Q1 2025 Arcus Biosciences Inc Earnings Call
Robert Rickenberg-Hammond Lea Klohe-Weidmüller Matt Lilcich MIZ
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Speaker Change: In that vein, we are thrilled that our abstract describing initial data from the cash plus Cabo cohort of arc <unk> was accepted for an oral presentation at <unk>.
This is the same combination we're evaluating our first phase.
Speaker Change: Good quarter and these data should provide further support for the study.
Speaker Change: This will also be the third oral presentation of data at a major medical conference in just seven months and there are a lot more to come.
Speaker Change: Now some important granularity around the <unk> program.
Speaker Change: In our phase <unk> study, we now have eight cohorts evaluating different dosing regimens combination settings for gas in clear cell RCC. This.
Speaker Change: This way, our 'twenty will generate meaningful data over the next two years that will serve several important purposes.
Speaker Change: First continued elucidation of kept the other fans differentiated efficacy profile relative to the other build to suit a fan and derisking of our first phase III study pick one.
Speaker Change: Second continuing to drive the already extraordinary investigator enthusiasm for peak one to support its rapid enrollment.
Speaker Change: Third demonstrating the opportunity for <unk> they have been in earlier line settings with gas has the potential to ultimately displacing <unk>.
Speaker Change: Before I turn the call over to Richard I'd like to touch on a few additional topics starting with our development plan and our long term vision for tests that are fine.
Speaker Change: Our phase III trial peak, one will evaluate <unk> plus cabo versus Cabo in clear cell RCC patients who have received prior immunotherapy.
Speaker Change: First Registrational trial, we chose to combine cast with Cabo because Cabo is the gold standard in most widely used <unk> in the city in fact in our 'twenty monotherapy cohorts, 78% of patients received prior Cabo that's greater than three times more than any other TK.
Speaker Change: Clinicians are extremely comfortable administering and managing toxicities of Cabo and because of this there is an extraordinary amount of interest in peak one.
Speaker Change: Also because <unk> two alpha inhibition before it's relatively benign safety profile with the primary aes being on target anemia, and hypoxia, we do not believe cast we will have meaningful overlapping toxicities with travel.
Speaker Change: Such the key objectives of our upcoming <unk> presentation are to clearly demonstrate these two molecules can be safely combined and that we can add efficacy to be out of Cabo monotherapy.
Speaker Change: Expect the data shared the ESCO will demonstrate exactly this.
Speaker Change: Longer term given the strength of cast is the efficacy and safety profile of <unk>.
Speaker Change: <unk> developed task and Teekay, <unk> free regimens and even to displace <unk> in earlier lines of RCC treatment.
Speaker Change: You guys have been very effective in treating RCC.
Speaker Change: Most every RCC patient receives a T T I during the course of their treatment.
Speaker Change: But <unk> come with debilitating side effects that are meaningfully impact quality of life just cannot be overstated. So we believe there is a huge opportunity to develop Cas in earlier lines driving a long sought paradigm shift enabling patients to avoid teekay <unk> therapy for as long as possible.
Speaker Change: This in fact reflects a core element of ARCUS as high level strategy in oncology driven by the advances in the understanding of tumor biology last decade being the leader in the development of innovative cancer therapeutics with improved efficacy that preserve quality of life during treatment specifically.
Speaker Change: Operating with Astrazeneca, the combined test with their anti PD, one anti CTO for bi specific antibody for Rus to make to create the first teekay <unk> free hip too well for combination option for first line RCC I wonder repeat that this will be the first TK Eric free if you will for combination arm.
Speaker Change: <unk> looked at in first line RCC.
Speaker Change: Anti PD one anti <unk> four is one of the most commonly and widely used first line regimen, particularly at academic centers, because it is teekay free and conveniently prolong survival.
Speaker Change: Astrazeneca will operationalize the study as part of <unk> portfolio. So this collaboration enables us to develop cast.
Speaker Change: First line, setting and extremely cost and resource efficient manner, and with a world class drug developer in oncology.
Speaker Change: The study is designed to demonstrate the safety of the combination to support late stage development. This provides another opportunity to generate confidence enhancing data for <unk> based regimens over the next 18 to 24 months.
Speaker Change: Beyond evolve we've added three cohorts to arc 20 to evaluate cast and other early line Teekay <unk> free settings. These are cast all of them are in.
Speaker Change: And a PD one antibody in first line all comers clear cell RCC <unk> monotherapy in first line of favorable risk patients and <unk> monotherapy in patients that have received prior I O, but have not yet received a teekay all three cohorts recently opened for enrollment and they've generated significant.
Speaker Change: Interest in the investigator community demonstrating building on the robust interest in cash and in Teekay <unk> free regiments. As a result, these cohort should enroll quickly and generate efficacy data over the next couple of years informing future development opportunities.
Speaker Change: While Canada has moved front and center in our portfolio are two other registrational programs, which are targeting massive patient population with substantial unmet need continued to advance towards data.
Speaker Change: For our <unk>.
Speaker Change: Antibody them vanilla, Matt the first phase III study to readout will be start to two one for which we have guided to 2026. This study is evaluating <unk> plus chemo versus Knievel plus chemo. These standard of care in first line gastric cancer later this year, we'll be sharing over.
Speaker Change: We're all survival data OS data from the corresponding phase II study.
District. This is evaluating the same regimen in <unk>.
Speaker Change: I'm setting to start two to one <unk>.
Speaker Change: We expect these data to reinforce confidence and start to two one which has an overall survival primary endpoint.
