Arvinas Q2 2025 Earnings Call Transcript

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Provided by Quartr
August 6, 2025

Key Takeaways

  • Positive Sentiment: Strong pipeline momentum with enrollment in three Phase I trials including the KRAS G12D degrader ARV-806 and compelling first-in-human data for the LRRK2 degrader ARV-102.
  • Positive Sentiment: NDA submission for second-line monotherapy VetDeg marks the first PROTAC degrader New Drug Application backed by positive Phase III VERITEC II data and a New England Journal of Medicine publication.
  • Positive Sentiment: Lexdegalutamide, licensed to Novartis, has advanced into two Phase II prostate cancer trials, supporting up to $1 billion in milestones and validating the PROTAC platform.
  • Positive Sentiment: Company-wide restructuring, including pipeline reprioritization and a one-third workforce reduction, has extended the cash runway into 2028 and improved operational efficiency.
  • Neutral Sentiment: Arvinas is actively renegotiating its 50/50 partnership with Pfizer on VetDeg to reflect the focus on second-line monotherapy and exploring options for commercialization or re-partnering.
AI Generated. May Contain Errors.
Earnings Conference Call
Arvinas Q2 2025
00:00 / 00:00

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Operator

Thank you for standing by. At this time, I would like to welcome everyone to Aurinia's Second Quarter twenty twenty five Earnings Call. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question and answer session. Thank you.

Operator

I would now like to turn the conference over to Jeff Boyle, Arvina's Vice President of Investor Relations. Please go ahead.

Jeff Boyle
Jeff Boyle
VP - IR at Arvinas

Good morning, everyone, and thank you for joining us. Earlier today, we issued a press release with our second quarter twenty twenty five financial results, which is available on the Investor and Media section of our website at arvinas.com. Joining the call today are John Hewson, Arvinus' Chief Executive Officer, President and Chairperson Noah Berkowitz, our Chief Medical Officer Angela Cacasse, 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.

Jeff Boyle
Jeff Boyle
VP - IR at Arvinas

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 Houston
John Houston
Chairperson, CEO & President at Arvinas

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 Arvindis with significant clinical and regulatory progress across our pipeline of ProTag degraders. We continued making significant strides across our early stage programs, where we are enrolling patients in three Phase I trials across our neuro and oncology portfolio, including the recently initiated trial with our KRAS G12D degrader, ARV-eight zero six.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

During the quarter, we also presented compelling first in human data from ARV-one hundred two, our LAR2 degrader, and preclinical data for our VCL6 degrader, ARV-three ninety three. I'm also pleased to share an update on our antigen receptor degrader, lux degalutamide, which we licensed to Novartis in 2024. We are pleased to see that Novartis is rapidly progressing the asset and announced the recent initiation of two combination phase two trials that will further advance lexdegalutamide 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.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

As a reminder, our license agreement with Novartis includes up to $1,000,000,000 in development, regulatory and commercial milestones as well as tiered royalties. The accomplishments from across our portfolio are the latest in the long stream of successes at Arvinis. At the same time, we have recognized the ongoing need to enhance our financial position and set Arvinis 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.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

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 vet tech towards commercial launch. Second, achieving critical data milestones from our pipeline in the next twelve months. And third, carefully allocating capital to support those milestones efficiently.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

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 Arvinis. 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 seemed 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.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

The board is fully engaged and intent on finding the right CEO to lead Arvinis 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 honoured to continue as chair of the Arvinus board once I step down from the CEO role. For now, our long term strategy is driven by the imperatives I mentioned above, advancing vet deck to launch by Pfizer or another partner, achieving critical data milestones and efficiently allocating capital. I'll spend a few minutes discussing our VetDeg 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.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

First, regarding VetDeg, our collaboration with Pfizer was signed in 2021 with the intention for VetDeg to be developed as a monotherapy and in combinations across the adjuvant first and second line settings. With that plan, the idea of having fiftyfifty co development and commercialization was very attractive. We are now on the threshold of VetDeg potentially becoming a best in class treatment in its first indication, second line monotherapy 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 Pfizer has created a situation where a fiftyfifty co commercialization agreement no longer makes sense, and we're actively reworking our collaboration. Should the negotiations lead to VetDeg being returned to VetDeg, we are prepared to seek a party to commercialize and further develop VetDeg.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

Reaching a positive conclusion for VetDeg is a critical step in maximizing its value while also allowing us to focus on a promising clinical pipeline. Preclinical data has shown that ARV102, ARV-three ninety three and ARV-eight zero six 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 PRO TAC 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
Chief Medical Officer at Arvinas

Thanks, John, and good morning, everyone. Our pipeline continues to progress at a remarkable pace, demonstrating the vast potential of our ProTech platform. I'll begin with our most advanced neuroscience program, ARB102. We have designed investigational oral PROTAC degraders to cross the blood brain barrier and selectively degrade leucine rich repeat kinase two, or LRRK2. LRRK2 is a large multi domain scaffolding kinase that plays a critical role in effective endolysosomal trafficking.

Noah Berkowitz
Chief Medical Officer at Arvinas

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, ARB102, 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 neurodegeneration 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 LARC two mediated endolysosomal dysfunction, which again makes this a very rational therapeutic target.

