Arcus Biosciences, Inc. (NYSE:RCUS) Q3 2023 Earnings Call Transcript
Arcus Biosciences, Inc. (NYSE:RCUS) Q3 2023 Earnings Call Transcript November 8, 2023
Operator: Thank you and welcome to the call. Following prepared remarks from the Company, we will open the call for questions. [Operator instructions] This call is being recorded and will be available on the investors section of the ARCUS website. I will now turn the meeting over to Pia Eaves, Head of Investor Relations And Strategy
Pia Eaves: Hello everyone and thank you for joining us on today's conference call to discuss ARCUS's third quarter 2023 financial results and pipeline updates, including today's presentation of data from our EDGE Gastric trial at the ASCO monthly plenary. Today you will hear from Terry Rosen, Chief Executive Officer, Dimitry Nuyten, Chief Medical Officer, Jennifer Jarrett, Chief Operating Officer, and Bob Goeltz, Chief Financial Officer. For Q&A, we will also be joined by Juan Jaen, President and Head of Research. I'd like to remind you that on this call, management will be making forward-looking statements, including statements about our cash runway, our investigational products, our expected clinical development milestones and timelines, and the potential market opportunity and drug-treatable population of any indications being pursued by our program.
All statements, other than historical facts, involve risks and uncertainties that may cause our actual results to differ. Those risks and uncertainties are described in our most recent quarterly report on Form 10-Q that has been filed with the SEC. We strongly encourage you to review the filing. For today's call, please refer to our latest corporate deck, which can be found on the investor section of our website. With that, I'll turn the call over to Terry.
Terry Rosen: Thank you very much, Pia, and thank you all for those who are on the line. This is the first quarterly earnings call we've had in some time. So in addition to the Domvanalimab data that was just presented at Ascol Plenary, we're also going to discuss our other upcoming data readouts, specifically for AB521, our potentially best-in-class HIF-2a inhibitor, and Quemliclustat, our first-in-class small molecule CD73 inhibitor, both of which we'll be sharing data with you just in the next few months. So just a few hours ago, many of you likely watched Dr. Juan Jaen, present initial data from our Phase 2 study, Edge Gastric, for Domvanalimab and first-line metastatic upper GI adenocarcinomas. As a reminder, Dom is the only Fc-silent anti-TIGIT antibody in late-stage development, and we and our partner, Gilead, are pursuing a very broad development program that includes four Phase 3 studies in non-small cell lung and upper GI cancers.
Today's data are extremely encouraging on all fronts. ORR for the PD-L1 high population clearly exceeded historical benchmarks in this setting. Data in the overall patient population appears differentiated, particularly relative to the most contemporary Phase 3 studies in this patient population, or its keynote 859 in day genes rationale 305. Most importantly, six-month landmark PFS data for both the PD-L1 high and overall patient population appear to be quite differentiated from the benchmarks. These data are very supportive of our ongoing Phase 3 study, STAR-221, which is evaluating Dom in the same combination, same setting underlying today's dataset. STAR-221 is enrolling extraordinarily well, and we expect that today's data will further enhance interest and actually accelerate recruitment in this study.
In addition to Dom, we continue to execute on the remainder of our pipeline, including our HIF-2-alpha and adenosine pathway programs. Regarding our HIF-2-alpha inhibitor, AB521, early next year we will be sharing detailed safety, pharmacokinetic, pharmacodynamic, and preliminary efficacy data from the dose escalation portion of ARC20, which is a Phase 1, 1B trial for AB521. We're close to completing enrollment, in fact, of the dose expansion cohort that's evaluating 100 milligrams daily of AB521, a dose that we believe will hit the target substantially harder than the approved 120 milligram dose of Merck's Belzutepan. Merck's most recent datasets for Belzutepan presented at ESMO continue to enhance our conviction around the opportunity for AB521.
