EOS-984 / iTeos - LARVOL DELTA

Inhibition of ENT1 relieves intracellular adenosine-mediated T cell suppression in cancer. (PubMed, Nat Immunol) - "A combination of EOS301984 with anti-PD-1 led to synergistic control of tumor growth in a humanized mouse model of triple-negative breast cancer. ENT1 inhibition, therefore, augments anti-cancer immune responses through the restoration of pyrimidine nucleotide synthesis in T cells suppressed by adenosine."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • SLC29A1

iTeos Reports First Quarter 2025 Financial Results and Provides Business Updates (GlobeNewswire) - "Program Highlights:...APT-008: Completed enrollment of the second dose cohort of the EOS-984 + pembrolizumab combination portion and continued advancement in the combination dose escalation of the Phase 1 trial in advanced malignancies. Topline data assessing EOS-984 as a monotherapy and in combination with pembrolizumab in patients with advanced solid tumors anticipated in 2H25."

P1 data • Solid Tumor

iTeos Announces 2025 Strategic Priorities and Anticipated Milestones (GlobeNewswire) - "APT-008: Topline data assessing EOS-984 as a monotherapy and in combination with pembrolizumab in patients with advanced solid tumors anticipated in 2H25....TRM-010: Investigative New Drug (IND) application for EOS-215 anticipated in 1Q25."

IND • P1 data • Oncology • Solid Tumor

Intracellular adenosine drives profound lymphocyte suppression and can be reversed with EOS-984: A potent ENT1 antagonist (ESMO-IO 2024) - "EOS-984 blocked intracellular adenosine transport, rescuing proliferation and function of T cells stimulated in the presence of adenosine in vitro. In a humanized mouse model of anti-PD-1-resistant TNBC (MDA-MB-231), EOS-984 controlled tumor growth synergistically with nivolumab.Conclusions In conclusion, intracellular adenosine metabolism is a novel mechanism of T cell immunosuppression, amenable to ENT1 inhibition to enhance anti-cancer immune responses."

IO biomarker • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • CD8 • SLC29A1

iTeos Reports Third Quarter 2024 Financial Results and Provides Business Updates (GlobeNewswire) - "Program Highlights:...EOS-984:...(i) Completed enrollment of monotherapy dose escalation and initiated dosing of first cohort of EOS-984 + pembrolizumab combination portion in the Phase 1 APT-008 trial; (ii) Two poster presentations on preclinical and translational data highlighting the novel mechanism of action, monotherapy and combination activity combination activity with anti-PD-1 therapy, and the adenosine signature biomarker to be presented at the ESMO IO Congress 2024; (iii) Topline data from the Phase 1 APT-008 trial anticipated in 2025."

Clinical data • Enrollment status • P1 data • Preclinical • Solid Tumor

Adenosine drives profound lymphocyte immunosuppression via a previously underappreciated mechanism and can be reversed with EOS-984, a potent ENT1 antagonist (CRI-ENCI-AACR ICIC 2024) - "Finally, in a humanized mouse model of triple negative breast cancer resistant to anti-PD-1 blockade (MDA-MB-231), combination of EOS-984 with nivolumab synergistically led to control of tumor growth. Thus, ENT1 inhibition represents a novel approach to augment anti-cancer immune responses through restoring pyrimidine nucleotide synthesis in T cells suppressed by adenosine."

IO biomarker • Breast Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Triple Negative Breast Cancer • CD8 • SLC29A1

iTeos Reports Second Quarter 2024 Financial Results and Provides Business Updates (GlobeNewswire) - "Program Highlights:....(i) A2A-005: Data from the dose escalation portion of the Phase 2 trial with inupadenant and platinum-doublet chemotherapy in post-IO metastatic non-squamous NSCLC anticipated in late 2024; (ii) EOS-984:...Topline data from the Phase 1 trial anticipated in the second half of 2024."

P1 data • P2 data • Non Small Cell Lung Cancer

A First-in-Human Study of EOS301984 as Monotherapy or Combination Therapy in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=84 | Recruiting | Sponsor: iTeos Therapeutics

Combination therapy • Metastases • Monotherapy • New P1 trial • Oncology • Solid Tumor

Discovery of EOS-984, a potent and selective ENT1 inhibitor (ACS-Fall 2024) - "ENT1 expression increases upon T cell activation, suggesting uptake of extracellular adenosine is a mechanism to limit T cell responses in high adenosine environments.EOS-984 is a first-in-class small molecule highly potent and selective inhibitor of ENT1, currently being evaluated in patients with advanced solid tumors. The medicinal chemistry efforts that lead to the discovery of EOS-984 will be detailed."

