On February 25, 2025 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for patients with cancer, reported financial results for the fourth quarter and full year ended December 31, 2024, and provided a pipeline update on its clinical-stage investigational molecules across multiple common cancers (Press release, Arcus Biosciences, FEB 25, 2025, View Source [SID1234650516]).

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"Last week, we presented data from nearly 90 ccRCC patients demonstrating casdatifan’s potential best-in-class profile," said Terry Rosen, Ph.D., chief executive officer of Arcus. "Given the strong efficacy and preferable safety profile relative to standard-of-care VEGFR tyrosine kinase inhibitors, we believe casdatifan can play an important role in the treatment of every patient diagnosed with ccRCC. Arcus now has full developmental and commercial control of casdatifan, and we are pursuing a robust development plan in multiple ccRCC settings, which include our first Phase 3 trial, PEAK-1, expected to initiate next quarter, as well as our clinical collaboration with AstraZeneca. We are extremely well capitalized to execute on these plans, and we continue to evaluate and pursue opportunities to conserve capital and allocate greater resources to maximizing the potential of casdatifan."

Pipeline Highlights:

Casdatifan (HIF-2a inhibitor)
Casdatifan Updates:
•New clinical data from three monotherapy expansion cohorts in ARC-20 were presented in a rapid oral session at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (GU) Cancers Symposium in February. At the time of data cut-off (DCO, January 3, 2025), the efficacy-evaluable population included a total of 87 patients with ccRCC who had received at least two prior lines of therapy, including both an anti-PD-1 and a VEGFR tyrosine kinase inhibitor (TKI) therapy. These data support the potential for casdatifan to be a best-in-class HIF-2a inhibitor for the treatment of ccRCC:
◦Despite limited follow-up, two of the cohorts exceeded 30% confirmed ORR (inclusive of one partial response that confirmed after the DCO)

◦Rates of primary progressive disease (progression at or before their first disease assessment) ranged from 14% to 19%
◦Most patients (81-87%) experienced disease control with either a partial response or stable disease
◦Only two confirmed responders out of the 26 across all cohorts had discontinued due to progression, indicating the potential for a long duration of response
◦A 9.7-month median PFS was reached for the 50mg twice-daily casdatifan monotherapy cohort; median PFS was not yet reached for other cohorts
◦No unexpected safety signals were observed at the time of DCO, and casdatifan had an acceptable and manageable safety profile across all doses
Planned Data Readouts:
•Mid 2025: Safety and initial efficacy data for the ARC-20 cohort evaluating casdatifan plus cabozantinib in IO-experienced patients.
•Fall 2025: More mature data from the cohorts evaluating casdatifan monotherapy in patients who had progressed on both an anti-PD-1 and a TKI therapy.
•2026: More mature data from the casdatifan + cabozantinib cohort and initial data from the new ARC-20 cohorts evaluating casdatifan in the first-line (1L) and IO-experienced settings.

Upcoming Study and Cohort Initiations:
•Three new expansion cohorts within ARC-20 will be initiated in the first quarter of 2025:
◦Casdatifan plus zimberelimab in all-comer 1L ccRCC
◦Casdatifan monotherapy in favorable-risk 1L ccRCC
◦Casdatifan monotherapy in the IO-experienced setting for patients with ccRCC who have not received a VEGFR-TKI therapy
•The Phase 3 PEAK-1 study evaluating casdatifan in combination with cabozantinib versus cabozantinib in IO-experienced ccRCC is expected to initiate in the second quarter of 2025.
•A Phase 1b study, part of AstraZeneca’s eVOLVE portfolio of trials, evaluating casdatifan in combination with volrustomig, AstraZeneca’s investigational PD-1/CTLA-4 bispecific antibody, in IO-naive patients, is expected to initiate in 2025. AstraZeneca is operationalizing this study.

Domvanalimab (Fc-silent anti-TIGIT antibody) plus Zimberelimab (anti-PD-1 antibody)
•Overall survival data from the Phase 2 EDGE-Gastric study, evaluating domvanalimab plus zimberelimab and chemotherapy in upper gastrointestinal (GI) adenocarcinomas, are expected to be presented in the fall of 2025.
•The first Phase 3 data readout for domvanalimab plus zimberelimab will be from the ongoing Phase 3 study STAR-221 evaluating domvanalimab plus zimberelimab and chemotherapy in PD-L1 all-comer 1L metastatic upper GI adenocarcinomas and is expected in 2026.

CD73-Adenosine Axis: Quemliclustat (small-molecule CD73 inhibitor) and Etrumadenant (A2a/A2b receptor antagonist)

Quemliclustat:
•In the fourth quarter of 2024, Arcus initiated PRISM-1, a Phase 3 trial of quemliclustat combined with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in pancreatic cancer. In February 2025, Arcus’s partner, Taiho, dosed their first patient in Japan for PRISM-1.
Etrumadenant:
•Arcus plans to meet with the FDA in the first half of 2025 to clarify next steps for ARC-9, evaluating etrumadenant plus zimberelimab, FOLFOX, chemotherapy and bevacizumab (EZFB) versus regorafenib in third-line metastatic colorectal cancer (mCRC).

Early Clinical Programs

•Evaluation of AB801, a potent and highly selective small-molecule AXL inhibitor, in the dose-escalation phase of a Phase 1/1b study in patients is ongoing. Arcus anticipates advancing this molecule into expansion cohorts in non-small cell lung cancer (NSCLC) in the second half of 2025.

