Innovative science for life-changing medicines

Platform Technology and Science

Inhibiting epichaperomes for a targeted impact on protein degradation

Epichaperomes are protein complexes formed under chronic cellular stress in diseases. They consist of regulatory proteins, chaperones and co-chaperones that stabilize aberrant proteins, facilitate abnormal protein-protein interactions, remodel cellular networks and contribute to the pathology of many diseases.

Our proprietary small molecule inhibitors – icapamespib (PU-AD/PU-HZ151) and zelavespib (PU-H71) – selectively target epichaperomes to inhibit their activities and initiate degradation of aberrant, disease-causing proteins restoring proteostasis.

Epichaperome Inhibition and Protein Degradation

Impact of Epichaperomes in Cancer

Cancer is caused and propagated by constitutively activated growth promoting oncoproteins and unregulated tumor growth. Epichaperomes are regulatory complexes in cancer and are absent in normal cells. They sustain the stability and activity of several oncogenic proteins required for cancer cell survival.

Inhibition of epichaperomes in nonclinical studies initiates aberrant protein degradation and tumor cell death (apoptosis).

We are commencing clinical development of icapamespib in patients with recurrent malignant glioma and with zelavespib in patients with hematological malignancies.

Impact of Epichaperomes in Neurodegenerative Diseases

The hallmark of neurodegenerative diseases is the breakdown of regulatory pathways that prevent the aggregation and accumulation of disease-associated aberrant proteins. Protein degradation systems such as the ubiquitin-mediated proteasome pathway or autophagy can become overburdened and fail to effectively degrade and clear aberrant proteins.

In nonclinical studies epichaperome inhibition initiates aberrant protein degradation and results in the recovery of neuronal functions.

We are presently focused on icapamespib for patients with amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease.

Our Epichaperome Inhibition Platform has Further Therapeutic Applications

The opportunity for extending our platform of epichaperome inhibitors to other indications has been explored in nonclinical studies for anti-viral therapy, mild traumatic brain injury, inflammatory disease, and more broadly for both hematological malignancies and solid tumors.