Those data were just what we've been expecting for months, if not the past year. Later in this call, we'll describe this program in much more detail. With respect to our adenosine programs, we'll discuss our ARC8 trial evaluating our CD73 inhibitor, Quemli. This is in combination with gemcitabine and nab-paclitaxel, with or without our anti-PD-1 Zimberelimab, in first-line pancreatic cancer. As you may recall, ARC8 completed enrollment way back in November of 2021. So the median follow-up, the most recent data cutoff, exceeded 21 months. And we just now achieved a sufficient number of events for mature median OES estimate. These data show clear differentiation from contemporary benchmarks for gemobraxain in this setting, one with huge medical need.
Furthermore, we've generated a rigorous synthetic-controlled dataset for gemobraxain, which also shows very meaningful differentiation from our combination therapy. We also continue to work tirelessly to advance new molecules into the clinic. We just initiated our Phase I study for AB801, our highly selective axon inhibitor, and we expect to select a development candidate with potential best-in-class properties for our KITT program for allergic diseases by year end. So I'll now turn the call over to Dimitri to describe in more detail the EDGE-Gastric data that were presented earlier today.
Dimitry Nuyten: Thank you, Terry. I'll start by directing our audience to slide nine of our updated corporate deck. The data presented today are from cohort A1 from our Phase II EDGE-Gastric platform study, which is evaluating DOM-based combinations in both the first- and second-line setting. The A1 cohort is evaluating dom +/- zim +/- mFOLFOX chemotherapy in 1L Gastric, Gastroesophageal Junction (GEJ) and Esophageal Adenocarcinoma (EAC). As Terry mentioned earlier, this is the same setting and setting we are evaluating in our Phase III study, STAR-221. This cohort was specifically designed to generate safety and efficacy data to support regulatory requirements for the initiation of STAR-221 in certain countries outside of the U.S. Turning to slide 11, we described the baseline characteristics of this cohort.
Forty-one patients were enrolled, and all patients are included in the efficacy analysis. The cohort enrolled a relatively diverse patient population from 20 different sites in the U.S., France, and South Korea. There was an even distribution of patients included in Asia versus the rest of the world, and 63 percent of patients had gastric cancer, 24 had junction tumors, and 12 percent Esophageal Adenocarcinoma. PD-L1 status was evaluated using the TAP scoring method, with 24 patients having TAP less than five, and 15 patients, or 37 percent, with a TAP greater than or equal to five. Two of the 41 patients included in the overall population did not have tumor samples available for PD-L1 testing. Note that the CPS and TAP are two methods for PD-L1 assessment, and both are used in gastric cancer.
We'll show you later on this call some of these methods, sorry, that these methods have a high concordance. BMS and Merck have historically used CPS for their phase 3 studies of anti-PD-L1 plus chemotherapy, while Beijing is using TAP, including in the phase 3 gastric cancer trial, rationale 305. The following slide describes the overall response rates of the data cutoff of September 4, 2023. In the TAP high population, we observed a 73 percent confirmed overall response rate and an 80 percent best overall response rate. These results exceed historical phase 3 benchmarks for anti-PD-L1 and chemotherapy. For example, in JETMATE 649 and Keynote 859, the overall response rate was 60% or 61% for anti-PD-L1 plus chemotherapy in the CPS high arms of the study, and in rationale 305, Beijing's study in gastric cancer, which is the most contemporary phase 3 data set in this setting, there's a 50 percent overall response rate in the TAP high population.
For the overall population in EDGE-Gastric, the confirmed overall response rate was 59 percent, which is very encouraging, particular given that approximately 60 percent of our patients are TAP low, which is higher than the 40 percent PD-L1 low patients in JETMATE 649. The overall response rate in Merck's Keynote 859 trial was 51 percent. I'd also note that we have seen two confirmed complete responses so far. The median duration of response has not been reached, and given the time it takes to get to a complete response and the fact that many of our patients are still on treatment, the CR rate might go up over time. We believe that the overall response rate results seen in EDGE-Gastric demonstrate the additive benefit that an anti-digit agent can provide above and beyond PD-1 chemotherapy PD-1, excuse me, and chemotherapy in upper GI cancers.
