cells

Discovery Pipeline

DISCOVERY PIPELINE

icon

HIF-2𝛂 Inhibitor

Transcription factor

Cancer cell intrinsic target; potential non-oncology indications

HIF-2α is a master transcriptional regulator of multiple genes involved in tumor progression.1

icon

AXL Inhibitor

Tyrosine kinase

Cancer cell intrinsic target

AXL overexpression is associated with tumor resistance to chemotherapy and immunotherapy drugs.2

icon

PI3Kγ Inhibitor

Glycolipid kinase

Immune (TAM, MDSC) target

PI3Kγ is required for the immunosuppressive activity of tumor-infiltrating macrophages and myeloid-derived suppressor cells.3

icon

PAK4 Inhibitor

Serine kinase

Cancer cell intrinsic target

PAK4 overexpression is responsible for T cell exclusion from immune desert tumors.4

icon

Anti-TIM-3 Antibody

Immune Checkpoint

Cancer cell intrinsic and immune (T cell) target

TIM-3 is an immune checkpoint highly overexpressed by leukemic cells (eg, MDS, AML) and exhausted T cells.5

AML, acute myeloid leukemia; HIF-2𝛂, hypoxia-inducible factor 2-alpha; MDS, myelodysplastic syndromes; PAK-4, p21-activated kinase 4; PI3Kγ, phosphatidylinositol 3-kinase-gamma; TIM-3, T cell immunoglobulin and mucin-domain containing-3.

References: 1. Murugesan T, Rajajeyabalachandran G, Kumar S, Nagaraju S, Kumar S. Targeting HIF-2α as therapy for advanced cancers. Drug Discov Today. 2018;23(7):1444-1451. 2. Axelrod HD, Valkenburg KC, Amend SR, et al. AXL is a putative tumor suppressor and dormancy regulator in prostate cancer. Mol Cancer Res. 2019;17(2):356-369. 3. Foubert P, Kaneda MM, Varner JA. PI3Kγ activates integrin α4 and promotes immune suppressive myeloid cell polarization during tumor progression. Cancer Immunol Res. 2017;5(11):957-968. 4. Abril-Rodriguez G, Torrejon DY, Liu W, et al. PAK4 inhibition improves PD-1 blockade immunotherapy. Nature Cancer. 2020;1:46-58. 5. Toshio A, Tamura H, Ishibashi M, et al. Functional expression of Tim-3 on blasts and clinical impact of its ligand galectin-9 in myelodysplastic syndromes. Oncotarget. 2017;8(51):88904-88917.