion as we shared that about 61000 patients in the United States would.
Speaker Change: We found that on average about four 7% of dose.
Phil Nadeau: It would be RNA positive and eligible for for treatment for a regimen. So that's sort of the breakdown of how we go to a pick up to the numbers.
Mark Eisner: It's a universal mask. It's the only clinically validated mask in terms of having clinical validation and other platforms, such as the drug Altuvia, a hemophilia drug. And we do think that we have a really very favorable safety profile. We demonstrated in our January update that we have a very low rate of CRS. We do not use any prophylactic steroids. We know that every other T cell engager program needs some form of prophylaxis and despite the lack of use of corticosteroids, we have this very low grade CRS and also no evidence of significant IL-6 elevations. And despite that, we are seeing some nice, really early activity.
Speaker Change: The patients are delta antibody positive.
Speaker Change: And again that further drilling down so that.
Speaker Change: And then your first question related to 5500 don't thing maybe any time you go to college.
Speaker Change: You're about 90 to 1000 patients sexually in the United States, but if you don't think about the patients that are actually going to get treated those are the patients that are RNA positive you know that our active heave ironic and so again based on a lot of.
Speaker Change: And as we have continued that dose escalation both at the Q week on the Q3 week dosing.
Speaker Change: But really we are not prepared to make any comments yeah. We are encouraged with it.
Speaker Change: So she came to the conclusion as we shared that about 61000 patients in the United States would.
Speaker Change: 818 data that also showed a nice dose response, we had that one patient, but clearly had a dose response within that what wahid, a intra patient dose escalated a colorectal cancer patient who went from 60 micrograms per kg I'm up to 600 micrograms per kg and continue.
Speaker Change: Would be RNA positive and eligible for treatment for a regimen. So that's sort of the breakdown of how we go to a pick up to the numbers.
Speaker Change: And then your first question related to 5500 dosing, maybe my colleagues can comment.
Mark Eisner: The other big differentiator, which I think is important, both for safety and is in the front line, is that we have a longer half-life of 8 to 10 days, which enables our 2-3 week dosing schedule. We know that for convenience and quality of life in the front line setting for prostate cancer in particular, these types of differentiation is going to be critically important for overall tolerability, a huge unmet need where we think these drugs could potentially offer significant convenience for that.
Speaker Change: And as we have.
Speaker Change: To have a long durability of response.
Speaker Change: Continue the dose escalation both at the Q week on the Q3 week dosing.
Speaker Change: Last thing over 18 months so.
Speaker Change: But really we are not prepared to make any comments yeah. We are encouraged with it.
Speaker Change: But.
Speaker Change: And sit tight and hopefully we'll be able to say something so.
Speaker Change: Yeah.
Speaker Change: When eight data that also showed a nice dose response, we had that one patient, but clearly had a dose response with them. That's what wahid intra patient dose escalated a colorectal cancer patient who went from 60 micrograms per kg up to 600 micrograms per kg and continue.
Alec Stranahan: Your next question comes from line of Alec Stranahan with Bank of America. Please go ahead.
Speaker Change: Okay.
Speaker Change: Hey, guys. This is Matthew on for Alex here, Thanks for taking our questions.
Speaker Change: A couple from my phone 50, 525, Yeah I saw recently that the trial sign on Quintin trials for 50 525.
Mark Eisner: All right, great. Thank you.
Speaker Change: Need to have a long durability of response.
Eric Joseph: The next question comes from the line of Eric Joseph with JPMorgan. Please go ahead. Hi guys, this is Ron on for Eric.
Speaker Change: <unk> four parts monotherapy escalation price expansion.
Speaker Change: Last thing over 18 months, so but.
Combos with Pembroke Escalations flash expansion.
Speaker Change: But.
Speaker Change: Sit tight and hopefully we'll be able to say something so.
Speaker Change: It would be helpful to have any color on why you chose that guy maybe it'd be ordering parts and whether you would still explore combination options with initial monotherapy data looks good.
Ron: I wanted to ask, how does the recent Bolivarotide update impact your thinking around potential finite versus long term chronic treatment with a combination for HDV? Sure. Mark, do you want to take that? Yeah, sure. So I think your question is about Belabor Tide and their long-term outcome data and their ability to achieve finite treatment. How does that affect our program? So we, just to remind everybody, I mean, we achieve in our SOLSTICE study, very high rates of target not detected or complete viral suppression. We're achieving it in the majority of patients by week 24 and week 36.
