Arcus Biosciences, Inc.

Hello all and welcome to Arcus Biosciences first quarter 2024 earnings form. My name is Lydia and I'll be your operator today. If you'd like to ask a question during the Q&A, you can do so by pressing star followed by one on your telephone keypad. I'll now hand you over to Pia Eaves, Vice President of Investor Relations and Strategy.

Hello, everyone, and thank you for joining us on today's conference call to discuss ARCIS' first quarter 2024 financial results and pipeline updates. I'd like to remind you that on this call, management will make forward-looking statements, including statements about our cash runway and our expected clinical development milestones and 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 annual report on Form 10-K and quarterly report on Form 10-Q, which have been filed with the SEC. We strongly encourage you to review our filings. Today, you'll hear from our CEO, Terry Rosen, COO, Jennifer Jarrett, and CFO, Bob Gels. We'll also be joined first by our CMO, Dimitri Naughton, and President, Juan Jaen, for questions after the prepared remarks. For ease of listening, we will be referring to abbreviations of our molecule names, Dom Vanalamab as Dom, Zimbirellamab as Zim, Casdatifan as Cas, Quimliclustat as Quimli, and Etrumatident as Etruma. 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 turn the call over to our CEO, Terry Rosen.

Thanks very much, Pia, and thanks to all of you on the call for listening in today. As you know, 2024 is shaping up to be an incredibly catalyst-rich year for ARCIS. By the end of this year, we'll have data that support all four of our later stage clinical programs, DOMSIM in lung and upper GI cancers, CAS in clear cell RCC, Pemlin pancreatic cancer, and Etruma in colorectal cancer. We'll spend most of the call today setting the stage for these upcoming data events. With over $1 billion of cash on hand, runway into 2027, partnerships with Gilead, AstraZeneca, Taiho, others, along with a very diversified pipeline, we're extremely well positioned to capitalize on these data sets and advance our potential first and also best of class treatments towards approval and commercialization quickly and efficiently. Let me start with ASCO. ASCO is less than a month away, so we're almost there. We're thrilled and honored to have two oral presentations, both of which will provide strong support for our efforts and programs in the GI cancer field. Importantly, both data sets are in settings where there's limited competition and huge unmet need. These are genuine opportunities to make a meaningful difference for patients. So first off, on Saturday, June 1st, we'll have updated data from cohort A1 the Phase II EDGE gastric study, evaluating DOM plus ZIM plus chemo in first-line gastric cancer. As you're aware, DOM is the only FC silent antitiget antibody in late-stage clinical development, and we believe that the data presented to date indicate that DOM may potentially have an improved safety profile when combined with chemotherapy relative to that of the FC-enabled antitiget antibodies when they're combined with chemotherapy. As a reminder, we presented initial data from this cohort of edge gastric at the ESCO virtual plenary session in November of last year. At the time, median PFS was immature. However, we did present mature landmark six-month PFS numbers, which you can see on slide 16 of our corporate deck. What you can see is that six-month landmark PFS was 77% for the overall population, and 93% for the PD-L1 high population. So given that the median PFS for standard care in the setting ranges from seven to eight months, these data were obviously very, very encouraging. At ASCO, we're very excited to be presenting mature median PFS data. We expect the updated data will further support the potential for DomZim to provide clinically meaningful benefit relative to the standard of care in gastric cancer. Importantly, edge gastric evaluated the same setting and similar patient population as our ongoing phase three study, STAR-221. So therefore, we expect these data to foreshadow our confidence in our STAR-221 study. In that context, enrollment in STAR-221 is expected to complete by mid-year. The incredibly rapid enrollment of the study is indicative of the lack of competition in gastric cancer market and the immense need for new therapeutic options, particularly with overall survival in this patient population, ranging from only 13 to 14 months in studies with anti-PD-1 antibodies and chemotherapy. We also felt that we actually achieved some tailwinds with our data presentation at the end of last year. So putting this all together, you can infer that there's a line of sight to data and that DomZim will have a very substantial head start over potential competitors, given there are no other anti-tigit antibodies in phase three development for the setting. So we think we're