Q2 2025 Arvinas Inc Earnings Call

Operator: Thank you for standing by. At this time, I would like to welcome everyone to ARVINAS' second quarter 2025 earnings call. All lines have been placed on mute to prevent any background noise. After this speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. Thank you. I would now like to turn the conference over to Jeff Boyle, ARVINAS' Vice President of Investor Relations. Please go ahead.

Thank you for standing by at this time, I would like to welcome everyone. To Venus second quarter 2025 earnings call allies have been pleased to mute to prevent any background noise. After this speakers remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star followed by the number 1 on your telephone keypad. Thank you. I would now like to turn the conference over to Jeff Bole or Venus vice president of investor relations. Please go ahead.

Jeff Boyle: Good morning, everyone, and thank you for joining us. Earlier today, we issued a press release with our second quarter 2025 financial results, which is available on the Investor and Media section of our website at arvinas.com. Joining the call today are John Houston, Arvinas' Chief Executive Officer, President and Chairperson; Noah Berkowitz, our Chief Medical Officer; Angela Cacace, our Chief Scientific Officer; and Andrew Saik, our Chief Financial Officer. Before we begin the call, I will remind you that today's discussion contains forward-looking statements that involve risks, uncertainties, and assumptions. These risks and uncertainties are outlined in today's press release and in the company's recent filing with the Securities and Exchange Commission, which I urge you to read. Our actual results may differ materially from what is discussed on today's call. Now I will turn the call over to John. John?

Good morning everyone and thank you for joining us.

Earlier today, we issued a press release with our second quarter 2025 financial results, which are available in the investor and media section of our website and on venice.com.

Joining the call today, are John Houston, our Venus's chief executive officer president and chairperson no of Berk our chief medical officer. Angela Casey, our chief scientific officer and Andrew sake, our Chief Financial Officer.

Before we begin the call, I'll remind you that today's discussion contains forward-looking statements that involve risks and uncertainties and assumptions.

These risks and uncertainties are outlined in today's press release and in the company's recent filing with the Securities and Exchange Commission, which I urge you to read our actual results, many different material from what is discussed on today's call. And now I'll turn the call over to John John.

John Houston: Thanks, Jeff. Good morning, everyone, and thank you for joining us today. As outlined in our second quarter earnings release this morning, our business is in a solid position with strong momentum. It was an eventful and exciting quarter at Arvinas, with significant clinical and regulatory progress across our pipeline of PROTAC protein degraders. We continued making significant strides across our early-stage programs, where we are enrolling patients in three Phase 1 trials across our neuro and oncology portfolio, including the recently initiated trial with our KRAS G12D degrader ARV-806. During the quarter, we also presented compelling first-in-human data from ARV-102, our AR degrader, and preclinical data for our BCL6 degrader ARV-393. I am also pleased to share an update on our androgen receptor degrader, Vepdegestrant, which we licensed to Pfizer in 2024.

Thanks, Jeff. Good morning, everyone. And thank you for joining us today as outlined in our second quarter earnings release this morning. Our business is in a solid position with strong momentum. It was an eventful and exciting quarter at our Venice with significant clinical and Regulatory programs across our pipeline of prototype. Degraders,

Including the recently initiated good trial with our cos g12d degree. Our arv 806

During the quarter. We also presented compelling first in human data from arv 102 or L2 degrader and preclinical data for our bcl6. Degrader arv. 393

John Houston: We are pleased to see that Pfizer is rapidly progressing the asset and announced the recent initiation of two combination Phase 2 trials that will further advance Vepdegestrant towards patients. One trial is in metastatic castration-resistant prostate cancer, and the other is metastatic hormone-sensitive prostate cancer, and both will identify recommended Phase 3 doses and we believe further validate our ability to develop potentially best-in-class protein degraders. As a reminder, our license agreement with Pfizer includes up to $1 billion in development, regulatory, and commercial milestones, as well as tiered royalties. The accomplishments from across our portfolio are the latest in a long stream of successes at Arvinas. At the same time, we have recognized the ongoing need to enhance our financial position and set Arvinas up for future success. To that end, last quarter, we announced a company-wide restructuring that extended our cash runway and included two key elements.

I'm also pleased to share an update on our antigen receptor degree that looks like alumite which realizes to navarus in 2024. We are pleased to see that Novant is rapidly progressing. The assets and announced the recent initiation of 2 combination, Phase 2 trials, that will further Advance. Let's take illumi towards patients.

1 file is a metastatic castration resistant, prostate cancer, and the other is metastatic hormone sensitive prostate, cancer, and both will identify recommended phase 3, Doses, and we believe further, validate our ability to develop potentially best-in-class protein degraders.

As a reminder, our license agreement with Novartis includes up to 1 billion dollars in development Regulatory and Commercial Milestones as well as to your royalties.

John Houston: First, we reprioritized our research pipeline, cutting a number of programs and continuing investment in our assets with the greatest potential value. Second, we streamlined operations across the organization by reducing our workforce by approximately one-third. While difficult, these decisive actions bolstered our financial profile and drove efficiencies across the company. They also enabled us to turn our full attention to our near-term imperatives, which are first, working with Pfizer or identifying another partner to advance Vepdegestrant towards commercial launch; second, achieving critical data milestones from our pipeline in the next 12 months; and third, carefully allocating capital to support those milestones efficiently. I will return to those three imperatives in a few moments, but I would first like to say a few words about the recent announcement of my planned retirement and a CEO transition for Arvinas.

The accomplishments from across our portfolio are the latest in the long stream of successes that are Venus. At the same time, we have recognized, the ongoing need to enhance our financial position and set our Venus up for future success to that end last quarter. We announced a companywide restructuring that extended our cash Runway and included 2 key elements first. We re prioritize our research pipeline cutting a number of programs.

And continuing investment in our assets with the greatest potential value. And second we streamline operations across the organization by reducing our Workforce by approximately 1/3.

While difficult, these designs of actions, both of our financial profile and drove efficiencies across the company.

They also enabled us to turn our full attention to our near-term imperatives which are first working with fisa or identifying another partner to advance towards commercial launch. Second achieving critical data Milestones from our pipeline in the next, 12 months. And third carefully, allocating Capital to support those Milestones efficiently.

John Houston: Having recently strengthened our financial profile and with a clear line of sight into those near-term imperatives, the board and I agreed it is the right time to initiate a search for a new CEO. As with any public company, succession planning is a priority for our board of directors, and I have been talking to the board about the potential timing of this transition for well over a year. While there never seems to be a good time, we agreed that waiting until after our first pivotal data readout was essential. We are now conducting a rigorous and thoughtful CEO search process, spearheaded by independent directors on our Nominating and Corporate Governance Committee, with the assistance of a leading executive search firm.

As we turn to those 3 pairs in a few moments. But I'd first like to say a few words about the recent announcement of my planned retirement, and the CEO transition for our Venice. Having recently, strengthened our financial profile and with a clear line of sight into those near-term, imperatives the board and I agreed, it is the right time to initiate a search for a new CEO.

As with any public company succession planning is a priority for our board of directors and I have been talking to the board about the potential timing of this transition for well, over a year while there never seems to be a good time. We agreed that waiting until after our first pivotal data readout was essential.

John Houston: The board is fully engaged and intent on finding the right CEO to lead Arvinas into our next chapter and help shape our long-term strategy to create value for shareholders and deliver on our mission to serve patients. I am also honored to continue as Chair of the Arvinas board once I step down from the CEO role. For now, our long-term strategy is driven by the imperatives I mentioned above: advancing Vepdegestrant to launch by Pfizer or another partner, achieving critical data milestones, and efficiently allocating capital. I will spend a few minutes discussing our Vepdegestrant strategy before turning the call over to Noah Berkowitz and Angela Cacace, who will provide updates and discuss upcoming milestones for our clinical programs. Andrew Saik will then provide a financial overview and some thoughts on capital planning.

We are now conducting a rigorous and thoughtful CEO, search process spearheaded by independent directors on our nominating and corporate governance committee with the assistance of a leading executive Search firm. The board is fully engaged and intent on finding the right CEO to lead our Venice into our next chapter and help shape our long-term strategy to create value for shareholders. And deliver on our mission to serve patients. I'm also honored to continue as chair of their Venice board. Once I step down from the CEO role

For now, our long-term strategy is driven by the imperatives I mentioned above: advancing the vet deck to launch by Pfizer or another partner, achieving critical data and milestones, and efficiently allocating capital.

I'll spend a few minutes. Discussing our vet deck strategy before turning the call over to Noah and Angela who will provide updates and discuss upcoming milestones for our clinical programs.

John Houston: First, regarding Vepdegestrant, our collaboration with Pfizer was signed in 2021 with the intention for Vepdegestrant to be developed as a monotherapy and in combinations across the adjuvant first and second-line settings. With that plan, the idea of having 50/50 co-development and commercialization was very attractive. We are now on the threshold of Vepdegestrant potentially becoming a best-in-class treatment in its first indication, second-line monotherapy treatment in ESR1 positive HER2 negative metastatic breast cancer. However, the recent decision to remove the combination pivotal trials from our development plans with Pfizer has created a situation where a 50/50 co-commercialization agreement no longer makes sense and we are actively reworking our collaboration. Should the negotiations lead to Vepdegestrant being returned to Arvinas, we are prepared to seek a party to commercialize and further develop Vepdegestrant.

Andrew will then provide a financial overview and some thoughts on Capital planning.

First regarding that day, our collaboration with fiser was signed in 2021 with the intention for vent de to be developed as a monastery. And in combination with the agent first and second line settings with that plan, the idea of having 50/50 co-development, and commercialization was very attractive.

We are now on the threshold of vent deck potentially becoming a best-in-class treatment in its first indication. Second line Monastery. Be treatment in esl1, ER, positive her2 negative metastatic breast cancer. However, the recent decision to remove the combination pivotal trials from our development, plans with fizer has created a situation for a 50/50 cool commercialization agreement, no longer make sense and we're actively reworking our collaboration.

John Houston: Reaching a positive conclusion for Vepdegestrant is a critical step in maximizing its value while also allowing us to focus on a promising clinical pipeline. Preclinical data has shown that ARV-102, ARV-393, and ARV-806 are all differentiated from inhibitors and other degraders. With compelling clinical data milestones over the next year, we believe our maturing pipeline will be a significant value driver for the company and our shareholders. Taken together, we are advancing a very exciting pipeline and applying our PROTAC protein degraders technology to new areas in both neuroscience and oncology, where we can truly differentiate from other mechanisms of action.

Should the negotiations lead to vent their being returned to our Venice. We are prepared to seek a party to commercialize and further develop vent egg.

Clinical pipeline.

Preclinical data has shown that ERV 102, ERV 393, and ARV 806 are all differentiated from inhibitors and other degraders.

With compelling clinical data, Milestones over the next year. We believe our maturing pipeline will be a significant value driver for the company and our shareholders.

John Houston: Operating from a strong financial position, underpinned by an extended cash runway, efficient capital allocation, and a development strategy that unlocks the potential of our platform to bring patients important treatments, we are confident in our path forward and in our ability to maximize value for shareholders and benefits for patients. With that, I will turn the call over to Noah.

Taken together, we are advancing at a very exciting pipeline, applying our PROTAC technology to new areas in both neuroscience and oncology, where we can truly differentiate from other mechanisms of action.

Operating from a strong financial position, underpinned by an extended cash, Runway efficient Capital, allocation and a development strategy, that unlocks the potential of our platform to bring patience important treatments. We are confident in our path forward and in our ability, to maximize value for shareholders and benefits. For patients with that, I'll turn the call over to Noah.

Noah Berkowitz: Thanks, John, and good morning, everyone. Our pipeline continues to progress at a remarkable pace, demonstrating the vast potential of our PROTAC platform. I will begin with our most advanced neuroscience program, ARV-102. We have designed investigational oral PROTAC degraders to cross the blood-brain barrier and selectively degrade leucine-rich repeat kinase 2, or LARK2. LARK2 is a large multi-domain scaffolding kinase that plays a critical role in effective endolysosomal trafficking. Unlike traditional small molecule inhibitors that only block LARK2's kinase activity, LARK2 degraders eliminate pathologic scaffolding function, GTPase activity, and the kinase activity of LARK2 implicated in this disease. We believe our lead LARK2 degrader, ARV-102, is particularly well positioned to be evaluated in two diseases where there are no disease-modifying therapies available. The first is Parkinson's disease, or PD, a disease where increased LARK2 expression and activity contributes to neurodegeneration and its pathogenesis, making it a rational therapeutic target.

Thanks John and good morning everyone. Our pipeline continues to progress at a remarkable taste demonstrating the vast potential of our protest platform. I'll begin with our most advanced Neuroscience program arv 102.