Speaker Change: Yeah.
Speaker Change: Your next question comes from line of Alec Stranahan with Bank of America. Please go ahead.
Speaker Change: Yeah.
Speaker Change: So yeah I'm happy to answer that thank you for the question. Yes, we're very excited about having a third pro extend T cell engage your program going into the clinic.
Speaker Change: Okay.
Speaker Change: Hey, guys. This is Matthew on for Alex here, Thanks for taking our questions.
Speaker Change: A couple from my phone 50 525, yes.
Speaker Change: Yeah, I saw recently that the trial sign on Quintin trials for 50 525.
Speaker Change: We believe we've shown some nice early proof of concept with a prior two molecules.
Speaker Change: Includes four parts monotherapy escalation cross expansion I'm combos with Pembroke Escalations Flash expansion would.
Speaker Change: And in terms of the trial design.
Speaker Change: We do know that.
Speaker Change: It would be helpful to have any color on why you chose us to die maybe the ordering of parts and whether you would still explore combination of options with initial monotherapy data looks good.
Speaker Change: There's a good scientific rationale for combining with the checkpoint inhibitor.
Speaker Change: What we've seen with prior T cell engagements is that you can see upregulation of PD L. One upon treatment with a T cell engagement and so.
Speaker Change: Okay.
Speaker Change: So yeah I'm happy to answer that thank you for the question. Yes, we're very excited about having a third CRO extend T cell engage your program going to the clinic.
Mark Eisner: And, you know, we're getting to 64% at week 36. So that compares to Belabor Tide in week 48 of only 12%. So we think we can achieve very high rates of viral suppression in terms of long-term suppression. You know, the Belabor Tide data that are related to, you know, finite treatment are with their higher dose. So that's one thing to consider. And, you know, it's not really something that's in their label right now. So, you know, we are aiming for chronic viral suppressive regimen. We think we can suppress the virus in the vast majority of patients.
It really makes sense in terms of.
Speaker Change: Combining with a checkpoint inhibitor as well with combination is again in the context of other type of T cell engaging <unk> is that we've seen deeper responses and more durable responses with a combination. Hence we are we are considering a combination for the five five to five program as well and as her.
Speaker Change: We believe we've shown some nice early proof of concept with a tier two molecules.
Speaker Change: And in terms of the trial design.
Speaker Change: We do know that that theres, good scientific rationale for combining with the checkpoint inhibitor.
Speaker Change: I mentioned there are four parts. The first part is dose escalation as monotherapy.
Speaker Change: What we've seen with prior T cell engagements is that you can see upregulation of PD L. One upon treatment with a T cell engagement and so it really makes sense in terms of.
Speaker Change: The second part is to look at specific indications and expansion cohorts as monotherapy and then part three and four is similar except in combination dose escalation component.
Speaker Change: Finding with a checkpoint inhibitor as well with combinations again in the context of other T cell engaging <unk> is that we've seen deeper responses and more durable responses with the combination.
Mark Eisner: We're also achieving three log declines in hepatitis B surface antigen. Again, just pointing to the potency and the depth and breadth of our viral suppression for Delta.
Speaker Change: With Pampa listen that followed by an expansion cohort.
Speaker Change: With a combination at again, a data driven decision on which combination or which indications that we would we would pursue.
Mark Eisner: So we're really excited to be moving into the phase three program.
Speaker Change: It's a we are we are considering the combination for the five five to five program as well and as I mentioned there are four parts. The first part is dose escalation as monotherapy.
Roanna Ruiz: The next question comes from the line of Roanna Ruiz with Leering Partners. Please go ahead. Hey, good afternoon.
Speaker Change: Your next question comes from the line of Patrick <unk> with.
Speaker Change: H C Wainwright.
Speaker Change: The second part is to look at specific indications and.
Speaker Change: Please go ahead.
Speaker Change: Yeah.
