Q4 2023 Arcus Biosciences Inc Earnings Call
Participants
Pia Eaves; Vice President, Investor Relations; Arcus Biosciences Inc
Terry Rosen; Chief Executive Officer; Arcus Biosciences Inc
Jennifer Jarrett; Chief Operating Officer; Arcus Biosciences Inc
Dimitry Nuyten; Chief Medical Officer; Arcus Biosciences Inc
Bob Goeltz; Chief Financial Officer; Arcus Biosciences Inc
Terence Flynn; Analyst; Morgan Stanley
Robyn Karnauskas; Analyst; Truist Securities
Daina Graybosch; Analyst; Leerink Partners
Li Watsek; Analyst; Cantor Fitzgerald
Presentation
Operator
Hello, and welcome to the Arcus Biosciences full year/Q4 2023 earnings call. My name is Elliott, and I'll be coordinating your call today. (Operator Instructions)
I'd now like to hand over to Pia Eaves, Vice President of Investor Relations. The floor is yours.
Pia Eaves
Yes, hello, everyone, and thank you for joining us on today's conference call to discuss our fourth quarter 2023 financial results and pipeline update. 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. Those risks and uncertainties are described in our annual report on Form 10 K, which has been filed with the SEC. We strongly encourage you to review our file.
Today you'll hear from our CEO, Terry Rosen, CEO, Jennifer Jarrett, CMO, Dmitry Nelson, and CFO, Bob Gallagher, who will also be joined by our President one high end for questions after the prepared remarks. During today's call, we'll refer to slides in our corporate deck, which can be found on the Investors section of our website with that, I'll now turn it over to Terry foods through most pure boom.
Terry Rosen
Thank you all for joining us today. We've really come a long way since our founding nine years ago. And I think it's fair to say we have evolved into an integrated biopharmaceutical company, got seven molecules in clinical development, a broad late-stage portfolio, multiple mid-stage clinical trials, a robust discovery engine and now something, I think new a line of sight to commercialization with 1.2 billion in cash and equivalents and runway into 2027. We're well positioned to deliver on the promise of the late-stage pipeline that we've built with our three new registrational trials. We're going to continue to invest in our early-stage programs. We also have a partnership with Veolia as well as collaborations with Taiho, Exelixis and AstraZeneca. And I think it's very fair to say without these partnerships and the resources that these companies provide would not be able to execute on everything that we're doing. All of our programs targeting markets that are massive and that, you know, really are the sweet spots of large pharmaceutical companies, all-comer patient populations in lung cancer, gastric cancer, pancreatic cancer and renal cell carcinoma RCC. Our funding and partnerships enable us to not only pursue these settings but to compete and compete effectively and aggressively. We're really doing what we're saying we're doing. We also continue to build for the long term with a broad pipeline of potential best-in-class and first-in-class product candidates that will continue to replenish organically with our drug discovery engine. Today, we have three advanced clinical-stage programs, Dom plus MRF. T cell and anti digit, very differentiated molecule nor anti-PD-1 antibody currently our small molecule CD73 inhibitor, and 85 to one, our HIF-2 alpha inhibitor, which is as of today known by its generic name DataBank for cash and Zoom is in Phase three, and we expect to initiate Phase three studies for both counts in cleanly by early next year. So we'll have four molecules all with distinct mechanisms in Phase three in 2025. We also have some exciting data sets coming in the first half of this year for another molecule in these really are exciting E trauma, that's our V2 receptor antagonist, and it's kind of the Engility, I believe, support further investment in molecule. We made a lot of progress across all these programs in 2023, presenting two large datasets for dump them in two different cancers than another large data set just last month equivalent in pancreatic cancer.
I want to start today by reviewing these programs and data center spend a few minutes on the recent Juliet partnership updates and finish with some new data for CASRF. two alpha inhibitor.
So starting with our antibiotic program comes in our primary competitors in this space are Merck and Roche. We have the only FC. sale in the United antibody in late-stage clinical development. So with Dan's potentially best-in-class profile, that's optimized dosing regimens as well as a broad development program focused on lung and gastric cancers. We're really in a very strong competitive position. Our conviction and dump them supported by good dataset that we presented in the last 12 months and are summarized on Slide 9 of our corporate deck. First, in Asco last year, we presented data from our randomized Phase two Arc seven study showing a PFS hazard ratio of 0.67 for dams and relative to Zim monotherapy in first-line PD-L1 high non-small cell lung cancer. We also presented data from our Phase two gastric study, where we evaluated data zim plus chemo in first-line upper GI cancers at the SK plenary session in November. These data demonstrated an impressive six month landmark PFS rates of 93% in PD-L1 high patients, 77%. All overall, this really compares quite favorably to the historical benchmarks for anti-PD-1 plus chemo that are in the 50% to 60% range.
Our development program for Dom Zoom is focused on cities where we have the best chance to be market leader. Today, we have three Phase three trials enrolling, and we expect both star one to one and star two to one, our chemo combo trials and PD-L1 all-comers for first-line non-small cell lung cancer in upper GI cancers. Respectively, to complete enrollment this year. In fact, we can share now today that we anticipate start two to one will be fully enrolled by the middle of this year due to the extremely rapid enrollment of START two to one and relatively short OS. for the standard of care, we expect start two to one to be the first of our Phase three trials to read out. And importantly, with no other Phase three trials ongoing with the impact of the antibodies in this setting, we expect to have a significant first-to-market advantage. Meanwhile, we continue to invest in the expansion of our dams and program. We and Gilead will initiate star one three one, which will be valued down zim plus chemo, peri-operative lung cancer this is an exciting early-stage and potentially curative setting. We also expect to initiate a fourth Phase two study in a setting outside of lung in GI cancers beyond our dams in the program today, we'll be sharing data from the dose escalation phase of our ARC 20 Phase Ib trial of test data for 85 to one 100 milligram expansion cohort of our 20 enrolled quickly and it completed enrollment ahead of schedule November of last year. Later today, we'll touch on what we're seeing so far in these data. The competitor here is Merck with their shift to alpha inhibitor, those who defend, which was just approved for advanced clear cell RCC. But we believe that cash has a best-in-class profile, and that's addressing a very well recognized limitation of builds in defense. What we've seen thus far, and ARC 20 has given us confidence that our molecule has a superior profile to data builds in defense. We're advancing cash rapidly and are on track to initiate a Phase three study early next year. And last for currently our CD73 inhibitor, we presented overall survival data in pancreatic cancer from our eight study at ASCOGI. last month with a large pool dataset, 100 to 22 patients, we showed 15.7 months median overall survival for commonly plus chemo, both with and without them. This compares to the median OS from historical gem nab-paclitaxel studies nine to 11 months in first-line pancreatic cancer. We also conducted a map synthetic control analysis that showed a statistically significant improvement in OS. with a hazard ratio of 0.63. Based on the strength of this data, we are on track to initiate a Phase three pancreatic cancer trial by early next year with Gilead equity investment in January, we had approximately 1.2 billion of cash on hand and we're really well capitalized to support the breadth of programs that we are pursuing at a high level.