Noah Berkowitz: The second is progressed supranuclear palsy, or PSP, a disease where genetic variations in LARK2 are associated with PSP progression. Additionally, we have published data associating the tau pathology of PSP with LARK2-mediated endolysosomal dysfunction, which again makes this a very rational therapeutic target. ARV-102 is the only PROTAC we know of in the clinic to demonstrate deep brain penetration in non-human primates and now blood-brain barrier penetration in humans. As presented at the ADPD Congress, ARV-102 is well tolerated at single doses up to 200 milligrams and at multiple doses up to 80 milligrams. No serious adverse events after single and multiple oral doses in healthy volunteers were observed. Single and multiple doses of ARV-102 demonstrated dose-dependent exposure in the central nervous system by cerebrospinal fluid, or CSF sampling.

We have designed investigational. Oral protect degraders to cross the blood brain barrier and selectively, degrade leucine-rich, repeat kinase 2, or Lark, 2, Lark, 2 is a large multi-domain scaffolding kinase. That plays a critical role in effective endolysosomal trafficking unlike traditional small molecule Inhibitors. That only block Lark 2's kinase activity. Lark, 2 degraders, eliminate pathologic scaffolding function, GPA activity, and the kindness activity of Lark 2, implicated in this disease. We believe our lead Lark 2. Degrader arv 102 is particularly well positioned to be evaluated in 2 diseases where there are no disease, modifying therapies available. The first is Parkinson's Disease or PD a disease where increased Lark to expression and activity contributes to neurodegeneration and its pathogenesis making it a rational therapeutic Target.

Target and the second is Progressive super nuclear policy or PSP a disease where genetic variations in. L2 are associated with PSP progression. Additionally, we have published data associating, the tal pathology of PSP with Lark 2, mediated endolysosomal dysfunction, which again makes this a very rational therapeutic Target arv. 102 is the Only protac We Know of in the clinic to demonstrate deep brain penetration in non-human primates and now

Blood brain barrier. Penetration in humans as presented at the adpd Congress arv. 102 is well, tolerated at single doses up to 200 milligrams and at multiple doses up to 80 milligrams, no serious Adverse Events after single and multiple oral doses in healthy, volunteers were observed.

Noah Berkowitz: This was associated with substantial degradation of LARK2 protein in the peripheral blood and the CSF and on-target activity with levels of engagement not reported with inhibitors currently in the clinic. We believe the high levels of target engagement, enhanced potency, and pathway engagement demonstrated with ARV-102 will differentiate it from clinical stage inhibitors, which in preclinical studies have not shown the same ability as ARV-102 to move important biomarkers in the CSF. These PK and PD properties and acceptable safety and tolerability profile support further study of LARK2 degraders in PD and PSP. Dosing of the Phase 1 single ascending dose cohort in patients with Parkinson's disease is complete, and we expect to present initial data confirming pathway engagement later this year.

Single and multiple doses of arv 102, demonstrated dose dependent exposure in the central nervous system by cerebral, spinal fluid or CSF sampling. This was associated with substantial degradation of Lark, 2, protein in the peripheral blood, and the CSF and on target activity, with levels of Engagement, not reported with Inhibitors, currently in the clinic.

Noah Berkowitz: We will also initiate multiple dose cohorts in patients with PD in the coming weeks, as well as a trial in PSP in the first half of 2026. In parallel to the advancement of ARV-102, we are making nice progress with ARV-393, our BCL6 degrader, and ARV-806, our KRAS G12D degrader, which entered the clinic in the second quarter. It is too early for me to share clinical results for these exciting new clinical stage assets, but Angela will share some of the compelling preclinical data supporting the advance of both in the clinic. First, I would like to provide some regulatory updates regarding Vepdegestrant. We have submitted the new drug application for Vepdegestrant. This represents another significant first for Arvinas, the first PROTAC protein degrader to enter clinical trial and have a positive readout in a Phase 3 trial.

We believe the high levels of Target engagement, enhance potency and pathway engagement. Demonstrated with arv 102 will differentiate it from Clinical stage Inhibitors which in preclinical Studies have not shown the same ability as arv 102 to move important biomarkers in the CSF. These PK and PD properties and acceptable, safety and tolerability profile supports further study of L2. Degraders in PD and PSP dosing of the phase 1, single ascending dose cohort and patients with Parkinson's diseases, complete, and we expect to present initial data confirming pathway engagement later. This year, we will also initiate multiple dose cohorts in patient.

With PD in the coming weeks as well as a trial in PSP in the first half of 2026.

In parallel, to the advancement of arv 102, we are making nice progress with arv. 393 our bcl6 degrader and arv 806 rkes g12d degrader, which entered the clinic in the second quarter, it is too early for me to share clinical results for these exciting new clinical stage assets. But Angela will share some of the compelling preclinical data supporting the advance of both in the clinic.

Noah Berkowitz: It's also the first ever new drug application submitted for a PROTAC. The NDA was supported by Veritac-2 data that were presented at the ASCO Oral Late-Breaking Session and simultaneously published in the New England Journal of Medicine. The enthusiasm among physicians generated by Veritac-2 data was very rewarding. Later this year, we plan to present the patient-reported outcomes data from the Veritac-2 trial. We believe these data disclosures reinforce Vepdegestrant's profile as a potential best-in-class monotherapy. I'll now turn the call over to Angela. Angela?

We have submitted the new drug application for vepe. This represents another significant first for our Venice. The first protect a greater to enter clinical trials and have a positive readout in a phase 3 trial. It's also the first ever new drug application submitted for a Protek

The NDA was supported by Varitek 2 data that were presented at the ASCO. Oral late breaking session and simultaneously published in the New England, Journal of Medicine. The enthusiasm among Physicians generated by Varitek. 2 Data was very rewarding later. This year, we plan to present the patient reported outcomes data from the veritech 2 trial. We believe these data disclosures reinforced Vex profile, as a potential best-in-class monotherapy. I'll now turn the call over to Angela Angela.

Angela Cacace: Thanks, Noah, and good morning, everyone. ARV-393, our investigational oral PROTAC designed to degrade B-cell lymphoma 6 protein, or BCL6, is an exciting asset that demonstrates the power and breadth of our platform. BCL6 is a previously undrugged transcription factor, a master regulator of multiple cellular processes during B-cell development, including proliferation, survival, and apoptosis. Altered BCL6 activity has been implicated as an oncogenic driver in several subtypes of non-Hodgkin lymphoma, making it a rational therapeutic target with initial clinical validation emerging. PROTAC-mediated degradation has the potential to overcome the historically undruggable nature of BCL6. With its iterative activity, ARV-393 potently and rapidly degrades the BCL6 protein, which is critical to overcoming its rapid resynthesis rate and sustaining anti-tumor activity. In Q2 2025, we presented two sets of preclinical data for ARV-393.

Thanks Noah and good morning, everyone. Arv 393 are investigational oral protac designed to degrade B cell lymphoma 6, protein, or bcl6 is an exciting asset that demonstrates, the power and breadth of our platform DCL. 6 is a previously, undruggable cellular processes, during B cell development, including proliferation survival and Aptos,

altered bcl6 activity has been implicated as an oncogenic driver in several subtypes of non-con, lymphoma making it a rational therapeutic Target with initial clinical validation emerging

Protac, mediated degradation has the potential to overcome. The historically, undruggable nature of bcl6.

With its iterative activity arv. 393 potently and rapidly degrades the bcl6 protein which is critical to overcoming. Its rapid resent assist rate and sustaining anti-tumor activity.

Angela Cacace: First, at the American Association for Cancer Research annual meeting in April, we presented new preclinical data highlighting the therapeutic potential of ARV-393 in combination with standard-of-care biologics, chemotherapy, and small molecule inhibitors targeting cooperative oncogenic drivers. ARV-393 combinations demonstrated increased tumor growth inhibition, including tumor regression in preclinical models of aggressive B-cell lymphoma. These data underscore the potential of ARV-393 to become a backbone therapy for the development of rational, mechanism-informed, chemo-free, or all-oral therapeutic options with the potential to improve patient outcomes and convenience. In June, at the European Hematology Association Conference, we presented new data demonstrating the potent single-agent efficacy of ARV-393 in patient-derived systemic models of angioimmunoblastic T-cell lymphoma and transformed follicular lymphoma. To our knowledge, these are the first preclinical evidence of an efficacious BCL6-targeted degrader in human models of these diseases.

In second quarter of 2025 we presented 2, sets of pre-clinical data for arv. 393 first at the American Association for cancer research, annual meeting in April, we presented new pre-clinical data highlighting the therapeutic potential of arv 393 in combination with standard of care, biologics chemotherapy, and small molecule Inhibitors targeting Cooperative conic drivers.

arv 393 combinations, demonstrated increased tumor growth inhibition, including tumor regressions, in preclinical models of aggressive B cell lymphoma

These data underscore the potential of arv. 393 to become a backbone therapy for development of rational mechanism, informed chemo, free or all oral therapeutic options with the potential to improve patient, outcomes and convenience.

In June at the European hematology Association conference, we presented new data demonstrating the potent, single agent efficacy of arv 393 and patient. Derived systemic models of angio immunog cell lymphoma and transformed follicular lymphoma

Angela Cacace: These data highlight the broad utility of ARV-393 across non-Hodgkin lymphoma subtypes with unmet need beyond DLBCL. Later this year, we also expect to share preclinical data showing the combinability of ARV-393 with glofitamab, a CD3/CD20 bispecific antibody, and an emerging standard of care for DLBCL that supports our plan to evaluate this combination in an upcoming trial. We are excited about the potential here given ARV-393's ability to increase CD20 expression, which provides rationale for the exploration of ARV-393 with CD20-targeted agents and in the context of low or loss of CD20 expression. We also plan to share the initial clinical data with ARV-393 later this year. As you have heard from Noah Berkowitz, I am pleased to report that we have initiated a Phase 1 clinical trial of ARV-102, our novel PROTAC protein degrader targeting KRAS G12D.

To our knowledge. These are the first pre-clinical evidence of an efficacious bcl6 targeted. Degrader in human models of these diseases.

These data highlights the broad utility of ARB 393 across non-hodgkin, lymphoma subtypes with unmet need Beyond dlbcl.

Later this year, we also expect to share preclinical data showing the combinability of ARB 393 with glofitamab, a CD3-CD20 bispecific antibody and an emerging standard of care for DLBCL, which supports our plan to evaluate this combination in an upcoming trial.

We are excited about the potential here. Given arvs 393 stability to increase cd20 expression, which provides rationale for the exploration of arv 393 with cd20, targeted agents and in the context of low for loss of cd20 expression,

We also plan to share the initial clinical data with arv. 393 later this year

Angela Cacace: The trial has progressed rapidly through the first patient cohort, reflecting strong interest from clinical investigators and underscoring the high unmet need for effective KRAS-targeted therapies. KRAS G12D is a well-characterized oncogenic driver associated with poor prognosis and resistance to standard treatments across major tumor types, including pancreatic, colorectal, and non-small cell lung cancers. ARV-102 has demonstrated compelling preclinical activity with high potency and clear differentiation from both KRAS inhibitors and other degraders currently in the clinic. Notably, because of the catalytic activity of our PROTAC protein degrader, ARV-102 has shown it can overcome KRAS resynthesis and increased expression, a major clinically relevant emerging mechanism of resistance that existing inhibitors have failed to address. Our PROTAC protein degrader binds to and degrades both the active and inactive forms of KRAS G12D, achieving potent and durable elimination of the target rather than inhibition in all models tested.

12d.

The trial has progressed rapidly through the first patient cohort, reflecting, strong interest from Clinical investigators and underscoring, the high unmet need for Effective KRA targeted Therapies.

KRA g12d is a well-characterized, encogen driver associated with poor prognosis, and resistance to standard treatments across major tumor types, including pancreatic colorectal, and non small cell lung cancers.

Arv 806 has demonstrated compelling pre-clinical activity, with high potency, and clear differentiation from both kras, Inhibitors and other degraders. Currently in the clinic notably because of the catalytic activity of our protacs airv 806 has shown it can overcome Kraft, recents this and increased expression.

A major clinically relevant emerging mechanism of resistance that existing Inhibitors have failed to address.

Angela Cacace: In preclinical studies, ARV-102 achieved in vitro potency approximately 25 times greater than KRAS inhibitors and 40 times greater than the leading clinical stage degrader, demonstrating strong potential for differentiation from both KRAS inhibitors and degraders currently in the clinic. Furthermore, ARV-102 exhibits dose-dependent, selective, robust anti-tumor activity, culminating in regressions across preclinical models of KRAS G12D mutant cancers. These results highlight the strong therapeutic potential of ARV-102 and support its continued and rapid advancement in the clinic. We look forward to updating you on our clinical progress and anticipate sharing preclinical data from ARV-102 and the first ever data from our oral pan-KRAS degrader program later this year. With that, I will turn the call over to Andrew Saik to review our quarterly financial information.

