Uncovering the potential of the body’s natural stress defense system

At Orphazyme, our work is focused on the treatment of neurodegenerative orphan diseases by harnessing the cell protective properties of the heat shock response, a natural defense mechanism system present in all our cells.

The heat shock response protects cells from the accumulation of misfolded proteins, aggregated proteins, and dysfunctional lysosomes (the cell’s recycling system), which could otherwise lead to toxicity and disease. The heat shock response is generated through the production of heat shock proteins (HSPs), such as heat shock protein 70 (HSP70).




Our lead investigational treatment is arimoclomol—a first-in-class heat shock protein (HSP) amplifier:

  • A small molecule manufactured in a capsule formulation; designed to be swallowed whole, opened to allow contents to be mixed with soft foods/liquids or delivered through a nasal gastric tube or PEG

  • Designed to cross the blood brain barrier to address neurodegenerative manifestations of disease
  • Safety data collected from clinical evaluation in more than 500 individuals

The first rare disease for which it is under evaluation is Niemann-Pick disease type C (NPC).

To date, Orphazyme has studied arimoclomol in seven Phase 1 trials, four Phase 2 trials, and one pivotal Phase 2/3 trial in various protein-misfolding diseases.


We are focused on understanding the cell-protective properties of heat shock proteins and translating this science to create new therapies for neurodegenerative orphan diseases. Our development program covers two types of disease:

LYSOSOMAL STORAGE DISEASES (LSDs) are inherited metabolic disorders in which enzyme deficiencies result in an accumulation of toxic materials in the cells of the body. These deficiencies are often caused by mutations leading to premature misfolding and degradation of the enzymes. In both NPC and Gaucher disease, as well as other LSDs, mutations lead to misfolding and loss of enzyme functions involved in the breakdown and recycling of critical cellular components within the cells recycling centers, the lysosomes. Our research in LSDs focuses on the natural cellular machinery that helps proteins to remain folded in their active state. In particular, we are evaluating heat-shock protein family members called HSP70. By amplifying the production of HSPs, this pathological cascade can be addressed by rescuing the function of the recycling enzymes and helping them perform better in the lysosomes.

PROTEIN-AGGREGATION DISEASES may occur as a consequence of protein misfolding and are a hallmark of many neurodegenerative diseases. Two neuromuscular diseases—inclusion body myositis (IBM) and amyotrophic lateral sclerosis (ALS)—are debilitating rare diseases with limited or no treatments today. Amplifying the production of heat shock proteins may help restore balance, repair the dysfunctional protein processing, and clear protein aggregation.

For a more detailed explanation of the science behind our approach, please see: Kirkegaard et al. Nature 2010; Science Translational Medicine 2016 .


We strive to develop expertise within our therapeutic areas of interest through close collaborations with academic experts and patient organizations around the world. Through these partnerships, we support the advancement of molecular and clinical understanding and perform preclinical evaluations in biological models of relevant diseases.

Orphazyme’s academic partners include professors and clinicians from institutions such as the University of Oxford, University Hospital of Udine, University of Helsinki, University College London, University of Miami, University of Cambridge, and University of Kansas.

As an example, we have been collaborating with the University of Oxford since nearly the inception of the Company. The University has distinctive expertise in lysosomal storage disease (LSD) research and pioneered the first pharmacological approach to treat these disorders. Through this collaboration, we have conducted a number of preclinical studies that have provided critical insights into the potential of heat shock protein-amplifying therapeutic strategies for LSDs.

Further, partnerships with the patient community have been instrumental in ensuring the assessment of patient-relevant outcomes as part of our scientific models and subsequently published in peer-reviewed scientific journals.