Earnings Call Transcript - ARVN Q2 2025

Operator, Operator

Thank you for being here. I would like to welcome everyone to Arvinas' Second Quarter 2025 Earnings Call. I will now hand the conference over to Jeff Boyle, Arvinas' Vice President of Investor Relations. Please proceed.

Jeff Boyle, VP of Investor Relations

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 Investors 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'll 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. And now I'll turn the call over to John. John?

John G. Houston, CEO

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 programs across our pipeline of PROTAC degraders. We continued making significant strides across our early stage programs where we are enrolling patients in 3 Phase I 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 LRRK2 degrader and preclinical data for our BCL6 degrader, ARV-393. I'm also pleased to share an update on our antigen receptor degrader, luxdegalutamide, which we licensed to Novartis in 2024. We are pleased to see that Novartis is rapidly progressing the assets and announced the recent initiation of two combination Phase II trials that will further advance luxdegalutamide 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 III 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 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. First, we reprioritized our research pipeline, cutting a number of programs and continuing investment in our assets with the greatest potential value. And 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 vepdeg 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'll return to those three imperatives 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 Arvinas. 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. 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'm 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 vepdeg to launch by Pfizer or another partner, achieving critical data milestones, and efficiently allocating capital. I'll spend a few minutes discussing our vepdeg strategy before turning the call over to Noah and Angela who will provide updates and discuss upcoming milestones for our clinical programs. Andrew will then provide a financial overview and some thoughts on capital planning. First, regarding vepdeg. Our collaboration with Pfizer was signed in 2021 with the intention for vepdeg to be developed as a monotherapy and in combinations across the adjuvant first and second line settings. With that plan, the idea of having a 50-50 co-development and commercialization was very attractive. We are now on the threshold of vepdeg potentially becoming a best-in-class treatment in its first indication. Second line monotherapy treatment in ESR1 ER+/HER2- metastatic breast cancer. However, the recent decision to remove the combination pivotal trials from our development plans with Pfizer has created a situation where the 50-50 co-commercialization agreement no longer makes sense and we're actively reworking our collaboration. Should the negotiation lead to vepdeg being returned to Arvinas, we are prepared to seek a party to commercialize and further develop vepdeg. Reaching a positive conclusion for vepdeg is a critical step in maximizing its value while also allowing us to focus on our 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, 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 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'll turn the call over to Noah.

Noah Berkowitz, CMO

Thanks, John, and good morning, everyone. Our pipeline continues to progress at a remarkable pace, demonstrating the vast potential of our PROTAC platform. I'll 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 LRRK2. LRRK2 is a large multi-domain scaffolding kinase that plays a critical role in effective endo-lysosomal trafficking. Unlike traditional small molecule inhibitors that only block LRRK2's kinase activity, LRRK2 degraders eliminate pathologic scaffolding function, GTPAse activity, and the kinase activity of LRRK2 implicated in this disease. We believe our lead LRRK2 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 LRRK2 expression and activity contributes to neuro degeneration and its pathogenesis, making it a rational therapeutic target. And the second is progressive supranuclear palsy, or PSP, a disease where genetic variations in LRRK2 are associated with PSP progression. Additionally, we have published data associating the tau pathology of PSP with LRRK2-mediated endo-lysosomal 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 AD/PD 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 cerebral spinal fluid or CSF sampling. This was associated with substantial degradation of LRRK2 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 supports further study of LRRK2 degraders in PD and PSP. Dosing of the Phase I 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. 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. But first, I would like to provide some regulatory updates regarding vepdeg. We have submitted the new drug application for vepdeg. This represents another significant first for Arvinas, the first PROTAC degrader to enter clinical trials and have a positive readout in a Phase III trial. 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 vepdeg's profile as a potential best-in-class monotherapy. I'll now turn the call over to Angela.

