Connected through the science of cellular metabolism

With nearly 15 years of focused study on cellular metabolism, we have a deep and mature understanding of this biology, which is involved in the healthy functioning of nearly every system in the body. This means we can rapidly identify and advance the areas where our discoveries can have the biggest impact.

Our focus is on applying this science to the treatment of genetically defined disease, with a near-term focus on diseases of hemolytic anemia. Our research engine offers a differentiated value proposition.

  • Publication history reflects nearly 15 years of leadership in the field of PK activation
  • Laboratory capabilities are specialized to enable complex, genetically defined disease studies
  • Research team with significant expertise in the field of cellular metabolism, biochemistry and drug discovery
  • Highly translatable work from murine and cell-based models recapitulating human disease yields deep insights into treating genetically defined diseases and disease adjacencies
  • Our focus on modulating pyruvate kinase activation, cellular bioenergetics and amino acid metabolism allows preclinical exploration of both clinical and novel assets in multiple indications

A path forward: activating pyruvate kinase

Pyruvate kinase (PK) is an enzyme that plays an important role in regulating cell metabolism. It is responsible for the final step in glycolysis in red blood cells, which is required for maintaining red blood cell energy levels and structure.

Diminished PK activity in patients with hemolytic anemia leads to a reduction in adenosine triphosphate (ATP) levels, increased levels of the metabolite 2,3-DPG (2,3-diphosphoglycerate) and shortened red blood cell lifespan.

Red blood cell lifespan in hemolytic anemias

Activating the PK pathway may improve the health, energy and lifespan of red blood cells for patients with hemolytic anemias by

  • Increasing ATP production, helping to match red blood cell energy needs
  • Decreasing 2,3-DPG which reversibly increases oxygen affinity for hemoglobin, potentially reducing sickling
  • Maintaining antioxidants, thereby reducing cellular damage

Healthy red blood cell versus red blood cell in hemolytic anemia patient

Expanding PK activation portfolio by exploring its expression in other cell types

Agios is the pioneer in the science of PK activation. While our most advanced efforts explore its application to red blood cells – known as PKR activation – we are also researching its application to other cell types.


We have multiple PK activator assets with complementary properties, including brain-penetrant molecules and assets that activate PK in mitochondria, which are known as PKM2 activators. These assets open exciting possibilities to explore their potential therapeutic value in neurological, renal, and mitochondrial diseases.

Leveraging expertise in cellular metabolism to discover new targets across a range of therapeutic areas

Our research pipeline extends far beyond PK activation.

Among our most advanced research programs are phenylalanine hydroxylate (PAH) stabilizers for the treatment of phenylketonuria (PKU) and branched chain amino acid aminotransferase-2 (BCAT2) inhibitors for the treatment of propionic and methylmalonic acidemia.

Phenylalanine hydroxylate (PAH) stabilizers for the treatment of phenylketonuria (PKU)

Disease Overview

  • PKU is a rare, inherited disease that causes phenylalanine to accumulate.
  • Disease management consists of a diet low in phenylalanine combined with approved therapies. Significant unmet need exists in PKU, despite approved drugs.
  • PKU affects people from infancy to adulthood.

Scientific Strategy

  • Agios’ PAH stabilizer is an investigational medicine designed for convenient oral administration.
  • Normalizing plasma phenylalanine concentrations may allow patients to increase natural protein intake and provide them with normal milestones and increased quality of life from childhood to old age.

Branched chain amino acid aminotransferase-2 (BCAT2) inhibitors for the treatment of propionic and methylmalonic acidemia

Disease Overview

  • Propionic and methylmalonic acidemia are a group of inherited in-born errors of metabolism, in which the body cannot break down branched chain amino acids, leading to an accumulation of toxic substances.

Scientific Strategy

  • Agios’ BCAT2 inhibitors are designed for convenient oral administration.
  • Substrate reduction therapy: BCAT2 inhibition reduces the formation of the toxic metabolites, methylmalonic acid (MMA) and propionic acid (PA).
  • BCAT2 can be employed in toxic substrate reduction for several additional genetically defined diseases.
  • Prevention of MMA and PA accumulation and metabolic crises will enable patients to have fewer dietary/other restrictions, providing them an arc of life with significantly improved or normal milestones.

Bruce Car,
Chief Scientific Officer

Along our journey, Agios has built tremendous depth in all areas of drug hunting around cellular metabolism, including biology, chemistry and biochemistry, pharmacology, data science, and translational medicine. We are now focusing these strengths on genetically defined diseases and are poised to transform the standard of care in these diseases. All of this is made possible because of our interconnectedness and integration across all of our drug hunting disciplines.

A pipeline of possibility

Our deep and differentiated understanding of cellular metabolism is foundational to our success and the connective thread that binds our people and our pipeline together.

View Our Pipeline

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Access our collection of scientific publications and recaps from medical conferences.

See Publications

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