Speaker Change: The competitive landscape in this field has seen a dramatic shift over the last six months with the FC salad anti <unk> antibodies, specifically ours and Astrazeneca is anti <unk> anti PD, one bispecific antibody now dominating the phase III landscape. These.
Speaker Change: These two molecules that generated similar positive data in phase two studies in both lung and Gi cancers.
Astrazeneca is now enrolling 10 different phase III studies for <unk> <unk> antibody.
Speaker Change: In addition, tourism one our phase III trial of Quinley, our small molecule <unk> 73 inhibitor in combination with chemotherapy in first line pancreatic cancer is enrolling rapidly theres been a tremendous enthusiasm for prism, one and as a result, we anticipate the study will now be full.
Speaker Change: We enrolled by the end of 2025 less than 12 months after initiation.
Speaker Change: Our second global Phase III study that will complete enrollment well ahead of initial expectations and our goal is to replicate the success with the enrollment of <unk>.
Speaker Change: This brings me to my final keep point today, we have a strong balance sheet with $1 billion in cash and investments.
Speaker Change: This is not an accident.
Speaker Change: While there has been a dramatic shift in the macro economic environment, We're always scrutinizing, our capital allocation prioritizing our molecules and programs and leveraging strategic collaborations for example, those with Gilead Tayo and Astrazeneca to maintain a strong balance sheet this will be particularly.
Speaker Change: True going forward to ensure that our capital stretch as long as possible and to enable us to continue funding our small molecule research programs with.
Speaker Change: The discovery of kicked out a fan and exceptionally high quality molecule.
Speaker Change: Against an extremely intractable target is a reflection of the secret sauce of <unk>, which is our research organization and small molecule drug discovery capability.
Speaker Change: Our next time these are likely to come from our inflammation and immunology programs, which have been quietly but rapidly advancing and our focus on the creation of potential first and best in class small molecule drug candidates against validated targets, we're going to share more about these programs later in this year.
Richard: With that I'd like to turn the call over to Richard speak about <unk> in greater detail.
Richard: Thanks Terry.
Richard: Ill first recap the highlights of our recent <unk> presentations for <unk> monotherapy in late line put yourself in a fault carcinoma.
Richard: After that I'll speak about our upcoming data presentations and near term development plans for cash.
Richard: I'll start with a reminder of the study design of our 'twenty on slide nine.
Richard: Our 28 cohorts evaluating <unk> monotherapy or <unk> combination in clear cell RCC.
Richard: As a reminder, our <unk> presentation included data from three of the monotherapy cohort in late line.
Richard: RCC.
Richard: I also want to highlight here the cohort evaluating 100 milligrams of cash plus 60 milligrams of Cabozantinib.
Richard: And this is the same combination and dosing regimen, we will evaluate and peak line.
Richard: And the cohort that is subject to the data presentation at this year's <unk>.
Richard: Patients in this cohort are all previously treated and have received one or two prior lines of therapy at their most recent prior line being an anti PD one.
And patients did not need to have received prior <unk> therapy. So this is a very similar population to that peak one.
Richard: On slide 14, we compare the efficacy assessments.
Richard: For the monotherapy cohorts relative to data from <unk> five <unk>.
Phase III study of <unk>.
Richard: Importantly, we enrolled and more advanced patient population than that of nitric oxide.
Richard: In fact, approximately one third of our patients would not have been eligible for life archive.
Richard: And we recognize the limitations of cross trial comparisons cast performed better on every efficacy measure and every cohort.
Richard: Tightness more advanced patient population.
Richard: <unk> primary progressive disease or close to half of that ability to fad.
Richard: Confirmed <unk> was consistently higher than that if you just had and two carts chief confirmed <unk> created at 30%.
Richard: The <unk> monotherapy studies have ranged from 18 to 21, 9%.
Richard: <unk> is trending about 50% higher.
Richard: Our disease control rate or D. C are over 80% of patients should benefit from <unk> versus just 61% for <unk>.
Richard: Lastly, a median PFS of nine seven months and the 50 milligram cohort was meaningfully longer than a $5 six months from now the defense.
Richard: And the median PFS had not even been reached and the 50 milligram QD and milligram QD cohorts. However, when the full data from the 50 milligram B I D 50 milligram QD cohorts.
Richard: The median PFS for 13 months, so significantly longer than that ability to fab.
Richard: Slide 11 shows the waterfall and Spider plots for the 100 milligram QD dose and these data give us confidence in the selection of a 100 milligrams QD as the dose for our phase III studies of Cas.
Richard: On slide 12, we show the Spider plots for the 50 milligram and 50 milligram QD cohorts, which highlight the durability of <unk> efficacy.
Richard: Across all three cohorts remarkably only two of the 26 confirmed responders had progressed.
Richard: And many of the stable disease patients clearly derive benefit and will therefore contribute meaningfully to the median PFS.
Richard: We have a number of upcoming data presentations for our 'twenty and these are summarized here on slide five.
Richard: First step will be initial data from our cash plus cabo cohort at ESCO.
Richard: A key objective of this dataset will be to demonstrate that these molecules can be safely combined.
Richard: In addition, given that we had approximately 25 patients enrolled by the end of the year, we plan to present overall response rate data.
Richard: Data for those patients who are eligible for two or more scans at the data cutoff.
Richard: To be clear.
Richard: The overall denominator will include all patients who enrolled at least 12 weeks prior to the data cutoff, regardless of the number of scans actually recorded.
