Another Path
Forward

IN SYSTEMIC SCLEROSIS

THE CB2 RECEPTOR IS IMPLICATED IN INFLAMMATION & FIBROSIS

The endocannabinoid system (ECS), and in particular the CB2 receptor, is involved in mediating inflammation and fibrosis. It may be an important piece of the systemic sclerosis (SSc) puzzle.

Not an actual patient.

THE CB2 RECEPTOR SHOWS PROMISE
FOR A DIFFERENT APPROACH TO SSc

CB2 IS A RELEVANT TARGET IN SSc

CB2 is expressed on cells that contribute to multiple aspects of disease pathogenesis, including activated immune cells, endothelial cells, and fibroblasts.1,2

CB2 REBALANCES DYSREGULATED IMMUNE RESPONSE

CB2 signaling decreases inflammatory cytokines (e.g. IL-6, TNFα, TGFβ), and increases pro-resolving cytokines, playing a key role in immune response and tissue repair.3-8

CB2 OFFERS THE POTENTIAL FOR IMMUNOMODULATION WITHOUT IMMUNOSUPPRESSION

CB2 agonists can leverage specific pharmacologic properties of the CB2 receptor, which could modify diseases without suppressing the immune system.9,10

CB2 IS PART OF THE ENDOCANNABINOID SYSTEM

The ECS is an endogenous system that plays a critical role in promoting homeostasis. The ECS, and in particular CB2, has been shown to have a regulatory effect on the inflammatory and fibrogenic processes that drive SSc.1,8,11

CB2 AND CB1 ARE KEY RECEPTORS
OF THE ENDOCANNABINOID SYSTEM

CB2 and CB1 are the two main receptors in the ECS, however there are critical differences between the mediating effects of these pathways.5,12,13

CB1 and CB2 receptors CB2 and CB1 both have seven transmembrane
protein domains.14

ACTS ON THE CNS

  • Predominantly expressed in the brain and central nervous system as well as on fibroblasts9,15
  • Stimulation of the CB1 receptor causes psychotropic effects and may increase potential for abuse and addiction9,13,16,17

ACTS PERIPHERALLY

  • Predominantly expressed in the immune system and peripheral tissues5,15
  • Demonstrates the ability to regulate tissue repair by modulating fibrotic signaling and limiting fibroblast proliferation6,9

THE ENDOCANNABINOID SYSTEM IS UBIQUITOUS THROUGHOUT THE BODY12

THE CANNABINOID RECEPTORS

CB2 and CB1 are the two main receptors in the ECS, however there are critical differences between the mediating effects of these pathways.5,12,13

- CB2

CB2 is primarily expressed throughout the body in immune cells and peripheral locations such as the cardiovascular system, GI tract, adipose tissue, bone, and reproductive system.18

- CB1

CB1 is primarily expressed in the brain and nervous system, and to a lesser extent in some peripheral tissues. It mediates a range of neurological activities and some local peripheral tissue functions.18

Human body
Artist's representation.

UNDERSTANDING CANNABINOIDS

Therapeutic applications of plant-based phytocannabinoids like cannabidiol (CBD) and tetrahydrocannabinol (THC), and endogenous cannabinoids (CB receptor ligands) for pain relief has yielded a surge of interest in targeting the ECS to treat autoimmune diseases.8,13,19

PLANT-BASED PHYTOCANNABINOIDS5,9,13,17

CBD & THC
  • Interest for pain relief applications
  • Indiscriminate CB receptor activation
  • Induce psychotropic effects and increased potential for addiction or abuse

ENDOGENOUS CANNABINOIDS20

CB RECEPTOR LIGANDS
  • Naturally produced by the body
  • Engage CB receptors and affect behaviour in a way partially similar to phytocannabinoids

TARGETING THE ECS WITH DIFFERENT MOLECULES

While phytocannabinoids that target CB1 have psychotropic effects, rationally-designed molecules are believed to preferentially bind to CB2 with limited psychotropic effects.5,9,10,16

RATIONALLY-DESIGNED MOLECULES5,9,10,16

  • Thought to mimic the selective properties of endocannabinoids
  • May limit psychotropic effects
  • Potential for ECS targeting without immunosuppression

ECS TARGETING MAY CHANGE HOW AUTOIMMUNE DISEASES CAN BE TREATED

Harnessing the homeostatic abilities of the ECS instead of relying on therapies that suppress the immune response offers a promising way forward in advancing the treatment of SSc.12,13

Intricate & highly regulated system

CB2 IS PART OF AN INTRICATE & HIGHLY REGULATED SYSTEM

The ECS is ubiquitous throughout the body and plays a critical role in promoting homeostasis.8,12

Reaching the underlying drivers of SSc

REACHING THE UNDERLYING DRIVERS OF SSc

Inflammation and fibrosis may be addressed by modulating the ECS through key receptors like CB2.1,8,11

CORBUS IS LEADING THE WAY IN
ENDOCANNABINOID SYSTEM RESEARCH

Corbus Pharmaceuticals is leading a new approach to treating inflammatory, fibrotic, and metabolic diseases by developing medicines that target the endocannabinoid system. Our pipeline of novel molecules is specifically designed to target this vital pathway to modulate inflammation and fibrosis.

Plants and greenery