Nick Gasic: This is Nick Gasic on for Roanna. Thanks for taking our questions. Maybe first on HBV, you know, how should we think about your expectations heading into the 24-week off treatment data for March and easel? You know, what are you hoping to see from a functional cure standpoint relative to the end of treatment data we got at ASLB? And maybe, you know, what implications could this new data have for potential partnership discussions in HBV? Thanks. Thanks for the question, Ed. Go ahead, Mark. No, no, go ahead.
Speaker Change: In expansion cohorts as monotherapy and then part three and four is similar except in combination dose escalation component.
Speaker Change: Okay.
Speaker Change: Hey, Patrick we cannot hear you.
Speaker Change: With Panther listen that followed by an expansion cohort.
Speaker Change: Sorry.
Speaker Change: With a combination at again, a data driven decision on which combination or which indications that we would we would pursue.
Speaker Change: Hi, there. Good afternoon, just the first question is on the CHP program I'm wondering if you can tell us.
Speaker Change: In terms of the functional cure rates that you're looking for would you be looking for those rates in kind of certain levels of.
Speaker Change: Your next question comes from the line of Patrick <unk> with H C. Wainwright.
Speaker Change: H B.
Speaker Change: Samad, Jim a baseline.
Speaker Change: Please go ahead.
Speaker Change: Separately I'm wondering on the HBV program do.
Speaker Change: Yeah.
Speaker Change: Yeah.
Mark Eisner: Yeah, so I was just going to say we are looking forward to presentation of our March data, 24-week off-treatment data this Friday at EASL. This will be the look at our functional cure rates. You know, as you might imagine, we are going into a quiet period because it is, you know, just a very short period between now and then. So we don't want to comment extensively except to say that we have been signaled in the past that we are looking for a 20% in the doublet and a 30% functional cure rate in the triplet. But, you know, I think, you know, stay tuned and you will see the full data at EASL in just a couple of days.
Speaker Change: Do you need data from all the eclipse trials in order to submit for regulatory approval or how should we think about potential for.
Speaker Change: Hey, Patrick we cannot hear you.
Speaker Change: Accelerated approval is that a possibility and then just the last question is just in terms of partnering or collaborations how should we think about both the CHP.
Speaker Change: Sorry.
Speaker Change: Hi, there. Good afternoon, just the first question was on the CHP program I'm wondering if you can tell us.
Speaker Change: In terms of the functional cure rates that you're looking for would you be looking for those rates in kind of certain levels of.
Program, but as well any of the products stem programs and in particular has been seven additional programs in preclinical development. Thanks, so much.
Speaker Change: H B.
Speaker Change: Cause damage them a baseline.
Speaker Change: Separately I'm wondering on the HBV program do.
Speaker Change: Yes. Thank you Patrick for that question, maybe I'll ask Mark first to address your questions on that.
Speaker Change: Do you need data from all of the Eclipse trial in order to submit for regulatory approval or how should we think about potential for.
Speaker Change: The hepatitis B and Delta programs.
Mark Eisner: Yeah, the only thing I would add is that, as we have already mentioned, in January, any further development on the HPV program is contingent on securing a worldwide development and commercial externalization.
Sure. Thanks for the question so for the.
Speaker Change: Accelerated approval is that a possibility and then just the last question is just in terms of partnering or collaborations how should we think about quality.
Speaker Change: March.
Speaker Change: Phase two study in chronic hepatitis b.
Speaker Change: We presented at <unk>, we saw the.
Speaker Change: The best responses at end of treatment in those patients with surface antigen levels of baseline Washington 1000.
Speaker Change: Both the CHP program, but as well the pellet stem programs and in particular has been seven additional programs in preclinical development. Thanks, so much.
Phil Nadeau: Your next question comes from the line of Phil Nadeau with TD Cowan. Please go ahead. Good afternoon, thanks for taking our questions. Two from us. First, on 5500, you mentioned that there have been multiple doses tested since the date in January. We're wondering if you would care to comment on whether those additional doses have continued to suggest a dose response in efficacy in terms of PSA response rate and durability. That's the first question. Then second, on HDV, the RNA positive figures that you gave for the prevalence of the condition, can you clarify, are those overall prevalence or are patients diagnosed?
Speaker Change: This is very consistent with what others are seeing with different mechanisms of action in the field that patients with low surface antigen at baseline or responding better than patients who have surface antigens that are that are very elevated baseline. So we will present the data both all comers and divided by surface antigen.