Richard: Last I want to point out that the data included in the <unk> abstract up from our prior data cut and the <unk> oral presentations will feature data from our more recent data cut.
Richard: Later in the year, we expect to present more mature data from all four monotherapy cohorts of our 'twenty and late line clear cell RCC.
Richard: In 2026, we plan to share more mature data from the cast plus Cabo combination card.
Richard: As well as an initial data from the newly added color.
Richard: The TGI free regimens and early line settings.
Richard: Now onto the development plan Slide 16, it shows the design of peak one.
Richard: And we are evaluating <unk>, plus cabo versus Canada and <unk>.
Richard: <unk> experienced patients who had one prior line of immunotherapy.
Richard: Target enrollment is 700 patients.
Richard: And we expect that the study will enroll quickly for several reasons.
Richard: First as Terry mentioned earlier, we are using cover the most widely used and preferred TPI in both arms of the study.
Richard: Second patients will be randomized to demand between the experimental arm and the control arm.
Richard: And third there is already a very substantial awareness of cast and the clinician community and.
Richard: And we expect to include multiple are 20 sites in the peak months study.
Richard: Merck is running a somewhat similar steady Cartwright spark 11, which is evaluating <unk> plus a TGI.
Richard: And is now expected to read out in 2027.
Richard: However, there are some important differences I'd like to highlight.
Richard: First while <unk> has cabo and both study arms.
Richard: <unk> 11 has been happening in the experimental arm that Cabo and the control arm.
Richard: Using different <unk> and the same experiment could add risk to the trial outcome for livestock 11.
Richard: In addition, we are using a single primary endpoint of PFS and peak fund rather than a dual endpoint of OS and PFS, which is being used in lifecycle 11.
Richard: And given how quickly we expect equal to enroll and the anticipated timing of the PFS primary endpoint, we have significantly narrowed the gap between our readout and that of Lightbox 11.
Richard: Meanwhile, in the Io naive setting our strategy is very different.
Richard: In this setting Merck is evaluating <unk> in combination with Enbrel and Labatt net.
Richard: In contrast, we are collaborating with Astrazeneca.
Richard: Evaluate class cast has more risk to make.
Richard: Astrazeneca is anti PD, one <unk> four by specific.
Richard: And as Jerry mentioned this is a highly attractive PKI free combination that may enable patients to remain on therapy for several years, while avoiding TGI related toxicities.
Richard: We have not yet disclosed the design of the study, but we expect to share more information very soon and we think you will be excited about our strategy in the setting.
Richard: I would now like to turn the call over to Jim to speak about the market opportunity for test Datacom.
Speaker Change: Thank you Richard RCC is a unique and policy Marco metastatic patients remain on therapy for many years.
Richard: Five year survival is becoming the norm.
Speaker Change: Ah patients will cycle through.
Speaker Change: <unk>.
Speaker Change: Often staying on treatment for well over a year.
Speaker Change: Here, even in the second line.
Speaker Change: As a result, we believe the revenue opportunity for a good practice.
al: Thanks Al.
al: On slide 17, we highlight the total market opportunity for the first two studies, we are pursuing for tax.
al: First we said the Io naive patient population, which we are addressing with caf.
al: The basketball Festival population here is about 13000 patients in the U S and 20000 in other major markets given that most of these patients progress in Ghana subsequent therapy.
al: Mexico patient population for the IL experience setting is very similar.
al: With a two plus year duration of therapy, and Io naive patients 12 months duration of therapy.
al: We believe the total market opportunity for <unk>.
al: It's $5 billion.
al: With a better molecule dental did a fan and differentiated combinations and development plan, we should capture a significant share of this market.
al: On Slide 18, we show U S market share by regimen T.
al: <unk> based regimen dominate the clear cell RCC market with approximately 65% share in first line with 75% in the second line setting.
al: This explains why our first phase III study will focus on our Caf GTI combination and you can see here, while we check Cabo as a combination partner, we believe there's a strong preference for.
al: Hello.
al: As Terry described earlier, our vision is that over time.
al: And we'll move up and lines of therapy and take share from Teekay Lng's regimens either.
al: For accommodation.
al: Okay.
al: Take care of late given cashless low rate of primary progressive disease relative to sort of one competitor.
al: We believe that the defense hiring of primary progressive disease and the key reason, Mike you today, primarily in the third line setting.
al: I will now turn the call over to Bob to review our financials. Thanks.
Bob: Thanks, Jen our cash as at the end of the first quarter was $1 billion as compared to $992 million as of the end of 2024, our cash position was bolstered by a $150 million equity financing, which we completed in February 2025, we expect our cash in existing facilities will enable us.
Bob: To fund operations through our initial pivotal readouts for Dom family and Cas, which include the peak one readout.
Bob: Given the faster than anticipated enrollment of our prism one trial in pancreatic cancer and the completion of enrollment of Star <unk>. One last year, we expect 2025 to be a peak year for development expenses, we expect both our dam related and aggregate development expenses to decline meaningfully.
Bob: <unk> in 2026, and 2027 inclusive of our investment cast out a fan.
Bob: As Terry mentioned, we are also carefully scrutinize, our capital allocation and have made pipeline priorities prioritization.
Bob: Nation decisions to ensure we maintain our strong financial position.
Bob: Turning to our P&L, we recognized GAAP revenue for the first quarter of $28 million, which compares to $36 million for the fourth quarter of last year, our revenues, primarily driven by our collaboration with Gilead.
Bob: We expect to recognize GAAP revenue of $75 million to $90 million for the full year 2025.