Gilead's investment accomplishes two things. First, it provides us with runway into 2027, while enabling us to fund Phase three programs for four different molecules. Second, it enables us to fund our precommercial activities and on the other end of the spectrum to continue supporting our robust discovery engine.
I'd like to turn things over to Jen right now to spend a few minutes on the details.
Jennifer Jarrett
Thanks, Terry. Jillian invested 320 million by purchasing our stock at $21 per share. We've represented an effective premium of nearly 40% to our share price just for 14, increasing their ownership to 33%. In parallel, Julia as Chief Commercial Officer, Jonathan Mercier joined our board for additional increases or board membership to three provides representation commensurate with our ownership and bring a very experienced commercial perspective to the Arcus board investment fell for two dynamics, one expansion of our late-stage clinical development plan and two-year extension of our cash runway into 2027 and through multiple data. Concurrent with the investment, we made a few strategic portfolio changes related to content and quality. First, for Dan Sam, we closed enrollment of our Phase three, our 10 study evaluating Johnson and PD-L1 high non-small cell lung to focus our resources and capital on areas with the highest unmet need and greatest market opportunity. Seminal factor that drove our decision with the evolution of the lung cancer treatment paradigm towards increased use of anti-PD-1 plus chemo for patients with PD-L1 high expressing tumors. Therefore, we believe this segment of the patient population is best addressed by our star one to one study. Our chemo combination study and PD-L1 all-comer non-small cell. The clinical trial landscape for PD-L1 high loans has also become increasingly crowded with several anti digit and other investigational therapies. And we were not expected to be first or second in the PD-L1 high chemo-free.
At closing our 10, we are now able to focus our energy and resources on rapidly completing enrollment for STAR one to one, which is addressing a much larger market opportunity. We'll have to initiate a fourth Phase three study for guns in Star went through one, a potential first-to-market opportunities. Second, frequently, we announced Arcus will be operationalizing and funding a Phase three study evaluating cleanly and pancreatic cancer. Gilead retains an option to the pancreatic cancer program with the opportunity to pay a premium to their share of the Phase three costs in the future on Gilead is not co-funding the study as you might imagine they are aware that proceeds from the investment will be used to fund the study. I'll now turn it back to Jerry.
Terry Rosen
Thanks, Jim. And I'd like to switch gears to cash, our shift to alpha inhibitor this year is essentially going to be coming out for this program as we're planning to release a lot of new data as well as more information on our future development plans. We believe that by hitting the shift to Alpha target harder than Merck's built ZFNs, we can improve outcomes for patients. We'll discuss the pharmacokinetics and pharmacodynamics that support this thesis in more detail shortly. But I'd like to start with the potential areas for differentiation versus dose with defense. We also found was recently granted approvals monotherapy in third line, clear cell RCC after just a three month FDA review process has really validated the mechanism and highlighted the high unmet need for new therapies in this market and Merck's Phase three light Spark oh five trial. Those who defend showed an improvement in PFS over Everolimus with a statistically significant hazard ratio of 0.74, which supported its approval. While these results are absolutely encouraging, study reveals multiple opportunities for new agents improve upon those new defense profile and provide even more benefit to patients.
First, on clinical efficacy in White Star all five, those would have been had a high rate of primary progression, specifically of 34% PD rate, which was actually higher than that of the Everolimus control arm at 22%. This means that over third of patients on bills do defense progress at or before their first scan. We believe that case data van could stabilize tumor growth faster, resulting in a lower PD rate, therefore, longer PFS, second, with an overall response rate of 21.9% in late start of oh five, we believe there is room for improvement.
Third, while wide Spark all five showed a statistically significant PSFPFS. hazard ratio, the median PFS was only 5.6 months past may result in more durable tumor stabilization restrictive, therefore, longer median PFS.
Fourth, and this is an important for We believe there's an opportunity for a better tolerated combination regimen does through defense T care partner in earlier line, PCRCC. studies is lenvatinib, which is perceived, and it's really as perceived that way to be less well-tolerated relative to other TKIs such as Kevo Envinsa.
Last, we are being very thoughtful in our development strategy for test, and we'll focus on settings and combinations where we believe we can be first to market or differentiated relative to build defense. And you'll hear more about this over the course of the year. As you may know, Merck is now projecting that those good events has blockbuster potential given the opportunity and we're pushing this program as hard as possible. And while our data will be more mature later this year, we want to share as much as possible today to illustrate why we're so excited about this program.
I'll now turn things over to Dmitry to share new data from our ARC 20 trial evaluating tests in cancer patients.
Dimitry Nuyten
Thanks, Terry. I'll start by turning to slide 29 of our corporate deck, which shows design of the trial, including both the dose escalation phase and expansion cohorts to dose escalation portion enrolled patients with any advanced solid tumor. While the dose expansion cohorts are only enrolling patients with second line or later clear cell RCC, there are three expansion cohorts, each of which will enroll 30 patients, first evaluated our go-forward dose of 100 milligrams per day and completed enrollment in November to satisfy the FDA's requirement for dose optimization we are also evaluating a 50 milligram dose cohort and another cohort at a higher dose than 100 milligram in the expansion phase of enrollment of the 50 milligram cohort is nearing completion. Collectively, these expansion cohorts will generate a lot of valuable safety data and efficacy data in clear cell RCC patients. The dose escalation portion employs a three by three design where three patients received 20 milligrams followed by three patients who received 50 milligrams, and then three patients who received 100 milligrams oral daily dosing regimens. The safety results of our healthy volunteer trial enabled us to start in our 20 patient trial at a relatively high and pharmacologically relevant dose. And we saw no dose-limiting toxicities allowing us to complete the dose escalation phase with only nine patients. We subsequently backfilled the 50 milligram dose cohort with three additional patients resulting in 12 patient data set for this portion of the study of the 12 patients, four patients have clear cell RCC.