Our protac binds to and degrades both the active and inactive forms of kft, g12d achieving potent and durable, elimination of the target, rather than inhibition in all models tested.

In pre-clinical studies. Arv 806, achieved in vitro potency, approximately 25 times greater than kras Inhibitors and 40 times greater than the leading clinical stage degrader demonstrating strong potential for differentiation from both kras, Inhibitors and degraders. Currently in the clinic,

Furthermore, arv 806 exhibits dose dependent selective robust anti-tumor activity. Culminating in regressions across pre-clinical models of KRA g12d mutant cancers,

These results highlight the strong therapeutic potential of are the 806 and support its continued and Rapid advancement in the clinic.

we look forward to updating you on our clinical progress and anticipate sharing pre-clinical data from arv 806 and the first ever data from our oral pan, KRA to Greater program later this year,

With that, I'll turn the call over to Andrew to review our quarterly financial information.

Andrew Saik: Thanks, Angela, and good morning, everyone. I am pleased to provide financial highlights for the second quarter ended June 30, 2025, and expand on our approach to capital allocation and development strategy. As a reminder, detailed financial results for the second quarter are included in the press release we issued this morning. During the quarter, we took significant action to reduce costs and increase efficiency across the organization. These actions included a reprioritization and reduction to our research portfolio, as well as a reduction of approximately one-third of our total workforce. When combined with the announced changes to our Vepdegestrant development plan, our cash runway was extended into the second half of 2028. These changes will make us leaner and more efficient as we work towards a promising stretch of catalysts over the next 12 months.

Thanks Angela, and good morning everyone. I'm pleased to provide financial highlights for the second quarter and in June 30th 2025 and expand on our approach to Capital allocation and development strategy.

As a reminder detailed Financial results for the second quarter are included, in the press release, we issued this morning.

During the quarter, we took significant action to reduce costs and increase efficiency across the organization.

These actions included a reprioritization and reduction to our research portfolio, as well as a reduction of approximately 1/3 of our total Workforce.

When combined with the announced changes to our vet development plan, our cash runway was extended into the second half of 2028.

Andrew Saik: As I mentioned previously, the restructuring was focused on reducing internal costs without having an impact on the clinical stage programs that will drive value over the next several years. We will maintain our disciplined and focused approach to capital allocation, and our development strategy will be focused on bringing pipeline programs to major clinical inflection points. With respect to Vepdegestrant, we anticipate relatively minimal costs to prepare the market in the coming months. Our current agreement with Pfizer includes establishing a go-to-market strategy that will benefit both sides of the partnership. While we continue to believe that Vepdegestrant is a potentially best-in-class asset, given the changes to the development plan, we have determined that it is no longer viable for us to build out our commercial infrastructure as we had previously planned.

These changes will make us leaner and more efficient as we work towards a promising. Stretch of catalysts over the next 12 months.

As I mentioned previously, the restructuring was focused on reducing internal costs without having an impact on the clinical stage programs that will drive value over the next several years. We will maintain our discipline and focused approach to capital allocation, and our development strategy will be centered on bringing pipeline programs through major clinical inflection points.

With respect to that day, we anticipate relatively minimal costs to prepare the market in the coming months.

Our current agreement with fiser includes establishing a go to market strategy, that will benefit both sides of the partnership.

Andrew Saik: As John Houston said earlier, we are in active discussions with Pfizer to rework our collaboration to determine the most efficient way to make this important drug available to patients if approved. Across our pipeline, we have a rich set of catalysts coming up in the next year for both our oncology and neuroscience portfolios. With our strong balance sheet, we have sufficient resources to move these exciting programs forward to key value inflection points. We have seen great clinical success here in the past, both in the development of Vepdegestrant in partnership with Pfizer and in the platform validating out-licensing of lexdegalutamide to Novartis. We are excited to continue the development of the next generation of Arvinas PROTAC protein degraders. I will now briefly touch on some key financial highlights for the second quarter of 2025.

While we continue to believe that Vets Egg is a potentially best-in-class asset, given the changes to the development plan, we have determined that it is no longer viable for us to build out our commercial infrastructure as we had previously planned.

As John said, earlier we are in active discussions with fizer to rework our collaboration to determine the most efficient way to make this important drug available to patients. If approved

Across our pipeline, we have a rich set of catalysts coming up in the next year for both our oncology and neuroscience portfolios.

With our strong balance sheet, we have sufficient resources to move these exciting programs forward to key value and collection points.

They diluted my to Novartis.

We are excited to continue development of the next generation of our Venice protects.

Andrew Saik: At the end of the second quarter, we had approximately $861.2 million in cash, tax equivalents, and marketable securities on the balance sheet, compared with $1.04 billion as of December 31, 2024. Revenue for the three months ended June 30, 2025, totaled $22.4 million, compared to $76.5 million for the three months ended June 30, 2024. The decrease of $54.1 million was primarily driven by $45.6 million of decreased revenue from the Novartis license agreement and the Novartis asset agreement, both of which were entered into during the three months ended June 30, 2024, and were completed by December 31, 2024, as the technology transfer of our ongoing planned clinical trials of lexdegalutamide were transitioned to Novartis. Revenue from the Vepdegestrant collaboration agreement with Pfizer decreased $6.8 million related to the removal of two phase 3 trials from the development plan during the first quarter of 2025.

I'll now briefly touch on some key financial highlights for the second quarter of 2025. At the end of the second quarter, we had approximately 861.2 million in cash, cash equivalents and marketable, securities on the balance sheet compared with 1.04 billion, as of December, 31st 2024,

Revenue for the 3 months and a June 30th 2025 total 2022.4 million compared to 76.5% of June 30th. 2024, the decrease of 54.1 million was primarily driven by 45.6 million of decreased revenue from the Novartis license agreement and the Novartis asset agreement both of which were entered into during the 3 months and the June 30th 2024 and were completed by December. 31st 2024 as the technology transfer of our ongoing plan. Clinical trials of Lexus mind were transitioned to Novartis

Andrew Saik: General and administrative expenses were $25.3 million in the second quarter, compared to $31.3 million for the same period of 2024. The decrease of $6 million was primarily driven by a decrease in personnel and infrastructure-related costs of $4.8 million and professional fees of $2.2 million, partially offset by an increase in costs related to developing our commercial operations of $1.1 million. Research and development expenses were $68.6 million in the second quarter, compared to $93.7 million for the same period of 2024. The decrease of $25.1 million was primarily driven by a decrease in the Vepdegestrant program of $10 million, a decrease in the lexdegalutamide program of $9.5 million, and decreases in personnel expenses and non-program-specific expenses of $10.3 million, offset by an increase in the LARK2 program of $2.1 million and the KRAS program of $1.5 million.

revenue from the vet deg collaboration agreement with fiser decreased, 6.8 million related to the removal of 2 phase 3 trials from the development plan, during the first quarter of 2025

General administrative. Expenses were 25.3 million in the second quarter compared to 31.3 million for the same period of 2024.

The decrease of 6 million was primarily driven by a decrease in personnel and infrastructure related costs of 4.8 million and professional fees of 2.2 million. Partially offset by an increase in costs related to developing our commercial operations of 1.1 million.

Recent development expenses were 68.6 million in the second quarter compared to 93.7 million for the same period of 2024.

Andrew Saik: Restructuring costs in the quarter amounted to $7.4 million of cash expenses, consisting primarily of employee-related expenses, which were offset by a reversal of non-cash employee stock compensation and bonus expenses of $6.4 million. The announced restructuring is now complete, and the full benefit in terms of cost reduction will be seen starting in the third quarter. We are maintaining our prior cash runway guidance into the second half of 2028. We are focused on staying disciplined by investing in areas that will maximize shareholder value as we move towards important catalysts in the coming months. In addition, we will continue to look at ways to reduce costs and increase efficiency while continuing to focus on our goals of progressing our very promising early pipeline. With that, I will turn the call over to John for closing remarks. John?

The decrease of 25.1 million was primarily driven by a decrease in the beta program, with 10 million, a decrease, in the Luxe stegal ludum of 9.5 million and decreases in Personnel, expenses and non-programmed specific expenses of 10.3 million offset by an increase and the Lark 2 program of 2.1 million and the kingra program of 1.5 million.

Restructuring costs in the quarter amounted to 7.4 million of cash expenses consisting. Primarily of employing related expenses which were offset by a reversal of non-cash Employee Stock compensation and bonus expenses of 6.4 million.

The announced restructuring is now complete, and the full benefit in terms of cost reduction will be seen starting in the third quarter.

We are maintaining our prior cash Runway guidance into the second half of 2028. We are focused on staying disciplined by investing in areas that will maximize shareholder value as we move towards important catalysts in the coming months.

in addition, we will continue to look at ways to reduce costs and increase efficiency while continuing to focus on our goals of progressing, our very promising, early pipeline,

With that, I'll turn the call over to John for closing remarks. John.

John Houston: Thanks, Andrew. As you have heard, we have seen multiple near-term milestones across our clinical development and regulatory efforts. Our programs offer a rich set of catalysts over the next 12 months, including clinical data from ARV-102 and ARV-393, and potentially initial clinical data from ARV-806, and of course, the potential for the first ever approval of a PROTAC protein degrader. During this time, we will also advance ARV-102 in its ongoing trial in patients with Parkinson's and initiate a trial with ARV-102 in progressive supranuclear palsy. Before opening the call for Q&A, I would like to reiterate our confidence in our near-term plan to create value for patients and shareholders. This includes advancing Vepdegestrant to launch by Pfizer or another party, achieving the important data milestones I just described, and allocating capital to ensure we reach those milestones efficiently.

thanks Andrew.

As your parents, we see multiple near-term milestones across our clinical development and regulatory efforts our programs offer. A rich set of catalysts over the next 12 months, including clinical data from ARB 102 and ARVC 93, and potentially initial clinical data from ERV 806, and of course the potential for the first-ever approval of our Protag.

During this time, we will also advance ARB 102 in its ongoing trial in patients with Parkinson's disease and initiate a trial with ARB 102 in progressive supranuclear palsy.

John Houston: While we made sweeping changes in the first half of 2025, we are always evaluating the best ways to create shareholder value. With that, I will turn the call over to Jeff to begin the Q&A portion of the call. Jeff?

Before opening a call for Q&A, I'd like to reiterate our confidence in our new attempt plan, to create value for patients and shareholders. This includes advancing bags to launch by fizer or another party, achieving the important data. Milestones I just described and allocating Capital to ensure we reach those Milestones efficiently.

Jeff Boyle: Thanks, John.

While we made sweeping changes in the first half of 2025, we are always evaluating the best ways to create shareholder value with that. I'll turn the call over to Jeff to begin the Q&A portion of the call Jeff.

John Houston: Operator, can you please open the queue?

Thanks John. Operator, can you please open the queue?

Operator: Thank you. A reminder to ask a question, you will need to press star then the number one on your telephone keypad. To withdraw your question, press star one again. Our first question comes from the line of Edward Tenthoff with Piper Sandler. Your line is open.

Thank you. A reminder to ask a question. You will need to press star then the number 1 on your telephone keypad. And to withdraw your question, press star 1 again.

Your line is open.

Edward Tenthoff: Thank you very much. Andrew, just one quick housekeeping. The restructuring contract you mentioned, was that primarily in the G&A line? Then I have a pipeline question for you guys.

Thank you very much. Um, Andrew just 1, quick housekeeping. The uh, restructuring charge that you mentioned, was that primarily in the GNA line, and then I have a pipeline question for you guys.

Andrew Saik: Yeah, hey, Ted. No, it was actually split up between research and development and G&A, and indeed most of the stock-based comps would have been recorded in the R&D section.

Edward Tenthoff: Great. That makes sense. Awesome. Can you give us a little bit more color on what to expect from ARV-102 data this year? I know that we've still got more to hear about the healthy volunteers for the multiple ascending cohorts, but what should we expect from the single ascending doses from Parkinson's patients? Thanks.

Yeah. Hey Ted know. It was actually split up between research and development and GNA and indeed most of the uh, stock-based comp would have been recorded in the R&D section.

John Houston: Thanks, Ted. The trials have been going well, and I will hand over to Noah to give you some of the details.

Great, that makes sense. Awesome. So um, can you give us a little bit more color on? What to expect from 1 102 data this year? I know that, um, we've still got more to hear about the healthy volunteers for the multiple ascending, uh, cohorts. But what should we expect from the single ascending doses from Parkinson's patients? Thanks.

