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Innovation Engine  

Context Therapeutics has leveraged its core capabilities in protein-protein interactions and precision medicine to build a product engine that is focused on hormone responsive cancers.

Apristor (Onapristone XR)

A First-in-Class Anti-Progestin For PR+ Breast Cancer

PR+ BREAST CANCER.  Approximately 60-70% of breast cancer patients express progesterone receptor (PR).  Onapristone is a type I progesterone antagonist that prevents PR monomers from dimerizing. In turn, onapristone inhibits ligand and kinase-induced PR activation, which prevents PR from activating pro-cancer survival gene transcription programs. These properties are unique to Onapristone within the antiprogestin class. The efficacy of onapristone has been documented in multiple preclinical tumor models, alone and in combination with other endocrine therapies, including aromatase inhibitors (AIs) and selective estrogen receptor degraders (SERDs). 

CLINICAL ACTIVITY.  An immediate release version of Onapristone has been administered to hundreds of healthy volunteers and cancer patients across Phase 1 through Phase 3 trials.  The drug completed two Phase 2 trials in 120 patients with metastatic breast cancer.  In first line metastatic breast cancer, Onapristone demonstrated objective responses (tumor shrinkage) in over 50% of the treated patients. 

FURTHER IMPROVING ACTIVITY.  Context Therapeutics is developing an extended release version of Onapristone (Apristor), which provides a significant advantage over immediate release versions as extended release Onapristone delivers complete progesterone receptor blockade over a 24-hour period.  Apristor has been tested in over 50 progesterone receptor positive breast and ovarian cancer patients wherein the drug was found to be active and well tolerated.

SIGMA1 Inhibitor

A First In Class Sigma1 Inhibitor For Abiraterone-Resistant Prostate Cancer

Drug Discovery. Sigma1 is an intracellular protein that engages in client protein complex formation to regulate the quality control, transport, and activity of client proteins.  By therapeutically modulating Sigma1 stabilization of client proteins, client protein transport is altered, leading to positive or negative regulation of client protein signaling pathways. Many of these client proteins are validated disease targets but are generally considered undruggable through small molecule approaches.  Indirect modulation of client protein stability and transport through Sigma1 expands the universe of opportunities for new drug discovery and new treatments for patients.

Abiraterone-Resistant Prostate Cancer.  Androgen receptor (AR) signaling is the primary driver of prostate cancer disease progression, resulting in about 30,000 deaths per year in the US. Current first line therapy with abiraterone may activate resistance mechanisms that drive AR transport and subsequent activation of AR signaling programs that promote cancer cell survival. 

Context scientists were the first to establish that enhanced Sigma1 expression and Sigma1-mediated transport of androgen receptor is associated with malignancy. Context has developed and characterized a series of drug-like small molecule Sigma1 modulators that disrupt Sigma1-mediated stabilization of AR as well as mutants and variants of AR that are resistant to all currently available therapeutic agents, allowing rapid translation of preclinical studies to Phase I trials. 

Sigma1 Research Consortium.  Our strategy includes collaborating with academic and biopharmaceutical partners.  We have a flexible resource sharing program - our Sigma1 Toolkit - to enable the expedited transfer of our chemical library, reagents, and biomarker tools for groups interested in our core research areas and outside.

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