Slide 30 is important and shows data forecasts and bells on Epo reductions. The peripheral or normal tissue biomarker for F. two alpha inhibition on the left hand side, the dotted line shows the Epo reductions reported for the 120 milligram or the approved dose of Bell who defend in clear cell RCC patients in contrast, gas achieves the same level of EPO suppression at just 20 milligrams, showing here with the purple line. And that is one-fifth of our go-forward dose of 100 milligrams This means that 20 milligrams, it's roughly equivalent from a BD perspective to the approved dose of Bell suit event. And therefore, 100 milligrams of cash has the potential to achieve a meaningfully greater shift to alpha inhibition.
On the right hand of the slide, you can see that gas has a linear, almost perfect dose dose-proportional pharmacokinetic profile. In addition, cash has a half-life of approximately 21 hours and this enables daily dosing.
Slide 31 emphasizes the ideal PK of cash relative to debt of Dell to defense. And it explains why those who defend cannot simply the dose higher to achieve greater of 12 ambition on the rights for gas, we show that we increased dose from 20 to 100 milligrams at steady-state, and we observed roughly five times increase in exposure by comparison, as you can see on the left, when Bell's does loss increased from 120 to 240 milligrams, the drug exposure only increased by about 30% at steady-state, a 30% increase in exposure is less than the typical patient-to-patient variability at any given dose and therefore, is not a clinically meaningful increase. This illustrates by doses higher than 120 milligrams of those who defend are unlikely to result in meaningfully better clinically active or clinical activity. And in fact, this was demonstrated by Merck in the light part 13 trial comparing the efficacy of 120 milligrams and 200 milligrams of Bell to defend In summary, these data show exactly what we have been predicting that gas has a best-in-class PK/PD profile, which should result in hitting the target harder and potentially in greater clinical activity relative to industrial defense.
Turning now to safety on slide 32, we showed reductions in hemoglobin levels at various doses of gas relative relative to that to the approved dose of those who defend hemoglobin reductions appear to plateau at doses above 50 milligrams forecast, likely due to competition story mechanisms. And you can see that 100 milligrams daily of cash resources and similar reductions of hemoglobin S best to defend, despite the fact that we are achieving higher doses, much higher doses of potency, corrected drug exposure forecast. For this reason, we expect cash safety profile to be manageable and not meaningfully different and also defense.
On the next slide, slide 33, we show the AE profile so far in the dose escalation phase of the study, anemia and hypoxia are expected on-target toxicities related to have two alpha inhibition, but we are watching very closely with a median follow-up across all dose levels of the escalation of about 8.8 months. So far, these rates do not appear to be higher than the rate seen with those who defend in historical clinical trials. These data demonstrates that while we believe that we are hitting the target, harder cast appears to have a similar safety profile to that of our suite of them.
So let me tie this together we are effectively able to deliver an exposure to gas that is fivefold greater than it, which achieves the same level of inhibition of the peripheral biomarker 42 alpha blockade, excuse me associated with the approved dose of those who defend with no apparent differences in safety profile. While efficacy was not the objective of the dose escalation phase, particularly given the advance stage of patients and the different doses evaluated and the different tumor types included.
On slide 34, we do summarize what we observed in RCC patients, specifically clear cell RCC patients as I mentioned earlier, there are four patients spread across the three different dose levels be evaluated 20 milligrams, 50 milligrams and 100 milligrams. These are only nine patients with a variety of prior treatment regimens, including at least one anti-VEGF treatment and one anti-PD-1 treatments. Three out of four patients are actually fourth line or later. And for these four RCC patients to have meaningful tumor reductions, just short of 30%. And the third patient did not experience any tumor growth for over 14 months and still remains on treatment.
The time on treatment is impressive for these patients in very late-line setting, ranging from 8.5 to 14.5 months, and two of the four patients still remain on treatment. This indicates the potential of very durable effects of cash, even with monotherapy in a very advanced patient population. We are also seeing signs of Keppel's ability to bring even aggressive tumor growth under control. For example, one of the <unk> four patients I mentioned was very heavily pretreated. It received three prior VEGF TKIs, anti-PD-1 treatment. And this patient had stable disease early on with slight increase in tumor volume, not meeting form of progression per resist. And after about 18 months, the tumor volume started to come down and now after about 10 months and still ongoing on treatment, the patient is nearing a response. I would like to emphasize that while the primary goal of an all-comers dose escalation study is to establish the safety profile and assess the pharmacokinetics and pharmacodynamics. We have already seen clear signs of anti-tumor activity in patients with advanced clear cell RCC. And we believe that tumor shrinkage and the duration beyond one year for patients who have exhausted all available treatment options are very clinically meaningful. The ongoing expansion portion of the phase is designed to give us a better read on the efficacy and this is already providing clear support for the initial observations in the dose escalation phase. And I would like to make a few comments on the early data of the expansion portion of the study. The 100 milligram cohort has completed enrollment in November. So we have a mature and rich data set in hand for 30 clear cell patients treated at 100 milligrams forecast. While these data are still early, we are already seeing glimpses of cases potential for differentiation, overdose defense, we'll share the full dataset at a medical conference later this year, but we did feel it was important to share some highlights of the data today. First, the majority of patients in the expansion cohort have only had one or two scans and we scan patients approximately every six weeks. So it's about 1.5 to 3 months of follow-up. Nonetheless, even with this very short duration of follow-up, the response rate we are seeing, which includes unconfirmed responses, given how limited the follow-up time is. It's already in line with the response rate seen for those who defend and made Spark zero zero five. We also have a substantial number of patients early on their treatments who have experienced tumor shrinkage, but have not yet crossed the formal threshold of 30% to meet a response, but this obviously can happen with longer duration of treatment on future scans.