Angela M. Cacace, CSO

Thanks, Noah, and good morning, everyone. ARV-393, our investigational oral PROTAC designed to degrade B-cell lymphoma 6, 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 the second quarter of 2025, we presented two sets of preclinical data for ARV-393. 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 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 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. These data highlights 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, I'm pleased to report that we have initiated a Phase I clinical trial of ARV-806, our novel PROTAC degrader targeting KRAS G12D. 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-806 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, ARV-806 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 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. In preclinical 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 preclinical models of KRAS G12D mutant cancers. These results highlight the strong therapeutic potential of ARV-806 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-806 and the first-ever data from our oral pan-KRAS degrader program later this year. With that, I'll turn the call over to Andrew to review our quarterly financial information.

Andrew R. Saik, CFO

Thanks, Angela, and good morning, everyone. I'm 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 vepdeg 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. 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 focused on bringing pipeline programs through major clinical inflection points. With respect to vepdeg, 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 vepdeg 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 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've seen great clinical success here in the past, both in the development of vepdeg in partnership with Pfizer, and in the platform validating out-licensing of luxdegalutamide to Novartis. We are excited to continue development of the next generation of Arvinas PROTACs. 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 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 luxdegalutamide were transitioned to Novartis. Revenue from the vepdeg collaboration agreement with Pfizer decreased $6.8 million related to the removal of two Phase III trials from the development plan during the first quarter of 2025. 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 vepdeg program of $10 million, a decrease in the luxdegalutamide 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 LRRK2 program of $2.1 million and the KRAS program of $1.5 million. 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'll turn the call over to John for closing remarks.

John G. Houston, CEO

Thanks, Andrew. As you've heard, 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 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. 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'd like to reiterate our confidence in our near-term plan to create value for patients and shareholders. This includes advancing vepdeg 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. 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 Boyle, VP of Investor Relations

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

Operator, Operator

And our first question comes from the line of Ted Tenthoff with Piper Sandler.

Edward Andrew Tenthoff, Analyst

Andrew, just one quick housekeeping. The restructuring charge that you mentioned, was that primarily in the G&A line? And then I have a pipeline question for you guys.

Andrew R. Saik, CFO

Yes. Ted, no, it was actually split up between research and development and G&A. And indeed, most of the stock-based compensation would have been recorded in the R&D section.

Edward Andrew Tenthoff, Analyst

Great. That makes sense. Awesome. So can you give us a little bit more color on what to expect from 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?

John G. Houston, CEO

Thanks, Ted. And yes, the trials are going well. And I'll hand over to Noah to give you some of the details.

Noah Berkowitz, CMO

Hi, Ted, thanks for the question. Yes, good morning. As you noted, we plan to provide a summary of the complete healthy volunteer data set at an upcoming conference. Additionally, if everything goes as planned, we will present some data on single ascending doses. While I won't go into specifics about the presentation, it should indicate that we are on track when compared to the findings from healthy volunteers.

Operator, Operator

Next question comes from the line of Jonathan Miller with Evercore ISI.

Jonathan Miller, Analyst

Congratulations on initiating your restructuring efforts. I would like to follow up on the question regarding the 102. It may be a bit early to know exactly what you will present regarding patients this year, but could you discuss what you aim to see in a more comprehensive patient data set? What are your criteria for success in patients that will provide you with confidence as you move forward with efficacy readouts?

John G. Houston, CEO

Thanks, Jonathan. Noah?

Noah Berkowitz, CMO

Sure. Jonathan, so, yes, thanks for the interest here. I think we've outlined that we expect to start a Parkinson's disease multiple dose study over the course of the next month or so. While I can't really comment about when those data will be presented, the idea is that we're enrolling patients with the insights gained from healthy volunteers regarding a dose range, and that will allow us to establish that in patients who have higher baseline LRRK2 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. 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-penetrant PROTAC 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 biomarkers that we can track and are going to be most predictive of an impact in the endo-lysosomal trafficking and neuroinflammation that is characteristic of Parkinson's disease and PSP. And so we expect we could start tracking this in real patients rather than healthy volunteers.

Jonathan Miller, Analyst

Awesome. And then maybe on the BCL6, you mentioned in the press release and this call that glofitamab, that combination results to present 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 may want to start with?

