Pipeline

CD200 fusion protein (CD200Fc)

CD200 is a transmembrane protein broadly expressed on a variety of cell types including lymphocytes, dendritic cells and neurons. Through binding to a specific receptor (CD200R) on macrophages and T cells, CD200 delivers an immunosuppressive signal. CD200Fc is a CD200R agonist that has shown efficacy in animal models of rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, pulmonary inflammation and transplantation. The global rights to this program have been licensed to a major US biotechnology company.

CD200-specific monoclonal antibody

Tumour cells exploit the suppressive properties of CD200 to escape attack from the immune system. Trillium is developing a CD200 blocking antibody to alleviate this suppression and thus augment anti-cancer immune responses. Industry watchers will know that Trillium was the first to identify CD200 as a target for cancer therapeutics, and has accordingly established a dominant patent position in this field. This is clear from the three US patents that have already been issued to Trillium, including broad claims for the treatment of cancer. This program is being co-developed with a major US biotechnology company.

CD47Fc

CD47 binds SIRPa on the surface of macrophages, and transmits a "do not eat" signal that protects cells from macrophage attack. Emerging evidence indicates that this pathway plays a critical role in promoting the survival of hematopoietic stem cells following transplantation. CD47Fc is a SIRPa agonist that suppresses macrophage-mediated clearance of hematopoietic stem cells. It is designed to improve hematopoietic stem cell engraftment, accelerate blood cell recovery post-transplantation and enable engraftment with lower doses of stem cells.

SIRPaFc

Cancer stem cells protect themselves from marcophage-mediated destruction by transmitting a "do not eat" signal throught the CD47-SIRPa pathway. Interference with this pathway can remove this suppression and promote anti-tumour responses. SIRPaFc is an antagonist of the CD47-SIRPa interaction, and is being developed as a treatment for acute myeloid leukemia.

TTI-314

Antibody-antigen (immune) complexes play a key role in tissue destruction in a number of autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and immune thrombocytopenia purpura (ITP). The binding of immune complex to FcgRIIa (CD32a), the most abundant IgG Fc receptor in humans, is a key trigger in the inflammatory response. TTI is developing a humanized monoclonal antibody. TTI-314, which prevents the binding of immune complexes to FcgRIIa. TTI-314 was recently tested in a preliminary toxicology study in non-human primates, and no untoward events were observed.

TTI-1612

TTI-1612 is a recombinant soluble form of HB-EGF, a growth factor that stimulates the proliferation of bladder epithelial cells and reduces their permeability. It is being developed as a treatment for interstitial cystitis (IC), a chronic bladder disease that is believe to be caused by a dysfunctional, "leaky" bladder epithelium. TTI is also developing TTI-1612 for the prevention of necrotizing enterocolitis (NEC), a life-threatening intestinal disorder that occurs predominantly in premature infants. Studies have demontrated that oral administration of recombinant HB-EGF significantly reduces the incidence and severity of NEC in a rat model. There is clear evidence in this system the HB-EGF restores gut barrier function and promotes the proliferation and migration of intestinal epithelial cells.