Secondly, we are seeing relatively low primary progression rate, and this is the percent percentage of patients whose best overall response is progressive disease. So these patients have tumor progression on the first scan. This may indicate that cast disability, a capturing of cash can stabilize tumor growth early on during treatment. And this will be an important parameter to monitor in the future as it represents an opportunity to prove our prove upon something that loss reported for best to defend In summary, we are very encouraged by these early dose escalation and expansion cohort data, which while early have provided an encouraging signal that Castle's PK/PD profile could translate into greater efficacy in the clinic by midyear, we will have a minimum of seven months of follow-up for all 30 patients in the 100 milligram expansion cohort, which should provide a mature look at the overall response rate, and we expect to present these data at a medical conference in the second half of the year.
As I mentioned earlier, our 20 includes two additional expansion cohorts and we extend we know we expect this to also be presented over the next 12 to 18 months. We also expect data from stellar oh nine. Our study evaluating gas together with since announcement sensitive this and have started also referred to a sensor sometime in 2025. We are full speed ahead to our Phase three study, and we expect to disclose more on our development plan in the coming months. Gary will outline our order catalysts for 2024, but first, I will turn things over to Bob to discuss our fourth quarter and full year financials.
Bob Goeltz
Thanks, Dmitry. As Terry outlined earlier, our focus continues to be in a very strong financial position. Our cash as of December 31st, 2023 was 866 million and increased to 1.2 billion after Gilead's January equity investment. Importantly, our partnership with Gilead is very capital efficient because we share the majority of costs for option programs, 50 50, including multiple Phase three studies for Dom Zim. Yulia has also committed to pay the $100 million option continuation payment due in July under the collaboration agreement. So we expect our cash balance at the end of 2024 to be between 870 and 920 million and now expect our cash to fund operations into 2027. This guidance excludes other potential opt-in payments and approval milestones from our partners.
Turning to our P&L, we recognized GAAP revenue for the fourth quarter of 31 million, which compares to 32 million for the third quarter of 2023. Our revenues, primarily driven by our collaboration with Gilead, and we are evaluating the impact of the recent amendment on our revenue for 2024 and beyond.
In addition to our partnership with Gilead, we have a partnership with Taiho for dominant Japan. In the fourth quarter, we received a milestone payment of 14 million from Tyco related to their participation in our start to two one pivotal study and we'll receive another $30 million in the first quarter of 2024 related to their participation in our star T. two one and star one to one pivotal studies. We are also eligible for additional milestone payments of $10 million in the first quarter of 2025 from Tyco related to Star one to one. Our R&D expenses for the fourth quarter are stated net of reimbursements from Gilead and were $93 million as compared to $82 million in the third quarter of 2023. In the fourth quarter, non-cash stock compensation represented 9 million of our R & D expenses. The increase in the fourth quarter was related to standard of care purchases for our clinical trials. We continue to expect modest increases in R&D expenses as our Phase three studies mature and spend will fluctuate primarily based on the timing of clinical manufacturing activities and the purchase of standard care therapeutics for our clinical trials.
G&a expenses were 29 million for the fourth quarter of 2023 compared to $30 million in the third quarter of 2023. Non-cash stock compensation represented 9 million of our G&A expenses for the fourth quarter, and we expect G&A to remain stable for 2024. For more details regarding our financial results, please refer to our earnings press release from earlier today and our 10 K. I'll now turn it back to Terry for concluding remarks.
Terry Rosen
Thanks very much, Mark. Before we open the floor to questions.
I'd like to briefly touch on upcoming catalysts for 2020. For beyond the arc 20 datasets that Dmitry highlighted highlighted, there's a lot this will be another data rich year for Arcus for the FIT program, we'll be presenting updated data from EDGE gastric, our Phase two study evaluating dams and plus chemo in upper GI cancers at Asco this year. We expect this dataset to include updated ORR and PFS data. We also look forward to announcing the completion of enrollment for Star 1 to one 32 to one which will obviously start the clock for potential regulatory filings. We also measure data and insights from our 10 at a future medical conference. As I mentioned earlier, we presented impressive overall survival data from our Phase Ib ARCADE trial that was evaluating cleanly in first-line pancreatic cancer. Also related to the adenosine pathway. We have two randomized datasets that we expect to share in the first half of the year for each tumor, our two receptor antagonist. And we believe these confirm our findings and our gate that adenosine modulation confirmed fourfold improvement on overall survival. So first off, Roche will be presenting data from MORPHEUS PDM. This is a randomized study operationalized by Roche that evaluated the trauma in combination with chemotherapy and tisle their anti-PD-L1 antibody versus chemo in pancreatic cancer. So a randomized study that involves the true months.
Second, we submitted data from the third line cohort of ARC nine presentation at a medical conference this cohort enrolled 105 patients and evaluated the tumor plus zim plus Bevan full Fox versus Rigel, the current standard of care in third-line colorectal cancer. The presentation will include mature PFS and importantly, OS data, which we believe are also very supportive of the potential for adenosine modulation when combined with immunogenic chemotherapy to robustly mean robustly, prolonged PFS and OS.
So in conclusion, we've covered a lot today, a lot of materials, but there's one thing to take away from today's call that Arcus is now fully enabled to execute on its diverse late-stage portfolio with funding into 2027, and that excludes potential future opt-in payments. Our portfolio includes six ongoing and planned Phase three trials, multiple Phase one two studies and in discovery engine that's just capable of generating at least one IND per year. Our trials are focused on huge markets by any standard lung and GI cancer, pancreatic cancer and RCC, where we're extremely well positioned to compete for potential first-to-market or best-in-class therapies. We have a lot going on a lot more to come this year.
Thanks for your interest and support for our business as we continue to broaden our portfolio of innovative combination cancer therapies, and we'll be working to bring these treatments to patients as soon as possible.
We'll now open the floor to questions.
Thank you.
Question and Answer Session
Operator
(Operator Instructions)
Terence Flynn, Morgan Stanley.
Terence Flynn
Okay, hi.
Thanks for taking the question. A two-part one for me.
Just wondering on cash that have two alpha program, slide 24, the dose expansion data can you just confirm what the ORR was and how many of those we're actually confirmed versus unconfirmed.
Terry Rosen
And then the second part of the question relates to a potential Gilead opt-in on this program.
Terence Flynn
Maybe, Terry, you could just remind us the mechanics of how that type of a decision would work in terms of how little or how much data you would provide to Gilead and then how long they have to make a decision.
Terry Rosen
Thank you.