John G. Houston, CEO

I think I've been indicating in discussions that we can clearly address our interest in BCL6 here. Our primary goal is to determine the appropriate dose for monotherapy, which is required of us. However, our major focus is on advancing combination therapies, particularly for DLBCL. It's important for everyone to recognize that bispecific therapies in second-line and eventually in first-line DLBCL will play a significant role. If we can successfully combine these with bispecifics in patients and achieve results akin to our preclinical findings, we believe we will be well-equipped to introduce a new therapy approach that effectively enhances the bispecific's activity. Additionally, one of the key benefits of this combination is our understanding that ARV-393 may boost CD20 expression, potentially increasing the bispecifics' efficacy. Furthermore, we have demonstrated impressive potency with our drug, and if that translates successfully in clinical settings, it will provide us with a substantial competitive edge over the only other degrader currently in clinical trials.

Operator, Operator

Next question comes from the line of Derek Archila with Wells Fargo.

Unidentified Analyst, Analyst

This is Karl calling in for Derek. So I guess for ARV-102, could you talk a little bit more on the elevated LRRK2 level in PD patients in terms of how much should we expect and how to maybe feel confident that similar more than 50% degradation can be achieved in CSF? And then on the vepdeg, the label potentially, could you talk about maybe the base case, what could be some potential differentiation you could expect versus your competitors?

John G. Houston, CEO

I think I captured the second question with vepdeg, but there was a lot of cracking of the transmission to the first question. Did anyone here catch that?

Jeff Boyle, VP of Investor Relations

Yes, if you could you maybe just repeat the first question. Just the first…

Unidentified Analyst, Analyst

Yes, of course. Sorry about that. for ARV-102, so I guess the question is the elevated LRRK2 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?

John G. Houston, CEO

Yes, that's a great question. It has been established by external sources that there is an increase in LRRK2 protein expression in the brain and cerebrospinal fluid of patients with Parkinson's disease. We have observed in our single ascending dose studies that baseline levels of LRRK2 in Parkinson's patients are higher than those in healthy volunteers, which aligns with our expectations. A key advantage of the degrader is that we have demonstrated effective target engagement in the brain among healthy volunteers, whereas inhibitors achieve only around 30% inhibition in the brain and are less effective in reaching deep brain regions. Our degrader enhances engagement and, due to its iterative property, allows for continuous degradation of the target even at lower exposures, making us confident in our ability to reduce LRRK2 levels. This premise has been supported by preclinical models, and we believe we can validate these findings in multiple doses among Parkinson's disease patients. Regarding the differentiation of our vepdeg from competitors, it primarily revolves around efficacy, particularly the superior progression-free survival compared to fulvestrant monotherapy, where we see an improvement of about three months, which other drugs have not matched. Additionally, we will share patient-reported outcomes data soon, indicating that patients tolerate the drug well. The adverse event profile is also more favorable, with significantly lower gastrointestinal toxicity compared to other agents in this space. This combination of benefit and risk clearly distinguishes vepdeg from other treatments.

Operator, Operator

Next question comes from the line of Tazeen Ahmad with Bank of America.

Tazeen Ahmad, Analyst

I maybe wanted to focus on some commercial questions. So as you think about vepdeg and the upcoming launch, you're obviously bullish about its place potentially in monotherapy, but you also talked about needing to be careful about how you're prepping for the launch. So 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? And then 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'd 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?

John G. Houston, CEO

Yes. No, thank you for the question. Yes. So in the second part, I'll tackle that first. Clearly we're in negotiation with Pfizer right now. The original deal that we signed in '21 was a 50-50 co-development, co-commercialization, very attractive deal at the time. We had planned for doing second-line monotherapy, first-line adjuvant. And 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 vep at the moment is only focused on second-line monotherapy. So a smaller market really doesn't move the dial for Pfizer in terms of 50-50 and not particularly attractive for Arvinas either. So the dialogue we've 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 vep and launch vep, which goes back to the first question, which is, as we stated, we are really not building out a sales force at all. Right now, we're focused on, first of all, getting vep approved and also getting launch ready, which is a relatively minimal amount of money that we'll be spending between now and the end of the year. So the idea would be that with that launch readiness, if we got the asset back, we'd run an active process and be in a position for another company to take on the development and launch of vep fairly rapidly. So we're hoping there wouldn't be a particular gap.