Bob: Our R&D expenses for the first quarter, our stated net of reimbursements from Gilead and were $122 million as compared to $111 million in the fourth quarter of last year.
Bob: G&A expenses were flat at $28 million for the first quarter compared to the fourth quarter of last year total.
Bob: Total noncash stock based compensation was $16 million for the first quarter compared to $17 million for the fourth quarter of last year.
Bob: For more details regarding our financial results. Please refer to our earnings press release from earlier today, and our 10-Q I will now turn it back to Terry Thanks, everyone for joining US. We appreciate your interest and your continued support of <unk> and we will now open the call for questions.
Bob: Thank you. Please press star followed by the number one if you'd like to ask a question I'm sure you to Washington mutual Nike retro attention.
Peter Wilson: Our first question comes from Peter Wilson with Barclays.
Speaker Change: Your line is open. Please go ahead.
Speaker Change: Great. Thank you so much.
Speaker Change: First question was just.
Speaker Change: So back to your comments about our pipeline.
Speaker Change: Re prioritization and wondering if you could talk to that a little bit more than that.
Speaker Change: Whether you're exploring the adenosine inhibitor further.
Speaker Change: That's the program ended.
Speaker Change: Thanks, Peter and I'll answer it all together so as I mentioned, we're always do.
Speaker Change: Doing this in.
Speaker Change: In the context of your <unk>.
Speaker Change: Question Bob.
Speaker Change: Dennis being modulator, and I think you're probably speaking to the <unk> two receptor antagonists trauma.
Speaker Change: Perfect example, so we did have a <unk>.
Speaker Change: Getting quite good meeting actually with the FDA on that.
Speaker Change: The path forward, but our plans right now are not to move forward at this time at least the way I think you should look at our portfolio and how we prioritize things as we have those three late stage programs.
Speaker Change: Our number one priority of course is just the Idefense Dom zoom as Bob articulated decided its natural trajectory. We're excited about data coming but spend is winding down.
Speaker Change: Won.
Speaker Change: Our other adenosine.
Speaker Change: Later molecule. So the CD 73 inhibitor will be fully enrolled this year, so that'll be heading towards data shortly keep in mind the <unk>.
Speaker Change: Standard of care there has an OS on the order of 10 months. So we're going to get to a readout pretty quick on that and then on the other side of things on our early stage portfolio.
Speaker Change: We've been evolving there too we're still have a number of oncology targets, but we've been quietly is.
Speaker Change: I described pushing along some really great inflammation and immunology.
Speaker Change: <unk> targets and so later this year I think we will disclose those and you'll find those exciting as well. So the way you can kind of look at it is strong investment biggest invest move later stage programs.
Speaker Change: Nothing overly.
Speaker Change: Heavy on the Middle and then keeping the sustainable pipeline with what's a relatively minimal investment, but with really the secret sauce to bark has to generate.
Speaker Change: Next IND candidates.
Speaker Change: Beyond those we talked about now.
Speaker Change: Got you and then on the <unk>.
Speaker Change: The presentation of <unk>, what should we expect to see in the abstract.
Speaker Change: Presentation, and what do you kind of press release beyond the abstract.
Speaker Change: Got it.
Speaker Change: I'm wondering if someone planted that question.
Speaker Change: When we think it's important.
Speaker Change: I think you should recognize everyone should recognize the abstract is more of a placeholder abstract and so the data cut that we will be sharing at <unk> will be a much more recent and whether we will include as you can think about is two populations first the safety population will be.
Speaker Change: <unk> 40 patients.
Speaker Change: Then.
Speaker Change: We will also want to give you a read on efficacy so even though.
Speaker Change: Probably the median time a follow up is barely over four months. What we've done is we've assembled all the patients who had at least two scans. So that gives them the opportunity to potentially have had a confirmed response and we'll be sharing.
Speaker Change: Efficacy data for that 25.
Speaker Change: So ah patients Youll see a waterfall plot, obviously the data to.
Speaker Change: Too mature to talk about maturity and I think the data I think you'll find them compelling, but you should recognize given that they are early they will likely continue to.
Speaker Change: To improve beyond what we shared this conference.
Speaker Change: Great. Thank you so much.
Peter Wilson: Thank you Peter.
Dana Guaymas: Our next question comes from Dana Guaymas with Leerink partners.
Speaker Change: Your line is open.
Speaker Change: Alright. Thank you I have two really different questions first.
Speaker Change: As you pointed out.
Speaker Change: Exchanges are dominated by the FCC silent.
Speaker Change: And ask you guys to assess it and let's say we assume I think you believe the FC silo is really the key to maximizing future benefit.
Speaker Change: Are you under investing and seeding leadership to Astra.
Speaker Change: Can you just remind us what you're learning in phase II.
Is there a success that you might actually ramped investment backup and then I have one on Casa caridad.
Speaker Change: I think.
Speaker Change: So first of all I think we feel very very good about the bets that we've made because theyre targeting some of the largest io market out there so.
Speaker Change: Got in line, so I would like to one is targeting all comer lung.
Speaker Change: Cancer patients.
Speaker Change: The market there is for anti PD, one and then our other HSA, particularly one is targeting an all comer gastric cancer patients, which is another really really bad market.
Speaker Change: So we feel like those are two great. That's today, we do have active discussions going on all the time about other things that we would want to do with those studies read out positively.
Speaker Change: Things that are keyed up and ready to go.
Speaker Change: If a first phase III readout for pathogen.
