Arcus Biosciences, Inc.

Good afternoon. Thank you for attending today's Arcus Biosciences third quarter 2024 earnings call. My name is Tamia and I will be your moderator for today's call. All lines will be muted during the presentation portion of the call with an opportunity for questions and answers at the end. If you would like to ask a question, please press star one on your telephone keypad. I would now like to pass the conference over to your host, Tia Eves, Vice President of Investor Relations. You may proceed.

Hello everyone, and thank you for joining us on today's conference call to discuss our third quarter, 2024 financial results and pipeline updates, including our upcoming presentation of our 10 data at 50. I'd like to remind you that on this call management will make forward looking statements, including statements about our cash runway and our expected clinical development milestones and timelines all statements other than historical facts. reflect the current beliefs and expectations of management, and involve risks and uncertainties that may cause our actual results to differ from those expressed. Those risks and uncertainties are described in our most recent quarterly report on Form 10-Q that has been filed with the SEC. Today, you'll hear from our CEO, Terry Rosen, CMO, Dimitri Naughton, COO, Jennifer Jarrett, and CFO, Bob Galtz. We'll also be joined by our President, Juan Jaen, for questions after the prepared remarks. With that, I'll turn the call over to Terry.

Thank you very much, Pia, and thank you all for joining us today. As we head into 2025, our highest priority is to launch our late-stage development program for our HIF-2-alpha inhibitor, Cas-Statafan. As you know, just two weeks ago, we presented initial data from our ARC-20 study, evaluating Cas in late-line clear cell RCC in an oral plenary session at the ENA meeting. These data clearly validate our conviction that Cas will be a best-in-class HIF-2-alpha inhibitor, demonstrating improvement in every key efficacy measure that we analyzed versus Belzudifan. As you know, Belzudifan is the only HIF-2-alpha inhibitor on the market today. So let's go to slide five, and I'll recap the highlights from our data set. First off, the rate of primary progression in the 100-milligram daily expansion cohort was only 19%. and it was similarly low in the 50 milligram daily expansion cohort. In fact, the rate of primary progression for the combined 60 patients in the 50 milligram and 100 milligram expansion cohorts was approximately half of what was observed in LightSpark 005. Keep in mind that the primary progression rate and disease control rate, DCR, are the only data points that are fully mature and will not change. So this is really a huge difference for the molecule. Second, we reported a 34% ORR and 25% confirmed ORR for the 100 milligram cohort with two of the three unconfirmed responses pending confirmation and also multiple stable disease patients still on therapy. As of the data cutoff, every responder across both cohorts remained on treatment with the exception of that one patient whose response did not confirm. The Belzunifam data actually provide good precedent for the kinetics of response with HIF-2-alpha inhibition. So this is important. Approximately 60% of responses occurred within six months of treatment, and an additional 20% occurred in each of the ensuing six-month periods. So that goes out to 18 months. These data illustrate why our ORR could, in reality, more likely should further improve across both cohorts. Keep in mind, those follow-up times are eight months and 11 months, respectively, for 50 and 100 milligrams. The ARC-20 data also demonstrated that the activity of CAS is extremely durable. As of the data cutoff, a median PFS had not been reached, even with that 11 months median follow-up. Recall that Belzutifan was approved based upon its PFS of 5.6 months, and our median PFS, which we expect to report in early 2025, should easily exceed that benchmark. Given that PFS is the registrational endpoint, this will be another important source of differentiation. Our SPDR plots show multiple patients either past or approaching the 52-week duration of treatment, and you also see deepening of responses with time. I want to emphasize these data were generated in a heavily pre-treated patient population relative to that of LightSpark 005. Specifically, approximately 25% of the patients enrolled in ARC20 wouldn't have been eligible for LightSpark 005. For the 50 milligram cohort, despite only eight months median follow-up at the data cutoff, we reported a 14% primary progression rate, a 25% ORR, and just over 21% confirmed ORR, with the one unconfirmed responder pending confirmation, and a very impressive, almost remarkable, DCR of 86%. One of the confirmed responders was a complete response. Beyond the responders, and again, another important point, nearly 40% of patients still continued on therapy with stable disease, including a few whom are extremely close already to the 30 percent response threshold, and you can see that in the spider plots. While this data set is still evolving and will continue to improve, we now have two different cohorts that are demonstrating clear efficacy differentiation relative to that of Belzudefin, and there's a lot more data to come. On slide six, we show the data that we expect to share from ARC-20 throughout 2025. plan to present additional data from the 100-milligram and 50-milligram cohorts of ARC-20, including more mature ORR and medium PFS. That will be early next year. Later in