Edward Tenthoff: Hi, Ted. Thanks for the question.

Thank you, Ted. And yeah the the child's wounds going well, and I'll hand over to Noah to give you some of the details.

Andrew Saik: Hey, Noah.

John Houston: Good morning.

Edward Tenthoff: As you said, I think you summed it up. We expect that an upcoming conference will summarize the full healthy volunteer data set that we assembled. In addition to that, if things work out, we will be able to present some SAS data, which I am not going to go into the details of what we will present exactly, but should be able to signal that we are on track when you compare it to the healthy volunteer fund.

I did. Thanks for the question. Yes. So um, so as you said, I think you summed it up, we're going. We expect at a conference, an upcoming conference, to some, uh, summarize the full healthy moment that your data set that we assembled. And in addition to that, if things work out, we'll be able to present, um, some sads data. You know, which will I'm not going to go into the details of of what we'll present. Exactly.

But you know, should be able to signal that we're on track with uh you know, when you compare it to the healthy volunteer funds.

Andrew Saik: Great. All right, looking forward to that and excited about the emerging pipeline.

Great. Uh, all right. Looking forward to that and excited about the emerging pipeline.

John Houston: Thanks, Ted.

Thanks, Ted.

Operator: Next question comes from the line of Jonathan Miller with Evercore ISI. Your line is open.

Next question comes from the line of Jonathan Miller with Evergreen ISI. Your line is open.

Jonathan Miller: Hi guys, thanks so much for taking my question and congrats on, as I should say, congrats maybe is the wrong word, but good job on getting your restructuring going. I would love to follow up on the ARV-102 question. Maybe it is a little too early to say exactly what you will give us in patients this year, but maybe could you talk a little bit about what you hope to see in a more full patient data set? What are your bars for success in patients that can give you confidence going into later on in efficacy readouts?

Edward Tenthoff: Thanks, Jonathan. Noah?

Uh, hi guys. Uh, thanks so much for taking my question and, uh, congrats on on I I, as I should say. Uh, uh, congrats is the wrong word, but good job on on getting your restructuring going. Um, I'd love to follow up on 1 of 102 and 102 question, you know? Maybe it's a little too early to say exactly what you'll give us in patience this year. But maybe could you talk a little bit about what you hope to see in a more full patient data set? What are your bars for success in patients? That can give you confidence going into later on in an efficacy readout.

Noah Berkowitz: Sure. Jonathan, so, thanks for the interest here. I think we have outlined that we expect to start a Parkinson's disease multiple dose study over the course of the next month or so. While I cannot really comment about when those data will be presented, the idea is that we are enrolling patients with the insights gained from healthy volunteers regarding a dose range. That will allow us to establish that in patients who have higher baseline LARK2 levels and also patients that are more elderly because healthy volunteers tend to be very young, like a little more than college age, and Parkinson's disease is going to be more than twice that on average, I suspect.

Thanks Jonathan. You know what? Sure uh Jonathan so yes thanks for the interest here. I think we've outlined that. We expect to start a Parkinson's disease multiple um multiple dose study uh over the course of the next month or so.

Noah Berkowitz: We will be able to demonstrate that we have the same exciting results that we previously reported in healthy volunteers of orally bioavailable brain-penetrant PROTAC protein degraders and the ability to move biomarkers, which also now we have much more insight into than we did many months ago. We continue to do work to understand what are the best biomarkers that we can track and are going to be most predictive of an impact in the endolysosomal trafficking and neuroinflammation that is characteristic of Parkinson's disease and PSP. We expect we could start tracking this in real patients rather than the healthy volunteers.

And what we? Well, I can't really comment about when those data will be presented. The idea is that we're, uh, enrolling patients with the insights gained from healthy volunteers, uh, regarding a dose range and that will allow us to establish the impatience who have higher uh, Baseline Lark 2 levels. Uh, and also patients that are more elderly because healthy volunteers tend to be very young, like a little more than College age and Parkinson's disease are going to be more than twice that on average. I suspect. Uh, so we'll be able to demonstrate that. We have the same exciting results that we previously reported in healthy volunteers of orally, bioavailable brain. Penetrance, uh, Protek and the ability to move biomarkers, which also now we have much more insight into than we did many months ago, right? So we continue to do work to understand what are the best biomark.

Markers that we can track and are going to be most predictive of uh, in Impact in the uh, Endo lysosomal trafficking and neuroinflammation. That is uh, characteristic of Parkinson's disease, and PSP. And so we expect we could start tracking this in real patients rather than the healthy volunteers.

Jonathan Miller: Awesome. Thank you. Then maybe on the BCL6 degrader, you mentioned in the press release in this call the glutathione combination result that you presented this year, but you've presented on a number of different combos preclinically. Can you give us a sense of where you might want to start in patients, what combo therapies you might want to start with?

Uh awesome. Thank you. And then maybe on the bcl6. Uh, you mentioned uh, in the press space, in this call The Cliff combination results to present this year but you you've presented on a number of different combos pre-clinical. Uh, can you give us a sense of where you might want to start in patients, what, what combo therapy you might want to start with?

Noah Berkowitz: I think we've been signaling in conversations, you can certainly speak clearly, very directly about it here, that our interest for BCL6 is to learn, find the dose in monotherapy. It's something we're obligated to do, but the real interest is moving forward in combinations, in particular in DLBCL. I think it should be clear to everyone that bispecifics and second-line plus DLBCL and maybe eventually not that far in the future in first-line are important drugs in that space. If we can combine with bispecifics in human beings and get results that look anything like what we've seen preclinically, we think we're well positioned for a new modality of therapy with a real orthogonal approach that enhances the activity of the bispecific.

I think we've been I've been signaling in conversations, you know, we can certainly, uh, speak clearly, you know, very directly about it here that our interests for bcl6 is to

Noah Berkowitz: Remember, one of the great combination properties here is that we recognize that ARV-393 can increase the expression of CD20, which could potentially make the bispecifics even more active. On top of that, we've been reporting out the great potency with our drug that if that translates into the clinic, then that gives us a great competitive advantage against the only other degrader that's in the clinic currently.

Just is moving forward in combinations in particular in dlbcl and I think it should be clear to everyone that uh by specifics and second line plus dlbcl and may be eventually in not that far in the future. In the first line are important drugs in that space. So if we can combine with by specifics in human beings and get results that, look, anything like what we've seen pre-clinical we think we're well positioned for a um for a new modality uh of therapy with a real orthogonal approach uh that that enhances the activity of the by specific. And remember 1 of the great combination properties here is that we recognize that um

That our our that 393 can increase the expression of cd20, which could potentially make the by specifics even more active. And, um, on on top of that, you know, we've been reporting out the great potency with our drones that if that translates into the clinic, then that gives us a great competitive advantage against the only other degrader that's in the clinic currently.

John Houston: Yeah, thank you so much.

Yeah, thank you so much.

Operator: Next question comes from the line of Derek Archila with Wells Fargo. Your line is open.

Next question comes from the line of Derek archila with Wells Fargo. Your line is open.

Speaker 11: Good morning. This is Carl calling in for Derek. Thank you for the question. For ARV-102, could you talk a little bit more on the elevated LARK2 level in PD patients in terms of how much to expect and how to maybe feel confident that similar more than 50% degradation can be achieved in CSF? Then on the Vepdegestrant label potentially, could you talk about maybe the base case? What could be some potential differentiations you could expect versus your competitors? Thank you so much.

Good morning. Uh this is Eric, thank you for the question. So I guess for a RV 102 um could you talk a little bit more on the elevated block to level in PD patients in some? How much 2 we expect and how to maybe feel confident that the similar more than 50% equation can be achieved CSS? Um and then um on the back, um the label potentially could you talk about maybe the base case, what could be some potential differentiations. You could expect but um your competitors, thank you so much.

Noah Berkowitz: I think I captured the second question with Vepdegestrant, but there was a lot of cracking in the transmission of the first question. Did anyone here catch that?

Andrew Saik: Could you maybe just repeat the first question?

John Houston: Yeah, of course.

I think I captured the second question with ve, but there was a lot of cracking of the, in the transmissions in the first question. Did anyone here catch that? Yes. Could you maybe just repeat the first question?

Andrew Saik: It was just the first.

John Houston: Sorry about that.

Yeah, of course. It's just the first story about that.

Speaker 11: For the ARV-102, I think the question is the elevated LARK2 level in PD patients. Could you talk about the expectation of the elevation and how to feel confident that more than 50% degradation in CSF can be achieved?

um, so for the, for the ARB 102, um, it's like the question is um the elevated lock to level in PD patients, could you talk about the expectation of the elevation and uh how to feel confident that more than 50% degradation in CSF can be achieved

Noah Berkowitz: Yeah, so I think it's a great question. Fundamentally, I think it's been established by external sources that there's increased LARK2 protein expression in the brain and in the CSF of patients with Parkinson's disease. In our own hands, we've already seen in the SAD that there are higher baseline levels of LARK2 than we observed in the healthy volunteers. That's already kind of consistent, but it's not a surprise to us at all. That was the expectation. In terms of one of the great properties of the degrader that I think differentiates it beautifully from an inhibitor is that we've already established in the healthy volunteers that we can get really good target engagement in the brain. We know that the inhibitors just don't do that well. They're only achieving 30% or so inhibition in the brain.

Yeah. So I think it's a great question. Um, so fundamental, I think it's been established by external sources that there's increased Lark to uh, protein expression in the in the brain and in the CSF of uh patients with Parkinson's disease.

Um in our own hands, we've already seen in the sad that there are higher Baseline levels of Parkinson's of uh L 2. Then we observed in the healthy volunteers. Uh so that's already kind of consistent but it's not a surprise to us at all that that was the expectation.

Um,

Noah Berkowitz: We know preclinically, they're not reaching deep brain regions as effectively as our degrader can. So we're getting higher engagement. Because we have a degrader here, which has that iterative property that at even lower exposures, you get continued degradation of the target, we think that should be, we should be well poised to reduce LARK2 levels. That's the underlying premise that's been borne out in preclinical models. We've shown it in healthy volunteers, and now we think we can confirm it in the multiple doses in Parkinson's disease patients. Regarding the second question, I think the question was what differentiates us essentially with our Vepdegestrant from competitors in the space.

In, in terms of 1 of the great properties of the degrader that I think differentiates it beautifully from an inhibitor is that we've already established in the healthy volunteers that we can get really good Target engagement in the brain, right? And we know that the Inhibitors just don't do that. Well right, they're only achieving 30% or so inhibition in the brain. They're not, uh, we know pre-clinical, they're not reaching deep brain regions as effectively as our degrade or can. So, we're getting higher engagements and because we have a degraded year, which has been that iterative property that at, uh, even lower exposures, you get

Continued degradation of the target. We think that should be, uh, we should be well poised to reduce luck to levels. That's the underlying premise that's been borne out in pre-clinical models. We've shown it in healthy volunteers and now we think we can confirm it in, uh, the multiple Doses and Parkinson's disease patients.

Noah Berkowitz: More or less, it comes down to efficacy, you know, the better PFF that's been seen when compared to fulvestrant control, you know, monotherapy control, which, you know, in our hands, we're talking about three months improvement, which other drugs really haven't achieved. On top of that, we have, we're leaning into some PRO data that you'll see soon that show that the patients experience the drug very well. Certainly, the adverse event profile is more attractive, which is to say that there's a lot of GI toxicity seen with other agents in this space. We have reported half or even 33% of that, you know, when you compare to different drugs. I think that that combination of benefit-risk really stands out for Vepdegestrant when compared to other agents.

You know, the the better PFS that's been seen when compared to, uh, to full veteran control, you know, monotherapy control, which, uh, you know, in our hands we're talking about, uh, 3 months Improvement, uh, which other drugs really haven't achieved on top of that. Um, we have, uh, we're leaning into some Pro Data that you'll see soon that show that the patient experienced the drug very well. Uh, certainly the adverse event profile is more attractive, uh, which is to say that there's a lot of GI toxicity seen with other agents in this space, we have reported half or 30 even 33% of that. Uh up to, you know, when you compare to different drugs and I think that that combination of benefit risk really stands out for that day when compared to other agents.

Speaker 11: Thank you.

Thank you.

Operator: Next question comes from the line of Tazeen Ahmad with Bank of America. Your line is open.

Next question comes from the line of tazeen Ahmad with Bank of America. Your line is open.