Speaker Change: Yes. Thank you Patrick for that question, maybe I'll ask Mark first to address your questions on that.
Speaker Change: The hepatitis B and Delta programs.
Mark: Sure. Thanks for the question so for the.
March.
Mark: Phase two study in chronic hepatitis b as we presented at <unk> we saw.
Speaker Change: As we did for the end of treatment data for the functional cure data.
You know in two days, so look forward to that for HPV question. Your question was do we need all three eclipse studies for approval.
Mark: The best responses at end of treatment.
Mark: And those patients with surface antigen levels at baseline was 2000.
Mark: This is very consistent with what others are seeing with different mechanisms of action in the field that patients with low surface antigen at baseline or responding better than patients who have surface antigens that are that are very elevated baseline. So we will present the data both all comers and divided by surface antigen.
Speaker Change: I believe so I believe we need.
Speaker Change: Clips one in eclipse two is our base case for filing package that should be sufficient for approval, we would be looking for an accelerated approval based on and eclipse one the composite of toric target not detected any LTE normalization and for eclipse two target not detected a virological.
Phil Nadeau: having positive RNA. And if it's not diagnosed, do you have a sense of what the diagnosis rate is? Thanks.
Mark Eisner: Yes, thank you, Phil. Maybe I'll start with your last question on delta prevalence. So what we did is we really looked across all available studies, all available reports on delta prevalence, and we sort of started out with determining that, you know, based on all the numbers we could get our about 2 million patients in the U.S. that are HPV positive. And, again, through a very extensive literature search, talking to KOLs, different sources, we found that, on average, about, you know, 4.7% of those B patients are delta antibody positive. And, again, then further down, so that gives you about 92,000 patients, actually, in the United States.
Mark: And as we did for the end of treatment data for the functional cure data.
Speaker Change: We are of course, we have breakthrough therapy designation in the U S and we have time in Europe as well as orphan in Europe. So we are in active dialogue with regulators globally about the program how to accelerate the program and how to get this.
Mark: In two days so look forward to that for HGTV question. Your question was do we need all three eclipse studies for approval.
Mark: I do not believe so I believe we need.
Mark: It clips one in eclipse two is our base case for filing package that should be sufficient for approval, we would be looking for an accelerated approval based on.
This drug combination to patients as quickly as possible because of the unmet need is so high.
Speaker Change: Just one other comment about partnering and I'll turn it back to Maryann as for hepatitis B as we said that we are only going to be able to move hepatitis b forward. If we have a global development and commercialization partner, whereas for hepatitis Delta we are and full study startup mode for all three Eclipse studies and we are all running those studies is very bad.
Mark: And it clips one the composite of toric target not detected in LTE normalization and for eclipse two target not detected virological point.
Mark: Of course, we have breakthrough therapy designation in the U S and we have time in Europe as well as orphan in Europe. So we are in.
Mark Eisner: But if you then think about the patients that are actually going to get treated, those are the patients that, you know, are RNA positive, you know, that are actively viremic. And so, again, based on a lot of sources, we came to the conclusion, as we shared, that about 61,000 patients in the United States would be RNA positive and eligible for treatment for our regimen. So that's sort of, you know, the breakdown of how we got to the numbers.
Speaker Change: Technology or on our own.
Mark: Dialog with regulators globally about the program how to accelerate the program and how to get this drug.
Speaker Change: Okay.
Thank you Mark and I would just add related to your question on partnering up the preclinical programs. Patrick I mean, what is really unique is that you know the universal nature of to put some platform.
Mark: Drug combination to patients as quickly as possible because of the unmet need is so high.
Speaker Change: Just one other comment about partnering and then I'll turn it back to Maryann as for hepatitis B as we said that we are only going to be able to move hepatitis b.
Speaker Change: Allows us to come up very efficiently with new.
Speaker Change: Potential molecule side, which are.
Speaker Change: Forward, if we have a global development and commercialization partner, whereas for hepatitis Delta we are and full study startup mode for all three Eclipse studies and we are all running those studies, it's very biotechnology or on our own.
