Pipeline

TTI-1612

TTI-1612 is a recombinant soluble form of heparin-binding epidermal growth factor-like growth factor (HB-EGF). It is being developed as a treatment for interstitial cystitis (IC), a chronic bladder disease characterized by low urinary HB-EGF levels and a dysfunctional, "leaky" bladder epithelium. TTI-1612 stimulates the proliferation of bladder epithelial cells and reduces their permeability. Unlike the current IC therapeutics, which are largely palliative in nature, TTI-1612 is designed to target the root cause of IC – dysfunction of the bladder urothelium caused by low levels of HB-EGF. TTI-1612 is also being developed 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.

SIRPaFc

CD47 binds SIRPa on the surface of macrophages, and transmits a "do not eat" signal that protects cells from macrophage attack. Newly emerging evidence indicates that this negative signal is used by cancer stem cells to protect themselves from marcophage-mediated destruction. SIRPaFc is an antagonist of the CD47-SIRPa interaction, and is designed to alieviate CD47-mediated suppression and promote anti-tumour responses. It is being developed as a treatment for acute myeloid leukemia, the most common acute leukemia in adults.

CD47Fc

The CD47-SIRPa interaction plays a critical role in promoting the survival of hematopoietic stem cells following transplantation. CD47Fc is a SIRPa agonist that delivers a “do not eat” signal to macrophages to protect 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.

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. TTI is currently seeking a partner to assist in the further development of this program.

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.