Speaker 11: Hi, good morning. Thanks for taking my question. I wanted to focus on some commercial questions. As you think about Vepdegestrant and the upcoming launch, you are obviously bullish about its place potentially in monotherapy, but you also talked about needing to be careful about how you are prepping for the launch. How does this work in terms of setting up a sales force? When do you start prepping for that? How has that plan changed relative to what you would have planned for before? Secondly, if Pfizer returns rights for the program to the company, would there be a gap in between when Pfizer returned the rights and when you would be able to secure a new partner, or are you kind of in process now for seeking a potential replacement should Pfizer return those rights? Thanks.

John Houston: Yeah, no, thank you for the question. So in the second part, I will tackle that first. Really, we are in negotiations with Pfizer right now. The original deal that we claimed in 2021 was the 50/50 co-development, co-commercialization, very attractive deal at the time. We had plans for doing second-line monotherapy, first-line, and even adjuvant. That would have been a very significant market and a very significant opportunity to share 50/50. With the decision not to go forward with first-line or the second-line combo, it puts us into a position where Vepdegestrant at the moment is only focused on second-line monotherapy. So a smaller market really does not move the dial for Pfizer in terms of 50/50 and not particularly attractive for Vepdegestrant either.

Hi, good morning. Thanks for taking my questions. I maybe wanted to focus on some um commercial uh, questions. So, as you think about that deck and the upcoming launch, um, you're obviously bullish about its place potentially in monotherapy. But you also talked about, um, needing to be careful about, um, how you're prepping for the launch. So how does this work in terms of, um, setting up a, um, a sales force? When do you start prepping for that? How has that plan changed relative to what you would have planned for before? And then, secondly, if fiser returns right for, um, the program to the company, would there be a gap in between when fiser returned the rights? And when you'd be able to secure a new partner or are you, you know kind of in process now for for seeking a potential replacement should fiser return those rights? Thanks.

Yeah, no, thank, thank you for for the question. Um, yeah, so in the second part of uh, we'll talk talk about first. Um, clearly we're in the negotiation with um,

With FISA right now, as the original deal that we signed in 2150, the code of elements, the code commercialization was a very attractive deal at the time. We had plans for doing second-line monotherapy. For the first line, I need an adjective, and that would have been a very significant market and a very significant opportunity to share 50/50.

Uh, with the decision not to go forward with this, uh, first line or the second line combo.

John Houston: So the dialogue we have been having actively with Pfizer is about how we redo the collaboration so that either they get more of the economics or we get more of the economics. In a scenario where potentially we get the asset back, our plan is clear that we would immediately look to find the next partner that would help to develop Vepdegestrant and launch Vepdegestrant, which gets back to the first question, which is, as we stated, we are really not building out a sales force at all. Right now, we are focused on, first of all, getting Vepdegestrant approved and also getting launch ready, which is a relatively minimal amount of money that we spend in between now and the end of the year.

It puts us into a position. Where vent at the moment is only focused on the second leg on a therapy. So a smaller Market um, really doesn't move the dial for fizer in terms of 50/50 and not particularly attractive for our vents either.

So the dialogue we've been having, uh, actively with Fiser is about how we redo the collaboration so that, uh, either they get more of the economics or we get more of the economics.

Um, and the scenario where uh, potentially um, me get the asset back. Um, our plan is clear that we would immediately Loop to find a next partner that would help to develop events and launch events.

John Houston: So the idea would be that with that launch readiness, if we got the asset back, we would run an active process and be in a position for another company to take on the development and launch of Vepdegestrant fairly rapidly. So we are hoping there would not be a particular gap.

Which goes back to the first question, which is as we stated that we are really not building out a sales force at all. Uh, right now we're focused on um first of all getting uh, best approved um and also getting launched ready, which is a relatively minimal amount of money that we spend in between now and the end of the year. So the idea would be that uh, with that launch Readiness. If we got the asset back, we'd run a active process and be the position for um another company to take on the uh development and launch of that fairly rapidly. So we're hoping there wouldn't be a particular 1.

Speaker 11: Okay, but as of today, could there be a gap between when it got approved and when it launched if you are not able to secure the right terms?

John Houston: No.

Speaker 11: Okay.

John Houston: Oh, sorry, say that last part again. Say the last part of the question, sorry.

Okay, but as of today um could there be a gap between when it got approved? And when it launched, if if you uh, are not able to secure the right term know, okay? Oh sorry. Say that last day again, the see the last question. Sorry.

Speaker 11: I just wanted to clarify whether there would be a gap in the launch if you wouldn't find a suitable partner in time once it's approved.

Uh, I just wanted to clarify whether there would be a gap in the launch if you wouldn't find a suitable partner in time.

John Houston: I see. So, instead of the suitable partner, at the moment, the plan is there would be no gap between getting approval, ideally having a partner in place, or having Pfizer launch. There would be no gap at all. I think your question there is if you do not get a, if you get the asset back and you do not get a partner, then we would be taking stock of that. Our plan is that we would find a partner.

Speaker 11: Okay.

John Houston: If we get it.

See. So yeah, they said the suitable partner, so at the moment, if the plan is to be no gap between, um, getting approval, ideally having a partner in place, or having fiser launch, uh, there'll be no Gap at all. I think your question there is, if you don't get a, if you get the asset back and you don't get a partner, um, then yeah. Yeah. We we'd be taking stock of that. Our, our plan is that we we'd find a part.

okay, if we get

Operator: Next question comes from the line of Andrew Saik with Leerink Partners. Your line is open.

Next question comes from the line of Andrew Barren with clearing Partners, your line is open.

Speaker 11: Hi, everyone. This is Amanda on Frankly. We wanted to get your thoughts on the recent readout from the Phase 3 trial evaluating Vepdegestrant in second-line HR positive breast cancer in patients that do not have a PI3CA mutation, which then would include some ESR1 mutant patients. We are wondering how this changes, or if this changes your outlook for second-line ESR1 mutation patients, and if you would ever consider a combination with Vepdegestrant to address a broader population. Thank you.

Hi everyone. This is Amanda from Andy. Um we wanted to get your thoughts on the recent readout from the face retrial evaluating to get a and second line HR positive breast cancer and patients that don't have a pick 3 C mutation which then would include some esr1 mutant patients and we're wondering how does this change um or if this changes your outlook second line? Yes, or 1 M patients and if you would ever consider a, a combination with, uh, get to address a broader population. Thank you.

John Houston: Thanks for the question, Noah.

Noah Berkowitz: Sure. Yeah, so we wouldn't, we really are not surprised by the result. We recognize the opportunity for PI3 mutation-directed drugs in breast cancer. There is overlap, as you had suggested, between ESR1 mutations and PI3CA. So the question comes down to, whether it's in our modeling. Overall, my impression is that it will have little impact on the modeling. I could turn it over to my colleague Alex from commercial to offer further comments. Part of your question was whether we would develop it with an agent like that. The answer to that is someone may, but we won't because we've already established that we're not doing further development on the drug, initiating new studies in combinations. It would be something that should be very much of interest to another company. We've already scouted that out, but it's not something we'll be involved in.

Thank you. Sure. Uh, yeah. So we wouldn't we really are not surprised by the results. We recognize the opportunity for um, I think 3 mutations directed drugs to uh in breast cancer. There is overlap as you have suggested between the sr1 mutations and uh, Pick 3 CA so um the question comes down to, you know, whether it's in our modeling and overall we're

You know, my impression is that it will have little impact on the modeling, I could turn it over to my colleague, Alex from commercial to offer further comments. Um, but part of your question was whether we would develop it with

An agent like that. And the answer to that is someone may, but we won't because we've already established that, we're not doing further development on the drug initiating, new studies and combinations, and it would be something that should be very much of interest to another company. We've already scouted that out, uh, but it's not something we'll be embarking on.

Operator: Next question comes from the line of Li Watsek with Cantor Fitzgerald. Your line is open.

Next question comes from the line of free WhatsApp with Cantor Fitzgerald. Your line is open

Speaker 11: Hey, good morning, guys. Thank you for taking our questions and nice progress on the pipeline. I guess for Vepdegestrant NDA submission, it sounds like the PDUFA date is very soon. Should we anticipate perhaps priority review here? And any guidance on your part for the global filing strategy? Do you need to wait for more mature OS data?

Uh, hey, good morning guys. Uh, thank you for taking out questions in nice progress on the pipeline. Um, I guess for vag. Uh, MDA submission sounds like, you know, the Padua date very soon. Uh, should we anticipate um priority review here? And uh any guidance on your part? Um, for the global uh, filing strategy? Um, do you need maybe to wait for more mature OS data?

John Houston: With the second part of that question, I will hand over to Noah. For the first part, we are still awaiting details from the FDA. As soon as we get that information, we will pass that on. We do not have the Purdue FedDate yet. Noah, do you want to tackle that second part of the question?

Noah Berkowitz: I, you know, what we've shared, what we've offered guidance to is our filing of the NDA in the U.S. Obviously, we're waiting on feedback regarding Purdue FedDate. But regarding global strategy, we haven't offered guidance on that yet. I think it would be premature.

Um, yeah, but the second part of that question, I'll hand over to Noah for the first part. Yeah, we're still awaiting, uh, uh, details from the FDA and as soon as it gets, uh, that information will will pass that on. So, we, uh, don't have to do just the date yet. No worries. You want to tackle that second part of the question? Yeah, I, you know, we what we've shared, what we've offered guidance to is our filing of the, uh, of the NDA in the US. And obviously, we're waiting on, uh, feedback regarding, uh, due today. But, uh, regarding Global strategy, we're, we have an author guidance on that yet, so I think it would be pretty short.

Speaker 11: Okay. Then, you know, in terms of finding maybe a potential new partner for Vepdegestrant in the case that you got the molecule back, can you elaborate some of the considerations that you prioritize? What is important for you guys in terms of maximizing the value?

Okay. Um and then, you know, in terms of finding uh maybe a potential new partner for a leap tag, in a case that you got the molecule bag. Um, can you elaborate some of the considerations that you prioritize? What's important for you guys in terms of maximizing the value,

John Houston: Yeah, it's a great question. Clearly, we believe Vepdegestrant is an important drug. We believe it has a lot of value. Because of the partnership we're in with Pfizer, decisions would be made. Maximizing that value is going to be somewhat difficult. That's why we're in discussion with Pfizer about changing the nature of the collaboration. Ideally, as I said, either Pfizer or Vepdegestrant should go forward with the asset more kind of solar economics. In the scenario where maybe we get the compound back, yes, we'd be looking to partner, ideally a partner that does have the kind of the deal and interest to develop the asset further, both from the U.S. and the global setting. Our involvement in that, I think, would be relatively minimal in terms of development.

Yeah, give me a question. I mean, clearly we believe that egg is an important drug. Uh, we believe it has a lot of value, um, because of the partnership we're in with fizer and the decisions are being made and maximizing that value. It's going to be somewhat difficult. So that's why we're in discussion with fiser about changing the nature of the collaboration. And ideally, as I said, either fiser or

John Houston: Our view is that we want Vepdegestrant in the hand of a partner, be it Pfizer or another company, that really takes the compound forward, launches it, and progresses it with further development.

We're finished to go forward with the asset more kind of solar economics and in the scenario where maybe we get the compound back. Yes, we'll be looking to partner and ideally a partner that does have the kind of the the deal and interest to develop the asset further both from the US and the global setting. Um our our involvement of that I think would be relatively uh minimal in terms of uh uh development. Um, our view is that we want bedding in the hand of a partner, the advisor or another company that really takes the compound forward launches it and progresses it with the further development.

Operator: Next question comes from the line of Akash Tewari with Jefferies. Your line is open.

Comes from the line of a cash February with Jeffries. Your line is open.

John Houston: Hey, this is Manoj on for others. Thanks for taking our question. What are your expectations around the DEN-ADLY LLRK2 data in the first half of next year? If that trial fails or does not meet expectations, what signals from that study would you be looking for to give confidence for your own degrader program? Thanks.

Hey, uh, this is mano. John for August, thanks for taking our question. What are your expectations around the Denali lrk to data in the first half of next year? And if that trial fails or doesn't meet expectation? What signals from that study? Would you be looking for to give confidence for your own, uh, degrader program? Thanks

Noah Berkowitz: Yes, thanks for the question. If the question was, you know, expectations for the DEN-ADLY program last year, I think it is a fantastic question. We think that LARK2 is an outstanding target, and I think the entire key opinion leader community would agree with us on that. The question is, what is the best drug to address that target? We see some virtue in an inhibitor, but it has challenges. I outlined that earlier, that the inhibitor does not seem to penetrate the brain as deeply as, let us say, our degrader. On top of it, it does not necessarily engage its target as effectively. We have a broader engagement. Not only are we binding it and degrading it, and we are eliminating because of that degradation, the LARK2 kinase activity, the GTPase activity, and scaffolding function. All of those features make a degrader more attractive than an inhibitor.

yes, thanks for the question. Um,

Yeah. Um I guess the question was, you know, expectations for the Denali program last year. I think it's a fantastic question.