Oncology • Solid Tumor • SLC29A1

iTeos Reports First Quarter 2024 Financial Results and Provides Business Updates (GlobeNewswire) - "Inupadenant (EOS-850): insurmountable small molecule antagonist targeting adenosine A2A receptor in second-line NSCLC. A2A-005: Completed enrollment of Phase 2 A2A-005 dose escalation. Data from the dose escalation portion of the Phase 2 trial with inupadenant and platinum-doublet chemotherapy in post-IO metastatic non-squamous NSCLC anticipated in late 2024....R&D expenses were $34.5 million for the quarter ended March 31, 2024, as compared to $25.6 million for the same quarter of 2023. The increase compared to the comparative period was primarily due to increases in activities related to the belrestotug, inupadenant, and EOS-984 programs, and included the addition of new R&D employees hired to help advance these programs."

Commercial • P2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

iTeos Presents EOS-984 Preclinical Data Demonstrating Restoration of T Cell Activity from Adenosine Suppression at the American Association for Cancer Research Annual Meeting 2024 (GlobeNewswire) - "In preclinical studies, blockade of intracellular adenosine accumulation by EOS-984 enabled proliferation of memory T cells and TILs despite high adenosine concentrations, resulting in the restoration of T cell function and enhanced tumor cell killing. Furthermore, combination of EOS-984 with anti-PD-1 therapy synergistically led to the control of tumor growth in a humanized mouse model of triple negative breast cancer resistant to anti-PD-1 blockade. Due to its mechanism of action, EOS-984 holds potential as a combination partner beyond anti-PD-1 therapy, including other immuno-oncology agents, cell therapies, and bispecific T cell engagers....Topline data from the Phase 1 trial is anticipated in the second half of 2024."

P1 data • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

iTeos to Highlight Preclinical Data on First-In-Class EOS-984 Targeting ENT1 at the American Association for Cancer Research Annual Meeting 2024 (GlobeNewswire) - "iTeos Therapeutics...announced a poster presentation of preclinical data on EOS-984, a first-in-class small molecule antagonist targeting equilibrative nucleoside transporter 1 (ENT1), at the American Association for Cancer Research (AACR) Annual Meeting, being held April 5-10, 2024 in San Diego, California."

Preclinical • Oncology

iTeos Announces 2024 Strategic Priorities and Anticipated Milestones (GlobeNewswire) - "EOS-984: Preclinical mechanism of action data anticipated in the second quarter of 2024; Topline data from the Phase 1 dose escalation trial in advanced malignancies anticipated in the second half of 2024."

P1 data • Preclinical • Oncology

iTeos Reports Third Quarter 2023 Financial Results and Provides Business Updates (GlobeNewswire) - "Inupadenant (EOS-850): Continued progression of the two-part A2A-005 Phase 2 trial with inupadenant and platinum-doublet chemotherapy in post-IO metastatic non-squamous NSCLC. Topline data from Phase 2 A2A-005 are anticipated in late 2024. EOS-984: Completed enrollment of the first dose cohort and continued advancement in the dose escalation of the Phase 1 trial in advanced malignancies. Topline data from the Phase 1 trial are anticipated in late 2024....R&D expenses were $30.6 million for the quarter ended September 30, 2023, as compared to $23.9 million for the same quarter of 2022. The increases in each comparative period were primarily due to increases in activities related to the belrestotug, inupadenant, and EOS-984 programs."

Commercial • P1 data • P2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

iTeos Reports First Quarter 2023 Financial Results and Provides Business Updates (GlobeNewswire) - "The company completed Investigational New Drug / Clinical Trials Application-enabling activities, including toxicity studies, and anticipates initiating clinical studies for EOS-984 mid-year 2023."

New trial • Oncology • Solid Tumor

iTeos Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Business Updates (GlobeNewswire) - "The company completed Investigational New Drug / Clinical Trials Application-enabling activities including toxicity studies and anticipates initiating clinical studies for EOS-984 in mid-2023."

IND • Oncology • Solid Tumor

iTeos Provides Business Updates and Clinical Development Plans for 2023 (GlobeNewswire) - "We expect to advance EOS-448, our anti-TIGIT, antibody, into Phase 3 in combination with GSK’s ant-PD-1, Jemperli (dostarlimab) and also continue to advance studies targeting the adenosine pathway through our inupadenant program. Additionally, EOS-984, a first-in-class therapy designed to inhibit a novel target in the adenosine pathway, is expected to enter the clinic in mid-2023..."

New P3 trial • New trial • Oncology