Arcus Biosciences Inc

NYSE:RCUS

Earnings Call Analysis

Arcus Biosciences' Strategic Phase III Trials and Solid Financial Outlook

Arcus Biosciences, in a strong financial position with $1 billion in cash, saw Q2 revenue at $39 million, down from $145 million. Pivotal Phase III trials are progressing, with STAR-221 enrollment complete and STAR-121 to be finalized this year. The company shifted focus towards advancing Casdatifan (cas) and predicted a peak in R&D spending for dom in 2024. They anticipate presenting multiple data sets, including initial Phase III readouts and upcoming trials in RCC. Financial guidance was adjusted modestly, expecting $885-$925 million by year-end, ensuring funding through 2027. Strategic partnerships with Gilead and Taiho continue to support their robust R&D pipeline.

Strong Financial Position Amid Revenue Fluctuations

As of June 30, 2024, Arcus Biosciences boasts a robust cash position of $1 billion, having slightly decreased from $1.1 billion at the end of March 2024. The company reported GAAP revenue of $39 million for Q2 2024, a significant decline from $145 million in Q1 2024, largely due to a one-time catch-up from a Gilead partnership which added $107 million to the first quarter's revenue. For the remainder of 2024, Arcus anticipates consistent GAAP revenue of about $30 million per quarter, signaling steady income generation from ongoing collaborations with Gilead and Taiho.

Ongoing Investments and Cost Management

Research and Development (R&D) expenses have increased modestly to $115 million in Q2 2024 from $109 million in Q1, driven primarily by higher clinical trial costs. Importantly, non-cash stock compensation accounted for $10 million within these expenses. Looking ahead, modest R&D expenditure increases are expected to continue through 2024, before leveling off in 2025 as focus shifts towards late-stage programs, particularly for the drug 'dom'. Meanwhile, General and Administrative (G&A) costs decreased to $30 million in Q2 from $32 million in Q1, reflecting effective cost control measures.

Exciting Pipeline Developments

Arcus is preparing for significant upcoming announcements and data presentations. The company is on track to initiate its first Phase III trial for casdatifan (cas), a HIF-2 alpha inhibitor, in the first half of 2025. Furthermore, promising data from multiple dose expansion cohorts are expected in the fall. The initial results from recent cohorts could validate cas's best-in-class potential, following a trend that indicates its superior capacity to manage tumor progression compared to existing therapies.

Strategic Focus on High-Potential Drug Candidates

The company remains highly focused on further developing both cas and dom, which have shown great promise in their respective clinical settings. They will soon present overall survival (OS) and progression-free survival (PFS) data from ongoing Phase III trials, anticipating favorable comparisons with competitive treatments. Importantly, the addressable market for these treatments could represent substantial financial opportunities, with estimates suggesting over $3 billion in the U.S. market alone for non-small cell lung cancers related to these therapies.

Optimism Around Strategic Collaborations

Arcus has solidified beneficial relationships with partners such as Gilead and Taiho. A pivotal ongoing collaboration is expected to yield additional financial support, including a $100 million payment from Gilead and a $15 million opc-in payment from Taiho. The relationships underscore Arcus's commitment to advancing their clinical portfolio, particularly for the quemli program targeting pancreatic cancer, which is also set to kick off a Phase III study, designated PRISM-1, in early 2025.

Future Guidance and Risk Considerations

The company revised its cash projections for 2024 upwards, anticipating a year-end balance between $885 million and $925 million, up from previous expectations of $870 million to $920 million. This well-capitalized position is projected to adequately fund ongoing operations into 2027. However, investors should remain aware of the inherent risks associated with biopharmaceutical developments, including potential setbacks in clinical trials or commercial adoption.

Earnings Call Transcript 2024-Q2

[Operator]

Good afternoon, thank you for attending today's Arcus Biosciences Second Quarter 2024 Earnings Call. My name is Tamiya and I will be your moderator for today's call. [Operator Instructions]

I would now like to pass the conference over to your host, Pia Eaves, Vice President of Investor Relations and Strategy. You may proceed.

[Pia Eaves, executive]

Hello, everyone, and thank you for joining us on today's conference call to discuss Arcus's second quarter 2024 financial results and pipeline updates. I'd like to remind you that on this call, management will make forward-looking statements, including statements about our cash runway and our expected clinical development milestones and timelines.

All statements, other than historical facts, reflect the current beliefs and expectations of management and involve risks and uncertainties that may cause our actual results to differ from those expressed. Those risks and uncertainties are described in our most recent annual report on Form 10-K and quarterly report on Form 10-Q, that has been filed with the SEC. We strongly encourage you to review our filings.