Noah Berkowitz
Chief Medical Officer at Arvinas

ARV102 is the only PROTAC we know of in the clinic to demonstrate deep brain penetration in nonhuman primates, and now blood brain barrier penetration in humans. As presented at the ADPD Congress, ARV102 is well tolerated at single doses up to two hundred milligrams, and at multiple doses up to eighty milligrams. No serious adverse events after single and multiple oral doses in healthy volunteers were observed. Single and multiple doses of ARV102 demonstrated dose dependent exposure in the central nervous system by cerebrosinal 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.

Noah Berkowitz
Chief Medical Officer at Arvinas

We believe the high levels of target engagement, enhanced potency, and pathway engagement demonstrated with ARV102 will differentiate it from clinical stage inhibitors, which in preclinical studies have not shown the same ability as ARV102 to move important biomarkers in the CSF. These PK and PD properties and acceptable safety and tolerability profile support further study of LRRK2 degraders in PD and PSP. Dosing of the phase one 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

Noah Berkowitz
Chief Medical Officer at Arvinas

2026. In parallel to the advancement of ARV102, we are making nice progress with ARV393, our Bcl6 degrader, and ARV806, 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.

Noah Berkowitz
Chief Medical Officer at Arvinas

We have submitted the new drug application for Vepdeg. This represents another significant first for Arvinus, the first PROTAC degrader to enter clinical trials, and have a positive readout in a phase three trial. It's also the first ever new drug application submitted for a PROTAC. The NDA was supported by Veritec II 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 Veritec II data was very rewarding.

Noah Berkowitz
Chief Medical Officer at Arvinas

Later this year, we plan to present the patient reported outcomes data from the VERITECK II trial. We believe these data disclosures reinforce Vepdeck's profile as a potential best in class monotherapy. I'll now turn the call over to Angela. Angela?

Angela Cacace
Angela Cacace
Chief Scientific Officer at Arvinas

Thanks, Noah, and good morning, everyone. ARB-three ninety three, our investigational oral PROTAC designed to degrade B cell lymphoma six protein, or BCL6, is an exciting asset that demonstrates the power and breadth of our platform. Bcl-six 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 Honschkin 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 Bcl-six.

Angela Cacace
Angela Cacace
Chief Scientific Officer at Arvinas

With its iterative activity, ARV393 potently and rapidly degrades the BCL six protein, which is critical to overcoming its rapid resynthesis rate and sustaining antitumor activity. In 2025, we presented two sets of preclinical data for ARV-three ninety three. First, at the American Association for Cancer Research Annual Meeting in April, we presented new preclinical data highlighting the therapeutic potential of ARV-three ninety three in combination with standard of care biologics, chemotherapy, and small molecule inhibitors targeting cooperative oncogenic drivers. ARV-three ninety three combinations demonstrated increased tumor growth inhibition, including tumor regressions in preclinical models of aggressive B cell lymphoma. These data underscore the potential of ARB-three ninety three 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.

Angela Cacace
Angela Cacace
Chief Scientific Officer at Arvinas

In June at the European Hematology Association Conference, we presented new data demonstrating the potent single agent efficacy of ARV-three ninety three 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 PCL6 targeted degrader in human models of these diseases. These data highlight the broad utility of ARB three ninety three 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-three ninety three with glufinumab, a CD3CD20 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 ARB ability to increase CD20 expression, which provides rationale for the exploration of ARV393 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 ARB-three ninety three later this year.

Angela Cacace
Angela Cacace
Chief Scientific Officer at Arvinas

As you have heard from NOAA, I'm pleased to report that we have initiated a phase one clinical trial of ARV-eight zero six, our novel protactograder 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 eight zero six 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, ARB-eight zero six has shown it can overcome KRAS resynthesis and increased expression.

Angela Cacace
Angela Cacace
Chief Scientific Officer at Arvinas

A major clinically relevant emerging mechanism of resistance that existing inhibitors have failed to address. Our PROPAC 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 eight zero six 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 eight zero six exhibits dose dependent selective robust anti tumor activity, culminating in regressions across preclinical models of KRAS G12B mutant cancers. These results highlight the strong therapeutic potential of ARV-eight zero six and support its continued and rapid advancement in the clinic.

Angela Cacace
Angela Cacace
Chief Scientific Officer at Arvinas

We look forward to updating you on our clinical progress and anticipate sharing preclinical data from ARB-eight zero six 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 Saik
Andrew Saik
CFO & Treasurer at Arvinas

Thanks, Angela, and good morning, everyone. I'm pleased to provide financial highlights for the second quarter ended 06/30/2025 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.

Andrew Saik
Andrew Saik
CFO & Treasurer at Arvinas

When combined with the announced changes to our Vepdev development plan, our cash runway was extended into the 2028. These changes will make us leaner and more efficient as we work towards a promising stretch of catalyst over the next twelve 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 disciplined 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 cost to prepare the market in the coming months.

Andrew Saik
Andrew Saik
CFO & Treasurer at Arvinas

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 VetZeg 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 lexdegalutamide to Novartis.