Financial Results for Fourth Quarter and Full Year 2024:
•Cash, Cash Equivalents and Marketable Securities were $992 million as of December 31, 2024, compared to $866 million as of December 31, 2023. The increase during the period is primarily due to the receipt of $320 million in cash from Gilead for their January 2024 equity investment, the receipt of the $100 million option continuation payment from Gilead in July 2024 and proceeds from our $50 million term loan, partially offset by the use of cash in research and development activities. Arcus expects its cash and investments, together with the proceeds from the equity financing in February 2025, will provide funding through our initial pivotal read-outs for domvanalimab, quemliclustat and casdatifan including STAR-221, PRISM-1 and PEAK-1.
•Revenues were $36 million for the fourth quarter 2024, compared to $31 million for the same period in 2023. In the fourth quarter 2024, Arcus recognized $28 million in License and development service revenues related to the advancement of programs under the Gilead collaboration, as well as $8 million in Other collaboration revenue related to Gilead’s ongoing rights to access Arcus’s research and development pipeline in accordance with the Gilead collaboration agreement.
•Research and Development (R&D) Expenses were $111 million for the fourth quarter 2024, compared to $93 million for the same period in 2023. The net increase of $18 million was primarily driven by higher costs associated with our early-stage R&D and preclinical program activities, driven by higher enrollment in our studies for casdatifan, higher expense incurred on Gilead-led studies for domvanalimab, as well as increases in compensation cost related to our growing headcount. Non-cash stock-based compensation expense was $9 million for each of the fourth quarter 2024 and 2023. For the fourth quarter 2024 and 2023, Arcus recognized gross reimbursements of $41 million and $42 million, respectively, for shared expenses from its collaborations, primarily the Gilead collaboration. Gross reimbursements were $165 million for the full year 2024, compared to $162 million for 2023. Our partnership reimbursements were flat compared to the prior year despite the increases in gross costs, due to increases in Gilead-led activities and programs fully funded by us. R&D expense by quarter may fluctuate due to the timing of clinical manufacturing and standard-of-care therapeutic purchases with a corresponding impact on reimbursements.
•General and Administrative (G&A) Expenses were $28 million for the fourth quarter 2024, compared to $29 million for the same period in 2023. Non-cash stock-based compensation expense was $8 million for the fourth quarter 2024, compared to $9 million for the same period in 2023.
•Net Loss was $94 million for the fourth quarter 2024, compared to $81 million for the same period in 2023.

Arcus Ongoing and Announced Clinical Studies:
Trial Name
Arms
Setting
Status
NCT No.
Kidney Cancer
PEAK-1
cas + cabo vs. cabo
Post-IO ccRCC
Planned Phase 3
TBD
AstraZeneca Collaboration (part of eVOLVE portfolio)
cas + volru
2L+ IO-Naive ccRCC
Planned Phase 1b
TBD
ARC-20
cas, cas + cabo
2L+ Cancer Patients/ccRCC
Ongoing Phase 1/1b
NCT05536141
Upper Gastrointestinal Cancers
STAR-221
dom + zim + chemo vs. nivo + chemo
1L Gastric, GEJ and EAC
Ongoing Registrational Phase 3
NCT05568095
EDGE-Gastric (ARC-21)
dom +/- zim +/- chemo
1L/2L Upper GI Malignancies
Ongoing
Randomized Phase 2
NCT05329766
Lung Cancer
STAR-121
dom + zim + chemo vs. pembro + chemo
1L NSCLC (PD-L1 all-comers)
Ongoing Registrational Phase 3
NCT05502237
PACIFIC-8
dom + durva vs. durva
Unresectable Stage 3 NSCLC
Ongoing Registrational Phase 3
NCT05211895
EDGE-Lung
dom +/- zim +/- quemli +/- chemo
1L/2L NSCLC (lung cancer platform study)
Ongoing Randomized Phase 2
NCT05676931
VELOCITY-Lung
dom +/- zim +/- sacituzumab govitecan-hziy or other combos
1L/2L NSCLC (lung cancer platform study)
Ongoing Randomized Phase 2
NCT05633667
Pancreatic Cancer
PRISM-1
quemli + gem/nab-pac vs. gem/nab-pac
1L PDAC
Ongoing Randomized Phase 3
NCT06608927
ARC-8
quemli + zim + gem/nab-pac vs. quemli + gem/nab-pac
1L PDAC
Ongoing Randomized Phase 1/1b
NCT04104672
Colorectal Cancer
ARC-9
etruma + zim + mFOLFOX vs. SOC
2L/3L/3L+ CRC
Ongoing
Randomized Phase 2
NCT04660812
Other
ARC-25
AB598
Gastric Cancer
Ongoing Phase 1
NCT05891171
ARC-27
AB801
NSCLC
Ongoing Phase 1
NCT06120075

cabo: cabozantinib; cas: casdatifan; ccRCC: clear cell renal cell carcinoma; CRC: colorectal cancer; dom: domvanalimab; durva: durvalumab; EAC: esophageal adenocarcinoma; etruma: etrumadenant; GEJ: gastroesophageal junction; gem/nab-pac: gemcitabine/nab-paclitaxel; GI: gastrointestinal; nivo: nivolumab; NSCLC: non-small cell lung cancer; PDAC: pancreatic ductal adenocarcinoma; pembro: pembrolizumab; quemli: quemliclustat; SOC: standard of care; zim: zimberelimab