Therapeutic Areas
Autoimmune/Inflammatory disease
Normally the immune system provides a powerful defence mechanism against
dangerous pathogens while sparing injury to host tissue. Under certain circumstances,
however, this delicate balance becomes disturbed, resulting in autoimmune
or chronic inflammatory disease. These conditions, which include rheumatoid
arthritis, multiple sclerosis, type 1 diabetes, psoriasis, inflammatory
bowel disease and lupus, have a staggering impact on public health. In the
United States alone, autoimmune diseases are estimated to affect 14 - 22
million people (5 - 8% of the population), about twice as many as cancer,
with the cost of treatment estimated at greater than $100 billion annually.
TTI is taking several parallel immune-mediated approaches to the treatment of autoimmune/inflammatory
diseases. One approach is to down-regulate the immune system through the CD200 pathway. The company's CD200Fc protein has demonstrated remarkable therapeutic effects in a number of animal models of disease. TTI is also developing a humanized monoclonal antibody to FcgRIIa (CD32a), an activating receptor that plays a major role in immune-complex mediated inflammatory disorders.
Cancer
Cancer remains one of the most serious public health issues. In the US, cancer is responsible for 23%
of all deaths (more than 500,000 per year), making it the second leading
killer behind heart disease. The total economic burden of this disease is
estimated to be $143 billion annually. Although the development of new therapeutics
has led to modest increases in patient survival, there is clearly a pressing
medical need for additional treatment strategies.
TTI’s approach to cancer treatment is
based upon the concept of blocking immunoregulatory pathways that tumour cells exploit in order to suppress a patient's own anti-cancer immune response. Two novel product opportunities are being pursued: a monoclonal antibody against CD200, to block the CD200-CD200R interaction, and a
SIRPaFc fusion protein, to inhibit the CD47-SIRPa interaction.
Hematopoietic stem cell transplantation
Hematopoietic stem cell transplantation (HSCT) is a medical procedure that replaces blood cells destroyed by disease, chemotherapy, and/or radiation with new, healthy cells. It is the most important clinical application of stem cell biology. HSCT is widely used in cancer treatment, as well as in the treatment of inherited genetic diseases such as thalassemia and bone marrow failure syndromes. Older and medically infirm patients, however, are often not eligible for HSCT because they cannot withstand the aggressive chemotherapy conditioning that precedes transplantation. In addition, graft failure remains a significant problem, and emerging data suggests that this failure may be due to macrophages attacking the transplanted cells.
TTI is developing a soluble fusion protein, CD47Fc, to enhance engraftment of hemotopoietic stem cells by suppressing the activity of macrophages. By inducing stem cell engraftment in recipients under reduced chemotheraphy conditioning, CD47Fc has the potential to unlock an unmet market in the HSCT field.
Interstitial cystitis
Interstitial cystitis (IC) is a chronic disease of the bladder characterized by urinary frequency, urgency, nocturia (night-time urination), and pelvic pain. It affects approximately 1 million people (mostly women) in the US alone. Although the causes of IC remain to be completely determined, increased permeability of the epithelial layer lining the inside of the bladder is believe to play a major role. IC patients often suffer from debilitating symptoms that impact their physical and emotional health, and many are unable to find relief with available therapies.
TTI's revolutionary approach to the treatment of IC is to repair the defective bladder lining through local (intravesical) administration of a recombinant growth factor.
Nectrotizing Enterocolitis
Necrotizing enterocolitis (NEC) is a life-threatening intestinal disorder that occurs predominantly in premature infants. NEC is a complex disease likely caused by a number of factors, including gut immaturity, enteral feeding, intestinal ischemia, bacterial colonization and inflammation. The current treatments are non-specific, involving use of intravenous antibiotics, supportive care for systemic sequellae, and possibly surgery to remove necrotic tissue. None of these approaches are particularly effective. The mortality rate from NEC is 30-50%, and has remained unchanged over the last three decades. Infants who survive NEC are frequently afflicted with long-term developmental problems and diseases such as short bowel syndrome. Thus, despite advances in many other areas of neonatal care, NEC remains a serious medical problem.
TTI's approach to prevention of NEC is to accelerate the development of the immature GI tract through oral treatment with a naturally occurring growth factor.
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