Andrew Saik
Andrew Saik
CFO & Treasurer at Arvinas

We are excited to continue development of the next generation of Arvinas Protechs. I'll now briefly touch on some key financial highlights for the 2025. At the end of the second quarter, we had approximately $861,200,000 in cash, cash equivalents and marketable securities on the balance sheet compared with $1,040,000,000 as of 12/31/2024. Revenue for the three months ended 06/30/2025 totaled $22,400,000 compared to $76,500,000 for the three months ended June 3024. The decrease of $54,100,000 was primarily driven by $45,600,000 of decreased revenue from the Novartis license agreement and the Novartis asset agreement, both of which were entered into during the three months ended 06/30/2024, and were completed by 12/31/2024 as the technology transfer of our ongoing planned clinical trials of lexbegolutamide were transitioned to Novartis.

Andrew Saik
Andrew Saik
CFO & Treasurer at Arvinas

Revenue from the Vetbeg collaboration agreement with Pfizer decreased $6,800,000 related to the removal of two phase three trials from the development plan during the 2025. General and administrative expenses were $25,300,000 in the second quarter compared to $31,300,000 for the same period of 2024. The decrease of $6,000,000 was primarily driven by a decrease in personnel and infrastructure related costs of $4,800,000 and professional fees of $2,200,000 partially offset by an increase in costs related to developing our commercial operations of $1,100,000 Research and development expenses were $68,600,000 in the second quarter compared to $93,700,000 for the same period of 2024. The decrease of $25,100,000 was primarily driven by a decrease in the Bevtab program of $10,000,000 a decrease in the Luxtegalutamide program of $9,500,000 and decreases in personnel expenses and nonprogram specific expenses of $10,300,000 offset by an increase in the LARC II program of $2,100,000 and the KRAS program of $1,500,000 Restructuring costs in the quarter amounted to $7,400,000 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 $6,400,000 The announced restructuring is now complete and the full benefit in terms of cost reduction will be seen starting in the third quarter.

Andrew Saik
Andrew Saik
CFO & Treasurer at Arvinas

We are maintaining our prior cash runway guidance into the 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
John Houston
Chairperson, CEO & President at Arvinas

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 twelve months, including clinical data from ARV-one hundred two and ARV393, and potentially initial clinical data from ARV806, and of course, the potential for the first ever approval of a PROTAG. During this time, we will also advance ARB-one hundred two in its ongoing trial in patients with Parkinson's and initiate a trial with ARB-one hundred two in progressive supranuclear palsy. Before opening the call for Q and A, I'd like to reiterate our confidence in our near term plan to create value for patients and shareholders.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

This includes advancing VetDeg 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 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 and A portion of the call. Jeff?

Jeff Boyle
Jeff Boyle
VP - IR at Arvinas

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

Operator

Thank you.

Operator

And our first question comes from the line of Ted Tanoff with Piper Sandler. Your line is open.

Ted Tenthoff
Ted Tenthoff
Biotech Equity Research Analyst at Piper Sandler Companies

Thank you very much. Andrew, just one quick housekeeping. Restocking cards that you mentioned, was that primarily in the g and a line? And then I have a pipeline question for you guys.

Andrew Saik
Andrew Saik
CFO & Treasurer at Arvinas

Yeah. Hey, Ted. No. It was actually split up between research and development and g and a, and indeed, most of the, stock based comp would have been recorded in the r and d section.

Ted Tenthoff
Ted Tenthoff
Biotech Equity Research Analyst at Piper Sandler Companies

Great. That makes sense. Awesome. So, can you give us a little bit more color on what to expect from one zero two data this year? I know that, we've still got more to hear about the healthy volunteers for the multiple ascending, cohorts.

Ted Tenthoff
Ted Tenthoff
Biotech Equity Research Analyst at Piper Sandler Companies

But what should we expect from the single ascending doses from Parkinson's patients? Thanks.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

Thanks, Ted. And, Deb, the trial is going well. And I'll hand over to Noah to give you some of the details.

Noah Berkowitz
Chief Medical Officer at Arvinas

Hi, Tim. Thanks for the question. So as you said, I think you summed it up, we're going we expect a conference, an upcoming conference, to some summarize the full healthy volunteer dataset that we assembled. And in addition to that, if things work out, we'll be able to present some SADS data, you know, which will I'm not gonna 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, know, you when you compare it to the healthy volunteer funds.

Ted Tenthoff
Ted Tenthoff
Biotech Equity Research Analyst at Piper Sandler Companies

Great. Alright. Looking forward to that and excited about the emerging pipeline.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

Thanks, Ted.

Operator

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

Jonathan Miller
MD - Biotech & Pharma Equity Research at Evercore ISI

Hi, guys. Thanks so much for taking my question and congrats on as I should say, congrats if it's the wrong word, but good job on getting your restructuring going. I'd love to follow-up Maybe it's a little too early to say exactly what you'll give us in patients this year. Maybe could you talk a little bit about what you hope to see in a more full patient dataset?

Jonathan Miller
MD - Biotech & Pharma Equity Research at Evercore ISI

What are your bars for success in patients that can give you confidence going into later on efficacy readouts?

Jeff Boyle
Jeff Boyle
VP - IR at Arvinas

Thanks, Jonathan. Noah?

Noah Berkowitz
Chief Medical Officer at Arvinas

Sure. Jonathan, so 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.

