Our Approach

At Osmol Therapeutics, we are focused on advancing OSM-0205, a patented drug with a unique, first-in-class mechanism for modulating intracellular calcium, a known trigger for chemotherapy-induced peripheral neuropathy (CIPN) and chemotherapy-induced cognitive impairment (CICI).

Mechanism

Taxanes, such as paclitaxel, are most commonly used in the treatment of breast cancer, however they are also used in the treatment of other solid tumor cancers including prostate, lung, ovarian, pancreatic, and head and neck cancer. During treatment, taxanes bind to neuronal calcium sensor-1 (NCS1), resulting in a surge of calcium. This calcium surge activates calpain (a protease), which degrades NCS1 and other proteins, resulting in neuronal dysfunction - a hallmark of CIPN.

Supportive Nonclinical Data for OSM-0205

Nonclinical data show that OSM-0205 blocks the calcium surge and prevents calpain activation, thus maintaining NCS1 and other proteins and protecting neuronal integrity.

^{InsP3R: inositol trisphosphate receptor
ER: endoplasmic reticulum}

OSM-0205 blockade of calcium surge leading to Maintenance of neuronal integrity

Proof of Concept in Nonclinical Model

Behavior

Chronic taxane administration in mice leads to pathological and behavioral features similar to CIPN. A rotarod test (“log rolling”) was used to assess the ability of the mice to maintain balance, demonstrating their somatosensory neuronal function.

Pretreatment with parenteral OSM-0205 prevented taxane-induced rotarod deficits.1

Cognitive Impairment

Chemotherapy-induced cognitive impairment (CICI) frequently includes problems in attention, concentration, working memory, and executive function.2 The Displaced Object Recognition model was used to assess the ability of mice to remember a displaced object. Taxanes produce cognitive deficits in mice (Blue bars) that are observed for the time spent with the displaced (unfamiliar) object. A normal mouse will spend more time with a displaced object. (Gray bars)

Pretreatment with OSM-0205 preserves cognition at a level indistinguishable from vehicle-treated controls (Purple bars).3

Pretreatment with OSM-0205 in taxane-treated mice, prevented taxane-induced spatial memory deficits.4

Morphology

The neuronal fibers from mice treated with vehicle (image on the left) show no damage whereas mice treated with paclitaxel + saline (center image) have been damaged. Arrows indicate axons occupied by debris-filled phagocytes as a result of taxane treatment. Mice receiving OSM-0205 prior to paclitaxel treatment (image on the right) are protected from damage, appearing similar to healthy neuronal cells (image on the left).1

^{NOTE: Taxol, Taxotere and Abraxane are called “taxanes.”}

^{1. Mo et al, FASEB J 2012}
^{2. Ahles et al, J Clin Oncol. 2012 Oct 20; 30(30): 3675–3686}
^{3. Nguyen, Fischer and Ehrlich, Mol Neurodegener 2021}
^{4. Huehnchen et al., 2017}

THERAPEUTIC AREAS

News & Media

Our Approach

At Osmol Therapeutics, we are focused on advancing OSM-0205, a patented drug with a unique, first-in-class mechanism for modulating intracellular calcium, a known trigger for chemotherapy-induced peripheral neuropathy (CIPN) and chemotherapy-induced cognitive impairment (CICI).

Mechanism

Supportive Nonclinical Data for OSM-0205

Proof of Concept in Nonclinical Model

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