Research

Our Research Platform

At our core, we are a science-driven research organization. We have built a discovery platform upon our expertise in the field of cellular metabolism, specifically in genetically defined diseases. We take a systems biology approach to deeply understand disease states, drive the discovery and validation of novel therapeutic targets and define patient selection strategies, thereby increasing the probability that our experimental medicines will have the desired therapeutic effect.

Cellular Metabolism

Cellular metabolism refers to the set of life-sustaining chemical transformations within the cells of living organisms. The conversion of nutrients into energy via enzyme-catalyzed reactions allows organisms to grow and reproduce, maintain their structures and respond to their environments. Additionally, metabolites serve as key regulators of diverse aspects of cellular biology, and pharmacologic targeting of metabolism can therefore have disease-modifying effects in a wide variety of pathologies.

The chemical reactions of metabolism are organized into metabolic pathways, in which one chemical is transformed through a series of steps into another chemical, by a sequence of enzymes. Enzymes catalyze quick and efficient reactions, serve as key regulators of metabolic pathways and respond to changes in the cell’s environment or signals from other cells. We believe our deep understanding of metabolic pathways within normal cells enables us to identify altered metabolic pathways within abnormal cells in genetically defined diseases.

Genetically Defined Diseases

Genetically defined diseases range from a broad group of more than 600 rare diseases caused by mutations of single genes to conditions resulting from alterations in one or many genes (polygenic diseases) that affect up to millions of patients worldwide. In these disorders, the defect of single or multiple genes leads to a deficient expression or function in one or several gene products which collectively manifest in organ dysfunction. As these conditions are by nature congenital and frequently hereditary, they are often detected either by genetic testing or phenotypic diagnosis in newborns or in early childhood.

Many of these diseases carry severe or life-threatening features and are likely to be under-diagnosed given the lack of available therapies or diagnostics, the rarity of the condition, or limited understanding of how the disease genetics relate to disease phenotype. Through the study of genetically defined diseases and other conditions, it has been shown that small molecule therapies able to specifically correct genetic deficiencies and their associated organ dysfunction may have application in conditions that arise independent of patient genetics but for which identical organ dysfunction occurs.

Despite the promising progress made for patients with a small group of these diseases, the majority of patients with genetically defined diseases have few therapeutic options, and the standard of care for many such conditions is palliative, meaning treatment of symptoms with no effect on underlying disease mechanisms.

Our Research Focus

Our goal is to develop mechanistically specific, small molecule approaches with the potential to have disease modifying and long term rather than palliative effects. We are taking a novel small molecule approach to correct the defects within diseased cells with a goal of developing transformative medicines for patients. We focus on genetically defined diseases that share the following common set of features:

  • Genetic definition of single or multiple gene sets linked to a consistent and recognizable disease phenotype;
  • severe clinical presentation coupled with significant unmet medical need and evidence that disease damage while progressive is potentially reversible;
  • sufficient patients to allow facile recruitment and statistical powering of prospective clinical trials; and
  • a rigorous validation of the target, based upon a detailed mutational, structural, cell biological and biochemical analysis, to determine if a small molecule approach to correcting or significantly modifying the disease is both safe and feasible in newborn to elderly patients.