Multiple sclerosis is a severely debilitating autoimmune disease caused by the degeneration and disruption of the myelin sheaths that surround axons of the brain and spinal cord. Myelin loss is associated to neural inflammation, axonal loss, and formation of scar tissue in the white matter, leading to a wide spectrum of neurological symptoms, including fatigue, spasticity, functional loss, and pain. The estimated worldwide number of people with multiple sclerosis has increased to 2.8 million in 2020 with a global prevalence of about 36 per 100,000 people. In most cases, the diagnosis occurs between 20 and 50 years of age, and the most common symptoms include fatigue, visual disturbances, numbness and tingling, muscle spasms, stiffness and weakness, mobility problems, pain, and problems with thinking, learning, and planning. Treatments for MS mainly target the management of symptoms and attempt to interrupt the damage to myelin sheets, and include anti-inflammatory or immuno-modulatory drugs that, given the chronic nature of the disease, expose the patient to serious side effects, with significant impact on their quality of life. Clinical patterns of appearance and progression of symptoms significantly vary, and about 10-15% of patients experience the primary progressive form of multiple sclerosis. In these patients, the direct administration of PD-L1-expressing hematopoietic stem and progenitor cells into the central nervous system may dampen the autoimmune mechanism at the basis of myelin disruption, inducing a significant clinical benefit.
Novel tumour-specific antigens to target liquid tumours
Altheia Science has developed a novel immunotherapy approach based on chimeric antigen receptor (CAR)-T cell technology using autologous cells for the treatment of myeloid disorders. This is achieved through the identification, via an innovative in silico discovery strategy, of new antigenic determinants specifically expressed on tumor cells that serve as tumor antigens. The approach involves engineering the patient’s T cells to express a specific CAR capable of selectively recognizing and eliminating tumor cells. Most importantly, the antigen expression is restricted to leukemic cells, sparing healthy cells and tissues, thus predicting a highly safe profile. Through an extensive preclinical program, Altheia Science has generated solid safety and efficacy data in animal disease models and patient-specific animal models, where the selected CAR-T cell constructs induce a significant increase in survival, along with rapid elimination of leukemic cells in the absence of in vitro and in vivo hematopoietic toxicity. The first clinical indication of this program is acute myeloid leukemia, a severe liquid tumour with highly unmet clinical need affecting children and adults.