Terence Flynn
In terms of so on the first question on, we didn't share specific or are intentionally on actually 70% of the patients have only had one or two scans so on, we will wait till the second half of the year to give that number. But we're seeing a number of responses.
Terry Rosen
And in fact, then there's double digit patients that are stable disease with tumor reduction that may convert our response.
Terence Flynn
The second part with respect to Gilead opt-in on we have defined very specific criteria together with them.
Terry Rosen
We haven't shared those exactly.
Terence Flynn
But if you and look at what we've described in general for the relationship that often occurs when we've generated proof-of-concept data so you can draw your own conclusions of what's coming later this year. And our belief is that they're very excited about the molecule and the program. But we'll see what they actually decide.
I'll make one last final point on that is a program that we obviously wouldn't mind taking forward ourself. And we also have had plenty of inbound interest from other companies that might see a strategic fit with the rest of their portfolio.
Operator
We now turn to Peter Lawson with Barclays. Your line is open. Please go ahead.
Great.
Terry Rosen
Thanks for the updating. So all the information on cash is that able to reduce the number of fast progresses you were talking about and you've seen any complexity in recruiting patients for upside if two alpha plus cents a unit, but two non-approved drugs, if that any way you think affects that patients you get to see.
Terence Flynn
So we actually have a number of discussions on this topic. We do not see that we're going to be well well, the flying on for the rest of world, the future development strategy, we're going into settings that we think makes sense on, including with Vans up. And we also are in parallel, we'll be exploring combination with cabo. So we'll have both of those under our belt but we feel very good about our ability to enroll and keep in mind we're not planning on, obviously in the context of this question to be on going after monotherapy at this point and so on will be going against the standard of care of it doesn't involve those who defend. And we feel like very well positioned to execute on those trials and in fact, a huge degree of excitement. We've already had the first ad board meeting and the enthusiasm for both hip two as a general mechanism from what investigators have seen with bells as well as their anecdotal experience, which is now starting to get to be substantial with caps on mix, I feel very exciting. So we actually expect very rapid enrollment as we've seen already for this molecule.
Terry Rosen
And then just on the the kind of the rapid progressors, you kind of seen that or reduction in.
Jennifer Jarrett
Yes, Phil and Ted, you look at like our fiber to the Phase three study for download a fan and you can look at what the primary progression rate was in that study and were lower than at the people we talk to investigators about like ours. Crs are five, the primary progression rate, which is relatively high. What sort of thing that stuck out for them that the results overall were very encouraging. But I think that's one thing that they would love to see improved upon was the primary progression rate, just the number of patients, this kind of blew right through dilutive in treatment. So like I said, you were saying at a lower number than that, we think it's another opportunity to improve upon this and building more to come on that later in the year.
Operator
Thank you much.
We're not trying to become very common with BTIG. Your line is open.
Jennifer Jarrett
Please go ahead and good evening and congrats on the progress, and thanks for taking my questions. We have four, five to one dose expansion data there or are the two provided Can you or can you tell us or provide any color on how pretreated these patients were compared to the like StarClose FIGHT trial and the trial, I believe, excludes patients with prior to Alpha treatment. But do you think higher exposure could make these patients respond to one.
Terence Flynn
So Dmitry, one, Hon Chew on talk a little bit about the treatment of those patients in the expansion study.
Dimitry Nuyten
Sure. And yes, thanks for the question. Regarding the prior treatments and the inclusion criteria for the expansion cohort allow for patients in a slightly earlier setting than in the dose escalation phase. So in the dose-escalation phase, we required people to have exhausted all reasonable treatment options. And therefore, third to fourth line was what we expect in the expansion cohort. We are still seeing a fairly similar profile of pretreatment. And that's something we think is, let's say what we are expecting. It also puts our early efficacy observations in a positive daylight, many of many patients in the expansion cohort also had two or three prior VEGF TKIs, and they all are required to have PD-1. So if I summarize it, we do allow slightly earlier stage patients second line and beyond. We are in the escalation phase, it would have been third-line and beyond. But overall, so far, the prior treatments are very, very similar as to the Bell to defend question. It is an interesting question, and it is something I think worthwhile thinking about, however, and including patients now with those who defend prior treatment, I think will make it really hard to interpret the data because one reason could be that patients did not respond because the the target wasn't hit hard enough. It could be complete, let's say, resistance for him to targeting. I think that looking at the best to defend data, if you look at the primary progression rate, a number of those patients presumably would have been hard to get under control, dose might benefit. But patients there could definitely be patients who have resistance to have two alpha targeting. And so I know it's not a simple answer I think for a clean efficacy signal right now, that's why we are excluding prior to treatment because it's too complicated. And one patient who progresses on those who defend would not be the other patient. So that would have to be explored in more detail setting.
Jennifer Jarrett
But you really capture the detail of prior treatments on the right company at Landmark, the fire lines of treatment in that expansion cohort negative dynamics that has been in front of me. So four of the 30 were second line. So it was a minority of the patients in that arm and nine were third line and then the remainder. So that's 19 were for fourth line or later as you then have all of our numbers. As a reminder, and as a reminder, unlike bark and five, again get a Phase three setting for Bell, the inclusion criteria was one to three prior lines. So patients with more than three prior lines were excluded from that study.
Terence Flynn
Good cobalt, or did you have a follow-up?
Jennifer Jarrett
I could count if I can ask another question for Morpheus. Peter, Sandy, can you tell us what you're expecting in terms of efficacy, especially all at end, whether you expect a true margin perform better or worse than currently and outcomes from this trial could change anything what are your plans to initiate it.
Terence Flynn
Three trials are currently so carry on it doesn't change anything. And what you'll see is on the OS. data, just say they're going to be similar to what you saw on for arcade.