We think that Lark 2 is an outstanding Target, and I think the entire, uh, key opinion leader Community would agree with us on that. The question is, what is the best drug to address that Target? And so we see some virtue in and inhibitor, but it has challenges, and I outlined that earlier that the inhibitor doesn't, um, de it doesn't seem to, uh,

Penetrate the brain as deeply as, let's say, our target. And on top of it, it doesn't necessarily engage its target as effectively. We have a broader engagement; not only are we binding it and degrading it, but we're also eliminating it because of that degradation. The Lark 2 time activity, the GTP activity.

Noah Berkowitz: We think that they may succeed. We know they have the right target, and we are looking forward to learning from their results, learning if there is something about patient selection that could be incorporated, and overall, whatever signals can come out of their trial. Thanks.

So all of those features make a degrader more attractive than inhibitor. So we think that they may succeed. We know they have the right target, um, and we're looking forward to learning from their results. Learning if there's something about patient selection that could be incorporated. And overall, you know, whatever signals can come out of their, their trial.

Thanks.

Operator: Next question comes from the line of Evan Seigerman with BMO Capital Markets. Your line is open.

Next question comes from the line of events, secret man, with BMO Capital markets. Your line is open.

Jonathan Miller: Hi there. This is Connor McKay on PREV, and thanks for taking our question. We just had a quick one on the submission of Vepdegestrant. Given the current environment at FDA, we were just wondering if you would be willing to characterize your recent interactions with the agency and, you know, maybe comment on the level of alignment there. Then just one quick follow-up on ARV-806. Would you be able to share a little bit more on how you are thinking about positioning this asset versus the PAN-KRAS agent you mentioned today? Thank you.

John Houston: Yeah, thanks for the question. The second one, I'll hand over to Noah and Angela. The first one, I'd have to say our whole process with the FDA has gone very smoothly. The interactions have been excellent. Their timing and sense of getting back to us would be really good. So even though we know that there's lots of other pressures on the FDA and it could impact timelines, we haven't seen that yet with our interactions on Vepdegestrant, which is a really good positive thing for us. Noah, do you want to tackle regarding ARV-806?

Hi, there. This is. Connor McKay on, for Evan, thanks for taking our question. Uh, we just had a quick 1 on the submission of epta, given the current environment and FDA. We were just wondering if you'd be willing to characterize, your recent interactions with the agency and, you know, maybe comment on level of alignment there and then, uh, just 1 quick, follow-up on arv 806, uh, would you be able to share a little bit more on how you're thinking about positioning this asset versus the tnk RAS agent? You mentioned today. Thank you.

Yeah, thanks for the information. The second 1, I'll hand over to Noah and Angela for the first 1.

Uh, I have to say, I hope process with the FDA has gone very smoothly, then tractions have been excellent. Um, they're they're timing and in terms of getting back to us, it's been really good. So, uh, even though I we know that uh, there's lots of, uh, other pressures uh, on the FDA and, uh, it could impact timelines. We haven't seen that yet with our interactions, uh, on that diagnosis, which is a really good positive thing for us.

um,

Noah Berkowitz: will make some comments about clinical, and I will turn it when I am done to Angela. We may have some comments about some of the interesting differentiation we have achieved preclinically. This drug entered the clinic a little faster than we expected because of great efficiencies at the team level. What we noticed is that there is tremendous appetite for drugs like ours in this space because our cohorts are in demand. We are advancing through early dose escalation now. Overall, we expect that there are going to be five or fewer dose levels in this escalation. That is going to at least give you a sense of where we are headed.

no, I want you to tell us regarding 806. I'll make some comments about clinical and I'll turn it when I'm done to Angelo. We have some comments about some of the interesting differentiation 3 clinically. Um, so we

This drug, uh, entered the clinic, a little faster than we expected because of great efficiencies that the team level.

Uh then what we noticed is that there's tremendous appetite for drugs like ours in the space because our cohorts are um in demand.

Uh so we're advancing through early dose escalation now. Um, we don't

Noah Berkowitz: The key is to look at where we are in monotherapy, compare ourselves to data that is out for inhibitors and the very, very modest and unimpressive data that have been presented by a degrader in the clinic, which is limited, has dose-limiting toxicity relating to a panic function. We will compare ourselves to that. We have good go-no-go criteria. The intention is to move our IV degrader, which has once a week, possibly once every two-week dosing. That is something we will learn from this escalation in combination with EGFR inhibitors and with chemotherapy. That is built into our plan, and that allows us to start moving into eventually first-line colorectal cancer and pancreatic cancer and also opportunities in non-small cell lung cancer. I will turn it to Angela.

Speaker 11: Sure. Thanks, Noah. Just to comment on some of the other differentiation features of our 806 molecule, it's very potent with respect to its activity. We're 25 times greater in terms of potency for antiproliferative activity with respect to the inhibitors, and then 40 times more effective than the clinical stage degrader. The other piece that I'll mention is that catalytic activity that we have overcomes this KRAS resynthesis rate that has been observed as a major mechanism of resistance in the clinic with RMC, certainly with RMC 6236. We're excited about it. We think this is a very strong differentiator. Of course, we'll see what happens clinically. I hope that helps.

tears and with chemotherapy and that's built into our plan and that allows us to start moving into, um, you know, eventually first line, uh, coloral cancer and pancreatic cancer and also opportunities in non small cell, lung cancer, I'll turn to Angela if you

Thanks so much. So just to comment on some of the other differentiation features of our 806 molecule. It's very potent with respect to its activity. We're 25 times, you know, greater in terms of potency, for anti-proliferative, activity, with respect to, um, the Inhibitors and then 40 times more effective than the clinical, um, stage to Greater. Um, the other piece that I'll mention is that catalytic activity that we have overcomes, this cos resynthesis rate that has been observed as a major mechanism of um,

Of resistance in the clinic with RMC. Um, certainly with the RMC 62, um, 36. So it's something, you know, we're excited about. We think this is a very strong differentiator, um, of course, you know, we'll see what happens clinically so,

I hope that helps.

John Houston: Yes, thank you.

Yes, thank you.

Operator: Next question comes from the line of Srikripa Devarakonda with Swiss Securities. Your line is open.

Next question comes from the line of free creeper de Vera with tree Securities, hairline is open.

Speaker 11: Hi, this is Anna on for Srikripa Devarakonda. Thanks for taking our question. In regards to ARV-102, I know you mentioned the elevated LRK2 level in Parkinson's. Could you remind us as to what percent of Parkinson's patients could be eligible for an LRK2 targeting drug? A second question, just in regards to new adjuvant Vepdegestrant and that potential data readout, how would this potentially inform any room for Vepdegestrant to be used earlier in the treatment paradigm and besides commercializing in second-line as monotherapy and that fixed combo? Any additional plans for development? Thank you.

Hi, this is Anna on for crypto authentication. So in regards to 102, um, I know you mentioned the elevated lk2 levels in Parkinson's. Could you remind us as to what percent of Parkinson's patients could be eligible for an LR?

K2 targeting drug. Um, and then a second question, in regards to new add event, um,

And that's potential of data read out. How would this potentially inform um, any room for decks be used earlier in the treatment Paradigm and besides commercializing in second lines as monotherapy and that have 6 combo, any additional plans for development.

John Houston: Again, thank you for the question. Noah, next, as long as you've got the LARK2.

Noah Berkowitz: Yeah, so LARK2 levels are higher in the Parkinson's disease patients. Now, we haven't made a choice that we're only treating patients with elevated LARK2. By the way, I should say that that's something that might be on the table. It's something that we're going to explore. We're going to look at our own data sets as they evolve. We'll look at what's coming out of the DEN-ADLY program if it's shared. So that's a possibility. If your question implies, you know, genetically, since LARK2 is so implicated genetically in diseases like Parkinson's disease, if we, you know, when we move forward in Parkinson's disease, what percentage of patients have LARK2 implicated disease? In idiopathic, well, in familial Parkinson's, about 15% of patients have LARK2 mutations. There's a higher percentage that have LARK2 pathway mutations that contribute to other types of familial Parkinson's disease.

Thank you. Yes, thank you for the question. Um, no. I just want to talk to you. Yeah. Um, so Lark 2, uh, levels are higher in the Parkinson's disease patients. Um, you now we haven't made a choice, but we're only treating patients with elevated. Lark 2, and by the way, I should say that. That's something that might be on the table. It's something that we're going to explore. We're going to look at our own data sets as they evolve. We'll look at what's coming out of the Denali program, if if it's shared. Um, so that's a possibility.

Noah Berkowitz: When you look at idiopathic, it's down in the few percent range. Beyond those LARK2 mutations themselves, there are all kinds of pathway perturbations that suggest that LARK2 could be at the center of this endolysosomal dysfunction that is characteristic of Parkinson's disease in PD. So you start to have 30% of patients that can have SNPs and other biomarkers that are associated with this LARK2 dysregulation and may lead to LARK2 elevation. We have a particular interest in that subset of patients. That's why we're engaging in a lot of biomarker analysis. We've been a long-time collaborator with the Michael J. Fox Parkinson's Disease Biomarker Initiative. This is bearing fruit for us. So I think that we have no kind of guidance yet about whether we're doing patient selection or patient enrichment or going for all comers.

If your question implies uh, you know genetically since L 2 is so implicated genetically in diseases like uh Parkinson's disease. Uh, if we, you know, when we move forward in Parkinson's disease, What patients, what percentage of patients have Lark 2 imp disease. Well, in idiopathic well in, uh, uh, familial Parkinson's about, 15% of patients are have L2 mutations and there's a higher percentage that have L2 that way, mutations that uh contribute to other types of familial part.

when you look at idiopathic, it's down in the few percent range um so but beyond those

Lark to, uh, mutations themselves. There are all kinds of pathway perturbations that, uh, suggest that Lark 2, could be at the center of this and the lysosomal dysfunction, that is characteristic of Parkinson's disease and PD. So you start to have 30% of patients that can have Snips and other biomarkers that are associated with this, uh, Lark to, um, dysregulation and may lead to Lark to Elevation. And we have a particular interest in, in that

Subset of patients. And that's why we're engaging in a lot of biomarker analysis. We've been a long-time collaborator with the um,

Noah Berkowitz: These are the types of questions we are investing in right now to ensure that we have the best development plan forward. Now, the second question was about neoadjuvant Vepdegestrant.

Plan.

John Houston: Our positioning, the potential for Vepdegestrant in an early stage.

Noah Berkowitz: Really, we have to keep in mind there has been no evidence to date to suggest that Vepdegestrant shouldn't be working in the adjuvant setting and in first-line. We have every reason to believe that we can be very effective in that space. We know the drug is very tolerable. Cross-study comparisons suggest maybe we are more tolerable than aromatase inhibitors. That could be very important in both of those settings. Ultimately, a decision is being made in this partnership that because of where we are with timing and the interest probably more than with our partner, in this case, Pfizer, in first-line, that we are just not going to be going forward in those early lines. That is why we have been giving so much guidance for our intent to out-license this or proceed with renegotiation with Pfizer.

Now, the second question was about Neo Aven uh, that egg. So um and how positioning the potential for event egg in an alias? Yeah. So, uh, so really we have to keep in mind, there have been no evidence.

To take to suggest that, that egg shouldn't be working in the Advan setting and in first line. Uh, we have every reason to believe that we can be

A very effective in that space. We know the drug is very tolerable cross study comparisons suggest. Maybe we're more tolerable than, um,

Than aromatase Inhibitors. Uh, that could be very important in both of those settings. There's

Noah Berkowitz: I do not think that we should draw any conclusions that there are any problems in the adjuvant setting or in first-line.

So but ultimately a decision is being made in this partnership that because of where we are with timing and the interests probably more than uh with our partner in this case, fiser in the first line that we're just not going to be going forward in those early find. And that's why we've been giving so much guidance to our uh for our intent to uh part out licenses this, you know, or or proceed with renegotiation with fiser. But I don't think that we should draw any conclusions that there are any problems in the Neo in the admin setting or in the first line.

Speaker 11: Great. Thank you so much.

Great, thank you so much.

Operator: Next question comes from the line of Jeet Mukherjee with BTIG. Your line is open.

Next question comes from the line of Chief McCrory with btig. Your line is open.

Jonathan Miller: Great. Thanks for taking my question. So perhaps just coming back to the discussions with Pfizer over Vepdegestrant, you've talked about scenarios where perhaps Pfizer gets more economics or you get more economics or perhaps you find a new partner altogether. So based upon where your discussions are right now, would you say that you and Pfizer have very different views on how to maximize value for Vepdegestrant? Are you in active dialogue with other partners? If yes, how are those discussions going? Thanks.

