Arcus Biosciences Q2 2024 Earnings Call Transcript

Quartr
Provided by Quartr
August 8, 2024

There are 12 speakers on the call.

Operator

Good afternoon. Thank you for attending today's Arcus Biosciences Second Quarter 2024 Earnings Call. My name is Tania, and I will be your moderator for today's call. All lines will be muted during the presentation portion of the call with an opportunity for questions and answers at the end. I would now like to pass the conference over to your host, Pia Eaves, Vice President of Investor Relations and Strategy.

Operator

You may proceed.

Speaker 1

Hello, everyone, and thank you for joining us on today's conference call to discuss Arcus' Q2 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 time lines. 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 ks and quarterly report on Form 10 Q that have been filed with the SEC. We strongly encourage you to review our filings.

Speaker 1

Today, you'll hear from our CEO, Terry Rosen COO, Jennifer Jarrett and CFO, Bob Geldt. We'll also be joined by our CMO, Dimitri Nowtien and President, Juan Haiyan for questions after the prepared remarks. With that, I'll turn the call over to Terry.

Speaker 2

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 1st Phase 3 trial, STAR-two twenty one, a 1,000 plus patient study in first line upper GI adenocarcinomas. And we're on the brink of advancing 2 additional molecules into Phase 3 studies, both of which are supported by strong data and targeting huge unmet needs and market opportunities. Casdatafan or Cas, our HIF-two alpha inhibitor will be our newest Phase 3 entrant.

Speaker 2

We're going to share a lot of information about this program today and in fact throughout the rest of the year. The HIF2 alpha inhibition mechanism has been clinically validated by the approval of Merx belzutafan, 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. Belzutafan is already generating over $500,000,000 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 belzutafam monotherapy achieving a response rate of roughly 20% and meaningful tumor reduction in a much higher percentage of the late line patient study population.

Speaker 2

Probably one of the most exciting aspects of the HIF-two alpha mechanism is its durability. In the Phase onetwo study for belzutafan, 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 3 registrational LightSpark 5 trial at the time of the first data presentation, 4 times as many patients were still on treatment with dolzutefan than with the comparator ever alignments. This is pretty remarkable for the 3rd line plus setting and it contrasts with the many TKI therapies where patients may respond quickly, but then they rapidly progress. The tolerability of belzutafan was on mechanism anemia and hypoxia being the only meaningful treatment emergent adverse events enables patients to remain on treatment for long periods.

Speaker 2

And we've consistently heard from clinicians how well tolerated dolzutifen has been for patients, particularly relative to the PKIs. While belzutafin is a good molecule with cats, we have a potentially best in class molecule due to its excellent pharmacodynamic and dose proportional pharmacokinetic profile. It's really a great molecule. Casa's PKPD profile enables us to deliver 5 or more times the PD equivalent of the approved dose of belzutafen, which may result in more rapid onset and greater clinical efficacy relative to dose of belzutafen. And in fact, in our ARP-twenty study, we're already seeing this differentiation play out in the data, which we look forward to sharing later this year.

Speaker 2

To further leverage Ks improved profile, we're pursuing differentiated combinations relative to those being investigated with belzutafant. You're going to hear more about this today from Jen when we disclose for the first time the design of our first Phase 3 study for CASK PEAK1. 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, dombanilumab and STAR-two twenty one, our Phase 3 trial evaluating dom plus our anti PD-one ZIM plus chemo in first line upper GI cancers, in June, we completed enrollment of START-two twenty one enrolling over 1,000 patients in just 18 months and we expect STAR-one hundred and twenty one to complete enrollment later this year. So we're now turning our focus towards data readouts.

Speaker 2

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, stated driven and we remain convinced that the Fc silent configuration has significant advantages over the Fc active antibodies. This is because the Fc antigit 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 drug 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-one anti TIGIT therapy.

Speaker 2

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 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 in DAM is an Fccellin anti TIGIT antibody. I want to briefly comment on our CD73 and adenosine receptor programs, Quemly and etruma respectively. For etruma at ASCO, we presented data from our randomized ARK9 study, which showed unprecedented median overall survival of over 20 months for an Intrula based combination of 3rd line colorectal cancer. These results surpassed any survival results reported for clinical trials in 3rd line colorectal cancer.