Speaker Change: So we agree with what Youre, saying and then the other study to point out I'm curious just reminding me at this stage III lung cancer study that we're doing with Astrazeneca with Astrazeneca is Operationalized, Inc. Packet.
Speaker Change: <unk>, obviously seen a lot of our data.
Speaker Change: We have that partnership on package and so we do think that that's something else.
Speaker Change: It's given them even market conviction in their own PD one program.
Speaker Change: Awesome, and then on cash and the potential for cast mono to replace PKI. In second line. You have that are plenty cohort is there any particular bar for efficacy here looking forward that what gives you conviction to go head to head versus a T K.
Speaker Change: So I think at this point.
Speaker Change: We would look at those a little bit more exploratory.
Speaker Change: Exploratory diff.
Speaker Change: Different in the mono therapy keep in mind in the in those favorable risk patients.
Speaker Change: Basically the standard these days would be more just watch and wait so.
Speaker Change: You see reduction in meaningful reductions in tumor given the safety profile, we think that could encourage.
Speaker Change: People to want to invest in this and keep in mind, both patients could be a couple of years. So.
Speaker Change: Idea there is to get a sense.
Speaker Change: How it looks in those favorable risk patients.
Speaker Change: I know, that's not a patient populations with getting PKI, but that's sort of where were.
Speaker Change: One of those areas, where we don't necessarily have something numerically in mind, but we're looking to see if there's a signal and we think there's a really good opportunity there.
Speaker Change: Our society that are out there for PCI mono range anywhere from sort of high teens, 20%.
Speaker Change: <unk> high end of the range of 40%.
Speaker Change: If we can be in line with that with a better safety profile, we think that would be really exciting for clinicians who are actually just talking to your question yesterday that said one of the high rollers and our Caf combo cohort. She just put our first patient.
Speaker Change: On that cohort that youre asking about.
Speaker Change: The Caf model in second line patients.
Speaker Change: But I'm very excited about how that patient was doing and certainly look forward to hear anymore anecdotes like that I think the thing is is even if you look at our weight line study.
Speaker Change: It's already pointing to something that you know.
Speaker Change: <unk> got a good chance it could be better than PKI in.
Speaker Change: The enthusiasm there really does.
Speaker Change: Ramp up because of two things.
Speaker Change: <unk>.
Speaker Change:
Speaker Change: The.
Speaker Change: In fact it is.
Speaker Change: Teekay <unk> free and the safety profile, but also because of the low rate primary progression.
Speaker Change: Robley why you Havent seen bill.
Speaker Change: <unk> be able to go there.
Speaker Change: Yes, that's really important as you go to the earlier lines, but we feel like we're already seeing numbers.
Speaker Change: Even in the later line that would encourage us.
Speaker Change: For the opportunity going earlier as a model.
Speaker Change: Great. Thank you.
Dana Guaymas: Thanks Dana.
Dana Guaymas: The next question comes from Mr. <unk> with Citigroup.
Dana Guaymas: Your line is open. Please go ahead.
Speaker Change: Alright. Thanks.
Speaker Change: Can you just talk about the timing for peak one PFS primary and then you said light spark is going to be doable.
Speaker Change: <unk>, which is do we know which of these is coming first and if like spark hits on OS and PFS then what's the plan to answer that last question. The peak, one and under what timeframe would that happen relative to <unk>.
Speaker Change: Hey, Mark.
Speaker Change: Okay.
Speaker Change: Yes, so there's a lot of questions in there.
Speaker Change: So first of all it's alright.
Speaker Change: Sorry early for us to give.
Speaker Change: Very good.
Glenn: Question, Glenn I think it's too early given we're just about.
Glenn: To start the study to give guidance on when we might see PFS data.
Glenn: We talk to some of the commodities and back of the envelope math just based on how likely do you think it would take to complete enrollment based on other RCC studies.
Glenn: And then.
Glenn: With the PFS and you would expect in <unk> and that control arm and you could cut.
So when you might expect to see a readout.
Glenn: So it's not too far distant because we do think this is a study that's been a real quickly because it is the PFS readout.
Glenn: On your question on what we're doing as a key secondary endpoint. So to your point, yes, we do think it's important to collect that information and it is a key secondary endpoint in our studies that data will be collected as far as widespread <unk> when they had it as a dual primary endpoint of OS or PFS.
Glenn: So.
Glenn: One of those and the study will be successful and you do have to split alpha in that case, because there's two different endpoints versus what we're doing which is the sole primary so that can work against you.
Glenn: But yet they are waiting for that OSA endpoint that is what's giving us the opportunity to really catch up to them and narrow that gap between when our readout might a car versus theirs.
Glenn: Just put something out there that is out there.
Glenn: Merck recently pushed a bit.
Glenn: Study on clinical trials Gov for a second time after 2027, so whenever you do your back of the envelope calculations, while we haven't given guidance that even a potential delta is.
Glenn: Dramatically closed from when we first started contemplating this and we actually do feel we're going to have <unk>.
Glenn: <unk> comment on this but we've got a real tailwind as we launched this study investigator enthusiasm not only is very strong but from a practical standpoint, because we've invested pretty heavily in these monotherapy cohorts not only if we engendered a lot of enthusiasm all kinds of anecdotal studies.
Glenn: Every one of these investigators is their own interesting story of what they've seen so they wanted to.
Glenn: Jump on this but the other practical matter is that we've got 30 or 40 sites that are going to transition potentially into peak. One. So I think we're really going to be hitting the ground running in an unusual way versus.
Glenn: Going from a standing start.
