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. These learnings can be rapidly applied to our clinical trials with the goal of developing medicines that can have a significant impact for patients.

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

Agios is the pioneer in the science of pyruvate kinase (PK) activation. 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.

A path forward: activating pyruvate kinase

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

Leveraging expertise in cellular metabolism to advance research in genetically defined diseases

Our late-stage research programs include 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.

Sarah Gheuens, M.D., Ph.D.,
Chief Medical Officer

Right now, there are too many patients in need who do not have any or very few effective treatment options available. I am excited and motivated by the potential in our pipeline to change this paradigm. Nothing feels better than making a difference in how patients experience life.

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.

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

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for partnership

Great science requires great teamwork. By truly listening to and trusting partners, collaborators, healthcare providers, advocates, and patients we are able to identify and pursue the ideas that can make the biggest impact for people living with genetically defined diseases.

Explore our partnership opportunities and learn more about the ways we can work together to make a difference in patients’ lives.

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