Speaker Change: All going to be from a T cell engagement perspective, very well engineered because that's a capability. We've had here at fear for a very long time and he cannot combine with me David that masking capability. So to seven preclinical programs that we are that'd be had started with Dolby vision.
Mika Derynck: And then your first question related to 5500 dosing, maybe Mika you can comment. Yeah, we have continued the dose escalation, both at the Q week and the Q3 week dosing. But really, we are not prepared to make any comments. You know, we are encouraged with the 5818 data that also showed a nice dose response. We have that one patient who clearly had a dose who went from 60 micrograms per KG up to 600 micrograms per KG and continued to have a long durability of response lasting over 18 months. So, but sit tight and hopefully we'll be able to say something soon.
Speaker Change: Uh huh.
Speaker Change: Thank you Mark and I would just add related to your question on partnering up with preclinical programs. Patrick I mean, what is really unique is that the universal nature of the <unk> platform.
Speaker Change: Fish in a mix of approaches some of them will be kept for internal development of a number of so that's really high priority targets that align well with our strategic focus and some are open to partnerships and especially you know a dose where we think that could be complementary expertise elsewhere. So it's going to be really.
Speaker Change: Laos us to come up very efficiently with new.
Speaker Change: Sure.
Speaker Change: Molecule side, which.
Speaker Change: All going to be from a T cell engagement perspective, very well engineered because that's a capability. We've had here at CFO very little time, and he cannot combine with me David that Boston capability. So to seven preclinical programs that we are that we have started with Dolby vision.
Speaker Change: A mix of both strategy.
Joseph Stringer: Your next question comes from the line of Joseph Stringer with Needham and company. Please go ahead.
Joseph Stringer: Hi, Thanks for taking our questions just given some of your recent work updating our HCV patient estimates.
Speaker Change: The mix of approaches some of them will be kept for internal development of a number of select really high priority targets that align well with our strategic focus and some are open to partnerships and especially if you think that could be complementary expertise elsewhere. So it's going to be really.
Speaker Change: A question on Asia.
Speaker Change: HDD diagnosis.
Speaker Change: There have been any changes to U S guidelines in.
Matthew: Your next question comes from the line of Alec Stranahan with Bank of America. Please go ahead. Hey guys, this is Matthew on for Alec here. Thanks for taking our question. Maybe a couple from us on 5525. We saw recently that the trial design on QIN trials for 5525 includes four parts, monotherapy escalation slash expansion, and then combos with PEMBRO escalation slash expansion.
Speaker Change: I suppose you anticipate any updates to this.
Speaker Change: In the near term and how big of an impact could this be to.
Speaker Change: A mix of both strategy.
The potentially addressable patient population in the U S.
Speaker Change: Your next question comes from the line of Joseph Stringer with Needham and company. Please go ahead.
Speaker Change: <unk>.
Yeah. Thank you put up a question no change it yet to the to the guidelines for Delta.
Joseph Stringer: Hi, Thanks for taking our questions just given some of your recent work updating our HCV patient estimates.
Speaker Change: Diagnosis, all reflux testing here in the United States.
Mark Eisner: Would be helpful to have any color on why you chose this design, maybe the ordering of the parts, and whether you would still explore combination options if initial monotherapy data looked good. So yeah, I'm happy to answer that. Thank you for the question. Yes, we're very excited about having our third ProXtend T-Cell Engager program go into the clinic. We believe we've shown some nice early proof of concept with the prior two molecules. And in terms of the trial design, we do know that there's good scientific rationale for combining with a checkpoint inhibitor. What we've seen with prior T-Cell Engagers is that you can see upregulation of PD-L1 upon treatment with a T-Cell Engager.
Speaker Change: We do believe that there is a heightened awareness also into complex. Obviously, you know the American Association of.
Speaker Change: A question on <unk>.
Speaker Change: HBV diagnosis have there been any changes to U S guidelines and.
Speaker Change: Flavor diseases. So we are hopeful that we will continue to have that conversation, obviously and that's.
Speaker Change: I suppose do you anticipate any updates to this.
Speaker Change: In the near term and how big of an impact could this be a two.
Speaker Change: When we have <unk> coming up later in the year that that there might be some some announcements in that regard, but thus far no changes.
Speaker Change: The potentially addressable patient population in the U S. Thanks.