Noah Berkowitz
Chief Medical Officer at Arvinas

And we 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 LARC2 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 are 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. 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 impact in the endolifosomal trafficking and neuroinflammation that is characteristic of Parkinson's disease and PSP. And so we expect we can start tracking this in real patients rather than the healthy volunteers.

Jonathan Miller
MD - Biotech & Pharma Equity Research at Evercore ISI

Awesome. Thank you. And then maybe on the BCL6, you mentioned in the press release and this call the glafitamab 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 might want to start with?

John Houston
John Houston
Chairperson, CEO & President at Arvinas

I think we've been I've been signaling in conversations, we can certainly speak clearly, very directly about it here, That our interest for BCL6 is to 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. And I think it should be clear to everyone that bispecifics in second line plus DLBCL, and maybe eventually not that far in the future in first line, are important drugs in that space. So if we can combine with bispecifics in human beings and get results that look anything like what we've seen pre clinically, we think we're well positioned for a new modality of therapy, with a real orthogonal approach that enhances the activity of the bispecific.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

And remember, one of the great combination properties here is that we recognize that our AR-three ninety three can increase the expression of CD20, which could potentially make the bispecifics even more active. And on top of that, we've been reporting out the great potency with our drone 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. Thank you so much.

Operator

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

Analyst

Good morning. This is Carl calling in for Derek. Thank you for the question. So I guess for ARB one zero two, could you talk a little bit more on the elevated lab two 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 Mepdeq, the label potentially, could you talk about maybe the base case, what could be some potential differentiations you could expect for your competitors? Thank you so much.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

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

Jeff Boyle
Jeff Boyle
VP - IR at Arvinas

Yes. Could you maybe just repeat the first question?

Analyst

Yeah. Of course. Just the first Sorry about that.

Analyst

So for the ARB-one hundred two, I guess the question is the elevated block two 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 Houston
John Houston
Chairperson, CEO & President at Arvinas

Yeah. So I think it's a great question. So fundamentally, I think it's been established by external sources that there's increased LARC2 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 Parkinson's, of LARC2, than we observed in the healthy volunteers. So that's already kind of consistent, but 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. And we know that the inhibitors just don't do that well. They're only achieving 30% or so inhibition in the brain.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

We know pre clinically they're not reaching deep brain regions as effectively as our debrater can. So we're getting higher engagement. And because we have a debrater 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 LARC2 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.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

Regarding the second question, I think the question was, what differentiates us essentially from with our Beptegs from competitors in this space. And more or less it comes down to efficacy, the better PFS that's been seen when compared to fulvestrant control, monotherapy control, which in our hands we're talking about three months improvement, which other drugs really haven't achieved. On top of that, we're leaning into some PRO data that you'll see soon that show that the patients experienced 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 thirty three percent of that, when you compare to different drugs.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

And I think that that combination of benefitrisk really stands out for BepteG when compared to other agents.

Analyst

Thank you.

Operator

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

Tazeen Ahmad
Tazeen Ahmad
MD - US Equity Research at Bank of America

Hi, good morning. Thanks for taking my questions. I maybe wanted to focus on some commercial questions. So as you think about Bebdeg 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, a Salesforce? When do you start prepping for that? How has that plan changed relative to what you would have planned for before?

Tazeen Ahmad
Tazeen Ahmad
MD - US Equity Research at Bank of America

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, you know, kind of in process now for for seeking a potential replacement should Pfizer return those rights? Thanks.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

Yeah. No. Thank thank you for for the question. Yeah. So in the second part, I'll I'll talk about first.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

Clearly, we're in negotiation with with with with Pfizer right now. The original deal that we signed in 2021 was a fifty-fifty co development co commercialization. Very attractive deal at the time. We had plans for doing second line monotherapy, first line adjuvant. And that would have been a very significant market and a very significant opportunity to share fifty-fifty.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

With the decision not to go forward with the first line or the second line combo, It puts us into a position where Veth, 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 fiftyfifty, and not particularly attractive for our events 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 the 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 VEV and launch VEV. Which goes back to the first question, is, as we stated, we are really not building out a sales force at all.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

Right now we're focused on, first of all, them 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 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 that fairly rapidly. So we're hoping there wouldn't be a particular gap.

Tazeen Ahmad
Tazeen Ahmad
MD - US Equity Research at Bank of America

Okay. But as of today, could there be a gap between when it got approved and when it launched if if you, are not able to secure the right term? No. And Okay.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

Oh, sorry. Say the last bit again? The say the last bit of question. Sorry.

Tazeen Ahmad
Tazeen Ahmad
MD - US Equity Research at Bank of America

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 Houston
John Houston
Chairperson, CEO & President at Arvinas

Well, she said yeah. She said the suitable partner. So at the moment, if the plan is to be no gap between, getting approval, ideally having a partner in place or having Pfizer launch, there'd 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, then, yeah, we'd be taking stock of that. Our our plan is that we'd we'd find a a partner.