Speaker 2

In the second half of the year, we also plan to present biomarker data from this study that described the ability of Atroma 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 etruuminal in colorectal cancer. We're going to update you once we finalize next steps for this program. For Quemly, we expect to start our Phase 3 study in pancreatic cancer, which we're now calling PRISM-one by early next year.

Speaker 2

We're extremely excited that Taiho decided last month to exercise its option to the Quemly 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 for the costs of PRISM-one in Japan. Their exercise of this option further illustrates the potential for Quemly in pancreatic cancer. We expect Tayo to play a valuable role in the successful execution of the PRISM-one study.

Speaker 2

Finally, we're well enabled to continue to advance our large portfolio with $1,000,000,000 in cash and investments on hand plus the $100,000,000 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 DAAAM, including our 3 Phase 3 studies, one of which was 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 and D investment in DAP. With enrollment of START-two twenty one behind us, we're now preparing for data and potential registration.

Speaker 2

The timing of this is perfect. We're now able to shift resources and investment to our next strategic priority, casdatafen. CAS represents a very rare opportunity. We have a validated target in HIF-two alpha. Valsutafan has been embraced by physicians and patients as an important new standard of care despite what are very clear limitations.

Speaker 2

CASA 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 dolzutefan and our growing cast dataset. We expect to share a continuous flow of data and plans over the next year. Our initial Phase 3 trial PEAK1 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.

Speaker 3

Thanks, Teri. Slide 26 shows the design of ARC20, our Phase 1 study for cats 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 progressed on both an anti PD-one and TKI therapy in a metastatic setting to be eligible. We have submitted data from the 100 meg cohort for presentation at a fall medical conference.

Speaker 3

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 median of 3 prior lines of therapy and 25% of patients had 4 or more prior lines. In comparison, the Phase 3 trial for melzutafan, LightSpark O5 enrolled only patients who received 1 to 3 prior lines of therapy. And as a reminder, the ORR for LightSpark 5 was 21.9% and the primary progressive disease or primary PD rate was 33%. We expect our data presentation to support Casa's potential best in class profile, specifically better efficacy with comparable safety relative to that of belzutafin even when evaluated in a more advanced patient population than Leidstarco 5.

Speaker 3

Because of the significant interest in ARK20, we actually just reopened the 100 mg cohort and close to enrolling another 30 patients. This would bring us to 120 patients that have been enrolled in total in approximately a year across the 3 monotherapy cohorts, which is incredible

Speaker 4

for a

Speaker 3

Phase I study in a single tumor type. Moving on to the 50 mg 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 for the percent of patients that progressed at or before their first scan. Like we observed in 100 mg cohort, the primary PD rate is substantially less than the 33% observed in LightSpark O5.

Speaker 3

This is another data point demonstrating that CAS seems to bring tumor growth under control more quickly than belzutafan. Also like the 100 mg 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 LightSpark 05 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-twenty, including at least 120 patients worth of data for CAS monotherapy as well as potentially initial data from our CAS plus cabo combination cohort.

Speaker 3

These data will be used to support rapid initiation and enrollment of our first Phase 3 study, which brings me to our development plan for CAF. Following feedback from the FDA later this year, we plan to begin our 1st Phase 3 trial, PEAK1 in the first half of next year. The proposed design of PEAK1, 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.

Speaker 3

PEAC1 will enroll patients who would receive prior anti PD-one therapy. This includes patients who receive pembro in the adjuvant or post nephrectomy setting as well as patients who received anti PD-one in the first line metastatic setting. So PEQ1 will target a huge patient population and deep patient population that we believe will significantly benefit from HIF2 alpha inhibition. We plan to use the once daily dose of 100 mg of cats in this study. All of our PKPD 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 in this study will be PFS.

