inupadenant (EOS-850) / iTeos - LARVOL DELTA

A2A-005: Study of Inupadenant (EOS100850) With Chemotherapy as Second Line Treatment for Nonsquamous Non-small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=36 | Active, not recruiting | Sponsor: iTeos Therapeutics | Recruiting ➔ Active, not recruiting | N=186 ➔ 36 | Trial completion date: May 2025 ➔ Oct 2025

Enrollment change • Enrollment closed • Trial completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

iTeos Therapeutics Presents…Preclinical Data from Inupadenant at ESMO Immuno-Oncology Congress (GlobeNewswire) - "Inupadenant deprioritized to focus resources on other programs...'look forward to providing updates on our pipeline in 2025.'...In preclinical models, inupadenant counteracted the A2AR-mediated inhibition of B cell maturation into ASCs and immunoglobulin production in both in vitro and ex vivo systems by modulating B cells at the level of the germinal center (GC). These findings suggest that inupadenant restores or even enhances B cell maturation towards ASCs and GC reactions in both secondary lymphoid organs as well as the tumor in the presence of A2AR signaling. Furthermore, this process is essential for producing high-affinity antibodies and potentially for sustained anti-tumor immunity....Based on the spatial quantification of adenosine in human tumors, we developed the first adenosine gene signature, demonstrating its potential for indication selection."

Pipeline update • Preclinical • Lung Non-Squamous Non-Small Cell Cancer

iTeos Therapeutics Presents Interim A2A-005 Clinical Trial Data, Translational… (GlobeNewswire) - P2 | N=186 | NCT05403385 | Sponsor: iTeos Therapeutics | "As of the October 29, 2024 data cutoff, the topline data from the dose escalation portion of A2A-005 presented at the ESMO IO Congress were based on 36 patients eligible for safety and efficacy evaluation...The primary endpoint of the safety of inupadenant in combination with carboplatin/pemetrexed was observed to be manageable and tolerable, with no dose dependent toxicities; The secondary endpoint of ORR was 63.9% across all patients (53.3% at 40mg, 66.7% at 60mg, and 73.3% at 80mg); The secondary endpoint of mPFS was 7.7 months across all patients (5.6 months at 40mg and 6.6 months at 60mg; mPFS remains unreached at 80mg)...Based on monotherapy clinical and translational data, inupadenant demonstrated modulation of humoral responses....Furthermore, CXCL13 expression, a protein involved in immune cell recruitment, activation, and adaptive immune response regulation, increased in patients treated with inupadenant..."

P2 data • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer

The A2AR antagonist inupadenant promotes humoral responses in preclinical models (ESMO-IO 2024) - "The A2AR agonist CGS-21680 (in vitro and scRNAseq) or ATP (ex vivo) were added to trigger A2AR signaling, and B cells were stimulated with CpG (scRNAseq) or CD40L (ex vivo). This process is essential to produce high affinity antibodies and potentially for sustained anti-tumor immunity. Additional work is ongoing to confirm this novel mechanism in inupadenant-treated patients."

Preclinical • Lung Cancer • Oncology • Solid Tumor • ADORA2A • AICDA • CD40LG

Inupadenant Combined with Chemotherapy in Patients with Non-Squamous NSCLC Progressing On or After Immune Checkpoint Inhibitor Therapy: Results from Dose-Finding Part of the A2A-005 Trial (ESMO-IO 2024) - P2 | "Preliminary translational analyses indicate that serum CXCL13 increase may be associated with responses.Conclusions The combination of inupadenant and carboplatin-pemetrexed had a manageable safety profile and preliminary clinical activity in advanced NSCLC post ICI therapy. The study is ongoing and updated safety, efficacy, and translational data will be presented."

Checkpoint inhibition • Clinical • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CXCL13

The A2AR antagonist inupadenant promotes humoral responses in patients (ESMO-IO 2024) - P1 | "These effects may play a substantial role in delaying progression in end-stage patients. Additional work is ongoing to demonstrate this new mechanism of action across clinical settings and patient populations."

Clinical • Oncology • ADORA2A • CXCL13

iTeos Reports Third Quarter 2024 Financial Results and Provides Business Updates (GlobeNewswire) - "Program Highlights:...Inupadenant (EOS-850):...One poster presentation on preclinical data and two mini oral presentations featuring translational and clinical data from the dose escalation portion of the Phase 2 A2A-005 trial with inupadenant and platinum-doublet chemotherapy in post-IO metastatic non-squamous NSCLC to be presented at the European Society for Medical Oncology Immuno-oncology (ESMO IO) Congress 2024."

P2 data • Preclinical • Lung Non-Squamous Non-Small Cell Cancer

iTeos Therapeutics to Highlight Inupadenant Preclinical, Translational, and Phase 2 A2A-005 Clinical Trial Data in 2L NSCLC at ESMO Immuno-Oncology Congress (GlobeNewswire) - "iTeos Therapeutics, Inc...today announced that preclinical, translational, and clinical data from inupadenant will be presented at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) Congress 2024, being held December 11-13, 2024 in Geneva, Switzerland. The clinical and translational data from the dose escalation portion of A2A-005, the Phase 2 trial assessing inupadenant and platinum-doublet chemotherapy in post-immunotherapy metastatic non-small cell lung cancer (NSCLC) patients, will be presented as mini oral presentations. Preclinical data from inupadenant will be presented in the poster session."