On slide 13, we show the waterfall plot, and as you can see, the vast majority of patients experiences tumor volume reduction. While there is a difference in the overall response rates between the TAP high and low tumors, you can see in the chart that we have observed very deep responses in both patients with high and low expression. You can also see that in addition to the two complete responders, there are other patients with very significant tumor volume reductions that could convert to CRs over time. The next slide shows the time on treatment by patient. You can see here that there are six patients, both with PD-L1 high and low status, who continue to have stable disease and remain on treatment. On slide 15, we show the overall response rate table again, but here we show the data using both the TAP and the CPS method, and as you can see, there is strong concordance between these two methods.
The next slide, slide 16, shows the ketamine myocardial for progression-free survival. Here we call out the lab-marked six-month PFS, which is mature in our trial with a minimum follow-up of six months for all patients. These data are extremely promising for both the high and the low patient population. Specifically, we observe a 77% in the overall population and a very impressive 93% in the TAP high population for six-month lab-marked PFS. While we recognize that these are small numbers, these six-month PFS numbers compare very favorable to the benchmark phase three studies, which have been in the 50% to 60% range. You can see here in the curves that we have not reached the medium PFS for either the TAP high or overall population with a medium follow-up of 8.1 months.
Given that the historical benchmarks have shown a PFS in the range of seven to seven and a half months, we believe these data put us on track to exceed those benchmarks. And importantly, a substantial number, specifically 24 out of 41 patients enrolled in our study, continue to be on treatment at time of the data cutoff. Lastly, I will cover the safety and tolerability profile we've seen so far in edge gastric. The most common treatment emergent adverse events, which are shown on slide 17, are neutropenia, nausea, and anemia, which is very consistent with what we would expect from chemotherapy alone. In fact, the vast majority of grade three or higher drug-related treatment emergent adverse events were contributed to chemotherapy, and only 12% were contributed to dom or zim.
No serious treatment emergent adverse events were related to dom or zim. Of note, all infusion-related reactions shown on slide 18 were deemed related to oxaliplatin. Overall, the regimen was well tolerated with a similar AE profile to that expected from Folfax plus anti-PD-1. These results add to the growing body of evidence supporting a potentially differentiated safety and tolerability profile for DOM relative to FC-enabled anti-TIGID antibodies. Before I turn it over to Jen, I wanted to spend a minute on some key elements of the design of our phase three study, STAR-221, which is shown on slide number 20. First, we are stratifying by TEP greater than 5% or less than 5%, so this is well-balanced between the two treatment arms. We are also closely monitoring the percentage of patients who have tumors with a TEP score of more than 5% to ensure that the percentage of these patients in our study meets the pre-specified percentage per our statistical analysis plan.
Second, the study has dual primary endpoints of overall survival, one for the TEP more than 5% and the other one for the ITT population, so we have two opportunities to win in this study. With that, I'll turn it over to Jen to talk about the market opportunity for TIGID.
Jennifer Jarrett: Thanks, Dimitry. I'd like to start by talking about the TIGID field overall. Our most recent feedback from KOLs indicates a clear and growing data-driven enthusiasm for anti-TIGID as an innovative therapy. Following the release of data from the second interim analysis of Roche SKYSCRAPER-01, we engaged a third party to conduct a survey of 730 oncology KOLs regarding their sentiment on anti-TIGID. You can see these results on slide 35 of our investor deck. Approximately 80% of respondents believe it is likely that Turago plus Atezo, Roche's anti-TIGID and PD-L1 combination will receive FDA approval. Additionally, based on data they've seen to date, 83% expect anti-TIGID to play a moderate or larger role in the treatment of first-line PD-L1 high non-small cell lung cancer.
These survey results are telling. As the evidence on anti-TIGID accumulates, physicians are increasingly convinced of the potential for this mechanism to change the treatment paradigm in lung cancer. Since we are combining DOM with the current standard of care, FEMO plus anti-PD-L1 and adding almost no toxicity, this is a very easy value proposition for physicians. Today's results continue to demonstrate the potential for anti-TIGID to improve outcomes and indications where anti-PD-L1 is successful. As Terry mentioned, gastric GE junction and esophageal adenocarcinomas represent a $3 billion plus market opportunity with approximately 25,000 patients in the U.S. alone and over 100,000 patients across the G7 countries. Note that we are pursuing adenocarcinomas, a different histology than that which is being pursued by Rosh and Beijing in their respective phase 3 and 2 studies.