Tazeen Ahmad, Analyst

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 then?

John G. Houston, CEO

No, no. Sorry, say the last bit again. Say the last bit of your question, sorry?

Tazeen Ahmad, Analyst

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.

John G. Houston, CEO

So, yes, the suitable partner. At the moment, the plan is that there will be no gap between getting approval and having a partner in place or having Pfizer launch. I think your question is if we don't get a partner after getting the asset back, then yes, we've considered that. Our plan is to find a partner if we get…

Operator, Operator

Next question comes from the line of Andrew Berens with Leerink Partners.

Unidentified Analyst, Analyst

This is Amanda on for Andy. We wanted to get your thoughts on the recent readout from the Phase III trial evaluating second-line HR+ breast cancer in patients without a PIK3CA mutation, which includes some ESR1 mutant patients. We're wondering how this affects your outlook for second-line ESR1 mutation patients and if you would consider a combination to address a broader population.

John G. Houston, CEO

Thanks for the question. Noah?

Noah Berkowitz, CMO

Sure. We are not surprised by the result. We see the potential for PIK3 mutation-directed drugs in breast cancer. There is some overlap between ESR1 mutations and PIK3CA. The key question is whether it's factored into our modeling, and my overall impression is that it will have little impact. I can pass this to my colleague, Alex, in commercial for additional comments. Part of your inquiry was about our plans to develop it with such an agent. The answer is that someone might pursue that, but we will not since we have already decided against further development of the drug and initiating new studies or combinations. This is something that would be very interesting to another company, and we have already explored that option, but it’s not something we will pursue.

Operator, Operator

Next question comes from the line of Li Watsek with Cantor Fitzgerald.

Li Wang Watsek, Analyst

Nice progress on the pipeline. I guess for vepdeg NDA submission, it sounds like you know the PDUFA date very soon. Should we anticipate priority review here? And any guidance on your part for the global filing strategy? Do you need maybe to wait for more mature vep data?

John G. Houston, CEO

Yes. For the second part of that question, I'll hand over to Noah. For the first part, yes, we're still awaiting details from the FDA. And as soon as we get that information, we'll pass that on. So we and don't have the PDUFA date yet. Noah, do you want to tackle that second part of the question?

Noah Berkowitz, CMO

Yes. What we've shared, what we've offered guidance to is our filing of the NDA in the U.S. And obviously, we're waiting on feedback regarding the PDUFA date. But regarding global strategy, we haven't offered guidance on that yet. So I think it would be premature.

Li Wang Watsek, Analyst

Okay. And then in terms of finding maybe a potential new partner for vepdeg in the case that you got the molecule back, can you elaborate some of the considerations that you prioritize, what's important for you guys in terms of maximizing the value?

John G. Houston, CEO

Yes, great question. I mean, clearly, we believe vepdeg is an important drug. We believe it has a lot of value. Because of the partnership we're in with Pfizer and the decisions that have been made, maximizing that value is going to be somewhat difficult. So that's why we're in discussion with Pfizer about changing the nature of the collaboration. And ideally, as I said, either Pfizer or Arvinas should go forward with the asset more kind of fuller economics. And in the scenario where maybe we get the compound back, yes, we will be looking to partner, and 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. Our view is that we vepdeg in the hands of a partner, be it Pfizer or another company, that really takes the compound forward, launches it and progresses with further development.

Operator, Operator

Next question comes from the line of Akash Tewari with Jefferies.

Unidentified Analyst, Analyst

This is Manoj asking about the expectations for the Denali LRRK2 data in the first half of next year. If the trial does not succeed or fails to meet expectations, what indicators from that study would you look for to support confidence in your own degrader program?