Today, you'll hear from our CEO, Terry Rosen; COO, Jennifer Jarrett; and CFO, Bob Goeltz. We'll also be joined by our; CMO, Dimitry Nuyten; and President, Juan Jaen for questions after the prepared remarks.

With that, I'll turn the call over to Terry.

[Terry Rosen, executive]

Thanks very much, Pia, and thank you all for joining us this afternoon. 2024 has already been a very exciting year for us and also very consequential. We completed enrollment of our first Phase III trial, STAR-221, a 1,000-plus patient study and first-line upper GI adenocarcinomas. And we're on the brink of advancing 2 additional molecules into Phase III studies, both of which are supported by strong data and targeting huge unmet needs and market opportunities.

Casdatifan, or cas, our HIF-2 alpha inhibitor, will be our newest Phase III entrant. We're going to share a lot of information about this program today and, in fact, throughout the rest of the year. The HIF-2-alpha inhibition mechanism has been clinically validated by the approval of Merck's belzutifan, which has been shown to have robust single-agent activity in clear cell renal cell carcinoma, or clear cell RCC, as we'll call it throughout the call.

Belzutifan is already generating over $500 million in the annualized run rate sales just 6 months after approval in clear cell RCC. This clearly demonstrates the unmet need in this indication, the excitement around the mechanism, and the significant opportunity which we intend to capitalize upon. In addition to belzutifan monotherapy achieving a response rate of roughly 20% and meaningful tumor reduction in a much higher percentage of the late-line patient study population, probably one of the most exciting aspects of the HIF-2-alpha mechanism is its durability.

In the Phase I/II study for belzutifan, over 20% of patients had not progressed and remained on treatment beyond 2 years. And several of these patients, in fact, are now approaching 4 years on treatment. And in the Phase III registrational LITESPARK-005 trial, at the time of the first data presentation, 4 times as many patients were still on treatment with belzutifan than with the comparator everolimus.

This is pretty remarkable for the third-line plus setting, and it contrasts with the many TKI therapies where patients may respond quickly, but then they rapidly progress. The tolerability of belzutifan with on-mechanism anemia and hypoxia being the only meaningful treatment of emergent adverse events, enables patients to remain on treatment for long periods. And we've consistently heard from clinicians how well-tolerated belzutifan has been for patients, particularly relative to the TKIs.

While belzutifan is a good molecule with cas, we have a potentially best-in-class molecule due to its excellent pharmacodynamic and dose-proportional pharmacokinetic profile. It's a really great molecule. Cas's PK-PD profile enables us to deliver 5 or more times the PD equivalent of the approved dose of belzutifan, which may result in more rapid onset and greater clinical efficacy relative to those of belzutifan. And in fact, in our ARC-20 study, we're already seeing this differentiation play out in the data, which we look forward to sharing later this year.

To further leverage cas's improved profile, we're pursuing differentiated combinations relative to those being investigated with belzutifan. You're going to hear more about this today from Jen, when we disclose for the first time the design of our first Phase III study for cas PEAK-1. We have some other exciting studies in the works that we're going to talk more about in the near future.

Moving on to our Fc-silent anti-TIGIT antibody, domvanalimab, and STAR-221, our Phase III trial evaluating dom plus our anti-PD-1 zim plus chemo and first-line upper GI cancers. In June, we completed enrollment of STAR-221, enrolling over 1,000 patients in just 18 months. And we expect STAR-121 complete enrollment later this year. So we're now turning our focus towards data readouts.

While we recognize, the anti-TIGIT program and dom is a show-me story for many of you, our confidence is actually stronger than ever. It's data-driven, and we remain convinced that the Fc-silent configuration has significant advantages over the Fc active antibodies. This is because the FC-anti-TIGIT antibodies substantially deplete peripheral regulatory T cells and correspondingly increase immune-related AEs.

While increasing the incidence of AEs is obviously intrinsically undesirable, perhaps more detrimental is the need to withhold or discontinue drugs to manage these AEs, which may negatively impact efficacy. We've now seen 2 Merck studies where they explicitly called out greater rates of immune AEs, leading to treatment continuation as the primary reason for trial failure. Recall also that Merck is using a co-formulation strategy, necessitating simultaneous discontinuation of both components of their anti-PD-1 anti-TIGIT therapy.

Additionally, because TIGIT is expressed on several other types of immune cells, depleting TIGIT-bearing immune cells can be counterproductive for any therapeutic strategy that's designed to stimulate the immune system to eliminate cancer cells. We have 2 impactful data sets coming that we're going to talk about a bit later, both of which we believe will not only restore but enhance confidence in the potential of the TIGIT pathway. So TIGIT pathway in general. But in particular, dom is an FC-silent anti-TIGIT antibody.