Speaker Change: Yes. Thank you put up a question no change just yet to the to the guidelines for Delta.
Speaker Change: Reflex testing that is.
Speaker Change: However, very effectively already deployed in Europe and they are you know they are really seeing that if you just bayside notices based on risk factors et cetera that you're really not finding the patients. It's really only been patients are tested for hepatitis B and Monday found to be positive yeah.
Speaker Change: Diagnosis of reflux testing here in the United States.
Speaker Change: We do believe that there is a heightened awareness also in the context of the American Association of liver diseases. So we are hopeful that we will continue to have that conversation, obviously and that's when.
Speaker Change: <unk> got such a delta that you end up identifying many more patients.
Mark Eisner: And so it really makes sense in terms of combining with a checkpoint inhibitor as well with combinations, again, in the context of other T-Cell Engagers, is that we've seen deeper responses and more durable responses with the combination. Hence, we are considering the combination for the 5-5-2-5 program as well. And as you mentioned, there are four parts. The first part is dose escalation as monotherapy. The second part is to look at specific indications in expansion cohorts as monotherapy. And then parts three and four is similar, except in combination, a dose escalation component with a pembrolizumab, followed by an expansion cohort with a combination at, again, a data-driven decision on which combination or which indications that we would pursue.
Speaker Change: When we have <unk> coming up later in the year that there might be some some announcements that took ARPA, thus far no changes.
Speaker Change: Mark anything to add there from your perspective.
No I think you captured it very well Maryann just to state that we do believe that the.
Speaker Change: On reflex testing that is however.
Prevalence of diagnosed H D V or delta is underestimated because of the lack of reflux testing in the United States. Its just you know I think once.
Speaker Change: The effective fee already deployed in Europe, and you know they are really seeing that if you just bayside notices based on risk factors et cetera are you reading of finding the patients. It's treating only one patient sub tested for hepatitis B and Monday found to be positive yeah automatically to asset for Delta.
Speaker Change: We have our therapy approved on the market assuming a success that we would expect with such an effective product that this will drive more.
Speaker Change: More diagnosis and more disease prevalence I think there's other examples of similar cases like this in medicine, but to to your point, we were still not seeing.
You end up in identifying many more patients.
Mark: Mark anything to add there from your perspective.
Mark: No I think you captured it very well Maryann just state that we do believe that the.
Speaker Change: Reflex testing deployed the United States at this time.
Mark: Prevalence of diagnosed H D V or delta is underestimated because of the lack of reflux testing in the United States.
Speaker Change: Okay.
Rich Lucky: This concludes the Q&A session of the call. Thank you for participating and I will turn the call back over to rich.
Mark: It's just you know I think once.
Mark: We have <unk>.
Patrick Trucchio: Your next question comes from the line of Patrick Trucchio with HC Wainwright. Please go ahead. Hey, Patrick, we cannot hear you. Oh, sorry. Hi there. Good afternoon. Just the first question is on the CHB program.
Mark: Therapy approved on the market, assuming our success there.
Rich Lucky: Thank you Eric and thank you all for your continued support and for joining US today, we look forward to updating you on our progress in the coming months operator, you may now in the call.
Mark: We would expect with such an effective product that this will drive.
Mark: More diagnosis and more disease prevalence I think there's other examples of a similar cases like this in medicine, but to your point, we were still not seeing the.
Mark: Reflex testing deploy the United States at this time.
Mark Eisner: I'm wondering if you can tell us, you know, in terms of the functional cure rates that you're looking for, would you be looking for those rates in kind of certain levels of HB surface antigen baseline? And separately, I'm wondering on the HDV program, do you need data from all the Eclipse trials in order to submit for regulatory approval? Or how should we think about potential for, you know, accelerated approval? Is that a possibility?
Mark: Okay.
Rich: This concludes the Q&A session of the call. Thank you for participating and I will turn the call back over to rich.
Speaker Change: Thank you Eric and thank you all for your continued support for joining US today, we look forward to updating you on our progress in the coming months operator, you may now in the call.
Rich: Yeah.
Rich: Yeah.