In fact, we in Gilead have the only anti-TIGID in phase 3 development for first-line upper GI adenocarcinomas, which is one of the fastest-growing cancer types in the U.S. and Western Europe. Many of you are aware that there is another class of agents being developed in gastric cancer directed against CLADIN 18.2s, which were also discussed in today's plenary session. While the efficacy data are encouraging, published literature estimates that only anywhere from 20 percent to 40 percent of patients are high expressors of CLADIN 18.2, and these molecules are associated with significant GI toxicities. We also expect it will take several years for CLADIN 18.2 testing to be successfully rolled out. With anti-TIGID, we believe we have the potential to achieve similar efficacy without the toxicity associated with the anti-CLADINs and potentially avoid the need for any testing, allowing patients to go directly to treatment.
Today's data set will support both study recruitment and regulatory filings for a combination, and we are moving aggressively to secure our position as first-to-market and best-in-class in this indication. I'll now turn it back to Terry to discuss our HIF-2-alpha and CD73 programs.
Terry Rosen: Thanks very much, Jen. So, first let me start by level-setting a bit on HIF-2-alpha. It's a transcription factor, has no ligand-binding domain, and as a result, it's proven very difficult to create molecules that are high-quality inhibitors but also that have ideal drug properties against the target. That's why there are very few other HIF-2-alpha blockers in clinical development today. Belzutepin is the first and only HIF-2-alpha inhibitor to be approved to date, and it's only approved for BHL-associated cancers, although Merck recently filed for Belzutepin's first approval in Clear Cell RCC. Slide 47 of our corporate deck describes the value proposition for AB521. It's really pretty simple. The primary limitation of Belzutepin is substantial.
Its oral absorption saturates at a dose of 120 milligrams. So what does that mean? Even when higher doses of Belzutepin are administered, systemic drug exposure does not meaningfully increase. In fact, it's very clear from the published data for Belzutepin that the approved dose of 120 milligrams was chosen because doses beyond 120 milligrams did not result in meaningfully higher plasma levels. This had nothing to do with dose-limiting toxicity. Merck, in fact, just released results for LightSpark 13 at ESMO, which evaluated doses of 120 milligram versus 200 milligrams of Belzutepin. No surprises. They concluded that there was no difference in ORR between these two doses and that the results support their dose selection of 120 milligrams for their trials.
However, it's super important to note that they made no mention of whether they were achieving higher levels of drug exposure with the 200 milligram dose, and they did not share any PK or PD data for this study. So consistent with the previous literature, we just view this as more evidence of Belzutepin's PK and PD limitations and the inability, in fact, to achieve meaningfully greater plasma concentrations with doses that are above 120 milligrams, our fundamental thesis going into this program. The primary objective of our HIF-2 alpha program, then, was to create a molecule without this pharmacokinetic liability, enabling us to hit the target harder. In a Phase 1b study in second-line clear cell RCC, Belzutepin demonstrated an ORR of about 25 percent, and approximately half of these responses were not achieved until six months or more of treatment.
These ORR data were essentially recapitulated in the Phase 3 LightSpark 05 study, which showed a 22 percent ORR for Belzutepin versus 3.5 percent for Everolimus in a 5.6-month medium PFS. While these results are actually quite encouraging, we believe they show clearly room for improvement. And with AB521, we could observe a higher response rate, deeper responses, or faster response kinetics, all of which should translate into longer PFS. In our healthy volunteer study, we demonstrated that AB521 has an ideal profile, including dose-proportional pharmacokinetics. That's important. Dose-proportional pharmacokinetics is the huge differentiator here. In our dose escalation study in patients, we replicated the pharmacokinetics that we observed in healthy volunteers and now have dosed up to a daily dose of 100 milligrams, which we believe has the potential to achieve at least three times higher levels of AB521 than those equivalent to the approved dose of Belzutepin.