the year, we plan to present initial data from the 150-milligram and the 100-milligram once-daily tablet expansion cohorts, so that's another 60 patients' worth of data. We also plan to present initial safety data from our CAS plus CABO expansion cohorts. To date, the safety data from this cohort, which we already shared with the FDA as part of our pre-phase three meeting, are consistent with the profiles of the individual drugs, and the dose intensity of 100 milligrams of Cas and 60 milligrams of Cabo has been maintained. Given the importance of the ARC-20 data, and that's important to us, it's important to you, it's important to investigators, the ongoing evolution of the data set in the multiple cohorts that we've enrolled, we're considering additional opportunities to provide updates from this study in the more near term. We remain full steam ahead towards the initiation of our first phase two study, peak one. The investigator enthusiasm for this study is incredibly high, which we believe will support rapid enrollment. Now let me switch gears to donvonilamab, our FC silent antitigin antibody. Just yesterday, the CIDC abstract was released with data from part one of our ARB10 study, which evaluated Domplizimvirelumab, that's our anti-PD-1 antibody, versus Zim versus chemotherapy in first-line PD-L1 high non-small cell lung cancer. As a reminder, we terminated the study for strategic reasons to focus on STAR-121, our chemo combination study. But the early termination gave us both an opportunity to generate and now present a data set from a study that was conducted under Phase III conditions. On slide 27, we summarize the abstract. We show that Dom plus Zim exceeded Zim monotherapy on ORR, PFS, and OS. For both PFS and OS, we achieved a hazard ratio below 0.65, which is far better than the threshold considered clinically meaningful in the setting. With median PFS of 11.5 months, In median OS not reached for DOMZIM, these results are meaningfully above contemporary benchmark studies for anti-PD-1 monotherapy. Dimitri is going to discuss these data in detail, but I want to make two important points. First off, these data reaffirm the growing recognition that FC-sounding antitiget antibodies have a differentiated safety profile relative to that of FC-enabled antibodies. There are only two FC-silent TIGIT antibodies in late-stage clinical development today, DOM and AstraZeneca's anti-PD-1, anti-TIGIT bispecific antibody. In the last few months, AstraZeneca presented two datasets for their antibody in first-line non-small cell lung cancer and first-line gastric cancer. Interestingly, both datasets look very similar to our own. specifically similar efficacy as well as AE rates that are in line with anti-PD-1 therapy alone. That's an important component of the profile. In contrast, for the FC-enabled antitigin antibodies, we continue to see reports of higher rates of immune-related adverse events and treatment-related discontinuations. Combining the FC-enabled antibodies with chemotherapy absolutely seems to exacerbate these issues. The second point that I want to make is that with this ARC-10 data set, which will be presented in more detail at CITSE, the ARC-7 results in PD-L1 high non-small cell lung cancer that we shared last year, and the EDGE gastric data that we presented earlier in this year at ASCO, we now have three compelling data sets supporting the potential of DOMZEN in both lung and gastric cancers. For our EDGE gastric study, we showed a median PFS 13 months for DomZen and first-line gastric cancer, which meaningfully surpassed the PFS of seven to eight months seen in benchmark studies. And in the first half of next year, we expect to present mature overall survival from the study. Meanwhile, we continue to execute on our three phase three trials for DomZen. In first-line gastric cancer, with our STAR-221 study, we have the potential to be first to market with an antigen antibody in this setting. With this study fully enrolled, we're actively preparing for readout and potential submission to health authorities. We believe this setting alone is a $3 billion plus opportunity. In lung cancer, with our STAR-121 and PacificAID studies, the latter in partnership with AstraZeneca, we have a potentially differentiated antitigic combination in the two settings we're pursuing, first line and stage 3 non-small cell lung cancer. We continue to evaluate our statistical analysis plans for all our DomZim studies to ensure that they're optimized for probability of success, but also while addressing the largest number of patients. We also continue to advance the other programs in our pipeline. We've initiated PRISM-1, our phase three study, evaluating QEMLI plus chemo, that's QEMLI as our CD73 inhibitor, and first-line metastatic pancreatic cancer. And with tie-hose opt-in to this program, They're executing the study in Japan. We believe this could be a transformative first-line therapy in a disease you're aware with dismal outcomes for patients. Early next year, we expect to advance AB801, a highly selective axon inhibitor, into expansion cohorts in non-small cell lung cancer. Our relationships with Gilead, AstraZeneca, and Taiho are strong, and they've enabled us to aggressively advance all of our programs in a highly resource-efficient manner. With $1.1 billion in cash and investments and runway into mid-2027, we're comfortably funded through multiple clinical readouts. Before we go to the ARC-10 results, I'd like to turn it over to Jen to discuss our development plans and the market opportunity for CAS.