Speaker 3

We expect the PEQUA design to be extremely attractive number of reasons. First, simplicity. We are using cabo in both the experimental arm and the control arm. In contrast, in Merck's LightSpark 22, their similar studies, they are evaluating belzutafan with lenvatinib as the TKI and experimental arm versus cabo in the control arm. 2nd, our choice of combination partner is cabo, the most widely used TKI.

Speaker 3

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 lamvatinib. So cabo is used as relatively easy to titrate. And importantly, cabo has also been shown to have a more benign safety profile than that of lamvatinib. PEAK1 is just the beginning of our investment in a late stage development program for CAS and there's much more to come.

Speaker 3

We are in advanced stages of planning for a study with a collaboration partner that will evaluate CAS and 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 we'll share more on these over the coming months. The market opportunity for CAS is substantial. A class of TKIs primarily used for RCC now generate well over $5,000,000,000 in sales as shown on Slide 31 of our corporate debt. With an annual incidence of 12,000 patients per year in the U.

Speaker 3

S. Alone, it is a large population and patients frequently remain on therapy cycling through different treatments for many years. We believe our cat 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.

Speaker 2

Thanks very much, Jen. So at 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 2 trial evaluating Domzim plus chemo in upper GI cancers. As you can see on Slide 16 of our corporate deck, in a 40 patient cohort, the damsin combination demonstrated a pretty impressive median PFS of 12.9 months for the overall population and 13.8 months for the PD L1five population. These far exceed the benchmark PFS data for anti PD-one plus chemo that's in the 7th to 8th month range.

Speaker 2

And in fact, the median PFS data for edge gastric actually approached the benchmark median OS of 13 months to 14 months for anti PD-one 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 derisk our start-two twenty one Phase 3 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-two twenty one, these data should further enhance the likelihood of a successful outcome for our Phase 3 study.

Speaker 2

We continue to believe not only that anti TIGIT will be an important advance in anticancer therapy, but that DAAAM 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 twothree study, which evaluated tirago plus atezol plus chemo versus pembroke plus chemo is disappointing for patients. We've articulated to use the many important differences between our studies in SCI-six and we really think that most of you have agreed with us on these points. We've generated tremendous amount of data that support DAMA's potential to add meaningful clinical benefit in both non small cell lung cancer and upper GI cancers.

Speaker 2

And we expect to present 2 new data sets that will further support Dom's significant potential in lung and upper GI cancers. So first off, by year end, we and Gilead plan to report data from ARK10, Part 1, a randomized Phase 3 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-two-one hundred and twenty one. The initial design of ARK10 evaluated down plus ZYN versus ZYN versus ZYN versus chemotherapy.

Speaker 2

Approximately 40 patients were enrolled in each of the down plus ZYN and ZYN monotherapy arms and approximately 20 patients were enrolled in the chemotherapy arm. As we promised at the time, we shifted our focus to STAR-one hundred and twenty one. We will present both PFS and OS including hazard ratios and we believe that these data will reaffirm what we observed in ARC7 that Dom plus ZYN demonstrates clinically meaningful improvements over anti PD-one monotherapy in the setting with limited additional toxicities. 2nd, we and Gilead expect to present OS data from Edge Gastric in 2025. As I mentioned, given that our median PFS already in line with the OS results observed for anti PD-one plus chemotherapy alone, we expect to report very compelling overall survival data.

Speaker 2

And I can say today well over 50% of patients remain on study 18 months after enrollment completed in 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 3 studies and we have the potential best in class anti digit anti PD-one combination. This brings me to the potential timing of our Phase 3 readouts. We've consistently said that our first readout will most likely be start-two twenty one. So let me spend a minute on the study design, which we show on Slide 18.

Speaker 2

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 damsim 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, 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-one 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.

Speaker 2

S. Alone, approximately 50% of whom are PD L1 greater than 5 80% of whom are PD L1 greater than 1. This translates into a market opportunity of well over $3,000,000,000 in the U. S. Alone.

Speaker 2

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

Speaker 5

Thanks, Terry. Arcus continues to be in a strong financial position. Our cash as of June 30, $1,000,000,000 as compared to $1,100,000,000 as of March 31, 2024.