Noah Berkowitz, CMO

Yes, thank you for the question. If you were asking about expectations for the Denali program from last year, that's a great question. We believe that LRRK2 is an excellent target, and I think the key opinion leader community would agree. The main issue is determining the best drug to target that area. We see some potential in an inhibitor, though it comes with challenges. As I mentioned earlier, the inhibitor doesn't appear to penetrate the brain as effectively as our degrader does. Additionally, it may not engage its target as well. Our approach offers broader engagement; we are not just binding and degrading the target, but also eliminating the LRRK2 kinase activity and scaffold function through degradation. All these factors make a degrader more appealing than an inhibitor. While we think the inhibitors may succeed, we are confident they have the right target, and we look forward to learning from their results, including insights on patient selection and any signals that emerge from their trial.

Operator, Operator

Next question comes from the line of Evan Seigerman with BMO Capital Markets.

Conor Thomas MacKay, Analyst

This is Conor MacKay on for Evan. We just had a quick one on the submission of vepdeg. Given the current environment at the FDA, we were just wondering if you'd be willing to characterize your recent interactions with the agency and maybe comment on level of alignment there. And then just one quick follow-up on ARV-806. Would you be able to share a little bit more on how you're thinking about positioning this asset versus the pan-KRAS agent you mentioned today?

John G. Houston, CEO

That's a great question. I suppose it depends on how you define AI. Yes, we have certainly utilized a lot of artificial intelligence in our research programs, and Angela can provide details on the various features of that, although I am not sure if it was included in the actual NDA application.

Noah Berkowitz, CMO

Well, part of the NDA is a submission process. We do work with some vendors. So there is AI that's going on there through our vendors. But in terms of our business overall or the development part of our business, think of it AI as being able to help us with a lot of medical writing, right? So we're going to be able to take documents that we have previously generated across different assets and learn from them. These are things we're doing currently and learn from them to impact our medical writing cost 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 that there's more clear accountability and roles and responsibilities across different contracts for a company that does rely on a lot of externalized work in clinical ops. And then, obviously, we're using it in all the time with our status programming, like that's something that's 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 like in our development programs.

Angela M. Cacace, CSO

And I can comment on how we're using it in research. So we have computational chemistry and computational biology teams that use AI all the time in machine learning algorithms. 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 PROTAC designs much faster now. And so we're 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're using it all the time for how do we go about analyzing our ligand identification data. So this enables us to go after previously undrugged targets and optimize those warheads to utilize in PROTAC 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 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 and also our PSP as well as other neurodegenerative diseases and really mining CSF protein changes in those diseases and have set the clinical group up really well to understand how we might use those biologic features to stratify patients. So thank you for the question.

Operator, Operator

Next question comes from the line of Tyler Van Buren with TD Cowen.

Unidentified Analyst, Analyst

This is Ikan speaking on behalf of Tyler. I would like to revisit the collaboration surrounding vepdeg and Pfizer. Has Pfizer shown any interest in altering the collaboration or returning rights to vepdeg? What incentives might they have to return vepdeg considering the significant investments they have made so far? Additionally, would this necessitate a considerable cash expenditure from Arvinas? Are you open to using the current cash reserves, alongside milestones or royalties, for that purpose?

John G. Houston, CEO

Yes, to clarify, we're currently in a 50-50 arrangement. The initial appeal of this partnership was based on plans for second-line, first-line, and adjuvant trials. At present, however, we're left with only second-line monotherapy, which is less appealing in terms of market size for Pfizer. They have shown no interest in further developing that. This is the crucial point: Pfizer will not be developing it further. We are currently negotiating the best path forward to move away from the 50-50 collaboration we had, where Pfizer could either take the asset and launch it, benefiting economically, or return the compound to us. I want to be very clear: if the compound comes back to us, we won't allocate any funds toward further development of vepdeg. Our plan would be to seek a partner to launch and ideally further develop the drug, so we can benefit from it on the market. However, we have no intentions to develop it further if we receive the compound back.

Operator, Operator

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

John G. Houston, CEO

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

Operator, Operator

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