I want to briefly comment on our CD73 and Adenosine receptor programs, quemli and etruma, respectively. For etruma, at ASCO, we presented data from our randomized ARC-9 study, which showed unprecedented median overall survival of over 20 months for an etruma-based combination of third-line colorectal cancer. These results surpassed any survival results reported for clinical trials in third-line colorectal cancer.

In the second half of the year, we also plan to present biomarker data from this study that described the ability of etruma to block the effects of adenosine in tumors, as well as the relationship between CD73 expression and patient survival. So we're going to link mechanism to clinical outcomes. Both we and our clinical advisors are eager to advance etruma in colorectal cancer. We're going to update you once we finalize next steps for this program.

For quemli, we expect to start our Phase III study in pancreatic cancer, which we're now calling PRISM-1, by early next year. We're extremely excited that taiho decided last month to exercise its option to the quemli program. taiho will make a payment for the option exercise, and they're also obliged to pay us development milestones, which are expected to be triggered next year.

In return, taiho received development and commercialization rights to quemli in Japan, as well as other countries in Asia, but excluding Mainland China. They'll now operationalize and be responsible for the costs of PRISM-1 in Japan. The exercise of this option further illustrates the potential for quemli in pancreatic cancer. We expect taiho to play a valuable role in the successful execution of the PRISM-1 study.

Finally, we're well enabled to continue to advance our large portfolio with a billion dollars in cash and investments on hand, plus the $100 million continuation payment due from Gilead, as well as the multiple partnerships that provide significant funding for programs.

So let me summarize where we are today. We are extremely well positioned due to the investment that we've made in dom, including our 3 Phase III studies, one of which was a completed enrollment, and the second that is expected to complete enrollment this year.

As such, we anticipate 2024 will represent the peak of our R&D investment in dom. With enrollment of STAR-221 behind us, we're now preparing for data and potential registration. The timing of this is perfect. We're now able to shift resources and investment to our next strategic priority, casdatifan. cas represents a very rare opportunity. We have a validated target in HIF-2-alpha.

Belzutifan has been embraced by physicians and patients as an important new standard of care, despite what are very clear limitations. Cas has an improved profile, and this program is now central to our development focus. Our emphasis is on creating a comprehensive development program that fully leverages everything that we have been able to learn from belzutifan in our growing cas data set. We expect to share a continuous flow of data and plans over the next year. Our initial Phase III trial, PEAK-1, is the start of this transition and commitment.

I'd like to now turn things over to Jen to speak a bit about cas in greater detail.

[Jennifer Jarrett, executive]

Thanks, Terry. Slide 26 shows the design of ARC-20, our Phase I study for cas in late-line clear-cell RCC. It includes 3 monotherapy expansion cohorts, each initially enrolling approximately 30 patients that are evaluating 50 mgs, 100 mgs and 150 mgs of cas, as well as a combination cohort that is evaluating cas plus cabozantinib. Patients in the monotherapy cohorts had to have regressed on both an anti-PD-1 and TKI therapy in the metastatic setting to be eligible.

We have submitted data from the 100-meg cohort for presentation at a fall medical conference. The presentation will include safety and efficacy data, including ORRs, as well as waterfall charts and swimmer lanes, so that you will be able to assess the depth and duration of responses.

Patients in this cohort had a medium of 3 prior lines of therapy, and 25% of patients had 4 or more prior lines. In comparison, the Phase III trial for belzutifan, LITESPARK-005, enrolled only patients who received one to 3 prior lines of therapy.

And as a reminder, the ORR for LITESPARK-005 was 21.9%, and the primary progressive disease, or primary PD rate was 33%. We expect our data presentation to support cas's potential best-in-class profile, specifically better efficacy with comparable safety relative to that of belzutifan, even when evaluated in a more advanced patient population than LITESPARK-005.

Because of the significant interest in ARC-20, we actually just reopened the 100-meg cohort and are close to enrolling another 30 patients. This would bring us to 120 patients that have enrolled in total in approximately a year across the 3 monotherapy cohorts, which is incredible for a Phase I study in a single tumor type.

Moving on to the 50-meg cohort, which completed enrollment in April, these data are maturing very nicely, so we also now expect to share some information from this cohort in the fall. All patients are eligible to have had at least one scan, so we already know the primary PD rate, or the percent of patients that progressed before their first scan. Like we observed in the 100-meg cohort, the primary PD rate is substantially less than the 33% observed in LITESPARK-005. This is another data point demonstrating that cas seems to bring tumor growth under control more quickly than belzutifan.

Also, like the 100-meg cohort, we're seeing a very significant percentage of patients with tumor reduction. And the ORR for this cohort, including one response that is pending confirmation, is already higher than what was reported in LITESPARK-005, even with very limited follow-up.