Tazeen Ahmad
Tazeen Ahmad
MD - US Equity Research at Bank of America

Okay.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

If we get

Operator

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

Amanda Acosta-Ruiz
Associate - Biotechnology Equity Research at Leerink Partners

Hi, everyone. This is Amanda on for Andy. We wanted to get your thoughts on the recent readout from the Phase three trial evaluating gated CSF and second line HR positive breast cancer in patients that don't have a PIK3C mutation, which then would include some ESR1 mutant patients. And we're wondering how does this change, or if this changes your outlook for second line ESR1 mutation patients and if you would ever consider a combination with, GATA with GATA to address a broader population? Thank you.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

Thanks for the question. Noah?

Noah Berkowitz
Chief Medical Officer at Arvinas

Sure. Yeah, so we wouldn't we really are not surprised by the result. We recognize the opportunity for PIK3 mutation directed drugs to in breast cancer. There is overlap, as you had suggested, between ESR1 mutations and PIK3CA.

Noah Berkowitz
Chief Medical Officer at Arvinas

So the question comes down to whether it's in our modeling. And 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. 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.

Noah Berkowitz
Chief Medical Officer at Arvinas

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, but it's not something we'll be embarking.

Operator

Next question comes from the line of Li Watsak with Cantor Fitzgerald. Line is open.

Li Watsek
Director at Cantor Fitzgerald

Hey, good morning, guys. Thank you for taking our questions and nice progress on the pipeline. I guess for VipDag NDA submission, sounds like you know the PDUFA date very soon. Should we anticipate perhaps priority review here? And, any guidance on your part, for the global, filing strategy?

John Houston
John Houston
Chairperson, CEO & President at Arvinas

Yes. But 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 don't have the PDUFA date yet.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

Noah, do you want to tackle that second part of the question?

Noah Berkowitz
Chief Medical Officer at Arvinas

Yeah. I you know, we what we've shared, what we've offered guidance to is our filing of the of the NDA in The US. And obviously, we're waiting on feedback regarding PDUFA date. But regarding global strategy, haven't offered guidance on that yet, so I think it would be premature to me.

Li Watsek
Director at Cantor Fitzgerald

Okay. And then, you know, in terms of finding, maybe a potential new partner for vDAG 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 Houston
John Houston
Chairperson, CEO & President at Arvinas

Yes. Great question. Clearly, we believe VEDDAG 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 are being made, maximizing that value is going to be somewhat difficult.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

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 Vintage should go forward with the asset more sort of economics. And in the scenario where maybe we get the compound back, yes, we'd be looking to partner. Ideally a partner that does have the of the zeal and interest to develop the asset further both from The U. S.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

And the global setting. Our involvement of that I think would be relatively minimal in terms of development. Our view is that we want VetDeg in the hands of a partner, be it Pfizer or another company, that really takes the compound forward, launches it, and progresses it with further development.

Operator

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

Analyst

Hey. This is Manojo on for Agash. Thanks for taking our question. What are your expectations around the DENALI LLRK two 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 degrader program?

Noah Berkowitz
Chief Medical Officer at Arvinas

Yes. Thanks for the question.

Noah Berkowitz
Chief Medical Officer at Arvinas

Yes. If the question was expectations for the Denali program last year, I think it's a fantastic question. We think that LRRK2 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?

Noah Berkowitz
Chief Medical Officer at Arvinas

And so we see some virtue in an inhibitor, but it has challenges. And I outlined that earlier, that the inhibitor seem to penetrate the brain as deeply as, let's say, our degrader. 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, and that we're eliminating, because of that degradation, the LRRK2 kinase activity, the GTPS activity, gap holding function.

Noah Berkowitz
Chief Medical Officer at Arvinas

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

Noah Berkowitz
Chief Medical Officer at Arvinas

And overall, whatever signals can come out of their trial.

Analyst

Thanks.

Operator

Next question comes from the line of Ivan Sigerman with BMO Capital Markets. Your line is open.

Conor MacKay
Conor MacKay
Equity Research Senior Associate at BMO Capital Markets

Hi there. This is Connor McKay on for Evan. Thanks for taking our question. We just had a quick one on the submission of Vepdeg. Given the current environment in 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.

Conor MacKay
Conor MacKay
Equity Research Senior Associate at BMO Capital Markets

And then, just one quick follow-up on ARV eight zero six. 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? Thank you.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

Yes. 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.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

Their their timing in terms of getting back to us has been really good. So even though I 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 VEGF, which is a really good positive thing for us. Noah, do you want to tackle?

Noah Berkowitz
Chief Medical Officer at Arvinas

Regarding eight zero six, I'll I'll make some comments about clinical, and I'll turn it when I'm done to Angelo who may have some comments about some of the interesting differentiation preclinically. So this drug entered the clinic a little faster than we expected because of great efficiencies at the team level. Then what we noticed is that there is tremendous appetite for drugs like ours in this space because our cohorts are, in demand. So we're advancing through early dose escalation now.

Noah Berkowitz
Chief Medical Officer at Arvinas

We don't you know, overall, we expect that there are going to be five or fewer dose levels in this escalation. So that's going to at least give you a sense of where we're headed. The key is to look at where we are in monotherapy, compares ourselves to data that's out for inhibitors, and the very, very modest and unimpressive data that have been presented by a degrader in the clinic, which is limited, had dose limiting toxicity relating to hepatic function. So we'll compare ourselves to that. We have good gono go criteria. But then the intention is to move our IV degrader, which has once a week, possibly once every two week dosing.