gonna have a clear first to market advantage. This creates an exciting opportunity for us to be first in the setting with an addressable patient population of over 25,000 patients in the U.S. alone and 100,000 patients in the G7 countries. So this equates the potential worldwide market of over $3 billion. Now moving on to our second presentation at ASCO. On Sunday, June 2nd, we'll be presenting data from our ARC9 study in third-line colorectal cancer. This will be the first presentation on this study. The data will be from cohort B, which is evaluating the truma in combination with Zim, Folfax, and Bev, versus Regorafenib, one of the standard of care treatments for third-line colorectal cancer. On slide 41 of our corporate deck, you can see the study design and the conclusion criteria for this portion of the study. Patients in this cohort must have received Bev, unless contraindicated, a prior axalioplatin-based regimen, and an arenotecan-based regimen. These are the current standard of care therapies for first and second line CRC. One hundred and five patients were enrolled who were randomized two to one between the Atreuma arm and the Regorafenib arm. So this is a relatively large data set. ARC9 also included two additional randomized cohorts which evaluated Atreuma plus Vim plus Folfax and Bev versus Folfax and Bev in second line colorectal cancer. These data are not yet mature and will be presented at a later time. Second line setting, as you know, has a substantially longer OS. The ASCO presentation will include mature PFS and OS data with a median follow-up of over 20 months. And our data will include patients with and without liver mets. This is important since patients with liver mets tend to have a poor diagnosis and they're not always included in late-line CRC trials. As many of you know, there are very limited options in third-line plus colorectal cancer. Patients are typically treated with regorafenib, and more recently with a combination of Lansurf and Bev, based on the Sunlight Study, which showed a PFS of 5.6 months and OS of 10.8 months in third-line patient population. While acknowledging the limitation of cross-trial comparisons, but we all do it, based on our data, will be shared with you next month. The true combination regimen may represent a very substantial improvement over current options for patients in the third-line setting. I also want to point out a small data set of 35 patients that was just presented in a poster at AACR, which actually captured quite a bit of interest and further supports our hypothesis that adenosine blockade enhances the immune-activating benefits of chemotherapy. These data were from the Morpheus PDAC study, a randomized phase 1B2 trial operationalized by Roche that evaluated our molecule, Etrema, plus Roche's anti-PD-L1 atezone chemotherapy versus chemotherapy alone in first-line metastatic pancreatic cancer. We've highlighted the design on slide 37. On slide 38, we've shown the spider plots for both the control arm and the Etrema-based regimen which showed durable responses. In this trial, the Atruma-containing arm demonstrated a meaningful improvement in both PFS and OS, and we've shown these data on slides 39 and 40 of the corporate stack. Specifically, the PFS hazard ratio was 0.48, and the OS hazard ratio was 0.67, with the Atruma-based regimen yielding an absolute improvement in median over survival 4.4 months over chemotherapy alone. The median OS for the Atrumic-containing arm was 16.5 months, very similar to what we saw in ARC-8. Before we leave Atruma, I want to highlight that now, with the ARC-9 data presentation, we'll have three datasets presented in a very short period of time for our two molecules that inhibit the ATP adenosine pathway, Quimley and Atruma. Between ARC8, which evaluated Quimley in combination with chemotherapy in first-line pancreatic cancer. Morpheus PDAC, very similar, which evaluated Etrumo with chemo in first-line pancreatic cancer. And now ARC9, we have three independent but similar data sets, which together provide compelling evidence demonstrating that mitigating the immunosuppressive action of adenosine combined with immunogenic chemotherapy may prolong survival relative to that associated with chemotherapy alone. For those of you who've been following us for a long time, keep in mind, this was the original hypothesis which drove us to the adenosine axis in the first place. So we're getting to the point where the data are matching the hypothesis. Importantly, two of these studies showed meaningful improvement in OS versus the standard of care control And all three showed substantial improvement above historical benchmarks when adenosine blockade was combined with immunogenic chemotherapy. Now that we've covered what we'll be sharing at ASCO, I'd like to turn it over to Jen to discuss expectations for our HIF-2 alpha inhibitor program later this year.