Finally, we recently completed enrollment of the 150-meg expansion cohort. So between now and the end of 2025, we expect to present a steady stream of data from ARC-20, including at least 120 patients' worth of data for cas monotherapy, as well as potentially initial data from our cas plus cabo combination cohort. These data will be used to support rapid initiation and enrollment of our First Phase III study, which brings me to our development plan for cas.

Following feedback from the FDA later this year, we plan to begin our First Phase III trial, PEAK-1, in the first half of next year. The proposed design of PEAK-1, which is shown on slide 29 of our corporate deck, is simple. We will evaluate cas plus cabo versus cabo in clear cell RCC. cabo is the leading TKI prescribed for clear cell RCC, and cabo monotherapy is the standard of care in the post-IO setting.

PEAK-1 will enroll patients who have received prior anti-PD-1 therapy. This includes patients who received pembro in the adjuvant or post-nephrotomy setting, as well as patients who received anti-PD-1 in the first-line metastatic setting. So PEAK-1 will target a huge patient population and deep patient population that we believe will significantly benefit from HIF-2-alpha inhibition.

We plan to use the once-daily dose of 100 mg of cas in this study. All of our PK-PD exposure response and safety data from our dose escalation and expansion cohorts support 100 mg as a go-forward dose from our combination studies and the primary endpoint of this study will be PFS.

We expected PEAK-1 design to be extremely attractive for both clinicians and patients for a number of reasons. First, simplicity. We are using cabo in both the experimental arm and the control arm. In contrast, in Merck's LITESPARK-022, their similar study, they are evaluating Belzutifan with lamvatinib as the TKI in the experimental arm versus cabo in the control arm.

Second, our choice of combination partner is cabo, the most widely used TKI. We have received consistent feedback from physicians that cabo is preferred over other TKIs because of its proven efficacy, their comfort with managing cabo-related AEs, and the simplicity of dosing. Specifically, there are only 2 approved doses for cabo compared to 5 different doses for lenvatinib, so cabo is viewed as relatively easy to titrate. And importantly, cabo has also been shown to have a more benign safety profile than that of lenvatinib.

PEAK-1 is just the beginning of our investment in a late-stage development program for cas, and there is much more to come. We are in the advanced stages of planning for a study with a collaboration partner that will evaluate cas in a potential first-in-class combination and would expand our development plan into the first-line setting.

We are also in the process of evaluating multiple other opportunities for cas within the RCC space and potentially beyond, and will share more on these over the coming months. The market opportunity for cas is substantial. The class of TKIs primarily used for RCC now generate well over $5 billion in sales, as shown on Slide 31 of our corporate list.

With an annual incidence of 12,000 patients per year in the U.S. alone, it is a large population, and patients frequently remain on therapy, cycling through different treatments for many years. We believe our cas combinations have the potential to be best-in-class, allowing us to capture a significant share of this large and growing market.

I'll now turn the call back to Terry to discuss dom, our Fc-silent anti-TIGIT antibody.

[Terry Rosen, executive]

Thanks very much, Jen. So in ASCO in early June, we had 2 oral presentations, something we think is pretty incredible for a company of our size and stage. That included new data for EDGE-Gastric, our Phase II trial evaluating dom zim plus chemo in upper GI cancers. As you can see on Slide 16 of our corporate deck, in a 40-patient cohort, the dom zim combination demonstrated a pretty impressive median PFS of 12.9 months for the overall population and 13.8 months for the PD-L1 high population. These far exceed the benchmark PFS data for anti-PD-1 plus chemo that's in the 7- to 8-month range.

And in fact, the median PFS data for EDGE-Gastric actually approached the benchmark median OS of 13 to 14 months for anti-PD-1 plus chemo, as we've highlighted on Slide 17. Based on this outcome, our OS results should substantially exceed those from all of the benchmark studies. These results meaningfully de-risk our STAR-221 Phase III study, which is evaluating the same combination in the same setting as EDGE-Gastric.

We expect to have overall survival data for EDGE-Gastric in 2025. Given this is the primary endpoint for STAR-221, these data should further enhance the likelihood of a successful outcome for our Phase III study. We continue to believe not only that anti-TIGIT will be an important advance in anti-cancer therapy, but that dom will have important advantages over its FC-enabled counterparts. There continues to be a steady flow of data supporting this. While the failure of SKYSCRAPER-6, Roche's Phase II/III study, which evaluated Turago plus atezo plus chemo versus pembro plus chemo, is disappointing for patients, we've articulated to you the many important differences between our studies and SKY-6, and we really think that most of you have agreed with us on these points.

We've generated a tremendous amount of data that support dom's potential to add meaningful clinical benefit in both non-small cell lung cancer and upper GI cancers, and we expect to present two new data sets that will further support dom's significant potential in lung and Upper GI cancers.