Noah Berkowitz
Chief Medical Officer at Arvinas

That's something we learned from this dose escalation. In combination with EGFR inhibitors and with chemotherapy. And that's 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'll turn it to Angela.

Jeff Boyle
Jeff Boyle
VP - IR at Arvinas

Sure.

Angela Cacace
Angela Cacace
Chief Scientific Officer at Arvinas

Thanks, Noah. So just to comment on some of the other differentiation features of our eight zero six 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 resistance in the clinic with RMC, certainly with RMC 6,236. So it's something we're excited about.

Angela Cacace
Angela Cacace
Chief Scientific Officer at Arvinas

We think this is a very strong differentiator. Of course, we'll see what happens clinically. So I hope that helps.

Conor MacKay
Conor MacKay
Equity Research Senior Associate at BMO Capital Markets

Yes, thank you.

Operator

Next question comes from the line of Sri Priykripa Devarakonda with Ruiz Securities. This

Kripa Devarakonda
Kripa Devarakonda
VP - Biotechnology Equity Research at Truist Securities

is Anna on for Priykripa. So in regards to 01/2002, I know you mentioned the elevated LRRK2 levels in Parkinson's. Could you remind us as to what percent of Parkinson's patients could be eligible for an LRRK2 targeting drug? And then a second question, just in regards to neoadjuvant, BevDeg, and that potential data readout, how would this potentially inform, any room for bepdag to be used earlier in the treatment paradigm? And besides commercializing in second line monotherapy and that six combo, any additional plans for development? Thank you.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

Again, thank you for the question. Noah, next question for the LARC2.

Noah Berkowitz
Chief Medical Officer at Arvinas

Yeah. So LARC2 levels are higher in the Parkinson's disease patients. Now we haven't made a choice that we're only treating patients with elevated LARC two. 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.

Noah Berkowitz
Chief Medical Officer at Arvinas

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 it's shared. So that's a possibility. If your question implies genetically, since LARC2 is so implicated genetically in diseases like Parkinson's disease, when we move forward in Parkinson's disease, what percentage of patients have LRRK2 implicated disease? Well in idiopathic, well in familial Parkinson's, about fifteen percent of patients have LRRK2 mutations.

Noah Berkowitz
Chief Medical Officer at Arvinas

And there's a higher percentage that have LRRK2 pathway mutations that contribute to other types of familial Parkinson's disease. When you look at idiopathic, it's down in the few percent range. Beyond those LRRK2 mutations themselves, there are all kinds of pathway perturbations that suggest that LARC2 could be at the center of this endolysosomal dysfunction that is characteristic of Parkinson's disease and PD. So you start to have thirty percent of patients that can have SNPs and other biomarkers that are associated with this LRRK2 dysregulation, and may lead to LRRK2 elevation. And we have a particular interest in that subset of patients, and that's why we're engaging in a lot of biomarker analysis.

Noah Berkowitz
Chief Medical Officer at Arvinas

We've been a longtime collaborator with the Michael J. Fox Parkinson's Disease Biomarker Initiative. And this is bearing fruit for us. So I think that we'll we have no kind of guidance yet about whether we're doing patient selection or patient enrichment or going for all comers. But these are the types of questions we are investing in right now to ensure that we have the best development plan moving forward. Now the second question was about neoadjuvant, VEGF.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

How positioning the potential for VEGF in an ALICE.

Noah Berkowitz
Chief Medical Officer at Arvinas

Yeah. So really we have to keep in mind there have been no evidence to date to suggest that Vepdeg 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're more tolerable than aromatase inhibitors.

Noah Berkowitz
Chief Medical Officer at Arvinas

That could be very important in both of those settings. But 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're just not going to be going forward in those early lines. And that's why we've been giving so much guidance to our, for our intent to, out license this, you know, or proceed with renegotiation with Pfizer. But I don't think that we should draw any conclusions that there are any problems in the adjuvant setting or in first line.

Kripa Devarakonda
Kripa Devarakonda
VP - Biotechnology Equity Research at Truist Securities

Great. Thank you so much.

Operator

Next question comes from the line of Chit Mukherjee with BTIG. Your line is open.

Jeet Mukherjee
VP & Biotechnology Analyst at BTIG

Great. Thanks for taking my question. So perhaps just coming back to the discussions with Pfizer over Vepdeg. You know, 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 Vepdeg?

Jeet Mukherjee
VP & Biotechnology Analyst at BTIG

And are you in active dialogue with other partners? If yes, how are those discussions going? Thanks.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

Yes, great question. I would say that Pfizer and our business and the discussions we are having are aligned in terms of what the best way to get value for is. Even though we may have different views about the development future of VetDig, I think Pfizer in our business truly believes there's value they had there. That's why we're in these discussions. Clearly, if the asset does come back, and that's just one of the scenarios.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

The other scenario is that Pfizer takes the compound forward. But in the scenario where it comes to us, yes, we'd run an active process. But obviously, we cannot run an active process right now because we're in a collaboration with Pfizer and we don't have the ability to do that. Our belief is if we get the asset back, we run the process, there would be companies extremely interested in taking a near 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.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

Like I say, if they want to take it forward aggressively and they launch it themselves, that would be extremely positive. But if they don't and the outcome is we get the compound, then yes, we do run an active process.