Glenn: Presentation of the cap combo cohorts, obviously perfect title.
Glenn: I think investigators are particularly interested in Africa.
Glenn: Efficacy is obviously important but I think everyone believes we're going to add efficacy, but they really want to see safety and just make sure theres no. Additional toxicities are overlapping toxicities are.
Glenn: Discontinuation et cetera to worry about and so that will be a very important part of the data presentation.
Glenn: Okay. Okay got you and then post the Gilead decision on Taz.
Glenn: Now to just fund this fund is to completion yourselves or would you entertain.
Glenn: Help from another partner potentially.
Glenn: Yes, so the first thing I want to mention.
Glenn: I think it is.
Glenn: Important point, because a lot of the questions that.
Glenn: We're out there right at the time these new data.
Glenn: Our new so this will give you yet another look the <unk> combo data are we think quite exciting and obviously they were not mature data when gilead made their decision.
Glenn: Getting to the specific question.
Glenn: We feel really confident in our abilities for some of the reasons. We were just talking about we've been working with the molecule be working with the sites. We've got a steering committee that.
Glenn: Couldn't be better they're excited.
Glenn: We feel we're in a great position to execute this not only from a capital position as we've talked about we have the resources, but from the people standpoint, our team has been working with this all along so our plans are to execute peak one.
Glenn: On our own.
Glenn: With that said.
Glenn: Could there be some other collaborations we as we mentioned we'd like to use collaborations in an efficient manner. As an example, the astrazeneca.
Glenn: Collaboration we might.
Glenn: Do other things like that and of course on an opportunistic basis, there could be other things, we would do but the base case you should be thinking about is that we feel very good about our ability to execute this trial.
Glenn: Very.
Glenn: Efficient and.
Glenn: Strong strong manner.
Glenn: Alright, Thank you Terry Thanks, Dan.
Glenn: We should go.
Glenn: The next question comes from Andrew <unk> with Evercore.
Please go ahead.
Andrew: Hi, guys. Thanks for taking my question I have a few here if I may.
Andrew: Perhaps first the choice of dose being 100 milligrams for your first phase III, which admittedly is a cabo combo.
Andrew: Is there anything to read into the choice of that 100 milligram dose relative to any early data you are seeing on the $1 50, and 200 milligrams and then I have a couple of follow ups.
Speaker Change: Okay and you can have as many questions as you like.
Andrew: So the 100 nothing.
Andrew: Based upon any new data that we've seen.
Andrew: Had a really good discussion with the FDA in the context of project Optimus. The 100 milligram dose we talked about that we talked about essentially a 150, we talked about potentially 50 safety profile of the Hunter look great we feel based upon.
Andrew: All the data we've seen that the <unk> hundred is essentially on the asymptote for efficacy what we're seeing with 150 I think we'll share that at the end of the year, but I would just foreshadow that youre going to see something that looks pretty similar and we will see just how things play out.
The one thing Thats important to note for our 50 and 100 milligram doses, we still do not have medium PFS, maybe as we get towards the end of the year and we're sharing data will be there, but obviously, we'll have some sort of landmark PFS and it may be that there is a.
Andrew: Bid of more AE creeping in on the 150, I Couldnt, even say that with certainty.
Andrew: Now so I think the way to look at the 100 milligram dose is everything we've seen suggests that you're.
Andrew: Essentially mixing out efficacy there and it's a very safe profile. So there's not a whole lot of rationale to even be thinking about the $1 50.
Andrew: And what about 200.
Andrew: Oh, yes.
Andrew: The only really looked at 200 of the dose escalation and Didnt see any crts, which was good.
Andrew: But we haven't looked at it beyond the dose escalation and I think that's true based on everything we've seen so far so we now have 30 patients or 5800 800, because you make.
Data and I think that there's a lot of confidence in 100, Meg alright, though I think the other thing that we're actually thrilled about it's not a surprise, but and will draw your attention.
Andrew: When you look at Decaf combo data is.
Andrew: An important aspect of that is being able to keep patients on therapy and <unk>.
Andrew: The data look.
Andrew: We think pretty.
Andrew: <unk>, even though they're early and obviously with time.
Andrew: You might see otherwise, but I think youll come away feeling like.
Andrew: Efficacy on.
Andrew: Those patients that have <unk>.
Ed two scans.
Andrew: Looking good waterfall looks good and the Aes look like.
Andrew: Kabul by itself plus cast by itself in.
Andrew: You know very well tolerated combination.
Andrew: Exciting opportunities about the combination too is that if you are just getting TGI mono and you get 10 foot mouth syndrome, or Greg or hypertension or whatever it is and we typically have to come off you take AI for it that in this case, even though we're coming off of <unk> you are still getting it kicks off inhibitor. So you are still getting enacted dragged enough water.
Andrew: Things that I think positions the combination to perform very well relative to Cabo monotherapy catcher out.
Andrew: In most cases patients are going to be getting at least one of those two drugs.
Andrew: So if you do get TTM related toxicities that will stay on Caf.
Speaker Change: Got it so I guess that brings me to my sort of main question here, which is.
Speaker Change: What exactly is the makeup of this post Io court in our 'twenty. They were gonna see yet ask or the accord in general and I ask because you could have double aisle experienced or you could have IL plus that Jeff Teekay I experienced in my understanding is or are a little lower when its I O plus <unk> versus dual Io so what exactly.
Speaker Change: <unk> is that and is there any data to read into from your cask Mono arm, which is also a second line plus that may presumably have some of these post io patients as well.