So first off, by year end, we in Gilead plan to report data from ARC-10 Part 1, a randomized Phase III study in PD-L1 high non-small cell lung cancer. So let me just give you a reminder. We stopped enrollment for strategic reasons early this year to focus on the much larger opportunity with STAR-121. The initial design of ARC-10 evaluated dom plus zim versus zim versus chemotherapy. Approximately 40 patients were enrolled in each of the dom plus zim and zim monotherapy arms and approximately 20 patients were enrolled in the chemotherapy arm.

As we promised at the time, we shifted our focus to STAR-121. We will present both PFS and OS, including hazard ratios, and we believe that these data will reaffirm what we observed in ARC-7, that dom plus zim demonstrates clinically meaningful improvements over anti-PD-1 monotherapy in the setting with limited additional toxicities.

Second, we in Gilead expect to present OS data from EDGE-Gastric in 2025. As I mentioned, given that our median PFS is already in line with the OS results observed for anti-PD-1 plus chemotherapy alone, we expect to report very compelling overall survival data. And I can say today, well over 50% of patients remain on study 18 months after enrollment completed in this cohort.

We continuously evaluate the entirety of our data to confirm our confidence in our study designs, and we remain as confident as ever about our 3 Phase III studies, and we have the potential best-in-class anti-TIGIT, anti-PD-1 combination.

This brings me to the potential timing of our Phase III readouts. We have consistently said that our first readout will most likely be STAR-221, so let me spend a minute on the study design, which we show on Slide 18. Importantly, this trial has dual primary endpoints of OS in the PD-L1 high population and in the ITT population. So simply put, the study will be positive if the dom zim arm shows a statistical improvement in the PD-L1 high patients or in the ITT population.

The study is well-powered with over 1,000 patients, and we've closely monitored recruitment to ensure the ratio of PD-L1 high to PD-L1 low patients is consistent with the assumptions used for our statistical analysis plan. Given that OS has been in the 13-month range for anti-PD-1 plus chemo studies, and we completed enrollment in June, I think all of you can do the math on when we might get to a readout.

The addressable market here is enormous, with 24,000 patients in the U.S. alone, approximately 50% of whom are PD-L1 greater than 5, and 80% of whom are PD-L1 greater than 1. This translates into a market opportunity of well over $3 billion in the U.S. alone.

Before I close, I'm going to turn the call over to Bob to review our financial results for this quarter.

[Robert Goeltz, executive]

Thanks, Terry. Arcus continues to be in a strong financial position. Our cash as of June 30, 2024 was $1 billion, as compared to $1.1 billion as of March 31, 2024.

Turning to our P&L, we recognized GAAP revenue for the second quarter of $39 million, which compares to $145 million for the first quarter of this year. Our revenue is primarily driven by our collaborations with Gilead and Taiho, and in the first quarter, included a cumulative catch-up of $107 million, resulting from the Gilead amendment we executed in January. We continue to expect to recognize GAAP revenue of approximately $30 million per quarter for the remainder of 2024.

Our R&D expenses for the second quarter are stated net of reimbursements from Gilead, and were $115 million, as compared to $109 million in the first quarter of this year. In the second quarter, non-cash stock compensation represented $10 million of R&D expenses. The increase in the second quarter expenses was related to higher clinical trial costs offset partially by lower clinical manufacturing costs associated with our late-stage programs.

We continue to expect modest increases in R&D expenses through 2024, and for spend to level off heading into 2025, as our late-stage investments shift from dom towards cas and quemli over time. As Terry noted, we expect our R&D investment in dom to peak this year.

G&A expenses were $30 million for the second quarter, compared to $32 million in the first quarter of this year. Non-cash stock compensation represented $10 million of our G&A expenses for the second quarter, and we expect G&A expenses to remain stable for 2024. Finally, we now expect our cash and investments balance at the end of 2024 to be between $885 million and $925 million, as compared to our prior guidance of $870 million to $920 million. We continue to expect these resources to fund operations into 2027.

As a reminder, this guidance includes a $100 million partnership continuation payment from Gilead, and the quemli opt-in payment from Taiho of $15 million. Both payments are due in the third quarter. Our guidance excludes, however, additional potential opt-in payments and milestones from our partners. For more details regarding our financial results, please refer to our earnings press release from earlier today in our 10-Q.

I'll now turn it back to Terry for concluding remarks.

[Terry Rosen, executive]

Thank you very much, Bob. So please let me end by reviewing our near-term data events. They're both meaningful and very substantial. First, in the fall, we expect to present ORR and other data from the 100-milligram dose expansion cohort of cas. Those data will be followed closely by results from the 50-milligram and 150-milligram dose expansion cohorts, and then data from our cas cabo combination cohort in 2025. We also expect to initiate our first Phase III trial for cas in the first half of 2025.