Speaker 6

Turning to our

Speaker 5

P and L, we recognized GAAP revenue for the Q2 of $39,000,000 which compares to $145,000,000 for the Q1 of this year. Our revenues primarily driven by our collaborations with Gilead and Tahoe and in the Q1 included a cumulative catch up of $107,000,000 resulting from the Gilead amendment we executed in January. We continue to expect to recognize GAAP revenue of approximately $30,000,000 per quarter for the remainder of 2024.

Speaker 2

Our R

Speaker 5

and D expenses for the 2nd quarter are stated net of reimbursements from Gilead and were $115,000,000 as compared to $109,000,000 in the Q1 of this year. In the Q2, non cash stock compensation represented $10,000,000 of R and D expenses. The increase in the 2nd quarter expenses was related to higher clinical trial costs offset partially by lower clinical manufacturing costs associated with

Speaker 7

our late stage programs.

Speaker 5

We continue to expect modest increases in R and D expenses through 2024 and for spend to level off heading into 2025 as our late stage investments shift from Daum towards CAS and Quemly over time. As Terry noted, we expect our R and D investment in Daum to peak this year. G and A expenses were $30,000,000 for the 2nd quarter compared to $32,000,000 in the Q1 of this year. Non cash stock compensation represented $10,000,000 of our G and A expenses for the 2nd quarter and we expect G and A expenses to remain stable for 2024. Finally, we now expect our cash and investments balance at the end of 2024 to be between $885,000,000 $925,000,000 as compared to our prior guidance of $870,000,000 to $920,000,000 We continue to expect these resources to fund operations into 2027.

Speaker 5

As a reminder, this guidance includes $100,000,000 partnership continuation payment from Gilead and the Quemly opt in payment from Taiho of $15,000,000 Both payments are due in the Q3. 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.

Speaker 2

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.

Speaker 2

We also expect to initiate our 1st Phase 3 trial for Cas in the first half of twenty twenty five. With respect to DAMA, we expect to present a few important data sets ahead of our first Phase 3 readouts. These include PFS and very importantly OS data from our original ARK10 trial, which evaluated down plus ZYN versus ZYN versus chemo in PD L1 high lung cancer by year end followed by OS data from our EDGE gastric Phase 2 study in 2025. Meanwhile, we're continuing to advance our other programs, including the initiation of a Phase 3 trial for Quemly in pancreatic cancer and the evaluation of next steps for retrumum and colorectal cancer. All of these studies are enabled by the strength of our balance sheet and the great relationships with our partners.

Speaker 2

Lastly, we continue to have a robust discovery engine in ARCUS that enables a sustainable pipeline of future programs. The next program we expect to advance into mid stage studies is AB-eight zero one, our highly selective axil 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.

Speaker 2

Thank you.

Operator

We will now begin the question and answer session. The first comes from Ygal Nochomisitz with Citi. You may proceed.

Speaker 4

Hi, great. Terry and Jen and team, thank you. A lot of updates there. 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 PEAK1 Phase 3 trial? Is there some expected overlapping talks that you may or may not see with CAS and cabo?

Speaker 4

And is the goal there mainly just to clear on safety before moving into the Phase 3 with that combo? Thanks.

Speaker 2

Thanks, Yigal. Dmitry, why don't you give a clear and concise answer to that question?

Speaker 8

Thank you, Terry. Question. Yes, it's I won'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.

Speaker 8

Cabo, of course, is very well established. We don't expect any relevant overlap in 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 dalsutifen and cabozantinib that was published in Melanset, a series of about 55 patients showing indeed that the combination does not show any unexpected toxicities.

Speaker 4

Okay, great. Thanks. And I just wanted to confirm on 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 LightSpark 5 and we're going to get the 50 milligrams and 100 milligrams data separately from the 100 milligram data later this year. Is that correct?

Speaker 3

Yes. So first of all, heard correctly on primary progressive disease. So for, LightSpark 5, the primary progressive disease was 33%. And I said that for the 50 mg cohort, some of what we saw for the 100 mg cohort, we're seeing a significantly or substantially lower primary progressive disease rate. As far as data presentation, we would present the cohort separately.