Now the DA there, two interesting component there is actually they have a gem-Abraxane control arm in the study. So it is randomized study as you know, we conducted this synthetic control analysis, which gave us great data. The thing about ARC eight is that on the larger end, but on the other hand, on the MORPHEUS study, I have to randomize then a randomized arm and they both point to the same answer. So to me, that's the big takeaways. You have two studies that affect adenosine in two different ways, but bottom line are removing the effects of the data that they're both producing. What we would say are pretty profound effects on on overall survival, which is you know, to us very important insofar as the trauma versus family, we've had that question in mind for some time. At this point, we'll still say other than in some very specific settings where there may be on known nano CD 73 mechanisms for adenosine formation from adenosine triphosphate, we would say we'll hold judgment as to which might be better. You can make rationale for both de novo. If you forced me to pick one, I would still go with CD73 inhibition with the idea being that if you could block the formation of some thing versus have to reverse the actions of something that tends to be better, but that will play out it over time. I think by that time, the big take-home message is by the time you see these three datasets combined. I think it's going to read very positively on adenosine modulation as a mechanism that has a meaningful role, particularly in the context of immunogenic chemotherapy as a standard of care where there's headroom for improvement.
Jennifer Jarrett
That's very helpful.
Robyn Karnauskas
Thank you.
Terry Rosen
Thank you.
Operator
Our next question comes from Jonathan Miller with Evercore ISI.
Your line is open. Please go ahead.
Terry Rosen
Hi, guys. Thanks for taking the question.
Bob Goeltz
I would love to ask about him too time to response and maybe some context about how Aurora could evolve from here. Obviously, you're talking about already reaching a similar level to a light Park and hinting that you would expect to add or are to be mature by midyear. But what's the your expectation of what's the evolution from here to there? How much more are would you expect to see in later scans a? And then relatedly, given a linear PK up to 100 milligrams in the escalation cohorts so far, do you expect that 50 milligrams could also show differentiation versus Merck? Could you put a little bit of that dose optimization in context for me as well.
Terence Flynn
There are some great questions on. So I'll let me start with the first one that gets a little bit to your kinetics. So that's all anecdotal from to date, but let's first put a line in the sand lights for our goal. Five is roughly 3.8 months median time to response the way things are looking you played around with numbers. It looks like at least at the outset that we're doing and perhaps better than that and we'll see how that plays out. And obviously, they be the opportunity for deeper response longer PFS, all those are, as you know, those really aren't independent variables. So hitting that target harder at the outset on maybe driving kinetics that are known to be not particularly the of our total. We have seen a couple of you know, later patients having dramatic tumor reduction after multiple scans.
How your second question. But even though we didn't say anything about it in the script and it's even earlier, what I'll tell you is the 15 milligram cohort, it's almost fully enrolled. So that's going to be another 30 patient and honest with you just took a look and I know not even all the patients have had a single scan yet, but it actually works pretty good. And on the kinetics, that's where I would tell you on the first group of patients that have had scans. And so I don't want to get viewed as you know, I could get ahead of the skis because I tend to be pretty transparent with what we I've seen. But the first group of patients are seeing some pretty significant reductions and so feeling optimistic both about the kinetics and we're looking hard at fifty's. Clearly Are there more than pharmacologically relevant, and it does look like on the early early efficacy readout that's playing out. As we stated, 20 milligrams was essentially giving the same effect as the approved dose of bills with the fan on the PD marker in the 50 milligram dose certainly if you had 90 different and it was labeled 100 from what we've seen, you would say it fits right in, but you know that way too early to say that's how it's going to play out.
Bob Goeltz
Makes sense. And then one more also on the escalation side of things. Obviously, only very few of those patients were RCC patients. Could you tell us about some of the other indications in that escalation set. So where you might have seen clinical activity?
Jennifer Jarrett
Yes. So on there is a mix of tumor types. And so I would tell you that it really wasn't anything like any other tumor types. And they're all, you know, patients have received multiple prior lines of therapy. We did have two patients with RCC non-clear cell that are non-clear cell RCC. Interestingly, one of the patient has had a nice response, and it's still our treatments have not not at 30% tumor reduction but they've been on treatment for many, many months and continues to be on treatment.
So, you know, it seems to indicate that the drug has activity in non-clear cell.
Yes.
Terry Rosen
Okay.
Terence Flynn
Makes sense.
Operator
First, Joe and me now turn to Yigal Nochomovitz with Citigroup. Your line is open. Please go ahead.
Dimitry Nuyten
Hi, Gary and team.
Terry Rosen
Did you say what the doses were for the two RCC patients that showed the tumor reductions just short of 30%.
And then I have another question on this.
Terence Flynn
Sorry, was your question because I believe 100, Mig dose. And the other, I think was that when it correctly, you're throwing in Provo, the former version of G2 at all scrubber, both into I think, Jim, you got that right definitely one was 100 and definitely away.
Terry Rosen
The other one was either 20 or 50, they're probably looking well.
Okay.
Jennifer Jarrett
And then sorry, so it was for me, right?
Terry Rosen
The floor and then we'll go at this point.
And as far as what you would do for the Phase three dose, I mean, you finished the dose expansion for 100 milligram first doesn't mean that that's going to be the base case for Phase three, right? I mean, you could you could go at 50.
Bob Goeltz
You also said you have it.
Terry Rosen
You're evaluating a higher dose up to 200, although I don't know what that is. What's the base case for Phase three.
Bob Goeltz
That's still TBD.
Terence Flynn
Our conversion cases 100 we get and that really comes down to you go unless we see something dramatic on from any of the either of the other arms on which obviously are being done to support the know that we've got the optimal dose from a ultimately a regulatory standpoint. We feel that if you look at the Merck data and you look at what they've achieved and you look at their waterfalls and you look at their kinetics that once we've established that five fold increase over matching the peripheral PD marker that we felt like you should be on maximizing the response in the tumor. So as a practical call Vision, you know, oftentimes when you and it's unusual, more unusual in cancer, but when you have a very safe drug at some point, you say, Tom, you know this from a practical standpoint makes sense, but if we see something on, you know, in these other expansion cohort that would cause you to feel like there was something different we would consider doing something or alternatively, but right now we're on a trajectory to that 100 milligram dose.
Terry Rosen
The other thing that's nice about safety profile is appearing very clean and he does it very soon.
Jennifer Jarrett
But just to clarify that put two responses, one was a 100 meg and one way 15.
Terry Rosen
Okay, got it. And then mentioned Lightbox five a bunch of times. So obviously, that was versus everolimus. So so for Phase three, I'm assuming you'd want to go up against those who defend. But I don't know. Is that is that the right assumption?
Yes.
Terence Flynn
So the things we were in once we describe exactly what we're doing, so we're not going to be going into that same monotherapy on the setting. So we'll actually be going in a setting where does the rebound would be the standard of care and we will go against the standard of care, and we'll say a little bit more about that as the on your goes along.
