Developing therapeutics to unleash the immune system’s natural response to cancer

We are pioneering a new class of Immune-Oncology drugs to complement existing therapeutic modalities

Our immune-oncology efforts and programs reside under:

Unleashing the body’s natural immune response

Immune checkpoints are proteins involved with maintaining a balanced immune state, preventing over/under activation of immune signaling. Recent discoveries show that cancer cells modulate these immune checkpoints to evade the patient’s immune system, leading to uncontrolled cancer cell proliferation. Therapeutic attenuation of immune checkpoints can restore the natural immune response to tumors.

We are developing a diverse portfolio of first-in-class immune-checkpoint inhibitors and activators to treat a wide variety of oncology and immune diseases.

Pharmaceutical research on checkpoint inhibition by biologic drugs has dramatically expanded in recent years. Several biologics have gained FDA approval as checkpoint inhibitor drugs for use in multiple types of cancers and revolutionized cancer treatment

However, biological drugs have numerous limitations including cardiomyopathies, immune related adverse events, inability to access privileged sites (i.e. blood brain barrier), poor access to the tumor microenvironment, unmanageable pharmacokinetics not to mention costs. These challenges are an urgent call to develop small molecules that can overcome these shortcomings. However, many of these immune check points are difficult to develop potent drugs against. Our powerful platform has been successful at generating novel drug candidates that rival biologics in their potency yet are devoid of their limitations.

We are reframing the immune checkpoint landscape

1. Cell surface receptor checkpoints

Immune cell surface receptors mediate a plethora of responses from cell proliferation to inflammation. These effects result from the binding of stimulatory or inhibitory proteins to the receptors leading to the initiation of multi-step signaling cascades within the immune cell. Up-regulation or down-regulation of these receptors allows cancer cells to directly manipulate the activities of different immune cell types resulting in escape from the patient’s natural anti-tumor mechanisms. Our therapeutic strategies focus on restoring the cell surface receptor interactions between cancer and immune cells to their natural balance.

2. Metabolic checkpoints

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.

3. Soluble checkpoints

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.

4. Epigenetic checkpoints

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.