Speaker 3

But the point I was trying to make is that when we present the 100 mg cohort of data in the fall, we will likely at least say something about the 50 mg cohort, and probably show some data from that as well, but it wouldn't likely be pulled. They'd be showed separately.

Speaker 4

Okay. And then for the first line trial, which you yes, thank you. And then for the first line metastatic study, what sort of combo partners would you be considering there, TKI and PD-one or anything else?

Speaker 2

We're going to be disclosing that very shortly. We would love to be able to disclose it today, but it's probably a couple of weeks often. I think it will 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, 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 frontline 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.

Speaker 3

Yes. 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.

Speaker 4

Okay, got you. Thank you.

Speaker 2

Thanks, Yigal.

Operator

Thank you. The following comes from Terence Flynn with Morgan Stanley. You may proceed.

Speaker 9

Hello. This is Alex calling in for Terence. And thank you guys for taking our question. Prawik, can you give us any insights on potential presentation menu for this CAST, if 2 alpha inhibitor for R20 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?

Speaker 3

Yes, sure. 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. It won't be at ESMO, to be clear on that.

Speaker 3

And then, for the second part of your question, and I'm actually the second part of your question was?

Speaker 1

Patient number of patients.

Speaker 3

The number of patients. It will be about 30. It will be just a little bit above 30. And we'll have about 10 months of medium follow-up at that point in time.

Speaker 9

Okay. Thanks. And maybe just on

Speaker 3

the Phase 1 trial.

Speaker 9

Right, right. Thank you. And on your new trial design, like, 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?

Speaker 3

Yes. So when we said, so PEAK1 will enroll, somewhat healthier, less advanced patient population than what we're looking at in ARC-twenty. So obviously the fact that the drug is looking very good in our 20. Obviously, we think bodes positively for PEAK1. But the patient population that we would be looking at is a bit of a mix of first and second line.

Speaker 3

So it would include patients that receive PD-one 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-one in the first line metastatic setting. So they would then be part of our study as a second line metastatic patient.

Speaker 3

But as we've spent a lot of time analyzing all the data that's out there for the different light spark studies. We feel like this is a patient population that will benefit particularly well from HIF2 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.

Speaker 9

Great. Thank you very much.

Operator

Thank you. The next question comes from Jonathan Miller with Evercore. You may proceed.

Speaker 7

Hi, guys. Thanks for taking my question. Thanks for all the detail this afternoon. Jen, I just 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.

Speaker 7

And I just wanted to get some confirmation that that was what you said. And also,

Speaker 5

is the aura better

Speaker 7

in the 100 mg arm as well? I know you stopped short of saying that in the past. And then I guess given what you've seen so far with primary progression rates and ORR data that you got in hand, do you see a dose response in those higher dose cohorts, 50, 100, 150 at this point?

Speaker 3

Yes. So, good question, John. So, yes, so for 50 mg, I did say that we're seeing a higher ORR today than the 21.9% that was seen with LightSpark 05. I did also clarify that that's with one response of pending confirmation. We would be above the 21.9 percent and also pointed out that 50 mgs given that started enrollment after the 100 mgs, that's a much less mature cohort from a follow-up perspective relative to 100 mgs.

Speaker 3

And then the 100 mgs, yes, we're now north of where LightSpark O5 is. And I'll let Terry speak of that.

Speaker 2

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 milligram cohort is slightly more advanced patient population. As we've noted, it's a more advanced population when compared to LightSpark 5. But with that said, I would say at this point, particularly given that the 50 milligram cohort is somewhat or substantially less mature, it would be hard to distinguish.

Speaker 2

So I actually think given that they're each in the 30 ish range, as you might anticipate, John, 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 $50,000,000 is looking good enough that you won't be able to probably tell a difference between the $50,000,000 $100,000,000 The last point I want to remind you on that though is that to contextualize that you're actually even the 50 milligram cohort is at 2.5 the PD equivalent of belzutafan. And as you know, belzutafan was enough to really shift a change in the standard of care. So the nice thing about that, is all these data start to unfold as well there, 30 milligrams 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 dalzutifan.