Speaker Change: Yeah. So so you're right, it's going to be index, and we'll disclose that mix and it's in line actually with the lights part III study I'd like to cast with Colo.
Speaker Change: One thing that I would mentioned when you look at patients that got I O I O.
Speaker Change: First the patients that got Io plus that Jeff So far that are ours actually look very similar so there is not too different.
Speaker Change: If patients had gotten prior GTI versus just prior IL.
Speaker Change: Yes.
Speaker Change: Makes sense.
Speaker Change: And.
Speaker Change: Okay, and then do you acknowledged.
Speaker Change: Sir.
Speaker Change: Right and would you acknowledged.
Speaker Change: From Cabo point trial about low <unk> is the comp for Cabo monotherapy following Io therapy.
Richard: We'll go ahead Richard.
Speaker Change: I think the kind of alone has a range of.
Speaker Change: Or are is depending on what study you look at and what data source you have so kind of in the 20% to 40% of the Pic 30.
Speaker Change: That's one of the choices I'd say, but.
Speaker Change: It's quite a range across the different datasets there for a couple of alone.
Speaker Change: One other relevant.
Speaker Change: The one other relevant dataset as there was.
Speaker Change: Bill's combo arm.
Speaker Change: And that again on your front came in just over 30%.
Speaker Change: And it's PFS in that study, obviously, we won't have PFS to compare to yet with the PFS. There was on the order of 13 months.
Speaker Change: And again, just so I'm clear.
Speaker Change: We talked about 20 to 40 being the range, maybe thirtyish being the midpoint, which is also consistent with the Cabo point trial, but the critical thing is you guys are emphasizing safety not an efficacy advantage is that reasonable or do you want to have higher ore as well.
Speaker Change: Well, it's absolutely that Bose.
Speaker Change: Where do you think both as important I can make the point that safety is going to feed into advocacy because we wanted to keep patients on drug you want to avoid dose reduction.
Speaker Change: So the more we think we can safely combine these two drivers that should further enhance efficacy.
Speaker Change: Absolutely to showing improvement emphasis metrics.
Speaker Change: Efficacy and safety that you aren't getting adequate toxicity.
Speaker Change: Or even worst toxicity.
Speaker Change: Just alone.
Speaker Change: Thank you so much.
Speaker Change: Yes.
Speaker Change: Thanks.
Speaker Change: Next we have asked.
Speaker Change: <unk> with Jewish.
Speaker Change: Your line is open.
Karina: Hi, This is karina for ask you, but thanks for taking my question Adam.
Karina: I had a question on the <unk>. So beyond Astrazeneca study with stomach are there any plans to initiate a registrational study.
Speaker Change: Potential combinations with PD, one or is that not in frontline.
Karina: Yes.
Karina: Nothing registrational that we've disclosed so far so Terry talked about on the call. We did just open a cohort in our 'twenty, where we're combining <unk> with our anti PD ones in Berlin that and first line patients. So that's something we can ultimately to initiate a registrational study for some sort of.
Karina: Again guideline, enabling study, but that's the combination we're super excited about investigators are super excited about we think that cohort is going to enroll incredibly quickly.
Karina: Because again I think theres, a lot of interest and to avoid <unk> in the frontline setting where patients are still feeling really good.
Karina: In a relatively healthy.
Karina: Yes, so we'll see how that goes with some of these other cohorts that we started and there could be future Registrational studies for sure I think the way you should think about our approach is that basically we're not just going to be throwing a bunch of spaghetti up on the wall, where we jump.
Karina: We think we have a great molecule, but we're not just because there.
Karina: Peppering the world with Phase III studies. So we're we're gonna do early work to ensure that any phase III study, we do really makes sense.
Okay. That's helpful. Thank you.
Karina: Thank you.
Karina: The next question comes from Lee.
Karina: With Cantor Fitzgerald. Please go ahead.
Karina: Hey, this is Dan on for Lee.
Dan: I was wondering if you could kind of set expectations for your combination with Volcker rule and what Youre looking for in the Io naive setting and for a potential pivotal frontline trial.
Dan: What would you be comparing your doublets too.
Speaker Change: From a lot of good questions and it's a lot of information and we just haven't closed yet.
Speaker Change: And as Richard alluded to on the call probably around midyear.
Speaker Change: We should be able to talk a lot more about that study and so right now really all we can disclose is that the plan is to go buy cap with full rail in the first line setting.
The big issue with <unk> is really for US is that you do have a very high rate of primary progressive disease, So about 25% to 30% of patients don't respond if he NEVA slow breakthrough therapy and so that's why they actually <unk> typically used.
Speaker Change: <unk> that don't have really aggressive disease. So you know more.
Speaker Change: Hello, aircrafts tumors and so.
Speaker Change: So what are the reasons why I think Astro was very excited about combining for a cap is that opportunity to bring down the rate of primary progressive disease, given we're seeing a very low rate of primary progressive disease.
Speaker Change: So pharma cap and so what we will be looking for initially obviously that you can safely combine these two mechanisms, which today. We have no reason to think you put it and now we will be booking some of these early signs of efficacy, particularly.
Speaker Change: The rate of PD, and then eventually we'll be looking at or ours, etcetera, but yes, we do think that PD rate could be particularly interesting to look at because you do have that high grade or primary progressive disease with an email.
Speaker Change: [noise] huge amount of interest.
Speaker Change: And Kristina combination as whenever I talked about on the call. We just actually did some market research and I think we were actually even surprised about how much interest there is in the investigator.