Importantly, and this is a key finding, we have not seen any dose-limiting toxicities. So based on these data, we've initiated our 30-patient expansion cohort at a dose of 100 milligrams daily in clear cell RCC patients. There's been a great deal of investigator enthusiasm around the study. In fact, the cohort is almost fully enrolled. Early next year, we're very excited to have the opportunity to present PK pharmacodynamic safety data as well as the initial efficacy data from the 12 patients in the dose escalation portion of the study. Approximately half of these patients have RCC, and all were treated at a dose of 50 milligrams or 100 milligrams daily, so both of these doses are pharmacologically relevant. The safety data support our view that the enhanced target coverage by AB521 relative to that obtained by Belzutepin does not result in an increased safety liability.
We also expect to present data from the expansion cohort next year. We're progressing the molecule rapidly and expect to start a Phase II TKI combination study in second-line clear cell RCC by year end with the goal of getting a Phase III study for AB521 as quickly as possible. So now let me shift over to ARC-8. Really excited to talk about this study, our Phase I, I-B study that's evaluating QEMLI in first-line metastatic pancreatic cancer. QEMLI is a highly selective and extraordinarily potent small molecule inhibitor of CD73. A key differentiator of QEMLI compared to the most advanced CD73 antibody in clinical development is that it blocks both the membrane-bound and the soluble forms of CD73, enabling it to achieve complete inhibition of the enzymatic activity.
This is a huge difference because CD73 is readily shed from cells, resulting in significant levels of soluble CD73. So in contrast, the most advanced CD73 antibody is only partially effective in inhibiting the enzymatic activity of either membrane-bound or soluble CD73. So I think an important concept here is that although they share the same target, CD73, QEMLI is highly differentiated by its mechanism of action, which, as I said, enables it to fully inhibit both forms of the enzyme. We also believe that a small molecule may penetrate tumors better than an antibody. Pancreatic tumors are notorious for being very fibrotic. What does fibrotic mean? Think of it like scar-like tissue. This makes it hard for drugs to infiltrate the tumor, and therefore, a small molecule approach may be particularly advantageous in this setting.
We chose pancreatic cancer as the first indication for QEMLI because this tumor type is associated with extremely high CD73 levels, and in fact, high CD73 expression has been shown to result in poor overall survival outcomes in patients. Slide 42 highlights the design of our case. We enrolled approximately 30 patients evaluating 100 milligrams of QEMLI plus Zim + Gemma Braxane in the dose escalation and expansion portions of the study. Subsequently, we enrolled the randomized portion of the study, and this highlights the design of our case. We enrolled approximately 30 patients evaluating 100 milligrams of QEMLI plus Zim + Gemzar Abraxane in the dose escalation and expansion portions of the study. Subsequently, we enrolled the randomized portion of the study, and this evaluated QEMLI plus Subsequently, we enrolled the randomized portion of the study, and this evaluated QEMLI plus Gemma Braxane in the dose escalation and expansion portions of the study.
Subsequently, we enrolled the randomized portion of the study, and this evaluated QEMLI plus Subsequently, we enrolled the randomized portion of the study and this evaluated QEMLI plus Gemzar Abraxane with and without Zimbarellamab in 90 patients with the goal of determining whether anti-PD1 therapy provides any clinical benefit on top of what we're seeing from QEMLI in this setting. We've already disclosed that Zimbarellamab did not add any benefit to QEMLI plus Gemzar Abraxane in this study. We completed enrollment of this randomized portion in November of 2021. At the most recent data cutout, median follow-up was 21 months. The data set we will share early next year will therefore include mature overall survival data for all 122 patients enrolled in the study.
This is a substantial data set. They're all at the 100 milligram dose of QEMLI. There have been several recent data sets, good data sets that provide benchmarks for how Gemzar Abraxane performs in this setting. And overall survival for these contemporary data sets falls in the nine to 11 month range. The data are really pretty tight. The NAPLE3 study, which was just presented at ASCO this year demonstrated 9.2 months overall survival for the Gemzar Abraxane arm. [ph] Fofuranox is also used in this setting, but it's often reserved for healthier patients given its toxicity profile. [ph] Fofuranox demonstrated a median overall survival around 11 months in the NAPLE3 study. We plan to share the full data set from ARC-8 early next year. The disclosure will be comprehensive.