John Houston: Yeah, great question. I would say that Pfizer and our guidance and the discussions we are having are aligned in terms of what the best way to get value for Vepdegestrant is. Even though we may have different views about the development future of Vepdegestrant, I think that Pfizer and our guidance truly believe that the value to be had there. That is why we are in these discussions. Clearly, if the asset does come back, and again, that is just one of the scenarios. The other scenario is that Pfizer takes the compound forward. In the scenario where it comes to us, yes, we would run an active process, but obviously, we cannot run an active process right now because we are in a collaboration with Pfizer and we do not have the ability to do that.

Great. Thanks for taking my question. So perhaps just coming back to the discussions with fiser over vepe you know you've talked about scenarios where perhaps fiser gets more economics or you get more economics or perhaps you find a new partner all together. So based upon where your discussions are right now, would you say that you and fiser have very different views on how to maximize value for Vite and are you? Inactive dialogue with other partners if yes. How are those discussions going? Thanks.

John Houston: Our belief is if we get the asset back, we run a process, there would be companies extremely interested in taking a new approved drug and with the potential to develop it not only in the first-line setting, but even earlier. So we are very pleased with the progress in terms of discussion with Pfizer. Like I say, if they want to take it forward aggressively and the launch of themselves is going to be extremely positive. If they do not and the outcome is we get a compound, then yes, we would run an active process.

Yeah, great question. Um, I I would say that fiser and our Venice in the discussions. We are having are aligned in terms of what the best way to get value for a vet. I guess, even though, we may have different views about the the development future of vet deg, I think there's a ficer nervous, uh, truly believes those values, they had there. And that's, that's why we're in these discussions. Um, with clearly it's the, it's the asset does come back and that again, that's just 1 of the scenarios, the other scenarios that fizer takes the the component for, but in the scenario where it comes to us. Yes, we run an active process. But obviously we cannot run an active process right now because we're in a collaboration with fiser and we don't have the ability to do that and our relief is, if we get the asset back

On the process, there would be companies extremely interested in taking uh a near approved drug and uh with the potential to develop it, not only uh, in the uh, the first time planning, but even earlier. So um, we are very um uh pleased with the progress in terms of discussion with. Fisa like I say if they uh, want to take it Forward aggressively and the launch of themselves might be extremely positive but if they don't and uh the outcome is, we get the compound then yes we run an active process.

Operator: Next question comes from the line of Ellie Merle with UBS. Your line is open.

Next question comes from the line of early M with UPS, your line is open.

Jonathan Miller: Hi, this is Tejas on for Ellie Merle. Thanks for taking our question. I think you talked a little bit about some of the preclinical data for the KRAS G12D degrader. Can you talk a little bit more about what we should expect with more data later this year, and how might that inform what we think about in the Phase 1?

Hi, this is Ted on for Ellie, thanks for taking our question.

I think you talked a little bit about some of the pre-clinical data for the kras Inhibitors. Um, can you talk a little bit more about what we should expect? Um, with more data later this year and you know, how might that inform what we think about in the uh, Phase 1?

John Houston: Great. Thanks for the question, Amanda. Over to Angela.

Great. Thanks for the question. I'll hand that over to Angela.

Speaker 11: For the KRAS G12D degrader, certainly, you can expect to see some preclinical data just showing the differentiation profile that we see relative to inhibitors that are in the clinic. We will also show some additional data just showing the combinability of the molecule. Noah Berkowitz had mentioned with EGFR mechanisms that is difficult with the PAN inhibitors, certainly in the clinic, showing some side effects that would basically preclude that combination. We will also show data that we think is really compelling from our oral KRAS G12D degrader program, showing that we are making really great strides there as well. Other additional comparative.

So, for the kras inhibitors for, for 806 certainly, you can expect to, um, see some preclinical data, just showing the differentiation profile that we see relative, um, to Inhibitors that are in the clinic. We'll also show some additional data just showing the combination of the molecule. Um, Noah had mentioned with, um, egfr mechanisms that's uh, difficult with the pan Inhibitors, certainly in the clinic um, showing some side effects that would, you know, basically preclude um, that combination we'll also show data uh, that we think is really compelling from our oral and kras program.

Operator: data that we'll have will include some other models where we're looking at combinability with immuno-oncology approaches and some of the unique features of PROTACs, we think, in this space. Also, with respect to the resistance mechanisms and overcoming that upregulation that is seen clinically with the inhibitors as well. So we think we have a very differential profile, and it's an exciting opportunity, certainly. We're seeing that with the over-enrollment and the interest from the investigators that treat patients. So I think it's an exciting time, and I'm sure Noah Berkowitz and your team will be sharing clinical data as soon as we have it. Hope that helps.

Is there as well, um, other additional, um, comparative data that will have will include, um, some other models where we're looking at combination, um, with immuno-oncology, um, approaches and some of the unique features of protacs. Uh, we think in this space, um, also with respect to the resistance mechanisms and overcoming, um, that upregulation that is seen clinically, um, with the Inhibitors as well. So we think we have a very differential profile and it's and it's an exciting opportunity certainly. Um, and we're seeing that with the over-enrollment and the interest from the investigators, um, that treat patients. So

I think it's an exciting time and I'm sure no 1 and the team will be sharing clinical data as soon as we have it.

Hope that helps.

Jeff Boyle: Next question comes from the line of Peter Lawson with Barclays. Your line is open.

John Houston: Great. Thank you so much. Maybe just leading on from the prior question, for the KRAS G12D degrader and the update, when should we expect the initial, first-in-human data update? If you could talk through how enrollment is going and the number of sites that are open and any other details around that trial. Then I have a follow-up.

Next question comes from the line of Peter Lawson with Barclays, your line is open.

Noah Berkowitz: Thanks, Peter. Noah's right. Thank you so much. Peter, we just announced that we opened this study for enrollment a little ahead of schedule, and the immediate reaction seems to be very favorable. It's, we haven't offered guidance yet on when we will be sharing data, but you know you're going to get it soon. You'll get the guidance soon, meaning it'll be sometime next year, obviously. In terms of, you know, I would suggest just track things on clinicaltrials.gov because it's not, you know, we wouldn't typically be giving you site numbers and things like that for a Phase I study.

Great. Thank you so much. Maybe just leading on from the prior question, um, for the g12, the and the the updates. Um, you know, when, when should we expect the initial first in human data update and kind of, if you could talk through how enrollment is going and the number of sites that are open in any other details around that trial and then I have a follow

John Houston: Gotcha. Thank you. I apologize. I arrived late on the call for the BCL6 degrader, so that's ARV-393. The data in the second half, what should we focus on as regards to the data, other metrics that we may be delivering in that dataset? Thank you.

Thanks Peter. Um, no 1 advice. Sure. Um so Peter we you know, we just announced that we opened this study for enrollment a little ahead of schedule. And the immediate reaction seems to be very favorable. I its, we have an offer guidance yet on when we will be sharing data. Um, but you know, you're going to get it soon. Uh, you'll get the guidance. Meaning, it'll be sometime next year, obviously. Um, in terms of, you know, I would suggest just track things on clinical trials.gov because it's not, you know, we wouldn't typically be giving you cite numbers and things like that for a baseline stuff.

Gotcha, thank you. And I apologize. I, I arrived late on the call for the, but for the BCL set, so that's what 353, um, the data in the second half. And what, what should we focus on uh as regards to the data? Um kind of other metrics that we may be delivering in that data set. Thank you.

Noah Berkowitz: Sure. We have shared that we will provide some update of our dataset in the second half of this year. I really do not want to get ahead of ourselves and share what that disclosure will be, but the idea is that we are advancing through our dose escalation program. Obviously, in dose escalation programs, the data that you are going to see are going to be more like, before you are done with it, safety, PK, and early signs of efficacy. I think you can look for those. Obviously, as we approach the completion of that, or as we achieve the completion of that dose escalation or ready for expansion, we would be armed with more efficacy data, but still a focus on target engagement through PK and PD.

No.

Um, sure. So we've shared that we'll provide some update of our data set, uh, you know, in the second half of this year. Um,

John Houston: Gotcha. Would that be kind of like the range of like 10 to 20 patients, and I presume kind of heavily pretreated? Any details there?

I really don't want to get ahead of ourselves and share what that disclosure will be. Uh, but the idea is that we're advancing through our um, our dose escalation program, and obviously in dose escalation programs the data that you're going to see are going to be more like, uh, but before you're done with it, safety and PK an early signs of, uh, of efficacy. So I think you can look for those obviously, as we approach the completion of that. Whereas, we achieve the completion of that dose escalation or ready for expansion. We, you know, we we be armed with more efficacy data, but but still a focus on, um, targeting engagement through pkp data.

Gotcha, would would that be kind of like the range of like 10 to 20 patients or

Noah Berkowitz: Yeah, I would say that's a reasonable guess.

John Houston: Perfect. Thank you so much.

and I I presume kind of heavily pre-treated any details there. Yeah, I would say that's a reasonable guess.

Thank you so much.

Jeff Boyle: Next question comes from the line of Sudan Loganathan with Stephens. Your line is open.

Next question comes from the line of Sudan loan Nissan with Stevens. Your line is open.

Angela Cacace: Hey, this is Keith Alva on behalf of Sudan. Thank you for taking our question. Regarding the recent clinical data published by Cell Signaling Technology under Advanced Breast Cancer Asset, could you comment on your insights and what your perspective on that data is, and where do you see Vepdegestrant's competitive positioning within the treatment landscape? Thank you.

Hey, this is uh, Keith Salve on behalf of Sudan. Thank you for taking our question. Um, so regarding the recent clinical data

John Houston: No, thank you for the question. Noah, I know you started the survey.

Published by, uh, celui on their Advanced Breast, Cancer asset, could you kind of just comment on your insights and what your perspective? Uh, on that data is and where do you like, uh, see that begs competitive positioning within the treatment landscape. Thank you.

Noah Berkowitz: Yeah, I'm not sure if I have more to add than what was said earlier. We have always recognized that a drug like Vepdegestrant could demonstrate attractive benefit-risk in the second-line setting and the first-line setting. There is overlap between ESR-1 mutant and PI3 kinase targeting agents. In the end, what physicians are looking for are oral PROTACs, oral degraders. So in our case, it's PROTAC that has an attractive benefit-risk profile. So we think we're delivering that. And physicians kind of want to avoid toxicity as much as possible, and you get all the benefits they can after first-line therapy, before adding drugs that have some toxicity. So, the impact on market opportunity in that second-line setting is probably modest, but we haven't been offering specific guidance on market opportunities, so it's difficult to measure that modesty for you.

No, thank you for the question. Um, no. I know you're talking to the family. Yeah, I I'm not sure if I have more to add than what was said earlier. Uh,

We recognize have always recognized that um that the drug like sell cuties could uh demonstrate. Uh,

Um, there is overlap between ESR1 mutant and, uh, PI3 kinase, uh, targeting agents. Um,

you know, in the end, what positions are looking for? Are oral protects. I orals degraders. So, in our case of protac that has an attractive benefit risk profile. Uh, so we think we're delivering that and Physicians kind of want to avoid toxicity as much as possible and eat at all, the benefits they can after first-line therapy uh, before adding drugs without some toxicity. So,

You know, the impact on Market opportunity in that second line setting is probably modest but, you know, we haven't been offering specific guidance on Market opportunities. So it's difficult to to measure that modesty for you.

John Houston: Thank you.

Thank you.

Jeff Boyle: Next question comes from the line of Michael Schmidt with Guggenheim Partners. Your line is open.

Next question comes from the line of Michael Schmidt with Guggenheim Partners. Your line is open.

Andrew Saik: Hi, this is Sarah on to Michael. Thanks so much for taking my question. I wanted to quickly circle back to the oral pain care system that you mentioned. I would love to hear more details on that, and specifically, how you would expect to differentiate from later-stage pain care.

Hi. This is Sarah and I'm from Michael. Thanks so much for

Taking my question. Um, I wanted to quickly Circle back to the oral being here as something that you mentioned.

Um, I would love to hear more details on that, um, and specifically, uh, how you would expect to differentiate from later seed Panera.

John Houston: Sorry, we couldn't understand the question. Could you repeat it one more time?

Angela Cacace: There's a lot of echo.

I'm sorry, sorry, we couldn't understand the question. Could you repeat it one more time? There's a lot of echo.

Andrew Saik: One second.

oh um, 1 second

John Houston: Before pan-cae RAS, I have a differentiation for other KRAS.

and have a different.

Andrew Saik: Yes, exactly. The question was about the pan-RAS and any thoughts on differentiating from later-stage pan-RAS and pan-RAS programs.

