Arimoclomol’s MECHANISM of Action

The production of HSPs is regulated by a transcription factor, heat shock factor 1 (“HSF1”). A transcription factor is a protein that regulates production of other proteins in the cell. In the case of HSF1, the proteins being regulated are HSPs. Activation of HSF1 starts the production of the major stress-inducible HSP70-chaperone along with other HSP-chaperones, which help reshape the cells’ misfolded proteins and take care of the recycling systems. Under normal cellular conditions, HSF1 is inactive. However, the transcription factor can be activated by an initial cellular stress, such as protein misfolding, and becomes fully activated under a sustained stress signal.

Arimoclomol amplifies and prolongs the activated, HSP-producing state of HSF1. This leads to an amplification in the production of cell protective HSPs, but only in physiologically stressed cells. 


Clinical profile and uses of arimoclomol

The clinical experience with arimoclomol supports its continued development. 


As of the date hereof, no safety risks from taking arimoclomol have been identified in seven Phase I trials and three Phase II trials, and, overall, tolerability of arimoclomol (i.e. the degree to which an overt adverse effect can be tolerated by the subject/patient) was comparable to a placebo. 


Arimoclomol is orally administered and has a bioavailability of 80-90%. High bioavailability reduces the amount of drug administered while achieving the desired pharmacological effect.

In addition, arimoclomol readily crosses the blood-brain barrier. The blood-brain barrier is a selectively permeable membrane which prevents large compounds from entering the cerebrospinal fluid (“CSF”) (liquid surrounding the brain and spinal column). Arimoclomol reaches CSF drug concentrations comparable to the concentration found in circulating blood. Good brain penetrance is key to treatment of many central neurological diseases.


Arimoclomol has achieved a clinical proof-of-concept in ALS (1) and sIBM (1). Phase II trials in both indications have shown consistent trends of clinically relevant efficacy in pre-defined analyses.


(1) Clinical proof-of-concept in ALS and sIBM achieved by demonstrating benefit across efficacy endpoints and assessments as compiled evidence, also in absence of statistical significance.