Speaker Change: No need to combine these two mechanisms and to try to avoid U K is on the front lines.
Speaker Change: Okay, great. Thank you.
Speaker Change: Yeah.
Our next question is from Sylvan Richter with Goldman Sachs.
Speaker Change: Your line is open.
Matt: Great. Thanks, This is Matt on for solving.
Speaker Change: Maybe first just on Cas to follow up on a prior question is it fair to say you guys would consider a commercialization partnership post peak one or when you are close to reading out peak, one or is that no longer of interest to you.
Speaker Change: And then on the broader portfolio any thoughts on the newly announced CVR director from just kind of a portfolio risk perspective. Thank you.
Speaker Change: Yeah.
Speaker Change: Yes so.
Speaker Change: On the first question our intent is to commercialize we wanted to fully leverage the opportunity. We think this is really.
Speaker Change: Huge for Argus, I think we'd probably consider.
Speaker Change: Our partner in Europe.
But we feel really good about.
Speaker Change: Taking this forward commercializing the whole the whole piece for us seems very many.
Speaker Change: Manageable.
Speaker Change: I don't have any comments on.
Speaker Change: But with the rental fleet.
Speaker Change: Yeah. It does.
Speaker Change: In macro I would even elevate that.
Speaker Change: Our whole.
Speaker Change: It's about everything happening at the FDA when it comes to what we're doing what we're executing.
Speaker Change:
Speaker Change: Things have just been business as usual as far as we can do so.
Speaker Change: What's happening in the news I have no comment, but from a practical standpoint.
We're pretty comfortable with everything we're doing right now that it's it's.
Speaker Change: Proceeding just as it would have.
Speaker Change: Six months or one year ago.
Speaker Change: Thank you.
Speaker Change: Sure. Thanks.
Speaker Change: Our next question is from <unk> <unk> with Wells Fargo. Please go ahead.
Speaker Change: Hi, Thanks for taking my questions a couple from US first on the fall 2025 update forecast can you just provide a bit more color on like expectation here in terms of like the different cohorts number of patients on duration of follow up on this.
Speaker Change: Second question is you mentioned, an emerging ini franchise.
Speaker Change: We expect to learn more about this would this be more towards the end of the year R&D day type of event.
Speaker Change: Yes.
Speaker Change: Just the first part of the question is with regards to the follow up in the fall and its really looking at again at the monotherapy data we had in Africa, a G. U I will have more mature data coming so we'll have another data cut there. We haven't stated are selected FIS will be at a medical conference or other ways of sharing that data, but we will.
Speaker Change: Being able to provide updates to that data center will have matured a fair bit since the kind of at the beginning of this year.
Speaker Change: And on the.
Speaker Change: Immunology inflammation front I think the way to think about that as you know.
Speaker Change: Conceptually, whether it's an R&D day or part of one of our other releases.
Speaker Change: We will find a form.
Speaker Change: To describe.
Speaker Change: The breadth of what we're doing and where we sit.
I think it's an exciting portfolio takes advantage of what we do well and I think that'll be highlighted the small molecules were challenging targets were.
Speaker Change: The targets are highly validated, but there's not a great amount.
Speaker Change: So we've been building on that.
Speaker Change: I'll remind you because we're like a real company in terms of with people.
Speaker Change: And we have a biology group we have.
Speaker Change: Medchem group good in all of the associated.
Functions.
Speaker Change: There is but our biology is actually more immunology because the roots are in.
Speaker Change: Oncology and so even though we're oncology has been our clinical endpoint.
Speaker Change: We have a strong immunology group in fact.
Speaker Change: We've invested in that and.
Speaker Change: No we're getting to the point, where we can start to talk about those.
Speaker Change: Those programs.
Speaker Change: We'd like to talk about things when we've got tangible manner not Glenn.
Speaker Change: Well I think that.
Speaker Change: Yes.
Speaker Change: We'll be very tangible.
Speaker Change: Yeah.
Speaker Change: And all done with machine learning.
Speaker Change: [laughter].
Speaker Change: But we havent machines.
Speaker Change: We'll take one more question for blending and our final question comes from Anthony <unk> with H C. Wainwright. Please go ahead.
Anthony: Hi, Thanks for taking the questions My first one for the mono therapy dose.
Speaker Change: Can you comment on how the 100, Meg QD cohort, it's progressing relative to the female BRD cohort.
If you're starting to see some more results in terms of median PFS.
Speaker Change: If you could just comment on timing for the star Once you one trial for Dom and lung cancer and if there's any timing updates for the top line results.
Speaker Change: Yes, so there's really no timing update yet on one to one study.
Speaker Change: Uh huh.
Speaker Change: Two things, it's still enrolling and then as a <unk> for the standard of care.
Speaker Change: Over 20 months, so it's premature, it's obviously enrolled well and will continue to enroll.
Speaker Change: We haven't said anything on timing there.
Speaker Change: Nothing to say really on the.
Speaker Change: Maturing data other than to point out that we.
Speaker Change: We haven't reached a median PFS and so I think as we get towards the end of the year, we don't even know for sure that will be there, but if we're not we still will be sharing data and it would then undoubtedly include those sort of landmark PFS.
Speaker Change: Yeah.
Speaker Change: Okay got it thank you.
Speaker Change: Thank you.
Speaker Change: Thank you. This concludes our Q&A session today as well as the call. Thank you everyone for joining you may now disconnect your lines.
Speaker Change: Thank you.
Speaker Change: Goodbye.
Speaker Change: [music].