Mark Eisner: And then just the last question is, just in terms of partnering or collaboration, how should we think about both the CHB program, but as well any of the ProXtend programs? And in particular, there's seven additional programs in preclinical development. Thanks so much. Yes, thank you, Patrick, for that question. Maybe I'll ask Mark first to address your questions on the Hepatitis B and Delta program. Sure, thanks for the question. So for the March Phase 2 study in chronic hepatitis B, you know, as we presented at ASLD, we saw the best responses at end of treatment in those patients with surface antigen levels at baseline of less than 1000.
Mark Eisner: This is very consistent with what others are seeing with different mechanisms of action in the field that patients with low surface antigen baseline are responding better than patients who have surface antigens that are very elevated at baseline. So we will present the data, both all comers and divided by surface antigen, as we did for the end of treatment data for the functional cure data, you know, in two days. So look forward to that. For your HDV question, your question was, you know, do we need all three ECLIPSE studies for approval? I do not believe so.
Mark Eisner: I believe we need ECLIPSE 1 and ECLIPSE 2 as our base case for a filing package that should be sufficient for approval. We would be looking for an accelerated approval based on ECLIPSE 1, the composite of target not detected in ALT normalization, and for ECLIPSE 2, target not detected at a virologic endpoint. We are, of course, we have breakthrough therapy designation in the U.S., and we have crime in Europe, as well as orphan in Europe. So we are in active dialogue with regulators globally about, you know, the program, how to accelerate the program, and how to get this drug combination to patients as quickly as possible because of the unmet need is so high.
Marianne DeBacker: Just one other comment about partnering, and I'll turn back to Marianne, is for hepatitis B, as we've said, that we are only going to be able to move hepatitis B forward if we have a global development and commercialization partner, whereas for hepatitis delta, we are in full study startup mode for all three ECLIPSE studies, and we are running those studies as Vero biotechnology on our own. Thank you, Mark. And I would just add, related to your question on partnering of the pre-clinical programs, Patrick, I mean, what is really unique is that, you know, the universal nature of the PRO-EXTENSA platform allows us to come up very efficiently with new potential therapeutic molecules, right?
Marianne DeBacker: Which are going to be, from a T-cell engager perspective, very well engineered, because that's the capability we've had here for a very long time, and we can now combine it really with that masking capability. So, the seven pre-clinical programs that we are, that we have started will be, you know, we envision a mix of approaches. Some of them will be kept for internal development, you know, a number of select really high-priority targets that align well with our strategic focus. And some are open to partnerships, and especially, you know, those where we think there could be complementary expertise elsewhere.
Marianne DeBacker: So, it's going to be really a mix of both strategies.
Joseph Stringer: Your next question comes from the line of Joseph Stringer with Needham and Company. Please go ahead. Hi, thanks for taking our questions. Just given some of your recent work updating your HPV patient estimates, I had a question on HPV diagnosis. Have there been any changes to US guidelines? And I suppose, do you anticipate any updates to this in the near term? And how big of an impact could this be to the potentially addressable patient population in the US? Thanks. Yeah, thank you for that question.
No changes yet to the to the guidelines for delta diagnosis or reflex testing here in the United States. You know, we do believe that there is a heightened awareness also in the context of, you know, the American Association of Liver Diseases. So we are hopeful that, you know, we will continue to have conversation obviously, and that's when we have ASOT coming up later in the year that there might be some some announcements in that regard. But thus far, no changes on reflex testing that is, however, very effectively already deployed in Europe. And they're, you know, they are really seeing that if you just base diagnosis based on risk factors, etc, you're really not finding the patients.
It's really only when patients are tested for hepatitis B, and when they're found to be positive, they're automatically tested for delta, that you end up identifying many more patients.
Mark, anything to add there from your perspective? No, I think you captured it very well, Marianne, just to state that we do believe that the prevalence of diagnosed HDV or Delta is underestimated because of the lack of reflex testing in the United States. It's just, you know, I think once we have our therapy approved on the market, assuming success, that we would expect with such an effective product that this will drive more diagnosis and more disease prevalence. I think there's other examples of similar cases like this in medicine, but to your point, we're still not seeing the reflex testing deployed in the United States at this time.
This concludes the Q&A session of the call. Thank you for participating. And I'll turn the call back over to Richard. Thank you, Eric. And thank you all for your continued support for joining us today. We look forward to updating you on our progress in the coming months. Operator, you may now end the call.