PIPELINE
EP601 - GPR84
EPICS’ EP601 – GPR84, currently in preclinical development, is a first-in-class approach for the treatment of cancer and autoimmune disease
GPR84: Activate it where the immune system is silent. Restrain it where inflammation runs unchecked.
One target. Two directions. Multiple diseases.
EPICS Therapeutics is advancing EP601, a potent, selective, and orally available GPR84 agonist designed to activate or restrain immune responses where needed.
GPR84 sits at the intersection of metabolism, inflammation, and innate immunity, acting as a context-dependent amplifier of immune responses:
- In cancer, where immune responses are insufficient, activation is beneficial
- In autoimmune and inflammatory diseases, where immune activity is excessive, inhibition may be required
What is GPR84 and why it matters?
GPR84 is a metabolic receptor that controls how strongly the immune system responds to danger.
It translates lipid signals generated during tissue injury, infection, or metabolic stress into immune action mobilizing innate immune cells, including macrophages, neutrophils, and microglia, where they are needed most.
In diseases where immunity is suppressed, such as cancer, activating GPR84 can drive an acute immune response and/or restore immune function to thereby suppress tumor growth.
Conversely, in autoimmune diseases, controlled activation of GPR84 offers a strategy to rebalance dysregulated inflammation and re-establish immune homeostasis.
Therapeutic opportunities
Oncology: Reprogramming the tumor microenvironment
Tumors evade immune destruction by suppressing innate immune cells, particularly tumor-associated macrophages (TAMs).
GPR84 activation reverses this suppression, and EPICS’ EP601 program introduces a new axis in immuno-oncology by activating innate immunity to unlock adaptive responses.
EP601 may also restore immune function in the central nervous system
Brain tumors such as glioblastoma are characterized by a profoundly immunosuppressive environment dominated by dysfunctional microglia and macrophages (the brain’s resident immune cells).
GPR84 activation may restore immune function in these cells.
The gut–immune connection: Translating microbial signals into immunity
The molecules that activate GPR84 are produced by bacteria in the gut. Through this pathway, GPR84 translates microbial activity into immune responses, linking:
- microbiome composition
- metabolic output
- innate immune activation
Rather than attempting to reshape the microbiome directly, GPR84 activation enables control at the level of host signal interpretation.
This positions EPICS’ GPR84 agonist as a key regulator of the gut–immune axis, with implications across infection, inflammation, and systemic immune balance.
Neuroinflammation and cognition: A gut–brain immune connection
Microglia, the brain’s resident immune cells, express high levels of GPR84 and play a central role in regulating inflammation in the brain.
Recent research reveals that lipid signals derived from the gut can activate GPR84-dependent immune pathways and influence neural signaling linked to memory and cognition.
In this context, modulation of GPR84 activity may help control neuroinflammatory processes associated with aging, including impaired memory and cognitive decline.
The EPICS approach
Rather than broadly stimulating or suppressing the immune system, we aim to tune it with precision.
Most therapies act downstream, blocking cytokines, inhibiting checkpoints, or suppressing immune cells.
EP601 acts at an early immune decision point, influencing how innate immune cells interpret metabolic and damage signals, ultimately shaping downstream immune responses.
EPICS GPR84 agonist is designed to deliver:
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precise receptor-level control
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high potency and selectivity
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scalable, small-molecule solutions
The science behind GPR84
GPR84 is a G protein–coupled receptor expressed predominantly on innate immune cells. It responds to medium-chain fatty acids (MCFAs), lipid molecules generated during metabolic stress, tissue damage, and microbial activity, which act as endogenous danger signals.
When GPR84 is engaged, immune cells:
- migrate rapidly to sites of injury
- increase phagocytic activity (the ability of immune cells to clear harmful cells)
- produce inflammatory mediators
- adopt a pro-inflammatory, defense-oriented phenotype
In healthy physiology, this response supports rapid pathogen clearance and initiates tissue repair.
What makes GPR84 unique is its position at the interface of metabolism and immunity, a receptor that converts microbiome–derived signals into immune decisions.