Terry Rosen
But that was part of the strategy when we consider what would be the best place to go first.
Okay, understood. Thank you.
Operator
Salveen Richter, Goldman Sachs.
Hey, thanks. This is Matt on for Salveen. Maybe just following up on that last question. Could you share any additional details at this point on the Phase three design per case? And then secondly, you cited the changing treatment paradigm in first-line PD-L1 high lung cancer away from Keytruda mono as a reason for for discontinuing our tenants shifting to one 21 was just curious if you could share any details on what data this shifting trend is based on why you believe this is happening now? Thank you.
Terence Flynn
Thanks for the question. That's gone. I'm going to walk and chew gum at the same time.
So two different two different programs.
So what I'll comment is, and you can think about on RCC, it's from a standpoint of all of the volume and the need ultimately commercialization. It's there's multiple lines where you can think of going. And so we would probably move up a bit from where the third-line population was and you could think about patients that have received anti-PD-1 and or TKI. So and you'd be you wouldn't have bells as standard of care. We feel like that's a great place to go and so far as your question about on our trend and the strategy there. So clearly, well, let me let me give a couple of points on that. So clearly, like with main therapies and particularly in cancer. It's one of those places where obviously there's a Goldilocks, but but physicians do and patients tend to be more focused on efficacy and safety within a reasonable bounce. And I think as time goes along and physicians become both more comfortable with the liabilities of a therapy, how they're administered as well as you know, a conviction about the real efficacy. That's what's happened in a very continuous way in this high PD-L1 population, you know, going from, you know, anti-PD-1 alone and increasingly to our anti PD-1 plus chemo, particularly in a in a more healthy patient population or with a patient with a bulkier, more rapidly, our progressing tumor. We think that's only going to be more enhanced particularly with a molecule like Dom, which we're already seeing on from a study, for example, like Edge gastric, that essentially doesn't bring any additional side effect liability on top of anti-PD-1 our post-chemo. So we think that that's going to further cannibalize on that particular of approach to treating that population. So we do feel that star one to one best addresses on their population with the best opportunity to become the standard of care.
I know for for all covers what I'll also say from a biological standpoint, I think one of the important things is you move like down the spectrum from your toxic agents, IL beta tubulin inhibitors to things that are very much understand the biology, what you really want to start thinking about is less of the organ that you're treating, then the biology that you're treating and we do feel and the biology that supports anti-TIGIT a couple of things at the highest level CD. one 55 is a bad thing. If you've got CD. one, 55 of what C and what CD. one 55 is doing is keeping you from getting all of the mileage that you might otherwise out of anti PD one because anti PD one relies on CD. two 26 on to get its full efficacy. And so when you have CD. one 55 engaging the CD. two, 26, you're losing part of what you might otherwise gain. And that's the whole rationale and now what's being borne out clinically behind anti Tejas and why we feel like the best place to go for anti digit is where you already know that anti-PD-1 works and you know that PD-L1 all-comer population with chemo is absolutely right down the middle of the fairway for where you want to go with a molecule like down.
Terry Rosen
Helpful. Thank you.
Operator
Robyn Karnauskas, Truist.
Robyn Karnauskas
Hi, team or several question on thinking about the 200 milligrams of cash. Do you think there'll be a diminishing minute of return. If you actually would you think you could push the occupancy up higher? What are your thoughts in sooner milligram?
Second question is about auto on how it differs from Xansa and third might be, do you think you could leapfrog in how you are turning that a different trial leapfrogged into frontline with five Q1 is there a strategy there and like how do you incorporate your own and eight oh one into that process? There's a lot going on there.
Terry Rosen
Maybe you can take those that one so I mean, it's sort of interesting question on what would be advancing. Question was a one compound, the airline for a while.
Robyn Karnauskas
How is it differentiated from dense axle only? And could you incorporate that in your clinical trials, but are great. You're doing all these bands a clinical trial?
The second question would be 200 milligram. Can you like what do you think is going to happen there? Are you pushing a little bit already? Do you think you get greater efficacy? And third would be could you leapfrog ahead giving our phase one 2b trial and go into first line RCC because you've done really good things in the past by cutting things off and like skipping ahead of other people. And given the knowledge you have to get a first-line indication versus risk factor indication?
Terry Rosen
Great.
I'll start with the 200 milligram, and I'll be brief on that. We do think that's probably overdosing but we want to see it because it will also give us some additional safety data. If we do go higher does does it do anything else on the other physiological roles of F. two alpha. But we do think that the 100 milligram dose is really hitting on the target hard enough, but we'll see what we learn from 150 or or 200 milligrams. Why do you want to take the hit on one question?
Yes, sure, Tom.
Xansa as well as cabo is primarily a VEGF TKI. It inhibits axle with a both molecules with decreased potency, but that the clinical activity in the US is relieved. It generally accepted to be the result of VEGF inhibition. So the eight oh one, we believe is going to be a more surgically effective inhibitor of Axl, but probably not the first thing you would reach for in the context of RCC where rational We primarily to go after VEGF TKI.
Terence Flynn
So question, what was the actual going? Are things like, you know, STK11 mutant non-small cell lung cancer, by the way, I'm a don't want since you ask about a mobile call a bit. We have on completed the healthy volunteer dosing, PK profile and safety profile we've really got. So this is in our minds, the first molecule that have the selectivity to really test the actual hypothesis. So we're very excited about that molecule.
Terry Rosen
Jim, do you want to comment or Dimitri on the five to one leapfrogging into a frontline setting here, and I can appreciate that.
Yes, exhibitors.
Dimitry Nuyten
And so we are considering all options and we could leapfrog into the first line. We could keep talking to the adjuvant setting, but we really want to make sure we select the setting for the first registrational trial. That is a mix of different factors. It has to have the data let's say, safety and early efficacy data supported it has to be a sweet spot when it comes to comparative timelines to Merck.
And I guess other considerations about time lines to readout. A first line trial is an interesting market opportunity. But for example, the bar in first line is higher than in second line designed to readout is longer, of course, in first line and second line. So we are considering all these different options and we'll make a decision and communicate that in the near term future what our first opportunity would be that we pursue. It is a factor of a multiple multiple factors.
Terry Rosen
Great.