With respect to dom, we expect to present a few important data sets ahead of our first Phase III readouts. These include PFS and, very importantly, OS data from our original ARC-10 trial, which evaluated dom plus zim versus zim versus chemo in PD-L1 high lung cancer by year-end, followed by OS data from our EDGE-Gastric Phase II study in 2025.

Meanwhile, we are continuing to advance our other programs, including the initiation of a Phase III trial for quemli in pancreatic cancer and the evaluation of next steps for etruma and colorectal cancer. All of these studies are enabled by the strength of our balance sheet and the great relationships with our partners. Lastly, we continue to have a robust discovery engine at Arcus that enables a sustainable pipeline of future programs. The next program we expect to advance into mid-stage studies is AB801, our highly selective AXL inhibitor.

I want to conclude by thanking all of you. Thank you very much for your continued support of Arcus and our mission to bring innovative therapies to patients in need. And so we'll now open up the call for questions. Thank you.

[Operator]

[Operator Instructions] The first comes from Yigal Nochomovitz with Citi.

[Yigal Nochomovitz, analyst]

So on the expansion cohort that you're embarking on with cas and cabo, can you just explain, is that something that you need to check the box on before initiating the PEAK-1 Phase III trial? Is there some expected overlapping talks that you may or may not see with cas and cabo? And is the goal there mainly just to clear on safety before moving into the Phase III with that combo?

[Terry Rosen, executive]

Dimitry, why don't you give a clear and concise answer to that question, please?

[Dimitry Nuyten, executive]

Yes. I wouldn't call it a checkbox, but it's important to establish safety information for a specific combination before you start a larger trial. So that's what the cohort is designed for. I do have to say, to your point of overlapping toxicities based on the individual safety profiles, cas has now been studied in quite a few patients as monotherapy. cabo, of course, is very well established. We don't expect any relevant overlapping toxicity with the exception of fatigue, something that's impactful for patients, but typically can be managed with those interruptions.

Also, I'd like to note for cas, in our experience so far, it is really rare for people to have even to be dose reduced, let alone discontinued treatment for toxicity. It's a very well-tolerated agent where short interruptions is pretty much what we need to do in the case of drug-related toxicities. And then lastly, we can refer to the experience with belzutifan and cabozantinib, which was published in The Lancet, a series of about 55 patients showing, indeed, that the combination does not show any unexpected toxicities.

[Yigal Nochomovitz, analyst]

And I just wanted to confirm what you said, Jen, what you mentioned in terms of the data for the 50 milligrams, the primary progressive disease was less than the rate seen in LITESPARK-005, and we're going to get the 50 and 100-milligram data separately from the 100-milligram data later this year. Is that correct?

[Jennifer Jarrett, executive]

Yes. So first of all, you heard correctly on primary progressive disease. So for LITESPARK-005, the primary progressive disease was 33%, and I said that for the 50-mig cohort, some of what we saw for the 100-mig cohort were seeing a significantly or substantially lower primary progressive disease rate. As far as data presentation, we would present the cohort separately, but the point I was trying to make is that when we present the 100-mig cohort of data in the fall, we will likely at least say something about the 50-mig cohort, and probably show some data from that as well, but it wouldn't likely be pooled, it would be shown separately.

[Yigal Nochomovitz, analyst]

And then for the first-line metastatic study, what sort of combo partners would you be considering there? TKI and PD-1, or anything else?

[Terry Rosen, executive]

Yigal, we're going to be disclosing that very shortly. We would have loved to be able to disclose it today, but it's probably a couple weeks off, and I think it'll fit within something that would meet your expectations. But the key thing about it, and the reason we wanted to get it in today, is because we wanted to show sort of comprehensively both what data we're going to have and what we're going to be starting in the next year, and we want to make it really clear that we're going to be going into the front-line setting, and we're going to be doing it with a combination that Merck is not doing, and we feel we're going to be ahead of Merck.

[Jennifer Jarrett, executive]

And then one last thing to mention. We called out that we would be doing this with a collaboration partner, just to make it clear that we would be doing this in a very capital and resource-efficient manner.

[Operator]

The following comes from Terence Flynn with Morgan Stanley.

[Unknown Analyst]

This is Alex calling in for Terrence. Can you give us any insights on potential presentation venue for this cas HIF-2a inhibitor for ARC-20 data that you presented in the fall? And can you remind us on the number of patient and duration of the follow-up we should expect with this update?

