• Phase 1/1b results for the etrumadenant combination demonstrated a 4.2 month PFS, approximately double the 2 months reported for current standard of care therapies in the ≥3L mCRC setting
• ARC-9, a randomized Phase 1b/2 platform study, has been initiated to further evaluate etrumadenant-zimberelimab combinations in the 2L, 3L and ≥3L+ mCRC settings
• Our novel series of HIF-2α inhibitors, including AB521, a highly-potent molecule with a favorable pharmacokinetic profile, has been described for the first time; we remain on track to initiate clinical development for this program in 2H:21

Arcus Biosciences, Inc. (NYSE:RCUS), an oncology-focused biopharmaceutical company working to create best-in-class cancer therapies, today presented progression-free survival (PFS) and overall survival (OS) data in patients with advanced metastatic colorectal cancer (mCRC) from the ARC-3 study at the 2021 American Association for Cancer Research (AACR) Annual Meeting. ARC-3 was a Phase 1/1b, multicenter, open-label, dose-escalation and dose-expansion study that evaluated the safety, tolerability, PK and early clinical activity of etrumadenant, the first dual adenosine A_2a/A_2b receptor antagonist in the clinic, in subjects with mCRC.

Additionally, Arcus presented details of its Hypoxia-Inducible Factor 2α (HIF-2α) research program, including the design of a novel series of HIF-2α inhibitors, which has resulted in the identification of molecules such as AB521, with excellent potency, selectivity, biological activity and pharmacokinetic properties suitable for further development.

ARC-3: Updated Results of Etrumadenant (AB928) + mFOLFOX-6 in Patients with Metastatic Colorectal Cancer

Initial results from ARC-3 demonstrated that etrumadenant + modified FOLFOX-6 (mFOLFOX-6) in patients with mCRC was well tolerated and associated with a substantial disease control rate (DCR) across all lines of therapy, including in patients with microsatellite stable disease and RAS/BRAF-mutated mCRC^1,2.

Updated data from the 3L+ cohort (median of 3 and a range of 2 to 7 prior lines), in which 87% of the patients had received prior FOLFOX, demonstrated the following:

• Safety Results (n=23 safety-evaluable 3L+ patients as of the DCO of Feb. 26, 2021)
  • Etrumadenant + mFOLFOX-6 was well tolerated, and etrumadenant, at the evaluated doses of 75mg and 150mg once daily (QD), did not appear to add significant toxicity to that expected for mFOLFOX-6.
  • No grade 3 or above neuropathy events were observed in this heavily pretreated population.
  • The most common treatment emergent adverse events (TEAEs) for the etrumadement- mFOLFOX-3 combination were fatigue (70%), thrombocytopenia (57%), diarrhea (52%) and nausea (52%).

• Efficacy Results (n=22 efficacy-evaluable 3L+ patients as of the DCO of Feb. 26, 2021)
  • Median progression-free survival (PFS) of 4.2 months. Reported data for current standard-of-care (SOC) therapies have shown a median PFS of 2.0 and 1.9 months for trifluridine-tipiracil and regorafenib, respectively^3,4.
  • Median overall survival (OS) of 13.6 months. Reported data for trifluridine-tipiracil and regorafenib have shown a median OS of 7.1 and 6.4 months, respectively^3,4.
  • Objective response rate (ORR) of 9.1% and an encouraging 8-week DCR of 86%. Reported data for trifluridine-tipiracil and regorafenib have shown ORRs of 1.6% and 1%, respectively ^3,4.
  • Patients with higher tumor mutation burden and intra-tumoral expression of CD73 demonstrated improved outcomes compared to patients with lower levels of these biomarkers, consistent with previous findings¹, which may be reflective of an etrumadenant-mediated effect.

“Based on these very encouraging early results, we have advanced etrumadenant into ARC-9, a randomized Phase 2 platform study to evaluate this first-in-class molecule in combination with zimberelimab, our anti-PD-1 antibody, and FOLFOX +/- bevacizumab in second- and third-line mCRC,” said Bill Grossman, M.D., Ph.D., Chief Medical Officer of Arcus. “The results presented today, combined with our recent promising early data evaluating AB680, our small-molecule CD73 inhibitor, in pancreatic cancer, support an expanding rationale for targeting the ATP-adenosine axis to meet critical unmet needs in gastrointestinal cancers.”

“Few options exist today to treat third-line colorectal cancer, and these therapies are associated with significant toxicity and limited efficacy. While this was an early-stage study, etrumadenant’s efficacy in this difficult-to-treat patient population was impressive, particularly the doubling of progression-free and overall survival that was observed relative to what has been reported for current standard-of-care therapies,” said Michael Cecchini, MD, Assistant Professor of Medicine (Medical Oncology), Yale Cancer Center and Smilow Cancer Hospital. “Importantly, etrumadenant also added very little toxicity, enabling patients to remain on treatment for extended periods of time. I look forward to working with Arcus to advance etrumadenant, and Arcus’s other ATP-adenosine axis-targeting agents, into later-stage studies for gastrointestinal cancers in order to broaden access to these innovative potential therapies.”

Preliminary data from ARC-9, a global follow-on study to ARC-3, are expected to be presented in the first half of 2022. For additional information on this trial, please visit NCT04660812, at www.clinicaltrials.gov.