It's going to include ORR, PFS and OS, landmark 12 and landmark 18 month OS. We also plan, and this is an important update, we plan to share data from an externally generated synthetic control arm of Gemzar Abraxane which we believe will further validate the clear benefit that was observed with QEMLI. We'll also spend more time on the mechanism for QEMLI in pancreatic cancer and why we might be seeing such a meaningful benefit in overall survival. Briefly, we believe that there are two mechanisms at play, both of which are very well supported by extensive literature on the role of CD73 in pancreatic cancer. First, by inhibiting adenosine formation in response to chemotherapy and essentially blowing up cancer cells. We may be enhancing a T cell response in the tumor.
And second, by interfering with the effects of adenosine on well-known fibroblast biology and tumor fibrosis. We're really very excited about the data and we believe these results support further development of QEMLI for patients with this devastating cancer. There's really been no advances in this field for the better part of a decade. As you know, pancreatic cancer is a disease with extremely high unmet need. It affects 37,000 patients in the United States alone and we believe the global market opportunity could easily exceed $3 billion. I'd like to turn it over to Bob now to review our financials from the quarter.
Robert Goeltz: Thanks, Terry. Arcus continues to be in a very strong financial position. Our cash at the end of September 30, 2023 was $950 million and our net cash utilization through three quarters of 2023 has been $188 million. Importantly, we share cost 50-50 with our partner Gilead on a large portion of our portfolio, including all of our ongoing phase three studies. We now expect cash utilization for full year 2023 to be between 2$65 million and $290 million, down from our prior guidance of $295 million to $325 million. And we continue to expect our cash balance to fund operations into 2026. Our cash runway guidance excludes potential opt-in payments and approval milestones from our partners. Turning to our P&L, we recognize gap revenue for this quarter of $32 million, which compares to $29 million for the second quarter of this year.
Our revenue is primarily driven by our collaboration with Gilead and we expect to maintain similar levels of revenue in the near term with small fluctuations due to updates to our clinical development plans and timelines. In addition to our partnership with Gilead, Taiho is our partner for DOM in Japan. In the fourth quarter, we received a milestone payment of $14 million from Taiho related to their participation in our STAR 221 pivotal study, and will receive another $14 million in the first quarter of 2024. We are also eligible for additional milestone payments from Taiho related to STAR 121. Our R&D expenses for the third quarter are stated net of reimbursements from Gilead and were $82 million as compared to $84 million in the second quarter of this year.
In the current quarter, non-cash stock-based compensation represented $8 million of our R&D expenses. We expect modest increases in our R&D expenses as our phase three studies mature. However, spend may fluctuate based on the timing of clinical manufacturing activities and the purchase of standard of care therapeutics for our clinical trials. For example, in the third quarter, spend in these areas was lower than in the preceding quarters of this year. G&A expenses were $30 million for the third quarter of 2023 compared to $28 million in the second quarter of this year. Non-cash stock compensation represented $10 million of our G&A expenses for this quarter, and we expect G&A to remain stable over the remainder of 2023 and through 2024. For more details regarding our financial results, please refer to our earnings press release from earlier today and our 10Q.
I'll now turn the call back over to Terry for some closing remarks.
Terry Rosen: Thanks very much, Bob. So to wrap up, first off, we're really excited about today's data set. It provides evidence that supports DOM as potential best-in-class anti-TGIT and first-line upper GI adenocarcinomas, a setting we're well on track to be first to market, and first to market by a distance with an anti-TGIT antibody. I think it's also important that if you elevate a bit, it really continues to support DOM-ZIM as a best-of-class anti-TGIT, anti-PD-1 doublet, the combined holistic profile of efficacy and safety profile. As we execute on our four phase three trials for DOM, we continue to advance the remainder of our pipeline, and we're really looking forward to sharing more data in the very near term on QMLE and pancreatic cancer in our HIF-2-alpha program.
Both of these programs have been ongoing for some time. I think we're going to have some data that you can really look at as inflections for both. So with that, I'd like to thank you for your continued support as we work to develop, we believe, very innovative combination cancer therapies for patients that are in need. With that, I'll open up the floor for questions.
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