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2nd Generation STING Agonist

A signaling molecule that plays a critical role in the cytosolic detection of tumor-derived DNA

2nd Generation STING Agonist Proposed MoA

Status

Phase 1

Patient population

Solid Tumors

Combination partners

PD-1 inhibitor-ezabenlimab

Molecule

BI 1703880 is a systemic small-molecule agonist of STING.1 STING functions as a DNA sensor and is expressed in immune cells, stromal cells and tumor cells.1,2

Proposed MoA

STING pathway activation by 2nd generation STING agonist induces the production of type I IFN and inflammatory cytokine secretion in the TME, leading to innate immune cell activation, cross-priming, activation, and infiltration of cytotoxic T cells and subsequent tumor cell killing.1–3

Preclinical data have shown that BI 1703880 potently and highly selectively activates the STING pathway, resulting in dose-dependent cytokine secretion. 

Combination therapy

In vivo data (preclinical mouse tumor models) demonstrated induction of a tumor-specific immune response leading to complete antitumor response when administered in combination with anti–PD-1.4

BI 1703880 is currently being investigated in a Phase I trial in combination with ezabenlimab (PD-1 inhibitor) in patients with advanced solid tumors.5
 

Proposed MoA1

STING agonist (BI 1703880) mechanism of action

1. Harrington K, et al. SITC 2022. Abstract 626; 2. Woo SR. Immunity. 2014;41:830–842; 3. Barber GN. Nat Rev Immunol. 2015;15:760–770; 4. Gremel G, et al. Cancer Res. 2020;80(16 Suppl): Abstract 4522; 5. NCT05471856. https://clinicaltrials.gov/ct2/show/NCT05471856. Accessed April 2024.

Clinical Research and Development

2nd Generation STING Agonist Clinical Trial

Trial numberPhaseCompoundPatient populationStatus

NCT05471856 (1480.1)

1

BI 1703880 + ezabenlimab (PD-1 inhibitor)

Advanced solid tumors

Recruiting

 

  • BI 1703880 is a small molecule that is intended to bind to the stimulator of interferon genes (STING) 1,2

  • BI 1703880 may selectively activate the STING pathway, resulting in dose-dependent local tumor control and the induction of a tumor-specific immune response1

  • The 2nd generation STING agonist in combination with ezabenlimab is currently being evaluated in a Phase 1 clinical trial for the treatment of patients with advanced solid tumors3

1. Boehringer Ingelheim. Data on file; 2. Woo SR. Immunity. 2014;41(5):830–42; 3. NCT05471856. https://clinicaltrials.gov/ct2/show/NCT05471856. Accessed October 2023.
 

  1. Boehringer Ingelheim. Data on file.

  2. Woo SR. Immunity. 2014;41(5):830–42.

  3. NCT05471856. https://clinicaltrials.gov/ct2/show/NCT05471856. Accessed October 2023.

  4. Doi T, et al. JSMO 2022. Poster 370268.

     

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