Terence Flynn
And Robin, Laurie and I will since you asked about that, I would like to emphasize the point of your question conceptually, though, is really good. One to wealth is going to end up being really important. I think that's why Mark has started to call it out as Blockbuster, maybe five to one barring some weird unforeseen thing, it's a drug. And so the real question is how do you fully exploit that? And if you if you ask me about our portfolio. It's definitely something that as we aggressively move towards this first study, we want to look very hard at how do you expand the footprint of the hip to alpha program that's a really huge opportunity. And we actually think because it's so hard to get a good molecule. You're not going to have anyone come in with a better molecule than us so we feel we're going to end up better than bells. And it's it there's not going to be commodity here.
Robyn Karnauskas
And I like to think Dmitry, for making me feel not so bad for announcing all these names. So Xansa worked for me, cast work through.
Thank you very much.
Dimitry Nuyten
This military, appreciate this modulation.
Netsuite.
Terence Flynn
I'm going to kick off not cares to this.
Robyn Karnauskas
It's what I've been told so far worked on that very I'll work on that matter, and I can't tell the difference two points.
Operator
Daina Graybosch, Leerink Partners.
Daina Graybosch
Hi, guys. Thanks for the questions. I have three on task getting into the PKP. day PET data first start on page 31 where you show the area under the curve. I recall initially talking about the value proposition for cash that you expected a much higher absolute area under the curve. But what I see here at the 100 milligrams is pretty similar in range to the 120 and 240 milligrams for Belbuca fan So I wonder if you can talk to that that you're ending up in the same range. And then on pharmacodynamics, you have two different pharmacodynamic readouts here. First is the percent people change on page 30 and then the process hemoglobin or the absolute change in mean hemoglobin on page 32 and what should be of these PD readouts? Do you believe is more correlated to what you expect in efficacy. And if I look at the hemoglobin, you're sort of in range of both due to van and you're modestly higher or looks to be modestly higher percent ITO. So my final question is, how much better efficacy do you expect to drive with these similar to modest increases in pharmacodynamic markers versus does it the same thing.
Terence Flynn
But thanks, Dennis. So I'm going to tie it together. So I think the key point I'm going to define what's better PK and what's better PDCLPD., as you know, encompasses everything, tissue penetration, potency differences, pharmacokinetic differences. So the PD readout, what we're saying, and we think this is the value proposition, no question that at 20 milligrams of 85 to one, you're getting the same horsepower and let's use equal as the, um, marker that you get out of the approved and used dose of filters of defense. Now the PK advantage has nothing to do with an AUC relative to Bell sooner than the PK. advantage is that when we go to fivefold higher doses than the dose that gives you that equivalent on activity on the PD marker, we get five-fold higher exposures. So there's more water to be squeezed out of the activity stone. We're hitting that with fivefold the equivalent TD. dose of Belgium defense. So that down the value propositions of PK. advantage is that you can go higher from that maximal effect with respect to hemoglobin or bomb equal, we don't look at either of those per se is something that's predictive of a more or less predictive of the our activity in the tumor setting, it collects data back.
Daina Graybosch
So you're hitting at fivefold more dose than what gets you to the pharmacodynamic marker. And you believe that will give you a much better efficacy even though neither of these pharmacodynamic markers were fivefold greater dose really had that much more effect than does it feel after that?
Terence Flynn
Yes, it is correct, but no, is it correct.
Terry Rosen
And that's what's predicted.
Terence Flynn
And that's what that's the difference between the physiological on maximal hip do get, as you know, hip hip transcription factor. So regulates a hundred things. If effect on Epo have nothing to do with what's going on in the tumor. So we know going in that basically you're going to max out the shift to the pill or equal inhibition. And so that just becomes a marker for how hard are you hitting this this thing and then the fact that we can go five X on what you can get out of the Merck molecule. It's what makes us feel good about hitting the tumor harder.
Robyn Karnauskas
That's very helpful. Thank you.
Terry Rosen
Thanks, Dan.
Operator
Li Watsek, Cantor Fitzgerald.
Please go ahead and services.
Li Watsek
Rosemarie, on and thank you so much for taking our questions. And so to start with, can that them and do you happen to see any dose response when it comes to toxicity, the safety profile and do you have concerns for greater side effects when you go above 100 milligrams? And then one question on your own digital programs, correct.
We'll go ahead and finish your questions.
So the question for T.J., do you plan to show some data from the ARC 10 trial which was discontinued? And do you have any color on when this could be and what kind of data we would expect? And would it potentially impact any thinking around the trials that you still have going on? Thank you.
Terry Rosen
Yes. So on the dose response, to be clear, the 20 milligram dose that we used is our lowest dose is already pharmacologically relevant as we noted on, you're seeing essentially a maximal effect on Epo suppression at that point. So I would just say what we'll have three patients on each of the doses with six on the 50 on. We wouldn't say that we see any meaningful differences, nor do we expect that in a way because of what we know. And this was gets back to how I was answering Dana's question there, either feedback mechanisms or other non if two mediated on ways that on that Eagle is produced. And so you hit this maximal effect on that endpoint, which to date has been the primary side effect is very manageable. So that is the anemia that's a correlate of that equals suppression. And basically that's been very manageable. So at this point, we don't have any expectations that going higher will induce any more of a liability. And we certainly haven't seen it at the 100 milligram dose The other place where we're keeping a close eye is, in fact, on hypoxia that has to do with his two inhibition in the lung. Again, that may also be something that Max throughout its normal physiology on. It's something that we're paying attention to. Some of these things may also be yield dependent on individual patients, particularly when you think about equal, if their patients would have that have compromised on kidney function. But the date on we haven't seen anything of concern and we'll just see what happens when we go to a higher dose. And certainly under the initial 30 patients, nothing that we've seen to date has caused us concern. And to make the point we have not yet seen it's a DLT on the anti two-digit ARC 10 data. That's just something we're considering. We haven't made a decision on that, but if we did do that, the idea would be that we would do our cut of the data and a cleaning of the data when we with us extrapolate that we would have mature PFS minimally. And at this point with the data that we have in hand from our other study. It wouldn't affect any of the studies that were it would not be a decision making data.
Operator
And to Terry, ladies and gentlemen, this concludes our Q&A and today's conference call. We'd like to thank you for your participation.
You may now disconnect your lines to.
Yes.