P2 data • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor

Keynote A54: First-in-Human Study of EOS100850 (Inupadenant) in Patients with Cancer (clinicaltrials.gov) - P1 | N=119 | Completed | Sponsor: iTeos Therapeutics | Active, not recruiting ➔ Completed | Trial primary completion date: Jun 2023 ➔ May 2024

Combination therapy • Metastases • Trial completion • Trial primary completion date • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

New Formulation Study of Inupadenant (EOS100850) in Patients with Cancer (clinicaltrials.gov) - P1 | N=57 | Completed | Sponsor: iTeos Therapeutics | Recruiting ➔ Completed | Trial completion date: Nov 2023 ➔ May 2024 | Trial primary completion date: Oct 2023 ➔ May 2024

Metastases • Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

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

TIG-006: Study of EOS-448 With Standard of Care and/or Investigational Therapies in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=153 | Active, not recruiting | Sponsor: iTeos Belgium SA | Recruiting ➔ Active, not recruiting | N=254 ➔ 153 | Trial completion date: Jan 2025 ➔ Jul 2025

Combination therapy • Enrollment change • Enrollment closed • Metastases • Pan tumor • Trial completion date • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

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 Announces 2024 Strategic Priorities and Anticipated Milestones (GlobeNewswire) - "Inupadenant (EOS-850): A2A-005: topline 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; IO-001: completed enrollment of the Phase 2 IO-001 monotherapy high biomarker trial in advanced solid tumors. The Company plans to integrate IO-001 biomarker knowledge into the development strategy of future inupadenant clinical trials."

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

TIG-006: Study of EOS-448 With Standard of Care and/or Investigational Therapies in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=254 | Recruiting | Sponsor: iTeos Belgium SA | N=376 ➔ 254 | Trial completion date: Sep 2024 ➔ Jan 2025 | Trial primary completion date: Jan 2024 ➔ Sep 2024

Combination therapy • Enrollment change • Metastases • Pan tumor • Trial completion date • Trial primary completion date • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

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

Keynote A54: First-in-Human Study of EOS100850 in Patients With Cancer (clinicaltrials.gov) - P1 | N=119 | Active, not recruiting | Sponsor: iTeos Therapeutics | Recruiting ➔ Active, not recruiting | N=201 ➔ 119 | Trial completion date: Dec 2023 ➔ Jul 2024

Combination therapy • Enrollment change • Enrollment closed • Metastases • Trial completion date • Oncology • Solid Tumor

New Formulation Study of Inupadenant (EOS100850) in Patients With Cancer (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: iTeos Therapeutics | Trial completion date: Dec 2022 ➔ Nov 2023

Trial completion date • Oncology • Solid Tumor

A novel plasma cell-based mechanism of action of adenosine immunomodulation and A2AR antagonism (AACR 2023) - P1 | "Using B cells derived from peripheral blood, the A2AR agonist CGS-21680 was shown to inhibit the maturation of B cells into plasma cells, and that maturation could be fully restored by inupadenant. This is in line with recent reports showing that B cells, plasma cells and tertiary lymphoid structures are associated with favorable responses to cancer immunotherapy. Interestingly, four out of the five non-progressors treated with inupadenant as monotherapy and with available biomarker data showed a reduction in ASC infiltration after inupadenant treatment, suggesting that inupadenant may promote terminal plasma cell differentiation and migration out of the tumor tissue and to the bone marrow.Altogether, these data support a novel plasma cell-centric mechanism of action of inupadenant, which may complement its reported T cell-mediated anti-tumor activity."

Immunomodulating • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ADORA2A • ENTPD1

iTeos Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Business Updates (GlobeNewswire) - "Clinical Development Plans...Inupadenant (EOS-850): (i) Completed enrollment in the biomarker-high cohort evaluating inupadenant as a monotherapy in patients with advanced solid tumors selected for high biomarker expression; (ii) Completed enrollment in the Phase 2a trial evaluating inupadenant in combination with pembrolizumab in post-PD-1 melanoma; (iii) iTeos will present a poster at the upcoming American Association for Cancer Research (AACR) Annual Meeting...The poster presentation will further explore the biomarker findings and highlight a new mechanism of action of inupadenant based on the evaluation of tumor biopsies from treated patients and additional translational work."

Biomarker • Clinical data • Enrollment status • Melanoma • Oncology • Skin Cancer • 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

Study of Inupadenant (EOS100850) With Chemotherapy as Second Line Treatment for Nonsquamous Non-small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=192 | Recruiting | Sponsor: iTeos Belgium SA | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

iTeos Reports Second Quarter 2022 Financial Results and Provides Business Update (GlobeNewswire) - "The companies have initiated the Phase 1b trial evaluating the novel triplet of EOS-448 with Jemperli and GSK’s investigational anti-CD96 antibody. The companies also plan to initiate a Phase 1b trial with EOS-448, Jemperli, and inupadenant in the coming months."

Trial status • Oncology • Solid Tumor

Phase 2 Study Evaluating Inupadenant in Combination with Chemotherapy in Adults with NSCLC who Progressed on Immunotherapy (IASLC-WCLC 2022) - "Carboplatin plus Pemetrexed (C+P) is the preferred chemotherapy in nonsquamous mNSCLC. Correlative aims include assessing blood and tissue biomarkers for association with clinical benefit. The study will be conducted in approximately 11 countries in North America and Europe.Clinical trial information: EudraCT 2021-005487-22"

Clinical • Combination therapy • IO biomarker • P2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ADORA2A

New Formulation Study of Inupadenant (EOS100850) in Patients With Cancer (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: iTeos Therapeutics | Trial completion date: Jun 2022 ➔ Dec 2022

Trial completion date • Oncology • Solid Tumor