Speaker 7

All right, great. Makes sense. And then maybe one more question on CAS strategy. Obviously, you talked about a cabo combo going to Phase 3, this other mystery combo in 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?

Speaker 3

Yes. So, as I say over sort of the next 6 to 9 months, the 2 Phase 3 studies that we called out today will probably be it for us for now as far as Phase 3 studies. That's a lot. Market opportunity is massive. So we will be focused on getting the studies off the ground.

Speaker 3

Where you should expect to see some of the additional work is in our 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 HIFU alpha 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.

Speaker 3

Although interestingly, we're getting a lot of ISTA requests for studies at HCC. So there's definitely a lot of interest out there in the clinical community in evaluating cats and HCC in particular.

Speaker 7

All right. That makes sense. Thanks so much.

Operator

Thank you. Thank you. The next question comes from Salveen Richter with Goldman Sachs. You may proceed. Hi.

Operator

This is Lydia on for Salveen. Thanks so much for taking our question. We just have one on etruumab in colorectal cancer. Just given the Phase III 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?

Operator

Thank you so much.

Speaker 2

Thanks. 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 ask 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.

Speaker 2

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

Thanks so much.

Speaker 6

Thank you.

Operator

Thank you. The next question comes from Dana Greibosch with Leerink Partners. You may proceed. Hi. I have

Speaker 10

a question on TIGIT on ARC-ten.

Speaker 11

I wonder if you can help set expectations given this is from early in the ARC-ten 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

Speaker 2

patient demographics. But I'll just say that we believe that these data will be positive for the field, positive for Domzim and positive for Zim in terms of it being a really nice dataset. And then in fact, if you think about all of the randomized datasets out there, I would put this against any of them in terms of the information that it will convey with a good anti PD-one and the Fcsilin anti TIGIT. So you should we definitely want to lean into this being an important and a good data set. And I'll let Dmitry say a little bit about the patient population.

Speaker 8

Yes. So the patient population, just to break it down and also for others, so it was a 3 arm trial, ARC-ten Part 1. It was a 2:2:1 randomization. So it's about 40 patients, 4 0 on domain ZYN, another 40 on ZYN alone and then about 20 on chemotherapy. That does mean that the study was run ex U.

Speaker 8

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 around 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 time population.

Speaker 3

And I think one other thing to point out with that data set that's I think interesting is there's really 2 different readouts within the data set. 1 is down plus ZYN versus ZYN and the other is ZYN versus chemo, which is how the study was set up. So you'll also see that comparison of BIM versus chemo in that readout.

Operator

Thank you. The next question comes from Asthika Goonewarden with Truist Securities. You may proceed.

Speaker 6

Hey, guys. Thanks for taking my questions. Apologies if I ask something that already has been asked. We just recently jumped on the call here. But just very quickly, can you tell us when Cohort A of the tumor in CRC study is going to be reading out?

Speaker 6

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 KOLs combination, obviously, with cargo, that makes a lot of sense. And given the function on Treg, both PD-one and CPLA-four as good combination partners. I just want to get your thoughts on that.

Speaker 6

Thank you.

Speaker 2

Okay. So I'll take 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 sure at this point. So remind me of the second question.

Speaker 3

The second question was on yes, can you run the second question? Yes. When we think about HIF and

Speaker 6

in combination with PD-one, obviously, it makes sense to think about a combination of PD-one. But yes, how do you like?

Speaker 2

Yes. So actually, we're going to be disclosing very shortly, a second registrational trial that takes us into frontline setting. But your point about anti PD-one, anti CTLA-four combination thereof, obviously those are all reasonable combinations to be thinking about that would make a whole lot of sense to go with HIF2 inhibition.

Speaker 6

Thanks guys.

Speaker 2

Thank you.

Operator

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

Speaker 1

Thank you all for joining us.

Operator

We look forward to speaking with you.

Speaker 2

Thanks everybody.

Remove Ads
Powered by Quartr
Earnings Conference Call
Arcus Biosciences Q2 2024
00:00 / 00:00
Remove Ads