Plan yeah, yes, exactly. The question was about the pancake Ras and, um, any thoughts on differentiating from later stage Paneras and Paneras programs.

John Houston: Sure, sure. As you know, we differentiate at least with ARV-102 from what we said publicly. Our pan-KRAS program, we aim to have the same level of potency differentiation as well. We do bind to and degrade, so we degrade. We do not inhibit, so we avoid that upregulation that is observed clinically. As you are aware, the clinical inhibitors of the pan-RAS inhibitor have shown a major mechanism of upregulation of KRAS as a resistance mechanism in the clinic. They are claiming around 20% to 30% of patients are seeing this. It is pretty profound. We think we have an opportunity there. Our oral pan-KRAS also will have great combinability. We will speak a bit about some of the differential profiles of our molecule relative to the pan-RAS molecules that are in the clinic.

Sure, sure. So, you know, as, as you know, um, we differentiate at least with arv 806 from what we said publicly, um, but our pan cos, um program, we aim to have the same level of, um, potency differentiation as well. Um, we do bind to, and degrade. So we degrade, we don't, you know, we don't inhibit. Um, so we avoid that upregulation, that's observed clinically. So, as you're aware, um,

The clinical um Inhibitors of um the pan raft. Inhibitor has shown a major mechanism of um upregulation of kras um as a resistance mechanism in the clinic. So they're they're claiming around um you know, 20 to 30% of patients. They're saying this. So it's

Pretty profound.

Opportunity there.

Um,

John Houston: We expect that we will have greater combinability with the immune stimulatory mechanisms like Keytruda and other IO agents because we will not inhibit T-cell receptor activity. We think that combinability will also provide a major advantage to other mechanisms clinically. There is a number of other differential activities that we are observing that we will be discussing as we move forward and advance the program. It is an exciting time for us, so stay tuned for more data this year at the triple meeting.

um, cos also will have great combined ability. Um, we'll speak a bit about some of the differential profiles of our molecule relative to, um, the pan raft, um, molecules that are in the clinic we expect. Um, that we'll have greater combin ability, um, with the, um, immune stimulatory mechanisms like, you know, katuda and other IO, um, agents because we will not inhibit, uh, T-cell receptor activity. So we think that combination will also provide a major advantage to other mechanisms clinically. So there's a number of other um differential activities that we're observing um that will be discussing as we move forward and Advance the program but it's an exciting time for us. Um, so stay tuned for um more data this year.

At the triple meeting.

Andrew Saik: Good. Thank you.

okay, thank

Jeff Boyle: Next question comes from the line of Terence Flynn with Morgan Stanley. Your line is open.

Operator: Hi, good morning. This is Chris on for Terence. Just one question from us. For ARV-393, beyond safety, what do you need to see in order to advance the asset into a combo trial with BCL6 degrader? Thank you.

Next question comes from the line of Terren fleeing with Sandy. Your line is open.

Hi, good morning. Uh, this is Chris on for Terrace. Uh, just 1 question from us, um, for 393

Beyond safety. What do you need to see in order to advance the asset into a combo trial with groix? Thank you.

Noah Berkowitz: Thanks, Chris. Noah, do you want to?

John Houston: Sure.

Noah Berkowitz: We don't probably not a lot. We weren't expecting any hematopoietic toxicity, which would be the principal toxicity of GLOFIT beyond the CRS seen in the first cycle, but well managed with GLOFIT's dosing over the first month or first three weeks. It's just a matter of reinforcing that we're not seeing any unexpected toxicities. I don't have much more to add to that.

Uh, dosing dosing over the first month or the first 3 weeks. So um it's just a matter of of achieve, you know, reinforcing that we're not seeing uh any any unexpected toxicities. And

You know, I don't have much more to add to that.

John Houston: Pretty clean drug, pretty clinically. Yeah.

Operator: Thank you.

Pretty clean drug pretty funny. Yep.

Thank you.

Jeff Boyle: Next question comes from the line of Evan Nkomo with Citi. Your line is open.

Next question comes from the line of Eagle movie with City. Your line is open

Edward Tenthoff: Hi, this is Julian Kim on for you all. Thanks for taking our question. Maybe just one quick one from us. Can you comment on whether AI was utilized to facilitate the compilation and submission of modules for Vepdegestrant to the FDA? More broadly, any potential utilization in the early drug development pipeline? Thanks.

John Houston: is a great question. I suppose it is your definition of AI. We certainly use a lot of artificial intelligence in all of our research programs. Angela could talk to the different features of that. I went on that. I was using the actual NDA application. Noah, I am not sure if you learned.

Hi, this is Julian Kim on for your goal. Thanks for taking our question. Maybe just 1 quick 1 from us can can you comment on whether AI was utilized to facilitate the compilation and submission of modules for web deck to the FDA and more broadly any potential utilization of the early drug development pipeline? Thanks.

No, that's a great question. Um,

I suppose you know the definition of EI. Um, yeah. We've certainly used a lot of kind of, um, uh, artificial intelligence in all of our, uh, research programs, and Angela could talk to the different features of that. And whether or not I would use the actual, uh,

88 black application.

Noah Berkowitz: Well, you know, part of the NDA is the submission process. We do work with some vendors. So there is AI that is going on there through our vendors. But in terms of our business overall or the development part of our business, think of AI as being able to help us with a lot of medical writing, right? So we are going to be able to take documents that we have previously generated, you know, across different assets and learn from them. These are things we are doing currently and learn from them to impact our medical writing cost and efficiency in the future.

No, I'm not sure how much was that. Well

You know, part of the NDA is uh, submission process. We do work with

With some vendors. So there is AI. That's going on there through our vendors. But but in terms of our business overall or the development, uh, part of our business think of it, uh, AI is being able to help us with a lot of medical writing.

Right. So we're going to be able to take documents that uh we have previously generated, you know, across different uh across different assets.

Noah Berkowitz: Think of it also as something that helps in clinical operations to more efficiently review our vendor management, our contracts, so that there is more clear accountability and roles and responsibilities across different contracts for a company that does rely on a lot of externalized work in clin ops. Then obviously, we are using it all the time with our SaaS programming. That is something that has been ongoing. There are many other areas in the company that are beginning to use it, but at least that gives you a sense of how it could have been used for an NDA and in life in our development programs.

To learn from them. These are things we're doing currently and learn from them to impact our medical writing costs and efficiency in the future. Think of it. Also as something that helps in clinical operations to more efficiently review, our vendor management our contracts, uh, that there's more clear accountability and uh, roles and responsibilities across different contracts for a company that does rely on a lot of externalized. Um, a lot externalized work in Clin apps, and then, obviously, we're using it, um, in all the time with our staff programming, like, that's something that's been ongoing. Uh, there are many other areas in the company that are beginning to use it, but

That gives you a sense of how it could have been used for an NDA.

John Houston: I can comment on how we are using it in research. We have computational chemistry and computational biology teams that use AI all the time in machine learning algorithms. We have been applying AI to our PROTAC design features. As we have been in this for 13 years, we have actually accumulated a lot of real-world data on PROTAC activity and optimization. We are applying that and learning from it. We iterate our PROTAC design much faster now. We are seeing a big benefit in how we move with speed in research. This includes pharmacokinetic properties of these molecules and absorption features as well, which, as you probably know, is really key for PROTAC design. On the computational biology side, we are using it all the time for how we go about analyzing our ligand identification data.

And, uh, in like in our development programs.

And I can comment on how we're using it in research. So we have, uh, computational chemistry and computational biology teams that use AI all the time and machine learning algorithms. Um, we've been applying AI to our protac design features. As we've been in this for 13 years, we've actually accumulated a lot of real world data on protac activity and optimization. We are applying that and learning from it. So we iterate our protect designs much faster, um, now and so we're seeing a big benefit in how we move the speed and research. Um, and so this includes, um, you know, pharmaco kinetic properties of these molecules and absorption features as well which as you probably know is really key for protac design. Um, on the computational biology side, we're using it all the time for

John Houston: This enables us to go after previously undrugged targets and optimize those warheads to utilize in PROTACs for targeted protein degradation. In addition, I would say we use AI to mine real-world data from biomarker features that exist in publicly available datasets. This sets us up well for deep understanding of pathway biology. This is how we have been approaching our Parkinson's disease, and also our PSP, as well as other neurodegenerative diseases, and really mining CSF protein changes in those diseases and how to set a clinical group up really well to understand how we might use those biologic features to stratify patients. Thank you for the question.

How do we go about analyzing our, um, Ligon identification data? Um, so this enables us to go after previously on drugged targets and optimize those Warheads to utilize in protox, for targeted protein degradation in addition, I would say we use AI to mine real world data.

From, um, biomarker features that exist and publicly available data sets and this sets us up well for deep understanding of pathway biology. And this is how we've been approaching our Parkinson's disease, um, and also our PSP as well as other neuro degenerative, um, diseases. Um, and really mining CSF, protein changes, um, in those diseases and how to set the clinical group up really well to understand how we might use those biological features to stratify patients. So thank you for the question.

John Houston: Got it. Thanks so much.

Jeff Boyle: Next question comes from the line of Tyler Van Duren with TD Cowen. Your line is open.

Next question comes from the line of Tyler van Burren with TD Cowen. Your line is open.

Edward Tenthoff: Hi, this is Egon on for Tyler. Thank you for taking our question. Just to go back to the Vepdegestrant and Pfizer collaboration, has Pfizer indicated its willingness to revise the collaboration or give back rights to Arvinas? Why would they be motivated to give Arvinas back given the amount they have invested to date? Also, wouldn't that require a significant cash outlay by Arvinas? Are you willing to use the existing cash on hand with milestones or royalties to do that?

Hi. This is Dana on for Tyler. Thank you for taking our question. Um, just to go back to the vet Diagon fiser, collaboration has further indicated its willingness to revise a collaboration or give back rights to Vite. And why would that be motivated to give back given the amount they have invested to date. Um, also, wouldn't that require significant cash outlay by our Venice? And are you willing to use the existing cash on hand with Milestones or royalties to do that?

John Houston: Yeah, just to reiterate, we are in a current 50/50. The attractions of that 50/50 was the planning on second-line, first-line, and neoadjuvant, sorry, adjuvant trials. Now we are currently left in a situation where it is only second-line monotherapy, so less attractive in terms of our market size for Pfizer. They have shown no interest to develop Vepdegestrant further. So that is the first important thing, that Vepdegestrant will not be developed further by Pfizer. We are in a negotiation right now about what is the best way forward in terms of moving away from the 50/50 collaboration we had, where either Pfizer takes the asset, launches it, and gets more economics, or they hand the compound back to us. I have said really clearly, I will say it again, if the compound comes back to us, we are not spending any money on the further development of Vepdegestrant.

yeah, just to to be in to reiterate um,

We're in a foreign city 50/50 the um the attractions for that 50/50 was the planning on second line first line and new agent. Sorry, agent trials, know, we're currently left in a situation where there's only second lane monotherapy. So less attractive in terms of the market size for fiser. Uh, they have shown no interest to develop that further. So that's the first important thing that that would not be developed further by by Sizer. Um, we're in negotiation right now about what's the best way forward. In terms of moving away, from the 50/50 collaboration, we had where either uh fiser takes the asset and launches it and get gets uh more economics or they hand the component back to us.

John Houston: None at all. We would be running a process to find a partner who would then ideally launch the drug and ideally further develop the drug. We gain the benefit, the forward benefit of seeing the drug on the market. But we have no plans to further develop Vepdegestrant if we got the compound back.

I've saved really clearly, I'll say it again. If the compound comes back to us, we are not spending any money on the further development of that, none at all. Uh, we've been running a process to find a, a partner who would then ideally launch the drug, and I usually further develop the drug and we gain in the benefit. The forward benefit of seeing the drug on the market. But uh we have no plans to further develop

that if we got the contract back,

Noah Berkowitz: Thank you.

thank you.

Jeff Boyle: That concludes our Q&A session. I would like to turn the call back over to John Houston for closing remarks.

That concludes our Q&A session. I'd like to turn the call back over to John Houston for closing remarks.

John Houston: Thank you all for your time, and thanks, everyone, for joining us this morning and all the fabulous questions. Obviously, we look forward to providing additional updates in the coming months. Thank you so much for your time today.

Thank you, operator. And thanks everyone for joining us this morning in all the, The Fabulous questions. Obviously, we look forward to providing additional updates in the coming months, but thank you so much for your time today.

Jeff Boyle: Ladies and gentlemen, that concludes today's call. Thank you all for joining, and you may now disconnect.

ladies and gentlemen, that concludes today's call, thank you all for joining and you may now disconnect