R&D Focusing On TMERs for Innovative Medicine to Tackle Tumor Immune Escape

Tumor metabolic factors generate a unique microenvironment (TME) niche for tumor to escape body’s immune attack. Cancers use TME factors to engage receptors (TMERs) expressed on the cells of the immune system to evade anti-tumor immune surveillance. GPCRs are an important class of TMERs modulating the differentiation, development, and function of the immune systems, both innate and acquired, and play an important role in diseases of inflammatory, autoimmune, and cancer. Depending on the subtypes of G-protein coupled and differential intracellular signal transduction pathways, a GPCR, upon engagement by a TME factor, can inhibit tumor-killing immune cells such as CTL and NK cells, induce the formation of immune suppressive cells (iTreg, MDSC, mReg-DC), or cause chemotactic migration and redistribution of immune cells in favor of tumor survival and growth in a patient body.

At Crossignal Therapeutics, we are dedicated to cutting-edge research to identify which GPCR functions as a TMER, profile its immune cell expression, elucidate signal transduction pathways, and ultimately to validate the target for the discovery of "First-in-Class" new drug candidates. We established a Pathway-Precison Screen (PPS) assay platform to drive our compound screening. With deep-rooted experience in medicinal chemistry we are best positioned to achieve mission possible to bring a new generation of disruptive medicine to cancer patients.

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R&D Programs

TMER1-i
Small molecule Inhibitor
IO, First-in-Class
mono/combo with other CPI
Solid tumors: Colon, Pdac, Gastric, other
Block tumor-directed iTreg differentiation
Block MDSC chemotaxis to tumor
IND Enabling
TMER2-i
Small molecule Inhibitor
IO, First-in-Class
Solid Tumors
Hippo-YAP regulator, Treg/Th17 differentiation & function Hit-to-Lead SAR
TMER 3/4
Small molecule Inhibitor
IO
Solid Tumors
Effector T cell function enhancer Discovery
Adenosine Blocker
Small molecule
IO, "Best-in-Class"
Solid Tumors/adenosine-addictive, combo with CPI or Chemo
Highly potent triple antagonist (Ki = 0.37 nM [A2a],
1.76 nM [A2b], 1.26 nM [A1]);
Full A2a/A2b antagonism in high adenosine TME
Candidate Nominated for IND Enabling
PD1/PD-L1
Small molecule Blocker
IO
mono/combo with other TMERi
Hit-to-Lead SAR