Pipeline

 
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Apristor®

A First-in-Class, Oral Progesterone Receptor Antagonist

ABOUT HORMONE DRIVEN CANCERS

Over 100,000 patients with metastatic breast, ovarian, prostate, or uterine cancers die per year in the United States. For many of these patients, continuous progesterone and estrogen signaling drives disease progression. Currently, only medicines that block estrogen are approved, meaning that progesterone signaling continues in those patients receiving anti-estrogen therapy.

ABOUT APRISTOR

Apristor (onapristone extended release or “ER”) is an investigational medicine that prevents progesterone signaling by blocking the interaction between progesterone and its binding partner, progesterone receptor. Apristor is the only known full PR antagonist. 

ROLE OF PR IN CANCER

Under normal conditions, progesterone is primarily responsible for the development of sex organs and for regulating the menstrual cycle. Cancer cells hijack progesterone to stimulate cancer cell proliferation, metastases, regeneration, and immune evasion.

CLINICAL ACTIVITY

Monotherapy activity in a variety of patient populations with PR+ cancer, including first line metastatic breast cancer (56% ORR, 17.5 month DoR, 14 month mPFS), tamoxifen resistant breast cancer (25% ORR, 50% CBR), and heavily-pretreated Phase 1 population (17% CBR).

NOVEL FORMULATION

Early clinical studies employing an immediate release (IR) formulation of onapristone have shown that onapristone is well-tolerated except for transient, low grade enzyme elevations that may be attributed to plasma concentration fluctuations. Apristor (onapristone ER) was developed to provide a more tightly controlled release of onapristone.

 

CTX-30916

Fast-Follower, Oral Progesterone Receptor Antagonist

CTX-30916 is an Apristor analogue that exhibits unique pharmacological properties distinct from the parent compound. CTX-30916 may be developed across progesterone-driven diseases, including women’s health (endometriosis, uterine fibroids), rare disease (Charcot-Marie), or oncology.

 

Sigma1 Inhibitor

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

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.