Operator

Next question comes from the line of Eli Merle with UBS. Your line is open.

Analyst

Hi. This is Tejas on for Eli. Thanks for taking our question. I think you talked a little bit about some of the preclinical data for the KRAS inhibitors. Can you talk a little bit more about what we should expect with more data later this year?

Analyst

And how might that inform what we think about in the Phase one?

John Houston
John Houston
Chairperson, CEO & President at Arvinas

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

Angela Cacace
Angela Cacace
Chief Scientific Officer at Arvinas

So for the KRAS inhibitors for 08/2006, 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'll also show some additional data just showing the combinability of the molecule Noah had mentioned with EGFR mechanisms. That's difficult with the pan inhibitors certainly in the clinic, showing some side effects that would basically preclude that combination. We'll also show data that we think is really compelling from our oral and KRAS program, showing that we're making really great strides there as well. Other additional comparative 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 PROTAX, 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.

Angela Cacace
Angela Cacace
Chief Scientific Officer at Arvinas

So we think we have a very differential profile, and it's an exciting opportunity certainly. And 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 and the team will be sharing clinical data as soon as we have it.

Analyst

That helps.

Operator

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

Peter Lawson
Peter Lawson
MD - US Biotech Equity Analyst at Barclays Capital

Great. Thank you so much. Maybe just leading on from the prior question. For the G12P and the update, when should we expect the initial, first in human data update? And if you could talk through how enrollment is going and the number of sites that are open and any other details around that trial? And then I have a follow-up. Thank you.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

Thanks, Peter. No one would like to share.

Noah Berkowitz
Chief Medical Officer at Arvinas

So, Peter, we, you know, we just announced that we opened the study for enrollment a little ahead of schedule, and the immediate reaction seems to be very favorable. I it's we haven't offered guidance yet on when we will be sharing data, but, you know, you're gonna 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 one study.

Peter Lawson
Peter Lawson
MD - US Biotech Equity Analyst at Barclays Capital

Gotcha. Thank you. And I apologize. I I arrived, late on the call. For the for the BCL SIDS, so that's what, three five three, the data in the second half, what what should we focus on, and discuss the data and other metrics that we may be delivering in that dataset? Thank you.

Noah Berkowitz
Chief Medical Officer at Arvinas

Sure. So we've shared that we'll provide some update of our datasets in the second half of this year. I really don't want to get ahead of ourselves and share what that disclosure will be. But the idea is that we're advancing through our dose escalation program. And obviously in dose escalation programs, the data that you're going to see are going to be more like, but before you're done with it, safety and PK and early signs of efficacy.

Noah Berkowitz
Chief Medical Officer at Arvinas

So 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 PKPD.

Peter Lawson
Peter Lawson
MD - US Biotech Equity Analyst at Barclays Capital

Gotcha. Would that be kind of the range of 10 to 20 patients, or I presume kind of heavily pretreated. Any details there, Kinkley?

Noah Berkowitz
Chief Medical Officer at Arvinas

Yeah. I would say that's a reasonable guess.

Peter Lawson
Peter Lawson
MD - US Biotech Equity Analyst at Barclays Capital

Perfect. Thank you so much.

Operator

Next question comes from the line of Sudan Laganathan with Stephens. Your line is open.

Analyst

Hey, this is Keith Alve on behalf of Sudan. Thank you for taking our question. So regarding the recent clinical data published by Celcuity on their advanced breast cancer asset, could you kind of just comment on your insights and what your perspective on that data is and where do you like see VetBag's competitive positioning within the treatment landscape? Thank you.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

No, thank you for the questions. Noah, I know you've tackled this earlier.

Noah Berkowitz
Chief Medical Officer at Arvinas

Yes, I'm not sure if I have more to add than what was said earlier. We have always recognized that a drug like salcuities could demonstrate attractive benefit risk in the second line setting and the first line setting. There is overlap between ESR1 mutant and PI3 kinase targeting agents. In the end, what physicians are looking for are oral protax, oral degraders, so in our case, a protax, that has an attractive benefit risk profile. So we think we're delivering that.

Noah Berkowitz
Chief Medical Officer at Arvinas

And physicians kind of want to avoid toxicity as much as possible and eke out all the benefit they can after first line therapy before adding drugs without some toxicity. So you know, 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 measure that modesty for you. Thank you.

Operator

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

Analyst

Hi. This is Sarah on for Michael. Thanks so much for taking my question. I wanted to quickly circle back to the oral PKRF program that you mentioned. I would love to hear more details on that, and specifically, how you expect to differentiate from later stage PanCera.

Noah Berkowitz
Chief Medical Officer at Arvinas

Sorry. We couldn't understand the question. Could you, repeat it one more time? There's a lot of echo.

Analyst

Oh, one second.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

The people and KRAS and how it differentiates from other KRAS?

Analyst

Yes, exactly. So question was about the pan KRAS and any thoughts on differentiating from later stage pan KRAS and pan RAS programs.

Angela Cacace
Angela Cacace
Chief Scientific Officer at Arvinas

Sure, sure. So as you know, we differentiate at least with ARB-eight zero six from what we've said publicly. But 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 inhibit.