[Jennifer Jarrett, executive]

So we're not going to unfortunately disclose the medical meeting that we've submitted the data for presentation at. It's in the fall. You may be able to guess it, since we're running out of conferences that it could be presented at. It won't be at ESMO, just to be clear on that. And then for the second part of your question, and I actually forget what the second part of your question was. The number of patients. It'll be about 30. It'll be just a little bit above 30, and we'll have about 10 months of median follow-up at that point in time.

[Unknown Analyst]

And on your new trial design, can we do any read-through from your expansion cohort that you're currently enrolling? Is it going to be the same patient population? Anything you can comment on that?

[Jennifer Jarrett, executive]

Yes. So what we said, so PEAK-1 will enroll a somewhat healthier, less advanced patient population than what we're looking at in ARC-20. So obviously the fact that the drug is looking very good in ARC-20, obviously we think that bodes positively for PEAK-1. But the patient population that we would be looking at is a bit of a mix of first and second line. So it would include patients that receive PD-1 therapy in the adjuvant setting. So as a reminder, pembro is approved in the adjuvant setting.

So that is used in patients post-nephrotomy that are at high risk of recurrence will go on pembro. And then we'll also include patients that receive PD-1 in the first-line metastatic setting. So that would then be part of our study as a second-line metastatic patient. But as we've spent a lot of time analyzing all the data that's out there for the different LITESPARK studies, we feel like this is a patient population that will benefit particularly well from HIF-2-alpha inhibition. So we spent a lot of time working with our advisors to identify what we think is the best patient population for this drug. And this is what we've decided upon.

[Operator]

The next question comes from Jonathan Miller with Evercore.

[Jonathan Miller, analyst]

Jen, I feel like I missed it, and I wanted to get clarification. You suggested that the ORR was better than Merck in the 50-milligram cas cohort? And I just wanted to get some confirmation that that was what you said? And also, is the ORR better in the 100-mg arm as well? I know you've sort of stopped short of saying that in the past. And then, I guess, given what you've seen so far with primary progression rates and the ORR data that you've got in hand, do you see a dose response in those higher-dose cohorts, 50, 100, 150, at this point?

[Jennifer Jarrett, executive]

So for 50-mg, I did say that we're seeing a higher ORR today than the 21.9% that was seen with LITESPARK-005. I did also clarify that that's with one response as pending confirmation. We would be above the 21.9%. And I also pointed out that 50-mg, given that started enrollment after the 100-mg, that's a much less mature cohort from a follow-up perspective relative to the 100-mg. And then, the 100-mg, yes, we're now north of where LITESPARK-005 is. And I'll let Terry speak about that.

[Terry Rosen, executive]

I'll take the dose response question. So the first thing to sort of caveat is that the patient populations also are slightly different. So the 100-mg cohort is slightly more advanced patient population, and as we've noted, it's a more advanced population when compared to LITESPARK-005. But with that said, I would say at this point, particularly given that the 50-mg cohort is somewhat or substantially less mature, it would be hard to distinguish.

So I actually think, given that they're each in the 30-ish range, as you might anticipate, Jon, more likely than not, any distinguishing that we'll be able to do between them will probably potentially be reflected in durability. So I don't think you're going to -- the 50 is looking good enough that you won't be able to probably tell a difference between the 50 and 100.

The last point I want to remind you on that, though, is that to contextualize that, you're actually -- even the 50-mg cohort is at 2.5, the PD equivalent of belzutifan, and as you know, belzutifan was enough to really shift the change in the standard of care. So the nice thing about that, as all these data start to unfold as well there 30 milligram -- I'm sorry, 30-patient cohorts, while we're not going to combine the data from just an understanding of the program and the potential of the molecule.

You're going to start to be able to look at these and treat these cohorts, not like one was at homeopathic, one was at medium, one was sitting at heart. You're going to have doses that let you sort of look at these patients in total and make an assessment of how you feel our molecule looks compared to anything you've seen with belzutifan.

[Jonathan Miller, analyst]

And then maybe one more question on cas strategy. Obviously, you talked about a cabo combo going to Phase III, this other mystery combo in the first-line setting. Should we expect to see -- how broad should we expect to see the late-stage development program for cas get in terms of number of different combos, number of different settings, maybe beyond RCC as well?

[Jennifer Jarrett, executive]

So as I say, over sort of the next 6 to 9 months, the 2 Phase III studies that we called out today will probably be it for us for now as far as Phase III studies. That's a lot. Market opportunity is massive, so we will be focused on getting the studies off the ground. Where you should expect to see some of the additional work is in ARC-20, where we're looking at some other interesting patient populations that we want to explore within that study that could then lead to later stage studies in the future. But we have some really interesting populations in mind where we think HIF-2a inhibition, even as monotherapy, can have a really interesting effect. And so we'll talk more about those over the coming months.

