We are reframing the immune checkpoint landscape
We are developing therapeutics that target multiple facets of immune checkpoint regulation through novel small molecules and biologics.
1. Cell Surface Receptor based checkpoints
2. Metabolic checkpoints
3. Soluble checkpoints
4. Epigenetic checkpoints
Cell Surface Receptor based checkpoints
Immune cell surface receptors mediate a plethora of responses from cell proliferation to inflammation. These responses result from the binding of co-stimulatory or inhibitory factors to the receptors leading to the initiation of multi-step signaling cascades that are precisely orchestrated. Up-regulation of these receptors, or their modulating factors, allows cancerous cells to directly control the activities of different immune cell types resulting in escape from our own natural anti-tumor surveillance mechanisms. Conformation-X focuses on correcting the endogenous anti-tumor activities of membrane associated immune checkpoint proteins.
Certain metabolic components serve as critical checkpoints in immune homeostasis and controlling tumorigenesis. Numerous studies confirm that metabolic requirements for successful T-cell functionality in the tumor milieu are an important node for therapeutic intervention, including the activation, differentiation, and migration of immune cells. While immuno-metabolism is an emerging field, we are rationally designing drugs that are profoundly selective with no off-target effects.
A variety of secreted proteins, peptides and factors circulate throughout the body and regulate the activation and proliferation of immune cells. These checkpoints possess either pro-inflammatory or anti-inflammatory roles that can be disturbed by tumor cells. We are developing therapeutics that target soluble checkpoints to coordinate an anti-cancer effect and restore immune homeostasis.
Epigenetic changes are discrete, reversible, chemical modifications of genetic material in cells that serve as important regulators of gene transcription and cellular outcomes. Aberrant epigenetic changes in cancer and immune cells lead to down regulation of immune surveillance, tumor immune escape, cancer cell survival and drug resistance. Our work in this area has led to the development of this new sub-class of immune-targeted anticancer therapies