Angela Cacace
Angela Cacace
Chief Scientific Officer at Arvinas

So we avoid that upregulation that's observed clinically. So as you're aware, the clinical inhibitors of pan RAF inhibitor has shown a major mechanism of upregulation of KRAS as a resistance mechanism in the clinic. So they're claiming around twenty percent to thirty percent of patients that are seeing this. So it's pretty profound. So we think we have an opportunity there.

Angela Cacace
Angela Cacace
Chief Scientific Officer at Arvinas

Our oral pan KRAS also will have great combinability. We'll speak a bit about some of the differential profiles of our molecule relative to the pan RAF molecules that are in the clinic. We expect that we'll have greater combinability with the immune stimulatory mechanisms, like KEYTRUDA and other IO agents because we will not inhibit T cell receptor activity. So we think that combinability will also provide a major advantage to other mechanisms clinically. So there's a number of other differential activities that we're observing that we'll be discussing as we move forward and advance the program.

Angela Cacace
Angela Cacace
Chief Scientific Officer at Arvinas

But it's an exciting time for us. So stay tuned for more data this year at the triple meeting.

Operator

Next question comes from the line of Terence Flynn with Morgan Stanley. This

Analyst

is Chris on for Terence. Just one question from us. For $3.93, beyond safety, what do you need to see in order to advance the asset into a combo trial with Glovy? Thank you. Thanks, Chris.

Noah Berkowitz
Chief Medical Officer at Arvinas

Noah, do want to Sure. So we don't probably not a lot. Like, we weren't expecting any any hematopoietic toxicity, which would be the principal toxicity of GloFit the CRS seen in the first cycle, but well managed with GLOFIS dosing over the first month, or the first three weeks. So it's just a matter of, you know, reinforcing that we're not seeing, any unexpected toxicities. You know, I don't have much more to add to that. Pretty clean Yep. Drug. Pretty Thank you.

Operator

Next question comes from the line of Yigal Nochomovitz with Citi. Your line is open.

Analyst

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

John Houston
John Houston
Chairperson, CEO & President at Arvinas

That's a great question. I suppose it's your definition of AI. Yeah. We've certainly used a lot of artificial intelligence in all of our research programs, and Angela can talk to the different features of that. I've been on that, but we've used the actual NDA application. Noah, I'm not sure how much of that. Well,

Noah Berkowitz
Chief Medical Officer at Arvinas

part of the NDA is 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 AI as being able to help us with a lot of medical writing. Right?

Noah Berkowitz
Chief Medical Officer at Arvinas

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 clin ops. And then obviously we're using it all the time with our stats programming.

Noah Berkowitz
Chief Medical Officer at Arvinas

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 our development programs.

Angela Cacace
Angela Cacace
Chief Scientific Officer at Arvinas

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 thirteen 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.

Angela Cacace
Angela Cacace
Chief Scientific Officer at Arvinas

And so we're seeing a big benefit in how we move with speed in research. And so this includes, you know, 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 PROTOX 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.

Angela Cacace
Angela Cacace
Chief Scientific Officer at Arvinas

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 how to 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.

Analyst

Got it. Thanks so much.

Operator

Next question comes from the line of Tyler Van Guren with TD Cowen. Your line is open.

Ikenna C. O
Equity Research Associate at TD Cowen

Hi. This is Ikenna on for Tyler. Thank you for taking our question. Just to go back to the Vepdeg and Pfizer collaboration, has Pfizer indicated its willingness to revise the collaboration or give back rights to Vepdeg? And why would they be motivated to give Vepdeg back given the amount they have invested to date?

Ikenna C. O
Equity Research Associate at TD Cowen

Also, wouldn't that require a significant cash outlay by Aventis? And are you willing to use the existing cash on hand with milestones or royalties to do that?

John Houston
John Houston
Chairperson, CEO & President at Arvinas

Yes. Just to reiterate, we're in a current fifty-fifty. The attraction for that fifty-fifty was the planning on second line, first line and adjuvant trials. Now we're currently left in a situation where it's only second line monotherapy, so less attractive in terms of the market size for Pfizer. They have shown no interest to develop that further.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

So that's the first important thing, that that will not be developed further by Pfizer. We're in negotiation right now about what's the best way forward in terms of moving away from the fifty-fifty collaboration we had, where either Pfizer takes the asset and launches it and gets more economics, or they hand the compound back to us. I've said 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. We'd be running a process to find a partner who would then ideally launch the drug and ideally further develop the drug.

John Houston
John Houston
Chairperson, CEO & President at Arvinas

And we gain the forward benefit of seeing the drug on the market. But we have no plans to further develop that if we got the contract back.

Ikenna C. O
Equity Research Associate at TD Cowen

Thank you.

Operator

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

John Houston
John Houston
Chairperson, CEO & President at Arvinas

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

Operator

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

Executives
    • Jeff Boyle
      Jeff Boyle
      VP - IR
    • John Houston
      John Houston
      Chairperson, CEO & President
    • Angela Cacace
      Angela Cacace
      Chief Scientific Officer
    • Andrew Saik
      Andrew Saik
      CFO & Treasurer
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