Next Generation Oral Therapeutics Targeting the Immune Response
FLX Bio is developing a pipeline of orally-available small-molecule drugs to control the immune response. Our deep expertise in regulators of the immune system has led to the development of potent, selective first-in-class cancer therapeutics. We believe our powerful integrated drug discovery engine and big data approach to drug discovery allows us to identify a broader range of immune system targets, including intracellular proteins and pathways that play a role diseases beyond cancer including inflammation.
“Immune-targeted therapies are already impacting the lives of patients afflicted by a growing number of cancer types. Modulation of tumor-infiltrating regulatory T cells represents a promising unexploited therapeutic approach, creating the opportunity to complement, and work in combination with, the growing list of immune checkpoint inhibitors and other non-immunological therapeutic modalities.”
—Alexander Rudensky, Ph.D., Chairman, FLX Bio SAB
The Immune System
The human immune system protects the body from threats, external and internal, by distinguishing foreign from self. Using a mechanism called “immune surveillance,” the immune system recognizes and kills tumor cells that arise in the body. However, when immune surveillance fails, cancer can develop. Conversely, certain tissues can become overstimulated, causing an unwanted inflammatory response (e.g. allergic asthma, atopic dermatitis).
For over a century, researchers have tried to boost the immune response to fight cancer. Though earlier interventions had limited efficacy and significant toxicity, the recent use of checkpoint inhibitors such as anti-CTLA-4 and anti-PD-1/PD-L1 antibodies has resulted in deep and durable antitumor immune responses in multiple types of cancer. While this progress in the oncology field has positively impacted a proportion of cancer patients, additional efforts are needed to improve the lives of even more people.
In cancer, we are focusing on an underexplored but critical area of the antitumor immune response, suppressive cells in the tumor microenvironment. The tumor microenvironment is the local environment in which the tumor occupies. Both antitumor and immune-suppressive cells are recruited to the tumor microenvironment, but in growing tumors, the balance favors tumor growth. Our goal is to inhibit immune-suppressive cells within the tumor microenvironment, tipping the balance in favor of the immune system attacking the tumor, while limiting the immune attack on healthy tissues.
The primary cells that interfere with the immune system’s ability to execute an effective antitumor response include regulatory T (Treg) cells and myeloid cells including myeloid-derived suppressor cells (MDSCs).
In diseases such as atopic dermatitis and asthma, the immune system is overstimulated and is not able to turn itself off, causing damage of tissues and other harmful symptoms. We are targeting known pathways within the allergic inflammatory response to mitigate the recruitment of certain immune cells, reducing inflammation and reversing tissue injury.
- FLX475, a CCR4 antagonist for cancer
- FLX193, a CCR4 antagonist for allergy and asthma
- GCN2, a stress response kinase that detects amino acid starvation in the tumor microenvironment
- Discovery Programs
- CCR4, a chemokine receptor
- Regulatory T Cells
- Myeloid-Derived Suppressor Cells
- Helper T Type 2 (Th2) cells