And then I would say, your question on other tumor types. We do think there's some interesting opportunities there as well. But I think over the near term, you should expect to see more out of us from RCC, which is kind of keeping our hands full. Although, interestingly, we're getting a lot of IST requests for studies in HCC. So there's definitely a lot of interest out there in the clinical community in evaluating cas and HCC in particular.

[Operator]

[Operator Instructions] The next question comes from Salveen Richter with Goldman Sachs.

[Unknown Analyst]

Hi, this is Lydia on for Salveen. We just have one on etruma in colorectal cancer. Just given the Phase I/II data that you shared at ASCO, what do you see as the likely registrational path here? And when do you expect to share next steps for this program?

[Terry Rosen, executive]

So obviously, you can tell from what we've been talking about today, we've been doing a lot of planning and execution. And that's certainly a program that we're very excited about. Gilead is very excited about. We're working through. I'll just toss out there, since you asked a question, we like to give answers. We have had a lot of push from our ad board that it might be smart to move this towards the frontline setting, move a little earlier than where we were, but we haven't sorted through all that. And we're literally in the midst of those discussions to decide exactly where we might go, but you shouldn't be surprised if we end up going in that direction.

[Operator]

The next question comes from Daina Graybosch with Leerink Partners.

[Daina Graybosch, analyst]

I have a question on TIGIT on ARC-10. I wonder if you can help set expectations given this is from early in the ARC-10 design about the type of patients you enrolled in terms of prognosis and region so that we can think about comparing the data to the other trials in the setting, including ARC-7?

[Terry Rosen, executive]

So I'll set a little bit of expectations on the data and then I'm going to let Dimitry get to the specifics of your question on patient demographics. But I'll just say that, we believe that these data will be positive for the field, positive for dom zim and positive for zim in terms of it being a really nice data set. And in fact, if you think about all of the randomized data sets out there, I would put this against any of them in terms of the information that'll convey with a good anti-PD-1 and the Fc-silent anti-TIGIT. So you should -- we definitely want to lean into this being an important, a good data set. And I'll let Dimitry say a little bit about the patient population.

[Dimitry Nuyten, executive]

So the patient population, just to break it down and also for others, so it was a 3-arm trial, ARC-10 Part 1. It was a two-to-two-to-one randomization. So it's about 40 patients, four zero on dom and zim, another 40 on zim alone, and then about 20 on chemotherapy. That does mean that the study was run ex-U.S. and did not include some of the core European countries because of the availability of checkpoint inhibitors as standard of care and monotherapy there.

However, it is still a, let's say, by inclusion criteria, very comparable to other trials run in this space. And it has the chemotherapy control arm that of course can be compared to other chemotherapy trials that were run slightly earlier. And I think that's going to be very helpful to benchmark the population. But in principle, it's a fairly straightforward first-line population.

[Jennifer Jarrett, executive]

And one other thing to point out with that data set I think interesting is there's really 2 different readouts within the data set. One is dom plus zim versus zim, and the other is zim versus chemo, which is how the study was set up. So you'll also see that comparison of zim versus chemo in that readout.

[Operator]

The next question comes from Asthika Goonewardene with Truist Securities.

[Asthika Goonewardene, analyst]

Apologies if I ask something that's already has been asked, just briefly jumped on the call here, but just very quickly, can you tell us when cohort A of the etruma in CRC study is going to be reading out? You just made a comment about how the KOLs are pointing that that's a suitable tumor type to go into. So just wondering about that. And then when you think about the HIF combination, obviously with carbo, that makes a lot of sense. And given the function on Treg, we can rush both PD-1 and CTLA4 as good combination partners. I just want to get your thoughts on that?

[Terry Rosen, executive]

So let me take the question on the second cohort. It'll be likely sometime next year. It's simply, again, the OS in that setting is substantially longer. And data simply aren't mature at this point. So remind me of the second question.

[Jennifer Jarrett, executive]

The second question was on PD-1. Can you remind us of the second question?

[Asthika Goonewardene, analyst]

When you think about HIF and in combination with PD-1, obviously it makes sense to think about a combination. PD-1, but yeah. How do you like --

[Terry Rosen, executive]

So actually, we're going to be disclosing very shortly a second registrational trial that takes us into the frontline setting. But your point about anti-PD-1, anti-CTLA4, combination thereof, obviously those are all reasonable combinations to be thinking about that would make a whole lot of sense to go with HIF-2 inhibition.

[Operator]

There are currently no other questions queued at this time. I will pass it back over to the management team for closing remarks.

[Pia Eaves, executive]

Thank you all for joining us. We look forward to speaking with you.

[Terry Rosen, executive]

Thanks, everybody.

[Operator]

This concludes the conference call. Thank you for your participation. You may now disconnect your line.