Discovery and Characterization of AB521, a Novel, Potent, and Selective HIF-2 α Inhibitor

Preclinical and clinical evidence indicate that HIF-2α inhibition is a validated approach for the treatment of clear cell renal cell carcinoma (ccRCC) and tumors associated with mutant/deficient Von Hippel-Lindau (VHL). Arcus has developed a broad research program to identify drug candidates against this target. Despite the inherent difficulties in identifying drug-like inhibitors of HIF-2α, Arcus scientists have generated highly optimized inhibitors, including AB521, which exhibit high potency, selectivity and biological activity, as well as a favorable pharmacokinetic profile in preclinical species, that we expect will facilitate achieving optimal plasma levels of drug in the clinic.

We expect to initiate clinical development for our lead HIF-2α inhibitor in the second half of 2021 and plan to combine this molecule with other product candidates from our pipeline, including our first-in-class adenosine axis-targeting agents.

Additional information about these presentations may be found on the Arcus website at Arcus Publications.

About Etrumadenant

Etrumadenant (AB928), the first dual A_2a/A_2b adenosine receptor antagonist in the clinic, is designed to maximally inhibit the adenosine-driven impairment of tumor-infiltrating lymphocytes (mainly CD8+ T cells and NK cells) and myeloid cells (dendritic cells, macrophages), mediated by A_2aR and A_2bR, respectively. A_2bR is also upregulated by certain cancer cells, such as in prostate cancer and KRAS- mutated cancers. As a result, etrumadenant may uniquely block adenosine’s immunosuppressive and cancer cell-intrinsic effects. Developed specifically for the oncology setting, etrumadenant achieves high penetration of tumor tissue, robust potency in the presence of high adenosine concentrations, and minimal shift in potency from non-specific protein binding. Etrumadenant has demonstrated a favorable safety profile with a variety of combination regimens and exhibits pharmacokinetics / pharmacodynamics consistent with once-daily dosing. AB928 is currently being evaluated in several Phase 1b/2 studies across multiple indications.

About Arcus Biosciences

Arcus Biosciences is an oncology-focused biopharmaceutical company leveraging its deep cross-disciplinary expertise to discover highly differentiated therapies and to develop a broad portfolio of novel combinations addressing significant unmet needs. Arcus currently has five molecules in clinical development: Etrumadenant (AB928), the first dual A_2a/A_2b adenosine receptor antagonist to enter the clinic, is being evaluated in multiple Phase 2 and 1b studies across different indications, including prostate, colorectal, non-small cell lung, and pancreatic cancers. AB680, the first small-molecule CD73 inhibitor to enter the clinic, is in Phase 1/1b development for first-line treatment of metastatic pancreatic cancer in combination with zimberelimab and gemcitabine/nab-paclitaxel. Domvanalimab (AB154), an anti-TIGIT monoclonal antibody and new potential immuno-oncology backbone therapy, is in a three-arm randomized Phase 2 study for first-line treatment of PD-L1 ≥ 50% metastatic non-small cell lung cancer (NSCLC) evaluating zimberelimab monotherapy, domvanalimab with zimberelimab and domvanalimab plus etrumadenant with zimberelimab. In addition, domvanalimab has advanced into ARC-10, Arcus’s “two in one trial” to support the potential approvals of both zimberelimab and zimberelimab + domvanalimab and is expected to advance into a registrational study, in collaboration with AstraZeneca, evaluating the curative-intent stage 3 NSCLC setting later this year. AB308, an anti-TIGIT antibody that is FcR-enabled, advanced into clinical development to investigate additional indications, with a focus on hematological malignancies. Zimberelimab (AB122), Arcus’s anti-PD-1 monoclonal antibody, was in-licensed to enable the development of Arcus’s combination regimens and is being evaluated in various combinations across the portfolio. For more information about Arcus Biosciences, please visit www.arcusbio.com.

Forward-Looking Statements

This press release contains forward-looking statements. All statements regarding events or results to occur in the future contained herein, including, but not limited to, potential benefits of etrumadenant and Arcus’s other ATP-adenosine axis-targeting agents, anticipated milestones and associated timelines are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All forward-looking statements involve known and unknown risks, uncertainties and other important factors that may cause Arcus’s actual results, performance or achievements to differ significantly from those expressed or implied. Factors that could cause or contribute to such differences include, but are not limited to: the inherent uncertainty associated with the COVID-19 pandemic, including the duration and/or severity of the outbreak and actions by government authorities to contain or slow the spread of the virus; the inherent uncertainty associated with pharmaceutical product development and clinical trials; delays in our clinical trials due to difficulties or delays in the regulatory process, enrolling subjects or manufacturing or supplying product for such clinical trials; the emergence of adverse events or other undesirable side effects; risks associated with data from early-stage studies and the applicability of the results described herein to Arcus’s subsequent clinical trials; changes in the competitive landscape for our programs; and our dependence on our collaboration with Gilead for the successful development and commercialization of our investigational products. Risks and uncertainties facing Arcus are described more fully in Arcus’s annual report on Form 10-K for the year ended December 31, 2020 filed on February 24, 2021 with the SEC. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date of this press release. Arcus disclaims any obligation or undertaking to update, supplement or revise any forward-looking statements contained in this press release.

References

1. Udyavar AR, et al. SITC 2020. Abstract 338.

2. Cecchini M, et al. AACR 2020.Abstract 9953.

3. Maher RJ, et al. N Eng J Med. 2015;372(20):1909-1919.

4. Grothey A, et al. Lancet. 2013; 381(9863):303-312.

Source: Arcus Biosciences

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